Publications by authors named "Shuang Liang"

729 Publications

Cholesterol and matrisome pathways dysregulated in astrocytes and microglia.

Cell 2022 Jun;185(13):2213-2233.e25

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 enhances de novo cholesterol synthesis despite elevated intracellular cholesterol due to lysosomal cholesterol sequestration in astrocytes. Further, matrisome dysregulation is associated with upregulated chemotaxis, glial activation, and lipid biosynthesis in astrocytes co-cultured with neurons, which recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk.
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http://dx.doi.org/10.1016/j.cell.2022.05.017DOI Listing
June 2022

Development, Validation, and Comparison of Image-Based, Clinical Feature-Based and Fusion Artificial Intelligence Diagnostic Models in Differentiating Benign and Malignant Pulmonary Ground-Glass Nodules.

Front Oncol 2022 7;12:892890. Epub 2022 Jun 7.

Department of Radiology, Changzheng Hospital, Navy Medical University, Shanghai, China.

Objective: This study aimed to develop effective artificial intelligence (AI) diagnostic models based on CT images of pulmonary nodules only, on descriptional and quantitative clinical or image features, or on a combination of both to differentiate benign and malignant ground-glass nodules (GGNs) to assist in the determination of surgical intervention.

Methods: Our study included a total of 867 nodules (benign nodules: 112; malignant nodules: 755) with postoperative pathological diagnoses from two centers. For the diagnostic models to discriminate between benign and malignant GGNs, we adopted three different artificial intelligence (AI) approaches: a) an image-based deep learning approach to build a deep neural network (DNN); b) a clinical feature-based machine learning approach based on the clinical and image features of nodules; c) a fusion diagnostic model integrating the original images and the clinical and image features. The performance of the models was evaluated on an internal test dataset (the "Changzheng Dataset") and an independent test dataset collected from an external institute (the "Longyan Dataset"). In addition, the performance of automatic diagnostic models was compared with that of manual evaluations by two radiologists on the 'Longyan dataset'.

Results: The image-based deep learning model achieved an appealing diagnostic performance, yielding AUC values of 0.75 (95% confidence interval [CI]: 0.62, 0.89) and 0.76 (95% CI: 0.61, 0.90), respectively, on both the Changzheng and Longyan datasets. The clinical feature-based machine learning model performed well on the Changzheng dataset (AUC, 0.80 [95% CI: 0.64, 0.96]), whereas it performed poorly on the Longyan dataset (AUC, 0.62 [95% CI: 0.42, 0.83]). The fusion diagnostic model achieved the best performance on both the Changzheng dataset (AUC, 0.82 [95% CI: 0.71-0.93]) and the Longyan dataset (AUC, 0.83 [95% CI: 0.70-0.96]), and it achieved a better specificity (0.69) than the radiologists (0.33-0.44) on the Longyan dataset.

Conclusion: The deep learning models, including both the image-based deep learning model and the fusion model, have the ability to assist radiologists in differentiating between benign and malignant nodules for the precise management of patients with GGNs.
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http://dx.doi.org/10.3389/fonc.2022.892890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209648PMC
June 2022

cAMP Is a Promising Regulatory Molecule for Plant Adaptation to Heat Stress.

Life (Basel) 2022 Jun 14;12(6). Epub 2022 Jun 14.

State Key Laboratory of Wheat & Maize Crop Science, College of Life Science, Henan Agricultural University, Zhengzhou 450002, China.

With gradual warming or increased frequency and magnitude of high temperature, heat stress adversely affects plant growth and eventually reduces plant productivity and quality. Plants have evolved complex mechanisms to sense and respond to heat stress which are crucial to avoiding cell damage and maintaining cellular homeostasis. Recently, 33″,55″-cyclic adenosine monophosphate (cAMP) has been proved to be an important signaling molecule participating in plant adaptation to heat stress by affecting multi-level regulatory networks. Significant progress has been made on many fronts of cAMP research, particularly in understanding the downstream signaling events that culminate in the activation of stress-responsive genes, mRNA translation initiation, vesicle trafficking, the ubiquitin-proteasome system, autophagy, HSPs-assisted protein processing, and cellular ion homeostasis to prevent heat-related damage and to preserve cellular and metabolic functions. In this present review, we summarize recent works on the genetic and molecular mechanisms of cAMP in plant response to heat stress which could be useful in finding thermotolerant key genes to develop heat stress-resistant varieties and that have the potential for utilizing cAMP as a chemical regulator to improve plant thermotolerance. New directions for future studies on cAMP are discussed.
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http://dx.doi.org/10.3390/life12060885DOI Listing
June 2022

Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease.

Sci Transl Med 2022 Jun 22;14(650):eabo4474. Epub 2022 Jun 22.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)-NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1 dendritic cells and dysfunctional CD8 T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high- and low-risk patients, respectively) or HCC experienced (de novo HCC recurrence rates at 5 years were 71.8 and 42.9% in high- and low-risk patients, respectively). PLS-NAFLD was bioinformatically translated into a four-protein secretome signature, PLSec-NAFLD, which was validated in an independent cohort of HCC-naïve patients with NAFLD and cirrhosis (HCC incidence rates at 15 years were 37.6 and 0% in high- and low-risk patients, respectively). Combination of PLSec-NAFLD with our previously defined etiology-agnostic PLSec-AFP yielded improved HCC risk stratification. PLS-NAFLD was modified by bariatric surgery, lipophilic statin, and IDO1 inhibitor, suggesting that the signature can be used for drug discovery and as a surrogate end point in HCC chemoprevention clinical trials. Collectively, PLS/PLSec-NAFLD may enable NAFLD-specific HCC risk prediction and facilitate clinical translation of NAFLD-directed HCC chemoprevention.
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http://dx.doi.org/10.1126/scitranslmed.abo4474DOI Listing
June 2022

More Active Intestinal Immunity Developed by Obese Mice Than Non-Obese Mice After Challenged by .

Front Vet Sci 2022 3;9:851226. Epub 2022 Jun 3.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.

