Publications by authors named "Xi Chen"

5,918 Publications

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Cross border project in China-Pakistan economic corridor and its influence on women empowerment perspectives.

PLoS One 2022 24;17(6):e0269025. Epub 2022 Jun 24.

Business School, Sichuan University, Chengdu, China.

The China-Pakistan Economic Corridor (CPEC) is a significant and inaugural project of the "Belt and Road" initiative which is considered as structure and manifesto for panoramic and fundamental collaboration between China and Pakistan. The CPEC project was initiated to develop economic growth and facilitate free trade between both countries. However, it has generated immense employment opportunities, education facilities, and improved quality of life for local citizens, specifically women, as well as international overreach. This study investigates and examines the benefits of CPEC project and its influence on women empowerment. Based on the background of the CPEC, this study has been carried out by applying a mixture of qualitative and quantitative methods to fill the gap. Data was aggregated with the help of a survey questionnaire and interviews from the residents of the Thar region of Pakistan, which comes under CPEC route. In total, 306 samples were acquired and analysed using different statistical tools such as SPSS (Statistical package for social sciences) and PLS (Partial least squares) to formulate the study results. The findings revealed that the development of CPEC has remarkably improved the quality of life for women by providing enormous employment opportunities, education facilities, skills enhancement programs, and training facilities. The analyzed results will guide government policymakers and officials to promote operational activities in the region, develop new educational institutions, and create employment opportunities for the local community and women to obtain further development of CPEC projects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269025PLOS
June 2022

[Variation of Main Postoperative Symptoms in Lung Cancer Patients 
Undergoing Video-assisted Thoracoscopic Surgery].

Zhongguo Fei Ai Za Zhi 2022 Jun;25(6):396-400

Department of Thoracic Surgery, 
West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu 610041, China.

Background: Patients with pulmonary nodules are treated by minimally invasive surgery, and postoperative symptoms have become the main factors affecting patients' emotion and quality of life. This study aimed to analyze the changes of postoperative symptoms in lung cancer patients with pulmonary nodules.

Methods: The clinical data of eighty-eight lung cancer patients admitted to the same medical group of Department of Thoracic Surgery, West China Hospital of Sichuan University from June 2021 to September 2021 were prospectively collected and analyzed. The types and severity of clinical symptoms before operation, on discharge day, 30-day and 90-day after operation were analyzed.

Results: The incidence of postoperative symptoms in lung cancer patients was 79.5%, and most patients suffered from mild (54.3%) and moderate (32.9%) symptoms. The main postoperative symptoms of lung cancer patients were pain (55.7%) and cough (37.2%). The incidence of pain at discharge (55.7%) was significantly higher than that at 30-day (23.7%, P=0.01) and 90-day (12.0%, P=0.01) after discharge. The incidence of cough was significantly higher at 30-day (66.1%) and 90-day (66.0%) than that at discharge (37.2%) (P=0.01, P=0.04).

Conclusions: The main postoperative symptoms of lung cancer patients with pulmonary nodules are pain and cough. The incidence and severity of pain decreases with time, and the incidence of cough increases but the severity decreased gradually.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2022.101.23DOI Listing
June 2022

Maternal High-Fat Diet Aggravates Allergic Asthma in Offspring via Modulating CD4 T-Cell Differentiation.

Nutrients 2022 Jun 16;14(12). Epub 2022 Jun 16.

Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai 200011, China.

Maternal improper nutrition has been reported to trigger respiratory disorders in offspring. Here, we characterized the effects of high-fat environment in the fetal period on mice and human cord blood CD4 T-lymphocytes, and investigated their roles in susceptibility to asthma. Mice born to mothers that consumed a high-fat diet (HFD) throughout the gestation period were sensitized by ovalbumin to establish an experimental asthma model. To further extrapolate to humans, we collected cord blood from neonates of hypercholesterolemic (HC) mothers ( = 18) and control mothers ( = 20). In mice, aggravated airway hyperresponsiveness and inflammation revealed that maternal high-fat diet could lead to exacerbated allergic asthma in adult offspring. It was partially due to augmented activation and proliferation of CD4 T-cells, where upregulated mRNA levels may be potentially involved. Notably, naïve HFD CD4 T-cells had enhanced T2-based immune response both in vivo and in vitro, resulting from DNA hypomethylation of the promoter region. Moreover, in human, T2 cytokines transcripts were enhanced in CD4 T-cells of the HC group, which was associated with an increased risk of developing allergic diseases at 3 years old. Together, our study indicated that early life improper nutrition-triggered epigenetic changes in T-cells may contribute to long-lasting alterations in allergic diseases.
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http://dx.doi.org/10.3390/nu14122508DOI Listing
June 2022

Preparation and Performance of Ternesite-Ye'elimite Cement.

Materials (Basel) 2022 Jun 20;15(12). Epub 2022 Jun 20.

College of Material Science and Engineering, Chongqing University, Chongqing 400045, China.

Ternesite-ye'elimite (TCSA) cement is a new type of environmentally advantageous binder prepared by introducing ternesite, a reactive phase, into belite calcium sulfoaluminate cement clinker. This paper reports the laboratory production of TCSA cement by the addition of minor elements to achieve the coexistence of ternesite and ye'elimite. The influence of dopants on the mineralogical composition of clinkers and the clinkering conditions for the preparation of TCSA cement clinkers were investigated by X-ray powder diffraction and scanning electron microscopy. The mechanical properties and hydration products of the cement pastes were also studied. The results indicated that the addition of CaF, PO and NaO can promote the coexistence of ternesite and ye'elimite, and that NaO is the most effective candidate. TCSA cement clinkers could be successfully prepared at 1150 °C for 30 min by doping 0.3% NaO. The TCSA cement clinkers exhibited shorter setting times than the BCSA cement clinkers. The later strength of TCSA cement showed a significant increase compared with BCSA cement. The effect of NaO was different on the strength development for TCSA and BCSA cement. The dissolution of ternesite could promote the formation of ettringite. The reactivity of belite was higher in TCSA cement due to the formation of strätlingite.
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http://dx.doi.org/10.3390/ma15124369DOI Listing
June 2022

Evaluating China Food's Fertilizer Reduction and Efficiency Initiative Using a Double Stochastic Meta-Frontier Method.

