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Abstract Background The initial clinical symptoms of severe fever with thrombocytopenia syndrome (SFTS) mainly include high fever, thrombocytopenia and gastrointestinal symptoms, and severe patients may suffer from severe complications such as multiple organ failure, which can lead to death. Studies have shown that central nervous system symptoms are associated with severe adverse outcomes of SFTS, but there are few reports on confirmed cases of SFTS encephalitis. This is a special case in which her initial SFTS symptoms were atypical, while the disease deteriorated rapidly after the appearance of encephalitis. The purpose of this study was to report the clinical and epidemiological features of this case, isolate and trace the SFTS virus (SFTSV) strain, identify the genotype of the strain, and speculate on the infection route to provide an important reference for the diagnosis and control of SFTSV. Methods Cerebrospinal fluid and serum samples were collected, multipathogen detection was performed via next-generation sequencing (NGS), and SFTSV virus isolation was performed via inoculation of the samples with Vero cells. The serum of key populations closed to patients, parasitic ticks on the surface of domestic animal bodies and environmentally free ticks were collected for SFTSV monitoring. The whole genomes of the virus strains and positive nucleic acid samples were sequenced and compared with the GenBank reference sequence to construct a phylogenetic analysis tree. Results This patient was diagnosed with SFTSV encephalitis, and the viral strain was successfully isolated. The SFTSV strain is closely related to the Hubei strain HB2017-02, and the SFTSV M and L fragments belong to the B genotype, whereas the M fragments belong to the F genotype. In addition, the similarities of coding sequences of case strain to those of tick-carried SFTSV strain in the residence were more than 99.9%. Conclusions The patient was confirmed to have SFTSV-infected encephalitis and died rapidly. The SFTSV strain was of Chinese local origin, and tick bites were the most likely route of infection.

In the last 40 years, there has been a notable rise in the occurrence of diabetes within China, leading to the country now having the highest number of individuals affected by this condition globally. This prospective observational study examined the effect of different baseline relative leukocyte telomere length (RTL) and the combined effect of baseline RTL and plasma phospholipid fatty acid (PPFA) on the risk of developing diabetes. Adults from Ningxia Province who underwent baseline and follow-up surveys were included in the study. The correlation between the baseline RTL and PPFA was investigated using a multiple linear regression model. The combined effects of baseline RTL and PPFA levels on the risk of developing type 2 diabetes mellitus (T2DM) were investigated using a Cox regression model with time as the covariate. A total of 1461 study subjects were included in this study. According to the diagnostic criteria of the Chinese Diabetes Society, 141 subjects developed T2DM during the follow-up period. The baseline age was negatively correlated with RTL. After adjustment for age, C16:0, C18:1 n-9, C20:4 n-6, C20:3 n-3, and monounsaturated fatty acid (MUFA) concentrations were negatively correlated with RTL. Multiple linear regression analysis showed that C16:0 and MUFA concentrations influenced RTL. Subjects with shorter RTL at baseline had a higher risk of developing diabetes than those with longer RTL. Subjects with shorter RTL and higher C16:0 and MUFA concentrations at baseline had a higher risk of developing T2DM than those with longer RTL and lower C16:0 and MUFA concentrations. Our findings indicated that PPFA affects changes in RTL. In addition, RTL and PPFA are associated with the occurrence of T2DM.

Lupus nephritis (LN) is a chronic complication of systemic lupus erythematosus (SLE). At present, no drugs are capable of delaying the progression of LN without a risk of serious side effects. There is thus a pressing need for further studies of LN pathogenesis to identify novel therapeutic targets and aid in the development of new approaches to treating this debilitating disease. In this study, a multi-omics approach was used to characterize the pathogenesis of LN and to identify disease-related targets, ultimately leading to the identification and validation of Yin Yang 1 (YY1) as a promising therapeutic target in LN. A rapid approach to efficiently screening for candidate YY1 ligands was implemented using drug databases that established rebamipide as a YY1 antagonist suitable for use in the management of LN. Specifically, the YY1 antagonist activity of rebamipide was found to regulate lymphocyte activity, reduce autoantibody production, limit immune complex deposition, and suppress macrophage activation while improving symptoms in a murine model of LN. Results supportive of a similar pathologic mechanism of action were also obtained when analyzing renal tissue sections from LN patients, underscoring the potential clinical significance of YY1 and its antagonist rebamipide, suggesting that rebamipide may have positive effects on lymphocytes and may improve symptoms in treated patients. This study provides a robust foundation for further research focused on the pathogenesis and treatment of LN.

IntroductionSARS-CoV-2 infection drove senescent cells and the senescence-associated phenotypes were reported playing roles in disease progression, which contributes to severe COVID-19 and related sequelae. Cdc42 is involved in the regulation of cellular senescence. This study, aimed to investigate the mechanism of the SARS-CoV-2 spike protein regulating cellular senescence through Cdc42.MethodsK18-hACE2 mice were infected with SARS-CoV-2 Omicron BA.4 or stimulated with spike protein through the airway, the senescent cells and Cdc42 expression in lung tissue were detected. Overexpression of spike protein or exogenous incubation of spike protein was used to simulate the induction of cellular senescence by spike protein. Mechanistic insights into the role of Cdc42 were mainly explored using Western Blot and qRT-PCR.ResultsSpike protein, SARS-CoV-2 infection related, accelerates cell aging by upregulating Cdc42 expression, which furtherly activated the Wnt/β-catenin signaling pathway. Conversely, treatment with ML141 in animal models, a Cdc42 inhibitor, reduced cellular senescence and ameliorated lung injury and inflammation. These results suggest that the upregulation of Cdc42 by the SARS-CoV-2 spike protein induces cellular senescence and enhances β-catenin nuclear translocation.DiscussionThis study provides insights into the mechanisms underlying cellular senescence induced by the SARS-CoV-2 spike protein, offering potential strategies to mitigate the inflammatory response and complications associated with COVID-19 in both the acute and long-term phases.

