Publications by authors named "Li Liu"

6,542 Publications

  • Page 1 of 1

First-in-human phase I study of TQ-B3139 (CT-711) in advanced non-small cell lung cancer patients with ALK and ROS1 rearrangements.

Eur J Cancer 2022 Aug 5;173:238-249. Epub 2022 Aug 5.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address:

Background: TQ-B3139 is a novel ALK tyrosine kinase inhibitor (TKI) against a broad range of ALK mutations. The aim of this first-in-human phase I trial was to investigate the safety, tolerability, pharmacokinetics, and clinical efficacy of TQ-B3139 in ALK or ROS1 positive advanced NSCLC patients.

Methods: Following a 3 + 3 design, patients received escalating daily dose of TQ-B3139 (50-800 mg) continuously in 28-day cycles. Expansion stage started at dose of 200 mg twice daily (BID). The primary objectives were the safety, dose-limited toxicities (DLT) and recommended phase II dose (RP2D); secondary objectives included pharmacokinetics and antitumor activity. Non-obligatory tumor samples at baseline were collected and sequenced.

Results: The study enrolled 63 patients. Fifty-nine (93.4%) patients experienced treatment-related adverse events (TRAEs), mostly grade 1-2 vomiting (79.3%), diarrhea (76.1%) or nausea (68.2%). 1 (1/6) DLT occurred at 600 mg BID and 1 (1/3) at 800 mg BID. Based on safety and pharmacokinetics data, the RP2D was selected as 600 mg BID. At a dose level ≥200 mg BID, the overall response rate (ORR) was 76.7% (33/43), and the median progression free survival (mPFS) was 25.2 months (95%CI 11.9-NR) for TKI-naive patients. For TKI-treated patients, the ORR was 37.5% (6/16), and the mPFS was 5.4 months (95%CI 3.6-9.1). The ORR was 66.7% (2/3) in patients with ROS1 fusion at dose level ≥200 mg BID. In patients with measurable brain metastases, the intracranial ORR was 70% (7/10), with median intracranial PFS of 15.9 months. In TKI-treated patients, variant 3 and TP53 alteration were associated with poor PFS.

Conclusions: TQ-B3139 was well-tolerated and exhibited promising anti-tumor activities in patients with ALK and ROS1 positive advanced NSCLC.

Clinical Trial Number: NCT03099330.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2022.06.037DOI Listing
August 2022

Population pharmacokinetics and model-informed precision dosing of lamivudine in Chinese HIV-infected patients with mild and moderate impaired renal function.

Expert Rev Clin Pharmacol 2022 May 6;15(5):647-655. Epub 2022 Jun 6.

Department of Clinical Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background: Lamivudine is a first-line medication used for human immunodeficiency virus (HIV) treatment. To date, the population pharmacokinetics of lamivudine in Chinese HIV-infected adults have not been assessed. This study aimed to develop a population pharmacokinetic model for oral lamivudine in Chinese HIV-infected adults and to determine the optimal lamivudine dosage regimens.

Research Design And Methods: A total of 1113 samples, from 828 Chinese HIV-infected patients treated with lamivudine 300 mg every 24 hours, were pooled from two open-label, prospective clinical trials. A population pharmacokinetics analysis was performed using a nonlinear mixed-effects modeling method. A Monte Carlo simulation was conducted to optimize lamivudine dosing.

Results: A two-compartment model adequately described the population pharmacokinetics of lamivudine. The typical population estimate for apparent clearance was 28.3 L/h. Creatinine clearance was identified as a significant factor influencing apparent clearance. According to the Monte Carlo simulation, patients with creatinine clearance between 50 and 70 mL/min should receive lamivudine 200 mg every 24 h or 300 mg every 36 h, to achieve optimal lamivudine exposure.

Conclusions: No obvious ethnic differences were observed in lamivudine pharmacokinetics between Chinese and Caucasian populations. Additionally, a model-informed dosage regimen is recommended for patients with impaired renal function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17512433.2022.2078306DOI Listing
May 2022

Cytotoxic indole alkaloids and polyketides produced by a marine-derived fungus DS720.

Front Microbiol 2022 22;13:959754. Epub 2022 Jul 22.

Department of Thyroid and Breast Surgery, Northern Jiangsu People's Hospital, Yangzhou, China.

Marine-derived microorganisms possess the unique metabolic pathways to produce structurally novel secondary metabolites with potent biological activities. In this study, bioactivity-guided isolation of the marine deep-sea-derived fungus DS720 led to the characterization of four indole alkaloids (compounds -) and four polyketides (compounds -), such as two new indoles, flavonoids A () and B () with a C-6 reversed prenylation, and a new azaphilone, flaviazaphilone A (). Their chemical structures were unambiguously established by an extensive interpretation of spectroscopic data, such as 1D/2D NMR and HRESIMS data. The absolute configurations of the new compound were solved by comparing the experimental and calculated Electronic Circular Dichroism (ECD) spectra. Since sufficient amount of flavonoids A () was obtained, was subjected to a large-scale cytotoxic activity screening against 20 different human tumor cell lines. The results revealed that showed broad-spectrum cytotoxicities against HeLa, 5637, CAL-62, PATU8988T, A-375, and A-673 cell lines, with the inhibition rates of more than 90%. This study indicated that the newly discovered indole alkaloid may possess certain potential for the development of lead compounds in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2022.959754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355579PMC
July 2022

Index of multiple deprivation contributed to common psychiatric disorders: a systematic review and comprehensive analysis.

Neurosci Biobehav Rev 2022 Aug 1:104806. Epub 2022 Aug 1.

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, P. R. China. Electronic address:

Background: Limited studies have been conducted to explore the interaction effects of social environmental and genetic factors on the risks of common psychiatric disorders.

Methods: 56,613-106,695 individuals were collected from the UK Biobank cohort. Logistic or liner regression models were first used to evaluate the associations of index of multiple deprivation (IMD) with bipolar disorder (BD), depression and anxiety in UK Biobank cohort. Then, for the significant IMD associated with BD, depression and anxiety, genome-wide gene-environment interaction study (GWEIS) was performed by PLINK 2.0.

Result: Totally, the higher levels of IMD were significantly associated with higher risks of BD, depression and anxiety. For BD, GWEIS identified multiple significant SNPs interacting with IMD, such as rs75182167 for income and rs111841503 for education. For depression and anxiety, GWEIS found significant SNPs interacting with income and education, such as rs147013419 for income and rs142366753 for education.

