Publications by authors named "Rui Zhou"

1,152 Publications

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The Metabolic Adaptation in Response to Nitrate Is Critical for Actinobacillus pleuropneumoniae Growth and Pathogenicity under the Regulation of NarQ/P.

Infect Immun 2022 Aug 8:e0023922. Epub 2022 Aug 8.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural Universitygrid.35155.37, Wuhan, Hubei, China.

Nitrate metabolism is an adaptation mechanism used by many bacteria for survival in anaerobic environments. As a by-product of inflammation, nitrate is used by the intestinal bacterial pathogens to enable gut infection. However, the responses of bacterial respiratory pathogens to nitrate are less well understood. Actinobacillus pleuropneumoniae is an important bacterial respiratory pathogen of swine. Previous studies have suggested that adaptation of A. pleuropneumoniae to anaerobiosis is important for infection. In this work, A. pleuropneumoniae growth and pathogenesis in response to the nitrate were investigated. Nitrate significantly promoted A. pleuropneumoniae growth under anaerobic conditions and lethality in mice. By using and deletion mutants and single-residue-mutated complementary strains of Δ, the two-component system NarQ/P was confirmed to be critical for nitrate-induced growth, with Arg50 in NarQ as an essential functional residue. Transcriptome analysis showed that nitrate upregulated multiple energy-generating pathways, including nitrate metabolism, mannose and pentose metabolism, and glycerolipid metabolism via the regulation of NarQ/P. Furthermore, , , and its target gene encoding the nitrate reductase Nap contributed to the pathogenicity of A. pleuropneumoniae. The Nap inhibitor tungstate significantly reduced the survival of A. pleuropneumoniae , suggesting that Nap is a potential drug target. These results give new insights into how the respiratory pathogen A. pleuropneumoniae utilizes the alternative electron acceptor nitrate to overcome the hypoxia microenvironment, which can occur in the inflammatory or necrotic infected tissues.
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http://dx.doi.org/10.1128/iai.00239-22DOI Listing
August 2022

Dynamic photoelectron transport in stepwise-doped GaAs photocathodes.

Sci Rep 2022 Jul 28;12(1):12936. Epub 2022 Jul 28.

Department of Physics & Astronomy, The University of Alabama in Huntsville, Huntsville, 35899, USA.

We present a theoretical model describing photoelectron transport dynamics in stepwise-doped GaAs photocathodes. Built-in electric field caused by the doping structure is analyzed, and the time-evolution of electron concentration in the active layer induced by a femtosecond laser pulse is solved. The predictions of the model show excellent agreement with the experimental data measured with pump-probe transient reflectometry, demonstrating the capability of the theoretical model in predicting photoelectron behaviors in real devices. Comparisons are also made between this stepwise doping model and the conventional gradient doping model with a continuous doping profile, thereby providing the first quantitative evaluation of the effectiveness and the limitation of the gradient doping model in describing actual stepwise-doped devices.
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http://dx.doi.org/10.1038/s41598-022-16993-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334615PMC
July 2022

Repurposing of the antihistamine mebhydrolin napadisylate for treatment of Zika virus infection.

Bioorg Chem 2022 Jul 22;128:106024. Epub 2022 Jul 22.

CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing 100050 China. Electronic address:

Zika virus (ZIKV) infection can lead to severe neurological disorders and fetal defects, which has become a public health problem worldwide. However, effective clinical treatment for ZIKV infection was still arduous. Antihistamines are attractive candidates for drug repurposing due to their low price and widespread availability. Here we screened FDA-approved antihistamine drugs to obtain anti-ZIKV candidate compounds and identified mebhydrolin napadisylate (MHL) that exhibits the potent inhibition of ZIKV infection in various cell lines in a histamine H1 receptor-independent manner. Mechanistic studies suggest that MHL acts as a ZIKV NS5 RNA-dependent RNA polymerase (RdRp) inhibitor, supported by a structure-activity relationship (SAR) analysis showing the correlation between the inhibitory effect upon viral RNA synthesis and ZIKV infectivity. Furthermore, MHL was shown to bind ZIKV NS5 RdRp in vitro and predicted to interact with key residues at the active site of ZIKV NS5 RdRp by molecular docking analysis. Our data together suggest that MHL suppresses ZIKV infection through the inhibition of ZIKV NS5 RdRp activity. This study highlights that MHL might be a promising clinical anti-ZIKV therapeutic.
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http://dx.doi.org/10.1016/j.bioorg.2022.106024DOI Listing
July 2022

Sustainable Economic Development, Digital Payment, and Consumer Demand: Evidence from China.

Authors:
Rui Zhou

Int J Environ Res Public Health 2022 Jul 20;19(14). Epub 2022 Jul 20.

School of Economics, Fudan University, Shanghai 200433, China.

In this era, the global COVID-19 pandemic has hit the economy hard. In the context of great challenges to sustainable economic development, it is of great practical significance to study how digital payment can promote consumer demand and sustainable economic development. From the perspective of sustainable economic development, this paper selects panel data of various provinces in China from 2011 to 2020 to test the correlation between digital payment and consumer demand by constructing econometric models and selecting relevant indicators, so as to reveal the impact of digital payment on consumer demand and sustainable economic development. Research shows that: (1) in the context of the COVID-19 pandemic, digital payments play a special and very important role in promoting household consumption and sustainable economic development; (2) the empirical results show that digital payment has a significant positive impact on consumer demand, which indicates that digital payment has an obvious promotion effect on consumer demand; (3) further research shows that the impact of digital payment on consumer demand has obvious heterogeneity. From the perspective of regional differences, digital payment has a significant positive impact on consumer demand in the eastern and western regions, while the impact is not obvious in the northeast and central regions, even though it also has a positive impact. From the perspective of urban-rural differences, digital payment has a significant impact on consumer demand in both urban and rural areas, and this impact is greater in rural areas than in urban areas. However, from the perspective of development stage, the stage characteristics of digital payment's impact on consumer demand in each region are not obvious, which may be caused by the short sample range. In addition, this paper also puts forward relevant suggestions for other countries to learn from.
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http://dx.doi.org/10.3390/ijerph19148819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319053PMC
July 2022

Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.

