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Three isostructural transition metal-organic frameworks, [M(bta) 0.5 (bpt)(H 2 O) 2 ]·2H 2 O (M = Co ( 1 ), Ni ( 2 ), Zn ( 3 ), H 4 bta = 1,2,4,5-benzenetetracarboxylic acid, bpt = 4-amino-3,5-bis(4-pyridyl)-1,2,4-triazole), were successfully constructed using different metal cations. These frameworks exhibit a three-dimensional network structure with multiple coordinated and lattice water molecules within the framework, contributing to high stability and a rich hydrogen-bond network. Proton conduction studies revealed that, at 333 K and 98% relative humidity, the proton conductivities (σ) of MOFs 1-3 reached 1.42 × 10 -2 , 1.02 × 10 -2 , and 6.82 × 10 -3 S cm -1 , respectively. Compared to the proton conductivity of the initial ligands, the σ values of the complexes increased by 2 orders of magnitude, with the activation energies decreasing from 0.36 to 0.18 eV for 1 , 0.09 eV for 2 , and 0.12 eV for 3 . An in-depth analysis of the correlation between different metal centers and proton conduction performance indicated that the varying coordination abilities of the metal cations and the water absorption capacities of the frameworks might account for the differences in conductivity. Additionally, the potential of 1 as a supercapacitor electrode material was assessed. 1 exhibited a specific capacitance of 61.13 F g -1 at a current density of 0.5 A g -1 , with a capacitance retention of 82.4% after 5000 cycles, making it a promising candidate for energy storage applications.

Diabetes, a common metabolic condition, is recognized by the worldwide public health community as a serious chronic illness. International new drug discovery has long been dominated by the study and creation of blood glucose-lowering medications. Important phases in the development process of these medications include the in vitro assessment model and screening methods, which can dramatically lower the costs and risks of subsequent clinical trials and increase the effectiveness and efficiency of drug development. This article reviews the classic and latest cutting-edge in vitro assessment models, principles, methods, and key technologies for blood glucose-lowering medications both domestically and internationally. By objectively evaluating their advantages, disadvantages, characteristics, applicability, experimental design, and data analysis, this article aims to improve the standardization and consensus of in vitro assessment models and screening methods and serve the research and development of blood glucose-lowering medications.

Aim: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery., Methods: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients., Results: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P <0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P <0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P =0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P =0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P =0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P =0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities ( r Han =0.48, r Uyghur =0.44, P <0.001), while AL was negatively correlated with Kf ( r Han =-0.42, r Uyghur =-0.64, P <0.001) and Ks ( r Han =-0.38, r Uyghur =-0.66, P <0.001). Additionally, Kf was positively correlated with Ks ( r Han =0.89, r Uyghur =0.93, P <0.001)., Conclusion: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures., Competing Interests: Conflicts of Interest: Xu Z, None; Wang LM, None; Feng Q, None; Zhang DD, None; Tuerdimaimaiti A, None; Guo RR, None; Sun J, None; Dong LJ, None; Wei RH, None; Liu AH, None., (International Journal of Ophthalmology Press.)

Objective: To explore the differences in metabolites and metabolic pathways in the aqueous humor between patients with presenile cataracts and senile cataracts. Methods: This metabolomic study was conducted at Tianjin Medical University Eye Hospital from August 2020 to September 2022. Eight patients with presenile cataracts (8 eyes) and 8 patients with senile cataracts (9 eyes) were included. Data were collected, including age, gender, preoperative uncorrected visual acuity, intraocular pressure, lens dysfunction index, and axial length. Aqueous humor and anterior capsule tissue samples were obtained during cataract surgery. Metabolites in the aqueous humor were detected using Liquid Chromatography-Mass Spectrometry in a non-targeted approach. The principal component analysis, differential analysis, clustering analysis, and correlation analysis were performed to identify differentially expressed metabolites. These metabolites were ranked based on the fold change (FC). The receiver operating characteristic (ROC) curve analysis and metabolic enrichment analysis were used to identify differential pathways and potential biomarkers for presenile cataracts. Immunohistochemistry was conducted on anterior capsule tissues, and pyruvate levels were measured by colorimetry to validate metabolomic results. Results: Patients with presenile cataracts included 7 males and 1 female, with a mean age of (37.50±4.90) years. Patients with senile cataracts were 7 males and 1 female, with a mean age of (73.44±5.22) years. Except for age, there were no significant differences in baseline data ( P >0.05). A total of 347 differential metabolites were identified, 10 of which were potential biomarkers for presenile cataract according to the ROC curve analysis (all P <0.05), including propoxycaine (log 2 FC=7.26), 2-methyl-2, 3, 4, 5-tetrahydro-1, 5-benzodiazepine-4-ketone (log 2 FC=6.35), l -pyroglutamic acid (log 2 FC=-1.72), leanly-proline (log 2 FC=-0.77), and choline (log 2 FC=-0.56) in the positive ion mode, and N-phenylacetyl glutamine (log 2 FC=-1.84), pyruvate (log 2 FC=1.07), ascorbic acid (log 2 FC=0.92), pseudouracil nucleoside (log 2 FC=-0.68), and palmitic acid (log 2 FC=-0.51) in the negative ion mode. The metabolic enrichment analysis identified 72 differential pathways (32 cationic and 40 anionic), with significant differences in glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle ( P <0.05). The experimental validation showed reduced lactate dehydrogenase and increased pyruvate levels in patients with presenile cataracts ( P <0.05). Conclusions: Pyruvate and nine other metabolites may serve as potential biomarkers for presenile cataracts. Pathways involving glutathione metabolism, cysteine and methionine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, and the citric acid cycle are notably dysregulated in patients with presenile cataracts.

Lithium-ion batteries, with high energy density and long cycle life, have become the battery of choice for most vehicles and portable electronic devices; however, energy density, safety and cycle life require further improvements. Single-functional group electrolyte additives are very limited in practical applications, a ternary polymer bifunctional electrolyte additive copolymer (acrylonitrile-butyl hexafluoro methacrylate- poly (ethylene glycol) methacrylate- methyl ether) (PMANHF) was synthesized by free radical polymerization of acrylonitrile, 2, 2, 3, 4, 4, 4-hexafluorobutyl methacrylate and poly (ethylene glycol) methyl ether methacrylate. A series of characterizations show that in Li metal anodes, the preferential reduction of PMANHF is conducive to the formation of a uniform and stable solid electrolyte interphase layer, and Li deposition is uniform and dense. At the NCM811 cathode, a film composed of LiF- and Li 3 N-rich is formed at the cathode-electrolyte interface, mitigating the side reaction at the interface. At 1.0 mA cm -2 , the Li/Li cell can be stabilized for 1000 cycles. In addition, the Li/NCM811 cell can stabilize 200 cycles with a cathode capacity of 153.7 mAh g -1 , with the capacity retention of 89.93 %, at a negative/positive capacity ratio of 2.5. This study brings to light essential ideas for the fabrication of additives for lithium-metal batteries., (© 2024 Wiley-VCH GmbH.)

