Publications by authors named "Wei Zou"

697 Publications

Real-world data prognostic model of overall survival in patients with advanced NSCLC receiving anti-PD-1/PD-L1 immune checkpoint inhibitors as second-line monotherapy.

Cancer Rep (Hoboken) 2022 Jan 24:e1578. Epub 2022 Jan 24.

Genentech, Inc, South San Francisco, California, USA.

Background And Aim: The objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) and to develop a novel prognostic model.

Methods: A total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second-line monotherapy were selected from a real-world deidentified database to build the cohort. Patients could not have received first-line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte-associated protein 4 therapies.

Results: Patients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real-world data cohort. The risk-increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk-decreasing prognostic factors were PD-L1 positivity, longer time from advanced diagnosis to start of first-line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c-index for the OAK trial validation cohort was 0.65 and 0.67 for the real-world data cohort.

Conclusions: Based on baseline demographic and clinical factors from a real-world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second-line monotherapy, and it performed well in the real-world data and clinical trial cohorts.
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http://dx.doi.org/10.1002/cnr2.1578DOI Listing
January 2022

Antibiotic resistomes in water supply reservoirs sediments of central China: main biotic drivers and distribution pattern.

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

MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, No.38, Tongyan Road, Haihe Education Park, Tianjin, 300350, China.

Water supply reservoirs form one of the critical drinking water resources. Their water quality directly affects human health. However, reservoir sediments have not received adequate attention in antibiotic resistance genes (ARGs) dissemination, though they reflect long-term ARGs contamination of water supply reservoirs. Moreover, the physicochemical parameters in water supply reservoir sediments are generally better than those in the other media. Thus, the main ARGs biotic drivers of the media would demonstrate their unique characteristics. In this study, sediment samples were collected from 10 water supply reservoirs in central China, and the antibiotic resistomes were determined with the metagenomic method. As revealed from the results, 174 ARGs (18 ARG types) were detected in the reservoir sediment. Besides, multidrug-, sulfonamide-, and vancomycin-ARGs were the dominant ARGs in the sediment samples. The macrolide-resistant Microcystis was prevalent (100% detection frequency with 0.35% average percentage) in reservoir sediments and posed potential risks to human health. Furthermore, the results of the Mantel test and VPA demonstrated that mobile genetic elements (MGEs) were the more essential biotic drivers in ARG contents of reservoir sediments rather than the bacteria community.
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http://dx.doi.org/10.1007/s11356-021-18095-wDOI Listing
January 2022

Temporal dependence of chlorophyll a-nutrient relationships in Lake Taihu: Drivers and management implications.

J Environ Manage 2022 Jan 17;306:114476. Epub 2022 Jan 17.

Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.

Eutrophication and its associated algal blooms are principal environmental challenges confronting lakes worldwide. The empirical relationships between nutrient (total nitrogen, TN; total phosphorus, TP) and chlorophyll a (Chla) level are widely used as a theoretical basis for lake eutrophication management. Here, seasonal environmental variables and Chla from 2005 to 2020 in Chinese shallow eutrophic Lake Taihu were examined and Chla-nutrient equations in the entire period and annually from 2005 to 2020 were explored using 95% quantile regression model. The results showed robust linear relationships of logChla-logTN and logChla-logTP in the vast majority of cases. Based on Chla-nutrient equations in the entire study period, 0.69 mg/L TN and 52 μg/L TP are recommended as nutrient threshold in Lake Taihu. Furthermore, the results revealed increasing Chla sensitivity to nutrient for each study month (i.e. February, May, August, and November) from 2005 to 2020, whose drivers included increase in water temperature and water level, decrease in wind speed, mass ratio of nitrogen to phosphorus, and grazing effect. It is noteworthy that atmospheric stilling is likely to be the key climatic factor promoting annual peak Chla in Lake Taihu. For one, the deviations of the sub-index of Trophic State Index indicated that light is a critical limiting factor of summer Chla in Lake Taihu. For another, calmer water mainly due to atmospheric stilling decreased near 40% non-algal turbidity and a substantially increased buoyant cyanobacteria during the study period, improving phytoplankton "light niche". Thus, increasing algal sensitivity to nutrient occurred until the additional algal-turbidity induce further light limitations or the exhaustion of TN (or TP) cause nutrient limitation. Given atmospheric stilling is a global phenomenon, this study would affect future algal bloom mitigation efforts in shallow lakes as temperature is always the focus in the recent literatures on global climate change.
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http://dx.doi.org/10.1016/j.jenvman.2022.114476DOI Listing
January 2022

Hydrogen Sulfide Attenuates the Cognitive Dysfunction in Parkinson's Disease Rats via Promoting Hippocampal Microglia M2 Polarization by Enhancement of Hippocampal Warburg Effect.

Oxid Med Cell Longev 2022 4;2022:2792348. Epub 2022 Jan 4.

Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang, 421001 Hunan, China.

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson's disease (PD) is urgently needed. Hydrogen sulfide (HS) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether HS attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of HS) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated HS-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that HS inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.
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http://dx.doi.org/10.1155/2022/2792348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752224PMC
January 2022

ctDNA Predicts Overall Survival in Patients With NSCLC Treated With PD-L1 Blockade or With Chemotherapy.

JCO Precis Oncol 2021 Nov;5:827-838

Genentech, South San Francisco, CA.

Purpose: Identification of predictors for overall survival (OS) allows timely detection of clinical efficacy signals and therefore facilitates treatment decisions. We assessed the association between circulating tumor DNA (ctDNA) metrics and the primary end point of OS in a subset of previously treated patients with locally advanced or metastatic non-small-cell lung cancer, who underwent atezolizumab or docetaxel treatment in the open-label randomized phase III OAK trial.