Conclusion: Social environmental deprivations contributed to the risks of psychiatric disorders. Besides, we reported multiple candidate genetic loci interacting with IMD, providing novel insights into the biological mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2022.104806DOI Listing
August 2022

Grading detection of "Red Fuji" apple in Luochuan based on machine vision and near-infrared spectroscopy.

PLoS One 2022 4;17(8):e0271352. Epub 2022 Aug 4.

College of Mechanical and Electronic Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China.

A quality detection system for the "Red Fuji" apple in Luochuan was designed for automatic grading. According to the Chinese national standard, the grading principles of apple appearance quality and Brix detection were determined. Based on machine vision and image processing, the classifier models of apple defect, contour, and size were constructed. And then, the grading thresholds were set to detect the defective pixel ratio t, aspect ratio λ, and the cross-sectional diameter Wp in the image of the apple. Spectral information of apples in the wavelength range of 400 nm~1000 nm was collected and the multiple scattering correction (MSC) and standard normal variable (SNV) transformation methods were used to preprocess spectral reflectance data. The competitive adaptive reweighted sampling (CARS) algorithm and the successive projections algorithm (SPA) were used to extract characteristic wavelength points containing Brix information, and the CARS-PLS (partial least squares) algorithm was used to establish a Brix prediction model. Apple defect, contour, size, and Brix were combined as grading indicators. The apple quality online grading detection platform was built, and apple's comprehensive grading detection algorithm and upper computer software were designed. The experiments showed that the average accuracy of apple defect, contour, and size grading detection was 96.67%, 95.00%, and 94.67% respectively, and the correlation coefficient Rp of the Brix prediction set was 0.9469. The total accuracy of apple defect, contour, size, and Brix grading was 96.67%, indicating that the detection system designed in this paper is feasible to classify "Red Fuji" apple in Luochuan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271352PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352003PMC
August 2022

Microbial diversity and adaptive strategies in the Mars-like Qaidam Basin, North Tibetan Plateau, China.

Environ Microbiol Rep 2022 Aug 4. Epub 2022 Aug 4.

Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing, China.

The Qaidam Basin on the northern Tibetan Plateau, China, is one of the driest deserts at high elevations, and it has been considered a representative Mars analogue site. Despite recent advances in the diversity of microbial communities in the Qaidam Basin, our understanding of their genomic information, functional potential and adaptive strategies remains very limited. Here, we conducted a combination of physicochemical and metagenomic analyses to investigate the taxonomic composition and adaptive strategies of microbial life in the regolith across the Qaidam Basin. 16S ribosomal RNA (rRNA) gene-based and metagenomic analyses both reveal that microbial communities in the Qaidam Basin are dominated by the bacterial phylum Actinobacteria. The low levels of moisture and organic carbon contents appear to have essential constraints on microbial biomass and diversity. A total of 50 high-quality metagenome-assembled genomes were reconstructed and analysed. Our results reveal the potential of microorganisms to use ambient trace gases to meet energy and carbon needs in this nutrient-limited desert. Furthermore, we find that DNA repair mechanisms and protein protection are likely essential for microbial life in response to stressors of hyperaridity, intense ultraviolet radiation and tremendous temperature fluctuations in this Mars analogue. These findings shed light on the diversity and survival strategies of microbial life inhabiting Mar-like environments, which provide implications for potential life on early Mars.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1758-2229.13111DOI Listing
August 2022

[Value of serum amyloid protein dynamic changes on evaluating condition and prognosis of patients with viral and mycoplasma community-acquired pneumonia].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 Jun;34(6):592-596

Department of Intensive Care Unit, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China. Corresponding author: Cao Xiangyuan, Email:

Objective: To investigate the predictive role of dynamic changes of plasma biomarkers in patients with viral and mycoplasma community-acquired pneumonia (CAP).

Methods: From January 2020 to June 2020, 141 patients with viral and mycoplasma CAP in People's Hospital of Ningxia Hui Autonomous Region were enrolled. Pneumonia severity index (PSI) scores [grade I-II (PSI score ≤ 70), grade III (PSI score 71-90) and grade IV-V (PSI score ≥ 91)], serum amyloid A (SAA), hypersensitive C-reactive protein (hs-CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) on the 1 day after admission were compared between the different pathogens (viral and mycoplasma) or different disease severity. The change in level of SAA, hs-CRP on the third day (Δ = 1 d-3 d) were compared among different disease outcome groups (patients were divided into improved group, stable group and exacerbation group based on PSI scores or lung CT images on the third day). The change in the level of SAA, hs-CRP on the seventh day (Δ = 1 d-7 d) were compared among different disease prognosis groups (patients were divided into survival group and death group based on 28-day survival data). The receiver operating characteristic curve (ROC) were drawn to evaluate the value of SAA in the evaluation of disease and prediction prognosis.

Results: The level of SAA in mycoplasma group (43 cases) was significantly higher than that in virus group (98 cases) on the 1 day after admission. There were no significant differences in other plasma biomarkers between the two groups. The more severe the illness, the higher the SAA level on the 1 day after admission. The trends of other plasma biomarkers in the two groups were consistent with SAA. The levels of SAA in the patients with exacerbation of the virus group and mycoplasma group (12 cases, 9 cases) were significantly higher than those of the improved group (57 cases, 26 cases) and the stable group (29 cases, 8 cases). SAA increased gradually in the exacerbation group, decreased gradually in the improved group, and slightly increased in the stable group. ΔSAA were differences among three groups. The change trend of hs-CPR was consistent with SAA. The level of SAA in the death group was higher than that in the survival group on the seventh day. SAA increased in the death group and decreased in survival group with time from hospital admission. There were differences according to ΔSAA between death group and survival group. The change trend of hs-CPR was consistent with SAA. ROC curve showed that the value of SAA was better than hs-CRP in assessing the severity of patients on admission day, and the area under ROC curve (AUC) was respectively 0.777 [95% confidence interval (95%CI) was 0.669-0.886], 0.729 (95%CI was 0.628-0.830). The value of ΔSAA was better than SAA on the third day predicting disease trends, and AUC was respectively 0.979 (95%CI was 0.921-1.000), 0.850 (95%CI was 0.660-1.000). hs-CRP on the third day and Δhs-CRP had no predictive value. Both SAA on the seventh day and ΔSAA have predictive value for prognosis. AUC was respectively 0.954 (95%CI was 0.898-0.993) and 0.890 (95%CI was 0.689-1.000). SAA on the seventh day and ΔSAA were better than hs-CRP on the seventh day. Δhs-CRP have no predictive value.