Front Oncol 2022 8;12:838637. Epub 2022 Jul 8.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

DNA replication is a process fundamental in all living organisms in which deregulation, known as replication stress, often leads to genomic instability, a hallmark of cancer. Most malignant tumors sustain persistent proliferation and tolerate replication stress increasing reliance to the replication stress response. So whilst replication stress induces genomic instability and tumorigenesis, the replication stress response exhibits a unique cancer-specific vulnerability that can be targeted to induce catastrophic cell proliferation. Radiation therapy, most used in cancer treatment, induces a plethora of DNA lesions that affect DNA integrity and, in-turn, DNA replication. Owing to radiation dose limitations for specific organs and tumor tissue resistance, the therapeutic window is narrow. Thus, a means to eliminate or reduce tumor radioresistance is urgently needed. Current research trends have highlighted the potential of combining replication stress regulators with radiation therapy to capitalize on the high replication stress of tumors. Here, we review the current body of evidence regarding the role of replication stress in tumor progression and discuss potential means of enhancing tumor radiosensitivity by targeting the replication stress response. We offer new insights into the possibility of combining radiation therapy with replication stress drugs for clinical use.
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http://dx.doi.org/10.3389/fonc.2022.838637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305609PMC
July 2022

Efficacy of thymosin α1 in management of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043).

Int J Radiat Oncol Biol Phys 2022 Jul 20. Epub 2022 Jul 20.

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

Purpose: To evaluate the efficacy of thymosin α1 in management of radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemoradiotherapy (CCRT).

Methods And Materials: This phase II, single-arm trial enrolled patients with unresectable LANSCLC of 18 to 75 years' old and an Eastern Cooperative Oncology Group performance status of 0 to 1. Eligible patients received definitive CCRT and weekly thymosin α1 from the start of CCRT till 2 months after CCRT. Patients were administered 51 Gy in 17 daily fractions or 40 Gy in 10 daily fractions in the first course followed by a re-evaluation and those patients without disease progression had an adaptive plan of 15 Gy in 5 daily fractions or 24 Gy in 6 daily fractions as a boost. Concurrent chemotherapy consisted of weekly docetaxel (25 mg/m) and nedaplatin (25 mg/m) during radiation therapy. The primary endpoint was the incidence of Grade (G) ≥2 RP. Secondary endpoints included the incidence of late pulmonary fibrosis, total lymphocyte count (TLC), serum C-reactive protein (CRP) levels, and the composition of gut microbiota. TLC and CRP data were collected at baseline, 2-3 weeks during CCRT, the end of CCRT, 2 and 6 months after CCRT. Fecal samples were collected at baseline and the end of CCRT. Patients treated with CCRT but without thymosin α1 intervention during the same period were selected as the control group by the propensity score matching method.

Results: Sixty-nine patients were enrolled in the study, and another 69 patients were selected as the control group. The incidence of G≥2 RP was lower in the study group compared with control cases (36.2% vs 53.6%, P=0.040). G1 late pulmonary fibrosis occurred in 2 (3.7%) patients of the control group compared with no event in the study group (P=0.243). Compared with the control group, the incidence of G3-4 lymphopenia (19.1% vs. 62.1%, P<0.001) was lower, and the median TLC nadir (0.51 k/µL vs. 0.30 k/µL, P<0.001) was higher in the study group. The proportion of patients with maximum CRP≥100 mg/L was lower in the study group (13.8% vs. 29.7% P=0.029). The diversity and community composition of the gut microbiota were not significantly different between the two groups.

Conclusions: Administration of thymosin α1 during and after CCRT was associated with significant reductions in G≥2 RP and G3-4 lymphopenia in patients with LANSCLC compared to historic controls.
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http://dx.doi.org/10.1016/j.ijrobp.2022.07.009DOI Listing
July 2022

Activated amino acid response pathway generates apatinib resistance by reprograming glutamine metabolism in non-small-cell lung cancer.

Cell Death Dis 2022 Jul 21;13(7):636. Epub 2022 Jul 21.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

The efficacy of apatinib has been confirmed in the treatment of solid tumors, including non-small-cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by apatinib and the precise mechanisms of drug resistance are largely unknown. In this study, we demonstrated that apatinib could reprogram glutamine metabolism in human NSCLC via a mechanism involved in amino acid metabolic imbalances. Apatinib repressed the expression of GLS1, the initial and rate-limiting enzyme of glutamine catabolism. However, the broken metabolic balance led to the activation of the amino acid response (AAR) pathway, known as the GCN2/eIF2α/ATF4 pathway. Moreover, activation of ATF4 was responsible for the induction of SLC1A5 and ASNS, which promoted the consumption and metabolization of glutamine. Interestingly, the combination of apatinib and ATF4 silencing abolished glutamine metabolism in NSCLC cells. Moreover, knockdown of ATF4 enhanced the antitumor effect of apatinib both in vitro and in vivo. In summary, this study showed that apatinib could reprogram glutamine metabolism through the activation of the AAR pathway in human NSCLC cells and indicated that targeting ATF4 is a potential therapeutic strategy for relieving apatinib resistance.
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http://dx.doi.org/10.1038/s41419-022-05079-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304404PMC
July 2022

Investigation of Titanium Mesh and Nano-Hydroxyapatite/Polyamide 66 Bone Graft in Cervical Reconstruction of Spondylosis After Sub-Total Vertebral Body Resection.

J Biomed Nanotechnol 2022 Apr;18(4):1187-1195

Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, 226000, China.

The nano-hydroxyapatite/polyamide 66 (n-HA/PA66) bionic bone column, as a high-performance tissue repair and replacement material, introduced as a high osteo-induction ability agent. Nanomaterial has significantly taken a place in orthopedic surgery, however, the efficacy of using n-HA/PA66 is yet to be established. In this regard, this study evaluated various sagittal parameters (such as imaging measurement) and clinical efficacy in postoperative patients, whom underwent cervical reconstruction surgery due to cervical spondylosis myelopathy (CSM). In this study, total 62 CSM cases were enrolled between October 2016 to March 2020, and were hospitalized for cervical reconstruction surgery. 31 cases were grafted with titanium mesh and 31 cases were grafted with n-HA/P66. The sagittal parameters such as cervical spine lateral radiographs (CCoob, CCoob, T1S, CSVA, and TIA) were taken before operation, after operation (within 1 week), 3, 6, and 9 months after operation. In order to evaluate the clinical efficacy, we used JOA scores before, after, 3 months, 6 months and 9 months after operation. Results showed that JOA scores after the re-examination in the two groups (titanium and n-HA/P66) were significantly higher than before the operation, suggesting a well postoperative functional recovery after surgery in both groups; however, there was no significant difference in JOA score and JOA improvement index between the two groups. In regard of angles measurement (CCobb, CCobb, T1S, CSVA, and TIA), we observed no significant difference between these two groups before and after the operation. In addition, we showed that CCobb and CCobb angle had a significant positive correlation; and CCobb angle is positively correlated with T1S, and negatively correlated with CSVA. Both titanium mesh and n-HA/PA66 can be well improved and maintained within 9 months after surgery with clinical efficacy, however, using n-HA/PA66 might have more benefits.
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http://dx.doi.org/10.1166/jbn.2022.3316DOI Listing
April 2022

Traceable machine learning real-time quality control based on patient data.