Materials And Methods: Plasma from 94 patients at baseline and at subsequent cycles of therapy every 3 weeks was analyzed retrospectively for ctDNA. ctDNA was measured by allele frequency and mutant molecules per milliliter (MMPM). Concordance between various per-sample metrics and clinical outcome were assessed using C index.

Results: Of all the ctDNA metrics tested, the association of median MMPM at 6 weeks with OS in patients treated with atezolizumab or docetaxel had a C index > 0.7. The OS hazard ratios relative to high ctDNA above median MMPM within each arm were 0.28 (95% CI, 0.11 to 0.75) for atezolizumab and 0.19 (95% CI, 0.08 to 0.48) for docetaxel. For patients who had ctDNA median MMPM levels of < 4.79, the median survival time was more than 17 months in docetaxel-treated patients and the median survival time was not reached in the atezolizumab-treated patients.

Conclusion: ctDNA MMPM levels measured at 6 weeks post-treatment are associated with OS in advanced non-small-cell lung cancer. Our results suggest that ctDNA has the potential for a noninvasive early liquid biopsy predictor for OS that warrants further studies to demonstrate its utility in clinical development.
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http://dx.doi.org/10.1200/PO.21.00057DOI Listing
November 2021

Immune Score Predicts Outcomes of Gastric Cancer Patients Treated with Adjuvant Chemoradiotherapy.

J Oncol 2021 27;2021:9344124. Epub 2021 Dec 27.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Background: Substantial evidence has demonstrated that tumor-infiltrating lymphocytes (TILs) are correlated with patient prognosis. The TIL-based immune score (IS) affects prognosis in various cancers, but its prognostic impact in gastric cancer (GC) patients treated with adjuvant chemoradiotherapy remains unclear.

Methods: A total of 101 GC patients who received chemoradiotherapy after gastrectomy were retrospectively analyzed in this study. Immunohistochemistry staining for CD3+ and CD8+ T-cell counts in both tumor center (CT) and invasive margin (IM) regions was built into the IS. Patients were then divided into three groups based on their differential IS levels. The correlation between IS and clinical parameters was analyzed. The prognostic impact of IS and clinical parameters was evaluated using Kaplan-Meier analysis and Cox proportional hazard regression analysis. Receiver operating characteristic (ROC) curves were plotted to compare the area under the curve (AUC) of IS with other clinical parameters. Nomograms for disease-free survival (DFS) and overall survival (OS) prediction were constructed based on the identified parameters.

Results: Finally, 20 (19.8%), 57 (56.4%), and 24 (23.8%) GC patients were identified with low, intermediate, and high IS levels, respectively. GC patients with higher IS levels exhibited better DFS ( < 0.001) and OS ( < 0.001). IS was an independent prognostic factor for both DFS ( < 0.001) and OS ( < 0.001) in multivariate analysis. IS presented a better predictive ability than the traditional pathological tumor-node-metastasis (pTNM) staging system (AUC: 0.801 vs. 0.677 and 0.800 vs. 0.660, respectively) with respect to both DFS and OS. The C-index of the nomograms for DFS and OS prediction was 0.737 and 0.774, respectively.

Conclusions: IS is a strong predictive factor for both DFS and OS in GC patients treated with adjuvant chemoradiotherapy, which may complement the traditional pTNM staging system.
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http://dx.doi.org/10.1155/2021/9344124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8723845PMC
December 2021

Scalp Acupuncture Attenuates Brain Damage After Intracerebral Hemorrhage Through Enhanced Mitophagy and Reduced Apoptosis in Rats.

Front Aging Neurosci 2021 20;13:718631. Epub 2021 Dec 20.

First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.

To study the effect of scalp acupuncture (SA) on the mitophagy signaling pathway in the caudate nucleus of Sprague-Dawley rats following intracerebral hemorrhage (ICH). An ICH model was established by injecting autologous arterial blood into the caudate nucleus in 200 male Sprague-Dawley rats, which were divided into five groups: sham, ICH, 3-methyladenine group (3-MA, 30 mg/kg), SA, and SA+3-MA. Animals were analyzed at 6 and 24 h as well as at 3 and 7 days. Composite neurological scale score was significantly higher in the SA group than in the ICH group. Transmission electron microscopy showed less structural damage and more autophagic vacuoles within brain in the SA group than in the ICH group. SA group showed higher levels of Beclin1, Parkin, PINK1, NIX protein, and a lower level of Caspase-9 in brain tissue. These animals consequently showed less neural cell apoptosis. Compared with the SA group, however, the neural function score and levels of mitophagy protein in the SA+3-MA group were decreased, neural cell apoptosis was increased with more severe structural damage, which suggested that 3-MA may antagonize the protective effect of SA on brain in rats with ICH. SA may mitigate the neurologic impairment after ICH by enhancing mitophagy and reducing apoptosis.
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http://dx.doi.org/10.3389/fnagi.2021.718631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720963PMC
December 2021

Dynamics of nitrogen and phosphorus profile and its driving forces in a subtropical deep reservoir.

Environ Sci Pollut Res Int 2022 Jan 4. Epub 2022 Jan 4.

Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China.