Conclusions: SAA is a sensitive and valuable indicator for CAP patients with viruses and mycoplasma. Dynamic monitoring of SAA can evaluate the patient's progression, prognosis, and assist diagnosis and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.cn121430-20210223-00273DOI Listing
June 2022

Clinical Analysis and Risk Factors of Bronchiolitis Obliterans After Mycoplasma Pneumoniae Pneumonia.

Infect Drug Resist 2022 28;15:4101-4108. Epub 2022 Jul 28.

Department of Pediatrics, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China.

Purpose: Severe mycoplasma pneumoniae (MP) pneumonia can cause bronchiolitis obliterans (BO). In order to improve the prognosis of BO, it is necessary to grasp the clinical characteristics and risk factors of BO after severe MP pneumonia and intervene as soon as possible.

Patients And Methods: This study retrospectively analyzed the clinical data of 110 patients with severe MP pneumonia, and divided them into BO group (22 cases) and non-BO group (88 cases). The clinical characteristics of BO group were analyzed, and the clinical data of two groups were compared to identify the risk factors of BO.

Results: At the time of diagnosis, all BO patients had symptoms of cough and wheezing, and 10 (45.45%) had decreased exercise intolerance. Lung function showed moderate to severe obstructive ventilatory dysfunction, high-resolution computed tomography (HRCT) showed mosaic perfusion patterns. Multivariate binomial regression analysis showed that higher levels of serum lactate dehydrogenase (LDH) and hypoxemia were independent risk factors for BO after severe MP pneumonia.

Conclusion: Higher levels of serum LDH and hypoxemia were independent risk factors for BO after severe MP pneumonia. For patients with risk factors, clinicians should regular follow-up for early diagnosis and intervention of BO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S372940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343175PMC
July 2022

Financial toxicity among older cancer survivors in China: a qualitative study of oncology providers' perceptions and practices.

Support Care Cancer 2022 Aug 2. Epub 2022 Aug 2.

School of Public Health, Centre for Health Management and Policy Research, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, Shandong, China.

Objective: Despite oncology providers' significant roles in patient care, few studies have been conducted to investigate oncology providers' understanding of financial toxicity. This study aimed to explore oncology providers' perceptions and practices relating to the financial toxicity of older cancer survivors in China.

Methods: A qualitative study was conducted. Individual interviews were conducted with 14 oncology providers at four general hospitals and two cancer specialist hospitals in China. Qualitative data was analyzed using descriptive coding and thematic analysis methods.

Results: The perceptions of participants about the financial toxicity of older cancer survivors include (1) older adults with cancer are especially vulnerable to financial toxicity; (2) inadequate social support may lead to financial toxicity; and (3) cancer-related financial toxicity increased the risk of poor treatment outcomes. The interventions to mitigate its negative effects include (1) effective communication about the cancer-related costs; (2) improving the professional ability to care for the patient; (3) cancer education program as a way to reduce knowledge gaps; and (4) clinical empathy as an effective treatment strategy.

Conclusion: Oncology providers perceive that older cancer patients' financial toxicity plays a key role in increasing the negative effects of diagnosis and treatment of cancer, as well as possibly worsening cancer outcomes. Some potential practices of providers to mitigate financial toxicity include utilizing effective cost communication, improving professional ability in geriatric oncology care, and promoting further cancer education and clinical empathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-022-07303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343566PMC
August 2022

Identification of key pathways and genes in the progression of silicosis based on WGCNA.

Inhal Toxicol 2022 Aug 1:1-15. Epub 2022 Aug 1.

Department of Toxicology, Key Lab of Chemical Safety and health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.

Silicosis, induced by inhaling silica particles in workplaces, is one of the most common occupational diseases. The prognosis of silicosis and its consequent fibrosis is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. In this study, a Wistar rat model for silicosis fibrosis was established by intratracheal instillation of silica (0, 50, 100 and 200 mg/mL, 1 mL) with the evidence of Hematoxylin and Eosin (HE) and Masson staining and the expressions of inflammatory and fibrotic proteins of rats' lung tissues. RNA of lung tissues of rats exposed to 200 mg/mL silica particles and normal saline for 14 d and 28 d was extracted and sequenced to detect differentially expressed genes (DEGs) and to identify silicosis fibrosis-associated modules and hub genes by Weighted gene co-expression network analysis (WGCNA). Predictions of gene functions and signaling pathways were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. In this study, it has been demonstrated the promising role of the Hippo signaling pathway in silicosis fibrosis, which will be conducive to elucidating the specific mechanism of pulmonary fibrosis induced by silica and to determining molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08958378.2022.2102700DOI Listing
August 2022

Myocardin regulates exon usage in smooth muscle cells through induction of splicing regulatory factors.

Cell Mol Life Sci 2022 Aug 1;79(8):459. Epub 2022 Aug 1.

Department of Experimental Medical Science, BMC D12, SE-22184, Lund, Sweden.

Differentiation of smooth muscle cells (SMCs) depends on serum response factor (SRF) and its co-activator myocardin (MYOCD). The role of MYOCD for the SMC program of gene transcription is well established. In contrast, the role of MYOCD in control of SMC-specific alternative exon usage, including exon splicing, has not been explored. In the current work we identified four splicing factors (MBNL1, RBPMS, RBPMS2, and RBFOX2) that correlate with MYOCD across human SMC tissues. Forced expression of MYOCD family members in human coronary artery SMCs in vitro upregulated expression of these splicing factors. For global profiling of transcript diversity, we performed RNA-sequencing after MYOCD transduction. We analyzed alternative transcripts with three different methods. Exon-based analysis identified 1637 features with differential exon usage. For example, usage of 3´ exons in MYLK that encode telokin increased relative to 5´ exons, as did the 17 kDa telokin to 130 kDa MYLK protein ratio. Dedicated event-based analysis identified 239 MYOCD-driven splicing events. Events involving MBNL1, MCAM, and ACTN1 were among the most prominent, and this was confirmed using variant-specific PCR analyses. In support of a role for RBPMS and RBFOX2 in MYOCD-driven splicing we found enrichment of their binding motifs around differentially spliced exons. Moreover, knockdown of either RBPMS or RBFOX2 antagonized splicing events stimulated by MYOCD, including those involving ACTN1, VCL, and MBNL1. Supporting an in vivo role of MYOCD-SRF-driven splicing, we demonstrate altered Rbpms expression and splicing in inducible and SMC-specific Srf knockout mice. We conclude that MYOCD-SRF, in part via RBPMS and RBFOX2, induce a program of differential exon usage and alternative splicing as part of the broader program of SMC differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-022-04497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343278PMC
August 2022