Aims: This study aimed to identify different profiles of chronic disease resource utilization among patients with coronary heart disease in Tibet and explore the relationship between these profiles and quality of life., Design: A cross-sectional study., Methods: Patients with coronary heart disease who were treated in a tertiary hospital in Tibet and its cooperative points from January 2021 to July 2021 were selected as the study participants. All participants completed a general information questionnaire, the Chronic Disease Resource Utilization Questionnaire (CIRS) and the Health Status Survey Short Form (SF-36). Chronic disease resource utilization was profiled, and its relationship to quality of life was explored using hierarchical linear regression., Results: A total of 382 patients were enrolled in this study. Regarding chronic disease resource utilization, the participants were divided into three latent profiles: 'Poor utilization group' (n = 151), 'Effective utilization group' (n = 155) and 'Full utilization group' (n = 76). Different profiles of chronic disease resource utilization of patients were significantly associated with quality of life (R 2  = .126, p < .001)., Conclusion: Healthcare providers should identify patients with different profiles, define their utilization features of chronic disease resources and adopt targeted interventions to guide them in acquiring enough disease support resources to improve their quality of life., Implication: Understanding different resources using preferences of coronary heart disease patients can help healthcare providers and related sectors to provide other supports based on different profiles of patients, thus enhancing their quality of life., Reporting Method: The study followed the STROBE guideline., No Patient or Public Contribution: There was no patient or public involvement in the design of the study., (© 2023 John Wiley & Sons Ltd.)

An organocatalytic enantioselective alkylation of α,α-disubstituted aldehydes with 3-bromooxindoles is reported. Enantioenriched oxindoles with vicinal quaternary stereocenters are accessed by an asymmetric conjugate addition process of branched aldehydes with o -azaxylylene intermediates (indol-2-ones). Key to the success of highly diastereo- and enantioselective transformations is the combined use of a triphenylsilyl-protected β-amino alcohol catalyst derived from the spiropyrrolidine scaffold and 3,5-dinitrobenzoic acid. This study also presents a rare example of aldehyde alkylation with the formation of consecutive quaternary stereocenters.

Objective: Intramedullary nails are commonly used for the purposes of internal fixation in the repair of tubular bone fractures, allowing for optimal fixation while minimizing intraoperative bleeding, surgical incision size, and associated stress. These nails are thus often utilized to repair hip and peripheral fractures, femur fractures, tibial fractures, humerus fractures, and clavicle fractures. Recent life expectancy increases, rising economic standards, and technological innovations have led to the application of a wider range of materials and techniques in the context of orthopedic device production, further expanding the clinical indications for intramedullary nailing. Despite the growing importance of this technique, there is currently a lack of any bibliometric or visual analyses that provide a robust overview of recent progress in the intramedullary nailing research space. Accordingly, this study was developed to succinctly and comprehensively summarize the current research status and major hotspots in this field through a bibliometric review of major relevant scientific articles focused on intramedullary nailing published in recent years., Materials and Methods: For this analysis, the top 100 most-cited articles focused on intramedullary nails published between 2018 and 2022 were identified through a search of the Web of Science Core Collection database. Countries, institutions, journals, and other specific parameters associated with these articles were then analyzed using tools including CiteSpace, VOS-viewer, Origin, and SCImago Graphica in an effort to more clearly define the latest trends in the intramedullary nail-related research space., Results: The top 3 most-cited articles related to intramedullary nailing over the past five years were "Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium", "Diaphyseal long bone nonunions - types, etiology, economics, and treatment recommendations", and "Epidemiology, treatment, and mortality of trochanteric and subtrochanteric hip fractures: data from the Swedish fracture register", all of which were published in 2018, respectively exhibiting 93, 83, and 81 citations. Of the 100 most-cited intramedullary nailing-related articles, 38, 20, and 12 were respectively published by researchers from the USA, China, and the UK, while research groups from Italy and Spain each published 7 articles. Four of this field's most highly cited articles were published by individuals affiliated with the US-based University of California System and the University System of Ohio. Of the 15 journals that published the largest number of these top 100 articles, the "Injury International Journal of The Care of The Injured" and the "Journal of Orthopaedic Trauma" published 9 manuscripts each, which was more than any other journal, while the "Journal of Orthopaedic Surgery" and the "Journal of Pediatric Orthopaedics" published 7 each. In total, 73 highly cited articles focused on utilizing intramedullary nailing in orthopedic applications. Rozbruch SR from the USA published 3 high-quality articles in this research space, while the Chinese researchers Chang Shi Min, Du Shou Chao, Hou Zhi Yong, and Hu Sun Jun exhibited a total linkage strength of 21 in global interaction analyses. The most common keywords associated with intramedullary nail-related research identified in these analyses included "Hip fracture", "Nonunion", "Limb lengthening", "Proximal humeral fractures", "Additive manufacturing", "Induced membrane", and "Endoprosthetic replacement". Promising areas of potential future research focus may include "Limb reconstruction", "Pediatric deformity", and "Congenital femoral deficiency"., Conclusions: This analysis revealed that the highest volume of high-impact research output focused on intramedullary nailing over the past 5 years has been produced by the USA, followed by China and the UK. The most influential journals in this research space were Injury International Journal of The Care of The Injured and the Journal of Orthopaedic Trauma, while the institutions associated with the most highly cited articles were the University of California System and the University System of Ohio. Intramedullary nailing is commonly utilized to treat intertrochanteric fractures and other tubular bone fractures. In the future, the application of augmented and virtual reality technologies may help shorten the learning curve for orthopedic surgeons and trauma surgeons who are learning intramedullary nailing-related techniques, and the combination of intramedullary nailing with antibacterial drugs, metal alloys, 3D navigation, and sensor devices may help improve patient outcomes.

Objective: To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis., Methods: A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study., Results: The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk., Conclusion: The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: This study aimed to analyze the relationship between health literacy and quality of life in patients with TB in Tibet and explore the mediating effects of self-efficacy and self-management in the relationship between health literacy and quality of life., Methods: We used a convenience sampling method to select 271 cases of patients with TB in Tibet to conduct a survey of their general information, health literacy, self-management, self-efficacy and quality of life, and to construct structural equation models., Results: The total health literacy score of patients with TB in Tibet was 84.28±18.57, while the lowest score was for information acquisition ability (55.99±25.66). Scores for quality of life were generally lower than the norm (patients with chronic diseases from other cities in China) (p<0.01). Moreover, self-efficacy and self-management mediated the relationship between health literacy and quality of life (p<0.05)., Conclusions: In Tibet, patients with TB have a low level of health literacy and an average level of quality of life. Emphasis should be placed on improving information access literacy, role-physicals and role-emotional to improve overall quality of life. The mediating roles of self-efficacy and self-management between health literacy and quality of life may provide a basis for further interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objective: This meta-analysis was performed to evaluate the diagnostic efficacy of lung ultrasound (LUS) in cardiogenic pulmonary edema., Materials and Methods: An electronic search of databases, including MEDLINE, Embase, PubMed, and Web of Science, was performed to collect clinical studies on ultrasound diagnosis of cardiogenic pulmonary edema from inception to 23 March 2023. The number of patients with true-positive, true-negative, false-positive, and false-negative cardiogenic pulmonary edema diagnosed by LUS was collected, and the R package was used to analyze the diagnostic efficacy of LUS., Results: Nine pieces of literature were finally included with 2,097 participants, including 1,047 patients with cardiogenic heart failure. Across the nine included papers, the pooled sensitivity of LUS in the included studies was 0.92 (95% CI: 0.84, 0.97) with a maximum sensitivity of 0.99 (95% CI: 0.96 to 1.00) and a minimum of 0.59 (95% CI: 0.50, 0.68). The pooled specificity of the included studies was 0.87 (95% CI: 0. 82, 0.91) with a maximum specificity of 0.93 (95% CI: 0.90-0.95) and a minimum of 0.80 (95% CI: 0.67, 0.89). The pooled AUC was 0.93 (95% CI: 0.84 to 0.97), suggesting a high diagnostic value of LUS in cardiogenic pulmonary edema., Conclusions: Lung ultrasound offers a good diagnostic efficacy for cardiogenic pulmonary edema. Further standardization of the examination method is required to provide a reference for the clinical use of LUS.

