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Abstract Background Malaria remains a serious public health problem worldwide, particularly in Africa. Resistance to antimalarial drugs is an essential issue for malaria control and elimination. Currently, polymerase chain reaction (PCR) combined with Sanger sequencing is regarded as the gold standard for mutation detection. However, this method fails to meet the requirements of point-of-care testing (POCT) because of its time-consuming, expensive instruments and professional dependence. To support this strategy, we developed a novel diagnostic platform that combines recombinase polymerase amplification (RPA) with the Pyrococcus furiosus argonaute (PfAgo) protein and was designed to detect gene mutations related to antimalarial drug resistance. The Pfcrt haplotypes CVMNK and CVIET of chloroquine resistance (CQR) were used as examples and were assessed in this study. Methods By meticulously designing strategies, RPA primers, guide DNAs, and probes were screened, the reaction was optimized, and the resulting parameters were employed to ascertain the genotype of Pfcrt. The recombinant plasmids pUC57/Pfcrt-CVIET and pUC57/Pfcrt-CVMNK were constructed and diluted for sensitivity detection. The pUC57/Pfcrt-CVIET plasmid mixture was added to the pUC57/Pfcrt-CVMNK plasmid mixture in different additions to configure several specific proportions of mixed plasmid mixtures. The RPA-PfAgo platform was used, and the mixed plasmid was detected simultaneously via nest-PCR (nPCR) and Sanger sequencing. The platform was then evaluated on 85 clinical samples and compared with Sanger sequencing. Results The entire process achieves the key mutation Pfcrt-CVMNK/CVIET genotype identification of CQR within 90 min. The platform achieved 1.8 × 104 copies/μL sensitivity and could detect as little as 3% CVIET in mixed plasmids, which is a higher sensitivity than that of Sanger sequencing (5%). Notably, the platform shows 100% concordance with the gold standard method when 85 clinical samples are tested. The sensitivity and specificity were 100% for the 85 clinical samples. Conclusions This study established an RPA-PfAgo platform for genotyping the key mutation Pfcrt-CVMNK/CVIET of CQR. This method can rapidly produce reliable results and avoid the disadvantages of nPCR with sequencing. This approach has the characteristics of a short operation time, low device dependence, and a good match to the POCT strategy, suggesting that the platform can be easily applied locally or on site. Graphical abstract

Abstract Background The Onyx™ Liquid Embolic System is a non-adhesive liquid embolic agent, which has been proved by the US FDA for embolization of lesions in the peripheral and neurovasculature since 2005. We reported a case of ischemic optic neuropathy after using Onyx-18 to embolize the anterior ethmoid arteries that feeding dural arteriovenous fistulas (DAVF). Case presentation A 57-year-old Asian male presented with anterior cranial fossa DAVF underwent embolotherapy by delivering Onyx-18 through a microcatheter into the anterior ethmoid arteries under angiography guidance. The interventional procedure was successful and no clear evidence was found pointing to untargeted occlusive embolus. But after the surgery the patient experienced delayed painless vision loss in the right eye (RE). The fundoscopy showed unilateral papilledema with pale optic disc in RE, accompanied by significant edema and thickening in the retinal nerve fiber layer (RNFL) of macula. The fundus fluorescence angiography showed that most of the optic disc in RE had postponed or absent fluorescence filling. Visual evoked potential (VEP) confirmed that the amplitude of the P100 component was decreased in RE without significant prolongation of the latency. The patient was diagnosed with anterior ischemic optic neuropathy, but immediate pulse steroid therapy failed to rescue his vision. Conclusion Preoperative evaluation of the patient’s hemodynamic status and fundus examination are essential for assessing the risk of ischemic ocular complications, and the non-adhesive liquid embolic agent Onyx-18 should be used cautiously during endovascular embolization of intracranial artery.

Pregnant women are a high-risk group for several infectious diseases. Vaccination is the most economical and effective way to prevent infectious diseases in the general population, but for pregnant women, vaccination can present both risks and benefits. On one hand, vaccinated during pregnancy may protect the pregnant woman, fetus, and newborn from harm from vaccine-preventable diseases; on the other hand, it may also increase the risk of adverse events. Therefore, conducting safety assessments of vaccination during pregnancy not only provides evidence-based support for developing immunization program strategies but is also critical for ensuring maternal and infant health and preventing maternal and infant adverse events caused by vaccination. This article classifies relevant vaccines according to the principles of immunization during pregnancy in various guidelines and reviews national and international research on the safety of immunization during pregnancy. By comprehensively understanding the current status of research on the safety of immunization during pregnancy, it provides a reliable basis for improving China′s immunization strategies.