Nitrogen and phosphorus stratification is crucial for ecosystem dynamics in deep lakes and reservoirs. It is critical for water quality management to understand the characteristics of nitrogen and phosphorus stratification and its driving forces. In this study, high-frequency total nitrogen (TN) and total phosphorus (TP) from January 2017 to October 2019 were estimated using the datasets of high-frequency buoy parameters, including water temperature, pH, chlorophyll-a, oxidation-reduction potential, dissolved oxygen, and fluorescent dissolved organic matter. The results revealed that both nitrogen and phosphorus in water column were periodically stratified. Specifically, the stratification of nitrogen and phosphorus occurred from April to December or January of the following year. Moreover, indices of TN stratification (IC-TN) and TP stratification (IC-TP) were - 0.29 ~ 0.05 and - 0.78 ~ 0.28, respectively. Significant (P < 0.01) positive correlations were observed between RWCS (an index of thermal stability) and IC-TN (or IC-TP), indicating thermal stratification may be the main driving force of nutrient stratification at inter-month scales. Further analysis indicated that the thermal stratification may affect nitrogen and phosphorus stratification though (1) influencing algal growth and (2) affecting the release of internal sources and the material exchange between water columns. Furthermore, precipitation is also suggested as an important factor affecting the stability of nitrogen and phosphorus vertical profile in the flood season. These findings may provide important information for optimizing water quality management efforts in Qiandaohu and other subtropical deep reservoirs. In addition, the knowledge of the effect of temperature and precipitation on nutrient stratification are essential to understand future ecosystem dynamics of deep reservoirs.
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http://dx.doi.org/10.1007/s11356-021-17877-6DOI Listing
January 2022

Oxic urban rivers as a potential source of atmospheric methane.

Environ Pollut 2022 Mar 29;297:118769. Epub 2021 Dec 29.

State Key Laboratory of Lake and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, PR China.

Urban rivers play a vital role in global methane (CH) emissions. Previous studies have mainly focused on CH concentrations in urban rivers with a large amount of organic sediment. However, to date, the CH concentration in gravel-bed urban rivers with very little organic sediment has not been well documented. Here, we collected water samples from an oxic urban river (Xin'an River, China; annual mean dissolved oxygen concentration was 9.91 ± 1.99 mg L) with a stony riverbed containing very little organic sediment. Dissolved CH concentrations were measured using a membrane inlet mass spectrometer to investigate whether such rivers potentially act as an important source of atmospheric CH and the corresponding potential drivers. The results showed that CH was supersaturated at all sampling sites in the five sampling months. The mean CH saturation ratio (ratio of river dissolved CH concentration to the corresponding CH concentration that is in equilibrium with the atmosphere) across all sampling sites in the five sampling months was 204 ± 257, suggesting that the Xin'an River had a large CH emission potential. The CH concentration was significantly higher in the downstream river than in the upstream river (p < 0.05), which suggested that human activities along the river greatly impacted the CH level. Statistical analyses and incubation experiments indicated that algae can produce CH under oxic conditions, which may contribute to the significantly higher CH concentration in August 2020 (p < 0.001) when a severe algal bloom occurred. Furthermore, other factors, such as heavy rainfall events, dissolved organic carbon concentration, and water temperature, may also be vital factors affecting CH concentration. Our study enhances the understanding of dissolved CH dynamics in oxic urban rivers with very little organic sediment and further proposes feasible measures to control the CH concentration in urban rivers.
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http://dx.doi.org/10.1016/j.envpol.2021.118769DOI Listing
March 2022

SAG1 targeting host cell S100A6 for parasite invasion and host immunity.

iScience 2021 Dec 26;24(12):103514. Epub 2021 Nov 26.

Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province 510515, P R China.

surface antigen 1 (SAG1) is a surface protein of tachyzoites, which plays a crucial role in infection and host cell immune regulation. However, how SAG1 regulates these processes remains elucidated. We utilized the biotin ligase -TurboID fusion with SAG1 to identify the host proteins interacting with SAG1, and identified that S100A6 was co-localized with SAG1 when attached to the host cell. S100A6, either knocking down or blocking its functional epitopes resulted in inhibited parasites invasion. Meanwhile, S100A6 overexpression in host cells promoted infection. We further verified that SAG1 could inhibit the interaction of host cell vimentin with S100A6 for cytoskeleton organization during invasion. As an immunogen, SAG1 could promote the secretion of tumor necrosis factor alpha (TNF-α) through S100A6-Vimentin/PKCθ-NF-κB signaling pathway. In summary, our findings revealed a mechanism for how SAG1 functioned in parasitic invasion and host immune regulation.
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http://dx.doi.org/10.1016/j.isci.2021.103514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671940PMC
December 2021

New insights into eutrophication management: Importance of temperature and water residence time.

J Environ Sci (China) 2022 Jan 10;111:229-239. Epub 2021 Apr 10.

State Key Laboratory of Lake and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China; School of Environmental and Civil Engineering, Jiangnan University, Wuxi 214122, China.

Eutrophication and harmful cyanobacterial blooms threaten water resources all over the world. There is a great controversy about controlling only phosphorus or controlling both nitrogen and phosphorus in the management of lake eutrophication. The primary argument against the dual nutrients control of eutrophication is that nitrogen fixation can compensate the nitrogen deficits. Thus, it is of great necessary to study the factors that can significantly affect the nitrogen fixation. Due to the difference of climate and human influence, the water quality of different lakes (such as water temperature, N:P ratio and water residence time) is also quite different. Numerous studies have reported that the low N:P ratio can intensify the nitrogen fixation capacities. However, the effects of temperature and water residence time on the nitrogen fixation remain unclear. Thus, 30 shallows freshwater lakes in the eastern plain of China were selected to measure dissolved N and Ar concentrations through N: Ar method using a membrane inlet mass spectrometer to quantify the nitrogen fixation capacities and investigate whether the temperature and water residence time have a great impact on nitrogen fixation. The results have shown that the short lake water residence time can severely inhibit the nitrogen fixation capacities through inhibiting the growth of nitrogen-fixing cyanobacteria, changing the N:P ratio and resuspending the solids from sediments. Similarly, lakes with low water temperature also have a low nitrogen fixation capacity, suggesting that controlling nitrogen in such lakes is feasible if the growth of cyanobacteria is limited by nitrogen.
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http://dx.doi.org/10.1016/j.jes.2021.02.033DOI Listing
January 2022

Atmospheric Stilling Promotes Summer Algal Growth in Eutrophic Shallow Lakes.