Abstract Background Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length. Methods The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for β-Cell Function (HOMA-β), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL. Results The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-β, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-β, ΔQUICKI, and ΔLEP do not affect ΔRLTL. Conclusions Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.

Abstract Background Higher intakes of dietary antioxidants have been linked to a lower type 2 diabetes mellitus (T2DM) risk. However, few studies have comprehensively examined the overall dietary antioxidant capacity, assessed by dietary antioxidant quality scores (DAQS) and dietary total antioxidant capacity (DTAC), related to T2DM risk, especially in populations consuming relatively monotonous diets. This study aimed to evaluate the associations of DAQS, DTAC, and T2DM among rural Chinese adults. Methods Data from 12,467 participants from the Natural Population Cohort of Northwest China: Ningxia Project was analyzed. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. DAQS were calculated based on vitamins A, C, and E, zinc (Zn), and selenium (Se) intake. DTAC was estimated using the ferric-reducing ability of plasma assay. Logistic regression models were used to evaluate the associations of DAQS and DTAC with T2DM risk. Restricted cubic splines were used to assess potential non-linear relationships between DTAC and T2DM. Results T2DM was observed in 1,238 (9.9%) participants. After adjusting for confounders, compared to the lowest tertiles (T1) of DAQS, the odds ratios (ORs) for T2DM were 1.03 (95% CI 0.82–1.30) in T2 and 0.85 (95% CI 0.68–1.06) in T3 (P = 0.010). Compared to T1, the ORs for T2DM in the highest T3 were 0.78 (95% CI 0.67–0.91, P-trend = 0.008) for vitamin A, 1.34 (95% CI 1.15–1.56, P-trend

Abstract Background Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients. Methods In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN. Results Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo. Conclusion In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.

Abstract Malnutrition is a prevalent and severe issue in hospitalized patients with chronic diseases. However, malnutrition screening is often overlooked or inaccurate due to lack of awareness and experience among health care providers. This study aimed to develop and validate a novel digital smartphone‐based self‐administered tool that uses facial features, especially the ocular area, as indicators of malnutrition in inpatient patients with chronic diseases. Facial photographs and malnutrition screening scales were collected from 619 patients in four different hospitals. A machine learning model based on back propagation neural network was trained, validated, and tested using these data. The model showed a significant correlation (p

Abstract Background Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. Method Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. Result The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. Conclusion Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health. Graphical Abstract

Abstract Background and aims Leukocyte telomere length (LTL) as a ‘biological clock’ of aging is closely related to human health, its association with an aging-related disease, dyslipidemia, has been less studied and mainly focused on cross-sectional investigations. Methods Two rounds of information and blood collections were conducted on a cohort of 1624 individuals residing in rural Ningxia, located in northwest China, with an average time gap of 9.8 years. The relative telomere length (RTL) of peripheral blood leukocytes was assessed using real-time quantitative PCR. To investigate the association between dyslipidemia, blood lipid levels, and alterations in RTL, multiple linear regression and generalized linear models were employed. Results After conducting the follow-up analysis, it was observed that 83.3% of the participants in the study exhibited a reduction in telomere length, while 16.7% experienced an increase in telomere length. The results suggested that dyslipidemia at baseline or follow-up may increase longitudinal changes in telomere length, but it was more significant in the healthy group, especially in those aged ≥ 60 years. Furthermore, HDL-C levels in baseline and follow-up were found to be associated with longitudinal changes in telomere length, and lower HDL-C levels may be associated with increased longitudinal changes in telomere length. Conclusions The change in telomere length is correlated with dyslipidemia and its lipid indicators especially HDL-C. Persistent dyslipidemia and a reduction in HDL-C levels may be associated with elevated longitudinal fluctuations in telomere length.

In the mechanized harvesting of Lycium barbarum L. (L. barbarum), there are prominent problems such as low harvesting efficiency, high damage rate, incomplete separation of leaves and delayed transportation. Therefore, an integrated L. barbarum harvester was designed and developed in this study, which has the functions of picking, undertaking, transportation, winnowing and collection. The design requirements and constraints were identified by cultivation agronomy. Through simulation and physical tests, the tarpaulin was determined as the undertaking material. This machine achieved efficient picking with a vibrating picker with a multi-degree-of-freedom picking arm. The two-stage conveyor belts and the intermediate receiving plate were designed for low loss transportation of fruit. The axial flow fan and secondary buffer device were used to realize winnowing and reduce the damage rate. Through the three-factor and three-level orthogonal test, an optimal working parameter combination was determined: the vibration frequency of the picker was 20 Hz, the conveyor speed was 4 m/min, the airflow speed of the fan was 7 m/s. A field test was conducted under these parameters, and the results showed that the harvesting efficiency was about five times that of manual harvesting. The integrated L. barbarum harvester basically met the harvesting requirements and provided a new scheme for mechanized harvesting.

The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl− channel, is closely associated with multiple pathogen infections, such as SARS-CoV-2. However, whether the function of the CFTR is involved in herpes simplex virus (HSV) infection has not been reported. To evaluate the association of CFTR activity with HSV infection, the antiviral effect of CFTR inhibitors in epithelial cells and HSV-infected mice was tested in this study. The data showed that treatment with CFTR inhibitors in different concentrations, Glyh-101 (5–20 μM), CFTRi-172 (5–20 μM) and IOWH-032 (5–20 μM), or the gene silence of the CFTR could suppress herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) replication in human HaCaT keratinocytes cells, and that a CFTR inhibitor, Glyh-101 (10–20 μM), protected mice from HSV-1 and HSV-2 infection. Intracellular Cl− concentration ([Cl−]i) was decreased after HSV infection via the activation of adenylyl cyclase (AC)-cAMP signaling pathways. CFTR inhibitors (20 μM) increased the reduced [Cl−]i caused by HSV infection in host epithelial cells. Additionally, CFTR inhibitors reduced the activity and phosphorylation of SGK1 in infected cells and tissues (from the eye and vagina). Our study found that CFTR inhibitors can effectively suppress HSV-1 and HSV-2 infection, revealing a previously unknown role of CFTR inhibitors in HSV infection and suggesting new perspectives on the mechanisms governing HSV infection in host epithelial cells, as well as leading to potential novel treatments.