A Rh(I)-catalyzed [5 + 2]/[2 + 2] cycloaddition cascade has been developed to afford a complex and highly strained [4-5-6-7] tetracyclic framework in good yields and excellent diastereoselectivities. During this transformation, three rings, three C-C bonds, and four contiguous stereocenters were formed efficiently. Mechanistically, the rare sterically congested multisubstituted cyclobutanes are constructed readily through Michael addition and a Mannich reaction cascade.

Background: The disease burden of coronary heart disease patients in Tibet, China, ranks high in the country. Due to the local culture and environment, patients with coronary heart disease have increased risk factors for the disease, and their survival is worrisome., Objectives: The purpose of this study was to determine the relationship between health literacy and quality of life for patients with coronary heart disease in Tibet, China, and to explore the mediating roles of self-efficacy and self-management., Methods: A cross-sectional study was conducted from August 2020 to July 2021 in Tibet. A total of 258 patients with coronary heart disease in Tibet participated. Self-reported questionnaires were used to assess health literacy, self-efficacy, self-management, and quality of life. Pearson correlation analysis and the SPSS PROCESS macro were used to analyze the data., Results: The mean total score for the health literacy of patients with coronary heart disease in Tibet was 3.59 ± 0.80 points, showing the existence of a limited level of literacy. The quality of life was of an average level, with scores of 57.20 ± 21.70 points and 63.63 ± 20.66 points for physical and mental status, respectively. Self-efficacy and self-management mediated the relationship between health literacy and quality of life., Conclusions: Self-efficacy and self-management mediate the relationship between health literacy and quality of life. Targeted interventions for health literacy, self-efficacy, and self-management skills are important to improve the quality of life of Tibetan patients with coronary heart disease., Competing Interests: Declaration of Competing Interest There is no conflict of interest has been declared by the authors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Most existing action quality assessment (AQA) methods provide only an overall quality score for the input video and lack an evaluation of each substage of the movement process; thus, these methods cannot provide detailed feedback for users. Moreover, the existing datasets do not provide labels for substage quality assessment. To address these problems, in this work, a new label-reconstruction-based pseudo-subscore learning (PSL) method is proposed for AQA in sporting events. In the proposed method, the overall score of an action is not only regarded as a quality label but also used as a feature of the training set. A label-reconstruction-based learning algorithm is built to generate pseudo-subscore labels for the training set. Moreover, based on the pseudo-subscore labels and overall score labels, a multi-substage AQA model is fine-tuned from the PSL model to predict the action quality score of each substage and the overall score for an athlete. Several ablation experiments are performed to verify the effectiveness of each module. The experimental results show that our approach achieves state-of-the-art performance., Competing Interests: • Conflict of interest: The authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The persistence of the HIV-1 reservoir is still the main obstacle to the cure of HIV. In clinical research, reliable biomarkers are needed to label it. HIV-1 DNA can be continuously detected in the HIV-1 reservoir. It has significant application value in diagnosing HIV-1 infection, the timing of antiretroviral therapy, the prediction of virus rebound, and monitoring treatment effects. The detection technology based on polymerase chain reaction (PCR) is the most commonly used HIV-1 DNA detection method in clinical practice. The continuous innovation and advancement of technology can accurately detect the total, integrated, and unintegrated HIV-1 DNA in infected cells using qualitative or quantitative methods. Different forms of HIV-1 DNA in infected cells have been increasingly reported as biomarkers in HIV infection monitoring and AIDS treatment-related research. This article reviews the progress of HIV-1 DNA.

Objective: To investigate the possible role of pyroptosis of lens epithelial cells (LECs) in the occurrence of diabetic cataract. Methods: Experimental research. A total of 70 cataract lens anterior capsule and aqueous humor samples were obtained from 70 eyes (70 patients) with cataracts in the operation room of Tianjin Medical University Eye Hospital between March 2020 and November 2020. Patients were divided into the non-diabetic and diabetic groups, with 35 patients (35 eyes) in each group. The expressions of Nod like receptor protein 3 (NLRP3), cysteine-aspartic proteases 1 (caspase-1) and Gasdermin D protein (GSDMD) in the lens anterior capsule were detected by Western blotting, real-time quantitative PCR and immunohistochemical staining. Interleukin (IL)-1β and IL-18 inaqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). The independent sample t -test was used for statistical analysis. Results: The age was (70±9) years in the diabetic group and (71±8) years in the non-diabetic group. There was no significant difference in age and gender distribution between the two groups (both P> 0.05). Western blotting analysis showed that the expression levels of NLRP3, caspase-1 and GSDMD protein in the LECs of anterior capsule were 1.11±0.06, 0.95±0.04 and 0.39±0.03 in the diabetic group, significantly higher than those of the non-diabetic group (0.81±0.04, 0.33±0.11 and 0.16±0.04; t =4.38, 5.36, 4.63; all P <0.05). Real-time quantitative PCR showed that the levels of NLRP3, caspase-1 and GSDMD mRNA in the LECs of anterior capsule were 1.98±0.07, 54.36±4.88 and 6.98±1.18 in the diabetic group, significantly higher than those of the non-diabetic group (1.38±0.16, 15.31±1.51 and 2.41±0.95; t =3.49, 7.64, 3.00, all P <0.05). Immunohistochemical staining showed that the average gray values of NLRP3, caspase-1 and GSDMD in the diabetic group were higher than those of the non-diabetic group (all P ˂0.01). ELISA showed that the levels of IL-1β and IL-18 in the aqueous humor were (4.178±0.028) fg/L and (20.983±0.018) fg/L in the diabetic group, significantly higher than those of the non-diabetic group [(4.063±0.017) fg/L and (20.509±0.073) fg/L; t =20.63, 37.21; both P ˂0.01]. Conclusion: Caspase-1-mediated pyroptosis of LECs and the release of inflammatory mediators induced by pyroptosis may be involved in the occurrence and development of diabetic cataract.

Background: MicroRNA-423 (miR-423) rs6505162 polymorphism is found to be associated with breast cancer (BC) risk. However, the results were inconsistent. This study meta-analyzed the literature on possible association between rs6505162 polymorphism and BC risk., Methods: PubMed, Embase, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association between rs6505162 polymorphism and BC., Results: None of the five genetic models suggested a significant association between rs6505162 polymorphism and BC risk: allelic model, OR 1.02, 95% CI 0.18-1.28, P =0.85; recessive model, OR 0.99, 95% CI 0.72-1.38, P =0.97; dominant model, OR 0.93, 95% CI 0.72-1.21, P =0.60; homozygous model, OR 1.04, 95% CI 0.66-1.65, P =0.87; and heterozygous model, OR 1.07, 95% CI 0.90-1.28, P =0.45. Similar results were obtained in subgroup analyses of Asian, Chinese, and Caucasian patients., Conclusion: The available evidence suggests no significant association between rs6505162 polymorphism and BC risk. These conclusions should be verified in large, well-designed studies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Zhi Li et al.)

