Publications by authors named "Wei Xu"

5,034 Publications

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Web-Based Data to Quantify Meteorological and Geographical Effects on Heat Stroke: Case Study in China.

Geohealth 2022 Aug 1;6(8):e2022GH000587. Epub 2022 Aug 1.

State Key Laboratory of Earth Surface Processes and Resource Ecology Beijing Normal University Beijing China.

Heat stroke is a serious heat-related health outcome that can eventually lead to death. Due to the poor accessibility of heat stroke data, the large-scale relationship between heat stroke and meteorological factors is still unclear. This work aims to clarify the potential relationship between meteorological variables and heat stroke, and quantify the meteorological threshold that affected the severity of heat stroke. We collected daily heat stroke search index (HSSI) and meteorological data for the period 2013-2020 in 333 Chinese cities to analyze the relationship between meteorological variables and HSSI using correlation analysis and Random forest (RF) model. Temperature and relative humidity (RH) accounted for 62% and 9% of the changes of HSSI, respectively. In China, cases of heat stroke may start to occur when temperature exceeds 36°C and RH exceeds 58%. This threshold was 34.5°C and 79% in the north of China, and 36°C and 48% in the south of China. Compared to RH, the threshold of temperature showed a more evident difference affected by altitude and distance from the ocean, which was 35.5°C in inland cities and 36.5°C in coastal cities; 35.5°C in high-altitude cities and 36°C in low-altitude cities. Our findings provide a possible way to analyze the interaction effect of meteorological variables on heat-related illnesses, and emphasizes the effects of geographical environment. The meteorological threshold quantified in this research can also support policymaker to establish a better meteorological warning system for public health.
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http://dx.doi.org/10.1029/2022GH000587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356531PMC
August 2022

Circular RNA circVPRBP serves as a microRNA-106b-5p sponge to regulate proliferation and metastasis of cervical cancer cells via tripartite motif-containing protein 3.

Anticancer Drugs 2022 Aug 10. Epub 2022 Aug 10.

Department of Obstetrics and Gynecology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.

Cervical cancer is a common malignant gynecological tumor for females all over the world. Circular RNAs (circRNAs) are being found to have relevance to various human cancers, including cervical cancer. This study is designed to explore the role and mechanism of circRNA DDB1- and CUL4-associated factor 1 (circVPRBP, also known as hsa_circ_0065898) on the progression of cervical cancer. CircVPRBP, microRNA-106b-5p (miR-106b-5p), and tripartite motif-containing protein 3 (TRIM3) levels were determined by real-time quantitative PCR. Cell proliferative ability, apoptosis rate, cell cycle progression, migration, and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, colony formation assay, flow cytometry, and transwell assays. Protein levels of matrix metallopeptidase 2 (MMP2) and matrix MMP9, and TRIM3 were measured by western blot assay. The binding relationship between miR-106b-5p and circVPRBP or TRIM3 was predicted by Starbase and then verified by a dual-luciferase reporter and RNA immunoprecipitation assays. The biological role of circVPRBP on cervical tumor growth was examined by the xenograft tumor model in vivo. CircVPRBP and TRIM3 were decreased, and miR-106b-5p was increased in cervical cancer tissues and cell lines. Furthermore, circVPRBP could suppress cell growth and metastasis of cervical cancer cells in vitro. Mechanically, circVPRBP could regulate TRIM3 expression by sponging miR-106b-5p. Also, circVPRBP upregulation repressed tumor growth of cervical cancer cells in vivo. CircVPRBP could inhibit the malignant biological behavior of cervical cancer cells by miR-106b-5p/TRIM3 axis, providing a promising therapeutic target for cervical cancer treatment.
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http://dx.doi.org/10.1097/CAD.0000000000001335DOI Listing
August 2022

Changes of the liver metabolome following an intravenous lipopolysaccharide injection in Holstein cows supplemented with dietary carnitine.

J Anim Sci Biotechnol 2022 Aug 10;13(1):94. Epub 2022 Aug 10.

Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim, 70599, Stuttgart, Germany.

Background: Carnitine facilitates the flux of long-chain fatty acids for hepatic mitochondrial beta-oxidation, which acts to ameliorate the negative energy balance commonly affecting high-yielding dairy cows. Inflammation triggered by lipopolysaccharide (LPS) load can however pose a challenge to the metabolic integrity via the expression of pro-inflammatory mediators, leading to immune system activation and respective metabolic alterations. The effect of enhanced carnitine availability on hepatic metabolome profiles during an inflammatory challenge has not yet been determined in dairy cows. Herein, Holstein cows were supplemented with 25 g/d rumen-protected carnitine from 42 d prepartum until 126 d postpartum (n = 16) or assigned to the control group with no supplementation during the same period (n = 14). We biopsied the liver of the cows before (100 d postpartum) and after (112 d postpartum) an intravenous injection of 0.5 µg/kg LPS. Liver samples were subjected to a targeted metabolomics analysis using the AbsoluteIDQ p180 Kit (Biocrates Life Sciences AG, Innsbruck, Austria).  RESULTS: Multivariate statistical analyses revealed that hepatic metabolome profiles changed in relation to both the carnitine supplementation and the LPS challenge. Comparing the metabolite profiles on 100 d, carnitine increased the concentration of short- and long-chain acyl-carnitines, which may be explained by an enhanced mitochondrial fatty acid shuttle and hence greater energy availability. The LPS injection affected hepatic metabolite profiles only in the carnitine supplemented group, particularly altering the concentration of biogenic amines.