Abstract Systemic lupus erythematosus (SLE) is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family and is associated with vascular-related damages. To date, association between ET-1 and pathogenesis of SLE remains unclear. This case–control study was carried out by 314 SLE, 252 non-SLE diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with Kompetitive Allele-Specific PCR. SLE patients had high levels of ET-1, which were correlated with some clinical, laboratory features. Serum CCN3, IL-28B levels were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to SLE patients with alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with SLE patients with pericarditis, pyuria and fever manifestation, respectively. Rs3087459 (CC) and rs9369217 (TC) were related to SLE patients with positive anti-SSB antibody. Rs5369 (AA) was associated with IgG and CRP levels in SLE patients. In conclusion, elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were related to SLE susceptibility.

Abstract Background Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together. Methods Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer. Bivariate logistic regression and multiplicative interaction analyses were used to assess the impact of estradiol level and vitamin D status on low SMM, as well as the combined impact of estradiol and low vitamin D status on low SMM. Results A total of 287 (9.49%) participants had low SMM, which had lower levels of estradiol and vitamin D concentration than normal SMM group. While, after adjusting the confounding variables, these correlations were maintained in estradiol Q1, Q2, Q3 and vitamin D Q1. Furthermore, the significant combined effect of the highest quartile of estradiol concentrations and non-vitamin D deficiency, and interactions between vitamin D Q1 and estradiol Q2, vitamin D Q1 and estradiol Q3, vitamin D Q2 and estradiol Q1, vitamin D Q3 and estradiol Q3 on low SMM were stably reflected (P for interaction

Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01–1.03), 1.04 (1.02–1.06), and 1.02 (1.00–1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05–1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01–1.03), 1.33 (1.18–1.50), and 1.07 (1.03–1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females.

Abstract The authors conducted an observational study to explore the association between body fat composition and the risk of hyperhomocysteinemia (HHcy) and their combined effect on the risk of developing cardiovascular disease (CVD). Adults aged 18–74 years from the Northwest China Natural Population Cohort: Ningxia Project (CNC‐NX) were recruited in this study. Association between body fat composition and HHcy was evaluated by logistic regression model. Restricted cubic spline was used to find nonlinear association. The impact of the interaction between HHcy and body fat composition on CVD was evaluated using the addition interaction model and mediation effect model. In total, 16 419 participants were included in this research. Body fat percentage, visceral fat level, and abdominal fat thickness were positively associated with overall HHcy (p for trend

Abstract To investigate the associations of composite dietary antioxidant index (CDAI) with risk of cardiovascular disease (CVD) mortality among individuals with type 2 diabetes (T2D). This prospective cohort study included 7551 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2018. Death statistics were gathered by connecting the cohort database to the National Death Index through December 31, 2019. Multivariable Cox proportional hazards regression models were utilized to calculate hazard ratios and 95% CIs for the relationship of CDAI with risks of CVD and all-cause mortality. Three multivariable models were built. Restricted cubic spline analyses were utilized to explore the nonlinear association of CDAI with CVD mortality, and nonlinearity was tested by the likelihood ratio test. This cohort study included data from 7551 participants with T2D (mean [SE] age, 61.4 (0.2) years; 3811 male [weighted, 50.5%] and 3740 female [weighted, 49.5%]; median CDAI level, − 2.19 [IQR, − 2.19 ~ − 0.22]). A total of 2227 all-cause deaths and 746 CVD deaths were identified during an average of 98 months of follow-up. Nonlinear associations were observed for CDAI (P

Abstract Electrochromic (EC) materials for smart windows must exhibit a dark colour and block visible light (wavelength = 380–780 nm) to reduce environmental impact. In particular, black tones are also desired, and there are many reports of attempts to create these dark tones using organic materials such as polymers. However, their fabrication methods are complicated, expensive, and may even use hazardous substances; moreover, they are often not sufficiently durable, such as upon exposure to ultraviolet light. There are some reported cases of black materials using the CuO system as an inorganic material, but the synthesis method was complicated and the functionality was not stable. We have found a method to synthesize CuO nanoparticles by simply heating basic copper carbonate and adjusting the pH with citric acid to easily obtain a suspension. The formation and functionality of CuO thin films were also demonstrated using the developed suspension. This research will enable the creation of EC smart windows using existing inorganic materials and methods, such as printing technology, and is the first step towards developing environment-friendly, cost-effective, and functional dark inorganic materials.

Cardiovascular risk models developed may have limitations when applied to rural Chinese. This study validated and compared the Framingham Risk Score (FRS) and Prediction for Atherosclerotic Cardiovascular Disease Risk in China (PAR) models in predicting 10-year risk of coronary heart disease (CHD) in a rural cohort in Ningxia, China from 2008 to 2019. The FRS and PAR models were validated by estimating predicted events, C index, calibration χ2 and plots. 1381 adults without CHD at baseline were followed up for 9.75 years on average. 168 CHD cases were observed. The FRS and PAR underestimated CHD events by 22 % and 46 % for the total population, while overestimated for males by 152 % and 78 %, respectively. The C index was slightly higher for PAR than FRS. Both models showed weak calibration with chi-square values above 20 (p