Obese mice presented lower mortality to non-fatal pneumonia induced by () than the non-obese mice. However, it remained obscure whether the intestine contributed to the protective effect of obese mice with infection. The 64 non-obese (NOB) mice were divided into NOB-uninfected and NOB- groups, while 64 high-fat diet-induced obesity (DIO) mice were divided into DIO-uninfected and DIO- groups. Mice in groups were intranasally instilled with 40 μl (4.0 ×10 colony-forming units [CFUs]), while uninfected groups with the same volume of phosphate buffer saline (PBS). The T subsets of Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) in the intestine were collected for flow cytometry analysis at 0, 12, 24, and 72 h post-infection, also the duodenum and colon were harvested to survey histopathological change. The results showed that the percentage of CD3T cells in LPLs in DIO- group was significantly lower than that in the DIO-uninfected group after infection ( < 0.05). The percentage of CD4T cells in IELs in NOB- was significantly lower than that in DIO- after infection ( < 0.05). The percentage of CD8T cells in LPLs in NOB- was significantly lower than that in DIO- at 12 and 24 h ( < 0.05). The immunoglobulin A (IgA) cells in DIO-uninfected were higher than that in NOB-uninfected at all time points ( < 0.05). The IgA cells in DIO- were higher than that in DIO-uninfected at 12, 24, and 72 h ( < 0.05). The results revealed that the level of intestinal mucosal immunity in obese mice was more active than that in non-obese mice.
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http://dx.doi.org/10.3389/fvets.2022.851226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205201PMC
June 2022

Melatonin Alleviates PM-Induced Hepatic Steatosis and Metabolic-Associated Fatty Liver Disease in ApoE Mice.

Oxid Med Cell Longev 2022 8;2022:8688643. Epub 2022 Jun 8.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China.

Background: Exposure to fine particulate matter (PM) is associated with the risk of developing metabolic-associated fatty liver disease (MAFLD). Melatonin is the main secreted product of the pineal gland and has been reported to prevent hepatic lipid metabolism disorders. However, it remains uncertain whether melatonin could protect against PM-induced MAFLD.

Methods And Results: The purpose of our study was to investigate the mitigating effects of melatonin on hepatic fatty degeneration accelerated by PM in vivo and in vitro. Histopathological analysis and ultrastructural images showed that PM induced hepatic steatosis and lipid vacuolation in ApoE mice, which could be effectively alleviated by melatonin administration. Increased ROS production and decreased expression of antioxidant enzymes were detected in the PM-treated group, whereas melatonin showed recovery effects after PM-induced oxidative damage in both the liver and L02 cells. Further investigation revealed that PM induced oxidative stress to activate PTP1B, which in turn had a positive feedback regulation effect on ROS release. When a PTP1B inhibitor or melatonin was administered, SP1/SREBP-1 signalling was effectively suppressed, while Nrf2/Keap1 signalling was activated in the PM-treated groups.

Conclusion: Our study is the first to show that melatonin alleviates the disturbance of PM-triggered hepatic steatosis and liver damage by regulating the ROS-mediated PTP1B and Nrf2 signalling pathways in ApoE mice. These results suggest that melatonin administration might be a prospective therapy for the prevention and treatment of MAFLD associated with air pollution.
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http://dx.doi.org/10.1155/2022/8688643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200552PMC
June 2022

Effect of humic acid on phenanthrene removal by constructed wetlands using birnessite as a substrate.

RSC Adv 2022 May 18;12(24):15231-15239. Epub 2022 May 18.

School of Civil and Environmental Engineering, University of Technology Sydney Broadway NSW 2007 Australia.

The binding of polycyclic aromatic hydrocarbons (PAHs) to humic acid (HA) can boost the complexation-flocculation process and promote pollutant oxidation through the role of HA as an electron shuttle. HA-coated biochar (BA) was added to study the effects of HA on phenanthrene (PHE) removal by constructed wetlands (CWs) using birnessite as a substrate. HA reduced the average PHE concentration of effluent by 26.58% due to its role as a complexing agent, based on Fourier-transform infrared spectroscopy analysis. For CWs with birnessite, the PHE removal performance was further enhanced due to the role of electron shuttles. X-ray photoelectron spectroscopy and illumina high-throughput analysis revealed an enhanced Mn-Fe cycle. The total relative proportions of Mn-oxidizing bacteria and iron-oxidizing bacteria in VFBCW-HA/BA were 2.33 and 5.50 times as high as those in VFBCW-BA and VFCW-HA/BA. Humic acid also accelerated the biodegradation of PAHs and the quantity of PAH degradative bacteria in VFBCW-HA/BA was 6.29 times greater than in VFBCW-BA.
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http://dx.doi.org/10.1039/d1ra06927fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115771PMC
May 2022

Intestinal-targeted nanotubes-in-microgels composite carriers for capsaicin delivery and their effect for alleviation of Salmonella induced enteritis.

Biomaterials 2022 Jun 1;287:121613. Epub 2022 Jun 1.

Key Laboratory of Precision Nutrition and Food Quality, Research Center of Food Colloids and Delivery of Functionality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China. Electronic address:

Salmonella is a word-wide food-borne pathogen, which can cause severe enteritis and intestinal microbiota imbalance. Capsaicin (Cap), a food-based bioactive ingredient, has antibacterial and anti-inflammatory properties. However, its low solubility, low bioavailability and the irritation to digestive tract greatly limit its applications. Here, an intestinal responsively "nanotubes-in-microgel" composite carrier was constructed by capturing α-lactalbumin (α-lac) nanotubes in low-methoxy pectin microgels (LMP-NT) (52 μm). Cap was loaded in such system via hydrophobic interaction with a loading capacity of 38.02 mg/g. The LMP microgels remained stable and protected NT/Cap from early releasing in the gastric condition. It showed an excellent mucoadhesive capacity, which can prolong the intestinal retention up to 12 h and control release NT/Cap in intestine. Afterward, NT/Cap could penetrate across the mucus layer deeply and enter the intestinal villi epithelial cells efficiently. LMP-NT microgels achieved a mucoadhesive-to-penetrating transition in response to intestinal pH, improving the epithelium absorption and the in vivo bioavailability of Cap. Oral administration of LMP-NT/Cap could effectively alleviate enteritis caused by Salmonella infection and maintain the homeostasis of gut microbiota. Overall, this work suggested that LMP-NT composite microgels were promising for intestine-targeted and oral delivery of hydrophobic bioactive food compounds.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121613DOI Listing
June 2022

Osteocalcin association with vascular function in chronic kidney disease.

J Clin Hypertens (Greenwich) 2022 Jun 10. Epub 2022 Jun 10.

Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, China.