Conclusions: Our results point to interactions between an acute hepatic inflammatory response and biogenic amine metabolism, depending on energy availability.
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http://dx.doi.org/10.1186/s40104-022-00741-zDOI Listing
August 2022

Chemical structures and anti-tyrosinase activity of the constituents from Elephantopus scaber L.

Fitoterapia 2022 Aug 3;162:105259. Epub 2022 Aug 3.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Engineering Research Center of Natural Medicine Active Molecule Research & Development, Key Laboratory of Natural Bioactive Compounds Discovery & Modification, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address:

Four undescribed compounds including one germacrane-type sesquiterpene lactones (1), alkaloid (2) along with two neolignans (3-4) were isolated from Elephantopus scaber L. Their structures and absolute configurations were elucidated unambiguously by means of 1D and 2D NMR spectroscopic data analysis, and quantum chemical electronic circular dichroism calculations, as well as single-crystal X-ray crystallography. Their anti-tyrosinase activities have been evaluated in vitro and compound 2 exhibited significant inhibitory activity. Furthermore, molecular docking was performed to study the interaction patterns between 2 and the tyrosinase.
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http://dx.doi.org/10.1016/j.fitote.2022.105259DOI Listing
August 2022

Flexible surface-enhanced Raman scatting substrates: recent advances in their principles, design strategies, diversified material selections and applications.

Crit Rev Food Sci Nutr 2022 Aug 5:1-45. Epub 2022 Aug 5.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China.

Surface-enhanced Raman scattering (SERS) is widely used as a powerful analytical technology in cutting-edge areas such as food safety, biology, chemistry, and medical diagnosis, providing ultra-fast, ultra-sensitive, nondestructive characterization and achieving ultra-high detection sensitivity even down to the single-molecule level. Development of Raman spectroscopy is strongly dependent on high-performance SERS substrates, which have long evolved from the early days of rough metal electrodes to periodic nanopatterned arrays building on solid supporting substrates. For rigid SERS substrates, however, their applications are restricted by sophisticated pretreatments for detecting solid samples with non-planar surfaces. It is therefore essential to reassert the principles in constructing flexible SERS substrates. Herein, we comprehensively review the state-of-the-art in understanding, preparing and using flexible SERS. The basic mechanisms behind the flexible SERS are briefly outlined, typical design strategies are highlighted and diversified selection of materials in preparing flexible SERS substrates are reviewed. Then the recent achievements of various interdisciplinary applications based on flexible SERS substrates are summarized. Finally, the challenges and perspectives for future evolution of flexible SERS and their applications are demonstrated. We propose new research directions focused on stimulating the real potential of SERS as an advanced analytical technique for commercialization.
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http://dx.doi.org/10.1080/10408398.2022.2106547DOI Listing
August 2022

Clinical effect of pulmonary rehabilitation combined with diaphragm pacemaker therapy in the treatment of severely ill patients with mechanical ventilation.

Int J Rehabil Res 2022 Sep 23;45(3):195-200. Epub 2022 Jun 23.

Department of Rehabilitation, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

To investigate the effect of pulmonary rehabilitation combined with diaphragm pacemaker therapy on the diaphragm function of severely ill patients on mechanical ventilation. Forty patients were randomly divided into the control group (CG; n = 20) and experimental group (EG; n = 20). The CG was given basic ICU nursing and conventional rehabilitation treatment. The EG added a diaphragm pacemaker and pulmonary rehabilitation therapies along with basic ICU nursing and conventional rehabilitation treatment. The relevant indexes were compared at baseline and postintervention, including the Glasgow Coma Scale (GCS), Acute Physiology, Chronic Health Evaluation II (APACHE II) scores, diaphragm mobility and thickness. The indexes of mechanical ventilation time, ICU and total hospital stays were compared between the two groups. There was no difference in the GCS and APACHE II scores, and diaphragm mobility and thickness between the two groups before treatment (P > 0.05). After 30 days of treatment, the GCS scores increased in both groups, the APACHE II scores decreased significantly, and diaphragm mobility and thickness decreased compared with before treatment (P < 0.05), but the improvement of each index in the EG was more evident than in the CG. Compared with the CG, the indexes of the EG, including offline, ICU and total hospitalization times, were significantly shorter (P < 0.05). Additionally, there were no adverse events such as accidental tube detachment or falling out of bed during treatment. Pulmonary rehabilitation combined with a diaphragm pacemaker is safe and effective in treating severely ill mechanically ventilated patients.
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http://dx.doi.org/10.1097/MRR.0000000000000535DOI Listing
September 2022

[Thoughts on Improving Joint Review of Combination Products].

Zhongguo Yi Liao Qi Xie Za Zhi 2022 Jul;46(4):365-367

Center for Medical Device Evaluation, NMPA, Beijing, 100081.

This article combines the joint review of combination products in recent years, sorts out the links and common problems in the joint review process, introduces the work carried out to optimize the joint review process of combination products, and puts forward relevant suggestions for improvement, aim to improving the work of joint review and providing reference for relevant product declaration.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2022.04.003DOI Listing
July 2022

Antimicrobial application of chitosan derivatives and their nanocomposites.

Curr Med Chem 2022 Aug 3. Epub 2022 Aug 3.

Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou Zhejiang 318000, China.