Abstract As global environmental challenges intensify, manufacturing firms face increasing pressure to innovate sustainably. Green innovation, characterized by the development of environmentally friendly products, processes, and technologies, has become essential for firms striving to remain competitive. This study aims to investigate the influence of key factors—green logistics, green finance, and green technology—on green innovation within manufacturing firms, while exploring the mediating role of green technology in these relationships. A multi-method approach was employed, combining partial least squares structural equation modeling, fuzzy-set qualitative comparative analysis, and necessity condition analysis. 447 responses were collected from manufacturing companies in Dhaka city, Bangladesh, using structured questionnaires. The analysis revealed that green logistics and green finance have a significant positive impact on green innovation, while the influence of the green work environment was found to be positive but statistically insignificant. Additionally, green technology was identified as a significant mediator in the relationships between green finance, green logistics, and green innovation. This study offers a comprehensive green innovation model while green technology is a mediator. Furthermore, this study advances the resource-based view theory by integrating green technology as a pivotal resource that enhances a firm's competitive advantage in sustainable markets. By adopting a multi-method approach, this research provides a rigorous examination of the research questions, offering a comprehensive understanding of the dynamic interactions between green finance, green logistics, and green technology in driving innovation. Thus, this research has thought provoking implications to prioritize investments in green finance, logistics, and technology, manufacturing firms can enhance their competitiveness, improve operational efficiency, and meet evolving environmental regulations and consumer preferences.

Abstract Background The impact of weather on human health has been proven, but the impact of extreme weather events on cardiometabolic multimorbidity (CMM) needs to be urgently explored. Objectives Investigating the impact of extreme temperature, relative humidity (RH), and laboratory testing parameters at admission on adverse events in CMM hospitalizations. Designs Time-stratified case-crossover design. Methods A distributional lag nonlinear model with a time-stratified case-crossover design was used to explore the nonlinear lagged association between environmental factors and CMM. Subsequently, unbalanced data were processed by 1:2 propensity score matching (PSM) and conditional logistic regression was employed to analyze the association between laboratory indicators and unplanned readmissions for CMM. Finally, the previously identified environmental factors and relevant laboratory indicators were incorporated into different machine learning models to predict the risk of unplanned readmission for CMM. Results There are nonlinear associations and hysteresis effects between temperature, RH and hospital admissions for a variety of CMM. In addition, the risk of admission is higher under low temperature and high RH conditions with the addition of particulate matter (PM, PM2.5 and PM10) and O3_8h. The risk is greater for females and adults aged 65 and older. Compared with first quartile (Q1), the fourth quartile (Q4) had a higher association between serum calcium (HR = 1.3632, 95% CI: 1.0732 ~ 1.7334), serum creatinine (HR = 1.7987, 95% CI: 1.3528 ~ 2.3958), fasting plasma glucose (HR = 1.2579, 95% CI: 1.0839 ~ 1.4770), aspartate aminotransferase/ alanine aminotransferase ratio (HR = 2.3131, 95% CI: 1.9844 ~ 2.6418), alanine aminotransferase (HR = 1.7687, 95% CI: 1.2388 ~ 2.2986), and gamma-glutamyltransferase (HR = 1.4951, 95% CI: 1.2551 ~ 1.7351) were independently and positively associated with unplanned readmission for CMM. However, serum total bilirubin and High-Density Lipoprotein (HDL) showed negative correlations. After incorporating environmental factors and their lagged terms, eXtreme Gradient Boosting (XGBoost) demonstrated a more prominent predictive performance for unplanned readmission of CMM patients, with an average area under the receiver operating characteristic curve (AUC) of 0.767 (95% CI:0.7486 ~ 0.7854). Conclusions Extreme cold or wet weather is linked to worsened adverse health effects in female patients with CMM and in individuals aged 65 years and older. Moreover, meteorologic factors and environmental pollutants may elevate the likelihood of unplanned readmissions for CMM.