Clin Chem Lab Med 2022 Jul 19. Epub 2022 Jul 19.

Department of Laboratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, P.R. China.

Objectives: Patient-based real-time quality control (PBRTQC) has gained attention as an alternative/integrative tool for internal quality control (iQC). However, it is still doubted for its performance and its application in real clinical settings. We aim to generate a newly and easy-to-access patient-based real-time QC by machine learning (ML) traceable to standard reference data with assigned values by National Institute of Metrology of China (NIM), and to compare it with PBRTQC for clinical validity evaluation.

Methods: For five representative biochemistry analytes, 1,195 000 patient testing results each were collected. After data processing, independent training and test sets were divided. Machine learning internal quality control (MLiQC) was set up by Random Forest in ML and was validated by way of both metrology algorithm traceability and 4 PBRTQC methods recommended by IFCC analytical working group.

Results: MLiQC were established. As an example of albumin (ALB) at the critical bias, the uncertainty of MLiQC was 0.14%, which was evaluated by standard reference data produced by NIM. Compared with four optimal PBRTQC methods at critical bias, the average of the number of patient samples from a bias introduced until detected (ANPed) of MLiQC averagely decreased from 600 to 20. The median and 95 quantiles of NPeds (MNPed and 95NPed) of MLiQC were superior to all optimal PBRTQCs above 90% for all test items.

Conclusions: MLiQC is highly superior to PBRTQC and well-suited in real settings. The validation of the model from two aspects of algorithm traceability and clinical effectiveness confirms its satisfactory performance.
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http://dx.doi.org/10.1515/cclm-2022-0548DOI Listing
July 2022

A multi-model fusion algorithm as a real-time quality control tool for small shift detection.

Comput Biol Med 2022 Jul 12;148:105866. Epub 2022 Jul 12.

Department of Laboratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, PR China; Beijing Center for Clinical Laboratories, Beijing, PR China. Electronic address:

Background: Patient-based real-time quality control (PBRTQC), a complement to traditional QC, may eliminate matrix effect from QC materials, realize real-time monitoring as well as cut costs. However, the accuracy of PBRTQC has not been satisfactory as physicians expect till now. Our aim is to set up a artificial intelligence-based QC for small error detection in real laboratory settings. Taking tPSA as our unique research subject, data extraction, data stimulation, data partition, model construction and evaluation were designed.

Methods: 84241 deidentified results for tPSA were extracted from Laboratory Information System of Aviation General Hospital. The data set was accumulated by way of data simulation. Independent training and test datasets were separated. After three classification models (RF, SVM and DNN) in ML constructed and weighted by information entropy, a multi-model fusion algorithm was generated. Performance of the fusion model was evaluated by comparing with optimal PBRTQC.

Results: For 4 PBRTQC methods, MovSO showed overall better performance for 0.2 μg/L bias and optimal MNPed was equal to 200. For the fusion model, MNPeds were less than 12 for all biases, and ACC surpassed MovSO nearly 100 times. Except for 0.01 μg/L bias, ACC was more than 0.9 for the rest of biases. FPR was apparently lower than MovSO, only 0.2% and 0.1%.

Conclusion: The fusion model shows outstanding performance and reduces incorrect and omitting error detection, adaptable for the real settings.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105866DOI Listing
July 2022

Internet addiction in adolescent psychiatric patient population: A hospital-based Study from China.

Clin Child Psychol Psychiatry 2022 Jul 15:13591045221115289. Epub 2022 Jul 15.

The Second School of Clinical Medicine, 70570Southern Medical University, China.

Background: Internet is gradually reshaping adolescents' behaviors in China. It is important to identify the prevalence and risk factors to predict Internet addiction among adolescent psychiatric patients.

Methods: The survey was conducted among inpatient or outpatient adolescent patients with mental disorders. All participants were interviewed face-to-face and completed Young Internet Addiction Test and other relevant assessments. Binary logistic regression analysis was used to exam between-group differences of internet addiction.

Result: The prevalence for internet addiction (mild to severe) in adolescent psychiatric patients was 80.2%, where the prevalence for "medium and severe internet addiction was 25.5%. Logistic regression analysis identified two independent predictors for "medium and severe internet addiction" including the total score of Adolescent Non-suicidal-self-injury (NSSI) Behavior Function Assessment Scale (ANBFAS) and the diagnosis of generalized anxiety disorder (GAD) (R =0.27, = .02 for total ANBFAS score, = .01 for GAD) in psychiatric adolescent patients.

Conclusion: The prevalence of internet addiction is notably high among adolescent psychiatric patients in China. Coping for Internet addiction in adolescent psychiatric patients should conclude the coping of NSSI and GAD.
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http://dx.doi.org/10.1177/13591045221115289DOI Listing
July 2022

Engineering and screening of novel β-1,3-xylanases with desired hydrolysate type by optimized ancestor sequence reconstruction and data mining.

Comput Struct Biotechnol J 2022 27;20:3313-3321. Epub 2022 Jun 27.

Department of Bioengineering and Biotechnology, Huaqiao University, Xiamen, Fujian Province 361021, China.

Engineering of hydrolases to shift their hydrolysate types has not been attempted so far, though computer-assisted enzyme design has been successful. A novel integrative strategy for engineering and screening the β-1,3-xylanase with desired hydrolysate types was proposed, with the purpose to solve problems that the separation and preparation of β-1,3--oligosaccharides was in high cost yet in low yield as monosaccharides existed in the hydrolysates. By classifying the hydrolysate types and coding them into numerical values, two robust mathematical models with five selected attributes from molecular docking were established based on LogitBoost and partial least squares regression with overall accuracy of 83.3% and 100%, respectively. Then, they were adopted for efficient screening the potential mutagenesis library of β-1,3-xylanases that only product oligosaccharides. The virtually designed AncXyl10 was selected and experimentally verified to produce only β-1,3-xylobiose (60.38%) and β-1,3-xylotriose (39.62%), which facilitated the preparation of oligosaccharides with high purity. The underlying mechanism of AncXyl10 may associated with the gap processing and ancestral amino acid substitution in the process of ancestral sequence reconstruction. Since many carbohydrate-active enzymes have highly conserved active sites, the strategy and their biomolecular basis will shield a new light for engineering carbohydrates hydrolase to produce specific oligosaccharides.
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http://dx.doi.org/10.1016/j.csbj.2022.06.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251504PMC
June 2022

Assessing dynamic metabolic heterogeneity in non-small cell lung cancer patients via ultra-high sensitivity total-body [F]FDG PET/CT imaging: quantitative analysis of [F]FDG uptake in primary tumors and metastatic lymph nodes.