Chitosan is derived from chitin polysaccharide, the main component of crustacean shells. Chitosan is a biocompatible, nontoxic, and biodegradable polymer soluble in acidic solutions. It is widely used in the medical and pharmaceutical fields. Antimicrobial activities of chitosan against different bacterial, fungal, and viral pathogens have been considered one of its attractive properties, making chitosan valuable for biological applications, including textiles, food, tissue engineering, agriculture, and environmental protection. Additionally, chitosan has beneficial effects on livestock, poultry, fish, and crustaceans, which can enhance immunity, improve feed conversion, and promote growth. However, the water solubility of chitosan influences antimicrobial capabilities, limiting its application. In the present work, we reviewed the preparation, factors affecting antimicrobial activity, morphological structure, antimicrobial mechanism, and application of chitosan derivatives, and the problems and prospects were pointed out. Collectively, this review provided an update on the application of chitosan derivatives and their potential for further advanced applications in the antimicrobial field.
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http://dx.doi.org/10.2174/0929867329666220803114729DOI Listing
August 2022

Dynamic evaluation of the ecological civilization of Jiangxi Province: GIS and AHP approaches.

PLoS One 2022 4;17(8):e0271768. Epub 2022 Aug 4.

School of Economics and Management, China University of Geosciences, Wuhan, China.

Faced with the increasingly severe ecological environment, China promotes the construction of ecological civilization vigorously. Therefore, it is of great significance to adopt scientific, effective and comprehensive methods to evaluate development status of ecological civilization. Based on the panel data from 2010 to 2014, this paper employs GIS and AHP methods to dynamically examine the level of ecological civilization construction in Jiangxi Province. The results indicate that: (1) The ecological civilization construction in Jiangxi Province is 13.23% higher than the national average, whereas there is an imbalance in the development of different cities within the province; (2) The ecological civilization construction in the whole province rises first and then falls; (3) The performances of the cities vary in different dimensions of the construction of ecological civilization that cities in Jiangxi province perform well in the dimension of ecological environment, but perform poorly in the dimension of social development. Finally, we put forward policy recommendations for improving ecological environment to realize harmonious development between human and nature.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271768PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352063PMC
August 2022

From Mechanobiology to Mechanical Repair Strategies: A Bibliometric Analysis of Biomechanical Studies of Intervertebral Discs.

J Pain Res 2022 28;15:2105-2122. Epub 2022 Jul 28.

Department of Spinal Surgery, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.

Neck pain and low back pain are major challenges in public health, and intervertebral disc (IVD) biomechanics is an important multidisciplinary field. To date, no bibliometric literature review of the relevant literature has been performed, so we explored the emerging trends, landmark studies, and major contributors to IVD biomechanics research. We searched the Web of Science core collection (1900-2022) using keywords mainly composed of "biomechanics" and "intervertebral disc" to conduct a bibliometric analysis of original papers and their references, focusing on citations, authors, journals, and countries/regions. A co-citation analysis and clustering of the references were also completed. A total of 3189 records met the inclusion criteria. In the co-citation network, cluster #0, labeled as "annulus fibrosus tissue engineering", and cluster #1, labeled as "micromechanical environment", were the biggest clusters. References by MacLean et al and Holzapfel et al were positioned exactly between them and had high betweenness centrality. There existed a research topic evolution between mechanobiology and mechanical repair strategies of IVDs, and the latter had been identified as an emerging trend in IVD biomechanics. Numerous landmark studies had contributed to several fields, including mechanical testing of normal and pathological IVDs, mechanical evaluation of new repair strategies and development of finite element model. Adams MA was the author most cited by IVD biomechanics papers. , the , and the were the three journals where the most original articles and their references have been published. The United States has contributed most to the literature (n = 1277 papers); however, the research output of China is increasing. In conclusion, the present study suggests that IVD repair is an emerging trend in IVD biomechanics.
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http://dx.doi.org/10.2147/JPR.S361938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342884PMC
July 2022

Heterogeneous iodine-organic chemistry fast-tracks marine new particle formation.

Proc Natl Acad Sci U S A 2022 Aug 2;119(32):e2201729119. Epub 2022 Aug 2.

School of Physics, Ryan Institute's Centre for Climate and Air Pollution Studies, National University of Ireland Galway, Galway H91 CF50, Ireland.

The gas-phase formation of new particles less than 1 nm in size and their subsequent growth significantly alters the availability of cloud condensation nuclei (CCN, >30-50 nm), leading to impacts on cloud reflectance and the global radiative budget. However, this growth cannot be accounted for by condensation of typical species driving the initial nucleation. Here, we present evidence that nucleated iodine oxide clusters provide unique sites for the accelerated growth of organic vapors to overcome the coagulation sink. Heterogeneous reactions form low-volatility organic acids and alkylaminium salts in the particle phase, while further oligomerization of small α-dicarbonyls (e.g., glyoxal) drives the particle growth. This identified heterogeneous mechanism explains the occurrence of particle production events at organic vapor concentrations almost an order of magnitude lower than those required for growth via condensation alone. A notable fraction of iodine associated with these growing particles is recycled back into the gas phase, suggesting an effective transport mechanism for iodine to remote regions, acting as a "catalyst" for nucleation and subsequent new particle production in marine air.
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http://dx.doi.org/10.1073/pnas.2201729119DOI Listing
August 2022

Molecular Mechanism of Antimicrobial Excipient-Induced Aggregation in Parenteral Formulations of Peptide Therapeutics.

Mol Pharm 2022 Aug 2. Epub 2022 Aug 2.