Biology (Basel) 2021 Nov 23;10(12). Epub 2021 Nov 23.

Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China.

Algal blooms are environmental challenges confronting lakes worldwide and are significantly influenced by chlorophyll yields per unit phosphorus (Chl/TP), or nitrogen (Chl/TN). Here, the influence of inter-annual hydrometeorological variations on Chl/TP and Chl/TN were evaluated in eutrophic shallow Lake Taihu, China. Our results demonstrated significant increases ( < 0.001) in both Chl/TN and Chl/TP from 2005 to 2017, and increased Chl yields during the winter months were mainly correlated with higher water temperature and longer sunshine hours, which may cause severer blooms in winter and spring. In remaining months from 2005 to 2017, typical associations between atmospheric stilling (or water level elevation) and higher Chl yields were observed. The results also indicate that atmospheric stilling and water level elevation significantly ( < 0.001) decreased background turbidity and promoted buoyant cyanobacterial biomass, alleviating phytoplankton light limitation. Given the subtropical location, eutrophic status, and high background turbidity of Lake Taihu, light may be the critical limiting factor for summer phytoplankton growth; thus, improved light availability would promote Chl yields until self-shading caused further light limitations. If the mechanism is general, promoting the effect of atmospheric stilling on annual peak Chl in shallow lakes may be greatly underestimated, and our finding will affect future bloom mitigation efforts in such systems.
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http://dx.doi.org/10.3390/biology10121222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698560PMC
November 2021

HIV-1 Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells.

Biol Direct 2021 12 20;16(1):27. Epub 2021 Dec 20.

Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, 330006, Jiangxi, China.

Background: A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection.

Results: In the current study we investigated the influence of HIV-1 Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs.

Conclusions: Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.
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http://dx.doi.org/10.1186/s13062-021-00317-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686389PMC
December 2021

Exploring Microenvironment Strategies to Delay Mesenchymal Stem Cell Senescence.

Stem Cells Dev 2022 Jan 21. Epub 2022 Jan 21.

Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Mesenchymal stem cells (MSCs) have recently emerged as an important candidate for cell therapy and tissue regeneration. However, some limitations in translational research and therapies still exist, such as insufficient cell supply, inadequate differentiation potential, and decreased immune capacity, all of which result from replicative senescence during long-term in vitro culture. In vitro, stem cells lack a protective microenvironment owing to the absence of physical and biochemical cues compared with the in vivo niche, which provides dynamic physicochemical and biological cues. This difference results in accelerated aging after long-term in vitro culture. Therefore, it remains a great challenge to delay replicative senescence in culture. Constructing a microenvironment to delay replicative senescence of MSCs by maintaining their phenotypes, properties, and functions is a feasible strategy to solve this problem, and has made measurable progress both in preclinical studies and in clinical trials. Here, we review the current knowledge on the characteristics of senescent MSCs, explore the molecular mechanisms of MSCs senescence, describe the niche of MSCs, and discuss some current microenvironment strategies to delay MSCs replicative senescence that can broaden their range of therapeutic applications.
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http://dx.doi.org/10.1089/scd.2021.0254DOI Listing
January 2022

Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking.

Front Pharmacol 2021 29;12:746208. Epub 2021 Nov 29.

Biopharmaceutics, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.

The kidneys are a pair of important organs that excretes endogenous waste and exogenous biological agents from the body. Numerous transporters are involved in the excretion process. The levels of these transporters could affect the pharmacokinetics of many drugs, such as organic anion drugs, organic cationic drugs, and peptide drugs. Eleven drug transporters in the kidney (OAT1, OAT3, OATP4C1, OCT2, MDR1, BCRP, MATE1, MATE2-K, OAT4, MRP2, and MRP4) have become necessary research items in the development of innovative drugs. However, the levels of these transporters vary between different species, sex-genders, ages, and disease statuses, which may lead to different pharmacokinetics of drugs. Here, we review the differences of the important transports in the mentioned conditions, in order to help clinicians to improve clinical prescriptions for patients. To predict drug-drug interactions (DDIs) caused by renal drug transporters, the molecular docking method is used for rapid screening of substrates or inhibitors of the drug transporters. Here, we review a large number of natural products that represent potential substrates and/or inhibitors of transporters by the molecular docking method.
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http://dx.doi.org/10.3389/fphar.2021.746208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666590PMC
November 2021

Deep learning for automatic target volume segmentation in radiation therapy: a review.

Quant Imaging Med Surg 2021 Dec;11(12):4847-4858

Department of Radaition Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Deep learning, a new branch of machine learning algorithm, has emerged as a fast growing trend in medical imaging and become the state-of-the-art method in various clinical applications such as Radiology, Histo-pathology and Radiation Oncology. Specifically in radiation oncology, deep learning has shown its power in performing automatic segmentation tasks in radiation therapy for Organs-At-Risks (OAR), given its potential in improving the efficiency of OAR contouring and reducing the inter- and intra-observer variabilities. The similar interests were shared for target volume segmentation, an essential step of radiation therapy treatment planning, where the gross tumor volume is defined and microscopic spread is encompassed. The deep learning-based automatic segmentation method has recently been expanded into target volume automatic segmentation. In this paper, the authors summarized the major deep learning architectures of supervised learning fashion related to target volume segmentation, reviewed the mechanism of each infrastructure, surveyed the use of these models in various imaging domains (including Computational Tomography with and without contrast, Magnetic Resonant Imaging and Positron Emission Tomography) and multiple clinical sites, and compared the performance of different models using standard geometric evaluation metrics. The paper concluded with a discussion of open challenges and potential paths of future research in target volume automatic segmentation and how it may benefit the clinical practice.
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http://dx.doi.org/10.21037/qims-21-168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611469PMC
December 2021

[Advances of using microfluidic chips for research and diagnosis of pulmonary inflammatory diseases].