Eur J Nucl Med Mol Imaging 2022 Jul 11. Epub 2022 Jul 11.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

Purpose: This study aimed to quantitatively assess [F]FDG uptake in primary tumor (PT) and metastatic lymph node (mLN) in newly diagnosed non-small cell lung cancer (NSCLC) using the total-body [F]FDG PET/CT and to characterize the dynamic metabolic heterogeneity of NSCLC.

Methods: The 60-min dynamic total-body [F]FDG PET/CT was performed before treatment. The PTs and mLNs were manually delineated. An unsupervised K-means classification method was used to cluster patients based on the imaging features of PTs. The metabolic features, including Patlak-Ki, Patlak-Intercept, SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features, were extracted from PTs and mLNs. The targeted next-generation sequencing of tumor-associated genes was performed. The expression of Ki67, CD3, CD8, CD34, CD68, and CD163 in PTs was determined by immunohistochemistry.

Results: A total of 30 patients with stage IIIA-IV NSCLC were enrolled. Patients were divided into fast dynamic FDG metabolic group (F-DFM) and slow dynamic FDG metabolic group (S-DFM) by the unsupervised K-means classification of PTs. The F-DFM group showed significantly higher Patlak-Ki (P < 0.001) and SUV (P < 0.001) of PTs compared with the S-DFM group, while no significant difference was observed in Patlak-Ki and SUV of mLNs between the two groups. The texture analysis indicated that PTs in the S-DFM group were more heterogeneous in FDG uptake than those in the F-DFM group. Higher T cells (CD3/CD8) and macrophages (CD68/CD163) infiltration in the PTs were observed in the F-DFM group. No significant difference was observed in tumor mutational burden between the two groups.

Conclusion: The dynamic total-body [F]FDG PET/CT stratified NSCLC patients into the F-DFM and S-DFM groups, based on Patlak-Ki and SUV of PTs. PTs in the F-DFM group seemed to be more homogenous in terms of [F]FDG uptake than those in the S-DFM group. The higher infiltrations of T cells and macrophages were observed in the F-DFM group, which suggested a potential benefit from immunotherapy.
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http://dx.doi.org/10.1007/s00259-022-05904-8DOI Listing
July 2022

miR-19b-3p/PKNOX1 Regulates Viral Myocarditis by Regulating Macrophage Polarization.

Front Genet 2022 24;13:902453. Epub 2022 Jun 24.

Zhejiang Chinese Medical University, Hangzhou, China.

The purpose of this study was to study the role and mechanism of miR-19b-3p in regulating myocardial inflammation and injury of viral myocarditis in viral myocarditis induced by Coxsackievirus B3 (CVB3). A CVB3 infection mouse model was established, the survival rate of mice was recorded after different treatments, cardiac function was detected, the degree of myocardial inflammatory infiltration and injury was detected by immunohistochemical and biochemical analyses, miR-19b-3p and PKNOX1 expression in cardiac tissue and cardiac infiltrating macrophages was detected using RT-PCR, and isolated mouse bone marrow-derived macrophages and the differentiation of macrophages after different transfections were detected. Finally, the binding of miR-19b-3p and PKNOX1 was verified by the dual luciferase reporter gene. The results showed that the expression of miR-19b-3p was significantly downregulated in the cardiac tissue and infiltrating macrophages of CVB3-infected mice, while the expression of PKNOX1 was upregulated. Upregulation of miR-19b-3p has protective effects against CVB3-induced myocardial injury in mice, such as weight gain, prolonged survival, increased left ventricular ejection fraction and left ventricular short axis shortening, reduced inflammation, creatine kinase isoenzyme (CK)-MB, and lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels decreased, while interferon-γ and interleukin-6 (IL-6) increased, and the M2/M1 cell ratio was upregulated. In conclusion, miR-19b-3p can regulate macrophage polarization by targeting PKNOX1, and has a protective effect against CVB3-induced inflammation and myocardial injury.
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http://dx.doi.org/10.3389/fgene.2022.902453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264346PMC
June 2022

Enhanced Therapeutic Efficacy of Combining Losartan and Chemo-Immunotherapy for Triple Negative Breast Cancer.

Front Immunol 2022 23;13:938439. Epub 2022 Jun 23.

Department of Nuclear Medicine and Positron Emission Tomography (PET) Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, which is relatively resistant to anti-programmed cell death-1 (α-PD1) therapy, characterized as non-immunogenic, dense stroma and accumulation of M2 tumor-associated macrophages (TAMs). Despite progress in strategies to deplete extracellular matrix (ECM) and enhance tumor-cell immunogenicity, the combinatorial anti-cancer effects with α-PD1 need to be explored. Here, we applied doxorubicin hydrochloride liposome (Dox-L) as immunogenic cell death (ICD)-inducing nano-chemotherapy and used losartan as stroma-depleting agent to improve α-PD1 efficacy (Losartan + Dox-L + α-PD1). The results showed that losartan could cause ECM reduction, facilitating enhanced delivery of Dox-L and further dendritic cell (DC) maturation. Additionally, losartan could also alleviate hypoxia for TNBC, thus reprogramming pro-cancer M2 TAMs to anti-cancer M1 TAMs, successfully overcoming immune-suppressive microenvironment. These modifications led to a significant increase in T cells' infiltration and augmented anti-tumor immunity as exemplified by the notable reduction in tumor size and lung metastases. In summary, our findings support that combined treatment of losartan with Dox-L normalizes immunological-cold microenvironment, improves immuno-stimulation and optimizes the efficacy of TNBC immunotherapy. A novel combinational strategy with FDA-approved compounds proposed by the study may potentially be useful in TNBC clinical treatment.
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http://dx.doi.org/10.3389/fimmu.2022.938439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259940PMC
June 2022

Efficacy and safety of oral Chinese medicine on cancer-related fatigue for lung cancer patients after chemotherapy: Protocol for systematic review and meta-analysis.