Type 2 diabetes (T2D) has emerged as a global epidemic, and conventional treatment approaches often face limitations in achieving long-term glycemic control and preventing complications. Traditional Chinese Medicine (TCM) offers a valuable alternative for managing T2D, with a long history of effectively using herbal formulations in clinical practice. However, the modular characteristics of these herbs and their specific mechanisms of action remain poorly understood. To comprehensively investigate the modular characteristics and mechanisms of Chinese herbs in treating T2D, as well as explore the synergistic interactions among different herbs and their modular components, we employed data mining, systematic pharmacology, and molecular docking. Our aim was to gain a comprehensive understanding of the potential therapeutic targets and pathways involved in herbal T2D treatment. In this study, a total of 1114 studies investigating the effects of TCM interventions in the treatment of T2D in adults were included. The analysis revealed 170 distinct types of Chinese herbs, 118 active components, and 238 common targets shared between the medicine and T2D. Additionally, this study identified six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two key chemicals (Diosgenin and Formononetin) found in TCM-mediated T2D suppression. It was observed that these proteins could bind with the ingredients. The MMP2-Diosgenin interaction exhibited the lowest binding free energy (−13.05 kJ/mol) and was primarily driven by hydrogen bonds with ALA-165. TNF-Diosgenin (−10.5 kcal/mol) showed three hydrogen bonds with LEU-37, ARG-82, and ASN-30. PTGS2 and Diosgenin (−8.71 kJ/mol) demonstrated a hydrogen bond with HIS-214. Furthermore, CASP9-Formononetin (−6.53 kcal/mol) exhibited the lowest binding free energy and hydrogen bonds with GLU-261 and SER-339 as the primary forces involved. CASP3-Formononetin (−6.07 kcal/mol) displayed three hydrogen bonds with ASN-342, TRP-348, and GLU-379. Lastly, CASP8 and Formononetin (−6.06 kJ/mol) formed a hydrogen bond with THR-390, TYR-392, and TYR-334. Moreover, critical therapeutic pathways, such as the immune inflammatory response, AGE-RAGE, and IL-17 signaling pathway, were found to be associated with T2D Chinese herb therapy. In conclusion, this study sheded light on the modular characteristics and mechanism of action of herbs used in Chinese Medicine for the treatment of T2D, which provided valuable insights for both researchers and practitioners in the field of Chinese Medicine, offering potential avenues for improved treatment strategies and personalized approaches to address the complex nature of T2D.

Abstract Background Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth. Methods One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve. Results Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P

Vascular endothelial injury in diabetes mellitus (DM) is the major cause of vascular disease, which is closely related to the occurrence and development of a series of vascular complications and has a serious negative impact on a patient’s health and quality of life. The primary function of normal vascular endothelium is to function as a barrier function. However, in the presence of DM, glucose and lipid metabolism disorders, insulin resistance, inflammatory reactions, oxidative stress, and other factors cause vascular endothelial injury, leading to vascular endothelial lesions from morphology to function. Recently, numerous studies have found that autophagy plays a vital role in regulating the progression of vascular endothelial injury. Therefore, this article compares the morphology and function of normal and diabetic vascular endothelium and focuses on the current regulatory mechanisms and the important role of autophagy in diabetic vascular endothelial injury caused by different signal pathways. We aim to provide some references for future research on the mechanism of vascular endothelial injury in DM, investigate autophagy’s protective or injurious effect, and study potential drugs using autophagy as a target.

ObjectiveThis study aimed to determine whether sarcopenia affects the all-cause mortality rate of patients with diabetic foot ulcers (DFUs).Research design and methodsThe clinic-based observational study included 217 patients treated at the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University during a 4-year period. All subjects underwent dual-energy X-ray absorptiometry to determine their body composition during hospitalization. Diagnosis of sarcopenia was based on the Baumgartner diagnostic criteria. Patients were followed up regularly by phone calls until April 1, 2019, and their survival status was recorded.Univariate and multivariate Cox risk ratio regression models were used to analyze factors influencing the all-cause mortality rate of patients with DFUs.ResultsOf the 217 patients, 158 people survived (82.7%), 33 died (17.3%), and 26 were lost to follow-up. The median follow-up time was 23 (Range 11–34) months. The majority of patients were male (68.6%), with a mean age of 67.29 ± 11.14 years. The 5-year survival rate was 68.3% and 45.9% for all study patients (n = 217) and sarcopenia patients (n = 81), respectively. Multivariate Cox risk regression model showed that age (HR 1.042[95%CI:1.006, 1.078], P = 0.021), sarcopenia (HR 5.051[95%CI:1.968, 12.961], P = 0.001), and serum creatinine (HR 1.007[95%CI: 1.003, 1.010], P < 0.001) were independent risk factors for all-cause mortality rate of patients with DFUs. Kaplan-Meier survival curve indicated that the survival rate of patients with sarcopenia was significantly lower than non-sarcopenia patients (P < 0.001).ConclusionsSarcopenia is an independent risk factor for all-cause mortality of patients with DFUs and hence an important prognostic factor for patients with DFUs. Active prevention and improvement of sarcopenia can potentially improve the survival outcomes of this patient population.

As isothermal, enzyme-free signal amplification strategies, hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) possess the advantages such as high amplification efficiency, excellent biocompatibility, mild reactions, and easy operation. Therefore, they have been widely applied in DNA-based biosensors for detecting small molecules, nucleic acids, and proteins. In this review, we summarize the recent progress of DNA-based sensors employing typical and advanced HCR and CHA strategies, including branched HCR or CHA, localized HCR or CHA, and cascaded reactions. In addition, the bottlenecks of implementing HCR and CHA in biosensing applications are discussed, such as high background signals, lower amplification efficiency than enzyme-assisted techniques, slow kinetics, poor stability, and internalization of DNA probes in cellular applications.

A collision tumor is a rare entity, particularly if occurring in the lung. We report a case of a 57-year-old woman with a primary pulmonary collision tumor comprising mixed squamous cell and glandular papilloma (MSGP) and glomus tumor (GT). An abnormal mass was discovered in the right lung by computed tomography (CT) of the chest. A right lower lobectomy with mediastinal lymph node dissection was performed. Histological examination of the surgical specimen suggested that the lung cancer was composed of two neoplastic components. To the best of our knowledge, this is the first report of a primary pulmonary collision tumor comprising two benign tumors of different origins, which were MSGP and GT.