Sheng Wu Gong Cheng Xue Bao 2021 Nov;37(11):3905-3914

Clinical Research Institute of Stem Cells, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China.

Microfluidic chip technology integrates the sample preparation, reaction, separation and detection on a chip. It consists a network of microchannels, which controls the whole system through fluid. With the advantages of portability, high throughput, and the ability to simulate the microenvironment in vivo, it has a broad application prospect in the research of disease diagnosis, pathogenesis and drug screening. Pulmonary inflammatory disease is a common disease usually caused by bacterial, viral and fungal infections. Early pneumonia is often difficult to diagnose due to lack of obvious respiratory symptoms or the symptoms are mostly atypical, but the disease progresses rapidly. Recently, microfluidic chip technology has been increasingly used to the study of pulmonary inflammatory diseases. In particular, it has been used to develop a "lung-on-a-chip" model, which can reproduce the key structure, function and mechanical properties of human alveolar capillary interface (i.e., the basic functional unit of a living lung), and well simulate the alveoli in vitro. Compared with the cell and animal models, this multifunctional micro experimental platform has great advantages. This article summarizes the advances of using microfluidic chips for the research and diagnosis of pulmonary inflammatory diseases, with the aim to provide new ideas for researchers in this area.
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http://dx.doi.org/10.13345/j.cjb.210025DOI Listing
November 2021

Targeting the Ang2/Tie2 Axis with Tanshinone IIA Elicits Vascular Normalization in Ischemic Injury and Colon Cancer.

Oxid Med Cell Longev 2021 10;2021:7037786. Epub 2021 Nov 10.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Pathological angiogenesis, as exhibited by aberrant vascular structure and function, has been well deemed to be a hallmark of cancer and various ischemic diseases. Therefore, strategies to normalize vasculature are of potential therapeutic interest in these diseases. Recently, identifying bioactive compounds from medicinal plant extracts to reverse abnormal vasculature has been gaining increasing attention. Tanshinone IIA (Tan IIA), an active component of , has been shown to play significant roles in improving blood circulation and delaying tumor progression. However, the underlying mechanisms responsible for the therapeutic effects of Tan IIA are not fully understood. Herein, we established animal models of HT-29 human colon cancer xenograft and hind limb ischemia to investigate the role of Tan IIA in regulating abnormal vasculature. Interestingly, our results demonstrated that Tan IIA could significantly promote the blood flow, alleviate the hypoxia, improve the muscle quality, and ameliorate the pathological damage after ischemic insult. Meanwhile, we also revealed that Tan IIA promoted the integrity of vascular structure, reduced vascular leakage, and attenuated the hypoxia in HT-29 tumors. Moreover, the circulating angiopoietin 2 (Ang2), which is extremely high in these two pathological states, was substantially depleted in the presence of Tan IIA. Also, the activation of Tie2 was potentiated by Tan IIA, resulting in decreased vascular permeability and elevated vascular integrity. Mechanistically, we uncovered that Tan IIA maintained vascular stability by targeting the Ang2-Tie2-AKT-MLCK cascade. Collectively, our data suggest that Tan IIA normalizes vessels in tumors and ischemic injury via regulating the Ang2/Tie2 signaling pathway.
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http://dx.doi.org/10.1155/2021/7037786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598375PMC
November 2021

Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction.

Ren Fail 2021 Dec;43(1):1496-1505

Department of Nephrology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.

In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon's effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-β1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-β1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-β1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.
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http://dx.doi.org/10.1080/0886022X.2021.1997764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583759PMC
December 2021

A proof-of-concept study of an in-situ partial-ring time-of-flight PET scanner for proton beam verification.

IEEE Trans Radiat Plasma Med Sci 2021 Sep 14;5(5):694-702. Epub 2020 Dec 14.

Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 USA.

Development of a PET system capable of imaging requires a design that can accommodate the proton treatment beam nozzle. Among the several PET instrumentation approaches developed thus far, the dual-panel PET scanner is often used as it is simpler to develop and integrate within the proton therapy gantry. Partial-angle coverage of these systems can however lead to limited-angle artefacts in the reconstructed PET image. We have previously demonstrated via simulations that time-of-flight (TOF) reconstruction reduces the artifacts accompanying limited-angle data, and permits proton range measurement with 1-2 mm accuracy and precision. In this work we show measured results from a small proof-of-concept dual-panel PET system that uses TOF information to reconstruct PET data acquired after proton irradiation. The PET scanner comprises of two detector modules, each comprised of an array of 4×4×30 mm lanthanum bromide scintillator. Measurements are performed with an oxygen-rich gel-water, an adipose tissue equivalent material, and tissue phantoms. For each phantom measurement, 2 Gy dose was deposited using 54 - 100 MeV proton beams. For each phantom, a Monte Carlo simulation generating the expected distribution of PET isotope from the corresponding proton irradiation was also performed. Proton range was calculated by drawing multiple depth-profiles over a central region encompassing the proton dose deposition. For each profile, proton range was calculated using two techniques (a) 50% pick-off from the distal edge of the profile, and (b) comparing the measured and Monte Carlo profile to minimize the absolute sum of differences over the entire profile. A 10 min PET acquisition acquired with minimal delay post proton-irradiation is compared with a 10 min PET scan acquired after a 20 min delay. Measurements show that PET acquisition with minimal delay is necessary to collect O signal, and maximize C signal collection with a short PET acquisition. In comparison with the 50% pick-off technique, the shift technique is more robust and offers better precision in measuring the proton range for the different phantoms. Range measurements from PET images acquired with minimal delay, and the shift technique demonstrate the ability to achieve <1.5 mm accuracy and precision in estimating proton range.
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http://dx.doi.org/10.1109/trpms.2020.3044326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570535PMC
September 2021

Photoaging enhanced the adverse effects of polyamide microplastics on the growth, intestinal health, and lipid absorption in developing zebrafish.