PLoS One 2022 30;17(6):e0270203. Epub 2022 Jun 30.

Department of Traditional Chinese Medicine/National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy for Medical Sciences and Peking Union Medical College, Beijing, China.

Introduction: Lung cancer has the highest mortality rate of about 18.0% among malignant tumors worldwide, and chemotherapy is the main treatment. 80% of patients receiving chemotherapy suffers from cancer-related fatigue, which is the most severe symptom, with a large effect on quality of life as well as prognosis. Oral Chinese medicine, a kind of complementary and alternative medicine, has been proved to benefit lung cancer patients. However, no studies have reviewed whether it can reduce fatigue in lung cancer patients after chemotherapy, which is the purpose of our study.

Methods: Two reviewers will systematically and independently retrieve papers, select studies for inclusion, extract data, and assess risk of bias. The following nine databases will be searched: China National Knowledge Infrastructure, Wan Fang database, Chinese Scientific Journals Database, Chinese biomedical literature service system, PubMed, Web of Science, OVID, Scopus, and EMBASE from inception to February, 2022. Included studies will only be randomized controlled trials. Primary outcome is cancer-related fatigue. Secondary outcomes are quality of life, immunologic function, and the incidence of adverse events. We will use RoB 2 tool to assess the risk of bias and RevMan to analyze data. Risk ratios will be calculated for dichotomous data and mean differences for continuous data. Random-effect model will be used to integrate statistical effects. Meta-regression, subgroup and sensitivity analyses will be carried out. We will evaluate the strength and overall quality of evidence with four levels: very low, low, moderate, and high.

Results: The review of current evidence of oral Chinese medicine on cancer-related fatigue for lung cancer patients after chemotherapy will be narratively summarized and quantitatively analyzed.

Conclusion: The definitive conclusion will help physicians to determine whether oral Chinese medicine is an effective treatment for reducing fatigue in lung cancer patients after chemotherapy in clinical settings.

Systematic Review Registration: PROSPERO CRD42021292576.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270203PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246193PMC
June 2022

Use of perampanel in children with refractory epilepsy of genetic aetiology

Epileptic Disord 2022 08;24(4):687-695

Department of Neurology, Children’s Hospital of Soochow University

Objective: Pathogenic mutations in refractory childhood epilepsy are being increasingly discovered. In this study, we analysed the efficacy and tolerability of perampanel as treatment for genetically-related refractory childhood epilepsy.

Methods: This prospective study, conducted in China, included 50 patients with refractory epilepsy of genetic aetiology, who were treated with adjunctive perampanel therapy. Perampanel treatment was considered effective when the seizure frequency was reduced by >50%. Perampanel treatment was evaluated over at least nine months, from January 2020.

Results: A total of 184 paediatric patients with refractory epilepsy received addon perampanel therapy, and of these, 128 received treatment for ≥nine months and underwent genetic analysis. Fifty children were identified with pathogenic or likely pathogenic variants. A total of 24 different causative monogenic mutations were found, and the most common causative monogenic variants were observed in the SCN1A gene (n = 15). The mean maximal dose of perampanel was 3.4±1.2 mg/day in responders. The response rates to perampanel in children with genetically-related refractory epilepsy (n=50) were 68.0%, 58.0%, and 46.0% at three, six and nine months post-initiation, respectively. Adverse events were reported in 23 patients (46.0%) with genetic aetiology. Somnolence, ataxia, and irritability were the most common adverse events. The response rates to perampanel in children with pathogenic or likely pathogenic variants associated with Dravet syndrome, tuberous sclerosis, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, Rett syndrome, and dentatorubral-pallidoluysian atrophy were high.

Significance: A low maintenance dose of perampanel may be effective and well-tolerated as adjunctive treatment in children with refractory epilepsy of genetic aetiology.
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http://dx.doi.org/10.1684/epd.2022.1443DOI Listing
August 2022

JrWRKY21 interacts with JrPTI5L to activate the expression of JrPR5L for resistance to Colletotrichum gloeosporioides in walnut.

Plant J 2022 Jun 29. Epub 2022 Jun 29.

College of Forestry, Shandong Agricultural University, Taian, Shandong Province, China.

Walnut (Juglans regia L.) anthracnose, induced by Colletotrichum gloeosporioides, is a catastrophic disease impacting the walnut industry in China. Although WRKY transcription factors play a key role in plant immunity, the function of the WRKY gene family in walnut resistance to C. gloeosporioides is not clear. Here, through transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR), we identified a differentially expressed gene, JrWRKY21, that was significantly upregulated upon C. gloeosporioides infection in walnut. JrWRKY21 positively regulated walnut resistance to C. gloeosporioides, as demonstrated by virus-induced gene silencing and transient gene overexpression. Additionally, JrWRKY21 directly interacted with the transcriptional activator of the pathogenesis-related (PR) gene JrPTI5L in vitro and in vivo, and could bind to the W-box in the JrPTI5L promoter for transcriptional activation. Moreover, JrPTI5L could induce the expression of the PR gene JrPR5L through binding to the GCCGAC motif in the promoter. Our data support that JrWRKY21 can indirectly activate the expression of the JrPR5L gene via the WRKY21-PTI5L protein complex to promote resistance against C. gloeosporioides in walnut. The results will enhance our understanding of the mechanism behind walnut disease resistance and facilitate the genetic improvement of walnut by molecular breeding for anthracnose-resistant varieties.
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http://dx.doi.org/10.1111/tpj.15883DOI Listing
June 2022

Dissecting the ferroptosis-related prognostic biomarker and immune microenvironment of driver gene-negative lung cancer.

Exp Biol Med (Maywood) 2022 Jun 28:15353702221102872. Epub 2022 Jun 28.

Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.