Thermal interface materials (TIMs) are used in the mounting of semiconductor devices for rapid heat transfer from heat source to heat sink. The advantages of using TIMs include a lower total cost, elimination of liquid cooling, lower system cooling, lower power consumption, longer operating life and safety, and improved performance. However, there exist various interfaces called “air gaps” between the heat source and heat sink, resulting in reduced heat transfer at the interface depending on the thermal conductivity of the air layer. In this study, the structure of a typical heat dissipation sheet was examined, and the results were correlated with the distribution characteristics of the thermophysical properties. The distribution of the thermal diffusivity depended on the dispersion and orientation of graphite in the resin, making it difficult to obtain uniform thermal properties. These results suggest the need to develop new TIMs that can adequately fill the voids at the device interface, especially in a heat-dissipating adhesive that is in the liquid form at the time of use.

Objectives: To evaluate the distribution and changes in different obesity metabolic phenotypes, as well as their impact on the incidence of type 2 diabetes mellitus (T2DM) in a northwest Chinese population sample.Methods: Data comes from prospective cohort study (n = 1,393, mean follow up = 9.46 years). Participants were classified into four groups through a combination of the Chinese Diabetes Society (CDS) diagnostic criteria for metabolic syndrome with anthropometric measurements: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Cox regression models with time-dependent covariates were used to evaluate changes in obesity metabolic phenotypes and risk of T2DM.Results: Participants in MUO state had the highest risk of developing T2DM, the incidence density was 12.10/1,000 person-year. The MHO and MUO groups showed an increased risk of incident diabetes based on body mass index (BMI) (HR, 1.29; 95% CI, 1.03–1.61; p = 0.026 and HR, 1.20; 95% CI, 1.02–1.40; p = 0.024 respectively.) Besides, the MHO group had an increased risk of incident diabetes based on waist circumference (WC) (HR, 1.41; 95% CI, 1.10–1.80; p = 0.006).Conclusion: Diabetes is more frequent in the MHO and MUO groups and co-occurrence of obesity and metabolic abnormalities (MA) contributes to the development of T2DM.

Background: Type 2 diabetes mellitus (T2DM) is a clinical metabolic syndrome characterized by persistent hyperglycemia, which is caused by defective insulin secretion and decreased function in regulating glucose metabolism. Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula that has been gradually used in T2DM treatment. A comprehensive analysis on the efficacy and safety of DCHD in T2DM treatment is necessary.Objective: This meta-analysis aimed to systematically assess the clinical efficacy and safety of DCHD in the T2DM treatment and provide a reference for subsequent research and clinical practice.Methods: Both Chinese and English databases were searched from their inceptions to November 2021. All retrieved studies were screened according to inclusion and exclusion criteria and randomized controlled trials about DCHD on T2DM were enrolled. The quality of the literature was assessed using the bias risk assessment tool in the Cochrane Handbook. Data extraction was performed on the selected studies. Review Manager 5.4 and Stata 16.0 were used for meta-analysis. Sources of heterogeneity were also explored by using meta-regression and subgroup analysis. Funnel plot and Egger’s test were used to assess publication bias and the evidence quality was assessed by GRADE.Results: 17 eligible studies, involving 1,525 patients, were included in this study. Compared with conventional treatment, combined treatment with DCHD was significantly better in improving HbA1c (MD = −0.90%, 95%CI: −1.20 to −0.60, p < 0.01), FBG (MD = −1.08 mmol/L, 95%CI: −1.28 to −0.87, p < 0.01), 2hPG (MD = −1.25 mmol/L, 95%CI: −1.42 to −1.09, p < 0.01), TC (MD = −0.50 mmol/L, 95%CI: −0.70 to −0.30, p < 0.01), TG (MD = −0.44 mmol/L, 95%CI: −0.61 to −0.26, p < 0.01), LDL-C (MD = −0.58 mmol/L, 95%CI: −0.85 to −0.31, p < 0.01), HOMA-IR (SMD = −2.04, 95%CI: −3.09 to −0.99, p < 0.01), HOMA-β (SMD = 2.48, 95%CI: 2.20 to 2.76, p < 0.01) and BMI (MD = −1.52 kg/m2, 95%CI: −2.55 to −0.49, p < 0.01). When DCHD used alone, it had a similar efficacy to conventional treatment in HbA1c (MD = −0.04%, 95%CI: −0.17 to 0.09, p = 0.57) and FBG (MD = 0.13 mmol/L, 95%CI: −0.09 to 0.36, p = 0.24). It can also reduce 2hPG, even if not as effective as conventional treatment (MD = 0.54 mmol/L, 95%CI: 0.19 to 0.89, p < 0.01). Due to the small number of included studies, it is unclear whether DCHD used alone has an improving effect on lipid metabolism, BMI, HOMA-IR and HOMA-β. Analysis of adverse events showed DCHD was relatively safe. No obvious publication bias was detected by Funnel plot and Egger’s test.Conclusion: Based on this meta-analysis, we found that the combination with DCHD in the T2DM treatment has more advantages than conventional treatment alone, which can further regulate the glucose and lipid metabolism, reduce insulin resistance, improve islet function and lower BMI. DCHD alone also plays a certain role in regulating glucose. Meanwhile, DCHD is relatively safe. However, limited by the quality and quantity of included studies, the efficacy and safety of DCHD remain uncertain. More high-quality studies are still needed to provide more reliable evidence for the clinical application of DCHD.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021296718, identifier CRD42021296718.