Objective: To understand the infection status of HCV and Treponema pallidum (TP) in HIV/AIDS cases in Yunnan province,and identify the risk factors. Methods: Between January 1 and June 30 in 2020,a cross-sectional survey was conducted in Yunnan. Two enzyme-linked immunosorbent assay (ELISA) kits were used to detect anti-HCV, the positive results of both two kits indicated HCV infection. ELISA and syphilis toluidine red untreated serum test were applied to identify TP infection. Both Excel 2016 and SPSS 22.0 software were used for statistical analysis, and logistic regression model was conducted to identify the relevant factors of HCV and TP infection. Results: A total of 5 922 HIV/AIDS cases were included in this study, the infection rates of HCV and TP were 6.5% (383/5 922) and 5.8% (344/5 922) respectively. The co-infection rate of HCV and TP was 0.4% (22/5 922). The risk for HCV infection in HIV/AIDS cases was higher in younger age groups compared with age group ≥50 years (15-19:a OR =3.53;20-29:a OR =3.02;30-39:a OR =2.91;40-49:a OR =3.61), in males than in females (a OR =2.31), in the married and unmarried than in the divorced or widowed (married:a OR =1.61;unmarried:a OR =1.63), in other ethnic groups than in Han ethnic group (a OR =1.70), in people with lower education level than in people with education level of college and above (primary school degree and below:a OR =4.69;middle school:a OR =3.96), in people living in the central and western Yunnan than in people living in eastern Yunnan (central Yunnan:a OR =2.46; western Yunnan:a OR =7.08), in injection drug users than in MSM (a OR =131.08). The risk of TP infection in HIV/AIDS cases was higher in people with education level of college and primary school than in middle school degree (primary school and below:a OR =1.73;college and above:a OR =1.77), in people with other occupations than in farmers (a OR =1.39), in people living in eastern Yunnan than in people living in western Yunnan (a OR =1.75); in MSM than in people with heterosex (a OR =9.75). Conclusions: A certain proportion of HIV/AIDS cases reported between January and June in 2020 in Yunnan were co-infected with HCV and TP, many factors were associated with the co-infection. It is suggested to strengthen HCV and TP tests in HIV/AIDS cases and conduct active treatment of the co-infection.

Glycolysis produces large amounts of adenosine triphosphate (ATP) in a short time. The retinal vascular endothelium feeds itself primarily through aerobic glycolysis with less ATP. But when it generates new vessels, aerobic glycolysis provides rapid and abundant ATP support for angiogenesis, and thus inhibition of glycolysis in endothelial cells can be a target for the treatment of neovascularization. Aerobic glycolysis has a protective effect on Müller cells, and it can provide with a target for visual protection and maintenance of the blood-retinal barrier. Under physiological conditions, the mitochondria of RPE can use lactic acid produced by photoreceptor cells as an energy source to provide ATP for survival. In pathological conditions, because RPE cells avoid their oxidative damage by increasing glycolysis, a large number of glycolysis products accumulate, which in turn has a toxic effect on photoreceptor cells. This shows that stabilizing the function of RPE mitochondria may become a target for the treatment of diseases such as retinal degeneration. The decrease of aerobic glycolysis leads to the decline of photoreceptor cell function and impaired vision; therefore, aerobic glycolysis of stable photoreceptor cells provides a reliable target for delaying vision loss. It is of great significance to study the role of glycolysis in various retinal cells for the targeted treatment of ocular fundus diseases., (International Journal of Ophthalmology Press.)

Respective detection of microplastics (MPs) and nanoplastics (NPs) is of great importance for their different environmental behaviors and toxicities. Using spherical polystyrene (PS) and poly(methyl methacrylate) (PMMA) plastics as models, the efficiency for sequential isolation of MPs and NPs by membrane filtration and cloud-point extraction was evaluated. After filtering through a glass membrane (1 μm pore size), over 90.7% of MPs were trapped on the membrane, whereas above 93.0% of NPs remained in the filtrate. The collected MPs together with the glass membrane were frozen in liquid nitrogen, ground, and suspended in water (1 mL) and subjected to pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) determination. The NPs in the filtrate were concentrated by cloud-point extraction, heated at 190 °C to degrade the extractant, and then determined by Py-GC/MS. For MPs and NPs spiked in pure water, the method detection limits are in the range of 0.05-1.9 μg/L. The proposed method is applied to analyze four real water samples, with the detection of 1.6-7.6 μg/L PS MPs and 0.6 μg/L PMMA MPs in three samples, and spiked recoveries of 75.0-102% for MPs and 67.8-87.2% for NPs. Our method offers a novel sample pretreatment approach for the respective determination of MPs and NPs.

The degree of retinal fibrosis increased in proliferative diabetic retinopathy (PDR) patients after administration of anti-Vascular endothelial growth factor (VEGF) injections. Previous studies showed that the balance between connective tissue growth factor (CTGF) and VEGF plays an important role. Therefore, in a high-glucose state, an anti-VEGF and CTGFshRNA dual-target model was used to simulate clinical dual-target treatment in PDR patients, and RNA sequencing (RNA-Seq) technology was used for whole transcriptome sequencing. A hypoxia model was constructed to verify the sequencing results at the cellular level, and the vitreous humor and proliferative membranes were collected from patients for verification. All sequencing results included Follistatin-like protein 1 ( FSTL1 ) and extracellular matrix (ECM) receptor pathway, indicated that anti-VEGF therapy may upregulate FSTL1 expression, while dual-target treatment downregulated FSTL1. Thus, we further studied the function of FSTL1 on the expression of VEGF and ECM factors by both overexpressing and silencing FSTL1 . In conclusion, our results suggested that FSTL1 may be involved in the pathogenesis of PDR and is related to fibrosis caused by the anti-VEGF treatment, thus providing a potential target for gene therapy in PDR.

Bone morphogenetic proteins (BMPs), a member of the transforming growth factor β (TGF- β ) superfamily, are abundant in human ocular tissues and play an important role in lens development. Targeted deletion of BMP-4 in mice results in failure of lens placode formation. Following lens maturation, the formation of senile cataracts is demonstrably associated with free radical-related oxidative stress. Previous studies reported that BMPs play an antiapoptotic role in cells under oxidative stress, and the BMP-4 signal is important in inflammation regulation and homeostasis. BMP-4 evidently suppressed the apoptosis of human lens epithelial cells (HLECS) under oxidative stress induced by H 2 O 2 . This protective antiapoptotic effect is partly due to a decrease in caspase-3 activity and reactive oxygen species (ROS) level. Furthermore, the expression of activating transcription factor- (ATF-) 6 and Krüppel-like factor- (KLF-) 6 increased under oxidative stress and decreased after BMP-4 treatment., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Bei Du et al.)

Objective: To study the expression levels of secretogranin Ⅲ (SCG3) in the peripheral blood and vitreous of patients with diabetic retinopathy (DR). Methods: Cross-sectional research. A total of 77 patients (41 men and 36 women, 77 eyes) received vitrectomy in Tianjin Medical University Eye Hospital from May to December 2018, with an average age of (60.75±11.34) years. According to the blood glucose level, diabetes history and fundus status, all the patients were divided into the DR group and the non-diabetic group. According to the patients' blood lipids and body mass index (BMI), patients were further divided into subgroups of high blood lipids, normal blood lipids, high BMI and normal BMI. All patients were tested with eye examinations, height and weight to calculate the BMI, and blood lipid levels in the peripheral blood. The vitreous was collected during the vitrectomy surgery, and the levels of SCG3 in the vitreous and peripheral blood were analyzed by ELISA. All the data were analyzed statistically with Wilcoxon rank sum test. Results: There were 43 patients in the DR group, among whom 25 had hyperlipidemia, 18 had normal blood lipids, 22 had a high BMI, and 21 had a normal BMI. There were 34 patients in the non-diabetic group, among whom 13 had hyperlipidemia, 21 had normal blood lipids, 17 had a high BMI, and 17 had a normal BMI. The level of SCG3 in the DR group [6.02 (4.34, 11.76) ng/ml] was higher than that in the non-diabetic group [4.30 (3.20, 10.78) ng/ml] ( Z =-2.339, P =0.019). The level of SCG3 in the hyperlipidemia subgroup of the DR patients [7.94 (5.33, 13.51) ng/ml] was higher than that in the normal blood lipid subgroup of the non-diabetic patients [4.04 (3.12, 7.77) ng/ml] ( Z =-3.473, P =0.001), and higher than that in the DR patients without hyperlipidemia [4.45 (3.71, 9.14) ng/ml] ( Z =-2.511, P =0.012). The level of SCG3 in the DR patients with a high BMI [7.12 (4.56, 13.12) ng/ml] was higher than that in the non-diabetic patients with a normal BMI [3.53 (3.16, 4.38) ng/ml] ( Z =-3.767, P =0.000). The level of SCG3 in the DR patients with a normal BMI [5.72 (4.10, 11.60) ng/ml] was higher than that in the non-diabetic patients with a normal BMI ( Z =-2.862, P = 0.004). SCG3 in the plasma was rare or can not be detected. Conclusions: The concentration of SCG3 in the vitreous increase in DR patients. However, SCG3 can not be detected in the healthy vascular system. (Chin J Ophthalmol, 2020, 56: 933-937) .

