Publications by authors named "Kexin Li"

223 Publications

Alanine Aminotransferase and Bilirubin Dynamic Evolution Pattern as a Novel Model for the Prediction of Acute Liver Failure in Drug-Induced Liver Injury.

Front Pharmacol 2022 22;13:934467. Epub 2022 Jul 22.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China.

To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients. The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts. The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%, < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682-0.756) in the discovery cohort and 0.828 (95% CI: 0.788-0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, < 0.05) with a higher degree of necrosis (29.2%, = 0.084). DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.
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http://dx.doi.org/10.3389/fphar.2022.934467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355525PMC
July 2022

Safety and Effectiveness of Moxibustion and Abdominal Massage in Hospitalized Older Patients With Constipation: A Retrospective Study.

Authors:
Kexin Li

Wound Manag Prev 2022 Aug;68(8):16-24

Geriatric department, Nanjing Drum Tower Hospital, Nanjing 210008, China.

Background: Evidence about moxibustion and abdominal massage for treating constipation in older hospitalized patients is limited.

Purpose: To investigate the safety and effectiveness of moxibustion and abdominal massage in hospitalized older patients with constipation.

Methods: Hospitalized older patients (age ≥60 years) with constipation were retrospectively categorized as 2 cohorts according to whether the patients received moxibustion and abdominal massage in addition to routine nursing care. Gastrointestinal symptoms, Constipation Assessment Scale (CAS) scores, and Geriatric Depression Scale (GDS) scores were compared before and after treatment between cohorts.

Results: The 2 cohorts (n = 100 for each) had similar baseline characteristics and gastrointestinal symptoms; the control cohort and the additional intervention cohort also had similar CAS scores (7.14 ± 3.67 vs 7.48 ± 2.96, respectively), and GDS scores (>17: 31% vs 29%, respectively). Improvement in the 2 scores from baseline was observed after 2 weeks in both the control cohort and the additional intervention cohort (CAS, 5.37 ± 5.34 and 3.80 ± 4.47, respectively; GDS, >17: 28% and 15%, respectively). The cohort with additional interventions had a lower ineffective rate (defined as persistent symptoms or absence of decrease in CAS, 49% vs 32%; P = .028) but had more diarrhea (9% vs 21%; P = .017).

Conclusion: Moxibustion and abdominal massage may help relieve constipation in hospitalized elderly patients, but attention should be paid to the increased occurrence of diarrhea. More study is needed.
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August 2022

Genome-Wide Characterization of the Aquaporin Gene Family in Radish and Functional Analysis of Involved in Salt Stress.

Front Plant Sci 2022 13;13:860742. Epub 2022 Jul 13.

National Key Laboratory of Crop Genetics and Germplasm Enhancement, Key Laboratory of Horticultural Crop Biology and Genetic Improvement (East China), Ministry of Agriculture and Rural Affairs, College of Horticulture, Nanjing Agricultural University, Nanjing, China.

Aquaporins (AQPs) constitute a highly diverse family of channel proteins that transport water and neutral solutes. play crucial roles in plant development and stress responses. However, the characterization and biological functions of in radish ( L.) remain elusive. In this study, 61 non-redundant members of AQP-encoding genes were identified from the radish genome database and located on nine chromosomes. Radish AQPs (RsAQPs) were divided into four subfamilies, including 21 plasma membrane intrinsic proteins (PIPs), 19 tonoplast intrinsic proteins (TIPs), 16 NOD-like intrinsic proteins (NIPs), and 5 small basic intrinsic proteins (SIPs), through phylogenetic analysis. All RsAQPs contained highly conserved motifs (motifs 1 and 4) and transmembrane regions, indicating the potential transmembrane transport function of RsAQPs. Tissue- and stage-specific expression patterns of AQP gene analysis based on RNA-seq data revealed that the expression levels of were generally higher than , , and in radish. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) revealed that seven selected , according to our previous transcriptome data (e.g., , , , , , , and ), exhibited significant upregulation in roots of salt-tolerant radish genotype. In particular, the transcriptional levels of dramatically increased after 6 h of 150 mM NaCl treatment during the taproot thickening stage. Additionally, overexpression of could enhance salt tolerance by -mediated transgenic radish hairy roots, which exhibited the mitigatory effects of plant growth reduction, leaf relative water content (RWC) reduction and alleviation of O in cells, as shown by nitro blue tetrazolium (NBT) staining, under salt stress. These findings are helpful for deeply dissecting the biological function of on the salt stress response, facilitating practical application and genetic improvement of abiotic stress resistance in radish.
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http://dx.doi.org/10.3389/fpls.2022.860742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337223PMC
July 2022

Identification evidence unraveled by strict proteomics rules toward forensic samples.

Electrophoresis 2022 Jul 30. Epub 2022 Jul 30.

State Key Laboratory of Toxicology and Medical Countermeasures, and Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, P. R. China.

Snake venom is a complex mixture of proteins and peptides secreted by venomous snakes from their poison glands. While proteomics for snake venom composition, interspecific differences, and developmental evolution has been developed for a decade, current diagnosis or identification techniques of snake venom in clinical intoxication and forensic science applications are mainly dependent on morphological and immunoassay. It could be expected the proteomics techniques directly offer great help. This work applied a bottom-up proteomics method to identify proteins' types and species attribution in suspected snake venom samples using ultra-high-performance liquid chromatography-quadrupole-electrostatic field Orbitrap tandem mass spectrometry technique, and cytotoxicity assay was amended to provide direct evidence of toxicity. Toward the suspicious samples seized in the security control, sample pretreatment (in sol and in-gel digestion) and data acquisition (non-target and targeted screening) modes complemented and validated each other. We have implemented two consequent approaches in identifying the species source of proteins in the samples via the points of venom proteomics and strict forensic identification. Firstly, we completed a workflow consisting of a proteomics database match toward an entire Swiss-Prot (date 20181122) database and a result-directed specific taxonomy database. The latter was a helpful hint to compare master protein kinds and reveal the insufficiency of specific venom proteomics characterization rules. Secondly, we suggested strict rules for protein identification to meet the requirements of forensic science on improved identification correctness, i.e., (1) Peptide spectrum matches confidence, peptide confidence, and protein confidence were both high (with the false-discovery ratio less than 1%); (2) the number of unique peptides was more than or equal to two in one protein, and (3) within unique peptides which at least 75% of the ∆m/z of the matched y and b ions were less than 5 ppm. We identified these samples as cobra venom containing ten highly abundant proteins (P00597, P82463, P60770, Q9YGI4, P62375, P49123, P80245, P60302, P01442, and P60304) from two snake venom protein families (acid phospholipase A2 and three-finger toxins), and the most abundant proteins were cytotoxins. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/elps.202200051DOI Listing
July 2022

Incipient Sympatric Speciation and Evolution of Soil Bacteria Revealed by Metagenomic and Structured Non-Coding RNAs Analysis.