Analytical Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Antimicrobial preservatives are used as functional excipients in multidose formulations of biological therapeutics to destroy or inhibit the growth of microbial contaminants, which may be introduced by repeatedly administering doses. Antimicrobial agents can also induce the biophysical instability of proteins and peptides, which presents a challenge in optimizing the drug product formulation. Elucidating the structural basis for aggregation aids in understanding the underlying mechanism and can offer valuable knowledge and rationale for designing drug substances and drug products; however, this remains largely unexplored due to the lack of high-resolution characterization. In this work, we utilize solution nuclear magnetic resonance (NMR) as an advanced biophysical tool to study an acylated 31-residue peptide, acyl-peptide A, and its interaction with commonly used antimicrobial agents, benzyl alcohol and -cresol. Our results suggest that acyl-peptide A forms soluble octamers in the aqueous solution, which tumble slowly due to an increased molecular weight as measured by diffusion ordered spectroscopy and H relaxation measurement. The addition of benzyl alcohol does not induce aggregation of acyl-peptide A and has no chemical shift perturbation in H-H NOESY spectra, suggesting no detectable interaction with the peptide. In contrast, the addition of 1% (w/v) -cresol results in insoluble aggregates composed of 25% (w/w) peptides after a 24-hour incubation at room temperature as quantified by H NMR. Interestingly, H-C heteronuclear single-quantum coherence and H-H total correlation experiment spectroscopy have identified -cresol and peptide interactions at specific residues, including Met, Lys, Glu, and Gln, suggesting that there may be a combination of hydrophobic, hydrogen bonding, and electrostatic interactions with -cresol driving this phenomenon. These site-specific interactions have promoted the formation of higher-order oligomerization such as dimers and trimers of octamers, eventually resulting in insoluble aggregates. Our study has elucidated a structural basis of -cresol-induced self-association that can inform the optimized design of drug substances and products. Moreover, it has demonstrated solution NMR as a high-resolution tool to investigate the structure and dynamics of biological drug products and provide an understanding of excipient-induced peptide and protein aggregation.
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http://dx.doi.org/10.1021/acs.molpharmaceut.2c00449DOI Listing
August 2022

Single-base methylome analysis reveals dynamic changes of genome-wide DNA methylation associated with rapid stem growth of woody bamboos.

Planta 2022 Aug 1;256(3):53. Epub 2022 Aug 1.

Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Kunming, 650201, Yunnan, China.

Main Conclusion: CG and CHG methylation levels in the rapid shoot growth stages (ST2-ST4) of woody bamboos were obviously decreased, which might regulate the internode elongation during rapid shoot growth, while CHH methylation was strongly associated with shoot developmental time or age. DNA methylation plays a critical role in the regulation of plant growth and development. Woody bamboos have a unique trait of rapid stem growth resulted from internode elongation at the shooting period. However, it is still unclear whether DNA methylation significantly controls the bamboo rapid stem growth. Here we present whole-genome DNA methylation profiles of the paleotropical woody bamboo Bonia amplexicaulis at five newly defined stages of shoot growth, named ST1-ST5. We found that CG and CHG methylation levels in the rapid shoot growth stages (ST2-ST4) were significantly lower than in the incubation (ST1) and plateau stages (ST5). The changes in methylation levels mainly occurred in flanking regions of genes and gene body regions, and 23647 differentially methylated regions (DMRs) were identified between ST1 and rapid shoot growth stages (ST2-ST4). Combined with transcriptome analysis, we found that DMR-related genes enriched in the auxin and jasmonic acid (JA) signal transduction, and other pathways closely related to plant growth. Intriguingly, CHH methylation was not involved in the rapid shoot growth, but strongly associated with shoot developmental time by gradually accumulating in transposable elements (TEs) regions. Overall, our results reveal the importance of DNA methylation in regulating the bamboo rapid shoot growth and suggest a role of DNA methylation associated with development time or age in woody bamboos.
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http://dx.doi.org/10.1007/s00425-022-03962-8DOI Listing
August 2022

Development and Validation of a Non-invasive Model to Predict Liver Histological Lesions in Chronic Hepatitis B Patients With Persistently Normal Alanine Aminotransferase and Detectable Viremia.

Front Med (Lausanne) 2022 13;9:944547. Epub 2022 Jul 13.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background: A critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA.

Methods: 398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set ( = 256) and validation set ( = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set.

Results: 132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index ≤ 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index ≥ 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%).

Conclusion: The SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.
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http://dx.doi.org/10.3389/fmed.2022.944547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326251PMC
July 2022

Discovering the Potential Value of Coenzyme Q10 in Oxidative Stress: Enlightenment From a Synthesis of Clinical Evidence Based on Various Population.

Front Pharmacol 2022 14;13:936233. Epub 2022 Jul 14.

Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Oxidative stress (OS) is associated with ferroptosis. Coenzyme Q10 (CoQ10), as an adjuvant treatment, has shown to be beneficial against OS. However, the efficacy of CoQ10 as a therapeutic agent against OS has not been promptly updated and systematically investigated. A systematic literature search was performed using the Medline, EMBASE, Web of science, Cochrane Central Register of Controlled Trials, CNKI, CBM, Science direct and clinical trial. gov to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. Twenty-one randomized clinical studies met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation increased the levels of antioxidant enzymes [including superoxide dismutase (SOD) (SMD = 0.63; 95% CI: 0.38 to 0.88; < 0.001), catalase (CAT) (SMD = 0.44; 95% CI:0.16 to 0.72; = 0.002)] significantly and the levels of malondialdehyde (MDA) (SMD = -0.68; 95% CI: 0.93 to -0.43; < 0.001) was decreased considerably. However, significant associations were not observed between this supplement and total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity. CoQ10 can improve OS as indicated by statistical significance in CAT and MDA concentrations, as well as SOD activity. Future studies focusing on long-term results and specific valuation of OS parameters are required to confirm the efficacy of CoQ10 on OS. We also believe that with the further research on ferroptosis, CoQ10 will gain more attention. [https://inplasy.com/], identifier [INPLASY2021120123].
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http://dx.doi.org/10.3389/fphar.2022.936233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330130PMC
July 2022

An odorant binding protein mediates Bactrocera dorsalis olfactory sensitivity to host plant volatiles and male attractant compounds.