Osteocalcin (OCN) is a bone-derived and vitamin K dependent hormone that affects energy metabolism and vascular calcification. The relationship between serum OCN and vascular function in patients with chronic kidney disease (CKD) is uncertain. This study investigated the association between serum OCN and vascular function as expressed with reactive hyperemia index (RHI) and augmentation index (AIx) measured by Endo-PAT 2000 device. This cross-sectional analysis was based on 256 pre-dialysis CKD patients who had completed the Endo-PAT 2000 test and serum OCN at the First Center of Chinese PLA Hospital from November 2017 to December 2019. Based on whether the RHI was less than 1.67, the patients were divided into endothelial dysfunction and normal endothelial function groups. Multiple logistic and linear regression were used to analyze the association between OCN and vascular function. Subgroup analyses were performed to examine the effects of OCN on vascular function in different CKD populations. After multivariate adjustment, CKD with low OCN were more likely to have endothelial dysfunction (OR: 0.794; 95%CI: 0.674-0.934; P = .006); on the contrary, patients with high OCN had a higher degree of arterial stiffness (standardized β: 0.174; P = .003). Subgroup analyses showed that higher OCN was associated with severe arterial stiffness but a better endothelial function in young (age < 65 years, P /P = .027/.011), male (P /P = .040/.016), patients with a history of hypertension (P /P = .004/.009) or diabetes (P /P = .005/.005), and in early CKD (P /P = .014/.015). In conclusion, serum OCN correlates with vascular function in CKD patients: beneficial for endothelial function but detrimental to arterial stiffness.
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http://dx.doi.org/10.1111/jch.14523DOI Listing
June 2022

A Prediction Model for Acute Kidney Injury in Adult Patients With Minimal Change Disease.

Front Med (Lausanne) 2022 24;9:862160. Epub 2022 May 24.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.

Background: Early prediction of acute kidney injury (AKI) can allow for timely interventions, but there are still few methods that are easy and convenient to apply in predicting AKI, specially targeted at patients with minimal change disease (MCD). Motivated by this, we aimed to develop a predicting model for AKI in patients with MCD within the KDIGO criteria.

Methods: Data on 401 hospitalized adult patients, whose biopsy was diagnosed as MCD from 12/31/2010 to 15/7/2021, were retrospectively collected. Among these data, patients underwent biopsy earlier formed the training set ( = 283), while the remaining patients formed the validation set ( = 118). Independent risk factors associated with AKI were analyzed. From this, the prediction model was developed and nomogram was plotted.

Results: AKI was found in 55 of 283 patients (19%) and 15 of 118 patients (13%) in the training and validation cohorts, respectively. According to the results from lasso regression and logistic regression, it was found that four factors, including mean arterial pressure, serum albumin, uric acid, and lymphocyte counts, were independent of the onset of AKI. Incorporating these factors, the nomogram achieved a reasonably good concordance index of 0.84 (95%CI 0.77-0.90) and 0.75 (95%CI 0.62-0.87) in predicting AKI in the training and validation cohorts, respectively. Decision curve analysis suggested clinical benefit of the prediction models.

Conclusions: Our predictive nomogram provides a feasible approach to identify high risk MCD patients who might develop AKI, which might facilitate the timely treatment.
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http://dx.doi.org/10.3389/fmed.2022.862160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170996PMC
May 2022

[Molecular polymorphism Analysis on CD36 Deficiency among Platelet Blood Donors in Shenzhen].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2022 Jun;30(3):884-889

Shenzhen Blood Center, Institution of Transfusion Medicine, Shenzhen 518035, Guangdong Province, China,E-mail:

Objective: To analyze the molecular polymorphisms of CD36 among 58 blood donors with CD36 deficiency and compare with CD36 positive controls.

Methods: A total of 58 donors with CD36 deficiency during a screening conducted in the laboratory from September 2019 to December 2020 were enrolled as the test group, including 39 males and 19 females, while 120 platelet donors with CD36 positive were randomly selected as the controls, including 76 males and 44 females. All of the subjects were Han nationality. The PCR-SBT method was used to detect coding region of CD36 gene, and molecular mutations were compared with those CD36 positive controls.

Results: Among the 58 donors with CD36 deficiency, mutations appears in 32 individuals. The detection rate for type I was 71.43% (5/7), and type II was 51.92% (27/52), while among the 120 controls, mutations appears in 12 donors (10%). In the CD36 antigen-deficient donors, 16 variations were found, in which 329-330 del AC with the highest frequency accounted for 20.69%, followed by 1228-1239 del ATTGTGCCTATT(15.52%) and 1156 C>T(10.34%). Two variations, 198-205 del GATCTTTG and 220 C>T, led to premature termination of translation; four mutations, 329-330 del AC, 560 ins T, 1011-1049 39bp dupl and 1343-1344 ins TCTT, caused translation frame shift; 1228-1239 del ATTGTGCCTATT led to deletion of four amino acids (Ile-Val-Pro-Ile) at sites 410-413 of the peptide chain. The 1140 T>A and 1275 G>A were synonymous mutations, and the other 7 mutations resulted in the substitution of single nucleotide. The platelet expression in the donors of CD36 positive with 329-330 del AC or 1228-1239 del ATTGTGCCTATT mutation (heterozygote) was lower than those CD36 positive individuals without mutations (homozygote).

Conclusion: Multiple gene mutations in the CD36 coding region may cause CD36 deficiency, and the heterozygous individuals with mutations may lead to CD36 antigen reduction or deletion. Mutation is not detected in 44.83% of CD36 deficient individuals, there may be some other reasons for the CD36 antigen deficiency.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2022.03.036DOI Listing
June 2022

Deciphering the pharmacological mechanisms of Scutellaria baicalensis Georgi on oral leukoplakia by combining network pharmacology, molecular docking and experimental evaluations.

Phytomedicine 2022 Aug 22;103:154195. Epub 2022 May 22.

Department of Oral Medicine, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan 030001, China. Electronic address:

Background: Oral leukoplakia (OLK), an uncharacterized pathological condition that occurs as a white patch in the oral mucosa, is the most common precancerous condition. Scutellaria baicalensis Georgi (SBG) is a medicinal plant with a wide range of pharmacological effects. Increased evidence shows that SBG has potential therapeutic effects on OLK. However, the therapeutic mechanisms of SBG against OLK have not yet been completely elucidated.

Purpose: This study aimed to clarify the active components and multi-target mechanisms of SBG against OLK via network pharmacology, molecular docking and experimental evaluations.

Study Design And Methods: The active components and related targets of SBG were screened by the TCMSP database and Swiss Target Prediction database. Potential therapeutic targets of OLK were collected using the GeneCards and OMIM databases. Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OLK via applying data mining techniques and topological parameters. Metascape database was utilized for GO and KEGG pathway analysis. Molecular docking techniques were used to estimate the binding force between the components and the hub genes. Subsequently, a series of in vitro experiments, specifically CCK-8 assay, clone formation assay, wound healing assay, flow cytometry, RT-qPCR and western blotting were conducted for further verification.