Despite significant advances in targeted and immune therapy for non-small cell lung cancer (NSCLC), effective therapies for wild-type epidermal growth factor receptor/anaplastic lymphoma kinase () with low expression of programmed death ligand-1 (PD-L1) NSCLC remain elusive. Numerous studies have shown that ferroptosis plays an essential role in antitumor activity. To identify the molecular regulation patterns associated with ferroptosis, 351 NSCLC samples with low-level PD-L1 were extracted from The Cancer Genome Atlas (TCGA) and clustered using the k-means clustering technique. The two clusters associated with ferroptosis showed significantly different prognoses. In total, 169 differential expression genes (DEGs) were identified. Cluster differential analysis revealed that Cluster 1 had a significantly poorer overall survival (OS) and was associated with more negative immune regulation. In addition, TCGA samples were randomly assigned in a 7:3 ratio to a training group or testing group. A signature of eight genes associated with ferroptosis was established in the training cohort using DEGs and validated in the test cohort and three independent cohorts (GSE72049, GSE41271, and GSE50081). The 5-year area under the curve (AUC) was 0.713, which was significantly higher than that of other predictors, including TNM stage and age. Furthermore, the risk score was associated with immune function, immune infiltration, and immunotherapy response, with high-risk patients having a worse prognosis, an immune-suppressing phenotype, and a poor response to immune checkpoint inhibitors. This study aims to contribute to our understanding of the biological role of ferroptosis in NSCLC with low-level PD-L1, laying the groundwork for the development of novel therapeutic strategies.
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http://dx.doi.org/10.1177/15353702221102872DOI Listing
June 2022

Transition in plant-plant facilitation in response to soil water and phosphorus availability in a legume-cereal intercropping system.

BMC Plant Biol 2022 Jun 28;22(1):311. Epub 2022 Jun 28.

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

Background: The tradeoff between negative and positive interactions of facilitated species and facilitators may depend on the degree of resource availability in agroecosystems. However, the rhizospheric mechanisms driving trade-offs that occur along phosphorus (P) and water availability gradients have not yet been systematically clarified. We established three types of root isolation conditions (no barrier, nylon barrier and solid barrier) at different P and water addition levels to address the above issue in a maize-grass pea intercropping system.

Results: The total yield and biomass net effect (NE) and the relative interaction index (RII) were significantly higher than 0 under all environmental conditions, demonstrating that plant-plant interactions generated positive effects in the intercropping system. The maize yield and biomass RII were 0.029-0.095 and 0.018-0.066, respectively, which indicated that maize growth was constantly facilitated. However, the RII for grass pea yield and biomass exhibited a different trend in comparison with maize. It was higher than 0 (as the facilitated species) under low soil P and moisture conditions and transitioned to values lower than 0 (facilitator species) under high P and moisture conditions, which showed that the type and intensity of plant-plant interactions steadily shifted with the applied stressors. Direct interactions decreased the maize rhizospheric soil pH by 1.5% and 1.9% under Low-P conditions. Notably, the rhizospheric soil acid and alkaline phosphatase secretions of maize and grass pea increased by 17.4-27.4% and 15.3-27.7%, respectively, in P-deficient soils. These results show that plant-plant interactions can effectively relieve P stress by mineralizing organophosphorus in P-deficient soils. Furthermore, the above tendency became more pronounced under drought-stressed conditions. The nylon barrier partially restricted the exchange and utilization of available nutrients and decreased the total yield and biomass by 1.8-7.8% and 1.1-7.8%, respectively. The presence of a solid barrier completely restricted interspecific rhizospheric interactions and decreased the total yield and biomass by 2.1-13.8% and 1.6-15.7%, respectively. Phytate and KHPO addition intensified asymmetric interspecific competition, and grass pea was consistently subjected to competitive pressures.

Conclusion: Briefly, the tradeoff between facilitation and competition was driven by rhizospheric interactions, and the transition in the intensity and type of interaction was highly dependent on resource availability in a biologically diverse system.
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http://dx.doi.org/10.1186/s12870-022-03706-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238078PMC
June 2022

Development and Application of Two Inducible Expression Systems for Streptococcus suis.

Microbiol Spectr 2022 Jun 27:e0036322. Epub 2022 Jun 27.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural Universitygrid.35155.37, Wuhan, China.

Streptococcus suis is an important zoonotic bacterial pathogen posing a threat to the pig industry as well as public health, for which the mechanisms of growth and cell division remain largely unknown. Developing convenient genetic tools that can achieve strictly controlled gene expression is of great value for investigating these fundamental physiological processes of S. suis. In this study, we first identified three strong constitutive promoters, P, P, and P, in S. suis. Promoter P was used to drive the expression of repressor genes and , and the operator sequences were added within promoters P and P. By optimizing the insertion sites of the operator sequence, we successfully constructed an anhydrotetracycline (ATc)-inducible expression system and an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible expression system in S. suis. We showed that these two systems provided inducer-concentration- and induction-time-dependent expression of the reporter gene. By using these tools, we investigated the subcellular localization of a key cell division protein, FtsZ, which showed that it could be correctly localized to the midcell region. In addition, we constructed a conditional knockout strain for the gene, which is an essential gene, and showed that our ATc-inducible promoter could provide strictly controlled expression of in , suggesting that our inducible expression systems can be used for deletion of essential genes in S. suis. Therefore, for the first time we developed two inducible expression systems in S. suis and showed their applications in the study of an important cell division protein and an essential gene. These genetic tools will further facilitate the functional study of other important genes of S. suis. Streptococcus suis is an important zoonotic bacterial pathogen. Studying the mechanisms of cell growth and division is important for the identification of novel antimicrobial drug targets. Inducible expression systems can provide strictly controlled expression of the protein of interest and are useful tools to study the functions of physiologically important proteins. However, there is a lack of convenient genetic tools that can achieve inducible protein expression in S. suis. In this study, we developed two (ATc-inducible and IPTG-inducible) inducible expression systems and showed their applications in a subcellular localization study of a cell division protein and the construction of conditional knockout of essential genes in S. suis. These systems will be useful for functional studies of important proteins of S. suis.
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http://dx.doi.org/10.1128/spectrum.00363-22DOI Listing
June 2022

A Combinatorial Vaccine Containing Inactivated Bacterin and Subunits Provides Protection Against Infection in Mice and Pigs.