Extreme heat events caused by climate change and rapid urbanization are major environmental issues affecting the health of urban populations, especially in metropolitan areas. However, few studies have employed a systematic risk assessment model to delineate heat health risk (HHR) in rapidly urbanizing metropolitan areas at a finer resolution, and rare studies have used epidemiological approaches for validation, as mortality is typically considered the most crucial indicator for assessing health impact. Here, a novel integrated socio-ecological-economic index (SEEI) was used to analyze the spatial distribution and evolution of HHR with a neighborhood resolution in Shanghai from 2000 to 2020, and four heat-related mortality indicators were applied to validate. The results showed that (1) the spatial distribution of the SEEI in Shanghai exhibited significant differences between urban and suburban areas, with the main urban areas having an average SEEI 2–3 times higher than suburban areas. (2) Overall, the SEEI peaked in 2010 and declined in 2020, with very high-risk neighborhoods decreasing from seven in 2000 to none in 2020. However, there was a slight trend towards a wider range of moderate-risk neighborhoods. (3) The heat-related mortality indicators exhibited significant correlations with SEEI, demonstrating the reliability of the SEEI as also confirmed by sensitivity analysis. The SEEI used in this study can provide a basis for decision-making for Shanghai as well as similar metropolitan areas to prevent extreme heat events.

Stigma maydis (SM) possesses remarkable nutritional value due to the presence of health-protective chemical constituents in it. Despite its commercial uses, there is a lack of information on changes in the nutritional profile of SM during Shenke 601 waxy corn development by following four different maturity stages (silking stage; blister stage; milky stage; dough stage). In this study, the ideal times for the development of seven active compounds (polysaccharides, saponin, rutin, luteolin, quercetin, kaempferol and chlorogenic acid) were at the silking stage. The total flavonoid and total phenol content increased as the SM matured. Except for the above-mentioned active compounds, the content of major nutritional components of dough stage was higher than that of three other stages. The extract of Stigma maydis exhibited good α-amylase, α-glucosidase and pancreatic lipase inhibition activities. The ethanolic SM extracts showed better inhibitory effects than aqueous SM extracts with a dose–effect relationship. The hypoglycemic activity of ethanolic extract was higher than that of aqueous extract at each stage. This provided an important basis for the application of SM.

Abstract Understanding the response of the injured brain to different transcranial direct current stimulation (tDCS) montages may help explain the variable tDCS treatment results on poststroke motor gains. Cortical connectivity has been found to reflect poststroke motor gains and cortical plasticity, but the changes in connectivity following tDCS remain unknown. We aimed to investigate the relationship between tDCS-induced changes in cortical connectivity and poststroke motor gains. In this study, participants were assigned to receive four tDCS montages (anodal, cathodal, bilateral, and sham) over the primary motor cortex (M1) according to a single-blind, randomized, crossover design. Electroencephalography (EEG) and Jebsen-Taylor hand function test (JTT) were performed before and after the intervention. Motor cortical connectivity was measured using beta-band coherence with the ipsilesional and contralesional M1 as seed regions. Motor gain was evaluated based on the JTT completion time. We examined the relationship between baseline connectivity and clinical characteristics and that between changes in connectivity and motor gains after different tDCS montages. Baseline functional connectivity, motor impairment, and poststroke duration were correlated. High ipsilesional M1–frontal–temporal connectivity was correlated with a good baseline motor status, and increased connectivity was accompanied by good functional improvement following anodal tDCS treatment. Low contralesional M1–frontal-central connectivity was correlated with a good baseline motor status, and decreased connectivity was accompanied by good functional improvement following cathodal tDCS treatment. In conclusion, EEG-based motor cortical connectivity was correlated with stroke characteristics, including motor impairment and poststroke duration, and motor gains induced by anodal and cathodal tDCS.

Background: Intrauterine exposure to gestational diabetes mellitus (GDM) poses significant risks to fetal development and future metabolic health. Despite its clinical importance, the role of microRNAs (miRNAs) in fetoplacental vascular endothelial cell (VEC) programming in the context of GDM remains elusive. This study aims to identify signature miRNA genes involved in this process using bioinformatics analysis via multiple algorithms. Methods: The dataset used in this study was acquired from Gene Expression Omnibus (GEO). Firstly, differentially expressed miRNA genes (DEMGs) were evaluated using limma package. Thereafter, an enrichment analysis of DEMGs was performed. Then, the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) were used as the other algorithms for screening candidate signature miRNA genes. Genes from the intersection of limma, LASSO, and SVM genes were used as the final signature miRNA genes. The receiver operator characteristic curve (ROC), the nomogram diagram, gene set enrichment analysis (GSEA), and signature miRNAs-target genes interaction network were implemented further to explore the features and functions of signature genes. Results: A total of 32 DEMGs, with 21 upregulated and 11 downregulated miRNA genes, were obtained from limma analysis. LASSO and SVM analyses identified 15 and 12 candidate signature miRNA genes, respectively. After the intersection of genes from limma, LASSO, and SVM analyses, MIR34A and MIR186 were found as the final signature genes related to fetoplacental VEC programming. MIR34A and MIR186 were highly expressed and were associated with an increased risk of fetoplacental VEC programming in GDM mothers. The area under the curve (AUC) of ROC for MIR34A and MIR186 were 0.960 and 0.935, respectively. GSEA analysis revealed that these signature genes positively participate in cellular processes related to VEC migration, cell differentiation, angiogenesis, programmed cell death, and inflammatory response. Finally, miRNAs-target genes interaction network analysis provides the interaction of signature miRNAs and their critical target genes, which may help further studies for miR-34a and miR-186 in GDM. Conclusions: MIR34A and MIR186 are novel signature miRNA genes related to fetoplacental VEC programming that may represent critical genes associated with placental function and fetal programming under GDM conditions.