Results: There were 25 active components and 31 related target genes in SBG against OLK. PPI analysis showed that Akt1, VEGFA, EGFR, HIF1A and PTGS2 shared the highest centrality among all target genes. KEGG pathway analysis found that PI3K-Akt signaling pathway may occupy core status in the anti-OLK system. Molecular docking results showed that the main active components of SBG had a strong binding affinity to the hub genes. In vitro experiments showed that the leading component baicalein may inhibit proliferation, block cells in the S phase, induce DOK cell apoptosis, and downregulate the mRNA expression of 5 hub genes by inhibiting PI3K/Akt signaling pathway activation.

Conclusion: The most predominant component of SBG against OLK was baicalein and the key pathway was PI3K/Akt. The main components and hub genes had robust binding abilities. In vitro experiments showed that baicalein could inhibit the proliferation of DOK cells, induce apoptosis, block the cell cycle, and inhibit the mRNA expression level of the hub genes by inhibiting the PI3K/Akt pathway.
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http://dx.doi.org/10.1016/j.phymed.2022.154195DOI Listing
August 2022

EEG-based vibrotactile evoked brain-computer interfaces system: A systematic review.

PLoS One 2022 3;17(6):e0269001. Epub 2022 Jun 3.

Centre for Smart Health, School of Nursing, The Hong Kong Polytechnic University, Hong Kong SAR, China.

Recently, a novel electroencephalogram-based brain-computer interface (EVE-BCI) using the vibrotactile stimulus shows great potential for an alternative to other typical motor imagery and visual-based ones. (i) Objective: in this review, crucial aspects of EVE-BCI are extracted from the literature to summarize its key factors, investigate the synthetic evidence of feasibility, and generate recommendations for further studies. (ii) Method: five major databases were searched for relevant publications. Multiple key concepts of EVE-BCI, including data collection, stimulation paradigm, vibrotactile control, EEG signal processing, and reported performance, were derived from each eligible article. We then analyzed these concepts to reach our objective. (iii) Results: (a) seventy-nine studies are eligible for inclusion; (b) EEG data are mostly collected among healthy people with an embodiment of EEG cap in EVE-BCI development; (c) P300 and Steady-State Somatosensory Evoked Potential are the two most popular paradigms; (d) only locations of vibration are heavily explored by previous researchers, while other vibrating factors draw little interest. (e) temporal features of EEG signal are usually extracted and used as the input to linear predictive models for EVE-BCI setup; (f) subject-dependent and offline evaluations remain popular assessments of EVE-BCI performance; (g) accuracies of EVE-BCI are significantly higher than chance levels among different populations. (iv) Significance: we summarize trends and gaps in the current EVE-BCI by identifying influential factors. A comprehensive overview of EVE-BCI can be quickly gained by reading this review. We also provide recommendations for the EVE-BCI design and formulate a checklist for a clear presentation of the research work. They are useful references for researchers to develop a more sophisticated and practical EVE-BCI in future studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269001PLOS
June 2022

PM induce the defective efferocytosis and promote atherosclerosis via HIF-1α activation in macrophage.

Nanotoxicology 2022 Jun 2:1-20. Epub 2022 Jun 2.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, P.R. China.

Epidemiological studies demonstrate that fine particulate matter (PM) promotes the development of atherosclerosis. However, the mechanism insight of PM-induced atherosclerosis is still lacking. The aim of this study was to explore the biological effects of hypoxia-inducible factor 1α (HIF-1α) on PM-triggered atherosclerosis. The vascular stiffness, carotid intima-media thickness (CIMT), lipid and atherosclerotic lesion were increased when von Hippel-Lindau (VHL)-null mice were exposed to PM. Yet, knockout of HIF-1α markedly decreased the PM-triggered atherosclerotic lesion. We firstly performed microarray analysis in PM-treated bone morrow-derived macrophages (BMDMs), which showed that PM significantly changed the genes expression patterns and affected biological processes such as phagocytosis, apoptotic cell clearance, cellular response to hypoxia, apoptotic process and inflammatory response. Moreover, the data showed knockout of HIF-1α remarkably relieved PM-induced defective efferocytosis. Mechanistically, PM inhibited the level of genes and proteins of efferocytosis receptor c-Mer tyrosine kinase (MerTK), especially in VHL-null BMDMs. In addition, PM increased the genes and proteins of a disintegrin and metallopeptidase domain 17 (ADAM17), which caused the MerTK cleavage to form soluble MerTK (sMer) in plasma and cellular supernatant. The sMer was significantly up-regulated in plasma of VHL-null PM-exposed mice. Moreover, PM could induce defective efferocytosis and activate inflammatory response through MerTK/IFNAR1/STAT1 signaling pathway in macrophages. Our results demonstrate that PM could induce defective efferocytosis and inflammation by activating HIF-1α in macrophages, ultimately resulting in accelerating atherosclerotic lesion formation and development. Our data suggest HIF-1α in macrophages might be a potential target for PM-related atherosclerosis.
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http://dx.doi.org/10.1080/17435390.2022.2083995DOI Listing
June 2022

Superior results of return to sport after double-bundle versus single-bundle anterior cruciate ligament reconstruction in young active patients.

Knee Surg Sports Traumatol Arthrosc 2022 Jun 2. Epub 2022 Jun 2.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan, 430030, People's Republic of China.

Purpose: To compare return to sport and clinical results in young active patients who underwent anatomic single-bundle (SB) versus double-bundle (DB) anterior cruciate ligament reconstruction (ACLR).

Methods: Young active patients undergoing SB or DB ACLR from 2017 to 2019 at our institution were retrospectively reviewed. The primary outcome measures were the rate and time to return to sports, with secondary measures including the Lachman test, pivot shift test, Lysholm scores, International Knee Documentation Committee (IKDC) scores and graft rupture.

Results: The study included a total of 90 patients (DB group, 42; SB group, 48), with a mean follow-up of 27.1 ± 6.1 months. Young active patients who underwent DB ACLR had a higher rate of return to pivoting sports than those who underwent SB ACLR (HR = 2.4; 95% confidence interval [CI]: 1.4, 4.1; p = 0.013). The DB group returned to pivoting sports at a mean ± SD of 11.0 ± 2.9 months compared with 12.7 ± 2.7 months in the SB group (p = 0.01). There was one traumatic failure in the SB group and one contralateral ACL rupture in the DB group. There was no significant difference in the rate and time to return to running, Lachman test, pivot-shift test, Lysholm or IKDC scores in either group.