Levamisole Suppresses CD4 T-Cell Proliferation and Antigen-Presenting Cell Activation in Aplastic Anemia by Regulating the JAK/STAT and TLR Signaling Pathways.

Front Immunol 2022 14;13:907808. Epub 2022 Jul 14.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Aplastic anemia (AA) is a life-threatening disease primarily caused by a metabolic disorder and an altered immune response in the bone marrow (BM) microenvironment, where cytotoxic immune cells attack resident cells and lead to hematopoietic failure. We previously reported an efficient strategy by applying cyclosporin (CSA) combined with levamisole (CSA+LMS-based regimen) in the treatment of AA, but the immunoregulatory mechanism of LMS was still unclear. Here, the therapeutic effects of LMS were examined using the BM failure murine model. Meanwhile, the proportion and related function of T cells were measured by flow cytometry and . The involved signaling pathways were screened by RNA-seq and virtual binding analysis, which were further verified by interference experiments using the specific antagonists on the targeting cells by RT-PCR . In this study, the CSA+LMS-based regimen showed a superior immune-suppressive response and higher recession rate than standard CSA therapy in the clinical retrospective study. LMS improved pancytopenia and extended the survival in an immune-mediated BM failure murine model by suppressing effector T cells and promoting regulatory T-cell expansion, which were also confirmed by experiments. By screening of binding targets, we found that JAK1/2 and TLR7 showed the highest docking score as LMS targeting molecules. In terms of the underlying molecular mechanisms, LMS could inhibit JAK/STAT and TLR7 signaling activity and downstream involved molecules. In summary, LMS treatment could inhibit T-cell activation and downregulate related molecules by the JAK/STAT and TLR signaling pathways, supporting the valuable clinical utility of LMS in the treatment of AA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.907808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331934PMC
August 2022

MiR-7 Regulates Pathogen-Induced Immune Response PAK1 in the Sea Cucumber .

Front Immunol 2022 14;13:927796. Epub 2022 Jul 14.

College of Life Science, Liaoning Normal University, Dalian, China.

MicroRNA-7 (miR-7) is a highly conserved short non-coding RNA involved in various bioprocesses the regulation of multiple target genes. To enrich our knowledge of the functions of miR-7 in innate immune regulation in echinoderms, we first investigated the targeting relationship between miR-7 and in the sea cucumber and then explored the functions of miR-7, the gene, and the miR-7/ axis in the pathogen-induced immune response of . Our results showed that miR-7 can bind to the 3'UTR of and negatively regulate the expression of in . Overexpression and inhibition of miR-7 and inhibition of the expression of can alter phagocytosis, cellular agglutination, and lysozyme contents in . Both miR-7 and the gene are involved in immune defense against infection; the miR-7/ axis showed immune regulatory function at 48 to 72 h post-infection (hpi) after infection in In summary, the results of this study established that miR-7 regulates the pathogen-induced immune response by targeting in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.927796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329918PMC
August 2022

Analysis of the Quantitative Evaluation of the Public Medical and Health System Costs During Pandemic Governance: Investigation Based on COVID-19.

Front Public Health 2022 13;10:942043. Epub 2022 Jul 13.

School of Tourism, Hainan University, Haikou, China.

It is of great reference significance for broadening the research perspective of pandemic governance, improving the efficiency of pandemic governance and the credibility of the government, to scientifically measure and analyze the public medical and health system costs. This article takes the typical case "pandemic prevention and control event of S city, China" as the research background. First, the concept of public medical and health system costs during pandemic governance is defined. Then, the public medical and health system costs are embedded into the pandemic governance system, and the generation process of the public medical and health system costs in the actual situation are investigated. Furthermore, through in-depth interview, multi-case grounded theory and fuzzy subordinate function analysis, the scientific construction of the public medical and health system cost index system are completed. Finally, based on G1 method/entropy method combined with weighting and fuzzy comprehensive evaluation method, the public medical and health system costs of the pandemic prevention and control events of S city is measured. The results show the following: (1) it is important that good single dimensions and reliable indicators are embodied in the public medical and health system costs scale. Among them, the behavioral public medical and health system costs of the masses is the largest proportion of all indicators; (2) after the pandemic prevention and control event is over, the public medical and health system cost are difficult to repair, and some lagging ideas and behaviors shown by local governments lead to a continuous expansion of the public medical and health system costs associated with pandemic governance; and (3) local governments should not conceal information asymmetry. Instead, local governments should give greater freedom to other actors to deal with pandemic governance, and governance entities should cooperate with each other. This will mitigate the effect of public medical and health system costs. Corresponding policy recommendations are proposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2022.942043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326215PMC
August 2022

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study.

Lancet Reg Health West Pac 2022 Sep 26;26:100520. Epub 2022 Jul 26.

Shanghai Municipal Center for Disease Control and Prevention, No. 1380 Zhongshan West Street, Changning District, Shanghai City 200051, China.

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China.

Methods: In 2020-2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death).

Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions.

Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms.

Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lanwpc.2022.100520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335373PMC
September 2022

Maternal Dietary Extract Supplementation Induces Changes in Offspring Antioxidant Status, Inflammatory Responses, Intestinal Development, and Microbial Community of Sows.

Front Vet Sci 2022 15;9:926822. Epub 2022 Jul 15.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Agricultural University, Beijing, China.