Systemic lupus erythematosus (SLE) is a rheumatic disease. Growth differentiation factor 15 (GDF-15) is a member of transforming growth factor-β superfamily. To date, association of GDF-15 with SLE pathogenesis is not clarified. This study discussed GDF-15 serum levels and gene polymorphisms in SLE patients and lupus mouse model further demonstrated the role of GDF-15 in lupus development. We conducted two independent case-control studies for SLE patients. One is to evaluate serum levels of GDF-15 in 54 SLE patients and 90 healthy controls, and the other one is to analyze gene polymorphisms of GDF-15 in 289 SLE patients and 525 healthy controls. Serum levels of GDF-15 were detected by ELISA. GDF-15 gene polymorphisms (rs1055150, rs1058587, rs1059519, rs1059369, rs1227731, rs4808793, and rs16982345) were genotyped by the Kompetitive Allele-Specific PCR (KASP) method. Addition of recombinant GDF-15 into pristane-induced lupus mice evaluated histological and serological changes. Results showed that serum levels of GDF-15 were overexpressed in SLE patients and associated with disease activity. Polymorphisms rs1055150, rs1059369, rs1059519, and rs4808793 of GDF-15 gene were related to SLE risk. Lupus mice showed splenomegaly, severe histological scores, and high levels of autoantibodies [antinuclear antibodies (ANA) and total immunoglobulin G (IgG)], whereas administration of GDF-15 into lupus mice reduced the histological changes. Percentages of CD8+, CD11b+, CD19+, CD11C+ cells, TH2 cells, and pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-21, and IL-22) were reduced after GDF-15 treatment in lupus mice. In conclusion, GDF-15 was related to lupus pathogenesis and inhibited lupus development.

Chan Yang, Qinghua Liu, et al. use in vitro and SNAT-null mouse models to investigate the role of melatonin in ovarian aging. Their results suggest that melatonin can delay ovarian aging by inhibiting follicle activation, growth and atresia, providing more insight into how melatonin impacts reproduction.

Virtual corporate social responsibility co-creation (VCSRC) became an effective strategic tool with which enterprises can fulfill social responsibilities and retain customers. This study investigated the drivers of consumers’ continuous participation in VCSRC based on online survey data collected from 336 VCSRC participants. From a new perspective of self-expansion theory and by integrating consumer engagement (CE), we constructed a theoretical model and proposed a set of hypotheses, which were tested by using the structural equation model (SEM). Our findings show that self-expansion (experience-based expansion, competence-based expansion, and identity-based expansion) has a significant positive impact on continuous participation, with CE (conscious attention, enthusiasm, and social connection) playing a partial mediating role. Our research not only theoretically contributes to the research on VCSRC and self-expansion theory, but also inspires the operation of VCSRC projects in motivating consumers’ continuous participation.

COVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 cells) and intracellular IFN-γ in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

ObjectivesThe relationship between smoking and subjective cognitive decline (SCD), which is defined as the subjective perception of cognitive decline, is not well known. This study aimed to investigate the relationship of various types of smoking, including E-cigarette smoking and the use of E-liquid, with the incidence of SCD among Korean adults.MethodsWe evaluated the 2018 Korean Community Health Survey data collected from community-dwelling people in Korea. A total of 104,453 non-smokers, 38,607 past smokers, and 26,776 current smokers with eligible data were included in the study. SCD was assessed using the Behavioral Risk Factor Surveillance System. The past or current smoking pack-years throughout each participant's entire life were calculated. Multiple regression analyses were carried out to estimate the adjusted odds ratios (ORs) as measures of the association between each type of smoking and SCD after adjustment for potential confounders.ResultsCompared to no exposure, passive smoking was associated with higher odds of SCD. Compared to non-smokers, past smokers had a higher OR for SCD; however, current smokers did not. There were no significant associations between passive smoking and SCD in the non-smoker and past smoker groups, but there was a significant relationship between them in the current smoker group. While the cumulative dose of smoking was correlated with an increased OR of SCD in each group of current smokers and past smokers, E-cigarette smoking and the use of E-liquid were not associated with higher ORs in the current smoker group.ConclusionOur findings support that passive smoking and past smoking are significantly associated with SCD and that more cumulative exposure to smoking is correlated with a higher OR of SCD.

ObjectivesDespite the numerous studies on coronavirus disease 2019 (COVID-19), data regarding the impact of pre-existing diagnoses of Alzheimer’s disease (AD) and Parkinson’s disease (PD) on the susceptibility to and outcome of COVID-19 are limited. We aimed to determine whether patients with AD/PD had a higher likelihood of contracting COVID-19 and experiencing worse outcomes.MethodsData from patients with confirmed diagnoses of COVID-19 (n = 8,070) from January to June 2020 and control participants (n = 121,050) who were randomly selected to match the patients on the basis of age and sex were extracted from the Korean National Health Insurance Database. Pre-existing diagnoses of AD and PD were identified based on medical claim codes. The associations of pre-existing AD or PD with contracting COVID-19, developing severe COVID-19 and dying due to COVID-19 were examined using a logistic regression model. The participants’ age, sex, income, comorbidity score, and history of hypertension/diabetes were assessed as covariates.ResultsCOVID-19 cases were more likely to have a pre-existing AD diagnosis (adjusted odds ratio [aOR] = 2.11, 95% confidence interval [CI] = 1.79–2.50, P-value < 0.001) than controls. COVID-19 cases were more likely to have a pre-existing PD diagnosis than controls, although this estimate did not quite reach statistical significance (aOR = 1.41, 95% CI = 1.00–2.00, P-value = 0.054). Pre-existing AD was related to severe disease and mortality from COVID-19 (aOR = 2.21, 95% CI = 1.64–2.98; aOR = 2.21, 95% CI = 1.00–2.00). Pre-existing PD was not associated with mortality (aOR = 1.54, 95% CI = 0.75–3.16) but was associated with severe disease (aOR = 2.89, 95% CI = 1.56–5.35).ConclusionWe found that COVID-19 infection was significantly associated with a pre-existing diagnosis of AD but not with a pre-existing diagnosis of PD. Patients with pre-existing AD had higher odds of developing severe COVID-19 and dying. Pre-existing PD was only associated with a higher odds of developing severe COVID-19.