Environ Int 2022 01 7;158:106922. Epub 2021 Oct 7.

Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.

The safety of microplastics (MPs) and associated health effects has been one of the major concerns worldwide. However, the role of photoaging toward the risk of MPs in water ecosystems remains inconclusive yet. In this study, the size of polyamide (PA, ∼32.50 μm) MPs was obviously decreased after photoaging in water containing fulvic acid (FA) and humic acid (HA) (∼19.75 and ∼24.30 μm, respectively). Nanoplastics were formed (4.65% and 2.03%, respectively) and hydrophilia and colloidal stability was improved due to the formation of oxygen-containing functional groups. FA-aged PA exhibited higher inhibition on body length and weight of developing zebrafish than HA-aged and pristine PA. Photoaged MPs in intestine were more difficult to be depurated by zebrafish, leading to the disappearance of intestinal folding, shedding of more enterocytes, and emaciation of intestinal microvilli. Dietary lipid digestion in larvae was inhibited by aged PA due to oxidative stress-triggered lipid peroxidation and inhibition of lipase activities and bile acids secretion. Exposure of photoaged MPs down-regulated genes (cd36, dgat1a, dgat2, mttp, etc.) associated with triglyceride resynthesis and transportation, resulting in lipid maladsorption and growth inhibition. Our findings highlight the potential negative effects of environmentally aged MPs on diet digestion and nutrient assimilation in fish.
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http://dx.doi.org/10.1016/j.envint.2021.106922DOI Listing
January 2022

Hydrogen sulfide antagonizes sleep deprivation-induced depression- and anxiety-like behaviors by inhibiting neuroinflammation in a hippocampal Sirt1-dependent manner.

Brain Res Bull 2021 Dec 5;177:194-202. Epub 2021 Oct 5.

The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address:

Increasing evidence confirms that sleep deprivation (SD), which induces hippocampal neuroinflammation, is a risk factor for depression. Hydrogen sulfide (HS) is a novel neuromodulator that plays antidepressant-like role. Silent mating type information regulation 2 homolog 1 (Sirt1) is well-characterized as a regulator of mood disorder. Furthermore, we have previously reported that HS upregulates Sirt1 expression in the hippocampus of SD-exposed rats. Here, we explored whether HS ameliorates depression- and anxiety-like behaviors as well as hippocampal neuroinflammatory in SD-exposed rats and whether Sirt1 mediates these protective roles of HS. In the present work, we showed that NaHS (a donor of HS) significantly alleviated depression- and anxiety-like behaviors in the SD-exposed rats tested by novelty-suppressed feeding test (NST), forced swim test (FST), tail suspension test (TST), and elevated plus maze test (EPMT) and that NaHS attenuates neuroinflammatory in the hippocampus of SD-exposed rats, as evidenced by reducing the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and chemokine CCL2, as well as increasing the levels of anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. However, Sirt1 inhibitor reversed the protective effects of HS against SD-induced depression- and anxiety-like behaviors as well as hippocampal neuroinflammatory. In conclusion, HS antagonizes SD-induced depression- and anxiety-like behaviors and neuroinflammation, which is required hippocampal Sirt1. These findings suggested that HS is a novel approach to prevent SD-induced depression and anxiety.
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http://dx.doi.org/10.1016/j.brainresbull.2021.10.002DOI Listing
December 2021

Impact of algal extracellular polymeric substances on the environmental fate and risk of molybdenum disulfide in aqueous media.

Water Res 2021 Oct 25;205:117708. Epub 2021 Sep 25.

Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education)/Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China. Electronic address:

Molybdenum disulfide (MoS) poses great potential in water treatment as a popular transition metal dichalcogenide, arousing considerable concern regarding its fates and risk in aquatic environments. This study revealed that the interplay with extracellular polymeric substances (EPS) of freshwater algae significantly changed the properties and toxicity of MoS to aquatic fish. The predominant binding of aromatic compounds, polysaccharides, and carboxyl-rich proteins in EPS on the 1T polymorph of MoS via hydrophilic effects and the preferential adsorption of carboxylic groups contributed to morphological alterations, structural disorders (band gap and phase alterations), and the attenuated aggregation of MoS in aqueous solutions. Electron charge transfer and n-π* interactions with EPS decreased the catalytic activity of MoS by inhibiting its capability of generating reactive intermediates. The dissolution of MoS slowed down after interacting with EPS (from 0.089 to 0.045 mg/L per day) owing to rapid initial oxidation (i.e., forming Mo-O bond) and carbon grafting. Notably, the morphological and structural alterations after EPS binding alleviated the toxicity (e.g., malformation and oxidative stress) of MoS to infantile zebrafish. Our findings provide insights into the environmental fate and risk of MoS by ubiquitous EPS in natural waters, serving as valuable information while developing water treatment processes accordingly.
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http://dx.doi.org/10.1016/j.watres.2021.117708DOI Listing
October 2021

Use of metoclopramide in the first trimester and risk of major congenital malformations: A systematic review and meta-analysis.

PLoS One 2021 20;16(9):e0257584. Epub 2021 Sep 20.

Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.

Background: Nausea and vomiting of pregnancy affects up to 80% of pregnant women, it typically occurs during the first trimester which is the most sensitive time for environmental exposures given organogenesis. Metoclopramide is an antiemetic drug used widely during NVP, but the findings of studies evaluating its safety of use in pregnancy is inconsistent. Therefore, we conducted a systematic review and meta-analysis to assess whether metoclopramide use during first trimester of pregnancy is associated with the risk of major congenital malformations.

Methods: The systematic search using database included Pubmed, Embase, Web of science, and Cochrane library. Studies written in English, comprising with an exposed group and a control group, reporting major congenital malformation as an outcome were included.

Results: Six studies assessing a total number of 33374 metoclopramide-exposed and 373498 controls infants were included in this meta-analysis. No significant increase in the rate of major congenital malformation was detected following metoclopramide use during first trimester (OR, 1.14; 95% CI, 0.93-1.38).

Conclusions: Metoclopramide use during first trimester of pregnancy was not associated with the risk of major congenital malformations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257584PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452057PMC
November 2021

Comparative genome analysis of Clostridium beijerinckii strains isolated from pit mud of Chinese strong flavor baijiu ecosystem.

G3 (Bethesda) 2021 10;11(11)

College of Bioengineering, Sichuan University of Science & Engineering, Yibin, Sichuan 644005, China.

Clostridium beijerinckii is a well-known anaerobic solventogenic bacterium which inhabits a wide range of different niches. Previously, we isolated five butyrate-producing C. beijerinckii strains from pit mud (PM) of strong-flavor baijiu (SFB) ecosystems. Genome annotation of the five strains showed that they could assimilate various carbon sources as well as ammonium to produce acetate, butyrate, lactate, hydrogen, and esters but did not produce the undesirable flavors isopropanol and acetone, making them useful for further exploration in SFB production. Our analysis of the genomes of an additional 233 C. beijerinckii strains revealed an open pangenome based on current sampling and will likely change with additional genomes. The core genome, accessory genome, and strain-specific genes comprised 1567, 8851, and 2154 genes, respectively. A total of 298 genes were found only in the five C. beijerinckii strains from PM, among which only 77 genes were assigned to Clusters of Orthologous Genes categories. In addition, 15 transposase and 12 phage integrase families were found in all five C. beijerinckii strains from PM. Between 18 and 21 genome islands were predicted for the five C. beijerinckii genomes. The existence of a large number of mobile genetic elements indicated that the genomes of the five C. beijerinckii strains evolved with the loss or insertion of DNA fragments in the PM of SFB ecosystems. This study presents a genomic framework of C. beijerinckii strains from PM that could be used for genetic diversification studies and further exploration of these strains.
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http://dx.doi.org/10.1093/g3journal/jkab317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527462PMC
October 2021

Sodium hydrosulfide reverses β-microglobulin-induced depressive-like behaviors of male Sprague-Dawley rats: Involving improvement of synaptic plasticity and enhancement of Warburg effect in hippocampus.

Behav Brain Res 2022 Jan 6;417:113562. Epub 2021 Sep 6.

Institute of Neurology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address:

Background: Our previous works demonstrated that β2-microglobulin (β2m), a systemic pro-aging factor, induce depressive-like behaviors. Hydrogen sulfide (HS) is identified as a potential target for treatment of depression. The aim of the present work is to explore whether HS antagonizes β2m-induced depressive-like behaviors and the underlying mechanisms.

Methods: The depressive-like behaviors were detected using the novelty suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The expressions of Warburg-related proteins, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), Lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase 1(PDK1), and synaptic plasticity-related proteins, including postsynaptic density protein 95 (PSD95) and synaptophysin1 (SYN1), were determined by western blotting.

Result: we found that NaHS (the donor of HS) attenuated the depressive-like behaviors in the β2m-exposed rats, as judged by NSFT, TST, FST, and OFT. We also demonstrated that NaHS enhanced the synaptic plasticity, as evidenced by the upregulations of PSD95 and SYN1 expressions in the hippocampus of β2m-exposed rats. Furthermore, NaHS improved the Warburg effect in the hippocampus of β2m-exposed rats, as evidenced by the upregulations of HK II, PKM2, LDHA and PDK1 expressions, and the downregulation of PDH expression.

Conclusion: HS prevents β2m-induced depressive-like behaviors, which is involved in improvement of hippocampal synaptic plasticity as a result of enhancement of hippocampal Warburg effect.
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http://dx.doi.org/10.1016/j.bbr.2021.113562DOI Listing
January 2022

Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re-establishing autophagic flux via promoting leptin signalling in a 6-hydroxydopamine rat model of Parkinson's disease.

Clin Exp Pharmacol Physiol 2022 01 22;49(1):122-133. Epub 2021 Sep 22.

The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Previous studies reveal that hydrogen sulphide (H S) exerts neuroprotection against neurotoxin-induced Parkinson's disease (PD), but the underlying mechanism remains elusive. The present study was aimed to investigate whether H S inhibits neuronal apoptosis of substantia nigra with the involvement of autophagy via promoting leptin signalling in 6-hydroxydopamine (6-OHDA)-induced PD rats. In this study, neuronal apoptosis was analysed by TUNEL staining, the activity of caspase-3 was measured by Caspase-3 fluorometric assay kit, the expressions of Bax, Bcl-2, Beclin-1, LC3II, P62 and leptin were determined by Western blot analysis, and the numbers of autophagosomes and autolysosomes were assessed by transmission electron microscopy. Results showed that NaHS, a donor of exogenous H S, mitigates 6-OHDA-induced the increases in the numbers of TUNEL-positive cells, the activity of caspase-3 and the expression of Bax, and attenuates 6-OHDA-induced a decrease in the expression of Bcl-2 in substantia nigra of rats. In addition, 6-OHDA enhanced the expressions of Beclin-1, LC3-II and P62, increased the number of autophagosomes, and decreased the number of autolysosomes in the substantia nigra, which were also blocked by administration of NaHS. Furthermore, NaHS reversed 6-OHDA-induced the down-regulation of leptin expression in the substantia nigra, and treatment with leptin-OBR, a blocking antibody of leptin receptor, attenuated the inhibition of NaHS on neuronal apoptosis and the improvement of NaHS on the blocked autophagic flux in substantia nigra of 6-OHDA-treated rats. Taken together, these results demonstrated that H S attenuates neuronal apoptosis of substantia nigra depending on restoring impaired autophagic flux through up-regulating leptin signalling in PD.
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http://dx.doi.org/10.1111/1440-1681.13587DOI Listing
January 2022