This experiment aims to investigate the effect of maternal diet supplemented with extract (FSE) on the performance, antioxidant status, inflammatory responses, intestinal development, and microbial community of sows. A total of 24 gestating sows (Landrace × Yorkshire) were assigned to 2 treatments with 12 sows per treatment. From d 107 of gestation to d 21 of lactation, sows were supplemented with a basal diet as control (CON) or an FSE diet (basal diet + 100 mg/kg FSE). Compared with CON, sows fed FSE showed lower ( < 0.05) wean-to-estrus interval, body weight loss, and higher ( < 0.05) average daily gain of suckling piglet. Sows fed FSE had reduced ( < 0.05) serum malondialdehyde (MDA) content and enhanced ( < 0.05) catalase and glutathione peroxidase (GSH-Px) contents at farrowing and weaning compared with CON. The suckling piglets of FSE-fed sows had increased ( < 0.05) mRNA expressions of nuclear factor erythroid-2 related factor 2, heme oxygenase-1 in the liver, and lower ( < 0.05) serum MDA content on d 0, 7, and 14 of lactation. Sows fed FSE had lower ( < 0.05) serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) contents at farrowing and reduced ( < 0.05) serum IL-6 and IL-8 contents at weaning compared with CON. Piglets from FSE-fed sows had enhanced ( ≤ 0.05) villus height and villus height to crypt depth ratio in the jejunum, and higher ( < 0.05) protein expression of Occludin in jejunal mucosa compared with CON. Sows fed FSE tended to have higher ( = 0.09) relative abundance of at genus level in feces at weaning compared with CON. Our results showed maternal diet supplemented with FSE in lactating sows could effectively induce improvement of performance, antioxidant status, anti-inflammatory function, intestinal morphology, barrier function, and microbial community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fvets.2022.926822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334818PMC
July 2022

Evaluating the role of rare genetic variation in sleep duration.

Sleep Health 2022 Jul 27. Epub 2022 Jul 27.

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Objectives: To explore the roles of rare and high-impact variants in sleep duration.

Design: Based on the recently released UK Biobank 200k exome dataset, an exome-wide association study was conducted to detect rare variants (minor allele frequency <0.01) contributing to sleep duration. Variant annotations were performed by the software tool ANNOVAR. Gene-based burden tests of sleep duration were conducted by the SKAT R-package. After quality control, 137,047 subjects were included in this study. CAUSALdb database was used to explore the related mental traits of identified genes.

Results: We detected 730,572 variants with MAF < 1%, including 3873 frameshift variants, 3977 nonframeshift variants, 449,632 nonsynonymous variants, 1293 startloss variants, 10,254 stopgain variants, 413 stoploss variants, 261,130 synonymous variants, and 3102 variants are annotated as unknown. The burden test of exonic variants detected two exome-wide significant associations for sleep duration including TMIE at 3p21.31 (P = 0.015) and ZIC2 at 13q32.3 (P = 0.047). There are only nonsynonymous contained in TMIE; as for ZIC2, we detected 2 annotations of variants: nonsynonymous (P =2.04 × 10) and nonframeshift (P =0.85). TMIE and ZIC2 were reported to be associated with several mental traits, such as chronotype, depression, and brain natriuretic peptide in published study.

Conclusion: This study reported 2 novel candidate genes for a sleep duration, supporting the roles of rare genetic variants in the regulation of sleep duration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleh.2022.05.007DOI Listing
July 2022

Porous activated carbons derived from bamboo pulp black liquor for effective adsorption removal of tetracycline hydrochloride and malachite green from water.

Water Sci Technol 2022 Jul;86(2):244-260

College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, China E-mail: Yibin Industrial Technology Research Institute of Sichuan University, Yibin, Sichuan, China.

As a kind of wastewater produced by papermaking industry, bamboo pulp black liquor (BPBL) discharged into water causes serious environmental problems. In this work, BPBL was successfully converted into porous carbon after activation with potassium hydroxide (KOH) through one-step carbonization, and adsorption properties of porous carbon derived from bamboo pulp black liquor (BLPC) for tetracycline hydrochloride (TCH) and malachite green (MG) were studied. The adsorption capacities of BLPC for TCH and MG are 1047 and 1277 mg/g, respectively, due to its large specific surface area of 1859.08 m/g. Kinetics and isotherm data are well fitted to the pseudo-second-order rate model and Langmuir model, respectively. Adsorption experiments and characterizations reveal that the adsorption mechanism involved in TCH and MG adsorption on BLPC mainly depends on the synergistic effect of pore filling, H-bonding, π-π interactions and weak electrostatic interactions. In addition, BLPC shows excellent photothermal properties, and the adsorption capacity of TCH and MG on BLPC can reach 584 and 847 mg/g under the irradiation of near infrared lamp for 50 min, respectively. The synthesized BLPC with high adsorption efficiency, good recovery ability, improved adsorption under near-infrared irradiation can be a promising and effective adsorbent for TCH or MG or other pollutes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2166/wst.2022.205DOI Listing
July 2022

Retaining nurses via organizational support and pay during COVID-19 pandemic: The moderating effect between intrinsic and extrinsic incentives.

Nurs Open 2022 Jul 30. Epub 2022 Jul 30.

Department of Physiological Nursing, School of Nursing and Department of Epidemiology & Biostatistics, School of Medicine, University of California San Francisco, San Francisco, California, USA.

Aim: There has been growing concern about the nurses' turnover intention as well as life satisfaction during COVID-19 pandemic in Iran. The past research has provided evidence on the effect of organizational support on nurses' job satisfaction and turnover intention. However, little is known about the underlying mechanism behind these associations.

Design: A cross-sectional survey was undertaken.

Methods: An online survey was conducted in Iran from May to June 2020 through Google Docs Forms. In total, 305 nurses were participated and completed the online survey. Data were analysed using structural equation modelling through (AMOS). This study was checked with the STROBE checklist.

Result: The results showed that nurses' perception of organizational support was positively related to their job satisfaction which in turn decreases the turnover intention. Likewise, the job satisfaction partially mediated the relationship between organizational support and nurses' life satisfaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nop2.1286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353281PMC
July 2022

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients with premature coronary artery disease: a retrospective cohort study.

Cardiovasc Diabetol 2022 Jul 29;21(1):142. Epub 2022 Jul 29.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.

Background: Premature coronary artery disease (PCAD) has become more common in recent years and is often associated with poor outcomes. Triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance (IR) and is an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients with PCAD remains uncertain. Thus, this study aimed to investigate the prognostic value and predictive performance of the TyG index in patients with PCAD.