In the present study, we investigated the changes of the coagulation state, bone microthrombus, microvascular bed and bone density levels in iron accumulation rats. Meanwhile,the effect of anticoagulation therapy on bone mineral density was further investigated. We established two groups: a control (Ctrl) group and an iron intervention (FAC) group. Changes in coagulation function, peripheral blood cell counts, bone microthrombus, bone vessels and bone mineral density were compared between the two groups. We designed the non-treatment group and treatment group to study the changes of bone mineral density by preventing microthrombus formation with the anticoagulant fondaparinux. We found that the fibrinogen and D-dimer contents were significantly higher, whereas the thrombin time (TT) and prothrombin time (PT) were significantly shorter in the FAC group. After ink staining, the microvascular bed in the FAC group was significantly reduced compared with that in the Ctrl group. HE and Martius Scarlet Blue (MSB) staining showed microthrombus in the bone marrow of the iron accumulation rats. Following anticoagulation therapy, the bone microcirculation vascular bed areas in the treatment group rats were significantly increased. Furthermore, the bone mineral density was increased in the treatment group compared with that in the non-treatment group. Through experiments, we found that the blood in iron accumulation rat was relatively hypercoagulable; moreover, there was microthrombus in the bone marrow, and the bone vascular bed was reduced. Additionally, anticoagulation was helpful for improving bone microcirculation, reducing microthrombus and decreasing bone loss.

Purpose: To report the surgical outcomes of primary rhegmatogenous retinal detachment (RRD) repaired by 27-gauge pars plana vitrectomy combined with Healaflow patch and air tamponade., Methods: In an initial vitro experiment, we observed and compared the dissolution and displacement of the dispersion spots of 0.05-mL Healaflow and sodium hyaluronate. We then performed a prospective, interventional cohort study on 38 eyes in 37 consecutive patients with primary rhegmatogenous retinal detachment. All eyes underwent pars plana vitrectomy combined with Healaflow patch and air tamponade; the postoperative period did not involve prone positioning. The primary and final anatomical attachment rate, best-corrected visual acuity, and intraoperative and postoperative complications were evaluated., Results: In the in vitro experiment, the viscoelastic Healaflow remained adherent with no change in the size of the area; however, the control dissolved completely in the balance solution. The patient study included 16 women (43.2%) and 21 men (56.8%) (mean age, 59.5 ± 9.5 years; mean follow-up period, 8.9 ± 3.8 months). A single break was present in 21 (55.3%) and 2 to 5 breaks in 17 cases (44.8%). The macula was involved in 25 (65.8%) and attached in 13 cases (34.2%) intraoperatively. Initial reattachment was achieved in 37 (97.4%) and final reattachment in 38 cases (100%). In one case (2.6%), the macula redetached because of failure of the chorioretinal scar to develop around the treated break. Mean preoperative and postoperative best-corrected visual acuities were 1.02 ± 0.82 logarithm of the minimum angle of resolution (median Snellen acuity: 20/125, range: 20/20,000-20/20) and 0.23 ± 0.17 logarithm of the minimum angle of resolution (median Snellen acuity: 20/32, range: 20/100-20/20), respectively (P < 0.001). Intraocular pressure was elevated transiently in 28 eyes (73.7%). There were no other intraoperative complications or postoperative scleral incision leakage., Conclusion: A 27-gauge pars plana vitrectomy combined with Healaflow patch, and air tamponade results in a high reattachment rate in the treatment of rhegmatogenous retinal detachment. Thus, patients can benefit from early visual recovery and less complications.

Objective: To understand the characteristics of HIV-1 genotypes and drug resistance among men who have sex with men in Kunming in 2018. Methods: A total of 193 plasma samples were collected from the newly reported HIV-1 infected MSM in Kunming from January to December 2018. Viral RNA was extracted, and the gag , pol , env gene segments were amplified by nested PCR. HIV-1 genotypes and drug resistance were also analyzed. Subsequently, the evolutionary characteristics of CRF55&#95;01B and CRF68&#95;01B among MSM in Kunming were analyzed by Bayesian Markov Chain Monte Carlo method. Results: Multiple HIV-1 genotypes were identified among these 193 samples, including CRF07&#95;BC (39.4%, 76/193), CRF01&#95;AE (34.2%, 66/193), unique recombinant forms (URFs) (20.2%, 39/193), CRF08&#95;BC (3.1%, 6/193), CRF55&#95;01B (1.6%, 3/193), subtype B (1.0%, 2/193) and CRF68&#95;01B (0.5%, 1/193). Results from the Bayesian evolutionary analysis showed that CRF55&#95;01B started to spread locally after being imported from other provinces, while CRF68&#95;01B was likely to have been brought in from the eastern provinces of China. Prevalence of HIV-1 drug resistant strains was 2.6%(5/190) before antiviral treatment, with mutation rates resistant to non-nucleoside reverse transcriptase inhibitors being the highest (2.1%, 4/190) among MSM in Kunming, 2018. Conclusion: The diversity of HIV-1 was increasing among MSM in Kunming. Although the resistance rate on pretreatment drug was relatively low, the emergence of multiple resistant strains to first-line antiviral drugs posed a challenge to antiretroviral therapy, in Kunming.

Objective: To analyze the characteristics of HIV-1 molecular network in men who have sex with men (MSM) from 2016 to 2018 in Kunming, Yunnan province, explore the risk factors associated with HIV-1 transmission network and provide evidence for the effective implementation of intervention. Methods: A total of 540 samples of newly reported HIV-1 positive MSM were consecutively collected in Kunming from 2016 to 2018, the pol gene fragments were amplified by nested polymerase chain reaction (PCR). HIV-1 molecular networks were constructed according to the bootstrap value of the maximum likelihood evolutionary tree over 95% and the genetic distance less than 3%. The factors associated with the subjects entering network and network growth were further analyzed. Results: Among 459 successfully sequenced samples, seven genotypes were found, in which CRF07&#95;BC (49.2%, 226/459) and CRF01&#95;AE (40.3%, 185/459 ) were predominant. Other genotypes included URFs (4.8%, 22/459), CRF08&#95;BC (3.1%, 14/459), CRF55&#95;01B (1.7%, 8/459), B (0.7%, 3/459) and CRF68&#95;01B (0.2%, 1/459). A total of 163 sequences entered the network, with an entry rate of 35.5%(163/459), forming 56 clusters with the number of individuals in the cluster was between 2 and 13. The analysis of the factors associated with entering network showed that the MSM who married and had multiple homosexual partners were more likely to be found in HIV-1 molecular networks. Multivariate logistic regression analysis showed that the number of sexual partners was the factor for the growth of HIV-1 molecular network. According to the criteria for the emergence of three or more newly reported cases in every year, six transmission clusters were judged as active transmission clusters, in which MSM who were not Kunming natives, had sexually transmitted diseases (STD), were divorced and students were the key targets of intervention. Conclusions: HIV-1 genotypes in MSM in Kunming were becoming complex, the risk factors associated with transmission networks in MSM in Kunming included being married and having multiple partners, the intervention targets in active transmission clusters included MSM who were not Kunming natives, had STD, were divorced and students. This study provided the basis for applying HIV-1 molecular networks to real-time intervention in this population.