BackgroundMaternal obesity significantly influences fetal development and health later in life; however, the molecular mechanisms behind it remain unclear. This study aims to investigate signature genes related to maternal obesity and fetal programming based on a genomic-wide transcriptional placental study using a combination of different bioinformatics tools.MethodsThe dataset (GSE128381) was obtained from Gene Expression Omnibus (GEO). The data of 100 normal body mass index (BMI) and 27 obese mothers were included in the analysis. Differentially expressed genes (DEGs) were evaluated by limma package. Thereafter, functional enrichment analysis was implemented. Then, weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) analysis were used to further screening of signature genes. Simple linear regression analysis was used to assess the correlation between signature genes and newborn birth weight. Gene set enrichment analysis (GSEA) was implemented to study signaling pathways related to signature genes. The expression of the signature genes was also explored in 48 overweight mothers in the same dataset.ResultsA total of 167 DEGs were obtained, of which 122 were up-regulated while 45 were down-regulated. The dataset was then clustered into 11 modules by WGCNA, and the MEbrown was found as the most significant module related to maternal obesity and fetal programming (cor = 0.2, p = 0.03). The LASSO analysis showed that PTX3, NCF2, HOXB5, ABCA6, and C1orf162 are signature genes related to maternal obesity and fetal programming, which were increased in the placenta of obese mothers compared to those with normal BMI. The area under the curve (AUC) of the signature genes in the receiver operating characteristic curve (ROC) was 0.709, 0.660, 0.674, 0.667, and 0.717, respectively. Simple linear regression analysis showed that HOXB5 was associated with newborn birth weight. GSEA analysis revealed that these signature genes positively participate in various signaling pathways/functions in the placenta.ConclusionPTX3, NCF2, HOXB5, ABCA6, and C1orf162 are novel signature genes related to maternal obesity and fetal programming, of which HOXB5 is implicated in newborn birth weight.

Abstract Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague–Dawley rats aged 2–3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1β for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague–Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1β-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.

Background and objectives: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5–10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5–10 on various types of cerebrovascular disease. Methods: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. Results: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 μg/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 μg/m3 rise in PM2.5–10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. Conclusions: Short-term exposures to both PM2.5 and PM2.5–10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.

Fresh red waxy corn is consumed worldwide because of its unique flavor and rich nutrients, but it is susceptible to deterioration with a short shelf life. This study explored the effect of slightly acidic electrolyzed water (SAEW) treatment on the quality and antioxidant capacity of fresh red waxy corn during postharvest cold storage up to 40 d. The SAEW treatment exhibited lower weight loss, softer firmness, and higher total soluble solids (TSS) and moisture content than the control group. Correspondingly, the SAEW maintained the microstructure of endosperm cell wall and starch granules of fresh red waxy corn kernels well, contributing to good sensory quality. Furthermore, SAEW effectively reduced the accumulation of H2O2 content, elevated the O2−· scavenging ability, maintained higher CAT and APX activities, and decreased the decline of the flavonoids and anthocyanin during the storage. These results revealed that the SAEW treatment could be a promising preservation method to maintain higher-quality attributes and the antioxidant capacity of fresh red waxy corn during postharvest cold storage.