Methods: A total of 526 young subjects (male < 45 years, female < 55 years) with angiographically proven CAD from January 2013 to December 2018 were included consecutively in this study. Their clinical and laboratory parameters were collected, and the TyG index was calculated as [Formula: see text]. The follow-up time after discharge was 40-112 months (median, 68 months; interquartile range, 49‒83 months). The primary endpoint was the occurrence of the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and non-fatal stroke.

Results: The TyG index was significantly associated with traditional cardiovascular risk factors and the Gensini score (GS). Kaplan-Meier survival (MACE-free) curves by tertiles of the TyG index showed statistically significant differences (log-rank test, p = 0.001). In the fully adjusted Cox regression model, the Hazard ratio (95% CI) of MACE was 2.17 (1.15-4.06) in tertile 3 and 1.45 (1.11-1.91) for per SD increase in the TyG index. Time-dependent ROC analyses of the TyG for prediction of MACE showed the area under the curves (AUC) reached 0.631 at 3 years, 0.643 at 6 years, and 0.710 at 9 years. Furthermore, adding TyG index to existing risk prediction model could improve outcome prediction [C-statistic increased from 0.715 to 0.719, p = 0.007; continuous net reclassification improvement (NRI) = 0.101, p = 0.362; integrated discrimination improvement (IDI) = 0.011, p = 0.017].

Conclusion: The TyG index is an independent predictor of MACE in patients with PCAD, suggesting that the TyG index has important clinical implications for risk stratification and early intervention of PCAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-022-01576-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338459PMC
July 2022

From Rate-Limiting Enzyme to Therapeutic Target: The Promise of NAMPT in Neurodegenerative Diseases.

Front Pharmacol 2022 12;13:920113. Epub 2022 Jul 12.

Innovation Center of Nursing Research, West China School of Nursing, Department of Gastrointestinal Surgery, National Clinical Research Center for Geriatrics, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD) salvage pathway in mammals. It is of great significance in the metabolic homeostasis and cell survival via synthesizing nicotinamide mononucleotide (NMN) through enzymatic activities, serving as a key protein involved in the host's defense mechanism. The NAMPT metabolic pathway connects NAD-dependent sirtuin (SIRT) signaling, constituting the NAMPT-NAD-SIRT cascade, which is validated as a strong intrinsic defense system. Neurodegenerative diseases belong to the central nervous system (CNS) disease that seriously endangers human health. The World Health Organization (WHO) proposed that neurodegenerative diseases will become the second leading cause of human death in the next two decades. However, effective drugs for neurodegenerative diseases are scant. NAMPT is specifically highly expressed in the hippocampus, which mediates cell self-renewal and proliferation and oligodendrocyte synthesis by inducing the biosynthesis of NAD in neural stem cells/progenitor cells. Owing to the active biological function of NAMPT in neurogenesis, targeting NAMPT may be a powerful therapeutic strategy for neurodegenerative diseases. This study aims to review the structure and biological functions, the correlation with neurodegenerative diseases, and treatment advance of NAMPT, aiming to provide a novel idea for targeted therapy of neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.920113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322656PMC
July 2022

Insight into the mechanism of deep NO photo-oxidation by bismuth tantalate with oxygen vacancies.

J Hazard Mater 2022 Jul 21;439:129637. Epub 2022 Jul 21.

Key Laboratory of Resources Conversion and Pollution Control of the State Ethnic Affairs Commission, College of Resources and Environmental Science, South-Central Minzu University, Wuhan 430074, China. Electronic address:

Deeply photocatalytic oxidation of nitrogen oxides is still difficult to achieve, mainly limited by few intrinsic active sites and inefficient carrier separation of photocatalysts. Accordingly, we develop a simple room temperature tactic to introduce oxygen vacancies (OVs) into BiTaO (BTO). Based on solid experimental and DFT theoretical supports, we explore the mechanism of NO removal over OVs decorated BTO (OVs-BTO). OVs can not only alter the distribution of local electrons to result in the formation of a fast charge transfer channel between OVs and the adjacent Ta atoms, which improves the transport rate of photogenerated carriers; but also function as active sites to adsorb small molecules (NO, O and HO), which being activated and positively drive the NO oxidation reaction. In order to investigate a possible reaction path, a combination of in-situ DRIFTS and simulated Gibbs free energy reveals that the intermediate products of OVs-BTO are helpful to promote the deep oxidation of NO to NO, while pristine BTO is more likely to produce NO intermediate toxic by-products, which greatly hinders the deep photocatalytic oxidation of NO. This work provides insights into the role of OVs in photocatalysts, and also points out a guideline for the mechanism of semiconductor photocatalysts in eliminating gaseous pollutants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2022.129637DOI Listing
July 2022

One-step algorithm for fast-track localization and multi-category classification of histological subtypes in lung cancer.

Eur J Radiol 2022 Jul 21;154:110443. Epub 2022 Jul 21.

Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Center for Intelligent Oncology, Chongqing University Cancer Hospital, Chongqing University School of Medicine, Chongqing Key Laboratory of Intelligent Oncology for Breast Cancer, Chongqing 400030, China. Electronic address:

Backgrounds: Accumulated evidence has proven that computer-derived features from computed tomography (CT) through radiomics and deep learning technologies can identify extensive characteristics of pulmonary malignancies, such as nodules detection and malignant lesion discrimination. However, there are few studies on whether CT images can reflect histological subtypes of lung cancer through computer-derived features.

Methods: Contrast-enhanced CT images prior treatment from 417 patients diagnosed with small cell lung cancer (SCLC), lung adenocarcinoma (ADC), or lung squamous cell carcinoma (SCC) were collected. ITK-SNAP software was used by trained radiologists for the manual delineation of tumor volume. Patients of each category (SCLC, ADC, SCC) were then randomly split into training datasets and test datasets in an approximately ratio of 8:2. After image pre-processing and augmentation, 25,042 CT images from the training datasets were used to train our self-developed deep learning model for fast-tracking tumor lesions and classifying corresponding histological subtypes simultaneously. The performance of the network was evaluated by accuracy, F1-score and weighted F1-average using 1,921 testing images based on parameters generated during training.