Discoid lupus erythematosus (DLE) is a chronic autoimmune skin disease that usually causes disfiguring scarring, dyspigmentation, and atrophy. Despite a range of available topical and systemic therapies, the treatment of DLE remains a therapeutic challenge, especially in some refractory cases. Here, we reported three male patients with long-term chronic lesions of unilateral facial localized DLE, who failed to have their disease controlled with many previous topical/systemic treatments, showed rapid and well response to intralesional injections of betamethasone (2 mg/mL, 0.2 mL/site) monotherapy once every 2 weeks for two, two, and four times of treatment, respectively. Intralesional betamethasone may provide a safe and effective alternative in the management of refractory localized DLE skin lesions., (© 2020 Wiley Periodicals LLC.)

Deficiency of endothelial progenitor cells, including endothelial colony-forming cells (ECFCs) and circulating angiogenic cells (CACs), plays an important role in retinal vascular degeneration in diabetic retinopathy (DR). Fenofibrate, an agonist of peroxisome proliferator-activated receptor α (PPARα), has shown therapeutic effects on DR in both patients and diabetic animal models. However, the function of PPARα in ECFC/CACs has not been defined. In this study, we determined the regulation of ECFC/CAC by PPARα. As shown by flow cytometry and Seahorse analysis, ECFC/CAC numbers and mitochondrial function were decreased in the bone marrow, circulation, and retina of db/db mice, correlating with PPARα downregulation. Activation of PPARα by fenofibrate normalized ECFC/CAC numbers and mitochondrial function in diabetes. In contrast, PPARα knockout exacerbated ECFC/CAC number decreases and mitochondrial dysfunction in diabetic mice. Primary ECFCs from PPARα -/- mice displayed impaired proliferation, migration, and tube formation. Furthermore, PPARα -/- ECFCs showed reduced mitochondrial oxidation and glycolysis compared with wild type, correlating with decreases of Akt phosphorylation and expression of its downstream genes regulating ECFC fate and metabolism. These findings suggest that PPARα is an endogenous regulator of ECFC/CAC metabolism and cell fate. Diabetes-induced downregulation of PPARα contributes to ECFC/CAC deficiency and retinal vascular degeneration in DR., (© 2019 by the American Diabetes Association.)

The local corrosion behavior and mechanism of Ni-P coatings in a 3.5 wt% sodium chloride solution with different flow speeds (0 m s -1 , 0.5 m s -1 , 1 m s -1 ) were investigated through a wire beam electrode (WBE) with morphological, elemental and electrochemical analyses as well as numerical simulations. It was found that the microstructure of the Ni-P coating was in the shape of broccoli and possessed satisfactory compactness and uniformity. The numerical simulations showed that the speed increased and the static pressure decreased at the local area. Combined with WBE, it was found that the average corrosion potential decreased at that area. The results indicated that the corrosion tendency and corrosion rate of the Ni-P coating were larger at higher speeds, and the corrosion resistance could be improved by the electroless Ni-P coating. WBE was helpful in revealing the local electrochemical information of the Ni-P coating., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To identify differentially expressed proteins between the patients with proliferative diabetic retinopathy (PDR) and vitreous floaters, and explore treatment target for PDR based on isobaric tags for relative and absolute quantification (iTRAQ) LC-MS/MS Proteomics. Method: Vitreous samples were collected from 28 eyes of patients with PDR and 4 eyes with vitreous floaters, which served as controls. For quantitative proteomics, vitreous samples were combined and proteins extracted and labeled with iTRAQ peptide-tagging reagents. Samples were fractionated by liquid chromatography (LC), analyzed by tandem mass spectrometry (MS/MS) and Gene Ontology (GO) analyses performed on differentially expressed proteins identified in the PDR samples. Results: In the PDR vitreous, 26 proteins were identified that were differentially expressed when compared to the controls. Of these, 7 showed a significant increase ( P< 0.05) and 19 a significant decrease ( P< 0.05)in expression in PDR patients. These included some high abundance proteins including Retinoic acid receptor reactive protein 2 (PDR 1=85.0, PDR 2=83.0, Control 1=119.6, Control 2=120.2, FC=0.710, P= 0.001), Semaphorin-4B(PDR 1=64.4, PDR 2=68.8, Control 1=135.4, Control 2=146.0, FC=0.473, P= 0.023), Apolipoprotein B (PDR 1=104.4, PDR 2=106.6, Control 1=89.0, Control 2=85.3, FC=1.211, P= 0.024), and Heat shock protein 70 (PDR 1=69.3, PDR 2=75.0, Control 1=137.7, Control 2=138.3, FC=0.523, P= 0.026), which are closely related to the pathological mechanism of PDR. GO analysis clustered the differentially expressed genes into three major functional domains: Biological Processes, Molecular Function and Cellular Component. Differential gene expression was found in the categories of cellular metabolism, organonitrogen compound and carbohydrate derivative metabolic processes, transferase activity and transmembrane signaling receptor activity. KEGG Pathway analysis indicate that Chemerin signaling through Akt, Sema4B signaling via PI3K, and HIF-1α signal pathways were all altered in the PDR samples. Conclusions: In this study we identified variations in expression of genes extensively involved in key biological processes in the retina including neovascularization, cellular metabolism and transmembrane signaling, which provide new insights into the pathophysiology of PDR. Extracellular matrix was degraded and endothelial cell migration was induced by Chemerin, in addition, the destruction of blood-retinal barrier and neuronal apoptosis were induced by ApoB. Chemerin and ApoB accelerated the development of PDR. Sema 4B participated in vascular protection, HSP70 conducted anti-apoptosis. These two cytokines protected the retinal neurovascular in PDR patients. Therefore, Chemerin, Sema 4B, ApoB and HSP70 may be the treatment target for PDR. (Chin J Ophthalmol, 2019, 55:769-776) .

A new method was developed to determine the nanoparticulate and ionic silver (Ag) species in bacteria ( Escherichia coli , E. coli ). By removal of the cell wall with lysozyme, the cell surface-adsorbed Ag species were separated from the intracellular Ag species, which were extracted by tetramethylammonium hydroxide and determined by size-exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICP-MS). The detection limit is 3 ng/10 7 CFU/mL (where CFU is colony-forming unit) for both silver nanoparticles (AgNPs) and ionic Ag(I) species. The cell wall-adsorbed Ag was calculated by subtracting the contents of the intra- and extracellular Ag from the total exposure dose of Ag, and therefore the biodistribution of Ag species was profiled. We then applied this strategy to quantitatively analyze extra- and intracellular Ag species in E. coli after respective exposure to Ag + and 10 and 30 nm AgNPs at different effective concentrations (EC 10 , EC 50 , and EC 90 ). Results showed that the intracellular and cell wall-bound Ag account for 5.98-15.21% and 25.13-64.43% of the exposed dose, respectively, and AgNPs could transform into complexed or free Ag + . Our method opens new avenues for the quantitative analysis of the uptake and biodistribution of nanoparticles and their transformation species in bacteria.