The bacterium Klebsiella pneumoniae (Kp) was the primary pathogen of hospital-acquired infection, but the current detection method could not rapidly and conveniently identify Kp. Recombinase polymerase amplification (RPA) was a fast and convenient isothermal amplification technology, and the clustered regularly interspaced short palindromic repeats (CRISPR) system could rapidly amplify the signal of RPA and improve its limit of detection (LOD). In this study, we designed three pairs of RPA primers for the rcsA gene of Kp, amplified the RPA signal through single-strand DNA reporter cleavage by CRISPR/Cas12a, and finally analyzed the cleavage signal using fluorescence detection (FD) and lateral flow test strips (LFTS). Our results indicated that the RPA-CRISPR/Cas12a platform could specifically identify Kp from eleven common clinical pathogens. The LOD of FD and LFTS were 1 fg/μL and 10 fg/μL, respectively. In clinical sample testing, the RPA-CRISPR/Cas12a platform was consistent with the culture method and qPCR method, and its sensitivity and specificity were 100% (16/16) and 100% (9/9), respectively. With the advantages of detection speed, simplicity, and accuracy, the RPA-CRISPR/Cas12a platform was expected to be a convenient tool for the early clinical detection of Kp.

In order to study the preservation effect of acidic calcium sulfate (ACS) on fresh waxy corn, the effects of diluted ACS (10−3) treatment on the nutritional quality and antioxidant activity of fresh waxy corn during storage (4 ℃) were studied. The results showed that ACS treatment could inhibit the weight loss, significantly slow down the increase of fruit skin hardness (P

Abstract Background Vaginectomy has been shown to be effective for select patients with vaginal high-grade squamous intraepithelial lesions (HSIL) and is favored by gynecologists, while there are few reports on the robotic-assisted laparoscopic vaginectomy (RALV). The aim of this study was to evaluate the safety and treatment outcomes between RALV and the conventional laparoscopic vaginectomy (CLV) for patients with vaginal HSIL. Methods This retrospective cohort study was conducted in 109 patients with vaginal HSIL who underwent either RALV (RALV group) or CLV (CLV group) from December 2013 to May 2022. The operative data, homogeneous HPV infection regression rate and vaginal HSIL regression rate were compared between the two groups. Student’s t-test, the Mann-Whitney U test, Pearson χ2 test or the Fisher exact test, Kaplan-Meier survival analysis and Cox proportional-hazards models were used for data analysis. Results There were 32 patients in the RALV group and 77 patients in the CLV group. Compared with the CLV group, patients in the RALV group demonstrated less estimated blood loss (41.6 ± 40.3 mL vs. 68.1 ± 56.4 mL, P = 0.017), lower intraoperative complications rate (6.3% vs. 24.7%, P = 0.026), and shorter flatus passing time (2.0 (1.0–2.0) vs. 2.0 (2.0–2.0), P 0.999) and vaginal HSIL regression rate (96.7% vs. 94.7%, P = 0.805) after vaginectomy. However, the RALV group had significantly higher hospital costs than that in the CLV group (53035.1 ± 9539.0 yuan vs. 32706.8 ± 6659.2 yuan, P

Abstract Osteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) treatment of OA in rodent OA models using a proteomic approach. First, N = 18 Sprague Dawley (SD) rats underwent sham surgery (n = 6) or ACL transection (n = 12), followed at an interval of one week by randomization of the ACL transection group to intra-articular administration of either 50 µL placebo (control group) or miR-1 agomir, a mimic of endogenous miR-1 (experimental group). After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and immunohistochemically stained for the presence of MMP-13. Second, N = 30 Col2a1-cre-ERT2 /GFPf1/fl -RFP-miR-1 transgenic mice were randomized to intra-articular administration of either placebo (control group, N = 15) or tamoxifen, an inducer of miR-1 expression (experimental group, N = 15), before undergoing surgical disruption of the medial meniscus (DMM) after an interval of five days. After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and underwent differential proteomic analysis. Specifically, tandem mass tagging (TMT) quantitative proteomic analysis was employed to identify inter-group differentially-expressed proteins (DEP), and selected DEPs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) technology. Immunohistochemically-detected MMP-13 expression was significantly lower in the experimental rat group, and proteomic analyses of mouse tissue homogenate demonstrated that of 3526 identified proteins, 345 were differentially expressed (relative up- and down-regulation) in the experimental group. Proteins Fn1, P4ha1, P4ha2, Acan, F2, Col3a1, Fga, Rps29, Rpl34, and Fgg were the *top ten most-connected proteins, implying that miR-1 may regulate an expression network involving these proteins. Of these ten proteins, three were selected for further validation by RT-qPCR: the transcript of Fn1, known to be associated with OA, exhibited relative upregulation in the experimental group, whereas the transcripts of P4ha1 and Acan exhibited relative downregulation. These proteins may thus represent key miR-1 targets during OA-regulatory mechanisms, and may provide additional insights regarding therapeutic mechanisms of miR-1 in context of OA.

