Publications by authors named "Wen Zhang"

3,424 Publications

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Ratiometric Fluorescent Metal-Organic Framework Biosensor for Ultrasensitive Detection of Acrylamide.

J Agric Food Chem 2022 Aug 8. Epub 2022 Aug 8.

School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.

Acrylamide is a neurotoxin and carcinogen that forms during the thermal processing of food, inflicting irreversible harm to human health. Herein, a ratiometric fluorescence biosensor based on a 6-carboxyfluorescein-labeled aptamer (FAM-ssDNA) and porphyrin metal-organic framework (PCN-224) was developed. PCN-224 exhibits strong adsorption capacity for FAM-ssDNA and also quenches the fluorescence of FAM-ssDNA via fluorescence resonance energy transfer and photoinduced electron transfer. FAM-ssDNA hybridizes with complementary DNA to form double-stranded DNA (FAM-dsDNA), which is liberated from the PCN-224 surface, resulting in fluorescence recovery. However, the intrinsic fluorescence of the ligand remains unchanged. Acrylamide can create an adduct with FAM-ssDNA and inhibit the hybridization of FAM-dsDNA, thus realizing ratiometric sensing of acrylamide. The proposed biosensor displays excellent detection performance from 10 nM∼0.5 mM with a limit of detection of 1.9 nM. In conclusion, a fabricated biosensor was successfully applied to detect acrylamide in thermally processed food, and the results were consistent with those of high-performance liquid chromatography.
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http://dx.doi.org/10.1021/acs.jafc.2c04756DOI Listing
August 2022

Effects of Carvedilol on Blood Pressure, Blood Sugar, and Blood Lipids in Elderly Patients with Refractory Hypertension.

Comput Math Methods Med 2022 27;2022:7889024. Epub 2022 Jul 27.

The First Hospital of Hunan University of Chinese Medicine, Department of Cardiovascular Diseases, No. 95 Shaoshan Middle Road, Yuhua District, Changsha City, Hunan Province, China.

Refractory hypertension seriously affects the life safety of patients. To investigate the effect of carvedilol combined with conventional antihypertensive therapy on blood pressure, blood sugar, blood lipids, and cardiovascular and cerebrovascular complications in elderly patients with refractory hypertension, a total of 80 elderly patients with refractory hypertension who were admitted from June 2019 to September 2021 were selected as the retrospective research objects and divided into the observation group and the control group according to the random number table method, 40 cases in each group, and the control group received conventional antihypertensive therapy. On this basis, the observation group was treated with carvedilol, and the effects of blood pressure, blood sugar, blood lipids, and cardiovascular and cerebrovascular complications were analyzed in the two groups. After treatment, the systolic blood pressure, diastolic blood pressure, adrenal medulla (AM), and endothelin (ET) of the observation group were significantly lower than those of the control group, but the heart rate and NO of the observation group were significantly higher than those of the control group. After treatment, the fasting blood glucose, insulin, triacylglycerol (TG), cholesterol (CHO), and low-density lipoprotein (LDL-C) of the observation group were significantly higher than those of the control group, but the ISI and HDL-C of the observation group were significantly lower than those of the control group. After treatment, the levels of IL-1, IL-6, TNF-, UAER, BUN, and SCr in the observation group were significantly lower than those in the control group. The TC of the observation group was lower than that of the control group. Combination therapy has a remarkably stable, sustained, and safe antihypertensive effect on patients with refractory hypertension.
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http://dx.doi.org/10.1155/2022/7889024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348927PMC
July 2022

Plasma fingerprint of free fatty acids and their correlations with the traditional cardiac biomarkers in patients with type 2 diabetes complicated by coronary heart disease.

Front Cardiovasc Med 2022 22;9:903412. Epub 2022 Jul 22.

Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular disease, with at least 2-3 fold higher risk of cardiovascular diseases than non-diabetics. Free fatty acids (FFAs) are believed to play important roles in the occurrence of cardiovascular disease in people with T2DM. The aim of this study was to investigate the fingerprint of plasma FFAs and their correlations with the tradition risk factors of cardiovascular disease in T2DM patients complicated by coronary heart disease (CHD-T2DM). A total of 401 participants, including healthy control (HC, = 143), T2DM patients ( = 134), and CHD-T2DM patients ( = 126) were enrolled in this study. Plasma levels of 36 FFAs with carbon chain length ranged from 3 to 22 were quantified by using reverse phase ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Tradition risk factors of cardiovascular disease were tested in clinical laboratory, including homocysteine (HCY), creatine kinase (CK), high sensitivity C reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) and so on. Almost all the FFAs with different carbon chain length and unsaturation were significantly upregulated in the T2DM-CHD groups, compared to the HC and T2DM groups. Both n-3 and n-6 polyunsaturated fatty acids (PUFA) were also found to be significantly upregulated in T2DM-CHD group compared to the T2DM group. However, no significantly differences of the n-6/n-3 PUFA ratio, arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio, and arachidonic acid/docosahexaenoic acid (AA/DHA) ratio were observed between T2DM-CHD and T2DM groups. Plasma FFA levels were found to be positively correlated with HCY, CK, hsCRP, NT-proBNP and other tradition risk factors of CHD. Multivariate logistic regression analysis indicated that a dozens of FFAs were the independent risk factors of CHD after adjustment for confounding factors and other risk factors. Excessively high plasma levels of FFAs were demonstrated to be independent risk factors for CHD in patients with T2DM, despite of the differences in chain length, unsaturation, and double bond position.
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http://dx.doi.org/10.3389/fcvm.2022.903412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355375PMC
July 2022

The regulation of yes-associated protein/transcriptional coactivator with PDZ-binding motif and their roles in vascular endothelium.

Front Cardiovasc Med 2022 22;9:925254. Epub 2022 Jul 22.

School of Rehabilitation Medicine, Weifang Medical University, Weifang, China.

Normal endothelial function plays a pivotal role in maintaining cardiovascular homeostasis, while endothelial dysfunction causes the occurrence and development of cardiovascular diseases. Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) serve as crucial nuclear effectors in the Hippo signaling pathway, which are regulated by mechanical stress, extracellular matrix stiffness, drugs, and other factors. Increasing evidence supports that YAP/TAZ play an important role in the regulation of endothelial-related functions, including oxidative stress, inflammation, and angiogenesis. Herein, we systematically review the factors affecting YAP/TAZ, downstream target genes regulated by YAP/TAZ and the roles of YAP/TAZ in regulating endothelial functions, in order to provide novel potential targets and effective approaches to prevent and treat cardiovascular diseases.
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http://dx.doi.org/10.3389/fcvm.2022.925254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354077PMC
July 2022

The second-tier status of fragile X syndrome testing for unexplained intellectual disability/global developmental delay in the era of next-generation sequencing.

Front Pediatr 2022 22;10:911805. Epub 2022 Jul 22.

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

Objective: Although many unexplained intellectual disability/global developmental delay (ID/GDD) individuals have benefited from the excellent detection yield of copy number variations and next-generation sequencing testing, many individuals still who suffer from ID/GDD of unexplained etiology. In this study, we investigated the applicability of fragile X syndrome (FXS) testing in unexplained ID/GDD individuals with negative or absent genetic testing.

Methods: In this study, we used the triplet repeat primed polymerase chain reaction to evaluate the value and application of fragile X testing in unexplained ID/GDD individuals with negative or absent genetic testing ( = 681) from three hospitals.

Results: Of the 681 ID/GDD individuals with negative or absent genetic testing results detected by FXS testing, 12 men and one woman were positive. This corresponded to a diagnostic yield of 1.9% for FXS testing in our cohort. All FXS individuals had either a family history of ID/GDD or suggestive clinical features. The detection yield of FXS testing in ID/GDD individuals who completed genetic testing (2.70%, 12/438) was significantly higher than in individuals without any genetic testing (0.40%, 1/243).

Conclusions: This is the first report of FXS testing in ID/GDD individuals who lacked previous genetic testing, which promotes standardization of the FXS diagnostic process. These results highlight the utility of FXS testing of unexplained ID/GDD individuals with negative results from standard genetic testing. In the era of next-generation sequencing, FXS testing is more suitable as a second-tier choice and provides clinicians and geneticists with auxiliary references for tracing the etiology of ID/GDD.
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http://dx.doi.org/10.3389/fped.2022.911805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353215PMC
July 2022

Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking.

J Integr Med 2022 Jul 28. Epub 2022 Jul 28.

Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Institute of Critical Care, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Objective: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.

Methods: Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.

Results: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.

Conclusion: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.
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http://dx.doi.org/10.1016/j.joim.2022.07.005DOI Listing
July 2022

Effect of GnRH-a pretreatment before frozen-thawed embryo transfer on pregnancy outcome of adenomyosis-associated infertile patients with 56 cm ≤ uterine volume ≤100 cm.

Ann Transl Med 2022 May;10(9):509

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

Background: Whether gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment before transferring frozen-thawed embryos (FETs) could improve the clinical outcome of adenomyosis-associated infertile patients with 56 cm ≤ uterine volume ≤100 cm is unclear.

Methods: Adenomyosis patients who underwent fertilization and frozen embryo transfers from January 2009 to December 2019 with 56 cm ≤ uterine volume ≤100 cm were included in this retrospective cohort study. The subjects were divided into two groups (GnRH-a treatment group GnRH-a-free group). The effect of GnRH-a treatment before FET on pregnancy outcomes was explored by univariate and multivariate analysis. In the GnRH-a treatment group, uterine volume before and after GnRH-a pretreatment was also compared by -tests.

Results: A total of 186 patients undergoing 263 cryopreserved embryo transfer cycles were included. There was no significant difference in terms of the clinical pregnancy rate between patients in the GnRH-a treatment group (24/45, 53.3%) and the GnRH-a-free group (86/218, 39.4%) (P=0.098). The miscarriage rate in the GnRH-a treatment group (3/24, 12.5%) was significantly lower than that in the GnRH-a-free group (32/86, 37.2%) (P=0.044). The live birth rate in the GnRH-a treatment group (21/45, 46.7%) was significantly higher than that in the GnRH-a-free group (54/218, 24.8%) (P=0.009). However, the uterine volume did not change significantly before (82.0±13.4 cm) or after GnRH-a treatment (79.3±14.0 cm), with a P=0.123.

Conclusions: GnRH-a pretreatment before FET reduced the miscarriage rate and improved the live birth rate among infertile women with adenomyosis whose uterine volume was 56-100 cm.
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http://dx.doi.org/10.21037/atm-21-6247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347030PMC
May 2022

Laparoscopic Surgery for Focal-Form Congenital Hyperinsulinism Located in Pancreatic Head.

Front Pediatr 2022 19;10:919238. Epub 2022 Jul 19.

Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background And Aims: Congenital hyperinsulinism of infancy (CHI) is a rare condition that may cause irreversible severe neurological damage in infants. For children in whom medical management fails, partial or near-total pancreatectomy is then required according to the type of lesion. Currently, open surgery of near-total pancreatic head resection is a mature technique for the treatment of focal-form CHI located in the head of the pancreas, but a minimally invasive laparoscopic procedure has not been reported yet. The aim of this study was to verify the feasibility, safety, and efficacy of laparoscopic pancreatic head resection and Roux-en-Y pancreaticojejunostomy for focal-form CHI.

Methods: Two infants with persistent hypoglycemia and increased insulin levels were diagnosed with CHI and underwent laparoscopic near-total pancreatic head resection due to a suboptimal response to medical therapy and the likelihood of focal disease amenable to surgery. Clinical records, operative findings, and postoperative follow-up were collected and analyzed.

Results: The operative duration was 300-330 min, and the intraoperative blood loss was minimal. The duration of postoperative abdominal drainage was 4-5 days. Neither intra- nor postoperative abdominal complications occurred. Oral feeding was resumed 3-4 days after the operation, and the blood glucose level was gradually stabilized to within the normal range. Normal blood glucose was observed in both patients over a follow-up period of 3-6 months.

Conclusions: Laparoscopic pancreatic head resection and Roux-en-Y pancreaticojejunostomy can be considered a safe and effective procedure with minimal morbidity and excellent outcomes for the treatment of focal CHI in the head of the pancreas.
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http://dx.doi.org/10.3389/fped.2022.919238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343681PMC
July 2022

Impact of transient and chronic loneliness on progression and reversion of frailty in community-dwelling older adults: four-year follow-up.

BMC Geriatr 2022 Aug 4;22(1):642. Epub 2022 Aug 4.

Department of Social Work and Social Administration, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.

Background: Frailty is a common condition in older adults that is characterized by transitions between frailty states in both directions (progression and reversion) over time. Loneliness has been reported to be associated with the incidence of frailty, but few studies have explored the impact of persistent loneliness over time on frailty. In this study, we aimed to whether and how two different types of loneliness, transient and chronic, were associated with changes in frailty status in older adults.

Methods: The analytic sample contained 2961 adults aged ≥ 60 years who completed interviews for both the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study. The logistic regression model was used to examine the relationship between transient and chronic loneliness and progression and reversion of frailty. Demographics (age, sex, education level, marital status, urban-rural residence), living alone, chronic conditions, physical function, and depressive symptoms from the 2011 wave were adjusted.

Results: After four years, 21% of the studied sample reported progression, 20% reported reversion in frailty, 31% reported transient loneliness, and 14% reported chronic loneliness. There was no significant difference in participants who reported transient loneliness (OR = 1.10, 95% CI [0.89,1.37]), or chronic loneliness (OR = 1.14, 95% CI [0.84,1.57]) on the progression of frailty, compared with no report of loneliness. Participants reporting chronic loneliness (OR = 0.68, 95% CI [0.50,0.93]) were less likely to report reversion in their level of frailty compared to participants who did not report loneliness but not transient loneliness (OR = 0.87, 95% CI [0.70,1.08]).

Conclusions: Roughly the same percentage, a fifth, of older Chinese adults progressed or reversed in frailty status without active intervention. Chronic loneliness was related to a lower probability of reversion in the frail group than in the no loneliness group, but not in the transient loneliness group. More attention should be given to older adults with chronic loneliness.
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http://dx.doi.org/10.1186/s12877-022-03283-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351253PMC
August 2022

Exploring Idiopathic Pulmonary Fibrosis Biomarker by Simultaneous Two-Photon Fluorescence Imaging of Cysteine and Peroxynitrite.

Anal Chem 2022 Aug 4. Epub 2022 Aug 4.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.

Idiopathic pulmonary fibrosis (IPF) has been characterized as a chronic inflammatory disease that leads to irreversible damage to pulmonary function. However, there is no specific IPF biomarker that can be used to distinguish IPF and not pneumonia. Endoplasmic reticulum (ER) stress is prominent in IPF. To search for a specific biomarker of IPF, we developed two ER-targeting two-photon (TP) fluorescent probes, TP-ONOO and TP-Cys, for peroxynitrite (ONOO) and cysteine (Cys) imaging, respectively. A significant increase in Cys levels in the lungs was discovered only in mice with IPF, which implied that Cys might be an IPF biomarker candidate. Furthermore, we uncovered the mechanism of glutathione (GSH) deficiency in IPF, which was not due to Cys shortage but instead was attributable to impaired glutamate cysteine ligase and glutathione synthetase activities ONOO-induced post-transcriptional modification. This work has potential to provide a new method for IPF early diagnosis and drug efficacy evaluation.
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http://dx.doi.org/10.1021/acs.analchem.2c01866DOI Listing
August 2022

Microwave-Assisted Enzymatic Extraction, Partial Characterization, and Antioxidant Potential of Polysaccharides from Sagittaria trifolia Tuber.

Chem Biodivers 2022 Aug 3:e202200219. Epub 2022 Aug 3.

School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, 215500, Jiangsu, China.

Sagittaria trifolia tuber is an aquatic vegetable. In this work, microwave-assisted enzymatic extraction (MEE) was used to extract S. trifolia tuber polysaccharides (STTPs). Optimum conditions were complex enzyme of 2 %, liquid-to-solid ratio of 43 : 1 mL g , microwave power of 506 W, and time of 8 min, under which STTPs yield was 36.22±0.69 %, higher than those of other methods. STTPs were sulfated polysaccharides with sulfur valence of S . STTPs comprised mannose, glucose, galactose, and arabinose at a mole ratio of 3.69 : 19.33 : 6.21 : 1.00, molecular weights of 3606 kDa and 149.6 kDa, particle size of 220 nm, and zeta potential of -5.02 mV. The surface of STTPs was full of bumps and holes, and abundant in O1s and non-functionalized C1s. STTPs would scavenge reactive oxygen species with advantage. It would provide an efficient MEE method to obtain antioxidant STTPs, also a clue for extracting polysaccharides from starch-rich crops.
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http://dx.doi.org/10.1002/cbdv.202200219DOI Listing
August 2022

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

J Nucl Cardiol 2022 Aug 2. Epub 2022 Aug 2.

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China.

Background: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients.

Methods: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke).

Results: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030).

Conclusion: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.
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http://dx.doi.org/10.1007/s12350-022-03038-wDOI Listing
August 2022

Final overall survival data of sintilimab plus pemetrexed and platinum as First-Line treatment for locally advanced or metastatic nonsquamous NSCLC in the Phase 3 ORIENT-11 study.

Lung Cancer 2022 Jul 19;171:56-60. Epub 2022 Jul 19.

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

Objectives: In ORIENT-11, first-line sintilimab + pemetrexed-platinum significantly improved PFS compared with placebo + pemetrexed-platinum in patients with advanced metastatic nonsquamous non-small-cell lung cancer (AMnsqNSCLC). The study met the primary endpoint of PFS as of 15November2019. Here we report final survival analysis from ORIENT-11 (NCT03607539) using a 15September2021 data cutoff.

Methods: Patients with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR or ALK genomic tumor aberrations were randomly assigned to sintilimab + pemetrexed-platinum (n = 266) or placebo + pemetrexed-platinum (n = 131). Patients were stratified by PD-L1 expression, platinum-chemotherapy, and gender. Treatment continued until PD, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo + pemetrexed-platinum arm could be sequenced to second-line sintilimab monotherapy, contingent upon PD. Response was assessed (RECISTv.1.1) by blinded independent radiographic review committee. Primary endpoint was PFS. OS was a secondary endpoint and defined from date of randomization to date of death due to any cause. Final OS analysis was defined as approximately 2 years after last patient randomized or when approximately 65 % of patients died, whichever first.

Results: At data cutoff of final OS analysis, median study follow-up was 30.8 months. Of 397 patients, 243 OS events were observed (sintilimab + pemetrexed-platinum:151[57 %];placebo + pemetrexed-platinum:92 [70 %]). Of the patients in placebo + pemetrexed-platinum arm, 47 % crossed over to sintilimab monotherapy per protocol. Median OS was 24.2 months in sintilimab + pemetrexed-platinum arm and 16.8 months in placebo + pemetrexed-platinum arm (HR:0.65[95 % CI:0.50,0.85]). Estimated 2-year OS rates were 50 %(sintilimab + pemetrexed-platinum) and 32 %(placebo + pemetrexed-platinum). After adjusting for the crossover effect, OS treatment effect was more pronounced with HR 0.52 (95 % CI:0.38,0.69). OS benefit across all prespecified subgroups was largely consistent with that observed in the ITT population.

Conclusions: In the ORIENT-11 final OS analysis, sintilimab + pemetrexed-platinum demonstrated improved OS compared to placebo + pemetrexed-platinum when administered as first-line therapy in AMnsqNSCLC without EGFR or ALK genomic tumor aberrations.
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http://dx.doi.org/10.1016/j.lungcan.2022.07.013DOI Listing
July 2022

Virome of Giant Panda-Infesting Ticks Reveals Novel Bunyaviruses and Other Viruses That Are Genetically Close to Those from Giant Pandas.

Microbiol Spectr 2022 Aug 2:e0203422. Epub 2022 Aug 2.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Tick infestations have been reported as one of the factors threatening the health of giant pandas, but studies of viral pathogens carried by ticks feeding on the blood of giant pandas are limited. To assess whether blood-sucking ticks of giant pandas can carry viral pathogens and if so, whether the viruses in ticks are associated with those previously detected in giant panda hosts, we determined the viromes of ticks detached from giant pandas in a field stocking area in Sichuan Province, southwest China. Using viral metagenomics we identified 32 viral species in ticks, half of which (including anellovirus [ = 9], circovirus [ = 3], and gemycircularvirus [ = 4]) showed homology to viruses carried by giant pandas and their associated host species (such as red pandas and mosquitoes) in the same living domain. Remarkably, several viruses in this study phylogenetically assigned as bunyavirus, hepe-like virus, and circovirus were detected with relatively high abundance, but whether these newly identified tick-associated viruses can replicate in ticks and then transmit to host animals during a blood meal will require further investigation. These findings further expand our understanding of the role of giant panda-infesting ticks in the local ecosystem, especially related to viral acquisition and transmission, and lay a foundation to assess the risk for giant panda exposure to tick-borne viruses. Ticks rank only second to mosquitoes as blood-feeding arthropods, capable of spreading pathogens (including viruses, bacteria, and parasites) to hosts during a blood meal. To better understand the relationship between viruses carried by ticks and viruses that have been reported in giant pandas, it is necessary to analyze the viromes of giant panda-parasitic blood-sucking ticks. This study collected 421 ticks on the body surface of giant pandas in Sichuan Province, China. We characterized the extensive genetic diversity of viruses harbored by these ticks and reported frequent communication of viruses between giant pandas and their ticks. While most of the virome discovered here are nonpathogenic viruses from giant pandas and potentially tick-specific viruses, we revealed some possible tick-borne viruses, represented by novel bunyaviruses. This research contributes to the literature because currently there are few studies on the virome of giant panda-infesting ticks.
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http://dx.doi.org/10.1128/spectrum.02034-22DOI Listing
August 2022

Protein Lysine Methyltransferase SMYD2: A Promising Small Molecule Target for Cancer Therapy.

J Med Chem 2022 Aug 1. Epub 2022 Aug 1.

College of Pharmaceutical Science, Zhejiang University of Technology, and Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, China.

In epigenetic research, the abnormality of protein methylation modification is closely related to the occurrence and development of tumors, which stimulates the interest of researchers in protein methyltransferase research and the efforts to develop corresponding specific small molecule inhibitors. Currently, the protein lysine methyltransferase SMYD2 has been identified as a promising new small molecule target for cancer therapy. But its biological functions have not been fully studied and relatively few inhibitors have been reported, thus this field needs to be further explored. This perspective provides a comprehensive and systematic review of the available resources in this field, including its research status, biological structure, related substrates and methylation mechanisms, and research status of inhibitors. In addition, this perspective elaborates in detail the current challenges in this field, our insights into what needs to be done next, rational drug design of novel SMYD2 inhibitors, and foreseeable development directions in the future.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00325DOI Listing
August 2022

Tunable 2D Hybrid Perovskites with Pd(II) Adsorption and Semiconducting Properties.

Inorg Chem 2022 Aug 1. Epub 2022 Aug 1.

Jiangsu Key Laboratory for Science and Applications of Molecular Ferroelectrics and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, People's Republic of China.

Layered hybrid perovskites, due to their broad application potential in optical, electrical, and luminescence fields, are attracting increasing attention. Herein, we report two novel two-dimensional hybrid organic-inorganic perovskites [CHNS]PbBr () and [CHNS]PbI () ([CHNS] is 3-ethylaminothiazolium), which possess phase transition and semiconductor properties. Intriguingly, has semiconductor properties with an optical band gap of 2.70 eV and a photocurrent to dark current ratio of 50 for the photoresponse. By varying the halogen, the band gap of is significantly reduced to 2.06 eV and the photocurrent to dark current ratio of the photoresponse reaches 10. Moreover, compounds and are able to adsorb Pd(II) resulting from the presence of -SH groups in the cation. The adsorption of Pd(II) can turn a semiconductor into an insulator, weaken the fluorescence intensity, and cause the phase transition behavior to disappear. This work has remarkable implications for the continuous development of hybrid perovskites with phase transitions, metal adsorption, and semiconductor properties.
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http://dx.doi.org/10.1021/acs.inorgchem.2c02044DOI Listing
August 2022

Hepatectomy and pneumectomy combined with targeted therapy for primary hepatic neuroendocrine carcinoma: Case report and review of the literature.

Front Surg 2022 15;9:920276. Epub 2022 Jul 15.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Primary hepatic neuroendocrine carcinoma (PHNEC) manifests as a rare type of liver tumor. PHNEC is not specifically clinical or radiographical and is often misdiagnosed and mistreated. Here, we present a case report of PHNEC in a 50-year-old woman who was admitted to our department with concealed pain in the right upper abdomen. The initial diagnosis was a probable hepatic space-occupying lesion with tumor bleeding. The patient was subjected to a partial right hemihepatectomy, cholecystectomy, partial resection of the lower lobe of the right lung, partial resection of the diaphragm, and resection of the right perirenal fat sac to alleviate her symptoms. After surgery, gene sequencing was performed to determine the possible cause of the condition. However, five months after discharge, the patient was hospitalized again because of retroperitoneal and peritoneal multiple metastases. Nine months after surgery, the patient died. This case is likely to aid in furthering our understanding of PHNEC to improve the future diagnosis and treatment of this disease.
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http://dx.doi.org/10.3389/fsurg.2022.920276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334775PMC
July 2022

Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial.

Lancet Oncol 2022 Jul 28. Epub 2022 Jul 28.

Department of Medical Science and Strategy Oncology, Innovent Biologics, Suzhou, China.

Background: VEGF inhibitors can enhance the efficacy of immunotherapy. However, despite high initial response rates, almost all patients eventually develop treatment resistance to EGFR tyrosine-kinase inhibitors. We aimed to evaluate the efficacy and safety of sintilimab with or without IBI305 plus pemetrexed and cisplatin, compared with pemetrexed and cisplatin alone, for the treatment of patients with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) who had disease progression after receiving EGFR tyrosine-kinase inhibitor therapy.

Methods: This randomised, double-blind, multicentre, phase 3 trial was conducted at 52 hospitals in China. Eligible participants were adults aged 18-75 years with locally advanced or metastatic NSCLC and EGFR who progressed after receiving a EGFR tyrosine-kinase inhibitor, had an Eastern Cooperative Oncology Group performance status of 0 or 1 with at least one measurable lesion, and an estimated life expectancy of at least 3 months. Participants were randomly assigned (1:1:1) to receive sintilimab (200 mg) plus IBI305 (15 mg/kg) plus pemetrexed (500 mg/m) and cisplatin (75 mg/m), sintilimab plus pemetrexed and cisplatin, or pemetrexed and cisplatin (chemotherapy alone) using block randomisation with stratification according to sex and presence or absence of brain metastases. All study drugs were administered intravenously on day 1 of each cycle, once every 3 weeks. Except for cisplatin, which was only given in the first four cycles, treatment was given for 24 months or until disease progression, intolerable toxic effects, withdrawal of consent, death, or other protocol-specified conditions, whichever occurred first. The primary endpoint was progression-free survival in the intention-to-treat population. We herein report the first planned interim analysis, with progression-free survival results for the comparison between sintilimab plus IBI305 plus chemotherapy versus chemotherapy alone. The progression-free survival results for the sintilimab plus pemetrexed and cisplatin group are immature and not reported here. This study is registered with ClinicalTrials.gov, NCT03802240 (recruiting).

Findings: Between July 11, 2019, and July 31, 2021, 936 patients were screened and 444 were randomly assigned (148 to the sintilimab plus IBI305 plus chemotherapy group, 145 to the sintilimab plus chemotherapy group, and 151 to the chemotherapy alone group). Data cutoff for this interim analysis was July 31, 2021. After a median follow-up of 9·8 months (IQR 4·4-13·3), progression-free survival was significantly longer in the sintilimab plus IBI305 plus chemotherapy group versus the chemotherapy alone group (median 6·9 months [95% CI 6·0-9.3] vs 4·3 months [4·1-5·4]; hazard ratio 0·46 [0·34-0·64]; p<0·0001). The most common grade 3 or 4 treatment-related adverse events were decreased neutrophil count (30 [20%] in the sintilimab plus IBI305 plus chemotherapy group vs 26 [18%] in the sintilimab plus chemotherapy group vs 27 [18%] in the chemotherapy alone group), decreased white blood cell count (17 [11%] vs 12 [8%] vs 13 [9%]), and anaemia (18 [12%] vs ten [7%] vs 15 [10%]). Potentially treatment-related deaths occurred in six patients (intestinal obstruction, gastrointestinal haemorrhage, and myelosuppression in one patient each, and three deaths of unknown cause) in the sintilimab plus IBI305 plus chemotherapy group, and in one patient in the chemotherapy alone group (unknown cause).

Interpretation: In this interim analysis, sintilimab plus IBI305 plus cisplatin and pemetrexed was generally efficacious and well tolerated in patients with EGFR-mutated NSCLC who progressed after receiving EGFR tyrosine-kinase inhibitor therapy.

Funding: Innovent Biologics and the National Natural Science Foundation of China.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(22)00382-5DOI Listing
July 2022

Benchmarking bioinformatics approaches for tumour mutational burden evaluation from a large cancer panel against whole-exome sequencing.

J Clin Pathol 2022 Jul 29. Epub 2022 Jul 29.

Pathology and Cell Biology, Columbia University Irving Medical Center, New York City, New York, USA

Tumour mutational burden (TMB) is used to predict response to immunotherapies. Although several groups have proposed calculation methods for TMB, a clear consensus has not yet emerged. In this study, we explored TMB calculation approaches with a 586-gene cancer panel (1.75 Mb) benchmarked to TMB measured by whole-exome sequencing (WES), using 30 samples across a range of tumour types. We explored variant allelic fraction (VAF) cut-offs of 5% and 10%, population database filtering at 0.001, 0.0001 and 0.000025, as well as different combinations of synonymous, insertion/deletion and intronic (splice site) variants, as well as exclusion of hotspot mutations, and examined the effect on TMB correlation. Good correlation (Spearman, range 0.66-0.78) between WES and panel TMB was seen across all methods evaluated. Each method of TMB calculation evaluated showed good positive per cent agreement and negative per cent agreement using 10 mutations/Mb as a cut-off, suggesting that multiple TMB calculation approaches may yield comparable results.
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http://dx.doi.org/10.1136/jcp-2022-208385DOI Listing
July 2022

Case Report: Tofacitinib as a possible treatment for arthritis in an APDS2 patient.

Rheumatology (Oxford) 2022 Jul 29. Epub 2022 Jul 29.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1093/rheumatology/keac436DOI Listing
July 2022

Review of Current Robotic Approaches for Precision Weed Management.

Curr Robot Rep 2022 Jul 22:1-13. Epub 2022 Jul 22.

Intelligent Equipment and Robotics Lab, Department of Automation, School of Mechatronic Engineering and Automation, Shanghai University, Shangda Street No. 99, Baoshan District, Shanghai, China.

Purpose Of Review: The goal of this review is to provide an overview of current robotic approaches to precision weed management. This includes an investigation into applications within this field during the past 5 years, identifying which major technical areas currently preclude more widespread use, and which key topics will drive future development and utilisation.

Recent Findings: Studies combining computer vision with traditional machine learning and deep learning are driving progress in weed detection and robotic approaches to mechanical weeding. Integrating key technologies for perception, decision-making, and control, autonomous weeding robots are emerging quickly. These effectively save effort while reducing environmental pollution caused by pesticide use.

Summary: This review assesses different weed detection methods and weeder robots used in precision weed management and summarises the trends in this area in recent years. The limitations of current systems are discussed, and ideas for future research directions are proposed.
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http://dx.doi.org/10.1007/s43154-022-00086-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305686PMC
July 2022

A Degradable and Osteogenic Mg-Based MAO-MT-PLGA Drug/Ion Delivery System for Treating an Osteoporotic Fracture.

Pharmaceutics 2022 Jul 16;14(7). Epub 2022 Jul 16.

Department of Orthopedics, The Fourth Hospital of China Medical University, No. 77 Puhe Road, Shenyang 110122, China.

Osteoporotic fractures are a very common bone disease that is difficult to completely cure. A large number of people worldwide suffer from pain caused by osteoporotic fractures every year, which can even cause disability and death. The compromised skeletal strength, lower density, trabecular microstructure, and bone-forming ability caused by osteoporotic fractures make them difficult to treat relative to normal fractures. An ideal scheme for osteoporotic fractures is to select internal fixation materials with matched mechanical and biological properties and carry anti-osteoporosis drugs on the plant to achieve bio-fixation and improve the condition of osteoporosis simultaneously. We designed a Mg-based MAO-MT-PLGA drug/ion delivery system (DDS) compatible with bone-like mechanical properties, degradation properties, and drug therapy. In this research, we evaluated the degradation behavior of Mg-based MAO-MT-PLGA DDS using immersion tests and electrochemical tests aided by SEM, EDS, XPS, XRD, and FT-IR. The DDS showed better corrosion resistance over Mg alloy and could release more Mg due to the degradation of PLGA. According to cell viability and cell adhesion, the DDS showed better osteogenic characteristics over control group I (Mg alloy) and control group II (Mg-based MAO alloy), especially in the cells co-cultured with the leaching solution for 72 h, in which the DDS group increased to about 15% cell viability compared with group I ( < 0.05). The mRNA relative expressions, including ALP, collagen I, OCN, OPG, and Runx-2, as well as extracellular matrix calcium deposits of the DDS, are 1.5~2 times over control group I and control group II ( < 0.05), demonstrating a better ability to promote bone formation and inhibit bone resorption. After the DDS was implanted into the castrated rat model for one month, the trabeculae in the treatment group were significantly denser and stronger than those in the control group, with a difference of about 1.5 times in bone volume fraction, bone density, and the number of trabeculae, as well as the magnesium content in the bone tissue ( < 0.05). The above results demonstrated that the Mg-based MAO-MT-PLGA drug/ion delivery system is a potential treatment for osteoporotic fractures.
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http://dx.doi.org/10.3390/pharmaceutics14071481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320112PMC
July 2022

Development and Validation of Nutrition Literacy Assessment Instrument for Chinese Pregnant Women.

Nutrients 2022 Jul 13;14(14). Epub 2022 Jul 13.

Department of Nutrition and Food Hygiene, School of Public Health, Peking University, NO. 38 Xueyuan Road, Beijing 100083, China.

The study was designed to develop and validate the nutrition literacy assessment instrument for pregnant women in China (NLAI-P). The dimension, components and questions of NLAI-P were identified via literature review and expert consultation. A panel of experts evaluated the content validity. The construct validity was evaluated by using the exploratory factor analyses (EFA) and confirmatory factor analyses (CFA). Cronbach's α coefficient and split-half reliability were applied for examining the reliability. The NLAI-P was divided into 3 dimensions including knowledge, behavior and skill dimension. Findings showed NLAI-P possessed the satisfactory content validity (content validity index = 0.98, content validity ratio = 0.97), acceptable construct validity (χ/ = 1.82, GFI = 0.86, AGFI = 0.84, RMSEA = 0.046) and good reliability (Cronbach's α coefficient = 0.82). The average scores of NLAI-P were 46.59 ± 9.27. With the adjustment of confounding factors, education level presented a significantly positive correlation with NLAI-P scores. In conclusion, NLAI-P were valid and reliable to inspect NL level of pregnant women in China. Poor NL was prevalent among Chinese pregnant women. Based on the education level, taking targeted propaganda and education measures would achieve the optimal effect. NLAI-P can be applied as the tool for monitoring and assessing NL of pregnant women, and facilitate the designation of targeted interventions policies.
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http://dx.doi.org/10.3390/nu14142863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320244PMC
July 2022

Clinical practice of Helicobacter pylori infection management by gastroenterologists in secondary and tertiary hospitals: A stratified sampling cross-sectional survey.

J Dig Dis 2022 Jul 26. Epub 2022 Jul 26.

Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

Aim: To investigate the management of Helicobacter pylori infection by gastroenterologists in secondary and tertiary hospitals in Shandong, a region with high Helicobacter pylori prevalence and gastric cancer incidence.

Methods: A questionnaire-based, stratified sampling survey was conducted from June 1 to August 30, 2021. The ratio of secondary to tertiary hospitals was set as 2:1. An electronic questionnaire was sent to all gastroenterologists via the WeChat platform.

Results: A total of 1053 (89.09%, 1053/1182) gastroenterologists were included. Overall, 34.19% and 60.59% of gastroenterologists supported universal screening for and treating Helicobacter pylori infection, respectively. The most preferred testing method in secondary and tertiary hospitals was the C-urea breath test (53.92% and 80.48%, respectively), but the reconfirmation rate of results close to the cut-off value was low (55.10% and 59.48%, respectively). Gastroenterologists in secondary and tertiary hospitals preferred bismuth-containing quadruple therapy (96.67% and 98.53%, respectively), but the antibiotic combination prescribed for patients with a penicillin allergy was suboptimal in secondary hospitals. The overall follow-up rate was 64.58%, and gastroenterologists in secondary hospitals were more proactive than those in tertiary hospitals (69.14% vs. 60.04%, P= 0.001). Less than 80% of gastroenterologist emphasized the importance of post-treatment confirmation to their patients. Only a minority of gastroenterologists in secondary and tertiary hospitals (30.79% and 34.36%, respectively) could achieve acceptable eradication rates (exceeding 80%).

Conclusions: Deficiencies exist in both secondary and tertiary hospitals, and the eradication rate is unacceptably low. Additional training programs for gastroenterologists are warranted to strengthen their comprehension of the guidelines.
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http://dx.doi.org/10.1111/1751-2980.13119DOI Listing
July 2022

Docetaxel resistance-derived LINC01085 contributes to the immunotherapy of hormone-independent prostate cancer by activating the STING/MAVS signaling pathway.

Cancer Lett 2022 Jul 19;545:215829. Epub 2022 Jul 19.

School of Life Sciences, Shanghai University, Shanghai, 200444, China. Electronic address:

Acquired docetaxel (doc) resistance, one of the major reasons for unfavorable prognosis in patients with aggressive hormone-independent prostate cancer (HIPC), is a major obstacle for patient treatment. Dysregulation of long non-coding RNAs promotes or suppresses chemoresistance in multiple cancers; however, the specific molecular mechanisms underlying HIPC remain unknown. In this study, we found that the LINC01085, as a tumor-suppressor, which showed significant clinically relevant in HIPC patients with doc-resistance. Mechanistically, in docetaxel-sensitive cells, LINC01085 could specifically bind to both TANK-binding kinase 1 (TBK1) and glycogen synthase kinase 3β (GSK3β), and higher LINC01085 RNA levels could inhibit TBK1 dimerization. Whereas, in doc-resistant cells, lower LINC01085 RNA level lost the strong binding with both, meanwhile, the interaction between TBK1 and GSK3β enhanced which accelerated TBK1 phosphorylation at the Ser-172 site, resulting in decreased expression levels of PD-L1 and NF-κB as well as the secretion of type I/III interferons. Thus, Overexpression of LINC01085 combined with immune checkpoint blockade is an effective strategy for the treatment of HIPC patients.
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http://dx.doi.org/10.1016/j.canlet.2022.215829DOI Listing
July 2022

Mechanical and hydrodynamic effects of stent expansion in tapered coronary vessels.

Biomech Model Mechanobiol 2022 Jul 22. Epub 2022 Jul 22.

School of Health Science and Engineering, University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai, 200093, China.

Percutaneous coronary intervention (PCI) has become the primary treatment for patients with coronary heart disease because of its minimally invasive nature and high efficiency. Anatomical studies have shown that most coronary vessels gradually shrink, and the vessels gradually become thinner from the proximal to the distal end. In this paper, the effects of different stent expansion methods on the mechanical and hemodynamic behaviors of coronary vessels and stents were studied. To perform a structural-mechanical analysis of stent implantation, the coronary vessels with branching vessels and the coronary vessels with large bending curvature are selected. The two characteristic structures are implanted in equal diameter expansion mode and conical expansion mode, and the stress and mechanical behaviors of the coronary vessels and stents are analyzed. The results of the structural-mechanical analysis showed that the mechanical behaviors and fatigue performance of the cobalt-chromium alloy stent were good, and the different expansion modes of the stent had little effect on the fatigue performance of the stent. However, the equal diameter expansion mode increased distal coronary artery stress and the risk of vascular injury. The computational fluid dynamics analysis results showed that different stent expansion methods had varied effects on coronary vessel hemodynamics and that the wall shear stress distribution of conical stent expansion is more uniform compared with equal diameter expansion. Additionally, the vortex phenomenon is not apparent, the blood flow velocity is slightly increased, the hydrodynamic environment is more reasonable, and the risk of coronary artery injury is reduced.
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http://dx.doi.org/10.1007/s10237-022-01605-1DOI Listing
July 2022

Relationship between intestinal flora, inflammation, BDNF gene polymorphism and generalized anxiety disorder: A clinical investigation.

Medicine (Baltimore) 2022 Jul 22;101(29):e28910. Epub 2022 Jul 22.

Shandong Mental Health Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Introduction: Understanding factors related to generalized anxiety disorder pathogenesis is critical for elucidating the mechanism and preventing its establishment. Intestinal flora and hereditary factors such as brain-derived neurotrophic factor (BDNF) gene polymorphism may have a role in the development of generalized anxiety disorder. This work explored the relationship between intestinal flora, inflammatory changes and BDNF gene polymorphisms and the occurrence of generalized anxiety disorder.

Methods: Forty-eight patients with generalized anxiety disorder and 57 healthy people were included in the study. As the disease group and control group, the polymorphisms of rs10767664 and rs7124442 of the BDNF gene, differences in the distribution of intestinal flora, and changes in inflammatory and immune indicators were analyzed.

Results: The distribution of BDNF gene alleles, genotypes and haplotypes in the disease group were different from those in the control group. The levels of TNF-α (P = .000), interleukin-4 (P = .000), interleukin-10 (P = .043) and IgG (P = .008) in patients with generalized anxiety disorder in the disease group were different from those in the control group. The distribution of gut microbes in patients with generalized anxiety disorder in the disease group was different from that in the control group.

Conclusion: The onset of generalized anxiety disorder is related to BDNF gene polymorphism, and is accompanied by changes in intestinal flora and inflammatory immune status in the body.
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http://dx.doi.org/10.1097/MD.0000000000028910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302347PMC
July 2022

Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review.

J Exp Clin Cancer Res 2022 Jul 21;41(1):227. Epub 2022 Jul 21.

Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

CD8+ T cells play a central role in anti-tumor immunity. Naïve CD8+ T cells are active upon tumor antigen stimulation, and then differentiate into functional cells and migrate towards the tumor sites. Activated CD8+ T cells can directly destroy tumor cells by releasing perforin and granzymes and inducing apoptosis mediated by the death ligand/death receptor. They also secrete cytokines to regulate the immune system against tumor cells. Mitochondria are the central hub of metabolism and signaling, required for polarization, and migration of CD8+ T cells. Many studies have demonstrated that mitochondrial dysfunction impairs the anti-tumor activity of CD8+ T cells through various pathways. Mitochondrial energy metabolism maladjustment will cause a cellular energy crisis in CD8+ T cells. Abnormally high levels of mitochondrial reactive oxygen species will damage the integrity and architecture of biofilms of CD8+ T cells. Disordered mitochondrial dynamics will affect the mitochondrial number and localization within cells, further affecting the function of CD8+ T cells. Increased mitochondria-mediated intrinsic apoptosis will decrease the lifespan and quantity of CD8+ T cells. Excessively low mitochondrial membrane potential will cause the release of cytochrome c and apoptosis of CD8+ T cells, while excessively high will exacerbate oxidative stress. Dysregulation of mitochondrial Ca2+ signaling will affect various physiological pathways in CD8+ T cells. To some extent, mitochondrial abnormality in CD8+ T cells contributes to cancer development. So far, targeting mitochondrial energy metabolism, mitochondrial dynamics, mitochondria-mediated cell apoptosis, and other mitochondrial physiological processes to rebuild the anti-tumor function of CD8+ T cells has proved effective in some cancer models. Thus, mitochondria in CD8+ T cells may be a potential and powerful target for cancer treatment in the future.
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http://dx.doi.org/10.1186/s13046-022-02439-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306053PMC
July 2022

Age-related twin-peak prevalence profiles of H. pylori infection, gastritis, GIN and gastric cancer: Analyses of 70,534 patients with gastroscopic biopsies.

PLoS One 2022 21;17(7):e0265885. Epub 2022 Jul 21.

Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.

Objectives: H. pylori (Hp) infection has been indicated in the pathogenesis of gastric diseases including gastric cancer (GC). This study aimed at exploring the relationships between Hp infection and gastric diseases including GC in a large dataset of routine patients undergoing gastroscopy.

Methods: From November 2007 to December 2017, 70,534 first-time visiting patients aged 18-94 years with gastroscopic biopsies were histologically diagnosed and analyzed. Patients' data were entered twice in an Excel spreadsheet database and analyzed using the SPSS (version 22.0) software package and statistical significance was defined as P<0.05 for all analyses.

Results: The first interesting observation was age-related twin-peak prevalence profiles (TPPs) for Hp infection, gastritis, and advanced diseases with different time spans (TS) between the first and second occurring peaks. Hp infection and gastritis had TPPs occurring at earlier ages than TPPs of gastric introepithelial neoplasia (GIN) and GC. More patients were clustered at the second occurring TPPs. The time spans (TS) from the first occurring peak of Hp infection to the first occurring peaks of other gastric diseases varied dramatically with 0-5 years for gastritis; 5-15 years for GINs, and 5-20 years for GC, respectively. The number of males with Hp infection and gastric diseases, excluding non-atrophic gastritis (NAG), was more than that of females (P<0.001).

Conclusions: We have first observed age-related twin-peak prevalence profiles for Hp infection, gastritis, GIN, and GC, respectively, among a large population of patients undergoing gastroscopy. The second prevalence peak of GC is at ages of 70-74 years indicating that many GC patients would be missed during screening because the cut-off age for screening is 69 years old in China.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302749PMC
July 2022

Electrocatalytic Upcycling of Nitrate Wastewater into an Ammonia Fertilizer via an Electrified Membrane.

Environ Sci Technol 2022 Jul 21. Epub 2022 Jul 21.

John A. Reif, Jr. Department of Civil and Environmental Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102, United States.

Electrochemically upcycling wastewater nitrogen such as nitrate (NO) and nitrite (NO) into an ammonia fertilizer is a promising yet challenging research topic in resource recovery and wastewater treatment. This study presents an electrified membrane made of a [email protected] foam and a polytetrafluoroethylene (PTFE) membrane for reducing NO to ammonia (NH) and upcycling NH into (NH)SO, a liquid fertilizer for ready-use. A paired electrolysis process without external acid/base consumption was achieved under a partial current density of 63.8 ± 4.4 mA·cm on the cathodic membrane, which removed 99.9% NO in the feed (150 mM NO) after a 5 h operation with an NH recovery rate of 99.5%. A recovery rate and energy consumption of 3100 ± 91 g-(NH)SO·m·d and 21.8 ± 3.8 kWh·kg-(NH)SO, respectively, almost outcompete the industrial ammonia production cost in the Haber-Bosch process. Density functional theory (DFT) calculations unraveled that the electrochemical conversion of Cu into Cu provides highly dynamic active species for NO reduction to NH. This electrified membrane process was demonstrated to achieve synergistic nitrate decontamination and nutrient recovery with durable catalytic activity and stability.
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http://dx.doi.org/10.1021/acs.est.1c08442DOI Listing
July 2022
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