Endothelial progenitor cells (EPCs) contribute to blood vessel formation. Canonical Wnt signaling plays an important role in physiological and pathological angiogenesis and EPC fate regulation. However, the mechanism for Wnt signaling to regulate EPC fate in neovascularization (NV) has not been clearly defined. Here, we showed that very low-density lipoprotein receptor knockout (Vldlr -/- ) mice, a model of ocular NV induced by Wnt signaling overactivation, have increased EPC numbers in the bone marrow, blood, and retina, as well as an elevated mitochondrial membrane potential indicating higher mitochondrial function of EPCs in the circulation. Isolated EPCs from Vldlr -/- mice showed overactivated Wnt signaling, correlating with increased mitochondrial function, mass, and DNA copy numbers, compared with WT EPCs. Our results also demonstrated that Wnt signaling upregulated mitochondrial biogenesis and function, while inhibiting glycolysis in EPCs, which further decreased EPC stemness and promoted EPCs to a more active state toward differentiation, which may contribute to pathologic vascular formation. Fenofibric acid, an active metabolite of fenofibrate, inhibited Wnt signaling and mitochondrial function in EPCs and decreased EPC numbers in Vldlr -/- mice. It also decreased mitochondrial biogenesis and reactive oxygen species production in Vldlr -/- EPCs, which may be responsible for its therapeutic effect on diabetic retinopathy. These findings demonstrated that Wnt signaling regulates EPC fate through metabolism, suggesting potential application of the EPC metabolic profile as predictor and therapeutic target for neovascular diseases. Stem Cells 2019;37:1331-1343., (©2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019.)

Objective: To analyze the difference among expression of aqueous humor proteins in acute primary angle-closure glaucoma (APACG). Methods: Case-control study. The patients with APACG combined cataract (APACG with cataract group) and patients with cataract (cataract group), who had undertaken surgical treatment at the Tianjin Medical University Eye Hospital from October 2016 to June2017 were collected. Upon receipt of patient's consent, 50 μl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access during the surgery, and then injected into a sterile collection tube to be stored at -80 ℃. Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry. The differential significance test was performed by Maxquant significances A approach. The differential proteins of the two groups were screened and determined with the conditions of P< 0.05 and difference multiple>2. The functions and signal pathway of differential proteins in aqueous humor were annotated in biological big data, on the basis gene ontology (GO) and the Kyoto gene and genomic encyclopedia (KEGG) analyses. Results: There were 3 males and 7 females with an average age of (68±6) years in the APACG group. The cataract group included 2 males and 8 females with an average age of (71±8) years. There were no statistical differences in gender ratio and age between the two groups (both P> 0.05). A total of 91 differential proteins were detected in this experiment, including 50 up-regulated proteins (annexinA1, vimentin, S100 calcium binding protein A8, interleukin 6, C reactive protein, laminin β2, etc.) and 41 down-regulated (keratin 85, γ-crystallin D, syntaxin-binding protein 5, semaphoring 4B, matrilin 2, cathepsin O, cadherin 4, semaphoring 3B, platelet-derived growth factor D, transforming growth factor β, etc.). On one hand, the functions of differential proteins involved in many aspects. AnnexinA1, CD163, S100 calcium-binding protein A8, C reactive protein, interleukin 6 are involved in the inflammatory reaction, cadherin 4 and laminin β2 regulate cell adhesion, matrilin 2, vimentin and laminin β2 participate in tissue fibrosis; on the other hand, KEGG analysis showed that the differential proteins participate diverse signaling pathways such as phosphatidylinositol-3-kinase-protein kinase B signaling pathway, transformation growth factor β signaling pathway, mitogen activated protein kinase signaling pathway, Toll-like receptor signaling pathway, the nuclear factor κ-light chain enhancer of the activated B cells signaling pathway, focal adhension and extracellular matrix receptor interaction pathway and so on. Conclusions: The expression of annexin A1 is significantly up-regulated in the aqueous humor in APACG, while some other factors such as transformation growth factor β, cadherin-4, and matrilin 2 are down-regulated. The change of proteins in aqueous humor is related with the outbreak of APACG. (Chin J Ophthalmol, 2019, 55: 687-694) .

To track transformations of silver nanoparticles (AgNPs) in vivo, HepG2 and A549 cells were cocultured with two enriched stable Ag isotopes ( 107 AgNPs and 109 AgNO 3 ) at nontoxic doses. After enzymatic digestion, 107 AgNPs, ionic 107 Ag + and 109 Ag + in exposed cells could be separated and quantified by liquid chromatography combined with ICP-MS. We found that ratios of 107 Ag + to total 107 Ag and proportions of 107 Ag + / 109 Ag + in cells increased gradually after exposure, proving that the Trojan-horse mechanism occurred, i.e., AgNPs released high contents of Ag + after internalization. While the presence of 109 Ag + (5 and 100 μg/L) has little influence on the uptake of 107 AgNPs (0.1 and 2 mg/L), the presence of 107 AgNPs at a high dose (2 mg/L) dramatically increases the ingestion of 109 Ag + , even though 107 AgNPs at a low dose (100 μg/L) showed negligible effects on the internalization of 109 Ag + . Cellular homeostasis may be perturbed under sublethal exposure of 107 AgNPs, and thus enhanced uptake of 109 Ag + . Our findings suggest that the widely adopted control experiments in toxicology studies, culturing organisms with AgNO 3 at the same concentration of Ag + in the AgNP exposure medium, may underestimate uptake of Ag + and thus cannot exclude suspected toxic effects of Ag + at high AgNP exposure doses.

Background: Invasive plants commonly occupy diverse habitats and thus must adapt to changing environmental pressures through altering their traits and economics spectra, and addressing these patterns and their drivers has an importantly ecological and/or evolutionary significance. However, few studies have considered the role of multiple biotic and abiotic factors in shaping trait variation and spectra. In this study, we determined seven leaf traits of 66 Solidago canadensis populations, and quantified the relative contributions of climate, soil properties, native plant diversity, and S. canadensis-community interactions (in total 16 factors) to leaf trait variation and spectrum with multimodel inference., Results: Overall, the seven leaf traits had high phenotypic variation, and this variation was highest for leaf dry matter content and lowest for leaf carbon concentration. The per capita contribution of climate to the mean leaf trait variation was highest (7.5%), followed by soil properties (6.2%), S. canadensis-community interactions (6.1%), and native plant diversity (5.4%); the dominant factors underlying trait variation varied with leaf traits. Leaf production potential was negatively associated with leaf stress-tolerance potential, and the relative contributions to this trade-off followed in order: native plant diversity (7.7%), climate (6.9%), S. canadensis-community interactions (6.2%), and soil properties (5.6%). Climate, diversity, soil, and interactions had positive, neutral or negative effects., Conclusions: Climate, soil, diversity, and interactions contribute differentially to the leaf trait variation and economics spectrum of S. canadensis, and their relative importance and directions depend on plant functional traits.