Results: The prediction accuracy of SCLC, ADC, and SCC were 0.83, 0.75 and 0.67, respectively. The weighted F1-average was 0.75. ADC obtained the best F1-score of 0.78, which was outperformed SCLC (0.77) and SCC (0.66). The corresponding AUC values of SCLC, ADC, and SCC were 0.87, 0.84, and 0.76, respectively. Only 0.24 s were required to simultaneously achieve functions of tumor localization and histological classification on a thoracic CT image slice. The heat map visualization illustrated the extracted tumor features to classify subtypes of lung cancer by the proposed model.

Conclusions: The newly developed multi-task algorithm provides a CNN-based DL approach in lung cancer for automatically fast-tracking tumor lesions and classifying corresponding histological subtypes in one-step.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2022.110443DOI Listing
July 2022

Specialized Pro-resolving lipid Mediators: Endogenous regulation vascular inflammation and remodeling.

Curr Pharm Des 2022 Jul 27. Epub 2022 Jul 27.

Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.

With the development of modern materials science, life science and medical science, the application of implant materials in clinical medicine is becoming more and more widespread. Vascular stent is an indispensable medical implantation device for the PTCA (Percutaneous Transluminal Coronary Angioplasty). However, the persistent inflammatory response after coronary stent implantation is one of the important reasons for in-stent neo-atherosclerosis (ISNA). This article starts with the current inflammatory problems caused by coronary stent implantation and discusses the formation mechanism of foam cells and key role of foam cells in the formation of atherosclerotic lesions. On this basis, we introduce a new type of endogenous bioactive molecules named Specialized Pro-resolving lipid Mediators (SPMs), which limit excessive inflammatory effects without causing immunosuppression and also promote tissue repair, and reviews its role in balancing inflammation and its potential application to regulate the vascular remodeling after PTCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612828666220727145038DOI Listing
July 2022

Biogeographic Patterns of Leaf Element Stoichiometry of L. in Degraded Grasslands on Inner Mongolia Plateau and Qinghai-Tibetan Plateau.

Plants (Basel) 2022 Jul 26;11(15). Epub 2022 Jul 26.

College of Grassland Science and Technology, China Agricultural University, Beijing 100193, China.

Plant leaf stoichiometry reflects its adaptation to the environment. Leaf stoichiometry variations across different environments have been extensively studied in grassland plants, but little is known about intraspecific leaf stoichiometry, especially for widely distributed species, such as L. We present the first study on the leaf stoichiometry of and evaluate its relationships with environmental variables. leaf and soil samples from 29 invaded sites in the two plateaus of distinct environments [the Inner Mongolian Plateau (IM) and Qinghai-Tibet Plateau (QT)] in Northern China were collected. Leaf C, N, P, and K and their stoichiometric ratios, and soil physicochemical properties were determined and compared with climate information from each sampling site. The results showed that mean leaf C, N, P, and K concentrations were 498.60, 19.95, 2.15, and 6.57 g kg; the average C:N, C:P, N:P, N:K and K:P ratios were 25.20, 245.57, 9.81, 3.13, and 3.21, respectively. The N:P:K-ratios in leaf might imply that its growth is restricted by K- or K+N. Moreover, the soil physicochemical properties in the -infested areas varied remarkably, and few significant correlations between leaf ecological stoichiometry and soil physicochemical properties were observed. These indicate the nutrient concentrations and stoichiometry of tend to be insensitive to variations in the soil nutrient availability, resulting in their broad distributions in China's grasslands. Besides, different homeostasis strength of the C, N, K, and their ratios in leaves across all sites were observed, which means could be more conservative in their use of nutrients improving their adaptation to diverse conditions. Moreover, the leaf C and N contents of were unaffected by any climate factors. However, the correlation between leaf P content and climate factors was significant only in IM, while the leaf K happened to be significant in QT. Besides, MAP or MAT contribution was stronger in the leaf elements than soil by using mixed effects models, which illustrated once more the relatively weak effect of the soil physicochemical properties on the leaf elements. Finally, partial least squares path modeling suggested that leaf P or K contents were affected by different mechanisms in QT and IM regions, suggesting that can adapt to changing environments by adjusting its relationships with the climate or soil factors to improve its survival opportunities in degraded grasslands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants11151943DOI Listing
July 2022

Brain Proteome-Wide Association Study Identifies Candidate Genes that Regulate Protein Abundance Associated with Post-Traumatic Stress Disorder.

Genes (Basel) 2022 Jul 27;13(8). Epub 2022 Jul 27.

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710000, China.

Although previous genome-wide association studies (GWASs) on post-traumatic stress disorder (PTSD) have identified multiple risk loci, how these loci confer risk of PTSD remains unclear. Through the FUSION pipeline, we integrated two human brain proteome reference datasets (ROS/MAP and Banner) with the PTSD GWAS dataset, respectively, to conduct a proteome-wide association study (PWAS) analysis. Then two transcriptome reference weights (Rnaseq and Splicing) were applied to a transcriptome-wide association study (TWAS) analysis. Finally, the PWAS and TWAS results were investigated through brain imaging analysis. In the PWAS analysis, 8 and 13 candidate genes were identified in the ROS/MAP and Banner reference weight groups, respectively. Examples included ( = 3.00 × 10) and ( = 7.07 × 10). Moreover, the TWAS also detected multiple candidate genes associated with PTSD in two different reference weight groups, including ( = 3.84 × 10), ( = 5.09 × 10), and ( = 4.81 × 10). Further comparison of the PWAS and TWAS results in different populations detected the overlapping genes: ( = 4.90 × 10, = 1.23 × 10) in the total population and ( = 4.89 × 10, = 1.41 × 10) in females. Brain imaging analysis revealed several different brain imaging phenotypes associated with and genes. Our study identified multiple candidate genes associated with PTSD in the proteome and transcriptome levels, which may provide new clues to the pathogenesis of PTSD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes13081341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332745PMC
July 2022

Marked shifts in gut microbial structure and neurotransmitter metabolism in fresh inmates revealed a close link between gut microbiota and mental health: A case-controlled study.

Int J Clin Health Psychol 2022 Sep-Dec;22(3):100323. Epub 2022 Jul 13.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Background/objective: The gut microbiota plays a pivotal role in psychological health, but the mechanistic perspective between gut microbiome and mental health remains poorly understood.