Int J Biol Macromol 2022 Jul 27. Epub 2022 Jul 27.

Chongqing Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China. Electronic address:

Odorant-binding proteins (OBPs) are believed to play critical roles in host-seeking behavior. However, little attention was paid to its different functions in male and female. The antenna-specific OBP gene from Bactrocera dorsalis, BdorOBP13, was cloned and its expression profile was examined. The results showed that BdorOBP13 was exclusively expressed in male and female adults, which exhibited a high transcript level in antennae. After injection of BdorOBP13 dsRNA, its transcript level in males and females decreased significantly. Electrophysiological responses of RNAi-injected flies to, methyl eugenol (male attractant) and γ-octalactone (female attractant) decreased significantly. However, no significant changes in the electrophysiological response were observed in RNAi-injected flies to benzothiazole, (+),dipentene, and ethyl tiglate. The behavioral bioassay showed that males treated with RNAi significantly reduced their preference to methyl eugenol, while RNAi-injected females showed a significantly lower preference to γ-octalactone, suggesting that BdorOBP13 may have different functions between males and females: it may be involved in the detection of methyl eugenol in males but is involved in the detection of γ-octalactone in females. These findings improve our understanding of insect OBPs and their roles in insect chemosensation, which may provide us with new molecular targets in the management of B. dorsalis.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.198DOI Listing
July 2022

Evaluation of risk-tailored individualized selection of radiation therapy target volume for Head and Neck Carcinoma of Unknown Primary.

Radiother Oncol 2022 Jul 26. Epub 2022 Jul 26.

Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Intensity-modulated radiation therapy (IMRT) has enabled risk-tailored approach to elective mucosal and nodal clinical target volumes (CTVs) in treatment of head and neck carcinoma of unknown primary (HNCUP). This study report outcomes following such approach.

Methods: HNCUP patients treated with definitive IMRT between 2005 and 2018 were reviewed. Local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS) and grade ≥3 late toxicity (LT) were analyzed. Multivariable analysis (MVA) was used to identify OS predictors for entire cohort and cN2-3 subgroup.

Results: A total of 203 patients were eligible: cN1 (7%), cN2a (14%), cN2b (46%), cN2c (14%) and cN3 (19%). Among 118 patients with known HPV status (by p16 staining), 81 (68%) were positive. IMRT target volume spared contralateral tonsil (55%), bilateral or contralateral sides of hypopharynx (72%), nasopharynx (72%), larynx (87%) and contralateral uninvolved neck (21%). Median follow-up was 5 years. Five-year LF, RF, DM, OS, and LT were 3%, 14%, 10%, 79%, and 7% respectively. Four patients developed mucosal recurrence: 3 within and 1 at the margin of the elective mucosal CTV. None of ipsilateral neck irradiation patients failed in the contralateral uninvolved neck. MVA identified cN2c-N3, HPV-negative status and older age as predictors for inferior OS. Within cN2-3 subgroup (n=189): cN2c-N3, HPV-negative status and older age predicted lower OS, while concurrent chemotherapy was associated with better OS.

Conclusion: Definitive IMRT with risk-adaptive radiation volume de-escalation for HNCUP resulted in high probability of tumor control with acceptable rate of late toxicity.
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http://dx.doi.org/10.1016/j.radonc.2022.07.016DOI Listing
July 2022

Successful pregnancy via in vitro fertilization in a primary infertile woman with primary lymphoma of the fallopian tube after surgery: A case report and literature review.

Medicine (Baltimore) 2022 Jul 29;101(30):e29353. Epub 2022 Jul 29.

State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Rationale: Primary extranodal marginal zone B-cell lymphomas of the fallopian tube is extremely rare. It is a great challenge for fertility and gynecology doctors to manage such cases and also fulfil the reproductive demands of these young women.

Patient Concerns: A 30-year-old woman consulted for a 5-year primary infertility.

Diagnosis: According to the Ann Arbor staging system, a stage IE extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma was diagnosed for this patient based on tumor pathology, bone marrow biopsy, hysteroscopy and whole-body positron emission tomography imaging. She also had endometriosis based on laparoscopy.

Interventions: The patient underwent a laparoscopic bilateral salpingostomy without additional surgery or radiotherapy and chemotherapy for fertility preservation, and received 5 months of long-acting gonadotropin releasing hormone agonist treatment for endometriosis.

Outcomes: Two years after the surgery, the patient delivered a healthy neonate through in vitro fertilization-embryo transfer procedures. The patient is now 3 years post-op and 1 year post-delivery, long-term follow-up suggested that the patient remained cancer-free up till now.

Lessons: More care should be taken when the newly diagnosed mass is combined with a rather high serum CA-125 level. Although endometriosis and ovarian cancer are more common, lymphoma cannot be ruled out.
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http://dx.doi.org/10.1097/MD.0000000000029353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333483PMC
July 2022

σ-σ Stacked supramolecular junctions.

Nat Chem 2022 Jul 28. Epub 2022 Jul 28.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering & Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM) & Pen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, Xiamen, China.