Conclusion: Both anatomical SB and DB techniques achieved satisfactory clinical outcomes. DB techniques led to superior performance of return to pivoting sports but nonsignificant differences in time and rate of return to running, passive stability measurement, subjective knee function outcome and graft rupture rate in both groups at the 2-year follow-up. The DB ACLR should be considered a viable option to treat young patients with high activity demands.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-022-07010-6DOI Listing
June 2022

The Pathway to China's Carbon Neutrality Based on an Endogenous Technology CGE Model.

Int J Environ Res Public Health 2022 05 20;19(10). Epub 2022 May 20.

School of Economics and Resource Management, Beijing Normal University, Beijing 100875, China.

Global warming resulting from greenhouse gas emissions has been a worldwide issue facing humanity. Simultaneously, governments have the challenging task of striking a judicious balance between increased economic growth and decreased carbon emissions. Based on the energy-environment-economy triple coupling (3E-CGE) model, we endogenously integrate climate-friendly technologies into the model's analysis framework through logic curves and refine and modify the CGE model's energy use and carbon emission modules. We conduct a scenario simulation and sensitivity analysis on carbon tax, carbon-trading, and climate-friendly technological progress, respectively. The results reveal that carbon tax and carbon trading contribute to reducing carbon emissions in the short-term but achieving the goals of peak carbon and carbon neutrality will cause the collapse of the economic system. In the long-term, climate-friendly technologies are key to achieving the dual carbon goal; the development of such technologies can also stimulate economic development. The best path for China to achieve its dual carbon goals and economic development in the next 40 years involves effectively combining the carbon tax, carbon trading, and a climate-friendly technological progress. Specifically, China can begin trading carbon in high-emissions industries then impose industry-wide carbon taxes.
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http://dx.doi.org/10.3390/ijerph19106251DOI Listing
May 2022

Serum uric acid is not associated with major depressive disorder in European and South American populations: a meta-analysis and two-sample bidirectional Mendelian Randomization study.

Eur J Clin Nutr 2022 May 25. Epub 2022 May 25.

School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China.

Objective: Although previous epidemiological studies have demonstrated that serum uric acid (SUA) is associated with major depressive disorder (MDD), these analyses are prone to biases. Here, we applied the Mendelian Randomization approach to determine whether SUA is causally associated with MDD.

Methods: We conducted a meta-analysis to evaluate the relationship between SUA and MDD, then applied summary data from the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium to estimate their causal effect using a two-sample bidirectional Mendelian Randomization (MR) analysis. Thereafter, the causal effect was further researched using genetic risk scores (GRS) as instrumental variables (IVs).

Results: Results of a meta-analysis of articles comprising 6975 and 13,589 MDD patients and controls, respectively, revealed that SUA was associated with MDD (SMD = -0.690, 95% CI: -0.930 to -0.440, I = 97.4%, P < 0.001). In addition, the five MR methods revealed no causal relationship existed between SUA and MDD, which corroborated the results obtained via the GRS approach.

Conclusion: This paper found little evidence that this association between SUA and MDD is casual. Genetically, there was no significant causal association between SUA and MDD.
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http://dx.doi.org/10.1038/s41430-022-01165-8DOI Listing
May 2022

Iron ore or manganese ore filled constructed wetlands enhanced removal performance and changed removal process of nitrogen under sulfamethoxazole and trimethoprim stress.

Environ Sci Pollut Res Int 2022 May 23. Epub 2022 May 23.

Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science & Engineering, Shandong University, Qingdao, 266237, China.

Iron ore and manganese ore were used as substrate of constructed wetlands (CWs) to enhance nitrogen (N) removal. However, the N purification performance in CWs filled with iron or manganese ore under antibiotics stress needs further study. In this study, three groups of CWs filled with river sand, limonite (a kind of iron ore), and manganese ore sand were constructed, which were named as C-CWs, Fe-CWs, and Mn-CWs, respectively. The effect and mechanism of the composite antibiotics sulfamethoxazole (SMX) and trimethoprim (TMP) on N removal in CWs were investigated. While the addition of SMX and TMP inhibited about 40% nitrification and promoted about 25% denitrification in all CWs, Fe-CWs and Mn-CWs always had better N removal performance than C-CWs. Changes in microbial community structure in CWs indicated that the better N removal performance in Fe-CWs and Mn-CWs was attributed to the presence of more abundant and diverse N-associated bacteria, especially Fe- and Mn-driven autotrophic denitrifying bacteria. What's more, the addition of iron ore or manganese ore contributed to the better N removal performance with highest relative abundance of N-transferring bacteria under antibiotics stress.
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http://dx.doi.org/10.1007/s11356-022-20103-6DOI Listing
May 2022

Applying Information Gain to Explore Factors Affecting Small-Incision Lenticule Extraction: A Multicenter Retrospective Study.

Front Med (Lausanne) 2022 3;9:837092. Epub 2022 May 3.

Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.

Purpose: This retrospective study aimed to identify the key factors influencing postoperative refraction after small-incision lenticule extraction (SMILE) using information gain.

Methods: This study comprised 2,350 eyes of 1,200 patients who underwent SMILE using a Visumax 500-kHz femtosecond laser (Carl Zeiss Meditec AG) in three ophthalmic centers: Tianjin Eye Hospital (center A), Jinan Mingshui Eye Hospital (center B), and Qingdao Eye Hospital (center C). Anterior segment features, including corneal curvature and central corneal thickness (CCT), were obtained from Pentacam HR (Oculus, Wetzlar, Germany). Information gain was calculated to analyze the importance of features affecting postoperative refraction.

Results: Preoperative and postoperative mean spherical equivalent (SE) refraction were -5.00 (-6.13, -3.88) D and 0.00 (-0.25, 0.13) D, respectively. None of the patients lost more than two lines of corrected distance visual acuity. The safety index was 1.32 ± 0.24, 1.03 ± 0.08, and 1.13 ± 0.16 in centers A, B, and C, respectively. The efficacy index was 1.31 ± 0.25, 1.02 ± 0.08, and 1.13 ± 0.17 in centers A, B, and C, respectively. At least 95% of the eyes were within ±1.00 D of the attempted correction. Postoperative refraction was related to preoperative spherical diopter refraction (r = 0.369, < 0.001), preoperative SE (r = 0.364, < 0.001), maximum lenticule thickness (r = -0.311, < 0.001), preoperative uncorrected distance visual acuity (r = 0.164, < 0.001), residual stromal thickness (r = 0.139, < 0.001), preoperative mean anterior corneal curvature (r = -0.127, < 0.001), preoperative flattest anterior corneal curvature (r = -0.122, < 0.001), nomogram (r = -0.100, < 0.001) and preoperative CCT (r = -0.058, = 0.005).