ObjectivesThyroid dysfunction is linked to an increased risk of cognitive impairment. However, studies on the relationships between thyroid diseases and Alzheimer’s disease (AD) have reported conflicting results. We investigated the associations between several thyroid diseases and AD in a nested case-control study.MethodsA total of 1,977 participants with AD were identified by claims data from 2002-2015 among a random sample of half a million people in the Korean National Health Insurance database. We recruited 16,473 age- and sex-matched (1:4 ratio) control participants and applied conditional logistic regression to estimate the relationships between thyroid diseases and AD, with adjustments for potential confounders, such as basic demographics, lifestyle factors, and various medical conditions or comorbidities.ResultsThe prevalence rates of hypothyroidism (odds ratio [OR]=1.14, 95% confidence interval [CI]=1.00-1.30), thyroiditis (OR=1.22, 95% CI=1.05-1.40), and hyperthyroidism (OR=1.13, 95% CI=1.01-1.28) were significantly higher in participants with AD than in control participants after adjustment for confounders.ConclusionIn this large national sample, we found significant relationships between several thyroid diseases and AD. Despite of the need for further investigation, these findings could better support to appreciate the pathophysiology of AD.

The sex pheromone receptors (SPRs) of Lepidopteran insects play important roles in chemical communication. In the sex pheromone detection processes, sex pheromone molecule (SPM), SPR, co-receptor (Orco), pheromone binding protein (PBP), sensory neuron membrane protein (SNMP), and pheromone degradation enzyme (PDE) play individual and cooperative roles. Commonly known as butterfly and moth, the Lepidopteran insects are widely distributed throughout the world, most of which are pests. Comprehensive knowledge of the SPRs of Lepidopteran insects would help the development of sex lure technology and the sex communication pathway research. In this review, we summarized SPR/Orco information from 10 families of Lepidopteran insects from corresponding studies. According to the research progress in the literature, we speculated the evolution of SPRs/Orcos and phylogenetically analyzed the Lepidopteran SPRs and Orcos with the neighbor-joining tree and further concluded the relationship between the cluster of SPRs and their ligands; we analyzed the predicted structural features of SPRs and gave our prediction results of SPRs and Orcos with Consensus Constrained TOPology Prediction (CCTOP) and SwissModel; we summarized the functional characterization of Lepidopteran SPRs and SPR-ligand interaction and then described the progress in the sex pheromone signaling pathways and metabotropic ion channel. Further studies are needed to work out the cryo-electron microscopy (EM) structure of SPR and the SPR-ligand docking pattern in a biophysical perspective, which will directly facilitate the understanding of sex pheromone signal transduction pathways and provide guidance in the sex lure technology in field pest control.

Abstract Background Castleman’s disease (CD) is an uncommon type of benign proliferation of the lymphoid tissue, characterized by local or systemic lymphadenopathy that most frequently appears in the mediastinum; involvement of the kidney is uncommon, and proliferation originating from the kidney is extremely rare. Herein, we report a rare case of hyaline vascular Castleman’s disease (HV-CD) in a 56-year-old male patient and discuss its morphological characteristics and differential diagnoses including mantle cell lymphoma (MCL), follicular lymphoma (FL), and nodal marginal zone lymphoma (NMZL). Case presentation A right upper-middle renal mass was detected after physical examination in a 56-year-old man without any clinical symptoms and a previous partial resection of the right kidney. Microscopically, the lymphoid follicles were increased in number and had expanded mantle zones and atrophic germinal centers. Vascular proliferation and hyalinization in the interfollicular zones were observed. Immunohistochemical staining showed CD20-positive cells in the mantle zones; CD21 and CD35 were expressed in the dendritic cells, CD3 was positive in a small number of T cells, and CD38 and CD138 were positive in the plasma cells. Additionally, Ki-67 expression was positive in the follicle centers. In contrast, staining for Bcl-2 in the germinal centers and cyclin D1 were negative. The immunohistochemical analysis combined with the morphological results supported the diagnosis of HV-CD. The patient recovered well after surgery. Conclusions Primarily renal HV-CD without lymph node hyperplasia or clinical symptoms is extraordinarily rare and different from the multicentric-type CD (MCD) with kidney involvement. Therefore, it is extremely important to improve the awareness of this diagnosis. Attention should be paid to the difference between HV-CD and common lymph node reactive hyperplasia, MCL, FL, NMZL, and so on. To avoid misdiagnosis as a renal malignant tumor requiring radical resection, distinguishing these diseases is crucial.

Abstract Background Aedes albopictus (Skuse) is an important vector of chikungunya, dengue, yellow fever and Zika viruses. In the absence of anti-viral medication and with limited availability of a commercial vaccine for public health use, vector control remains an effective means for reducing Aedes-borne disease morbidity. Knowledge about genetic mutations associated with insecticide resistance (IR) is a prerequisite for developing rapid resistance diagnosis, and the distribution and frequency of IR conferring mutations is important information for making smart vector control decisions. Methods Partial DNA sequences of domain II and domain III of Ae. albopictus voltage gated sodium channel (VGSC) gene were amplified from a total of 426 individuals, collected from 17 sites in the Beijing municipality. These DNA fragments were sequenced to discover the possible genetic mutations mediating knockdown resistance (kdr) to pyrethroids. The frequency and distribution of kdr mutations were assessed in the 17 Ae. albopictus populations. The origin of kdr mutations was investigated by haplotype clarification and phylogenetic analysis. Results Sequence alignments revealed the existence of multiple mutations (V1016G, I1532T, F1534S and F1534L) in VGSC. The highest frequency of the mutant 1016G allele (0.647) was found in Haidian, while 1016G was not detected in Huai Rou, Yan Qing, Ping Gu and Shun Yi. The frequency of 1532T was highest (0.537) in the population from the Olympic Forest Park (OFP, Chao Yang District), but not detectable in Huai Rou and Mi Yun. Two mutations were observed at codon 1534 with different distribution patterns: 1534L was only found in Tong Zhou (TZ) with a frequency of 0.017, while 1534S was distributed in TZ, OFP, Fang Shan, Da Xing and Shi Jing Shan with frequencies ranging from 0.019 (OFP) to 0.276 (TZ). One 1016G, one 1532T, one 1534L and two 1534S haplotypes were identified. Conclusions Multiple mutations (V1016G, I1532T, F1534L/S) in VGSC were found in Ae. albopictus in Beijing. This represents the first report of V1016G in Ae. albopictus. Sequence alignment and phylogenetic analysis revealed multiple origins of 1534S. The spatial heterogeneity in distribution and frequency of kdr mutations calls for a site-specific strategy for the monitoring of insecticide resistance. The relatively high frequencies of V1016G warn of a risk of pyrethroid resistance in mosquitoes in the urban zones.