Photoinduced transformation of silver ion by molybdenum disulfide nanoflakes at environmentally relevant concentrations attenuates its toxicity to freshwater algae.

J Hazard Mater 2021 08 7;416:126043. Epub 2021 May 7.

School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, International Joint Laboratory on Key Techniques in Water Treatment, Henan Normal University, Xinxiang 453007, China.

The transformation of Ag is strongly correlated with its risks in aquatic environment. Considering the wide application of molybdenum disulfide (MoS) and the inevitable release into the environment, the effects of MoS on Ag transformation and toxicity are of great concerns. This study revealed the pH-dependent reduction of Ag (0.5 mM) to Ag nanoparticles (AgNPs) by MoS (50 mg/L) and solar irradiation obviously accelerates the AgNPs formation (2.638 mg/L per day, pH=7.0) compared with dark condition (0.637 mg/L per day), ascribing to the electrons capture from electron-hole pairs of MoS by Ag. Ionic strengths and natural organic matter decreased the AgNPs yield. Metallic 1 T phase of MoS primarily participated in AgNPs formation and was oxidized to soluble ions (MoO) due to the oxygen generation in valance band. The above processes also occurred between Ag and MoS at environmentally relevant concentrations. Further, photoinduced transformation of Ag by MoS (10-100 μg/L) significantly lowered its toxicity to freshwater algae. The AgNPs formation on MoS reduced the bioavailability of Ag to algae, which was the mechanism for attenuated Ag toxicity. The provided data are helpful for better understanding the roles of MoS on the environmental fates and risks of metal ions under natural conditions.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126043DOI Listing
August 2021

An overview and future prospects of recombinant protein production in Bacillus subtilis.

Appl Microbiol Biotechnol 2021 Sep 1;105(18):6607-6626. Epub 2021 Sep 1.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.

Bacillus subtilis is a well-characterized Gram-positive bacterium and a valuable host for recombinant protein production because of its efficient secretion ability, high yield, and non-toxicity. Here, we comprehensively review the recent studies on recombinant protein production in B. subtilis to update and supplement other previous reviews. We have focused on several aspects, including optimization of B. subtilis strains, enhancement and regulation of expression, improvement of secretion level, surface display of proteins, and fermentation optimization. Among them, optimization of B. subtilis strains mainly involves undirected chemical/physical mutagenesis and selection and genetic manipulation; enhancement and regulation of expression comprises autonomous plasmid and integrated expression, promoter regulation and engineering, and fine-tuning gene expression based on proteases and molecular chaperones; improvement of secretion level predominantly involves secretion pathway and signal peptide screening and optimization; surface display of proteins includes surface display of proteins on spores or vegetative cells; and fermentation optimization incorporates medium optimization, process condition optimization, and feeding strategy optimization. Furthermore, we propose some novel methods and future challenges for recombinant protein production in B. subtilis.Key points• A comprehensive review on recombinant protein production in Bacillus subtilis.• Novel techniques facilitate recombinant protein expression and secretion.• Surface display of proteins has significant potential for different applications.
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http://dx.doi.org/10.1007/s00253-021-11533-2DOI Listing
September 2021

Comparison of FLASH Proton Entrance and the Spread-Out Bragg Peak Dose Regions in the Sparing of Mouse Intestinal Crypts and in a Pancreatic Tumor Model.

Cancers (Basel) 2021 Aug 23;13(16). Epub 2021 Aug 23.

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared to standard dose rate proton radiotherapy (S-PRT) in experiments using the entrance portion of the proton depth dose profile, while proton therapy uses a spread-out Bragg peak (SOBP) with unknown effects on FLASH toxicity sparing. To investigate, the biological effects of F-PRT using an SOBP and the entrance region were compared to S-PRT in mouse intestine. In this study, 8-10-week-old C57BL/6J mice underwent 15 Gy (absorbed dose) whole abdomen irradiation in four groups: (1) SOBP F-PRT, (2) SOBP S-PRT, (3) entrance F-PRT, and (4) entrance S-PRT. Mice were injected with EdU 3.5 days after irradiation, and jejunum segments were harvested and preserved. EdU-positive proliferating cells and regenerated intestinal crypts were quantified. The SOBP had a modulation (width) of 2.5 cm from the proximal to distal 90%. Dose rates with a SOBP for F-PRT or S-PRT were 108.2 ± 8.3 Gy/s or 0.82 ± 0.14 Gy/s, respectively. In the entrance region, dose rates were 107.1 ± 15.2 Gy/s and 0.83 ± 0.19 Gy/s, respectively. Both entrance and SOBP F-PRT preserved a significantly higher number of EdU + /crypt cells and percentage of regenerated crypts compared to S-PRT. Moreover, tumor growth studies showed no difference between SOBP and entrance for either of the treatment modalities.
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http://dx.doi.org/10.3390/cancers13164244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392865PMC
August 2021
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