Intermolecular charge transport plays an essential role in organic electronic materials and biological systems. To date, experimental investigations of intermolecular charge transport in molecular materials and electronic devices have been restricted to conjugated systems in which π-π stacking interactions are involved. Herein we demonstrate that the σ-σ stacking interactions between neighbouring non-conjugated molecules offer an efficient pathway for charge transport through supramolecular junctions. The conductance of σ-σ stacked molecular junctions formed between two non-conjugated cyclohexanethiol or single-anchored adamantane molecules is comparable to that of π-π stacked molecular junctions formed between π-conjugated benzene rings. The current-voltage characteristics and flicker noise analysis demonstrate the existence of stacked molecular junctions formed between the electrode pairs and exhibit the characteristics of through-space charge transport. Density functional theory calculations combined with the non-equilibrium Green's function method reveal that efficient charge transport occurs between two molecules configured with σ-σ stacking interactions.
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http://dx.doi.org/10.1038/s41557-022-01003-1DOI Listing
July 2022

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies.

Adv Ther 2022 Jul 28. Epub 2022 Jul 28.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Introduction: Zanubrutinib is a highly selective irreversible inhibitor of Bruton tyrosine kinase which has shown significant activity in lymphoid malignancies in early phase studies. We report here the long-term follow-up outcomes of zanubrutinib in various lines of therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Methods: This post hoc analysis pooled patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL/SLL receiving zanubrutinib monotherapy from three phase 1/2 studies (BGB-3111-1002, BGB-3111-AU-003, BGB-3111-205).

Results: A total of 211 patients with CLL/SLL (TN 19, R/R 192) were included. After weighting (TN 19, R/R 24), the overall response rate (ORR) was 95.4% and significantly higher in the TN group than in the R/R group (100 vs. 91.0%, p < 0.0001). ORR was also significantly higher in the TN group than in the one prior line of therapy group (100 vs. 98.9%, p < 0.0001). Among those with R/R disease, the ORR was 97.8% in patients with one prior line of therapy (n = 79) and 90.7% in those with > 1 prior lines of therapy (n = 85; p = 0.080). The median follow-up times were 50.1, 35.7, and 45.9 months for TN, R/R and all cohorts, respectively. Progression-free survival and overall survival were significantly longer in the TN group and only one prior line of therapy group compared with the > 1 prior lines of therapy group (all p < 0.05) and were similar in the TN group compared with the one prior line therapy group. Efficacy was similar regardless of the presence of genomic aberrations. Most frequent grade ≥ 3 adverse events were infections (41.7%), neutropenia (34.1%), and thrombocytopenia (9.4%). Atrial fibrillation occurred in only 1.9% of patients.

Conclusions: With extended follow-up, zanubrutinib yielded long-term benefits and demonstrated a favorable safety profile for patients with TN or RR CLL/SLL. Earlier utilization of zanubrutinib was associated with better outcomes.

Trial Registration: Clinical Trials.gov identifiers, NCT03189524, NCT02343120 (retrospectively registered), and NCT03206918 (retrospectively registered).
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http://dx.doi.org/10.1007/s12325-022-02238-7DOI Listing
July 2022

Chloral Hydrate Alters Brain Activation Induced by Methamphetamine-Associated Cue and Prevents Relapse.

Front Mol Neurosci 2022 11;15:934167. Epub 2022 Jul 11.

Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Chinese Academy of Sciences, Shenzhen, China.

Methamphetamine is a highly addictive drug and its abuse leads to serious health and social problems. Until now, no effective medications are yet available for the treatment of methamphetamine addiction. Our study reveals that chloral hydrate, a clinical sedative drug, suppresses the seeking desire for methamphetamine. After 5 days of continuous administration (subanesthetic dose 50 mg/kg and 100 mg/kg), methamphetamine-seeking behavior of rats was inhibited in the condition place preference and intravenous self-administration tests. Furthermore, chloral hydrate treatment robustly suppressed cue-induced methamphetamine relapse. The whole brain c-fos immunostaining revealed that chloral hydrate treatment suppressed neuronal activity in the rhomboid thalamic nucleus (Rh), dorsal endopiriform nucleus (dEn), and claustrum (Cl) while enhanced zona incerta (ZI) activity during cue-induced methamphetamine relapse. Therefore, chloral hydrate could remodel neural network activity and serve as a potential medicine to treat methamphetamine addiction.
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http://dx.doi.org/10.3389/fnmol.2022.934167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309691PMC
July 2022

A high mobility air-stable n-type organic small molecule semiconductor with high UV-visible-to-NIR photoresponse.

Light Sci Appl 2022 Jul 27;11(1):236. Epub 2022 Jul 27.

Institute of Advanced Materials and School of Chemistry and Chemical Engineering, Southeast University, 211189, Nanjing, China.

An organic semiconductor with high carrier mobility and efficient light absorption over a wide spectral range is of the most important yet challenging material for constructing a broadband responsive organic photodetector. However, the development of such organic semiconductors, especially for air-stable n-type organic small molecule semiconductors, is still at an early stage. Here we report the fabrication of high-performance n-type semiconducting crystalline nanosheets and the development of air-stable field-effect transistors, phototransistors, with high response over a broad spectrum. The n-type small molecule semiconductor is assembled into a crystalline nanosheet based on the solvent-phase interfacial self-assembly method. N-type field-effect transistors with high electron mobility are fabricated and their electrical performances exhibit excellent air stability. Impressively, the demonstrated phototransistors exhibit an ultrahigh responsivity over a wide spectral range from 365 to 940 nm, with a maximum photoresponsivity of 9.2 × 10 A W and specific detectivity of 5.26 × 10 Jones, which is the best performance among the reported n-type organic small molecule-based phototransistors.
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http://dx.doi.org/10.1038/s41377-022-00936-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329299PMC
July 2022

Roles of Cartilage-Resident Stem/Progenitor Cells in Cartilage Physiology, Development, Repair and Osteoarthritis.