Conclusions: SMILE was considered a safe and effective procedure for correcting myopia. Based on information gain, postoperative refraction was influenced by preoperative mean anterior corneal curvature, CCT, refraction, and residual stromal thickness.
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http://dx.doi.org/10.3389/fmed.2022.837092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110865PMC
May 2022

Predicted fat mass, lean body mass, and risk of hypertension: results from a Chinese male cohort study.

Obes Facts 2022 May 18. Epub 2022 May 18.

Introduction: Few studies have deciphered whether lean body mass (LBM) or fat mass (FM) is predominantly responsible for the body mass index (BMI)-hypertension association. This study aimed to assess the associations of predicted LBM and FM with hypertension risk among Chinese male adults.

Methods: A prospective cohort study was conducted among 2,812 male participants free of hypertension in the Fangchenggang Area Males Health and Examination Survey in 2009. We performed multivariable Cox models and restricted cubic spline (RCS) to examine the associations of predicted LBM and FM, and BMI with hypertension, and to further explore the mediating roles of lipid and glycemic traits in the relationship between predicted FM and blood pressure.

Results: Of 1,238 participants included in the cohort study, 306 (24.8%) hypertension cases were identified during a median follow-up of 3.8 years, with an incidence rate of 7.0 per 100 person-years. A positive linear-shaped association was consistently observed between BMI and hypertension (P for trend < 0.001). Multivariable adjusted Cox models including predicted LBM and FM observed a positive association between predicted FM and hypertension. Compared with those in the lowest quartile of predicted FM, men in the highest quartile had a hazard ratio (HR) of 1.83 (95% confidence interval (CI): 1.13 to 2.97) for hypertension. The HR per standard deviation (SD) increase of BMI and predicted FM was 1.11 (95% CI: 1.04 to 1.19) above 23.1 kg/m2 and 1.05 (95% CI: 1.02 to 1.15) above 14.6 kg, respectively. However, predicted LBM was not associated with hypertension. In addition, high-density lipoprotein cholesterol (HDL-c) and fasting blood glucose (FBG) mediated the relationship of predicted FM with systolic blood pressure, with a mediation ratio of 37.1% and 8.2%, respectively. Furthermore, total cholesterol (TC) and triglyceride (TG) positively mediated the association of predicted FM with diastolic blood pressure, with a mediation ratio of 9.5% and 9.9%, respectively.

Conclusion: Higher predicted FM might play a central role in the positive linear relationship of the BMI-hypertension association in Chinese male adults, and the link from predicted FM to blood pressure was partially mediated by TC, TG, HDL-c, and FBG.
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http://dx.doi.org/10.1159/000524653DOI Listing
May 2022

Nucleoporin37 may play a role in early embryo development in human and mice.

Mol Hum Reprod 2022 05;28(6)

State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.

Maternal-effect genes (MEGs) play an important role in maintaining the survival and development of mammalian embryos at the cleavage stage after fertilization. Despite long-term efforts, the MEGs that regulate preimplantation embryo development remain largely unknown. Here, using whole-exome sequencing and homozygosity mapping, we identified a potential candidate gene associated with early embryo development: nucleoporin37 (NUP37), a nucleoporin gene that encodes a member of the nuclear pore complexes and regulates nuclear pore permeability and nucleocytoplasmic transport. Moreover, we determined the temporal and spatial expression patterns of Nup37 in mouse oocytes and early embryos, and explored the role of NUP37 in oocyte maturation and preimplantation embryo development. Immunoprecipitation assays confirmed that yes-associated protein-1 (YAP1) binds to TEA domain transcription factor 4 (TEAD4) and NUP37. Furthermore, Nup37 gene knockdown reduced the nuclear import of YAP1 and down-regulated the expression of YAP1-TEAD pathway downstream genes Rrm2 and Rpl13 in early embryos. Our study provides evidence that maternal NUP37 contributes to the nuclear import of YAP1 and then activates the YAP1-TEAD pathway, a signalling pathway essential for zygotic genome activation. Nup37 may be a key gene involved in preimplantation embryo development in mammals.
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http://dx.doi.org/10.1093/molehr/gaac017DOI Listing
May 2022

Environmental impacts of antibiotics addition to algal-bacterial-based aquaponic system.

Appl Microbiol Biotechnol 2022 May 6;106(9-10):3777-3786. Epub 2022 May 6.

Shandong Key Laboratory of Environmental Processes and Health, School of Environmental Science and Engineering, Shandong University, Qingdao, 266237, People's Republic of China.

Antibiotics usage is a double-edged sword among the production promotion and environmental aggravation of aquaculture system. In this study, the effects of sulfadiazine addition on algal-bacterial-based aquaponic (AA) system were thoroughly investigated. Results showed that sulfadiazine addition increased the nitrogen (N) and carbon (C) recovery of AA system by 1.3 times and 2.9 times, respectively. Meanwhile, the global warming potential was increased by 63% due to aggravated nitrous oxide (NO) emission. This was mainly because sulfadiazine increased the abundance of nirS genes and decreased the abundance of nosZ genes, which subsequently led to higher NO accumulation. Furthermore, resistance gene (sul-1, sul-2, and intI-1) abundance in the treatment group was an order higher than that of the control group, which would give rise to the environmental risk for agroecological system. KEY POINTS: • Sulfadiazine addition increased NUE at expense of aggravated GHG emissions. • Sulfadiazine disrupted the balance between the abundance of nirS and nosZ genes. • Sulfadiazine addition increased the resistance gene abundance of AA system.
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http://dx.doi.org/10.1007/s00253-022-11944-9DOI Listing
May 2022

Optimization of a tannase-assisted process for obtaining teas rich in theaflavins from leaves.

Food Chem X 2022 Mar 3;13:100203. Epub 2022 Jan 3.

Tea Research Institute Chinese Academy of Agricultural Sciences, Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, 9 South Meiling Road, Hangzhou 310008, China.

This work aimed at optimizing the extraction of theaflavins for the development of a potentially functional tea beverage using different technological parameters as factors. Green tea leaves treated with tannase provided a beverage with significant higher amount (4.7-fold) of theaflavin (TF) compared to the pure withered leaf fermentation. For black tea, the optimized process conditions to produce a beverage with high TF (0.269 μg/mL) concentration were: 6 g of leaves/400 mL, a low fermentation temperature of 25 °C with the absence of buffer and pH control, an intermediate fermentation time (60 min) and a relatively low aeration rate (0.8-1.0 L/min). The tea liquid produced under optimized fermentation conditions appears to be ideal for making a black tea beverage with surplus summer tea leaves and brings economic benefits.
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http://dx.doi.org/10.1016/j.fochx.2022.100203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039937PMC
March 2022

Predictive factors of posterior corneal shift after small incision lenticule extraction: a 5-year follow-up study.