Front Vet Sci 2022 7;9:902497. Epub 2022 Jun 7.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

(APP) is the etiological agent of porcine contagious pleuropneumonia (PCP) that causes great economic losses in the swine industry. Currently, vaccination is still a commonly used strategy for the prevention of the disease. Commercially available vaccines of this disease, including inactivated bacterins and subunit vaccines, have clinical limitations such as side effects and low cross-protection. In this study, a combinatorial vaccine (Bac-sub) was developed, which contained inactivated bacterial cells of a serovar 1 strain and three recombinant protoxins (rApxIA, rApxIIA, and rApxIIIA). Its side effects, immune protection, and cross-protection were evaluated and compared with a commercial subunit vaccine and a commercial trivalent bacterin in a mouse infection model. The results revealed that the Bac-sub vaccine showed no obvious side effects, and induced higher levels of Apx toxin-specific IgG, IgG1, and IgG2a than the commercial vaccines after booster. After a challenge with virulent strains of serovars 1, 5, and 7, the Bac-sub vaccine provided greater protection (91.76%, 100%, and 100%, respectively) than commercial vaccines. Much lower lung bacterial loads (LBLs) and milder lung lesions were observed in the Bac-sub-vaccinated mice than in those vaccinated with the other two vaccines. The protective efficacy of the Bac-sub vaccine was further evaluated in pigs, which showed that vaccinated pigs displayed significantly milder clinical symptoms and lung lesions than the unvaccinated pigs after the challenge. Taken together, Bac-sub is a safe and effective vaccine that could provide high protection against infection in both mice and pigs.
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http://dx.doi.org/10.3389/fvets.2022.902497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212066PMC
June 2022

The Impact of Legal Recycling Constraints and Carbon Trading Mechanisms on Decision Making in Closed-Loop Supply Chain.

Int J Environ Res Public Health 2022 06 16;19(12). Epub 2022 Jun 16.

Department of Industrial and Systems Engineering, The University of Tennessee, Knoxville, TN 37996, USA.

To investigate how legal constraints on the recycling rate of used products and carbon trading mechanisms affect the profits and other decisions of supply chain system members, this paper develops and solves a two-cycle game model in which the manufacturer dominates while the retailer takes a secondary position; the manufacturer produces only non-low-carbon new products in the first cycle and both new and low-carbon remanufactured products in the second cycle. Simultaneously, the effects of parameters such as recovery rate, unit carbon trading price, and carbon emission reduction factor on the decision making of members of the supply chain system are also discussed. Finally, the conclusions are verified by numerical analysis: (1) When carbon reduction is low, the manufacturer will choose the highest recycling rate to obtain the highest profit, and when carbon reduction is high, manufacturers tend to choose not to recycle when the minimum recycling rate bound by law harms the interests of manufacturers. (2) Under the implementation of the carbon trading mechanism, the unit carbon trading price affects the profits of the members of the supply chain system depending on the size of the carbon emission reduction, and the two are negatively correlated at lower carbon emission reductions and positively correlated at higher carbon emission reductions. (3) From the perspective of supply chain system members' interests, legal constraints and the existence of carbon trading mechanisms are not always conducive to increasing the margins of members of the supply chain system, both relevant to the size of carbon emission reductions. (4) From the perspective of environmental benefits, supply chain members do not need to pay economic costs in all cases to contribute to environmental benefits, and the existence of minimum recycling rate constraints and carbon trading mechanisms are conducive to achieving carbon reduction targets.
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http://dx.doi.org/10.3390/ijerph19127400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224483PMC
June 2022

The Impact of Enhancing Diet Quality or Dietary Supplementation of Flavor and Multi-Enzymes on Primiparous Lactating Sows.

Animals (Basel) 2022 Jun 8;12(12). Epub 2022 Jun 8.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, 211 Huimin Road, Wenjiang District, Chengdu 611130, China.

This study was aimed to explore how a high-quality diet or a flavor plus multi-enzyme diet affects the feed intake, nutrient digestibility and antioxidation capacity of lactating sows and the growth of their progeny. Thirty primiparous sows were randomly assigned to three treatments from d 2 of lactation until weaning (d 21): control (CON), with a basal diet; high quality (HQ), with 200 kcal/kg higher net energy than CON; or the CON diet supplemented with 500 mg/kg flavor and 100 mg/kg multi-enzymes (F + E). Sows fed with the HQ or F + E diets improved piglets' live weight ( < 0.05) and average daily weight gain ( < 0.10), litter weight gain ( < 0.10) and piglet growth to milk yield ratio ( < 0.10). Compared with CON, the HQ and F + E groups increased the digestibility of ether extract, ash, neutral detergent fiber, crude fiber and phosphorus ( < 0.10), and the HQ group also increased dry matter, gross energy, crude protein, acid detergent fiber and energy intake ( < 0.05). Compared with CON, the F + E group decreased serum urea nitrogen and aspartate aminotransferase ( < 0.05) and enhanced superoxide dismutase, catalase and glutathione peroxidase, but it decreased malondialdehyde in milk supernatant ( < 0.05).
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http://dx.doi.org/10.3390/ani12121493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219450PMC
June 2022

Resilience and Prosocial Behavior Among Chinese University Students During COVID-19 Mitigation: Testing Mediation and Moderation Models of Social Support.

Psychol Res Behav Manag 2022 16;15:1531-1543. Epub 2022 Jun 16.

Department of Sociology & Psychology, School of Public Administration, Sichuan University, Chengdu, People's Republic of China.

Purpose: Suffering during events such as the COVID-19 pandemic threatens university students' physical and psychological health. Given the literature indicating the protective role of resilience and social support, the current study explored the mediating and moderating roles of social support in the association between resilience and prosocial behavior among university students in mainland China during COVID-19 mitigation.

Methods: We conducted an online survey using convenience sampling from 23rd February to 3rd March 2020 among Chinese university students who had encountered home-quarantine due to the COVID-19 pandemic. Self-report scales were used to measure levels of resilience (Connor-Davidson Resilience Scale), social support (the Social Support Scale), and prosocial behavior (Prosocial Tendencies Measure). A total of 313 university students participated in this online survey. Hayes PROCESS macro for SPSS was used to test the hypothesized mediating and moderating effects of social support in the relationship between resilience and prosocial behavior.

Results: Pearson's correlations analysis showed that all outcomes of interest were positively associated. Importantly, social support (subjective support, objective support, and support utilization) mediated the indirect link of resilience with prosocial behavior. Furthermore, moderation analyses indicated that support utilization played a moderating role in this link. Support utilization may reduce the negative influence of COVID-19 on university students' prosocial behavior and serve as a protective factor between resilience and prosocial behavior in highly stressful contexts.

Conclusion: Our findings enrich research on prosocial behavior by investigating the potential internal and external variables that influence such behavior during periods of suffering. Findings also provide evidence for the need to promote university students' prosocial behavior.
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http://dx.doi.org/10.2147/PRBM.S364356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208667PMC
June 2022

Therapeutic Effect of Astragali Radix Extract Injection Combined with Bone Marrow Mesenchymal Stem Cells in Bleomycin-Induced Pulmonary Fibrotic Rats.

Evid Based Complement Alternat Med 2022 13;2022:4933255. Epub 2022 Jun 13.