ABSTRACT Aims microRNA may be a new therapeutic direction for diabetes. As a typical tumor marker, miR‐31 is involved in a variety of metabolic diseases, but the specific role is still unclear. This study aimed to investigate the effect of miR‐31 on type 2 diabetes mellitus and its accompanying vascular injury, as well as on the effects of hypoxia‐inducible factor‐1α inhibitor (HIF1AN), hypoxia‐inducible factor (HIF)‐1α, and vascular endothelial growth factor (VEGF)‐A expression in vitro and in vivo. Materials and Methods In vitro, a model of high‐fat and high‐glucose‐induced human aortic endothelial cell (HAEC) injury was established to simulate diabetes mellitus (DM). Cell functions were compared between the control group, the DM damage group, and the group transfected with miR‐31 after DM damage. In vivo, overexpressing miR‐31 FVB mice and FVB mice were divided into the control and induced type 2 diabetes mellitus groups. Type 2 diabetes mellitus models were induced by a high‐fat diet combined with streptozotocin. The lipid metabolism levels, viscera, and vascular damage were compared between the control and type 2 diabetes mellitus groups. Results In vitro, miR‐31 improved the proliferation ability of damaged cells by targeting HIF1AN and up‐regulating the expression of HIF‐1α and VEGF‐A. In vivo, miR‐31 ameliorated the development of type 2 diabetes mellitus, disturbance of glucose and lipid metabolism, and damage to some organs. Meanwhile, miR‐31 had a protective effect on vascular damage complicated by type 2 diabetes mellitus by increasing the levels of HIF‐1α and VEGF‐A. Conclusion Our experiments show that miR‐31 can delay the progression of type 2 diabetes mellitus and ameliorate diabetic vascular injury.

Abstract Background Lipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored. Methods In the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior. Results It was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect. Conclusion This study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.

ObjectiveEvidence regarding the effects of particulate matter (PM) pollutants on cardiovascular disease (CVD) mortality remains limited in Shanghai, China. Our objective was to thoroughly evaluate associations between PM pollutants and CVD mortality.MethodsDaily data on CVD mortality, PM (PM10 and PM2.5) pollutants, and meteorological variables in Shanghai, China were gathered from 2003 to 2020. We utilized a time-series design with the generalized additive model to assess associations between PM pollutants and CVD mortality. Additionally, we conducted stratified analyses based on sex, age, education, and seasons using the same model.ResultsWe found that PM pollutants had a significant association with CVD mortality during the study period. Specifically, there was a 0.29% (95%CI: 0.14, 0.44) increase in CVD mortality for every 10 μg/m3 rise in a 2-day average (lag01) concentration of PM10. A 0.28% (95% CI: 0.07, 0.49) increase in CVD mortality was associated with every 10 μg/m3 rise in PM2.5 concentration at lag01. Overall, the estimated effects of PM10 and PM2.5 were larger in the warm period compared with the cold period. Furthermore, males and the older adult exhibited greater susceptibility to PM10 and PM2.5 exposure, and individuals with lower education levels experienced more significant effects from PM10 and PM2.5 than those with higher education levels.ConclusionOur findings suggested that PM pollutants have a substantial impact on increasing CVD mortality in Shanghai, China. Moreover, the impacts of air pollution on health may be altered by factors such as season, sex, age, and educational levels.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) poses a severe nosocomial threat, prompting a need for efficient detection methods. Traditional approaches, such as bacterial culture and PCR, are time-consuming and cumbersome. The CRISPR-based gene editing system offered a potential approach for point-of-care testing of CRAB.MethodsWe integrated recombinase polymerase amplification (RPA) and CRISPR-Cas12a system to swiftly diagnose CRAB-associated genes, OXA-51 and OXA-23. This multiplex RPA-CRISPR-Cas12a system eliminates bulky instruments, ensuring a simplified UV lamp-based outcome interpretation.ResultsOperating at 37°C to 40°C, the entire process achieves CRAB diagnosis within 90 minutes. Detection limits for OXA-51 and OXA-23 genes are 1.3 × 10−6 ng/μL, exhibiting exclusive CRAB detection without cross-reactivity to common pathogens. Notably, the platform shows 100% concordance with PCR when testing 30 clinical Acinetobacter baumannii strains.ConclusionIn conclusion, our multiplex RPA coupled with the CRISPR-Cas12a system provides a fast and sensitive CRAB detection method, overcoming limitations of traditional approaches and holding promise for efficient point-of-care testing.