Acta Ophthalmol 2022 Apr 30. Epub 2022 Apr 30.

Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.

Purpose: The aim of this study was to determine risk factors affecting changes in posterior corneal elevation (PCE) and predict the 5-year stability after small incision lenticule extraction (SMILE).

Methods: This retrospective, longitudinal study enrolled 161 patients post-SMILE. The PCE values were measured at the apex, thinnest, maximal and 24 other prespecified preoperative points and at 6 months, 1 year and 5 years postoperatively.

Results: Posterior corneas exhibited time-dependent, region-dependent and angle-dependent changes. For every dioptre increase in the absolute preoperative spherical equivalent (SE), 10-μm decrease in the central corneal thickness (CCT), 10-μm increase in the maximum lenticule thickness (MLT), 10-μm decrease in the residual bed thickness (RBT), 10% increase in the percentage ablation depth (PAD, MLT divided by CCT) and 10% decrease in the percentage stromal bed thickness (PSBT, RBT divided by CCT), PCE exhibited average forward displacements of 0.2-0.4, 0.2-0.7, 0.1-0.2, 0.1-0.3, 0.6-1.0 and 0.5-1.1 μm, respectively (p < 0.05). PSBT was the variable with the highest accuracy in predicting 5-year stability of posterior corneas (area under curve = 0.75). The cut-off values of SE, CCT, MLT, RBT, PAD and PSBT for increased PCE were -8.00 to -8.31 D, 481.0-498.5 μm, 139.5-144.5 μm, 255.5-263.5 μm, 26.9-28.3% and 48.9-52.6%, respectively.

Conclusion: Eyes with thinner corneas, higher myopia requiring greater MLT and lower RBT exhibited greater predispositions towards posterior protrusion. The thresholds for preventing forward posterior corneal displacement were 26.9-28.3% for PAD and 48.9-52.6% for PSBT. Prediction of posterior corneal stability is useful for assessing surgical risks post-SMILE.
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http://dx.doi.org/10.1111/aos.15166DOI Listing
April 2022

Carboxymethyl konjac glucomannan-chitosan complex nanogels stabilized double emulsions incorporated into alginate hydrogel beads for the encapsulation, protection and delivery of probiotics.

Carbohydr Polym 2022 Aug 2;289:119438. Epub 2022 Apr 2.

Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

In this study, we developed (W/O/W) double emulsions encapsulated by calcium-alginate hydrogel beads system (ACGs) for intestinal-targeted delivery of probiotics (Lactobacillus reuteri). Firstly, the carboxymethyl konjac glucomannan-chitosan (CMKGM-CS) nanogels were successfully fabricated by EDC/NHS initiated crosslinking, as concluded from the TEM images, FTIR spectra, XRD, etc. Then, double emulsions were prepared and encapsulated with various concentrations of alginate to form ACGs hydrogel beads. In vitro probiotic release experiments showed the lyophilized ACG-2 and ACG-3 hydrogel beads had a sustained release in simulated intestinal fluid (SIF), the viability of cells exceeded 10 CFU/mL at 6 h. The lyophilized ACG-3 hydrogel beads exhibited the viable release amount of 8.4 × 10 CFU/mL after storage for 90 d at 4 °C. Besides, the alginate concentration in the ACGs hydrogel beads influences the swelling behavior and structure of hydrogel beads by affecting the hydrogen bonds between alginate and CMKGM-CS, thereby mediating the release of probiotics.
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http://dx.doi.org/10.1016/j.carbpol.2022.119438DOI Listing
August 2022

Artificial Assembled Macrophage Co-Deliver Black Phosphorus Quantum Dot and CDK4/6 Inhibitor for Colorectal Cancer Triple-Therapy.

ACS Appl Mater Interfaces 2022 May 27;14(18):20628-20640. Epub 2022 Apr 27.

NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong Province 250012, China.

In recent years, therapeutic strategies based on macrophages have been inspiringly developed, but due to the high intricacy and immunosuppression of the tumor microenvironment, the widespread use of these strategies still faces significant challenges. Herein, an artificial assembled macrophage concept ([email protected]) was presented to imitate the main antitumor abilities of macrophages of tumor targeting, promoting the antitumor immunity, and direct tumor-killing effects. The artificial assembled macrophage ([email protected]) was prepared through an extrusion method, which is to fuse the macrophage membrane with abemaciclib and black phosphorus quantum dot (BPQD)-loaded liposomes. [email protected] showed good stability and tumor targeting ability with the help of macrophage membrane. Furthermore, [email protected] reversed the immunosuppressive tumor microenvironment by inhibiting regulatory T cells (Tregs) and stimulating the maturation of antigen-presenting cells to activate the antitumor immune response through triggering an immunogenic cell death effect. More importantly, in the colorectal tumor model in vivo, a strong cooperative therapeutic effect of photo/chemo/immunotherapy was observed with high tumor inhibition rate (95.3 ± 2.05%). In conclusion, [email protected] exhibits excellent antitumor efficacy by intelligently mimicking the abilities of macrophages. A promising therapeutic strategy for tumor treatment based on imitating macrophages was provided in this study.
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http://dx.doi.org/10.1021/acsami.2c01305DOI Listing
May 2022

Progesterone Changes the Pregnancy-Induced Adaptation of Cardiomyocyte Kv2.1 Channels via MicroRNA-29b.

Cardiovasc Ther 2022 7;2022:7145699. Epub 2022 Apr 7.

School of Medicine, Nankai University, Tianjin, China.

The cardiovascular system adaptation occurs during pregnancy to ensure adequate maternal circulation. Progesterone (P4) is widely used in hormone therapy to support pregnancy, but little is known about its effects on maternal cardiac function. In this study, we investigated the cardiac repolarization and ion channel expression in pregnant subjects and mice models and studied the effects of P4 administrations on these pregnancy-mediated adaptations. P4 administrations shortened the prolongation of QTC intervals and action potential duration (APD) that occurred during pregnancy, which was mainly attributable to the reduction in the voltage-gated potassium (Kv) current under basal conditions. studies indicated that P4 regulated the Kv2.1 channel in a bidirectional manner. At a low dose (1 M), P4 induced upregulation of Kv2.1 through P4 receptor, while at a higher dose (5 M), P4 downregulated Kv2.1 by targeting microRNA-29b (miR-29b). Our data showed that P4 modulated maternal cardiac repolarization by regulating Kv2.1 channel activity during pregnancy. Kv2.1, as well as miR-29b, might be used as potential therapeutic targets for adaptations of the maternal cardiovascular system or evaluation of progesterone medication during pregnancy.
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http://dx.doi.org/10.1155/2022/7145699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010150PMC
April 2022

Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient.