Method: The present case-controlled study recruited 30 unimprisoned subjects and 31 inmates that had been detained in jail for no more than a month. The mental health status, gut microbiota and blood NH3, H2S, 5-hydroxy trptamine and dopamine levels were measured.

Results: Compared with unimprisoned controls, the fresh inmates exhibited significantly higher scores on anxiety and depression. Both phylogenetic structure and functional genes of the gut microbiota markedly shifted in inmates. Inmates was more -dominated, while unimprisoned subjects were more -dominated. Short-chain fatty acids (SCFAs)-producing genera were largely decreased in inmates and were negatively related to mental disorder scores, while Bacteroidetes and Proteobacteria were positive to anxiety and depression scores. Simultaneously, the inmates possessed reduced genes that participate in amino acids, carbohydrates and vitamin cofactors metabolism, but enriched genes that involved in the neurotransmitter-producing Shikimate pathway. Correlation analysis revealed that and were negative to depression score, and was negative to anxiety score.

Conclusions: Our results revealed potential link between gut microbiota and mental health, leading further support to the microbiota-gut-brain axis theory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijchp.2022.100323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289638PMC
July 2022

Log P Determines Licorice Flavonoids Release Behaviors and Classification from CARBOMER Cross-Linked Hydrogel.

Pharmaceutics 2022 Jun 24;14(7). Epub 2022 Jun 24.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.

The dynamic drug release mechanisms from Carbomer 940 (CP) hydrogels have not been systematically explored elsewhere. This study aimed to investigate the quantitative structure-activity relationship of licorice flavonoids (LFs) compounds on their drug release from CP hydrogels based on LFs-CP interactions and drug solubility in the release medium. Ten LFs-CP hydrogels were formulated, and their in vitro release study was conducted. The intermolecular forces of LFs-CP systems were characterized by FTIR, molecular docking and molecular dynamic simulation. Ten LFs compounds were classified into I (high-release capability) LFs and II (low-release capability) LFs according to the different negative correlations between drug release percent at 48 h and intermolecular forces of drugs-CP, respectively. Moreover, high-release LFs possessed significantly lower log P and higher drug solubility in the release medium than low-release LFs. All I LFs release behaviors best followed the first-order equation, while II LFs release characteristics best fitted the zero-order equation except for isoliquiritigenin. Log P mainly affect the hydrogel relaxation process for I drugs release and the drug diffusion process for II drugs release. Higher log P values for LFs resulted in higher intermolecular strength for I drugs-CP systems and lower drug solubility in the release medium for II drugs, which hindered drug release. Hydrophobic association forces in drug-CP hydrogel played a more and more dominant role in hindering I LFs release with increasing release time. On the other hand, lower drug solubility in the release medium restricted II LFs release, and the dominant role of drug solubility in the release medium increased in 24 h followed by a significant decline after 36 h. Collectively, log P of LFs served as a bridge to determine LFs compound release behaviors and classification from CP hydrogels, which provided guidelines for reasonable design of LFs hydrogels in pharmaceutical topical formulations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics14071333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322780PMC
June 2022

A Rapid and Efficient Strategy for Quality Control of Clinopodii herba Encompassing Optimized Ultrasound-Assisted Extraction Coupled with Sensitive Variable Wavelength Detection.

Molecules 2022 Jul 10;27(14). Epub 2022 Jul 10.

Anhui College of Traditional Chinese Medicine, Wuhu 241000, China.

Clinopodii herba is a folk herbal medicine for treatments of hemorrhagic disorders. However, there is not even a quantitative standard for clinopodii herba deposited in the Chinese Pharmacopoeia. The development of a strategy for rapid and efficient extraction and simultaneous detection of multiple components in clinopodii herba is therefore of great value for its quality evaluation. Here, a variable wavelength strategy was firstly applied to quantity multiple components by segmental monitoring by UHPLC with diode array detector following ultrasound-assisted extraction. The parameters of ultrasound-assisted extraction were optimized using single factor optimization experiments and response surface methodology by a Box-Behnken design combined with overall desirability. Subsequently, a rapid, efficient, and sensitive method was applied for simultaneous determination of eleven compounds, which represented the major and main types of components in clinopodii herba. Moreover, the performance of the validated method was successfully applied for the quality control of various batches of clinopodii herba and provided sufficient supporting data for the optimum harvest time. The Box-Behnken-optimized ultrasound-assisted extraction coupled with variable wavelength detection strategy established in this work not only improves the quality control of clinopodii herba, but also serves as a powerful approach that can be extended to quality evaluation of other traditional Chinese medicines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules27144418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316769PMC
July 2022

Bile Duct Ligation Impairs Function and Expression of Mrp1 at Rat Blood-Retinal Barrier via Bilirubin-Induced P38 MAPK Pathway Activations.

Int J Mol Sci 2022 Jul 11;23(14). Epub 2022 Jul 11.

Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Liver injury is often associated with hepatic retinopathy, resulting from accumulation of retinal toxins due to blood-retinal barrier (BRB) dysfunction. Retinal pigment epithelium highly expresses MRP1/Mrp1. We aimed to investigate whether liver injury affects the function and expression of retinal Mrp1 using bile duct ligation (BDL) rats. Retinal distributions of fluorescein and 2,4-dinitrophenyl-S-glutathione were used for assessing Mrp1 function. BDL significantly increased distributions of the two substrates and bilirubin, downregulated Mrp1 protein, and upregulated phosphorylation of p38 and MK2 in the retina. BDL neither affected the retinal distribution of FITC-dextran nor expressions of ZO-1 and claudin-5, demonstrating intact BRB integrity. In ARPE-19 cells, BDL rat serum or bilirubin decreased MRP1 expression and enhanced p38 and MK2 phosphorylation. Both inhibiting and silencing p38 significantly reversed the bilirubin- and anisomycin-induced decreases in MRP1 protein. Apparent permeability coefficients of fluorescein in the A-to-B direction (P) across the ARPE-19 monolayer were greater than P. MK571 or bilirubin significantly decreased P of fluorescein. Bilirubin treatment significantly downregulated Mrp1 function and expression without affecting integrity of BRB and increased bilirubin levels and phosphorylation of p38 and MK2 in rat retina. In conclusion, BDL downregulates the expression and function of retina Mrp1 by activating the p38 MAPK pathway due to increased bilirubin levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23147666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318728PMC
July 2022
-->