Abstract Background Although highly heterogeneous among countries, the incidence rates of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) have been increasing globally over the past two decades. To better understand the cause of these secular trends, this study aimed to investigate the effects of age, period, and birth cohort on LBW, PTB, and SGA rates in Shanghai. Methods Data from 2,958,695 singleton live births at 24–41 gestational weeks between 2004 and 2020 were obtained for this study. Age-period-cohort models based on Poisson regression were used to evaluate the independent effects of maternal age, delivery period, and maternal birth cohort on the trends in LBW, PTB, and SGA. Results The overall prevalence rates of LBW, PTB, and SGA were 2.9%, 4.7%, and 9.3%, respectively, and significant changes were observed (average annual change: + 10.7‰, + 9.1‰, -11.9‰) from 2004 to 2020. Cohort effect increased steadily, from 1960 (risk ratio [RR] = 0.71, 95% confidence interval [CI]: 0.65–0.78) to 1993 (RR = 0.97, 95% CI: 0.94–1.01) for LBW and from 1960 (RR = 0.69, 95% CI: 0.64–0.75) to 2004 (RR = 1.02, 95% CI: 0.94–1.12) for PTB. A strong cohort effect was found with the highest risk of SGA (RR = 1.82, 95% CI: 1.72–1.93) in 1960 and the lowest risk (RR = 0.57, 95% CI: 0.54–0.61) in 2004, compared with the reference cohort of 1985. There was a “U-shaped” maternal age effect on LBW and PTB and a weak period effect on the three birth outcomes. Conclusions Our findings suggested a significant independent effect of age, period, and birth cohort on the three birth outcomes. The increasing rates of LBW and PTB motivated us to focus on young and advanced pregnant women. Meanwhile, the prevalence of SGA decreased steadily, illustrating the need for further research on the mechanisms underlying these trends.

To investigate the effects of near-freezing temperature treatment on the storage quality of fresh waxy corn, the 'Huhongnuo 1' waxy corn was used as experimental material in this experiment. The waxy corn was stored at 4 ℃ and near-freezing temperature (−1 ℃) for 40 days, respectively. The changes in quality and the activities of antioxidant enzymes of fresh waxy corn during storage were determined, and correlation analysis and principal component analysis were performed. The results showed that compared with refrigerated storage at 4 ℃, near-freezing temperature treatment could effectively reduce the weight loss, inhibit the rise of fruit skin hardness, and maintain the content of moisture, soluble solids (TSS), soluble sugar, soluble protein and secondary metabolites. In addition, near-freezing temperature treatment could maintain a high level of total phenols, flavonoids and anthocyanins, and increase the activity of catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX), which reduced the accumulation of H2O2, maintained the nutritional quality of fresh waxy corn, and delayed fruit senescence. Correlation analysis showed that the storage time of fresh waxy corn was significantly positively correlated with the weight loss rate, fruit skin hardness and H2O2 content and was significantly (P

Abstract The prevalence of high birth weight or large for gestational age (LGA) infants is increasing, with increasing evidence of pregnancy-related factors that may have long-term impacts on the health of the mother and baby. We aimed to determine the association between excessive fetal growth, specifically LGA and macrosomia, and subsequent maternal cancer by performing a prospective population-based cohort study. The data set was based on the Shanghai Birth Registry and Shanghai Cancer Registry, with medical records from the Shanghai Health Information Network as a supplement. Macrosomia and LGA prevalence was higher in women who developed cancer than in women who did not. Having an LGA child in the first delivery was associated with a subsequently increased risk of maternal cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04–1.11). Additionally, in the last and heaviest deliveries, there were similar associations between LGA births and maternal cancer rates (HR = 1.08, 95% CI 1.04–1.12; HR = 1.08, 95% CI 1.05–1.12, respectively). Furthermore, a substantially increased trend in the risk of maternal cancer was associated with birth weights exceeding 2500 g. Our study supports the association between LGA births and increased risks of maternal cancer, but this risk requires further investigation.