Microbiol Spectr 2022 Apr 25:e0262421. Epub 2022 Apr 25.

Department of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China.

The higher resistance rate to ceftazidime-avibactam (CZA) is mainly related to carbapenem resistance, especially New Delhi metallo-β-lactamase (NDM). The CZA-susceptible Klebsiella pneumoniae (K191663) and the later CZA-resistant isolates (K191724, K191725, K191773) co-producing NDM-4 and OXA-181 were obtained from the same hospitalized patient returning from Vietnam. Our study aims to elucidate the diversity of K. pneumoniae ST16 through comparative analysis of whole-genome sequencing (WGS) data and identify the potential evolution of plasmids by sequencing longitudinal clinical isolates during antibiotic treatment. Firstly, multilocus sequence typing analysis and phylogenic analysis suggested that these strains belong to the two lineages of K. pneumoniae ST16. Surprisingly, the CZA-resistant strains were closely related to K. pneumoniae ST16 described in South Korea, instead of the - or -carrying ST16 reported in Vietnam. Secondly, , , and co-existed on a self-conjugative IncFII(Yp)-like plasmid, which played a significant role in CZA resistance. It could transfer into the recipient Escherichia coli J53 at high frequency, indicating the risk of mobile carbapenemases. In addition, the loss of 12-kbp fragment occurred in -positive isolate (K191773), which was likely caused by insertion sequence-mediated homologous recombination. Last but not least, as a repressor of operon system, was truncated by a frameshift mutation in K191663. Thus, our study provided baseline information for monitoring the occurrence and development of bacterial resistance. As a leading health care-acquired infection pathogen, Klebsiella pneumoniae is threatening a large number of inpatients due to its diverse antibiotic resistance and virulence factors. Heretofore, with a growing number of reports about the coexistence of several carbapenemases in carbapenem-resistant K. pneumoniae (CRKP), epidemiologic surveillance has been strengthened. Nevertheless, the nosocomial outbreaks by CRKP ST16 are gradually increasing worldwide. Our study provides a deeper insight into the diversification of clinical isolates of CRKP ST16 in China. In addition, the comparison analysis of resistant plasmids may reveal the transmission of carbapenemase-encoding genes. Furthermore, our study also highlights the importance of longitudinal specimen collection and continuous monitoring during the treatment, which play a crucial role in understanding the development of antibiotic resistance and the evolution of resistance plasmids.
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http://dx.doi.org/10.1128/spectrum.02624-21DOI Listing
April 2022

A low-cost approach for soil moisture prediction using multi-sensor data and machine learning algorithm.

Sci Total Environ 2022 Aug 7;833:155066. Epub 2022 Apr 7.

NTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City, Viet Nam.

A high-resolution soil moisture prediction method has recently gained its importance in various fields such as forestry, agricultural and land management. However, accurate, robust and non- cost prohibitive spatially monitoring of soil moisture is challenging. In this research, a new approach involving the use of advance machine learning (ML) models, and multi-sensor data fusion including Sentinel-1(S1) C-band dual polarimetric synthetic aperture radar (SAR), Sentinel-2 (S2) multispectral data, and ALOS Global Digital Surface Model (ALOS DSM) to predict precisely soil moisture at 10 m spatial resolution across research areas in Australia. The total of 52 predictor variables generated from S1, S2 and ALOS DSM data fusion, including vegetation indices, soil indices, water index, SAR transformation indices, ALOS DSM derived indices like digital model elevation (DEM), slope, and topographic wetness index (TWI). The field soil data from Western Australia was employed. The performance capability of extreme gradient boosting regression (XGBR) together with the genetic algorithm (GA) optimizer for features selection and optimization for soil moisture prediction in bare lands was examined and compared with various scenarios and ML models. The proposed model (the XGBR-GA model) with 21 optimal features obtained from GA was yielded the highest performance (R = 0. 891; RMSE = 0.875%) compared to random forest regression (RFR), support vector machine (SVM), and CatBoost gradient boosting regression (CBR). Conclusively, the new approach using the XGBR-GA with features from combination of reliable free-of-charge remotely sensed data from Sentinel and ALOS imagery can effectively estimate the spatial variability of soil moisture. The described framework can further support precision agriculture and drought resilience programs via water use efficiency and smart irrigation management for crop production.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155066DOI Listing
August 2022

Multipoint Costriking Nanodevice Eliminates Primary Tumor Cells and Associated-Circulating Tumor Cells for Enhancing Metastasis Inhibition and Therapeutic Effect on HCC.

Adv Sci (Weinh) 2022 03 14;9(9):2101472. Epub 2022 Jan 14.

Department of Pharmaceutics Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University 44 Wenhuaxi Road Jinan Shandong Province 250012 China.

Eliminating primary tumor ("roots") and inhibiting associated-circulating tumor cells (associated-CTCs, "seeds") are vital issues that need to be urgently addressed in cancer therapy. Associated-CTCs, which include single CTCs, CTC clusters, and CTC-neutrophil clusters, are essential executors in metastasis and the cause of metastasis-related death in cancer patients. Herein, a "roots and seeds" multipoint costriking nanodevice (GV-Lipo/sorafenib (SF)/digitoxin (DT)) is developed to eliminate primary tumors and inhibit the spread of associated-CTCs for enhancing metastasis inhibition and the therapeutic effect on hepatocellular carcinoma (HCC). GV-Lipo/SF/DT eliminates primary tumor cells by the action of SF, thus reducing CTC production at the roots and improving the therapeutic effect on HCC. GV-Lipo/SF/DT inhibits associated-CTCs effectively via the enhanced identification and capture effects of glypican-3 and/or vascular cell adhesion molecule 1 (VCAM1) targeting, dissociating CTC clusters using DT, blocking the formation of CTC-neutrophil clusters using anti-VCAM1 monoclonal antibody, and killing CTCs with SF. It is successfully verified that GV-Lipo/SF/DT increases the CTC elimination efficiency in vivo, thus effectively preventing metastasis, and shows enhanced antitumor efficacy in both an H22-bearing tumor model and orthotopic HCC models. Overall, the "roots and seeds" multipoint costriking strategy may open a new cancer treatment model for the clinic.
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http://dx.doi.org/10.1002/advs.202101472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948568PMC
March 2022
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