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ 2 =4.968, P =0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate ( P <0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% ( RR =3.433, 95% CI 1.333-8.844, P =0.011) and not bridge to HSCT ( RR =4.996, 95% CI 1.852-13.474, P =0.001) were the independent risk factors. Conclusion: The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

The purpose of this study was to explore the role of microRNA-451a (miR-451a) in diabetic retinopathy through activating transcription factor 2 (ATF2). The epiretinal membrane samples from patients with proliferative diabetic retinopathy (PDR) were immunolabeled with an antibody for Ki-67 to identify the proliferative cells. The expression of miR-451a was measured by qRT-PCR in the retina of Akita mice and in RPE cells under diabetic conditions. The potential downstream targets of miR-451a were predicted by bioinformatics and confirmed by dual luciferase assay, qRT-PCR, and Western blotting. Mitochondrial function, cell proliferation, and migration assays were used to detect the functional change after transfection of miR-451a mimic and inhibitor. Proliferative RPE cells were identified in the epiretinal membrane from PDR patients. The expression of miR-451a was downregulated both in the retina of Akita mice and 4-hydroxynonenal (4-HNE)-treated RPE cells. Bioinformatic analysis and luciferase assay identified ATF2 as a potential target of miR-451a. miR-451a inhibited proliferation and migration of RPE cells. The mitochondrial function was enhanced by miR-451a mimic, but suppressed by miR-451a inhibitor. In diabetic conditions, miR-451a showed a protective effect on mitochondrial function. The results of qRT-PCR and Western blotting revealed that overexpression of miR-451a downregulated the expression of ATF2 and its downstream target genes CyclinA1, CyclinD1, and MMP2. In conclusion, miR-451a/ATF2 plays a vital role in the regulation of proliferation and migration in RPE cells through regulation of mitochondrial function, which may provide new perspectives for developing effective therapies for PDR.

Diabetic retinopathy (DR) is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor (CTGF) is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.

Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08&#95;BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01&#95;AE (15.8%), CRF07&#95;BC (14.4%), subtype C (2.7%), CRF55&#95;01B (0.7%), subtype B (0.3%) and CRF64&#95;BC (0.3%). CRF08&#95;BC and CRF01&#95;AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08&#95;BC, URFs, CRF01&#95;AE and CRF07&#95;BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01&#95;AE, CRF07&#95;BC and CRF08&#95;BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01&#95;AE and CRF07&#95;BC increased exponentially during 1991-1999 and 1994-1999, respectively. The EPS for CRF08&#95;BC underwent two exponential growth phases in 1994-1998 and 2001-2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

Objectives: Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed., Methods: Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot., Results: The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression., Conclusions: The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.

Objective: This study was to observe the effect of SMP-30 on ultraviolet B (UVB)-induced apoptosis of human lens epithelial cells(HLE-B3) in vitro . Methods: Experimental study. The SMP-30 cDNA was amplified by PCR and inserted into the pRFP-N1 expressing vector which had been double digested by XhoI/HindIII. HLE-B3 cells were cultured and divided into three groups: normal group, pRFP-N1 vector plasmid group and pRFP-N1-SMP-30 plasmid group (SMP-30). Then cells were exposed to UVB and the survival rate of cells was detected by MTT assay. The effects of SMP-30 on UVB-induced HLE-B3 apoptosis were measured by the Cell Death Detection ELISA kit. Meanwhile, the influence of SMP-30 on UVB-induced apoptosis-relative protein expression in HLE-B3 cells was tested by Western blots. Moreover, 2', 7'-Dichlorofluorescin diacetate staining was performed to monitor the protective effects of SMP-30 on UVB-induced HLE-B3 reactive oxygen species(ROS). One-way analysis of variance combined with Dunnett's statistical method were performed to analyze the data. Results: The full length of PSF cDNA fragment was correctly inserted into the pRFP-N1 vector, which was confirmed by DNA sequencing. The SMP-30 fragment was inserted to the plasmid pRFP-N1 correctly, which was also confirmed by DNA sequencing. The PRFP-N1-SMP-30 plasmid was transfected into HLE-B3 successfully. SMP-30 expression was up-regulated in the transfection group, compared with the control group. Data showed that the survival rate of HLE-B3 after the pRFP-N1-SMP-30 plasmid transfection was 0.90±0.14, while the apoptosis rate was 0.43±0.06 and the ROS production was 0.52±0.02, showing significant difference in comparison with the vector plasmid group and the normal group( t= 5.830, 9.934, 12.19, P< 0.05). In the meantime, SMP-30 overexpression down-regulated the levels of Bax and cleav-caspase-3, but up-regulated the Bcl-2 and Pro-caspase-3 expression levels under UVB irradiation. Conclusion: SMP-30 overexpression plays a protective role in UVB-induced apoptosis via regulating the expression of apoptosis-related proteins and inhibiting the production of ROS in HLE-B3 cells. (Chin J Ophthalmol, 2017, 53: 835-841) .

In order to study the influence of dust events on the airborne microbes in atmospheric bioaerosols, bioaerosol samples were continuously collected from March to April 2015 during two dust events using size-fractionated bioaerosol samplers in Lanzhou and Qingdao. The concentration of airborne microbes were measured using an epifluorescence microscope after staining with DAPI (4',6-diamidino-2-phenylindole). The results showed that the concentration of airborne microbes increased significantly during the period of dust ( P <0.05). The average concentrations of airborne microbes on sunny days were 5.61×10 5 cells·m -3 and 2.08×10 5 cells·m -3 in Lanzhou and Qingdao, respectively, whereas the mean concentrations on dusty days were 14.8 times and 6.42 times those on sunny days, respectively. The concentration of airborne microbes presented a bimodal size distribution on sunny days in Lanzhou and Qingdao, with a peak at>7.0 μm and the lowest values ranging from 4.7 μm to 7.0 μm. However, the second peak appeared at 3.3-4.7 μm and 1.1-2.1 μm in Lanzhou and Qingdao, respectively. The size distribution of airborne microbes changed during the dust period. The size distribution of microbes still presented a bimodal distribution in Lanzhou; however, one peak shifted from>7.0 μm to 1.1-2.1 μm. The size distribution in Qingdao changed from a bimodal distribution to a skewed distribution with the predominant fraction in coarse mode. The background values of microbial load in PM 10 before the dust were 2224 cells·μg -1 and 1550 cells·μg -1 in Lanzhou and Qingdao, respectively, and the highest value of such increased significantly to 26442 cells·μg -1 and 10250 cells·μg -1 during the dust events, respectively. This demonstrated that the high concentration of microbes in the dust events resulted not only from increased atmospheric particles but also from dust source and transportation path along with long-range transported dust particles.

The existing acoustic emission (AE) source location methods assume that acoustic waves propagate along straight lines, and the source location is determined by average wave velocity. Because of the heterogeneity of materials, location results often fail to meet the accuracy requirement. For this reason, an AE source location method considering refraction in different media was proposed in this paper. According to sensor coordinates, the arrival time of acoustic waves, the velocities of acoustic waves in two kinds of media, the space-time relation equations of the AE source point and the measuring point were established by the precise coordinates of the AE source based on Snell's law. The feasibility of the algorithm was verified by experiments, and the factors influencing location accuracy were also analysed. The results show that the algorithm proposed in this paper is applicable for both the same medium and different media, and the accuracy of localization is not affected by the ratio of wave velocities in two media or the distance from the AE source to the refraction surface.

To improve the phase-shifting accuracy, this paper presents a novel integrated framework for design, control and experimental validation of the piezoelectric actuated phase shifter with a trade-off between accuracy and cost. The piezoelectric actuators with built-in sensors are adopted to drive the double parallel four-bar linkage flexure hinge-based mechanisms. Three mechanisms form the tripod structure of the assembled phase shifter. Then, a semi-closed loop controller with inner feedback and outer feedforward loops via the external laser interferometer is developed for accurate positioning of the phase shifter. Finally, experiments related with travel range, step response, linearity and repeatability are carried out. The linearity error is 0.21% and the repeatability error of 10 μ m displacement is 3 nm. The results clearly demonstrate the good performance of the developed phase shifter and the feasibility of the proposed integrated framework.