Cells 2022 Jul 27;11(15). Epub 2022 Jul 27.

Trauma Centre, General Hospital of Western Theatre Command of PLA, Chengdu 610083, China.

Osteoarthritis (OA) is a degenerative disease that causes irreversible destruction of articular cartilage for which there is no effective treatment at present. Although articular cartilage lacks intrinsic reparative capacity, numerous studies have confirmed the existence of cartilage-resident stem/progenitor cells (CSPCs) in the superficial zone (SFZ) of articular cartilage. CSPCs are characterized by the expression of mesenchymal stromal cell (MSC)-related surface markers, multilineage differentiation ability, colony formation ability, and migration ability in response to injury. In contrast to MSCs and chondrocytes, CSPCs exhibit extensive proliferative and chondrogenic potential with no signs of hypertrophic differentiation, highlighting them as suitable cell sources for cartilage repair. In this review, we focus on the organizational distribution, markers, cytological features and roles of CSPCs in cartilage development, homeostasis and repair, and the application potential of CSPCs in cartilage repair and OA therapies.
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http://dx.doi.org/10.3390/cells11152305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332847PMC
July 2022

Testing an Iron Oxide Nanoparticle-Based Method for Magnetic Separation of Nanoplastics and Microplastics from Water.

Nanomaterials (Basel) 2022 Jul 9;12(14). Epub 2022 Jul 9.

Department of Life Sciences, Texas A&M University, Corpus Christi, TX 78412, USA.

Nanoplastic pollution is increasing worldwide and poses a threat to humans, animals, and ecological systems. High-throughput, reliable methods for the isolation and separation of NMPs from drinking water, wastewater, or environmental bodies of water are of interest. We investigated iron oxide nanoparticles (IONPs) with hydrophobic coatings to magnetize plastic particulate waste for removal. We produced and tested IONPs synthesized using air-free conditions and in atmospheric air, coated with several polydimethylsiloxane (PDMS)-based hydrophobic coatings. Particles were characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), superconducting quantum interference device (SQUID) magnetometry, dynamic light scattering (DLS), X-ray diffraction (XRD) and zeta potential. The IONPs synthesized in air contained a higher percentage of the magnetic spinel phase and stronger magnetization. Binding and recovery of NMPs from both salt and freshwater samples was demonstrated. Specifically, we were able to remove 100% of particles in a range of sizes, from 2-5 mm, and nearly 90% of nanoplastic particles with a size range from 100 nm to 1000 nm using a simple 2-inch permanent NdFeB magnet. Magnetization of NMPs using IONPs is a viable method for separation from water samples for quantification, characterization, and purification and remediation of water.
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http://dx.doi.org/10.3390/nano12142348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315505PMC
July 2022

On the Morphological Deviation in Additive Manufacturing of Porous Ti6Al4V Scaffold: A Design Consideration.

Materials (Basel) 2022 Jul 6;15(14). Epub 2022 Jul 6.

Institute of Orthopaedic & Musculoskeletal, Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, Stanmore, London HA7 4LP, UK.

Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 μm (2.5% excess) for vertical struts to 105.4 μm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 μm (4.2% excess) to 198.6 μm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 μm (-3.0% excess) for vertical struts to 92.8 μm (-8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 μm (-3.0% excess) to 168.7 μm (-21.1% excess). Compressive Young's modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young's modulus from α and β phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds.
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http://dx.doi.org/10.3390/ma15144729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319900PMC
July 2022

Neuregulin-1 signaling regulates cytokines and chemokines expression and secretion in granulosa cell.

J Ovarian Res 2022 Jul 26;15(1):86. Epub 2022 Jul 26.

Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive Southwest, Atlanta, GA, 30310, USA.

Background: Granulosa cells (GCs) are multilayered somatic cells within the follicle that provide physical support and microenvironment for the developing oocyte. In recent years, the role of Neuregulin-1 (NRG1), a member of the EGF-like factor family, has received considerable attention due to its neurodevelopmental and cardiac function. However, the exact physiological role of NRG1 in GC is mainly unknown. In order to confirm that NRG1 plays a regulatory role in rat GC functions, endogenous NRG1-knockdown studies were carried out in GCs using RNA interference methodology.

Results: Knockdown of NRG1 in GCs resulted in the enhanced expression and secretion of the cytokines and chemokines. In addition, the phosphorylation of PI3K/Akt/ERK1/2 was significantly low in GCs under these experimental conditions. Moreover, in vitro experimental studies suggest that tumor necrosis factor-α (TNFα) treatment causes the physical destruction of GCs by activating caspase-3/7 activity. In contrast, exogenous NRG1 co-treatment of GCs delayed the onset of TNFα-induced apoptosis and inhibited the activation of caspase-3/7 activity. Furthermore, current experimental studies suggest that gonadotropins promote differential expression of NRG1 and ErbB3 receptors in GCs of the antral follicle. Interestingly, NRG1 and ErbB3 were intensely co-localized in the mural and cumulus GCs and cumulus-oocyte complex of pre-ovulatory follicles in the estrus stage.

Conclusions: The present studies suggest that gonadotropins-dependent NRG1-signaling in GCs may require the balance of the cytokines and chemokines expression and secretion, ultimately which may be supporting the follicular maturation and oocyte competence for ovulation and preventing follicular atresia.
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http://dx.doi.org/10.1186/s13048-022-01021-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316729PMC
July 2022

Additive manufacturing of functionally graded porous titanium scaffolds for dental applications.

Biomater Adv 2022 Aug 6;139:213018. Epub 2022 Jul 6.

School of Engineering, RMIT University, Melbourne 3001, Australia.

Graded porous titanium scaffolds are gaining increasing attention as dental implants due to their ability to mimic the mechanical and biological properties of human bone. In this study, we have developed titanium scaffolds with graded primitive structures with porosities of 50.7 %, 61.0 %, 70.5 %, and 80.3 % (denoted as P50, P60, P70, and P80, respectively) for dental applications. The simulation results in the oral environment showed that the maximum von Mises strains and stress of cortical bone tissue around P50, P60, and P70 were lower than 3000 με and 60 MPa, respectively, which was beneficial for bone regeneration. The elastic modulus and yield strength of P50, P60, and P70 ranged within 5.2-13.8 GPa and 88.6-217.8 MPa, respectively. Among these, P60 exhibited the most favorable mechanical properties with a compression yield strength of 163.2 MPa and an elastic modulus of 9.7 GPa, which are desirable mechanical properties for dental material applications. The tested permeabilities of the fabricated specimens were in the range 0.66-6.88 × 10 m, which is within the range of human bone (0.01-12.10 × 10 m). In vitro biocompatibility assay results showed that P60 and P70 had better potential for cell viability and osteogenesis than P50. It can be concluded that P60, which has a compatible elastic modulus, high yield strength, high permeability, good cytocompatibility, and osteogenesis properties, is a promising candidate for bone-tissue engineering applications in dentistry.
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http://dx.doi.org/10.1016/j.bioadv.2022.213018DOI Listing
August 2022

[Design, manufacture and evaluation of a multi-parameter controllable automatic fire-acupuncture instrument].

Zhen Ci Yan Jiu 2022 Jul;47(7):649-54

Department of Dermatology, Chongqing First People's Hospital/Chongqing Hospital of Chinese Medicine, Chongqing 400011, China.

A multi-parameter controllable automatic fire-acupuncture instrument was developed by integrating traditional fire needling with modern medical device technology. A gun-like appearance was designed for easy hand-held operation, the electromagnetic induction was for heating needle body, a scale knob was for controlling the needle insertion depth, the combination of electromagnetic ejection and spring return was for the precise control of the needle retention time; and the changeable single ste-rile needle or multiple needles were adopted to meet individual demand, obtain high efficiency and prevent infection. All of these designs are associated with the overall process control system to ensure the exact controllability of needle body temperature, needling density, insertion depth and needle retention time. Besides, this device is advantageous at handy and aseptic operation with high efficiency, conformability and visualization. In this research, this instrument was tested in animals for the impacts of automatic fire needling on skin damage and fur growth. It is found that the accurate control of each parameter is of the significant advantage in the safety and effectiveness of treatment, which lays a solid foundation for the subsequent systematic review on safety and effectiveness.
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http://dx.doi.org/10.13702/j.1000-0607.20210545DOI Listing
July 2022

Clinical characteristics and thrombotic risk of atrial fibrillation with obstructive sleep apnea: results from a multi-center atrial fibrillation registry study.

BMC Cardiovasc Disord 2022 07 25;22(1):331. Epub 2022 Jul 25.

Emergency Center, National Center for Cardiovascular Disease, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, 100037, Beijing, People's Republic of China.

Background: Sleep apnea is a risk factor for atrial fibrillation (AF) but it is underdiagnosed. Whether obstructive sleep apnea (OSA) is correlated with thrombotic risk in AF remains unclear. The aim of the present study was to analyze the clinical characteristics and assess the thrombotic risk of AF with OSA.

Methods: In the present registry study,1990 consecutive patients with AF from 20 centers were enrolled. The patients were divided into 2 groups depending on whether they presented with both AF and OSA. All the patients were followed up for 1 year to evaluate the incidences of stroke and non-central nervous system (CNS) embolism.

Results: Of the 1990 AF patients, 70 (3.5%) and 1920 (96.5%) patients were in the OSA group and non-OSA group, respectively. The results of the multivariate logistic model analysis showed that male sex, body mass index (BMI), smoking, and major bleeding history were independent risk factors for patients with AF and OSA. The comparison of the Kaplan-Meier curves using the log-rank test revealed that AF with OSA was correlated with an increased risk of non-CNS embolism (p < 0.01). After multivariate adjustments were performed, OSA remained an independent risk factor for non-CNS embolism (HR 5.42, 95% CI 1.34-22.01, p = 0.02), but was not correlated with the risk of stroke in patients with AF.

Conclusions: The present study revealed that male sex, high BMI values, smoking, and major bleeding history were independent risk factors for patients with AF and OSA. Moreover, OSA was an independent risk factor for non-CNS embolism in AF. Our results indicate that non-CNS embolism requires focus in patients with AF and OSA.
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http://dx.doi.org/10.1186/s12872-022-02773-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310481PMC
July 2022

Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ.

Nat Commun 2022 Jul 25;13(1):4291. Epub 2022 Jul 25.

Obstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, 200438, Shanghai, P.R. China.

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation.
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http://dx.doi.org/10.1038/s41467-022-32000-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314339PMC
July 2022
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