Abstract Background In South Asia, the epidemiology of malaria is complex, and transmission mainly occurs in remote areas near international borders. Vector control has been implemented as a key strategy in malaria prevention for decades. A rising threat to the efficacy of vector control efforts is the development of insecticide resistance, thus it is important to monitor the type and frequency of insecticide resistant alleles in the disease vectors such as An. sinensis along the China-Vietnam border. Such information is needed to synthesize effective malaria vector control strategies. Methods A total of 208 adults of An. sinensis, collected from seven sites in southwest Guangxi along the China-Vietnam border, were inspected for the resistance-conferring G119S mutation in acetylcholinesterase (AChE) by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) and kdr mutations in the voltage-gated sodium channel (VGSC) by sequencing. In addition, the evolutionary origin of An. sinensis vgsc gene haplotypes was analyzed using Network 5.0. Results The frequencies of mutant 119S of AChE were between 0.61–0.85 in the seven An. sinensis populations. No susceptible homozygote (119GG) was detected in three of the seven sites (DXEC, LZSK and FCGDX). Very low frequencies of kdr (0.00–0.01) were detected in the seven populations, with most individuals being susceptible homozygote (1014LL). The 1014F mutation was detected only in the southeast part (FCGDX) at a low frequency of 0.03. The 1014S mutation was distributed in six of the seven populations with frequencies ranging from 0.04 to 0.08, but absent in JXXW. Diverse haplotypes of 1014L and 1014S were found in An. sinensis along the China-Vietnam border, while only one 1014F haplotype was detected in this study. Consistent with a previous report, resistant 1014S haplotypes did not have a single origin. Conclusions The G119S mutation of AChE was present at high frequencies (0.61–0.85) in the An. sinensis populations along the China-Vietnam border, suggesting that the vector control authorities should be cautious when considering carbamates and organophosphates as chemicals for vector control. The low frequencies (0.00–0.11) of kdr in these populations suggest that pyrethroids remain suitable for use against An. sinensis in these regions.

At present, the barrier to HIV-1 functional cure is the persistence of HIV-1 reservoirs. The “shock (reversing latency) and kill (antiretroviral therapy)” strategy sheds light on reducing or eliminating the latent reservoir of HIV-1. However, the current limits of latency-reversing agents (LRAs) are their toxicity or side effects, which limit their practicability pharmacologically and immunologically. Our previous research found that HSF1 is a key transcriptional regulatory factor in the reversion of HIV-1 latency. We then constructed the in vitro HSF1-knockout (HSF1-KO) HIV-1 latency models and found that HSF1 depletion inhibited the reactivation ability of LRAs including salubrinal, carfizomib, bortezomib, PR-957 and resveratrol, respectively. Furthermore, bortezomib/carfizomib treatment induced the increase of heat shock elements (HSEs) activity after HSF1-KO, suggesting that HSEs participated in reversing the latent HIV-1. Subsequent investigation showed that latent HIV-1-reversal by H2O2-induced DNA damage was inhibited by PARP1 inhibitors, while PARP1 was unable to down-regulate HSF1-depleted HSE activity, indicating that PARP1 could serve as a replaceable protein for HSF1 in HIV-1 latent cells. In summary, we succeeded in finding the mechanisms by which HSF1 reactivates the latent HIV-1, which also provides a theoretical basis for the further development of LRAs that specifically target HSF1.

Despite the weak, van der Waals interlayer coupling, photoinduced charge transfer vertically across atomically thin interfaces can occur within surprisingly fast, sub-50 fs time scales. An early theoretical understanding of charge transfer is based on a noninteracting picture, neglecting excitonic effects that dominate optical properties of such materials. We employ an ab initio many-body perturbation theory approach, which explicitly accounts for the excitons and phonons in the heterostructure. Our large-scale first-principles calculations directly probe the role of exciton-phonon coupling in the charge dynamics of the WS2/MoS2 heterobilayer. We find that the exciton-phonon interaction induced relaxation time of photoexcited excitons at the K valley of MoS2 and WS2 is 67 and 15 fs at 300 K, respectively, which sets a lower bound to the intralayer-to-interlayer exciton transfer time and is consistent with experiment reports. We further show that electron-hole correlations facilitate novel transfer pathways that are otherwise inaccessible to noninteracting electrons and holes.

Diabetic macroangiopathy is part of the most common serious complications of diabetes. Previous studies indicate that lncRNAs involved in the process of diabetes and another vascular disease. However, their detailed mechanism of the lncRNAs involved in diabetic macroangiopathy has not been well characterized. In the present study, we generated rat models of diabetic macroangiopathy induced by High fat of 16weeks. A total of 15 GK rats were constructed as a test group, along with 15 Wistar rats set as control group, and thoracic aorta tissue from each group was collected. Whole genomic RNA sequencing was performed on thoracic aorta tissue; 3223 novel lncRNAs and 20367 annotated lncRNAs were indemnified in thoracic aorta samples, and 864 lncRNAs were expressed differently in the test and control groups. Gene ontology term enrichment showed the apparent enrichment of inflammatory response and cell apoptosis, which consistent with the results of H&E Staining, TUNEL Assay, and ELISA; Extensive literature reveals inflammatory response and cell apoptosis play an important role in the process of diabetic macroangiopathy. The results of the present study indicated that lncRNAs, especially Nrep. bSep08, Col5a1, aSep0, soygee.aSep08-unspliced, NONRATT013247.2, votar.aSep08-unspliced, etc, both participate in and mediate the process of inflammatory response, cell apoptosis. What's more. Our research provides further insights into understanding of the basic molecular mechanisms underlying diabetic macroangiopathy.

The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell–cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants.