Publications by authors named "Min Xu"

1,873 Publications

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Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis.

Free Radic Biol Med 2021 Jun 15. Epub 2021 Jun 15.

Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, 323000, China; Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China. Electronic address:

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic recurrent and incurable gastrointestinal diseases with an unknown etiology that leads to a high risk of developing colitis-associated colorectal cancer (CRC).

Objectives: In this study, we measured the expression characteristics of MELK in IBD and CRC tissues and explored the regulatory effect of OTSSP167 (a MELK-selective inhibitor) on the mice models of colitis and colitis-associated carcinogenesis and analyzed the specific molecular mechanisms.

Methods: DSS-induced colitis and colitis-associated carcinogenesis (CAC) model were treated with MELK inhibitor OTSSP167 then the fight against effect of OTSSP167 in the clinical symptoms of colitis and CAC was measured. In addition, underlying mechanism of OTSSP167 treatment in vitro and vivo including anti-ferroptosis and anti-inflammatory response effect was further explored.

Results: We found that pharmacological inhibition of MELK was indicated to significantly alleviate the inflammatory response in mice with colitis, reduce intestinal damage, and effectively inhibit the occurrence and progression of colitis-propelled carcinogenesis, which was closely related to the regulation of gut microbial composition, and OTSSP167-mediated fecal microbiota transplantation effectively alleviated DSS-induced colitis. In addition, OTSSP167 treatment obviously inhibited ferroptosis in the intestinal tissue and suppressed macrophage infiltration and M1 polarization, which reduced the secretion of pro-inflammatory factors. Further exploration of the molecular mechanism revealed that OTSSP167 inhibited AKT/IKK/P65 and ERK/IKK/P65 signaling cascades both in vivo and in vitro, which may help alleviate intestinal inflammation and control the occurrence of cancer.

Conclusion: Our findings lay a theoretical foundation for the use of OTSSP167 as a treatment for IBD and its inhibition of the occurrence of colitis-associated carcinogenesis; additionally, MELK may be a potentially effective target molecule, thus providing more options for clinical treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.06.012DOI Listing
June 2021

Double-path parallel convolutional neural network for removing speckle noise in different types of OCT images.

Appl Opt 2021 May;60(15):4345-4355

Speckle noises widely exist in optical coherence tomography (OCT) images. We propose an improved double-path parallel convolutional neural network (called DPNet) to reduce speckles. We increase the network width to replace the network depth to extract deeper information from the original OCT images. In addition, we use dilated convolution and residual learning to increase the learning ability of our DPNet. We use 100 pairs of human retinal OCT images as the training dataset. Then we test the DPNet model for denoising speckles on four different types of OCT images, mainly including human retinal OCT images, skin OCT images, colon crypt OCT images, and quail embryo OCT images. We compare the DPNet model with the adaptive complex diffusion method, the curvelet shrinkage method, the shearlet-based total variation method, and the OCTNet method. We qualitatively and quantitatively evaluate these methods in terms of image smoothness, structural information protection, and edge clarity. Our experimental results prove the performance of the DPNet model, and it allows us to batch and quickly process different types of poor-quality OCT images without any parameter fine-tuning under a time-constrained situation.
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http://dx.doi.org/10.1364/AO.419871DOI Listing
May 2021

Characterization of volatile compounds of Pixian Douban fermented in closed system of gradient steady-state temperature field.

Food Sci Nutr 2021 Jun 29;9(6):2862-2876. Epub 2021 Mar 29.

College of Food and Bioengineering Xihua University Chengdu China.

As an essential flavor condiment in Sichuan cuisine, Pixian Douban (PXDB) is usually produced by open fermentation process in strip pools or ceramic vats. In this study, an experiment of PXDB fermentation was conducted for 90 days in a closed system of gradient steady-state temperature field (GSTF). To investigate the characterization of volatile compounds of PXDB in the closed system, the volatiles in three kinds of samples including samples of GSTF (SGT), samples of constant temperature (SCT), and samples of traditional fermentation (STF) were analyzed. The results showed that 75, 67, and 68 volatile compounds were detected in SGT, SCT, and STF, respectively. Compared with the traditional fermentation, the process in the closed system of GSTF was conducive to produce more kinds of esters and alcohols. A total of 22 major aroma active compounds were identified in three samples by combination analyses of gas chromatography-olfactometry (GC-O) and odor activity value (OAV). The appearance, smell, texture, and taste of the three different samples had shown different changes, but the sensory characteristics of the SGT were more similar to those of the STF by quantitative descriptive analysis (QDA) and principal component analysis (PCA). This study indicated that the closed system of GSTF could be applied in PXDB fermentation to obtain higher quality products, which brought a bright prospect of replacing the traditional fermentation process to realize the controllable industrialized production of PXDB.
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http://dx.doi.org/10.1002/fsn3.2242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194942PMC
June 2021

Temporal variations in reference evapotranspiration in the Tarim River basin, Central Asia.

PLoS One 2021 16;16(6):e0252840. Epub 2021 Jun 16.

College of Hydraulic Science and Engineering, Yangzhou University, Yangzhou, China.

Reference evapotranspiration (ET0) is important for agricultural production and the hydrological cycle. Knowledge of ET0 can aid the appropriate allocation of irrigation water in arid regions. This study analyzed the trends in ET0 over different timescales in the Tarim River basin (TRB), Central Asia. ET0 was calculated by the Penman-Monteith method using data from 1960-2017 from 30 meteorological stations located in the TRB. The Mann-Kendall (MK) test with trend-free prewhitening and Sen's slope estimator were applied to detect trends in ET0 variation. The results showed that the mean ET0 decreased at a rate of 0.49 mm·10 a-1 on an annual timescale. The mean ET0 exhibited a decreasing trend in summer and increasing trends in other seasons. The effects of climatic factors on ET0 were assessed by sensitivity analysis and contribution rate analysis. Maximum temperature (Tmax), relative humidity (RH) and wind speed (WS) showed important effects on ET0. However, WS, which decreased, was the key element that induced changes in ET0 in the TRB. This work provides an important baseline for the management of agricultural water resources and scientific planning in agriculture.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252840PLOS
June 2021

Correlation analysis of expression of CC and CXC chemokines in children with autism spectrum disorder.

Medicine (Baltimore) 2021 Jun;100(24):e26391

Huanggang Central Hospital, Huanggang, Hubei 438000, China.

Abstract: To investigate the relationship between the expression of CC and CXC chemokines and autism spectrum disorder (ASD).A total of 62 children with ASD (ASD group) and 60 gender- and age-matched normal children (control group) admitted to our hospital from January 2019 to January 2020 were included in the study. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), regulated upon activation, normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), monokine induced by interferon (IFN)-γ (MIG), and purified human interferon-γ-induced protein-10 (IP-10) were detected in the ASD group. The correlation between the above indexes and the severity of the ASD group was analyzed.Significantly increased MCP-1 levels (P < .01) along with the markedly decreased MIP-1α and MIP-1β levels (P < .01) were detected in the venous blood of the ASD group compared with the control group. In addition, they exhibited no significant difference (yet a downward trend) in the level of RANTES (P > .05). Children in the ASD group showed significantly decreased IP-10 levels (P < .01); however, they had no noticeable change (yet a decreasing trend) in the levels of IL-8 and MIG (P > .05). MCP-1 level was positively related to the Module 1 scores of Autism Diagnostic Observation Schedule-second edition (ADOS-2), whereas the levels of Childhood Autism Rating Scale MIP-1α, MIP-1β, IL-8, IP-10, and MIG were negatively correlated with the ADOS-2 Module 1 scores (P < .01). However, no significant correlation was found between RANTES and the ADOS-2 Module 1 scores (P > .05).The levels of CC chemokines (MCP-1, MIP-1α, MIP-1β, and RANTES) and CXC chemokines (IL-8, IP-10, and MIG) are positively correlated with the pathogenesis of ASD. Inflammation is an important contributing factor to ASD.
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http://dx.doi.org/10.1097/MD.0000000000026391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213293PMC
June 2021

New Nonalcoholic Fatty Liver Disease and Fibrosis Progression Associate With the Risk of Incident Chronic Kidney Disease.

J Clin Endocrinol Metab 2021 Jun 14. Epub 2021 Jun 14.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Context: Little is known about the link between nonalcoholic fatty liver disease (NAFLD) evolution and incident chronic kidney disease (CKD).

Objective: We aim to assess the associations of NALFD status changes and NAFLD fibrosis progression with the risk of incident CKD.

Methods: We conducted a community-based prospective study including participants aged 40 years or older and free of CKD at baseline in 2010, and followed up after a mean of 4.4 years. NAFLD was diagnosed by ultrasonography. NAFLD fibrosis score (NFS) was used to evaluate fibrosis stage and progression. CKD was defined by estimated glomerular filtration rate (eGFR) or urine albumin-to-creatinine ratio (UACR). All the measurements were performed at baseline and follow-up examination.

Results: Among 4,042 participants with four NAFLD status change groups, incident NAFLD was associated with an increased risk of incident CKD (Odds Ratio, OR = 1.44, 95% Confidence Interval [CI] 1.003 - 2.06; P = 0.048) compared to non-NAFLD after adjustments for the confounders including evolution of diabetes, hypertension and obesity in addition to the baseline levels. However, the risk of incident CKD was not significantly different between NAFLD resolution and persistent NAFLD. Among 534 participants in persistent NAFLD group, those with fibrosis progression from low NFS to intermediate or high NFS was associated with a significantly increased risk of incident CKD compared to those with fibrosis stable in low NFS (OR = 2.82, 95% CI 1.22 - 6.56; P = 0.016).

Conclusions: NAFLD development and fibrosis progression are associated with increased risk of incident CKD.
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http://dx.doi.org/10.1210/clinem/dgab425DOI Listing
June 2021

Effects of the association between APOE rs405509 polymorphisms and gene-environment interactions on hand grip strength among middle-aged and elderly people in a rural population in southern China.

J Orthop Surg Res 2021 Jun 11;16(1):372. Epub 2021 Jun 11.

School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, China.

Background: Hand grip strength is a complex phenotype. The current study aimed to identify the effects of the association between APOE rs405509 polymorphisms and gene-environment interactions on hand grip strength among middle-aged and elderly people in a rural population in Gongcheng, southern China.

Methods: APOE rs405509 polymorphisms in 1724 participants (695 men and 1029 women, aged 45-97 years old) were genotyped using the Sequenom MassARRAY platform. Statistical analysis was conducted using SPSS 21.0 and Plink 1.90.

Results: The APOE rs405509 G allele was associated with lower hand grip strength in all participants (β = -1.04, P value <0.001), and the correlation seemed to be even stronger among women. A significant gene-environment interaction was observed between APOE rs405509 and smoking, especially in men. The hand grip strength of male smokers carrying the GG genotype was significantly higher than that of nonsmokers (P value = 0.004).

Conclusions: APOE rs405509 polymorphisms might be genetic factors that affect hand grip strength in a rural population in Gongcheng, southern China. The APOE rs405509-smoking interaction has an impact on hand grip strength.
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http://dx.doi.org/10.1186/s13018-021-02522-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194121PMC
June 2021

Serum calprotectin as a prognostic predictor in severe traumatic brain injury.

Clin Chim Acta 2021 Jun 6;520:101-107. Epub 2021 Jun 6.

Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan 215300, Jiangsu Province, China. Electronic address:

Background: Calprotectin plays an important role during inflammation. We intended to explore the prognostic value of serum calprotectin levels in patients with severe traumatic brain injury (sTBI).

Methods: In this prospective cohort study of 149 sTBI patients, we determined the relationship between serum calprotectin levels and 90-day overall survival plus poor outcome (Glasgow outcome scale score of 1-3) after sTBI, and analyzed its associations with Rotterdam computerized tomography (CT) scores, Glasgow coma scale (GCS) scores and two markers of inflammatory reaction including serum C-reactive protein levels and blood leucocyte count.

Results: Serum calprotectin levels were significantly correlated with Rotterdam CT scores, GCS scores, serum C-reactive protein levels and blood leucocyte count. Patients with poor outcome at 90 days displayed higher serum calprotectin levels than the other remainders. Serum calprotectin appeared as an independent predictor for 90-day overall survival and poor outcome. Under receiver operating characteristic curve, serum calprotectin levels exhibited an efficient discrimination capacity for 90-day poor outcome.

Conclusions: Serum calprotectin levels are significantly correlated with inflammation, trauma severity and poor outcome at 90 days in sTBI patients, suggesting that serum calprotectin may be a biomarker for providing complementary prognostic information to identify patients at risk of poor outcome after sTBI.
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http://dx.doi.org/10.1016/j.cca.2021.06.009DOI Listing
June 2021

The impact of ultrasound-guided transmuscular quadratus lumborum block combined with local infiltration analgesia for arthroplasty on postoperative pain relief.

J Clin Anesth 2021 Oct 4;73:110372. Epub 2021 Jun 4.

Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Wainan Guoxue Road, Chengdu 610041, China. Electronic address:

Study Objective: This study aimed to evaluate the efficacy of ultrasound-guided transmuscular quadratus lumborum block (QLB) combined with local infiltration analgesia (LIA) for pain management and recovery in patients who have undergone total hip arthroplasty (THA) via a posterolateral approach.

Design: This was a prospective, randomized controlled trial.

Setting: We collected data in the preoperative area, operating room, and bed ward.

Patients: A total of 80 patients with American Society of Anesthesiology functional status scores of II-III were included and assigned to two groups, and all 80 patients were included in the final analysis.

Interventions: All included patients were randomly assigned to the nerve block (group N) or the control group (group C). Patients in the group N received transmuscular QLB combined with LIA, while patients in the group C received only LIA.

Measurements: The primary outcome was postoperative pain during the first active motion: it was measured at six hours after surgery and assessed using a visual analog scale (VAS). Secondary outcomes were the resting VAS scores in the post-anesthesia care unit (PACU) and at 2, 6, 12, 24, 48, and 72 h after surgery; VAS scores during motion at 12, 24, 48, and 72 h after surgery; intraoperative consumption of opioids; postoperative consumption of morphine hydrochloride; frequency of sleep interruption due to pain on the night of surgery; time until the first "walk out of the bed" after surgery; muscle strength of the quadriceps femoris; and postoperative adverse effects.

Main Results: Compared to the group C, patients in the group N had significantly lower VAS scores during motion at 6, 12, and 24 h after surgery, as well as lower resting VAS scores in the PACU and at 2, 6, 12, and 24 h after surgery. Patients in the group N also consumed significantly smaller amounts of intraoperative opioids and morphine after surgery. Patients in the group N reported significantly fewer interruptions in sleep due to pain on the night of surgery and were able to "walk out of the bed" significantly earlier than those in the group C. There was no significant difference between the two groups in muscle strength of the quadriceps femoris or incidence of postoperative adverse effects.

Conclusions: Compared to treatment with LIA alone, ultrasound-guided transmuscular QLB combined with LIA can provide better postoperative pain relief and enhance the recovery of THA patients, since it does not cause quadriceps femoris muscle weakness and is associated with significantly lower need for intraoperative opioids.
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http://dx.doi.org/10.1016/j.jclinane.2021.110372DOI Listing
October 2021

Novel sGC activators increase glomerular cGMP, induce vasodilation, and improve blood flow in the murine kidney.

Br J Pharmacol 2021 Jun 7. Epub 2021 Jun 7.

Bayer AG, Cardiovascular Research, Pharma Research Center, 42117, Wuppertal, Germany.

Background And Purpose: Generation of cGMP via NO-sensitive soluble guanylyl cyclase (sGC) has been implicated in the regulation of renal functions. Chronic kidney disease (CKD) is associated with decreased NO bioavailability, increased oxidative stress, and oxidation of sGC to its haem-free form, apo-sGC. Apo-sGC cannot be activated by NO, resulting in impaired cGMP signalling that is associated with CKD progression. We hypothesised that sGC activators, which activate apo-sGC independently of NO, increase renal cGMP production under conditions of oxidative stress, thereby improving renal blood flow (RBF) and kidney function.

Experimental Approach: Two novel sGC activators, runcaciguat and BAY-543, were tested on murine kidney. We measured cGMP levels in real time in kidney slices of cGMP sensor mice, vasodilation of pre-constricted glomerular arterioles, and RBF in isolated perfused kidneys. Experiments were performed at baseline conditions, under L-NAME-induced NO deficiency, and in the presence of oxidative stress induced by ODQ.

Key Results: Mouse glomeruli showed NO-induced cGMP increases. Under baseline conditions, sGC activator did not alter glomerular cGMP concentration or NO-induced cGMP generation. In the presence of ODQ, NO-induced glomerular cGMP signals were markedly reduced, while sGC activator induced strong cGMP increases. L-NAME and ODQ pre-treated isolated glomerular arterioles were strongly dilated by sGC activator. sGC activator also increased cGMP and RBF in ODQ-perfused kidneys.

Conclusion And Implication: sGC activators increase glomerular cGMP, dilate glomerular arterioles, and improve RBF under disease-relevant oxidative stress conditions. Therefore, sGC activators represent a promising class of drugs for CKD treatment.
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http://dx.doi.org/10.1111/bph.15586DOI Listing
June 2021

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

J Biochem Mol Toxicol 2021 Jun 6:e22822. Epub 2021 Jun 6.

Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.
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http://dx.doi.org/10.1002/jbt.22822DOI Listing
June 2021

A radiomic nomogram based on arterial phase of CT for differential diagnosis of ovarian cancer.

Abdom Radiol (NY) 2021 06 4;46(6):2384-2392. Epub 2021 Jun 4.

Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, Lishui, 323000, China.

Purpose: To develop and validate a radiomic nomogram based on arterial phase of CT to discriminate the primary ovarian cancers (POCs) and secondary ovarian cancers (SOCs).

Methods: A total of 110 ovarian cancer patients in our hospital were reviewed from January 2010 to December 2018. Radiomic features based on the arterial phase of CT were extracted by Artificial Intelligence Kit software (A.K. software). The least absolute shrinkage and selection operation regression (LASSO) was employed to select features and construct the radiomics score (Rad-score) for further radiomics signature calculation. Multivariable logistic regression analysis was used to develop the predicting model. The predictive nomogram model was composed of rad-score and clinical data. Nomogram discrimination and calibration were evaluated.

Results: Two radiomic features were selected to build the radiomics signature. The radiomics nomogram that incorporated 2 radiomics signature and 2 clinical factors (CA125 and CEA) showed good discrimination in training cohort (AUC 0.854), yielding the sensitivity of 78.8% and specificity of 90.7%, which outperformed the prediction model based on radiomics signature or clinical data alone. A visualized differential nomogram based on the radiomic score, CEA, and CA125 level was established. The calibration curve demonstrated the clinical usefulness of the proposed nomogram.

Conclusion: The presented nomogram, which incorporated radiomic features of arterial phase of CT with clinical features, could be useful for differentiating the primary and secondary ovarian cancers.
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http://dx.doi.org/10.1007/s00261-021-03120-wDOI Listing
June 2021

Use of Electronic Medical Records to Estimate Changes in Pregnancy and Birth Rates During the COVID-19 Pandemic.

JAMA Netw Open 2021 06 1;4(6):e2111621. Epub 2021 Jun 1.

Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor.

Importance: The influence of the COVID-19 pandemic on fertility rates has been suggested in the lay press and anticipated based on documented decreases in fertility and pregnancy rates during previous major societal and economic shifts. Anticipatory planning for birth rates is important for health care systems and government agencies to accurately estimate size of economy and model working and/or aging populations.

Objective: To use projection modeling based on electronic health care records in a large US university medical center to estimate changes in pregnancy and birth rates prior to and after the COVID-19 pandemic societal lockdowns.

Design, Setting, And Participants: This cohort study included all pregnancy episodes within a single US academic health care system retrospectively from 2017 and modeled prospectively to 2021. Data were analyzed September 2021.

Exposures: Pre- and post-COVID-19 pandemic societal shutdown measures.

Main Outcomes And Measures: The primary outcome was number of new pregnancy episodes initiated within the health care system and use of those episodes to project birth volumes. Interrupted time series analysis was used to assess the degree to which COVID-19 societal changes may have factored into pregnancy episode volume. Potential reasons for the changes in volumes were compared with historical pregnancy volumes, including delays in starting prenatal care, interruptions in reproductive endocrinology and infertility services, and preterm birth rates.

Results: This cohort study documented a steadily increasing number of pregnancy episodes over the study period, from 4100 pregnancies in 2017 to 4620 in 2020 (28 284 total pregnancies; median maternal [interquartile range] age, 30 [27-34] years; 18 728 [66.2%] White women, 3794 [13.4%] Black women; 2177 [7.7%] Asian women). A 14% reduction in pregnancy episode initiation was observed after the societal shutdown of the COVID-19 pandemic (risk ratio, 0.86; 95% CI, 0.79-0.92; P < .001). This decrease appeared to be due to a decrease in conceptions that followed the March 15 mandated COVID-19 pandemic societal shutdown. Prospective modeling of pregnancies currently suggests that a birth volume surge can be anticipated in summer 2021.

Conclusions And Relevance: This cohort study using electronic medical record surveillance found an initial decline in births associated with the COVID-19 pandemic societal changes and an anticipated increase in birth volume. Future studies can further explore how pregnancy episode volume changes can be monitored and birth rates projected in real-time during major societal events.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.11621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176329PMC
June 2021

Characterization of genotype-phenotype correlation with MORC2 mutated Axonal Charcot-Marie-Tooth disease in a cohort of Chinese patients.

Orphanet J Rare Dis 2021 May 31;16(1):244. Epub 2021 May 31.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Chang Chun Street, Beijing, 100053, People's Republic of China.

Background: Charcot-Marie-Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population.

Methods: With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families. Pathogenicity assessments of MORC2 variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing.

Results: We identified 4 different heterozygous MORC2 mutations in four unrelated families, accounting for 1.4% (4/284). A novel mutation c.1397A>G p. D466G was detected in family 1 and all affected patients presented with later onset axonal CMT with hyperCKemia. The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. The twin sisters in family 3 were identified as having the most common mutation c.754C>T p. R252W and suffered from axonal motor neuropathy with high variability in disease severity and duration. The patient in family 4 developed an early onset axonal motor and sensory neuropathy, with a reported mutation c.1220G>A p.C407Y. All identified mutations associated with MORC2-related neuropathies are localized in the N-terminal ATPase module.

Conclusions: Our study confirmed that MORC2-related neuropathies exist in the Chinese population at a relatively high mutation rate. We revealed a complex genotype-phenotype correlation with MORC2 mutations. This report adds a new piece to the puzzle of the genetics of CMT and contributes to a better understanding of the disease mechanisms.
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http://dx.doi.org/10.1186/s13023-021-01881-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166055PMC
May 2021

Impact of diabetes on subclinical atherosclerosis and major cardiovascular events in individuals with and without non-alcoholic fatty liver disease.

Diabetes Res Clin Pract 2021 May 26;177:108873. Epub 2021 May 26.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Aims: To investigate the impact of diabetes on subclinical atherosclerosis and cardiovascular disease (CVD) in individuals with and without non-alcoholic fatty liver disease (NAFLD).

Methods: The prospective cohort study included 8451 Chinese adults free of baseline CVD in 2010. NAFLD was diagnosed based on hepatic ultrasonography. Fibrosis-4 index as a non-invasive marker was used to evaluate the degree of fibrosis. Subclinical atherosclerosis was evaluated by carotid intima-media thickness, brachial-ankle pulse wave velocity, ankle-brachial index, and carotid plaque. At follow-up during 2014-2016, the composite of incident fatal or nonfatal CVD were ascertained.

Results: Of the 8451 participants, 2557 (30.3%) had NAFLD at baseline. Diabetes was associated with arterial stiffness and carotid plaque in participants with NAFLD (P < 0.001). Similar associations were observed in participants without NAFLD. During a mean 4.6 years of follow-up, 432 incident CVD events occurred. The multivariable-adjusted hazard ratio (HR) for CVD events associated with diabetes was 1.27 (95% CI 0.90-1.81) in participants with NAFLD and 1.73 (95% CI 1.32-2.26) in those without NAFLD (P for interaction = 0.21). Among participants with NAFLD who had pre-existing diabetes, those with ≥5 years of diabetes duration had an adjusted HR of 2.02 (95% CI 1.12-3.62) for CVD as compared to those with <2 years of duration. When categorizing participants with NAFLD by fibrosis severity, diabetes conferred an increased risk of CVD in those with potential advanced fibrosis.

Conclusions: Among participants with NAFLD, diabetes was associated with prevalent atherosclerosis, and a long duration of diabetes was associated with an increased risk of developing CVD. The effects of diabetes on cardiovascular outcomes did not appreciably differ by NAFLD status.
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http://dx.doi.org/10.1016/j.diabres.2021.108873DOI Listing
May 2021

miR-380-5p facilitates NRF2 and attenuates cerebral ischemia/reperfusion injury-induced neuronal cell death by directly targeting BACH1.

Authors:
Yibiao Wang Min Xu

Transl Neurosci 2021 Jan 18;12(1):210-217. Epub 2021 May 18.

Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, No. 189 Chaoyang Road, Kunshan City, Jiangsu Province, 215300, China.

Background: This study aimed to explore the role of miR-380-5p in cerebral ischemia/reperfusion (CIR) injury-induced neuronal cell death and the potential signaling pathway involved.

Methodology: Human neuroblastoma cell line SH-SY5Y cells were used in this study. Oxygen and glucose deprivation/reperfusion (OGD/R) model was used to mimic ischemia/reperfusion injury. CCK-8 assay and flow cytometry were used to examine cell survival. Quantitative real time PCR (RT-qPCR) assay and Western blotting were used to measure the change of RNA and protein expression, respectively. TargetScan and Luciferase assay was used to confirm the target of miR-380-5p. Malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured using commercial kits.

Results: miR-380-5p was downregulated in SH-SY5Y cells after OGD/R. Cell viability was increased by miR-380-5p, while cell apoptosis was reduced by miR-380-5p mimics. MDA was reduced by miR-380-5p mimics, while SOD and GSHPx were increased by miR-380-5p. Results of TargetScan and luciferase assay have showed that BACH1 is the direct target of miR-380-5p. Expression of NRF2 was upregulated after OGD/R, but was not affected by miR-380-5p. mRNA expression of HO-1 and NQO1 and ARE activity were increased by miR-380-5p. Overexpression of BACH1 reversed the antioxidant and neuroprotective effects of miR-380-5p.

Conclusion: miR-380-5p inhibited cell death induced by CIR injury through target BACH1 which also facilitated the activation of NRF2, indicating the antioxidant and neuroprotective effects of miR-380-5p.
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http://dx.doi.org/10.1515/tnsci-2020-0172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134798PMC
January 2021

Emergence of transferable ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae due to a novel CMY AmpC β-lactamase in China.

Clin Microbiol Infect 2021 May 24. Epub 2021 May 24.

Department of Respiratory Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Objectives: To evaluate the molecular mechanisms of ceftazidime/avibactam (CAZ/AVI) resistance in six Klebsiella pneumoniae strains that co-produce K. pneumoniae carbapenemase (KPC)-2 and a novel variant of CMY cephalosporinase in a Chinese hospital.

Methods: Antimicrobial susceptibility was determined by broth microdilution. Whole-genome sequencing (WGS) was performed to investigate potential resistance determinants. Plasmid conjugation, electroporation, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) hybridization and cloning experiment were carried out to investigate the resistance plasmids and genes.

Results: A high level of CAZ/AVI resistance was observed in six KPC-Kp strains (MIC 128 mg/L). Five strains were isolated in 2015 and one in 2016, before the approval of CAZ/AVI in China. Sequence analysis indicated that all the strains belonged to sequence type (ST) 11 and uniformly carried a novel CMY AmpC β-lactamase gene, designated bla. When compared with CMY-2, CMY-172 has a deletion of three consecutive amino acids (K290, V291 and A292) in the R2-loop region and a non-synonymous amino acid substitution at position 346 (NI). The bla-bearing plasmid, pKPCZA02_4, was 93.3 Kb, IncI1-I type, and conjugative; bla was located in an IS1294-mediated transposon. Plasmid conjugation and DNA fragment cloning proved that bla was responsible for CAZ/AVI resistance.

Conclusions: Our study identified conjugative plasmid-mediated bla as a new mechanism for CAZ/AVI resistance in clinical KPC-Kp strains. Careful monitoring of CAZ/AVI susceptibility is imperative for preventing the spread of the resistance gene.
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http://dx.doi.org/10.1016/j.cmi.2021.05.026DOI Listing
May 2021

A Novel Multidrug Combination Mitigates Rat Liver Steatosis Through Activating AMPK Pathway During Normothermic Machine Perfusion.

Transplantation 2021 Feb 8. Epub 2021 Feb 8.

1Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA 2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Background: Hepatic steatosis is now the leading cause of liver discards in deceased donors. Previous studies (Y defatting) have successfully reduced the fat content by treating rat steatotic livers on extracorporeal normothermic machine perfusion (NMP) with a multidrug combination including the GW compounds that were linked to an increased risk of carcinogenesis.

Methods: We developed a novel multidrug combination by replacing the GW compounds with 2 polyphenols, epigallocatechin-3-gallate (E) and resveratrol (R). Sixteen rat livers were placed on NMP and assigned to control, Y defatting, Y+E+R defatting, or Y'-GW+E+R defatting groups (Y'-GW=90% dose-reduced Y defatting, n=4/group).

Results: All livers in defatting groups had significant decreases in hepatic TG content at the end of the experiment. However, livers treated with our novel Y'-GW+E+R combination had evidence of increased metabolism, and less hepatocyte damage and carcinogenic potential. Our Y'-GW+E+R combination had increased phosphorylation of AMPK (P=0.019) and acetyl-coA carboxylase (P=0.023) compared with control; these were not increased in Y+E+R, and actually decreased in the Y groups. Furthermore, the Y'-GW+E+R group had less evidence of carcinogenic potential with no increase in AKT phosphorylation compared to control (P=0.089); the Y (P=0.031) and Y+E+R (P=0.035) groups had striking increases in AKT phosphorylation. Finally, our Y'-GW+E+R showed less evidence of hepatocyte damage with significantly lower perfusate ALT (P=0.007) and AST (P=0.014) levels.

Conclusions: We have developed a novel multidrug combination demonstrating promising defatting efficacy via activation of the AMPK pathway with an optimized safety profile and reduced hepatotoxicity during ex vivo NMP.Supplemental Visual Abstract; http://links.lww.com/TP/C139.
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http://dx.doi.org/10.1097/TP.0000000000003675DOI Listing
February 2021

EGCG decreases myocardial infarction in both I/R and MIRI rats through reducing intracellular Ca2+ and increasing TnT levels in cardiomyocytes.

Adv Clin Exp Med 2021 May 20. Epub 2021 May 20.

Department of Cardiovascular Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), China.

Background: Myocardial ischemia/reperfusion injury (MIRI) usually induces serious health problems.

Objectives: This study attempted to explore protective effects of (-)-epigallocatechin-3-gallate (EGCG) on MIRI and the associated mechanism.

Material And Methods: Ischemia/reperfusion of an isolated rat heart (I/R model) and the MIRI model were used in this study. Myocardial infarction was measured with staining with 2,3,5-triphenyltetrazolium chloride (TTC). Ca2+ and Tn-T concentrations in coronary perfusion fluid were evaluated using the chromatometry method. Ca2+ concentration in cardiomyocytes was determined with detecting Ca2+ fluorescence intensity. The ultrastructure of cardiomyocytes was observed using transmission electron microscopy (TEM). β-nicotinamide adenine dinucleotide (NAD+) of cardiomyocytes was also determined.

Results: The EGCG (I/R+EGCG) significantly reduced myocardial infarction size of isolated rat heart compared to I/R rats (p < 0.05), remarkably increased Ca2+ and decreased troponin T (TnT) concentrations in coronary perfusion fluid of I/R rats compared to the I/R model (p < 0.05), as well as markedly decreased intracellular Ca2+ concentration and promoted NAD+ concentration in cardiomyocytes compared to I/R rats (p < 0.05). It also obviously maintained the mitochondrial structure in cardiomyocytes of I/R rats and improved the ultrastructure of cardiomyocytes of MIRI rats. Lonidamine (LND) treatment (I/R+EGCG+LND group) significantly blocked the effects of EGCG on I/R injury compared to the I/R+EGCG group (p < 0.05). The EGCG (MIRI+EGCG) significantly decreased myocardial infarction size compared to MIRI rats (p < 0.05) and remarkably enhanced Ca2+ and reduced TnT concentrations in the pulmonary artery compared to that of MIRI rats (p < 0.05).

Conclusions: The EGCG decreased myocardial infarction size in both I/R models and MIRI models by reducing intracellular Ca2+ concentration, increasing TnT concentration, promoting NAD+ concentration, and improving the ultrastructure of cardiomyocytes.
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http://dx.doi.org/10.17219/acem/134021DOI Listing
May 2021

WRKY53 Integrates Classic Brassinosteroid Signaling and the Mitogen-Activated Protein Kinase Pathway to Regulate Rice Architecture and Seed Size.

Plant Cell 2021 May 18. Epub 2021 May 18.

Northeast Institute of Geography and Agroecology, Key Laboratory of Soybean Molecular Design Breeding, Chinese Academy of Sciences, Harbin 150081, China.

In rice (Oryza sativa) and other plants, plant architecture and seed size are closely related to yield. Brassinosteroid (BR) signaling and the mitogen-activated protein kinase (MAPK) pathway (MAPKKK10-MAPKK4-MAPK6) are two major regulatory pathways that control rice architecture and seed size. However, their possible relationship and crosstalk remain elusive. Here, we show that WRKY53 mediated the crosstalk between BR signaling and the MAPK pathway. Biochemical and genetic assays demonstrated that GSK2 phosphorylates WRKY53 and lowers its stability, indicating that WRKY53 is a substrate of GSK2 in BR signaling. WRKY53 interacted with BZR1; they function synergistically to regulate BR-related developmental processes. We also provide genetic evidence showing that WRKY53 functions in a common pathway with the MAPKKK10-MAPKK4-MAPK6 cascade in leaf angle and seed size control, suggesting that WRKY53 is a direct substrate of this pathway. Moreover, GSK2 phosphorylated MAPKK4 to suppress MAPK6 activity, suggesting that GSK2-mediated BR signaling might also regulated MAPK pathway. Together, our results revealed a critical role for WRKY53 and uncovered sophisticated levels of interplay between BR signaling and the MAPK pathway in regulating rice architecture and seed size.
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http://dx.doi.org/10.1093/plcell/koab137DOI Listing
May 2021

Diverged Early From CtpB and CtpC, CtpA Has Evolved to Process D1 Precursor in Oxygenic Photosynthetic Organisms.

Front Plant Sci 2021 30;12:676036. Epub 2021 Apr 30.

Chinese Education Ministry's Key Laboratory of Western Resources and Modern Biotechnology, Northwest University, Xi'an, China.

C-terminal peptidase (Ctp) cleaves the C-terminal extension of the D1 precursor (pD1) to form mature D1. Among the three homologs CtpA, CtpB, and CtpC in photosynthetic organisms only the first is capable of processing pD1 while the roles of CtpB and CtpC remain elusive. Phylogenetic analysis of Ctps from photosynthetic organisms revealed that CtpA has diverged early from CtpB and CtpC during evolution implying distinct roles for the Ctps. Analysis of Arabidopsis Ctp-deficient mutants revealed that pD1 processing was not affected in , , or mutants, demonstrating that AtCtpA, not AtCtpB or AtCtpC, is responsible for cleaving the pD1 C-terminal extension. Ectopic expression of from , , and in rescued the lethal phenotype of the mutant indicating that SeCtpA, CrCtpA, and PpCtpA could process pD1 in Arabidopsis. Enzyme activity assays showed that PpCtpA and CrCtpA could convert pD1 into mature D1 . In contrast, expressing CtpB or CtpC from Arabidopsis, , or in did not rescue its D1 maturation deficiency, and enzyme activity assays also showed that neither CtpB nor CtpC could process pD1 Taken together, we conclude that the function of pD1 processing by CtpA is conserved in photosynthetic organisms. It is possible that among other factors CtpA developed this function to initiate the formation of the oxygenic D1/D2 type PSII complex during evolution whereas CtpB or CtpC have other roles that are still unclear.
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http://dx.doi.org/10.3389/fpls.2021.676036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121967PMC
April 2021

CEBPA-AS1 knockdown alleviates OGD/R-induced neuron cell damage by the miR-24-3p/BOK axis.

Mol Cell Biol 2021 May 17. Epub 2021 May 17.

Department of Neurosurgery, Traditional Chinese Medicine Hospital of Kunshan, Kunshan 215300, China

Cerebral ischemia/reperfusion (I/R) can lead to serious brain function impairments. Long noncoding RNA (lncRNA) CCAAT enhancer binding protein α antisense RNA 1 () was shown to be upregulated in human ischemic stroke. This work investigated the function and mechanism of in I/R. An oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce I/R injury in SH-SY5Y cells in vitro. RT-qPCR examined the expression of , microRNA-24-3p (miR-24-3p), and Bcl-2-related ovarian killer (Bok). The cell viability, apoptosis, oxidative stress in OGD/R-treated cells were detected using CCK-8, flow cytometry, western blot, ELISA assays. The relationship among genes was tested by RNA pulldown and luciferase reporter assays. We found that OGD/R upregulated expression in SH-SY5Y cells. Functionally, depletion ameliorated OGD/R-induced apoptosis and oxidative stress in SH-SY5Y cells by reducing ROS production and superoxide dismutase (SOD) and glutathione (GSH). Mechanistic investigations indicated that acts as a sponge for miR-24-3p, and miR-24-3p binds to the BOK. Moreover, miR-24-3p upregulation or BOK downregulation antagonized the protective role of depletion in SH-SY5Y cells exposed to OGD/R. Overall, downregulation of exerts protective functions against OGD/R-induced injury by targeting the miR-24-3p/BOK axis.
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http://dx.doi.org/10.1128/MCB.00065-21DOI Listing
May 2021

DE-MR simulation imaging for prone radiotherapy after breast-conserving surgery: assessing its application in lumpectomy cavity delineation based on deformable image registration.

Radiat Oncol 2021 May 17;16(1):91. Epub 2021 May 17.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.

Background: The application of delayed-enhancement magnetic resonance (DE-MR) simulation imaging in lumpectomy cavity (LC) delineation for prone radiotherapy in patients with an invisible seroma or a low seroma clarity score (SCS) after breast-conserving surgery (BCS) based on deformable image registration (DIR) was assessed.

Methods: Twenty-six patients who were suitable for radiotherapy in prone positions after BCS were enrolled, and both computed tomography (CT) and DE-MR simulation scans were acquired. The LC delineated based on titanium surgical clips on CT images was denoted as LC. The LC delineated based on the signal of cavity boundaries on fat-suppressed T2-weighted imaging (T2WI) and multiphase delayed-enhancement T1-weighted imaging (DE-T1WI), which was performed at 2 min, 5 min and 10 min postinjection, were denoted as LC, LC, LC and LC, respectively. Afterwards, DIR was performed to compare the volumes and locations of the LCs with MIM software. The generalized conformity index (CIgen) of inter (intra) observer (Inter-CIgen and Intra-CIgen) was also used to explore the inter(intra) observer variation for LC delineation on each image modality.

Results: LC-LC provided the best conformal index (CI) and degree of inclusion (DI), increasing by 2.08% and 4.48% compared to LC-LC, 11.36% and 2.94% for LC-LC, and 8.89% and 7.69% for LC-LC, respectively. The center of mass (COM) of LC-LC decreased by 17.86%, 6.12% and 13.21% compared with that of LC-LC, LC-LC and LC-LC, respectively. The agreement of LC delineation was strongest for 10th min DE-TIWI (coefficient of variation, COV = 2.30%, Inter-CIgen = 87.06%, Intra-CIgen = 92.64%).

Conclusion: For patients with a low SCS (SCS ≤ 2) after BCS, it is feasible to contour the LC based on prone DE-MR simulation images. Furthermore, the LC derived from prone DE-T1WI at 10 min was found to be most similar to that derived from prone CT simulation scans using titanium surgical clips regardless of the volume and location of the LC. Inter (intra) variability was minimal for the delineation of the LC based on 10th min DE-TIWI.
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http://dx.doi.org/10.1186/s13014-021-01817-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130288PMC
May 2021

Genetic susceptibility, family history of diabetes and healthy lifestyle factors in relation to diabetes: A gene-environment interaction analysis in Chinese adults.

J Diabetes Investig 2021 May 16. Epub 2021 May 16.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aims/introduction: To analyze the associations and interactions of the genetic susceptibility and family history of diabetes with lifestyle factors in relation to diabetes among Chinese adults.

Materials And Methods: We constructed a genetic risk score of 34 single-nucleotide polymorphisms in 11,596 participants from Songnan and Youyi communities, Baoshan District, Shanghai, China. We determined a healthy lifestyle by a normal body mass index (<24 kg/m ), adequate fruit and vegetable intake (≥4.5 cups/day), never smoked or quit smoking >1 year prior, sufficient physical activity (≥600 metabolic equivalent minutes per week), and a sleep duration of ≥6 to ≤8 h/day. Logistic regression models were used to examine the associations and interactions between heritability and lifestyle on diabetes.

Results: A healthier lifestyle was associated with a lower prevalence of diabetes within any heritable risk groups categorized by the genetic risk score and family history of diabetes. In the combined communities, the odds ratio (95% confidence interval) for diabetes associated with each additional healthy lifestyle factor was 0.83 (0.77-0.89) among participants with a low genetic risk score and 0.86 (0.81-0.91) among participants with a high genetic risk score (P  = 0.66). Similar interaction patterns of family history (P  = 0.15) and the combination of family history and the genetic risk score with healthy lifestyle (P  = 0.55) on diabetes were observed.

Conclusions: A healthier lifestyle was associated with a significantly lower prevalence of diabetes regardless of heritable risk groups, highlighting the importance of adhering to a healthy lifestyle for diabetes prevention among the entire population.
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http://dx.doi.org/10.1111/jdi.13577DOI Listing
May 2021

Hierarchy in sensory processing reflected by innervation balance on cortical interneurons.

Sci Adv 2021 May 14;7(20). Epub 2021 May 14.

Center for Brain Science of Shanghai Children's Medical Center, Department of Anatomy and Physiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Sensory processing is subjected to modulation by behavioral contexts that are often mediated by long-range inputs to cortical interneurons, but their selectivity to different types of interneurons remains largely unknown. Using rabies-virus tracing and optogenetics-assisted recording, we analyzed the long-range connections to various brain regions along the hierarchy of visual processing, including primary visual cortex, medial association cortices, and frontal cortices. We found that hierarchical corticocortical and thalamocortical connectivity is reflected by the relative weights of inputs to parvalbumin-positive (PV) and vasoactive intestinal peptide-positive (VIP) neurons within the conserved local circuit motif, with bottom-up and top-down inputs preferring PV and VIP neurons, respectively. Our algorithms based on innervation weights for these two types of local interneurons generated testable predictions of the hierarchical position of many brain areas. These results support the notion that preferential long-range inputs to specific local interneurons are essential for the hierarchical information flow in the brain.
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http://dx.doi.org/10.1126/sciadv.abf5676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121429PMC
May 2021

A computed tomography (CT)-derived radiomics approach for predicting primary co-mutations involving and epidermal growth factor receptor () in patients with advanced lung adenocarcinomas (LUAD).

Ann Transl Med 2021 Apr;9(7):545

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Epidermal growth factor receptor () co-mutated with could reduce responsiveness to tyrosine kinase inhibitors (TKIs) and worsen patients' prognosis compared to wild type patients in.

Egfr: mutated lung adenocarcinomas (LUAD). To identify this genetically unique subset prior to treatment through computed tomography (CT) images had not been reported yet.

Methods: Stage III and IV LUAD with known mutation status of and from The First Affiliated Hospital of Sun Yat-sen University (May 1, 2017 to June 1, 2020) were collected. Characteristics of pretreatment enhanced-CT images were analyzed. One-versus-one was used as the multiclass classification strategy to distinguish the three subtypes of co-mutations: & , & , . The clinical model, semantic model, radiomics model and integrated model were built. Area under the receiver-operating characteristic curves (AUCs) were used to evaluate the prediction efficacy.

Results: A total of 199 patients were enrolled, including 83 (42%) cases of , 55 (28%) cases of & , 61 (31%) cases of & . Among the four different models, the integrated model displayed the best performance for all the three subtypes of co-mutations: (AUC, 0.857; accuracy, 0.817; sensitivity, 0.998; specificity, 0.663), & (AUC, 0.791; accuracy, 0.758; sensitivity, 0.762; specificity, 0.783), & (AUC, 0.761; accuracy, 0.813; sensitivity, 0.594; specificity, 0.977). The radiomics model was slightly inferior to the integrated model. The results for the clinical and the semantic models were dissatisfactory, with AUCs less than 0.700 for all the three subtypes.

Conclusions: CT imaging based artificial intelligence (AI) is expected to distinguish co-mutation status involving and . The proposed integrated model may serve as an important alternative marker for preselecting patients who will be adaptable to and sensitive to TKIs.
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http://dx.doi.org/10.21037/atm-20-6473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105857PMC
April 2021

Exploration of irradiation intensity dependent external in-band quantum yield for ZnO and CuO/ZnO photocatalysts.

Phys Chem Chem Phys 2021 May 31;23(18):10768-10779. Epub 2021 Mar 31.

College of Electrical Engineering, Southwest Minzu University, Chengdu 610041, China.

Decorating metal oxides with wide band-gap semiconductor nano-particles constitute an important approach for synthesizing nano-photocatalysts, where the photocatalytic activity is attributed to the band diagram related effective charge separation and external in-band quantum yield (EIQY). However, up to now, the correlation between the irradiation intensity and the functionalization of the in-band quantum yield has not yet been explained. In this work, by investigating the photocatalytic activity of ZnO and CuO/ZnO (CZO) nano-photocatalysts under various irradiative intensities, we show that the effective charge separation in the CuO/ZnO band alignment is sensitive to weak illumination, while ZnO exhibits a competitive photocatalytic activity with CZO under strong illumination. As a consequence, by modifying the irradiation intensity, the intrinsic ZnO can achieve a similar photocatalytic activity to that of metal oxide decorated ZnO. Besides, the optimal photocatalytic activity of CZO is found to be reachable by manipulating the pollutant concentration.
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http://dx.doi.org/10.1039/d0cp06649dDOI Listing
May 2021

Enhanced energy storage of aqueous zinc-carbon hybrid supercapacitors via employing alkaline medium and B, N dual doped carbon cathode.

J Colloid Interface Sci 2021 Oct 24;599:556-565. Epub 2021 Apr 24.

School of Physics and Electronic Science & Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai 200241, PR China. Electronic address:

Zinc-based energy storage systems (zinc-air, zinc-nickel and zinc-ion batteries and zinc-ion hybrid supercapacitors (ZHSs) are considered as promising power sources for wide applications from personal electronic devices to electric vehicles. However, these systems, especially the Zn-based hybrid supercapacitors, display unsatisfying power density and energy density, which should be enhanced for their large-scale applications. In this work, aqueous alkaline zinc-carbon hybrid supercapacitors (A-ZCHS) were designed, consisting of B, N dual doped carbon cathode, Zn anode and KOH electrolyte. The B, N dual doped carbon was prepared via thermal treatment of metal-organic frameworks and boric acid, which exhibits abundant hierarchical pore structure (micropore, mesopore and macropore) and suitable defect construction, promoting ion diffusion/charge transfer and providing more rapid surface pseudocapacitance reaction. More obviously, when the optimized B, N dual doped carbon was used as cathode in A-ZCHS and ZHS, more capacitive charge storage and rapider electrochemical kinetics can be observed in A-ZCHS than in ZHS. Therefore, the optimized A-ZCHS displays a high energy density of 115.7 Wh kg at the power density of 711.6 W kg with excellent stability, which is much better than most of ZHSs reported previously. The A-ZCHS should be a promising candidate for energy storage applications.
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http://dx.doi.org/10.1016/j.jcis.2021.04.114DOI Listing
October 2021

DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome.

J Clin Invest 2021 Jun;131(12)

Department of Stem Cell and Neural Regeneration, State Key Laboratory of Reproductive Medicine, School of Pharmacy, and.

Down syndrome (DS), caused by trisomy of chromosome 21, occurs in 1 of every 800 live births. Early defects in cortical development likely account for the cognitive impairments in DS, although the underlying molecular mechanism remains elusive. Here, we performed histological assays and unbiased single-cell RNA-Seq (scRNA-Seq) analysis on cerebral organoids derived from 4 euploid cell lines and from induced pluripotent stem cells (iPSCs) from 3 individuals with trisomy 21 to explore cell-type-specific abnormalities associated with DS during early brain development. We found that neurogenesis was significantly affected, given the diminished proliferation and decreased expression of layer II and IV markers in cortical neurons in the subcortical regions; this may have been responsible for the reduced size of the organoids. Furthermore, suppression of the DSCAM/PAK1 pathway, which showed enhanced activity in DS, using CRISPR/Cas9, CRISPR interference (CRISPRi), or small-molecule inhibitor treatment reversed abnormal neurogenesis, thereby increasing the size of organoids derived from DS iPSCs. Our study demonstrates that 3D cortical organoids developed in vitro are a valuable model of DS and provide a direct link between dysregulation of the DSCAM/PAK1 pathway and developmental brain defects in DS.
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http://dx.doi.org/10.1172/JCI135763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203468PMC
June 2021