Geriatrics Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.

Pulmonary fibrosis is a serious disease for which effective drugs are unavailable. Here, we treated rat models of bleomycin (BLM)-induced pulmonary fibrosis with Astragali Radix extract injection (AI) combined with or without bone marrow mesenchymal stem cells (BMSCs). We injected rats intratracheally with BLM and transplanted BMSCs tail vein injection 15 days later. We also intraperitoneally injected AI daily from days 15 to 28. Changes in lung pathology and function, as well as the levels of matrix metalloproteinases, collagen, C-X-C motif chemokine ligand 12 (CXCL12), and cluster of differentiation 90 (CD90) were assessed. The results revealed that compared with the BLM group, groups treated with ARE and BMSCs (alone or combined) reduced the expression levels of TGF-1 and collagens I and III, ameliorated pathological lung fibrotic damage, and improved lung function. The expression levels of MMP-1, MMP-3, and MMP-9 were reduced by either AI or BMSCs alone, whereas those of MMP-3, MMP-9, TIMP-1, CXCL12, and CD90 were elevated by combined AI and BMSCs compared with the BLM group. Overall, these findings demonstrated that AI and BMSCs both can reduce damage caused by PF in rats and that AI altered the expression of chemokines and surface markers in BMSCs.
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http://dx.doi.org/10.1155/2022/4933255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208943PMC
June 2022

-Heterocyclic Thione-Protected Ag Tetrahedra and Ag Cubes Cocrystallized in a Single Crystal.

Inorg Chem 2022 Jun 6;61(24):9251-9256. Epub 2022 Jun 6.

College of Chemistry and Materials Science, and Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University, Guangzhou 510632, China.

Polynuclear silver clusters have attracted intensive attention in the academic community owing to their rich physicochemical properties. The development of thione-protected silver clusters has been lagging behind the well-explored thiolate-protected silver-sulfide clusters. Herein, we report two -heterocyclic thione-protected silver clusters: [Ag(2-TBI)(SO)] () and [[email protected](2-TBI)(SO)] () (2-TBI = 2-thiobenzimidazol), which cocrystallize to form cluster-based molecular crystals with a CaF-type structure. The cocrystal shows high thermal stability in air. Notably, the two cluster-based layers are alternately assembled to exhibit a unique -vector-differential crystallographic arrangement. This work may lay a foundation for synthesis of atomically precise and stable silver clusters using readily available -heterocyclic thione ligands.
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http://dx.doi.org/10.1021/acs.inorgchem.2c00900DOI Listing
June 2022

A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis.

Cell Metab 2022 Aug 14;34(8):1168-1182.e6. Epub 2022 Jun 14.

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan 410008, China. Electronic address:

Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.
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http://dx.doi.org/10.1016/j.cmet.2022.05.009DOI Listing
August 2022

Combination of metformin and oxaliplatin inhibits gastric cancer cell proliferation and induces apoptosis.

Acta Biochim Pol 2022 Jun;69(2):321-326

Department of General Surgery, Wuhan No.4 Hospital, Wuhan, 430033, China.

Background: Gastric cancer is one of the most common cancers worldwide. The disease has a poor prognosis, especially when the tumor becomes inoperable. The present study investigated the potential synergistic effects of oxaliplatin and metformin in gastric cancer cells.

Methods: The effect of oxaliplatin and metformin on cell proliferation was assessed with CCK-8 assay in human gastric cancer cell lines SGC7901 and SNU-16, where , the IC50 and (combination index) CI values were determined. RT-PCR and Western blotting were used to determine mRNA and protein expression levels of cell cycle- and apoptosis-related genes. The apoptotic rate was detected with flow cytometry in SGC7901 and SNU-16 cells.

Results: The CCK-8 assay showed inhibited proliferation of SGC7901 and SNU-16 cells upon oxaliplatin or metformin treatment and an increase in inhibitory potency when the drugs were administered in combination. Similarly, cell apoptosis was increased in both cell lines in the combination group compared to the metformin and oxaliplatin groups. Both metformin and oxaliplatin reduced Bcl-2 and increased Bax and caspase-3 expression in SGC7901 and SNU-16; and these effects were enhanced when the drugs were used in combination.

Conclusion: The combination of metformin and oxaliplatin inhibited proliferation and induced apoptosis in gastric cancer cells. The underlying mechanisms may be related to the suppression of cyclin D1, Bcl-2 and the increase of expression of Bax and caspase-3.
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http://dx.doi.org/10.18388/abp.2020_5750DOI Listing
June 2022

Total thyroidectomy versus hemithyroidectomy with intraoperative radiofrequency ablation for unilateral thyroid cancer with contralateral nodules: A propensity score matching study.

J Otolaryngol Head Neck Surg 2022 Jun 11;51(1):26. Epub 2022 Jun 11.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, People's Republic of China.

Background: For unilateral papillary thyroid carcinoma (PTC) patients with contralateral benign nodules, optimal treatment decisions are made according to patient preference and the disease's pathological features. This study was performed to evaluate the efficacy and complications of hemithyroidectomy with intraoperative radiofrequency ablation (RFA) compared with total thyroidectomy.

Methods: Patients with unilateral PTC and cytologically benign contralateral nodules were enrolled from 2014 to 2018. Total thyroidectomy or hemithyroidectomy with intraoperative RFA of the contralateral nodule was offered to patients who had anxiety regarding their disease. The operation-related parameters, transient or permanent nerve injury, hypocalcemia and disease recurrence, were recorded and compared between the two groups.

Results: After propensity score matching, 191 patients who underwent total thyroidectomy and 224 contralateral nodules in 191 patients underwent hemithyroidectomy with intraoperative RFA (HTRFA) were included. The volume reduction ratios of the contralateral nodules were 67.7% at 12 months and 95.8% at 24 months. The total thyroidectomy group reported significantly higher hypocalcemia than HTRFA within one year (7.8% vs. 2.6%, p = 0.022). Supplemental levothyroxine was not required in 28.3% (54/191) of the patients one year after HTRFA. With a median follow-up of 4.1 years, three recurrences (1.6%) were observed in the HTRFA, and no recurrence occurred in the total thyroidectomy group (p = 0.246).

Conclusions: Hemithyroidectomy for unilateral PTC and intraoperative RFA for contralateral nodules were acceptable and effective treatment approaches and did not increase the risk of complications.
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http://dx.doi.org/10.1186/s40463-022-00578-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188696PMC
June 2022
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