Biology (Basel) 2022 Jul 26;11(8). Epub 2022 Jul 26.

State Key Laboratory of Grassland Agro-Ecosystem, College of Ecology, Lanzhou University, Lanzhou 730050, China.

Soil bacteria respond rapidly to changes in new environmental conditions. For adaptation to the new environment, they could mutate their genome, which impacts the alternation of the functional and regulatory landscape. Sometimes, these genetic and ecological changes may drive the bacterial evolution and sympatric speciation. Although sympatric speciation has been controversial since Darwin suggested it in 1859, there are several strong theoretical or empirical evidences to support it. Sympatric speciation associated with soil bacteria remains largely unexplored. Here, we provide potential evidence of sympatric speciation of soil bacteria by comparison of metagenomics from two sharply contrasting abutting divergence rock and soil types (Senonian chalk and its rendzina soil, and abutting Pleistocene basalt rock and basalt soil). We identified several bacterial species with significant genetic differences in the same species between the two soil types and ecologies. We show that the bacterial community composition has significantly diverged between the two soils; correspondingly, their functions were differentiated in order to adapt to the local ecological stresses. The ecologies, such as water availability and pH value, shaped the adaptation and speciation of soil bacteria revealed by the clear-cut genetic divergence. Furthermore, by a novel analysis scheme of riboswitches, we highlight significant differences in structured non-coding RNAs between the soil bacteria from two divergence soil types, which could be an important driver for functional adaptation. Our study provides new insight into the evolutionary divergence and incipient sympatric speciation of soil bacteria under microclimatic ecological differences.
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http://dx.doi.org/10.3390/biology11081110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331176PMC
July 2022

Ferroptosis Associates With Diagnosis and Prognosis by Promoting Antitumor Immune Response in Melanoma.

Front Cell Dev Biol 2022 8;10:915198. Epub 2022 Jul 8.

Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Immunotherapy has greatly improved the clinical benefits of cancer treatment, especially in melanoma. Ferroptosis is a novel mechanism of cell death which relates to immunity. This study aimed at understanding the potential link between ferroptosis and cancer immunocompetent in melanoma using multiple bioinformatics analyses. By the WGCNA assay, we first constructed a key module-gene of ferroptosis, which was strongly correlated with the diagnosis, prognosis, and infiltration of immune cells in melanoma. The elevated module-gene could effectively distinguish melanoma from normal tissues and acted as a good prognostic marker. The module-gene of ferroptosis was positively correlated with the infiltration of immune cells. In particular, the module was positively correlated with the expression of PD-L1 and sensitively increased after effective anti-PD-1 treatment. Furthermore, the differential expression of the module-gene between normal and tumor tissues was observed in pan-cancer. The similarity correlations of the module-gene with infiltration of immune cells and the expressions of PD-L1 were confirmed in the pan-cancer level. Our study demonstrated that the key module-gene of ferroptosis was closely related with diagnosis, prognosis, and anti-immune response in melanoma, as well as in pan-cancer.
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http://dx.doi.org/10.3389/fcell.2022.915198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304890PMC
July 2022

Retrospective Study of Aging and Sex-Specific Risk Factors of COVID-19 with Hypertension in China.

Cardiovasc Ther 2022 28;2022:5978314. Epub 2022 Jun 28.

School of Life and Health Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Background: Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients.

Methods: We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups.

Results: Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0-57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23-1.05; = 0.043) and triglycerides (OR: 1.173, 95% CI: 0.049-1.617; = 0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein.

Conclusions: Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.
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http://dx.doi.org/10.1155/2022/5978314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240958PMC
July 2022

Systematic review of mental health symptom changes by sex or gender in early-COVID-19 compared to pre-pandemic.

Sci Rep 2022 Jul 6;12(1):11417. Epub 2022 Jul 6.

Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Ste-Catherine, Pavilion H4.83, Montréal, QC, H3T 1E2, Canada.

Women and gender-diverse individuals have faced disproportionate socioeconomic burden during COVID-19. There have been reports of greater negative mental health changes compared to men based on cross-sectional research that has not accounted for pre-COVID-19 differences. We compared mental health changes from pre-COVID-19 to during COVID-19 by sex or gender. MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), EMBASE (Ovid), Web of Science Core Collection: Citation Indexes, China National Knowledge Infrastructure, Wanfang, medRxiv (preprints), and Open Science Framework Preprints (preprint server aggregator) were searched to August 30, 2021. Eligible studies included mental health symptom change data by sex or gender. 12 studies (10 unique cohorts) were included, all of which reported dichotomized sex or gender data. 9 cohorts reported results from March to June 2020, and 2 of these also reported on September or November to December 2020. One cohort included data pre-November 2020 data but did not provide dates. Continuous symptom change differences were not statistically significant for depression (standardized mean difference [SMD] = 0.12, 95% CI -0.09-0.33; 4 studies, 4,475 participants; I = 69.0%) and stress (SMD = - 0.10, 95% CI -0.21-0.01; 4 studies, 1,533 participants; I = 0.0%), but anxiety (SMD = 0.15, 95% CI 0.07-0.22; 4 studies, 4,344 participants; I = 3.0%) and general mental health (SMD = 0.15, 95% CI 0.12-0.18; 3 studies, 15,692 participants; I = 0.0%) worsened more among females/women than males/men. There were no significant differences in changes in proportions above cut-offs: anxiety (difference = - 0.05, 95% CI - 0.20-0.11; 1 study, 217 participants), depression (difference = 0.12, 95% CI -0.03-0.28; 1 study, 217 participants), general mental health (difference = - 0.03, 95% CI - 0.09-0.04; 3 studies, 18,985 participants; I = 94.0%), stress (difference = 0.04, 95% CI - 0.10-0.17; 1 study, 217 participants). Mental health outcomes did not differ or were worse by small amounts among women than men during early COVID-19.
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http://dx.doi.org/10.1038/s41598-022-14746-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258011PMC
July 2022

The Traditional Mongolian Medicine Qiqirigan-8 Effects on Lipid Metabolism and Inflammation in Obesity: Pharmacodynamic Evaluation and Relevant Metabolites.

Front Pharmacol 2022 15;13:863532. Epub 2022 Jun 15.

School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China.

Traditional Mongolian Medicine Qiqirigan-8 (MMQ-8) is a Chinese botanical drug with effective pharmacological properties in obesity. However, the pharmacological mechanism of MMQ-8 remains unclear. This study aimed to determine the active metabolites of MMQ-8 and its therapeutic effects on lipid metabolism and inflammation. The active metabolites of MMQ-8 were identified by ultrahigh-performance liquid chromatograph Q extractive mass spectrometry (UHPLC-QE-MS) assay and network analysis. An obesity rat model induced by high-fat diet was used in the study. Serum levels of lipids and inflammatory factors were detected using biochemical analysis and enzyme-linked immunosorbent assay (ELISA). Pathological analysis of liver tissues and arteries was conducted with hematoxylin and eosin (H&E) staining and immunohistochemistry. Protein expression of the tumor necrosis factor (TNF) signaling pathway was investigated by Western-blot. Simultaneously, bone marrow cells were used for RNA sequencing and relevant results were validated by cell culture and quantitative real-time polymerase chain reaction (RT-qPCR). We identified 69 active metabolites and 551 target genes of MMQ-8. Of these, there are 65 active metabolites and 225 target genes closely related to obesity and inflammation. , we observed that MMQ-8 had general decreasing effects on body weight, white adipose tissue weight, and serum lipids. MMQ-8 treatment notably decreased the liver function markers and hepatic steatosis, and significantly decreased inflammation. In serum, it notably decreased TNF-α, interleukin (IL)-6, and inducible nitric oxide synthase (INOS), while elevating IL-10 levels. MMQ-8 treatment also significantly inhibited proteins phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα), mitogen-activated protein kinase (p38), extracellular regulated kinase 1/2(ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and decreased vascular endothelium damage and macrophage infiltration and polarization to M1. These findings coincide with the RNA-sequencing data of bone marrow cells and results of experiments. We determined the pharmacological actions and relevant metabolites of MMQ-8 in obesity for the first time. Our study revealed MMQ-8 can optimize lipid metabolism and reduce chronic inflammation in obesity. However, more in-depth research is needed, for example, to understand the principle of compound compatibility and the inhibition effects on hepatic steatosis, T cell differentiation, and inflammatory signal transduction.
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http://dx.doi.org/10.3389/fphar.2022.863532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240606PMC
June 2022

A Self-amplifying ROS-sensitive prodrug-based nanodecoy for circumventing immune resistance in chemotherapy-sensitized immunotherapy.

Acta Biomater 2022 Jun 25. Epub 2022 Jun 25.

School of Pharmacy, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang, 110016, P.R. China. Electronic address:

Circumventing immune resistance and boosting immune response is the ultimate goal of cancer immunotherapy. Herein, we reported a tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle for specifically inducing immunogenic cell death (ICD) in combination with TAM depletion. A versatile ROS-cleavable camptothecin (CPT) prodrug (DCC) was synthesized through a thioacetal linker between CPT and the ROS generator cinnamaldehyde (CA), which could self-assemble into a uniform prodrug nanoparticle to realize a positive feedback loop of "ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation." This DCC was further modified with the TAM membrane (abbreviated as [email protected]), which could not only target both primary tumors and lung metastasis nodules through VCAM-1/αβ integrin interaction but also absorb CSF-1 secreted by tumor cells to disturb the interaction between TAMs and cancer cells. Our nanodecoy could effectively induce ICD cascade and deplete TAMs for priming tumor-specific effector T cell infiltration for antitumor immune response activation, which represents a versatile approach for cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle was fabricated for the first time. This ROS-cleavable camptothecin (CPT)/cinnamaldehyde (CA) prodrug (DCC) could self-assemble into a uniform nanoparticle to realize the positive feedback loop of "ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation." After TAM membrane coating, this system ([email protected]) could not only target both primary tumors and lung metastatic nodules but also scavenge CSF-1 secreted by tumor cells for TAM depletion for sufficient chemotherapy-sensitized immunotherapy.
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http://dx.doi.org/10.1016/j.actbio.2022.06.035DOI Listing
June 2022

Water quality evaluation and ecological-health risk assessment on trace elements in surface water of the northeastern Qinghai-Tibet Plateau.

Ecotoxicol Environ Saf 2022 Aug 15;241:113775. Epub 2022 Jun 15.

State Key Laboratory of Marine Geology, Tongji University, Shanghai 200092, China.

The Qinghai-Tibet Plateau is a unique area with water sources for approximately 40 % of the population in the world. Water resources and water quality are closely associated with ecological security and human health. Fifty-one trace elements in surface water samples (n = 40) were measured, and water quality, health and ecological risks were assessed. Trace elements showed significant variations in different surface water bodies in the study area. Concentrations of minor elements were relatively high in saline and salt lakes while those of REEs varied from 0.05 to 33.62 μg/L with an average value of 3.80 μg/L. The Nemerow pollution index (NP) values of trace elements ranged from 0.08 to 3.48, with an average value of 0.36 in rivers, fresh lakes and reservoir water samples; The heavy metal pollution index (HPI) values ranged from 3.70 to 21.18, indicating that most samples were within the critical limit; The heavy metal evaluation index (HEI) values and degree of contamination (DC) values indicated a free pollution status. The water quality index (WQI) values showed that 96 % of the samples belonged to excellent status in rivers, fresh lakes and reservoir water samples. More attention should be given to the Cr, Zn and Hg in the study area according to potential ecological risk assessment. Hazard quotients for residential children in 30 sites exceed 1.0 with maximal value of 10.97, suggesting the high non-carcinogenic risks for children in the study area. U, Zr and Cr for the ingestion pathway, Cr and U for the dermal pathway were primary contributors to the total health risk. Carcinogenic risk values of trace elements for residential and recreational receptors were in the range of 3.20 × 10-7.38 × 10 and 8.62 × 10-3.63 × 10, respectively. The carcinogenic risk values of Cr in surface water were higher than the target risk of 1 × 10, while the carcinogenic risk values of As were below the target risk. The results of this study provided information on trace elements for human health protection and water management in the northeastern Qinghai-Tibet Plateau.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113775DOI Listing
August 2022

Ethnicity evaluation of ferric pyrophosphate citrate among Asian and Non-Asian populations: a population pharmacokinetics analysis.

Eur J Clin Pharmacol 2022 Jun 17. Epub 2022 Jun 17.

Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Purpose: To evaluate the potential ethnic differences of ferric pyrophosphate citrate (FPC, Triferic) in healthy subjects and patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) and identify covariates that may influence pharmacokinetics (PK) of FPC.

Methods: Data were collected from 2 Asian and 4 non-Asian clinical studies involving healthy subjects and CKD-5HD patients. Three population PK models were developed: M1 for intravenous (IV) administration of FPC in healthy subjects; M2 for dialysate administration of FPC in CKD-5HD patients; M3 for pre-dialyzer administration of FPC in CKD-5HD patients. All the models were fitted to concentration versus time data of FPC using the nonlinear mixed effect approach with the NONMEM program. All statistical analyses were performed using SAS version 9.4.

Results: In total, 26 Asians and 65 non-Asians were included in the final model analysis database. Forty healthy subjects were administered FPC via intravenous (IV) route and 51 patients with CKD-5HD via dialysate (N = 50) and pre-dialyzer blood circuit administration (N = 51). The PK parameters of FPC IV were similar. The population PK model showed good parameter precision and reliability as shown by model evaluation, and no relevant influence of ethnicity on PK parameters was observed. In healthy subjects, the maximum observed plasma concentration (C) and area under the plasma concentration-time curve (AUC) decreased with increase in lean body mass (LBM) and the average serum total iron at 6 h before the baseline period (Fe), whereas, in both patient populations, C and AUC decreased with increase in LBM and decrease in Fe. Other factors such as gender, age, Fe, and ethnicity had no influence on PK exposures in patients. The influence of LBM on PK exposures in patients was smaller than that in healthy subjects (ratio of AUC for the 5th [68 kg] and 95th [45 kg] patient's LBM was almost 1). The influence of Fe and LBM on PK exposures was < 50%.

Conclusion: The population pharmacokinetics model successfully described the PK parameters of FPC in healthy subjects and CKD-5HD patients and were comparable between Asian and non-Asian populations.
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http://dx.doi.org/10.1007/s00228-022-03328-9DOI Listing
June 2022

Combination of resveratrol and luteolin ameliorates α-naphthylisothiocyanate-induced cholestasis by regulating the bile acid homeostasis and suppressing oxidative stress.

Food Funct 2022 Jul 4;13(13):7098-7111. Epub 2022 Jul 4.

Department of Pharmaceutical Analysis, Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.

Cholestasis is a common liver injury without any effective therapeutic drugs so far. Resveratrol (RES) and luteolin (LUT) are natural polyphenols that exert protective effects on multiple liver injuries. Coadministration of RES and LUT could significantly improve the bioavailability of LUT and increase the systemic exposure to RES, and the combined treatment could also benefit from their multi-component and multi-target characteristics. Our current aim is to study the protective effects of coadministration of RES and LUT on α-naphthylisothiocyanate (ANIT)-induced cholestasis. Serum biochemical indices and liver histopathology in rats indicated that coadministration of RES and LUT could improve liver function by suppressing oxidative stress. Dysregulated bile acid (BA) homeostasis is a significant pathological feature of cholestasis, which was determined to explore the potential biomarkers and to clarify the protection mechanism of coadministration of RES and LUT. The levels of cholic acid, chenodeoxycholic acid, taurine conjugates and glycine conjugates, and the ratios of taurine conjugates to their free forms could be used as diagnosis indicators for cholestasis in rats. Furthermore, the coadministration of RES and LUT could restore the BA levels and exert better protective effects than administration alone. This study suggested that the coadministration of RES and LUT could protect against ANIT-induced cholestasis and the mechanism was closely related to regulating BA homeostasis and suppressing oxidative stress.
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http://dx.doi.org/10.1039/d2fo00521bDOI Listing
July 2022

A phenolic based tumor-permeated nano-framework for immunogenic cell death induction combined with PD-L1 immune checkpoint blockade.

Biomater Sci 2022 Jul 12;10(14):3808-3822. Epub 2022 Jul 12.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, P.R. China.

A critical obstacle for programmed death ligand 1 (PD-L1) immune checkpoint blockade immunotherapy is the insufficient T cell infiltration and low immunogenicity of tumor cells. Improving tumor immunogenicity through immunogenic cell death (ICD) can make tumor sensitive to PD-L1 checkpoint blockade immunotherapy. Herein, a phenolic based tumor-permeated nano-framework (EGPt-NF) was fabricated by cross-linking phenylboric acid modified platinum nanoparticles (PBA-Pt, ICD inducer) and epigallocatechin-3--gallate (EGCG, PD-L1 inhibitor) pH-reversible borate ester. In particular, PBA-Pt could not only induce ICD cascade but also relieve tumor hypoxia. Consequently, EGPt-NF could effectively promote dendritic cell maturation and downregulate PD-L1 expression in tumor cells. Furthermore, EGPt-NF could also relieve tumor hypoxia to facilitate cytotoxic T lymphocyte infiltration and IFN-γ secretion. The synergistic effect of EGPt-NF could effectively improve tumor immunogenicity and amplify the therapeutic outcomes of cancer immunotherapy, resulting in a strong antitumor immune response in primary tumor and metastasis inhibition. Our simple approach expands the application of platinum-based drug delivery systems for cancer immunotherapy.
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http://dx.doi.org/10.1039/d2bm00455kDOI Listing
July 2022

Chinese Herbal Medicine for Primary Liver Cancer Therapy: Perspectives and Challenges.

Front Pharmacol 2022 5;13:889799. Epub 2022 May 5.

Graduate School, Beijing University of Chinese Medicine, Beijing, China.

Primary liver cancer (PLC) is one of the most common solid malignancies. However, PLC drug development has been slow, and first-line treatments are still needed; thus, studies exploring and developing alternative strategies for effective PLC treatment are urgently needed. Chinese herbal medicine (CHM) has long been applied in the clinic due to its advantages of low toxicity and targeting of multiple factors and pathways, and it has great potential for the development of novel natural drugs against PLC. This review aims to provide an update on the pharmacological mechanisms of Chinese patent medicines (CPMs) and the latest CHM-derived compounds for the treatment of PLC and relevant clinical evaluations. A systematic search of English literature databases, Chinese literature, the Clinical Trials Registry Platform, and the Chinese Clinical Trial Registry for studies of CHMs for PLC treatment was performed. In this review, we summarize the clinical trials and mechanisms of CPMs for PLC treatment that have entered the clinic with the approval of the Chinese medicine regulatory authority. These CPMs included Huaier granules, Ganfule granules, Fufang Banmao capsules, Jinlong capsules, Brucea oil emulsions, and compound kushen injections. We also summarize the latest , , and clinical studies of CHM-derived compounds against PLC: icaritin and ginsenoside Rg3. Dilemmas facing the development of CHMs, such as drug toxicity and low oral availability, and future developments are also discussed. This review provides a deeper the understanding of CHMs as PLC treatments and provides ideas for the development of new natural drugs against PLC.
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http://dx.doi.org/10.3389/fphar.2022.889799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117702PMC
May 2022

Safety and pharmacokinetic profile of pretomanid in healthy Chinese adults: Results of a phase I single dose escalation study.

Pulm Pharmacol Ther 2022 06 18;73-74:102132. Epub 2022 May 18.

Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Beijing, China. Electronic address:

We investigated the safety, tolerability and pharmacokinetic (PK) profile of pretomanid (formerly PA-824) in healthy Chinese volunteers. This was a single-center, double-blind, placebo-controlled, phase I dose escalation study, in which healthy volunteers were consecutively allocated to increasing pretomanid dose groups (50, 100, 200, 400, 600, 800, or 1000 mg) and randomized to receive pretomanid or matching placebo. The primary objective was to evaluate the safety, tolerability and PK profile of pretomanid. In total, 306 volunteers were screened, and 60 were assigned to treatment (pretomanid: n = 46, placebo: n = 14) of whom 83.3% were male, age ranged from 19 to 39 years and BMI ranged from 19.2 to 25.9 kg/m. At least one adverse event (AE) was reported by 67.4% of subjects assigned to pretomanid and 50.0% of those who received placebo, there were no serious AEs or AEs leading to withdrawal. Drug-related events that occurred in ≥5% of participants assigned to pretomanid were proteinuria (26.1%), insignificant microscopic hematuria (15.2%), conjugated hyperbilirubinemia (6.5%), hyperbilirubinemia (6.5%) and elevated uric acid (6.5%). No relationship between pretomanid dose and AEs was observed. In the PK analysis (n = 46), maximum pretomanid plasma concentration was reached in a median of 4 h in all dose groups except 800 mg (12 h) and the plasma half-life ranged from 20.2 to 25.2 h. No dose proportionality was observed for maximum plasma concentration, or area under the plasma concentration curve. In conclusion, single pretomanid doses from 50 to 1000 mg were well tolerated in healthy Chinese participants and the PK profile was generally consistent with findings in non-Chinese populations.
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http://dx.doi.org/10.1016/j.pupt.2022.102132DOI Listing
June 2022

Counterintuitive production of tumor-suppressive secretomes from Oct4- and c-Myc-overexpressing tumor cells and MSCs.

Theranostics 2022 28;12(7):3084-3103. Epub 2022 Mar 28.

Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.

Advanced breast cancer frequently metastasizes to bone, but inhibiting tumor progression in chemotherapy may occasionally enhance tumorigenesis. Here, we employed a counterintuitive approach of overexpressing Yamanaka factors (Oct4, c-Myc, Sox2, and Klf4) and examined a conditioned medium (CM)-based treatment option with induced tumor-suppressing cells (iTSCs). proliferation and migration assays were conducted using tumor cell lines derived from breast cancer, as well as prostate and pancreatic cancers, and osteosarcoma. The tumor-suppressing capability of iTSC-derived CM was evaluated using freshly isolated breast cancer tissues and a mouse model of mammary tumors and tumor-induced osteolysis. The regulatory mechanism was evaluated using Western blotting, immunoprecipitation, pull-down, gene overexpression, and RNA interference based on mass spectrometry-based proteomics data. The overexpression of Oct4 and c-Myc in tumor cells and MSCs, but not Sox2 or Klf4, generated anti-tumor CM, which suppressed the progression of mammary tumors and tumor-induced bone loss. Notably, CM downregulated histone demethylase, and PDL-1, a blocker of T-cell-based immune responses. Whole-genome proteomics predicted enolase 1 (Eno1), Hsp90ab1, Eef2, and vinculin as extracellular tumor suppressors. Specifically, CD44 was co-immunoprecipitated with Eno1 and the silencing of CD44 suppressed Eno1's anti-tumor action. The overexpression of Oct4 and c-Myc also generated secretomes that inhibited the development of bone-resorbing osteoclasts. In analogous to cell competition in which Myc-overexpressing cells in Drosophila and mouse embryos remove neighboring cells with a lower level of Myc, this study presented the possibility of eliminating tumor cells by the secretory proteomes derived from Myc/Oc4-overexpressing iTSCs.
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http://dx.doi.org/10.7150/thno.70549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065181PMC
May 2022

Effects of mental health interventions among people hospitalized with COVID-19 infection: A systematic review of randomized controlled trials.

Gen Hosp Psychiatry 2022 Jul-Aug;77:40-68. Epub 2022 Apr 9.

Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Psychology, McGill University, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada. Electronic address:

Objective: We evaluated the effects of mental health interventions among people hospitalized with COVID-19.

Methods: We conducted a systematic review and searched 9 databases (2 Chinese-language) from December 31, 2019 to June 28, 2021. Eligible randomized controlled trials assessed interventions among hospitalized COVID-19 patients that targeted mental health symptoms. Due to the poor quality of trials, we sought to verify accuracy of trial reports including results.

Results: We identified 47 randomized controlled trials from China (N = 42), Iran (N = 4) and Turkey (N = 1) of which 21 tested the efficacy of psychological interventions, 5 physical and breathing exercises, and 21 a combination of interventions. Trial information could only be verified for 3 trials of psychological interventions (cognitive behavioral, guided imagery, multicomponent online), and these were the only trials with low risk of bias on at least 4 of 7 domains. Results could not be pooled or interpreted with confidence due to the degree of poor reporting and trial quality, the frequency of what were deemed implausibly large effects, and heterogeneity.

Conclusion: Trials of interventions to address mental health in hospitalized COVID-19 patients, collectively, are not of sufficient quality to inform practice. Health care providers should refer to existing expert recommendations and standard hospital-based practices.

Registration: PROSPERO (CRD42020179703); registered on April 17, 2020.
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http://dx.doi.org/10.1016/j.genhosppsych.2022.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993417PMC
April 2022

Effects of seasons and parts on volatile N-nitrosamines and their exposure and risk assessment in raw chicken and duck meats.

J Food Sci Technol 2022 May 3;59(5):1831-1839. Epub 2021 Jul 3.

Department of Chemistry, College of Science, Beijing Forestry University, No. 35, Qinghua East Road, Haidian District, Beijing, 100083 People's Republic of China.

The N-nitrosamine (NA) concentrations and types in raw chicken and duck meats of different parts and seasons were estimated by headspace solid-phase micro-extraction with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The exposure level and hazard quotient of each detected volatile N-nitrosamine (VNA) were conducted. The selected chicken and duck samples were contaminated by VNAs to some extent. The major types and contents of VNAs in different parts of chicken and duck meats varied seasonally. For chicken samples, the order of the total VNA concentrations was as follows: autumn > spring > winter > summer. For duck samples, the order was changed as follows: winter > autumn > summer > spring (thigh samples) and autumn > spring > winter > summer (breast samples). The estimated exposure levels for adults caused by duck consumption were slightly higher than those by chickens, which was consistent with the tendency in 2-3 years old children. According to the linear regression correlation between the 10% benchmark dose limit (BMDL) and subtriplicate of median lethal dose (LD), BMDL values of each VNA were calculated. Due to this hypothesis, the risk assessments of each detected VNA and total VNAs posed by consuming chicken and duck meats in Tianjin, China were of low concern.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05195-1.
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http://dx.doi.org/10.1007/s13197-021-05195-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046479PMC
May 2022

Genomic insights into zokors' phylogeny and speciation in China.

Proc Natl Acad Sci U S A 2022 05 5;119(19):e2121819119. Epub 2022 May 5.

State Key Laboratory of Grassland Agro-Ecosystems, College of Ecology, Lanzhou University, Lanzhou 730000, China.

The phylogeny and speciation of subterranean zokors in China are unclear, as previous studies on morphology and limited molecular markers have generated conflicting results. This study unraveled the complex evolutionary history of eight zokor species in China based on de novo assembly at chromosome level and whole-genome sequencing of 23 populations. We found extensive phylogenetic discordances between nuclear and mitochondrial phylogenies, and different coalescent phylogenies, which could be explained by introgression and incomplete lineage sorting (ILS). The recent Qinghai-Tibet Plateau uplift (∼3.60 million y ago; Mya) drove Eospalax to speciate into clade A and clade B (∼3.22 Mya), and discordant phylogenies in this node were mainly attributed to introgression rather than ILS. Clade A rapidly diverged into three lineages due to geographical isolation and glaciation, while glaciation and C4 plant expansion contributed to the speciation of clade B. ILS contributed to the discordances of two rapidly radiated nodes rather than introgression. The effective population sizes (Ne’s) of all the species of Eospalax were affected by three glaciations. Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of all the species pairs. Positively selected genes putatively related to specific inhabitation adaptations were identified, such as heart development, neurogenesis, DNA repair, and immune response. Climate, geological tectonism, and C4 vegetation shaped the adaptation and speciation of zokors in China.
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http://dx.doi.org/10.1073/pnas.2121819119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171634PMC
May 2022

Prone Position in Treatment of Hypoxemia in Patients Who Underwent Type A Aortic Dissection Surgery.

Heart Surg Forum 2022 Apr 22;25(2):E300-E304. Epub 2022 Apr 22.

Department of Vascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.

Background: Postoperative hypoxemia is a high-risk complication after acute type A aortic dissection (TAAD) surgery. Prone position (PP) is an effective treatment for acute respiratory failure, which may improve the gas exchange of the injured lung and the patient's survival. PP is reported to improve the respiratory condition after cardiac surgery. However, limited data exist on the effect of PP in patients who underwent acute TAAD surgery.

Methods: We retrospectively analyzed the clinical outcomes of seven patients with severe hypoxemia who underwent PP after acute TAAD surgery. The results of arterial blood gas, chest X-ray, and survival were collected.

Results: Seven patients (3 female, mean age 48.3±11.7 years) were recruited in this study. All patients received total arch replacement and frozen elephant trunk implantation procedure. The PaO2 at day 1 after PP was higher than before PP (126.3±49.3 vs. 77.8±15.5 mmHg). The oxygenation index rose sharply from 83.0 (80.0, 87.0) to 188.3±56.5 at day 3 after PP. There was no significant difference in heart rate between before and after PP procedure. Chest X-ray showed the diffuse shadow was significantly improved after PP. All patients responded well to PP, and all patients were discharged except for one patient, who died perioperatively due to multiple organ failure.

Conclusions: PP is a safe and feasible option for severe hypoxemia patients after TAAD surgery.
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http://dx.doi.org/10.1532/hsf.4535DOI Listing
April 2022

Heat Shock Proteins and Ferroptosis.

Front Cell Dev Biol 2022 11;10:864635. Epub 2022 Apr 11.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

Ferroptosis is a new form of regulatory cell death named by Dixon in 2012, which is characterized by the accumulation of lipid peroxides and iron ions. Molecular chaperones are a class of evolutionarily conserved proteins in the cytoplasm. They recognize and bind incompletely folded or assembled proteins to help them fold, transport or prevent their aggregation, but they themselves do not participate in the formation of final products. As the largest number of molecular chaperones, heat shock proteins can be divided into five families: HSP110 (HSPH), HSP90 (HSPC), HSP70 (HSPA), HSP40 (DNAJ) and small heat shock proteins (HSPB). Different heat shock proteins play different roles in promoting or inhibiting ferroptosis in different diseases. It is known that ferroptosis is participated in tumors, nervous system diseases, renal injury and ischemia-reperfusion injury. However, there are few reviews about the relationship of heat shock proteins and ferroptosis. In this study, we systematically summarize the roles of heat shock proteins in the occurrence of ferroptosis, and predict the possible mechanisms of different families of heat shock proteins in the development of ferroptosis.
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http://dx.doi.org/10.3389/fcell.2022.864635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035830PMC
April 2022

Photocatalytic Chemical Crosslinking for Profiling RNA-Protein Interactions in Living Cells.

Angew Chem Int Ed Engl 2022 07 5;61(27):e202202008. Epub 2022 May 5.

College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing, 100871, China.

The dynamic interactions between RNAs and proteins play crucial roles in regulating diverse cellular processes. Proteome-wide characterization of these interactions in their native cellular context remains desirable but challenging. Herein, we developed a photocatalytic crosslinking (PhotoCAX) strategy coupled with mass spectrometry (PhotoCAX-MS) and RNA sequencing (PhotoCAX-seq) for the study of the composition and dynamics of protein-RNA interactions. By integrating the blue light-triggered photocatalyst with a dual-functional RNA-protein crosslinker (RP-linker) and the phase separation-based enrichment strategy, PhotoCAX-MS revealed a total of 2044 RBPs in human HEK293 cells. We further employed PhotoCAX to investigate the dynamic change of RBPome in macrophage cells upon LPS-stimulation, as well as the identification of RBPs interacting directly with the 5' untranslated regions of SARS-CoV-2 RNA.
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http://dx.doi.org/10.1002/anie.202202008DOI Listing
July 2022

The regulatory role of NAAG-mGluR3 signaling on cortical synaptic plasticity after hypoxic ischemia.

Cell Commun Signal 2022 04 20;20(1):55. Epub 2022 Apr 20.

Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, People's Republic of China.

Background: Synapses can adapt to changes in the intracerebral microenvironment by regulation of presynaptic neurotransmitter release and postsynaptic neurotransmitter receptor expression following hypoxic ischemia (HI) injury. The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) exerts a protective effect on neurons after HI and may be involved in maintaining the function of synaptic networks. In this study, we investigated the changes in the expression of NAAG, glutamic acid (Glu) and metabotropic glutamate receptors (mGluRs), as well as the dynamic regulation of neurotransmitters in the brain after HI, and assessed their effects on synaptic plasticity of the cerebral cortex.

Methods: Thirty-six Yorkshire newborn pigs (3-day-old, males, 1.0-1.5 kg) were selected and randomly divided into normal saline (NS) group (n = 18) and glutamate carboxypeptidase II inhibition group (n = 18), both groups were divided into control group, 0-6 h, 6-12 h, 12-24 h, 24-48 h and 48-72 h groups (all n = 3) according to different post-HI time. The content of Glu and NAAG after HI injury were detected by 1H-MRS scanning, immunofluorescence staining of mGluRs, synaptophysin (syph) along with postsynaptic density protein-95 (PSD95) and transmission electron microscopy were performed. ANOVA, Tukey and LSD test were used to compare the differences in metabolite and protein expression levels among subgroups. Correlation analysis was performed using Pearson analysis with a significance level of α = 0.05.

Results: We observed that the NAAG and mGluR3 expression levels in the brain increased and then decreased after HI and was significantly higher in the 12-24 h (P < 0.05, Tukey test). There was a significant positive correlation between Glu content and the expression of mGluR1/mGluR5 after HI with r = 0.521 (P = 0.027) and r = 0.477 (P = 0.045), respectively. NAAG content was significantly and positively correlated with the level of mGluR3 expression (r = 0.472, P = 0.048). When hydrolysis of NAAG was inhibited, the expression of synaptic protein PSD95 and syph decreased significantly.

Conclusions: After 12-24 h of HI injury, there was a one-time elevation in NAAG levels, which was consistent with the corresponding mGluR3 receptor expression trend; the NAAG maintains cortical synaptic plasticity and neurotransmitter homeostasis by inhibiting presynaptic glutamate vesicle release, regulating postsynaptic density proteins and postsynaptic receptor expression after pathway activation. Video abstract.
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http://dx.doi.org/10.1186/s12964-022-00866-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022257PMC
April 2022

Selective strategies for antibacterial regulation of nanomaterials.

RSC Adv 2022 Feb 9;12(8):4852-4864. Epub 2022 Feb 9.

College of Food and Bioengineering, Henan University of Science and Technology Luoyang Henan 471023 China

Recalcitrant bacterial infection, as a worldwide challenge, causes large problems for human health and is attracting great attention. The excessive antibiotic-dependent treatment of infections is prone to induce antibiotic resistance. A variety of unique nanomaterials provide an excellent toolkit for killing bacteria and preventing drug resistance. It is of great importance to summarize the design rules of nanomaterials for inhibiting the growth of pathogenic bacteria. We completed a review involving the strategies for regulating antibacterial nanomaterials. First, we discuss the antibacterial manipulation of nanomaterials, including the interaction between the nanomaterial and the bacteria, the damage of the bacterial structure, and the inactivation of biomolecules. Next, we identify six main factors for controlling the antibacterial activity of nanomaterials, including their element composition, size dimensions, surface charge, surface topography, shape selection and modification density. Every factor possesses a preferable standard for maximizing antibacterial activity, providing universal rules for antibacterial regulation of nanomaterials. We hope this comprehensive review will help researchers to precisely design and synthesize nanomaterials, developing intelligent antibacterial agents to address bacterial infections.
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http://dx.doi.org/10.1039/d1ra08996jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981418PMC
February 2022

Pharmacokinetics and Safety of Ferric Pyrophosphate Citrate in Chinese Subjects with and without Hemodialysis-Dependent Stage 5 Chronic Kidney Disease.

Drugs R D 2022 Jun 5;22(2):119-129. Epub 2022 Apr 5.

Department of Nephrology, Peking University People's Hospital, Unit 10C in Ward Building, 11 Xizhimennan Street, Xicheng District, Beijing, 100044, China.

Background And Objective: Anemia caused by iron depletion is common in patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) patients. To maintain the iron levels, external administration of iron is essential. Ferric pyrophosphate citrate (FPC) is a novel, water-soluble complex iron salt. The present study was conducted to evaluate the pharmacokinetic (PK) parameters and safety of FPC in adult healthy Chinese subjects and patients with CKD-5HD.

Methods: Two open-label, single-center studies were conducted in healthy subjects and patients with CKD-5HD. Healthy subjects received a single intravenous dose of 6.5 mg FPC solution, while CKD-5HD patients were randomized to two different sequences of FPC administration at two sequential hemodialysis (HD) treatments (dose 1 and dose 2). Patients received 27.2 mg of FPC at a dialysate concentration of 95 μg/L for 4 h or a single 6.5 mg dose of FPC administered intravenously via the pre-dialyzer blood circuit. The primary objective was to determine the PK parameters of total serum iron (Fe), while the secondary objective was the safety of the FPC solution. PK parameters were calculated using Phoenix WinNonlin 8.1 and other parameters were analyzed using SAS 9.4 software. Comparison between HD dose 2 and HD dose 1 was performed using the Wilcoxon rank-sum test and analysis of variance (ANOVA).

Results: A total of 14 healthy subjects with a mean age of 30.8 ± 5.92 years and 12 HD patients with a mean age of 54.3 ± 16.47 years were included. In healthy subjects, the peak serum concentration was reached at the end of infusion of FPC, with an adjusted mean maximum concentration (C) of 33.46 ± 4.83 μmol/L at a mean time to reach C (T) of 4.09 ± 0.19 h. In patients with CKD-5HD, the adjusted mean C of HD dose 2 was 25.37 ± 4.30 μmol/L at a T of 3.09 ± 0.32 h, whereas the C of HD dose 1 was 24.59 ± 4.77 μmol/L at a T of 3.96 ± 0.26 h. The Fe concentration-time curves were observed to be similar for both administration methods (HD doses 1 and 2), while the PK parameters differed significantly for T (p = 0.001; baseline correction) and area under the concentration-time curve from time zero to time t (AUC) [p = 0.031 for cycle variance; without baseline correction] between HD doses 1 and 2. The geometric mean ratios (HD dose 1/HD dose 2) for C and AUC were within the 85-125% range (C 96.56%; AUC 96.07%). A total of three and two incidences of adverse events were reported in healthy subjects and patients with CKD-5HD, respectively.

Conclusion: FPC showed a good PK and safety profile and hence can be used as maintenance therapy for patients with CKD-5HD by choosing a better method of administration based on clinical feasibility and requirement.

Clinical Trial Registration: CTR20181113 and CTR20181119.
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http://dx.doi.org/10.1007/s40268-022-00384-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167373PMC
June 2022

Antagonistic effects of selenium on lead-induced oxidative stress and apoptosis of Leydig cells in sheep.

Theriogenology 2022 Jun 25;185:43-49. Epub 2022 Mar 25.

College of Animal Science, Shanxi Agricultural University, Taigu, 030801, PR China; Laboratory of Animal Reproductive Biotechnology, Shanxi Agricultural University, Taigu, 030801, PR China.

The objective of this study was to investigate the antagonistic effects of selenium (Se) on lead (Pb)-induced oxidative stress and apoptosis of sheep Leydig cells and its underlying mechanism. Leydig cells collected from 8-month-old sheep were treated with Pb (40 μmol/L) and/or Se (2 μmol/L), respectively. CCK-8 assay was used to detect cell proliferation and apoptosis after cultured for 48 h. The abundances of pro-apoptosis (BAX, CASPASE 3 and CASPASE 8) and NRF2-related (NRF2, HO-1, NQO1 and γ-GCS) genes were detected by real-time PCR and western blot analysis, respectively. The results showed that the highest cell viability was observed in the Se group. Compared with the control group, Pb treatment led to the higher ROS level and greater abundances of BAX, CASPASE 3 and CASPASE 8 mRNA transcripts. Treatment with Pb + Se resulted in an increased (P < 0.05) abundances of NRF2, HO-1, NQO1 and γ-GCS mRNA transcripts and proteins. Compared with the Pb group, the Se + Pb treatment dramatically decreased (P < 0.05) the ROS level and relative abundances of pro-apoptosis genes. The greater (P < 0.05) abundances of pro-apoptosis and NRF2-related mRNA transcripts and proteins were also obtained in the Se + Pb group. The abundances of BAX, CASPASE 3 and CASPASE 8 genes in the Se group were greater (P < 0.05) than in the Se group. Compared with the corresponding groups without ML385, treatment with ML385 decreased (P < 0.05) cell viability and the relative abundances of pro-apoptosis and NRF2-related genes. These results indicate that Pb-induced oxidative stress can inhibit the viability of Leydig cells by modulating pro-apoptosis gene expression. NRF2 pathway could be involved in the antagonistic effect of Se on Pb-induced apoptosis of Leydig cells in sheep. This study is expected to provide some experimental evidences for Se treatment of Pb-induced reproductive disorders.
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http://dx.doi.org/10.1016/j.theriogenology.2022.03.023DOI Listing
June 2022

A Task Decomposing and Cell Comparing Method for Cervical Lesion Cell Detection.

IEEE Trans Med Imaging 2022 Mar 29;PP. Epub 2022 Mar 29.

Automatic detection of cervical lesion cells or cell clumps using cervical cytology images is critical to computer-aided diagnosis (CAD) for accurate, objective, and efficient cervical cancer screening. Recently, many methods based on modern object detectors were proposed and showed great potential for automatic cervical lesion detection. Although effective, several issues still hinder further performance improvement of such known methods, such as large appearance variances between single-cell and multi-cell lesion regions, neglecting normal cells, and visual similarity among abnormal cells. To tackle these issues, we propose a new task decomposing and cell comparing network, called TDCC-Net, for cervical lesion cell detection. Specifically, our task decomposing scheme decomposes the original detection task into two subtasks and models them separately, which aims to learn more efficient and useful feature representations for specific cell structures and then improve the detection performance of the original task. Our cell comparing scheme imitates clinical diagnosis of experts and performs cell comparison with a dynamic comparing module (normal-abnormal cells comparing) and an instance contrastive loss (abnormal-abnormal cells comparing). Comprehensive experiments on a large cervical cytology image dataset confirm the superiority of our method over state-of-the-art methods.
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http://dx.doi.org/10.1109/TMI.2022.3163171DOI Listing
March 2022

Sympatric speciation of the spiny mouse from Evolution Canyon in Israel substantiated genomically and methylomically.

Proc Natl Acad Sci U S A 2022 03 23;119(13):e2121822119. Epub 2022 Mar 23.

State Key Laboratory of Grassland Agro-ecosystems, Collage of Ecology, Lanzhou University, Lanzhou 730000, China.

SignificanceWhether sympatric speciation (SS) is rare or common is still debated. Two populations of the spiny mouse, , from Evolution Canyon I (EC I) in Israel have been depicted earlier as speciating sympatrically by molecular markers and transcriptome. Here, we investigated SS both genomically and methylomically, demonstrating that the opposite populations of spiny mice are sister taxa and split from the common ancestor around 20,000 years ago without an allopatric history. Mate choice, olfactory receptors, and speciation genes contributed to prezygotic/postzygotic reproductive isolation. The two populations showed different methylation patterns, facilitating adaptation to their local environment. They cope with abiotic and biotic stresses, due to high solar interslope radiation differences. We conclude that our new genomic and methylomic data substantiated SS.
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http://dx.doi.org/10.1073/pnas.2121822119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060526PMC
March 2022

The Impact of Entrepreneurship Competitions on Entrepreneurial Competence of Chinese College Students.

Front Psychol 2022 28;13:784225. Epub 2022 Feb 28.

Institute of China Innovation and Entrepreneurship Education, Wenzhou Medical University, Wenzhou, China.

Entrepreneurship competitions are an important way to implement entrepreneurship education in universities and the main way for many students improve their entrepreneurial competence. To clarify the mechanism of the role of entrepreneurship competition on the entrepreneurial competence of university students, based on data from a sample of 170,764 university students from 31 provinces in China, this study constructs a moderated mediation model that focuses on the mediating role of entrepreneurial spirit (ES) in entrepreneurial competition (ECompetition) and entrepreneurial competence (ECompetence) and the moderating role of entrepreneurial practice (EP). The results showed that ECompetition found to have a significant positive predictive effect on ECompetence. ES plays a mediating role in the relationship between ECompetition and competence. The direct predictive effect of ECompetition on ECompetence and the mediating effect of ES on their relationship is moderated by EP. The results provide a new perspective on the impact of entrepreneurship competition on college students' entrepreneurial competence and expands the experiential learning theory in entrepreneurship education.
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http://dx.doi.org/10.3389/fpsyg.2022.784225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918648PMC
February 2022
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