Int J Environ Res Public Health 2022 Jun 15;19(12). Epub 2022 Jun 15.

Institute of Agricultural Economics and Development, Chinese Academy of Agricultural Sciences, Beijing 100082, China.

Improving the efficiency of fertilizer usage is important to achieve sustainable agricultural production. As a major agricultural producer, China formally proposed a national fertilizer reduction and efficiency initiative in 2015. Using the double stochastic meta-frontier method to measure the fertilizer use efficiency of 31 provinces in mainland China from 2005 to 2019, this study evaluates the effectiveness of the said initiative on grain production. The results show that China's initiative has achieved some success, with the average value of fertilizer use efficiency in national grain production increasing by 2.53 percentage points. However, the changes in fertilizer use efficiency show regional heterogeneity. Specifically, the fertilizer use efficiency of the main grain-producing and marketing regions has increased significantly, while that of grain-producing-and-marketing-balanced regions has declined. Further investigation shows that this phenomenon may be related to the importance attached by local governments to the initiative and the uneven distribution of related resources.
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http://dx.doi.org/10.3390/ijerph19127342DOI Listing
June 2022

Transcriptional pathways of elevated fasting blood glucose associated with short-term exposure to ultrafine particles: A panel study in Beijing, China.

J Hazard Mater 2022 May 12;430:128486. Epub 2022 Feb 12.

SKL-ESPC and BIC-ESAT, College of Environmental Sciences and Engineering, Peking University, Beijing, China. Electronic address:

There is growing concern about the strong health effects of ultrafine particles (UFPs). However, less is known about the biological mechanisms. The objective of this study is to examine the association between short-term exposure to UFPs and fasting blood glucose (FBG) levels, and explore the potential physiological mechanisms at transcriptional levels. In a panel study of 135 participants, we measured FBG and the whole blood transcriptome repeatedly. The concentrations of ambient air pollutants were monitored continuously at a station. Linear mixed-effects models coupled with a mediating effect model were used to discriminate transcripts associated with air pollutant exposure and ln-transformed FBG levels. We found that FBG was significantly associated with interquartile range increase in the average UFPs concentrations 1-13 d prior to the clinical visits (ranging from 5.1% [95% CI 2.0-8.1%] in the 1-d time-window to 12.1% [95% CI 6.5-17.8%] in the 13-d time-window). Top 1000 transcripts associated with FBG increase following UFPs exposure were enriched into some biological pathways, such as pro-opiomelanocortin processing, negative regulation of hypoxia-inducible factor 1 A function, ubiquinone metabolism, and antigen presentation by major histocompatibility complex class I, classical pathway. These results suggest that elevated FBG associated with UFPs exposure may be related to regulation of metabolism, immune response, DNA damage, and apoptosis and survival.
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http://dx.doi.org/10.1016/j.jhazmat.2022.128486DOI Listing
May 2022

Circulation of heterogeneous Carnivore protoparvovirus 1 in diarrheal cats and prevalence of an A91S feline panleukopenia virus variant in China.

Transbound Emerg Dis 2022 Jun 23. Epub 2022 Jun 23.

College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, China.

Cats are susceptible to panleukopenia virus (FPV) and canine parvovirus type 2 (CPV-2) infection. FPV has been recognized as relatively conservative in genetic evolution compared to CPV-2, but information regarding FPV variations in cats are still limited. The aim of this study was to investigate the molecular prevalence of FPV and CPV-2 variants among cats in China. From April 2019 to December 2021, 193 diarrheal fecal samples of cats were collected from Southwest China and 127 (65.80 %) samples tested positive to Carnivore protoparvovirus 1. FPV, CPV-2 and some their genomic variants were identified from positive samples, indicating a heterogeneous Carnivore protoparvovirus 1 circulation in the cat population in China. Among FPV strains, an A91S FPV mutant reached the detection rate of 39.37 %, which showed that this FPV genomic variant has been prevalent in the tested cats. Moreover, 7 strains of A91S FPV variants were isolated and purified successfully using F81 cells, and the genomes were sequenced. Phylogenetic trees based on the nearly complete genomic sequences, VP2 and NS1 nucleotide sequences showed that the A91S FPV variants were located in the FPV clade, but all clustered into a separate branch. Structural prediction showed that A91S mutation in VP2 protein extended the random coil of aa residues from 92-95 to 91-95. Moreover, the analysis of all complete VP2 sequences of FPV and CPV-2 available in the GenBank database revealed that the A91S FPV variant has been prevalent in China since 2017 and has reported in four other countries in cats. Thus, our study revealed that heterogeneous Carnivore protoparvovirus 1 are circulating in the cat population in China, and first reported the prevalence and genomic characteristics of the A91S FPV variant, which contributed to a better understanding of the molecular prevalence and genetic evolution of FPV in cats. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/tbed.14641DOI Listing
June 2022

Irisin Attenuates Pathological Neovascularization in Oxygen-Induced Retinopathy Mice.

Invest Ophthalmol Vis Sci 2022 Jun;63(6):21

Department of Ophthalmology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China.

Purpose: Abnormal angiogenesis is a defining feature in a couple of ocular neovascular diseases. The application of anti-VEGFA therapy has achieved certain benefits in the clinic, accompanying side effects and poor responsiveness in many patients. The present study investigated the role of irisin in retinal neovascularization.

Methods: Western blot and quantitative PCR were used to determine irisin expression in the oxygen-induced retinopathy mice model. The pathological angiogenesis and inflammation index were examined after irisin administration. Primary retinal astrocytes were cultured and analyzed for VEGFA expression in vitro. Astrocyte-conditioned medium was collected for transwell assay and tube formation assay in human microvascular endothelial cells-1.

Results: Irisin was downregulated in the oxygen-induced retinopathy mice retinae. Additional irisin attenuated pathological angiogenesis, inflammation, and apoptosis in vivo. In vitro, irisin decreased astrocyte VEGFA production, and the conditioned medium suppressed human microvascular endothelial cells-1 migration. Last, irisin inhibited hypoxia-inducible factor-2α, nuclear factor-κB, and pNF-κB (Phospho-Nuclear Factor-κB) expression.

Conclusions: Irisin mitigates retinal pathological angiogenesis.

Chinese Abstract.
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http://dx.doi.org/10.1167/iovs.63.6.21DOI Listing
June 2022

FTO-mediated m A modification of SOCS1 mRNA promotes the progression of diabetic kidney disease.

Clin Transl Med 2022 Jun;12(6):e942

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.

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http://dx.doi.org/10.1002/ctm2.942DOI Listing
June 2022

Circ-CCNB1 modulates trophoblast proliferation and invasion in spontaneous abortion by regulating miR-223/SIAH1 axis.

Endocrinology 2022 Jun 22. Epub 2022 Jun 22.

Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.

Purpose: Spontaneous abortion (SA) is a common disorder in early pregnancy. Circular RNAs (circRNAs) have been reported to exert important regulatory effects on trophoblast function and embryo development. The aim of this study was to explore whether and how circRNAs regulate trophoblast function in SA during early pregnancy.

Methods: Cell proliferation, 5-bromo-2-deoxyuridine (BrdU) staining, transwell, immunofluorescence, western blot, RNA pull-down and dual-luciferase reporter assays were performed to investigate the effect of circRNA cyclin B1 (circ-CCNB1) on trophoblast function in HTR-8/SVneo and JEG-3 cells.

Results: An in vitro study demonstrated that upregulation of circ-CCNB1 significantly inhibited trophoblast proliferation and invasion compared with the controls using HTR-8/SVneo and JEG-3 cells, respectively. Moreover, miR-223 was downregulated in the villous tissues of patients with SA and was further predicted and shown to negatively interact with circ-CCNB1, which is involved in trophoblast proliferation and invasion. Using bioinformatics tools and subsequent RNA pull-down and dual luciferase assays, we found that miR-223 directly targets seven in absentia homolog-1 (SIAH1) and that upregulation of miR-223 decreased circ-CCNB1-induced SIAH1 expression levels in HTR-8/SVneo cells. Interestingly, upregulation of circ-CCNB1 suppressed trophoblast proliferation and invasion through inhibition of CCNB1 nuclear translocation induced by SIAH1. Downregulation of SIAH1 enhanced circ-CCNB1-suppressed CCNB1 nuclear protein expression in trophoblast cells.

Conclusions: Circ-CCNB1 served as a modulator of trophoblast proliferation and invasion by sponging miR-223, thus forming a regulatory network of circ-CCNB1/miR-223/SIAH1 in modulating CCNB1 nuclear translocation, which enabled us to elucidate the molecular mechanisms involved in normal embryo implantation or in SA.
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http://dx.doi.org/10.1210/endocr/bqac093DOI Listing
June 2022

Unraveling the behavior of nitrite on promoting short-chain fatty acids accumulation from waste activated sludge by peracetic acid pretreatment: Extracellular polymeric substance decomposition and underlying mechanism.

Sci Total Environ 2022 Jun 18:156793. Epub 2022 Jun 18.

College of Environmental Science and Engineering, Taiyuan University of Technology, Taiyuan, China; Shanxi Engineer Research Institute of Sludge Disposition and Resources, Taiyuan, China. Electronic address:

Peracetic acid (PAA) is an emerging oxidant for waste activated sludge (WAS) treatment due to its strong oxidization and few toxic byproducts. Nitrite which can be in-situ recovered from WAS fermentation liquor, its protonated form (free nitrous acid, FNA) is regarded as the cost-effective inactivator. The stubborn extracellular polymeric substance (EPS) is the rate-limiting step for energy/resource recovery from WAS. This work found that the co-pretreatment of PAA and FNA can effectively promote short-chain fatty acids (SCFAs) production during anaerobic fermentation. Higher PAA dosage (100 mg/g VSS, FP4WAS) in co-pretreatment was beneficial for organics release (1976.9 mg COD/L), remarkably increased by 10.3- 96.5 % than that of low PAA dosage (25- 75 mg/g VSS), and promoted by 105.1 % and 62.1 % than FNA (FWAS)/PAA (100 mg/g VSS, P4WAS)-pretreated WAS. Effective release of soluble organics contributed to the SCFAs accumulation (7679 ± 86 mg COD/L, 4 d), enhanced by 200.0 % and 19.0 % than FWAS and P4WAS, respectively. Acetic (HAc) and propionic acid (HPr) peaked at 6344.7 mg COD/L in FP4WAS (accounted for 82.6 %), which increased by 10.6- 899.0 % than other groups. Moreover, OH and O were detected in co-pretreatment, may play the synchronous effect with the crucial intermediates of NO, NO and ONOO/ONOOH on EPS decomposition.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156793DOI Listing
June 2022

Effects of changes in physical and sedentary behaviors on mental health and life satisfaction during the COVID-19 pandemic: Evidence from China.

PLoS One 2022 21;17(6):e0269237. Epub 2022 Jun 21.

Institute of Sociology, Chinese Academy of Social Sciences, Beijing, China.

Background: While restriction measures are critical in containing the COVID-19 outbreak, limited studies have investigated the behavioral and psychological impact of these measures. This study aimed to investigate the effects of physical and sedentary behavioral changes and online behavior during the COVID-19 pandemic on mental health and life satisfaction among the Chinese population.

Methods: The data were obtained from a cross-sectional survey of 2145 residents aged between 18 and 80 in Hubei province, China between March 23, 2020, and April 9, 2020.

Results: Participants who had high frequencies of physical activities before or during the COVID-19 outbreak exhibited higher levels of life satisfaction. Participants who increased their sitting time during the pandemic or kept sitting for more than eight hours before and during the pandemic reported worse mental health than those who maintained less sedentary behavior. Besides, participants who used the Internet for information seeking, communication, and entertainment more frequently reported better mental health and life satisfaction. In contrast, there was a positive association between commercial use of the Internet and symptoms of mental disorders.

Conclusion: Given the link between physical and sedentary behavioral changes with worse mental wellbeing, strategies to reduce sedentariness and increase physical activity during the COVID-19 pandemic are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269237PLOS
June 2022

Recharge of chondrocyte mitochondria by sustained release of melatonin protects cartilage matrix homeostasis in osteoarthritis.

J Pineal Res 2022 Jun 20. Epub 2022 Jun 20.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China.

Recent evidence indicates that the mitochondrial functions of chondrocytes are impaired in the pathogenesis of osteoarthritis (OA). Melatonin can attenuate cartilage degradation through its antioxidant functions. This study aims to investigate whether melatonin could rescue the impaired mitochondrial functions of OA chondrocytes and protect cartilage metabolism. OA chondrocytes showed a compromised matrix synthesis capacity associated with mitochondrial dysfunction and aberrant oxidative stress. In vitro treatments with melatonin promoted the expression of cartilage ECM components, improved adenosine triphosphate production, and attenuated mitochondrial oxidative stress. Mechanistically, either silencing of SOD2 or inhibition of SIRT1 abolished the protective effects of melatonin on mitochondrial functions and ECM synthesis. To achieve a sustained release effect, a melatonin-laden drug delivery system (DDS) was developed and intra-articular injection with DDS successfully improved cartilage matrix degeneration in a post-traumatic rat OA model. These findings demonstrate that melatonin-mediated recharge of mitochondria to rescue the mitochondrial functions of chondrocytes represents a promising therapeutic strategy to protect cartilage from OA. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jpi.12815DOI Listing
June 2022

Life course traumas and cardiovascular disease-The mediating role of accelerated aging.

Ann N Y Acad Sci 2022 Jun 20. Epub 2022 Jun 20.

Center for Clinical Big Data and Analytics of the Second Affiliated Hospital and Department of Big Data in Health Science School of Public Health, Zhejiang University School of Medicine, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China.

The complex relationship between life course traumas and cardiovascular disease (CVD) and the underpinning pathways are poorly understood. We aimed to (1) examine the associations of three separate assessments including childhood, adulthood (after 16 years of age), and lifetime traumas (childhood or adulthood) with CVD; (2) examine the associations between diverse life course traumatic profiles and CVD; and (3) examine the extent to which PhenoAge, a well-developed phenotypic aging measure, mediated these associations. Using data from 104,939 participants from the UK Biobank, we demonstrate that subgroups of childhood, adulthood, and lifetime traumas were associated with CVD. Furthermore, life course traumatic profiles were significantly associated with CVD. For instance, compared with the subgroup experiencing nonsevere traumas across life course, those who experienced nonsevere childhood and severe adulthood traumas, severe childhood and nonsevere adulthood traumas, or severe traumas across life course had significantly higher odds of CVD (odds ratios: 1.07-1.33). Formal mediation analyses suggested that phenotypic aging partially mediated the above associations. These findings suggest a potential pathway from life course traumas to CVD through phenotypic aging, and underscore the importance of policy programs targeting traumas over the life course in ameliorating inequalities in cardiovascular health.
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http://dx.doi.org/10.1111/nyas.14843DOI Listing
June 2022

ATP-sensitive potassium channels: a double-edged sword in neurodegenerative diseases.

Ageing Res Rev 2022 Jun 17:101676. Epub 2022 Jun 17.

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Medical College, Qingdao University, Qingdao, China; 11/30/2021; 4/15/2022; 6/14/2022. Electronic address:

ATP-sensitive potassium channels (K channels), a group of vital channels that link the electrical activity of the cell membrane with cell metabolism, were discovered on the ventricular myocytes of guinea pigs by Noma using the patch-clamp technique in 1983. Subsequently, K channels have been found to be expressed in pancreatic β cells, cardiomyocytes, skeletal muscle cells, and nerve cells in the substantia nigra (SN), hippocampus, cortex, and basal ganglia. K channel openers (KCO) diazoxide, nicorandil, minoxidil, and the K channel inhibitor glibenclamide have been shown to have anti-hypertensive, anti-myocardial ischemia, and insulin-releasing regulatory effects. Increasing evidence has suggested that K channels also play roles in Alzheimer's disease (AD), Parkinson's disease (PD), Vascular dementia (VD), Huntington's disease (HD) and other neurodegenerative diseases. KCOs and K channel inhibitors protect neurons from injury by regulating neuronal excitability and neurotransmitter release, inhibiting abnormal protein aggregation and Ca overload, reducing reactive oxygen species (ROS) production and microglia activation. However, K channels have dual effects in some cases. In this review, we focus on the roles of K channels and their related openers and inhibitors in neurodegenerative diseases. This will enable us to precisely take advantage of the K channels and provide new ideas for the treatment of neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.arr.2022.101676DOI Listing
June 2022

Relevance of Gene Polymorphisms of NAT2 and NR1I2 to anti-tuberculosis drug-induced hepatotoxicity.

Xenobiotica 2022 Jun 20:1-23. Epub 2022 Jun 20.

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China.

The recommended treatment regimen for tuberculosis is a combination of agents with antitubercular activity, during which hepatotoxicity is one of the most common side effects. In addition to the -acetyltransferase 2 () genotype, in nuclear receptor subfamily 1, group I, member 2 () has been demonstrated to be associated with anti-tuberculosis drug-induced hepatotoxicity (ATDH), but previous results have been inconsistent.A retrospective nested hospital-based case-control study was performed to investigate the association between genetic polymorphisms and the risk of ATDH. Fifteen genetic variants (13 SNPs and two null genotypes) in cytochrome P450 2E1, , UDP-glucuronosyltransferase 1A1, , superoxide dismutase 1, superoxide dismutase 2, and glutathione -transferases (, , were genotyped. Odds ratios with 95% confidence intervals were calculated with drug doses, body mass index comorbidity of diabetes mellitus, and baseline alanine transaminase value as covariates.Conditional logistic regression demonstrated that the slow acetylation genotype and the allele of in may contribute to susceptibility to ATDH.Stratified association analysis demonstrated that in non-slow acetylators, the allele of was a risk factor for ATDH, whereas the allele did not increase the susceptibility to ATDH in slow acetylators.
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http://dx.doi.org/10.1080/00498254.2022.2092783DOI Listing
June 2022

The relationship between serum exosome HBV-miR-3 and current virological markers and its dynamics in chronic hepatitis B patients on antiviral treatment.

Ann Transl Med 2022 May;10(10):536

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Hepatitis B virus (HBV) can encode microRNA-HBV-miR-3, which can be detected in both HBV-infected cell lines and peripheral blood exosomes of chronic hepatitis B (CHB) patients. This study was conducted to further evaluate its relationship with the current viral markers and their dynamics during antiviral therapy.

Methods: We used Stem-loop real time quantitative PCR (RT-qPCR) to quantify HBV-miR-3 in the serum exosomes of CHB patients by extracting exosomes using the Supbio exosome separation kit and designing primers and Taqman probes specific for HBV-miR-3. We conducted a cross-sectional study and two cohort studies. In the cross-sectional study, 48 treatment-naive (TN) CHB patients were enrolled. In the nucleoside analogues (NAs) cohort study, 20 hepatitis B e antigen (HBeAg) negative CHB patients with negative HBV DNA on NA therapy were followed up for 96 weeks. In the NAs + pegylated interferon (Peg-IFN) cohort study, 40 patients with hepatitis B surface antigen (HBsAg) <1,500 IU/mL, negative HBV DNA, and HBeAg after NAs treatment were enrolled and were switched to Peg-IFN therapy for 48 weeks. HBV-miR-3 titers and other viral markers were detected at different time points.

Results: HBV-miR-3 only existed in CHB patients with a concentration of 6.41±3.55 log10 copies/mL. HBV-miR-3 was positively correlated with HBV DNA, pregenomic RNA (pgRNA), and HBsAg. In the NAs cohort, HBsAg, pgRNA, and HBV-miR-3 levels showed little fluctuation during the 96 weeks of NA treatment (P>0.05). In the NAs + PEG-IFN cohort, HBsAg, pgRNA, and HBV-miR-3 levels declined significantly during the 48 weeks of sequential therapy (P<0.05).

Conclusions: HBV-miR-3 was positively correlated with HBV DNA, pgRNA, and particularly HBsAg in TN CHB patients. Peg-IFN following NA therapy had a positive impact on HBsAg, pgRNA, and HBV-miR-3 decrease.
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http://dx.doi.org/10.21037/atm-22-2119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201139PMC
May 2022

Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung .

Front Pharmacol 2022 2;13:897747. Epub 2022 Jun 2.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib dramatically suppresses PD-L1 protein expression in a dose-dependent manner. In parallel, cell membrane PD-L1 is also reduced by Bafetinib. We confirm that Bafetinib doesn't affect the protein half-life of PD-L1 but significantly inhibits the transcription of PD-L1. Among the transcription factors that regulate PD-L1 expression, c-Myc is downregulated by Bafetinib. Bafetinib caused PD-L1 inhibition is abolished when c-Myc is knocked-down. Further, we identified that Bafetinib reduced c-Myc expression because of transcription inhibition. By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression . In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1.
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http://dx.doi.org/10.3389/fphar.2022.897747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201485PMC
June 2022

Predicting Response of Severe Aplastic Anemia to Rabbit-Antithymocyte Immunoglobulin Based Immunosuppressive Therapy Combined With Eltrombopag.

Front Immunol 2022 26;13:884312. Epub 2022 May 26.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, =0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, =0.004), red cell distribution width - coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, =0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, =0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×10/L, 11.75%, and 1.06×10/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).

Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.
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http://dx.doi.org/10.3389/fimmu.2022.884312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204341PMC
June 2022

Engineered Tryptophan Synthase Balances Equilibrium Effects and Fast Dynamic Effects.

ACS Catal 2022 Jan 30;12(2):913-922. Epub 2021 Dec 30.

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, United States.

Creating efficient and stable enzymes for catalysis in pharmaceutical and industrial laboratories is an important research goal. Arnold et al. used directed evolution to engineer a natural tryptophan synthase to create a mutant that is operable under laboratory conditions without the need for a natural allosteric effector. The use of directed evolution allows researchers to improve enzymes without understanding the structure-activity relationship. Here, we present a transition path sampling study of a key chemical transformation in the tryptophan synthase catalytic cycle. We observed that while directed evolution does mimic the natural allosteric effect from a stability perspective, fast protein dynamics associated with chemistry has been dramatically altered. This work provides further evidence of the role of protein dynamics in catalysis and clearly demonstrates the multifaceted complexity of mutations associated with protein engineering. This study also demonstrates a fascinating contrast between allosteric and stand-alone functions at the femtosecond time scale.
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http://dx.doi.org/10.1021/acscatal.1c03913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202816PMC
January 2022

Cost-Effectiveness Analysis of a Three-Drug Regimen Containing Bevacizumab for the Treatment of Recurrent Pediatric in China: Based on a COG Randomized Phase II Screening Trial.

Front Public Health 2022 2;10:914536. Epub 2022 Jun 2.

Department of Integrated Care Management Center, West China Hospital, Sichuan University, Chengdu, China.

Background: is the most common malignant brain tumor of childhood, accounting for 6 to 7 percent of all childhood CNS tumors. The purpose of this study was to evaluate the economic efficacy of a bevacizumab combined with + irinotecan regimen for the treatment of recurrent pediatric in China.

Methods: The data analyzed were from a randomized phase II screening trial that showed an improved survival benefit in child patients with recurrent treated with a T+I+B combination regimen. A Markov model is constructed to estimate the incremental cost-effectiveness ratio (ICER) from the perspective of Chinese society. The uncertainty in the model is solved by one-way certainty and probabilistic sensitivity analysis.

Results: Our base case analysis showed that the total costs of treatment increased from $8,786.403 to $27,603.420 with the combination bevacizumab vs. the two-agent chemotherapy regimen. Treatment with T+I+B combination therapy was associated with an increase in effectiveness of 0.280 QALYs from 0.867 to 1.147 QALYs T+I regimen. The incremental cost-effectiveness ratio was $67,203.632/QALY, which exceeded our pre-specified willingness-to-pay threshold ($38,136.26/QALY). Cost changes associated with grade 3-4 AE management, tests used, or hospitalization costs had little effect on the ICER values predicted by sensitivity analysis.

Conclusions: Taken together, the results of this study suggest that the combination of bevacizumab with temozolomide and irinotecan is not a cost-effective option from the perspective of Chinese payers as a first-line treatment option for children with recurrent in China.
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http://dx.doi.org/10.3389/fpubh.2022.914536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201059PMC
June 2022

Dysregulated YAP1/Hippo pathway contributes to doxorubicin (ADM)-resistance in acute myeloid leukemia (AML).

Curr Pharm Biotechnol 2022 Jun 17. Epub 2022 Jun 17.

Department of Hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.

Background: Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML).

Methods: In this study, we established two ADM-resistant cell lines (THP-1/ ADM and K562/ ADM). Then cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real time PCR were performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot.

Results: We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM-resistance, evidenced by the increased expression in ADM-resistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding this role of YAP1 regulates AML resistance by affecting CSCs characteristics.

Conclusion: In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM-resistance in AML. YAP1 might be novel biomarkers for treatment of drug-resistance in AML.
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http://dx.doi.org/10.2174/1389201023666220617150346DOI Listing
June 2022

PDGFA-associated protein 1 is a novel target of c-Myc and contributes to colorectal cancer initiation and progression.

Cancer Commun (Lond) 2022 Jun 18. Epub 2022 Jun 18.

National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, P. R. China.

Background: The mechanism underlying colorectal cancer (CRC) initiation and progression remains elusive, and overall survival is far from satisfactory. Previous studies have shown that PDGFA-associated protein 1 (PDAP1) is upregulated in several cancers including CRC. Here, we aimed to identify the cause and consequence of PDAP1 dysregulation in CRC and evaluate its role as a potential therapeutic target.

Methods: Multi-omics data analysis was performed to identify potential key players in CRC initiation and progression. Immunohistochemistry (IHC) staining was applied to determine the expression pattern of PDAP1 in CRC tissues. Pdap1 conditional knockout mice were used to establish colitis and CRC mouse models. RNA sequencing, a phosphoprotein antibody array, western blotting, histological analysis, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and interactome analysis were applied to identify the underlying mechanisms of PDAP1. A human patient-derived xenograft (PDX) model was used to assess the potential of PDAP1 as a therapeutic target.

Results: PDAP1 was identified as a potential key player in CRC development using multi-omics data analysis. PDAP1 was overexpressed in CRC cells and correlated with reduced overall survival. Further investigation showed that PDAP1 was critical for the regulation of cell proliferation, migration, invasion, and metastasis. Significantly, depletion of Pdap1 in intestinal epithelial cells impaired mucosal restitution in dextran sulfate sodium salt-induced colitis and inhibited tumor initiation and growth in colitis-associated cancers. Mechanistic studies showed that c-Myc directly transactivated PDAP1, which contributed to the high PDAP1 expression in CRC cells. PDAP1 interacted with the juxtamembrane domain of epidermal growth factor receptor (EGFR) and facilitated EGFR-mitogen-activated protein kinase (MAPK) signaling activation, which resulted in FOS-related antigen 1 (FRA-1) expression, thereby facilitating CRC progression. Notably, silencing of PDAP1 could hinder the growth of patient-derived xenografts that sustain high PDAP1 levels.

Conclusions: PDAP1 facilitates mucosal restitution and carcinogenesis in colitis-associated cancer. c-Myc-driven upregulation of PDAP1 promotes proliferation, migration, invasion, and metastasis of CRC cells via the EGFR-MAPK-FRA-1 signaling axis. These findings indicated that PDAP1 inhibition is warranted for CRC patients with PDAP1 overexpression.
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http://dx.doi.org/10.1002/cac2.12322DOI Listing
June 2022

Deciphering Obesity-Related Gene Clusters Unearths SOCS3 Immune Infiltrates and 5mC/m6A Modifiers in Ossification of Ligamentum Flavum Pathogenesis.

Front Endocrinol (Lausanne) 2022 30;13:861567. Epub 2022 May 30.

Department of Orthopaedics, Peking University Third Hospital, Beijing, China.

Background: Ossification of ligamentum flavum (OLF) is an insidious and debilitating heterotopic ossifying disease with etiological heterogeneity and undefined pathogenesis. Obese individuals predispose to OLF, whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood. Therefore, this study aims to explore distinct obesity-related genes and their functional signatures in OLF.

Methods: The transcriptome sequencing data related to OLF were downloaded from the GSE106253 in the Gene Expression Omnibus (GEO) database. The obesity-related differentially expressed genes (ORDEGs) in OLF were screened, and functional and pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI), module analysis, transcription factor enrichment analysis (TFEA), and experiment validation were used to identify hub ORDEGs. The immune infiltration landscape in OLF was depicted, and correlation analysis between core gene SOCS3 and OLF-related infiltrating immune cells (OIICs) as well as 5mC/m6A modifiers in OLF was constructed.

Results: Ninety-nine ORDEGs were preliminarily identified, and functional annotations showed these genes were mainly involved in metabolism, inflammation, and immune-related biological functions and pathways. Integrative bioinformatic algorithms determined a crucial gene cluster associated with inflammatory/immune responses, such as TNF signaling pathway, JAK-STAT signaling pathway, and regulation of interferon-gamma-mediated signaling. Eight hub ORDEGs were validated, including 6 down-regulated genes (SOCS3, PPARG, ICAM-1, CCL2, MYC, and NT5E) and 2 up-regulated genes (PTGS2 and VEGFA). Furthermore, 14 differential OIICs were identified by ssGSEA and xCell, and SOCS3 was overlapped to be the core gene, which was associated with multiple immune infiltrates (dendritic cells, macrophage, and T cells) and six m6A modifiers as well as four 5mC regulators in OLF. Reduced SOCS3 and FTO expression and up-regulated DNMT1 level in OLF were validated by Western blotting.

Conclusion: This study deciphered immune/inflammatory signatures of obesity-related gene clusters for the first time, and defined SOCS3 as one core gene. The crosstalk between 5mC/m6A methylation may be a key mediator of SOCS3 expression and immune infiltration. These findings will provide more insights into molecular mechanisms and therapeutic targets of obesity-related OLF.
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http://dx.doi.org/10.3389/fendo.2022.861567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196192PMC
June 2022

spp. in Commercial Powdered Infant Formula Collected From Nine Provinces in China: Prevalence, Genotype, Biofilm Formation, and Antibiotic Susceptibility.

Front Microbiol 2022 27;13:900690. Epub 2022 May 27.

The Department of Food Science, Shenyang Medical College, Shenyang Medical College, Shenyang, China.

The purpose of this study was to investigate the prevalence of spp. in commercial powdered infant formula (PIF) from nine provinces in China from March 2018 to September 2020, and to reveal the genotype, biofilm-forming ability, and antibiotic susceptibility of these isolates. A total of 27 strains, consisting of 22 strains, 3 strains, 1 strain, and 1 strain, were isolated from 3,600 commercial PIF samples with a prevalence rate of 0.75%. Compared with the other 8 provinces, PIF from Shaanxi province had a higher prevalence rate (1.25%) of spp. These isolates were divided into 14 sequence types (STs), and 6 serotypes. The main STs were ST4, ST1, and ST64, and the dominant serotype was serotype O2. Approximately 88.89% of isolates had a strong ability (OD > 1) to form biofilms on tinplate, among which the strains with ST4 were more dominant. All isolates were susceptible to ampicillin-sulbactam, ceftriaxone, cefotaxime, sulfadiazine, sulfadoxine, trimethoprim-sulfamethoxazole, gentamicin, tetracycline, ciprofloxacin, and colistin, while 55.56 and 96.30% isolates were resistant to cephalothin and vancomycin, respectively. Taken together, our findings highlighted the contamination status and characterization of spp. in commercial PIF from nine provinces of China, and provided guidance for the effective prevention and control of this pathogen in the production of PIF.
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http://dx.doi.org/10.3389/fmicb.2022.900690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197194PMC
May 2022

Insights on ball milling enhanced iron magnesium layered double oxides bagasse biochar composite for ciprofloxacin adsorptive removal from water.

Bioresour Technol 2022 Jun 14;359:127468. Epub 2022 Jun 14.

Hubei Key Laboratory of Mineral Resources Processing and Environment, School of Resources and Environmental Engineering, State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, China; The James Hutton Institute, Craigiebuckler, Aberdeen AB15 8QH, UK. Electronic address:

Both ciprofloxacin (CIP) and sugarcane bagasse have brought enormous pressure on environmental safety. Here, an innovative technique combining Fe-Mg-layered double oxides and ball milling was presented for the first time to convert bagasse-waste into a new biochar adsorbent (BM-LDOs-BC) for aqueous CIP removal. The maximum theoretical adsorption capacity of BM-LDOs-BC reached up to 213.1 mg g due to abundant adsorption sites provided by well-developed pores characteristics and enhanced functional groups. The results of characterization, data fitting and environmental parameter revealed that pore filling, electrostatic interactions, H-bonding, complexation and π-π conjugation were the key mechanisms for CIP adsorptive removal. BM-LDOs-BC exhibited satisfactory environmental safety and outstanding adsorption capacity under various environmental situations (pH, inorganic salts, humic acid). Moreover, BM-LDOs-BC possessed excellent reusability. These superiorities illustrated that BM-LDOs-BC was a promising adsorbent and created a new avenue for rational placement of biowaste and high-efficiency synthesis of biochar for antibiotic removal.
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http://dx.doi.org/10.1016/j.biortech.2022.127468DOI Listing
June 2022

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Lung Adenocarcinoma by Comprehensive Bioinformatics Analysis and Study.

Front Oncol 2022 30;12:916947. Epub 2022 May 30.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China.

Family with sequence similarity 72B (FAM72B) has been characterized in the regulation of neuronal development. Nevertheless, the prognostic value of FAM72B expression and its function in the immune microenvironment of lung adenocarcinoma (LUAD) currently remains elusive. In this study, by adopting bioinformatics methodology and experimental verification, we found that FAM72B was upregulated in lung cancer tissues and cell lines, and a higher FAM72B level predicted an unfavorable clinical outcome in LUAD patients. The knockdown of FAM72B significantly inhibited cell proliferation, cell migration, and induced cell apoptosis in LUAD. The receiver operating characteristic curve suggested that FAM72B had a high predictive accuracy for the outcomes of LUAD. Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analyses confirmed that FAM72B-related genes were involved in cell proliferation and immune-response signaling pathway. Moreover, upregulated FAM72B expression was significantly associated with immune cell infiltration in the LUAD tumor microenvironment. Meanwhile, a potential ceRNA network was constructed to identify the lncRNA-AL360270.2/TMPO-AS1/AC125807.2/has-let-7a/7b/7c/7e/7f/FAM72B regulatory axis that regulates FAM72B overexpression in LUAD and is associated with a poor prognosis. We also confirmed that AL360270.2, TMPO-AS1, and AC125807.2 were significantly upregulated in LUAD cell lines than in human bronchial epithelial cells. In conclusion, FAM72B may serve as a novel biomarker in predicting the clinical prognosis and immune status for lung adenocarcinoma.
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http://dx.doi.org/10.3389/fonc.2022.916947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189382PMC
May 2022

Single Blind Randomized Controlled Trial of Modified Constraint-Induced Movement Therapy in Infants With the Sequelas of Unilateral Brachial Plexus Injury.

Front Hum Neurosci 2022 30;16:900214. Epub 2022 May 30.

Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Objective: To explore the effect of modified constraint-induced movement therapy (mCIMT) on upper limbs residual dysfunction for infancy with the sequelas of unilateral brachial plexus injury (uBPI).

Methods: Single blind randomized controlled trial of mCIMT vs. standard care. An enrolling 31 infants with a uBPI exhibiting residual dysfunction of the affected upper limb for over 6 months was conducted. And functional outcomes pertaining to the affected upper limb were assessed AMS, GRES, RHS, and MSS at 0, 3, and 6 months after treatment.

Results: No differences were found in baseline (acquisition phase) AMS, MSS, GRES, or RHS between the control and mCIMT groups [(1, 14) = 0.062, = 0.086; (1, 14) = 0.483, = 0.499; (1, 14) = 0.272, = 0.610; = -0.336, = 7.373]. At the 3- and 6-month follow-up time points, AMS, MSS, and GRES scores were significantly improved over baseline in both groups [mCIMT: (2, 30) = 183.750, 128.614, 110.085, < 0.05; Control: (2, 28) = 204.007, 75.246, 51.070, < 0.05]. No significant differences were found between two treatment groups at the 3-month follow-up time point [(1, 14) = 0.565, = 0.465; (1, 14) = 0.228, = 0.641; (1, 14) = 0.713, = 0.413; = -0.666, = 0.505]. However, at the 6-month follow-up time point, AMS and MSS scores were significantly improved in the mCIMT group relative to the control group [(1, 14) = 8.077, = 0.013; (1, 14) = 18.692, = 0.001].

Conclusion: mCIMT may benefit the rehabilitation of residual upper limb dysfunction associated with a uBPI in infants.

Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR1900022119].
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http://dx.doi.org/10.3389/fnhum.2022.900214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189277PMC
May 2022

Effect of steam explosion pretreatment on the composition and bioactive characteristic of phenolic compounds in Ramat cv. Hangbaiju powder with various sieve fractions.

Food Sci Nutr 2022 Jun 15;10(6):1888-1898. Epub 2022 Mar 15.

Beijing Laboratory of Food Quality and Safety Beijing Technology and Business University Beijing China.

Steam explosion (SE) pretreatment is an efficient technique to promote the fiber degradation and disrupt materials' cell wall. In this study, the effect of SE pretreatment on the changes in phenolic profile, and the in vitro digestion property of a Chinese indigenous herb "Hangbaiju" (HBJ) powder with various sieve fractions (150-, 180-, 250-, 425-, and 850-μm sieves) were studied. After SE pretreatment, the morphological structure, color attributes, and composition of phenolic compounds were altered significantly ( < .05). The composition and content of phenolic compounds were strongly correlated with particle sizes. The higher extraction yield of phenolic compounds was reached in the intermediate sieve fraction (ca. 250-μm sieves). During in vitro digestion, the changes in phenolic compounds were significant due to the transition from an acidic to the alkaline environment ( < .05). Based on the multivariate statistical analysis, apigenin-7-O-glucoside, luteolin-7-O-glucoside, and linarin, were viewed as the characteristic compounds among various samples. The results highlighted that the phytochemical properties mainly including the composition of phenolic compounds, and in vitro digestion properties of HBJ powder with intermediate sieve fraction could be improved after SE pretreatment.
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http://dx.doi.org/10.1002/fsn3.2805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179122PMC
June 2022

Distinct mechanisms of innate and adaptive immune regulation underlie poor oncologic outcomes associated with KRAS-TP53 co-alteration in pancreatic cancer.

Oncogene 2022 Jun 14. Epub 2022 Jun 14.

Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Co-occurrent KRAS and TP53 mutations define a majority of patients with pancreatic ductal adenocarcinoma (PDAC) and define its pro-metastatic proclivity. Here, we demonstrate that KRAS-TP53 co-alteration is associated with worse survival compared with either KRAS-alone or TP53-alone altered PDAC in 245 patients with metastatic disease treated at a tertiary referral cancer center, and validate this observation in two independent molecularly annotated datasets. Compared with non-TP53 mutated KRAS-altered tumors, KRAS-TP53 co-alteration engenders disproportionately innate immune-enriched and CD8 T-cell-excluded immune signatures. Leveraging in silico, in vitro, and in vivo models of human and murine PDAC, we discover a novel intersection between KRAS-TP53 co-altered transcriptomes, TP63-defined squamous trans-differentiation, and myeloid-cell migration into the tumor microenvironment. Comparison of single-cell transcriptomes between KRAS-TP53 co-altered and KRAS-altered/TP53 tumors revealed cancer cell-autonomous transcriptional programs that orchestrate innate immune trafficking and function. Moreover, we uncover granulocyte-derived inflammasome activation and TNF signaling as putative paracrine mediators of innate immunoregulatory transcriptional programs in KRAS-TP53 co-altered PDAC. Immune subtyping of KRAS-TP53 co-altered PDAC reveals conflation of intratumor heterogeneity with progenitor-like stemness properties. Coalescing these distinct molecular characteristics into a KRAS-TP53 co-altered "immunoregulatory program" predicts chemoresistance in metastatic PDAC patients enrolled in the COMPASS trial, as well as worse overall survival.
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http://dx.doi.org/10.1038/s41388-022-02368-wDOI Listing
June 2022
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