ObjectiveThis study aimed to investigate the influence of pine pollen (PP) on hepatocellular carcinoma (HCC) behavior in vitro and in vivo and explore its mechanism of action by focusing on the phosphatidylinositol 3-kinase/protein serine-threonine kinase (PI3K/AKT) signaling pathway and α-Enolase (ENO1) gene expression.MethodsWe performed a bioinformatics analysis of ENO1. HCC cells overexpressing ENO1 were developed by lentivirus transfection. Cell proliferation, invasion, and migration were assessed using the cell cytotoxicity kit-8 assay, transwell assay, cell scratch test, and ENO1 inhibiting proliferation experiment. Protein expression was analyzed using Western blot. The in vivo effects of PP on HCC xenografts were also assessed in mice. The serum of nude mice in each group was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT. The tumor blocks of nude mice were weighed, and proteins were extracted for Western blot.ResultsCompared to normal cells, the phosphorylation of ENO1 at the S27 site was most significant in HCC cells and was closely related to cell proliferation. In vitro, the PP solution inhibited the proliferation, invasion, and migration of ENO1 overexpressing cells compared with empty-vector-transfected cells. In mice bearing HCC, PP injection inhibited the overexpression of ENO1, affected serum ALT, AST, and AST/ALT levels, and reduced tumor weight. However, the expression of proliferation-related proteins in tumors overexpressing ENO1 was higher than in empty transfected tumors.ConclusionPP inhibits HCC by regulating the expression of ENO1 and MBP-1 and suppressing the PI3K/AKT pathway by inhibiting C-MYC and erb-B2 receptor tyrosine kinase 2.

BackgroundThere is no clear conclusion on the immunogenicity and adverse events of concomitant administration the viral respiratory infectious disease vaccines. We aimed to evaluate the impact of concomitant administering viral respiratory infectious disease vaccines on efficiencies, safety and influencing factors.MethodsThis meta-analysis included studies from PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, WHO COVID-19 Research, and ClinicalTrials.gov databases. Randomized controlled trials of the adult participants concomitant administered with viral respiratory infectious disease vaccine and other vaccines were included. The main outcomes were the seroconversion rate and seroprotection rate of each vaccine. Used the Mantel–Haenszel fixed effects method as the main analysis to estimate the pooled RRs and the corresponding 95% confidence intervals. The risk of bias for each trial was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, while evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system.ResultsA total of 21 studies comprising 14060 participants with two types of vaccines were retained for the meta-analysis. Concomitant immunization reduced the geometric mean titer (RR: 0.858, 95% CI: (0.785 to 0.939)) and the geometric mean fold rise (0.754 (0.629 to 0.902)) in the SARS-COV-2 vaccine group but increased the seroconversion rate (1.033 (1.0002 to 1.067)) in the seasonal influenza vaccine group. Concomitant administration were influenced by the type of vaccine, adjuvant content, booster immunization, and age and gender of the recipient.ConclusionThis meta-analysis suggested that the short-term protection and safety of concomitant administered were effective. Appropriate adjuvants, health promotion and counselling and booster vaccines could improve the efficiency and safety of Concomitant vaccination.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022343709.

The prevention, treatment, and rehabilitation of spinal cord injury (SCI) have always posed significant medical challenges. After mechanical injury, disturbances in microcirculation, edema formation, and the generation of free radicals lead to additional damage, impeding effective repair processes and potentially exacerbating further dysfunction. In this context, inflammatory responses, especially the activation of macrophages, play a pivotal role. Different phenotypes of macrophages have distinct effects on inflammation. Activation of classical macrophage cells (M1) promotes inflammation, while activation of alternative macrophage cells (M2) inhibits inflammation. The polarization of macrophages is crucial for disease healing. A non-coding RNA, known as microRNA (miRNA), governs the polarization of macrophages, thereby reducing inflammation following SCI and facilitating functional recovery. This study elucidates the inflammatory response to SCI, focusing on the infiltration of immune cells, specifically macrophages. It examines their phenotype and provides an explanation of their polarization mechanisms. Finally, this paper introduces several well-known miRNAs that contribute to macrophage polarization following SCI, including miR-155, miR-130a, and miR-27 for M1 polarization, as well as miR-22, miR-146a, miR-21, miR-124, miR-223, miR-93, miR-132, and miR-34a for M2 polarization. The emphasis is placed on their potential therapeutic role in SCI by modulating macrophage polarization, as well as the present developments and obstacles of miRNA clinical therapy.

Peach fruit is easy perishable with its high respiration and ethylene emission peak after postharvest at room temperature for its climacteric character. Cold storage is one of the most effective way to extend the storage shelf life, however, peach fruit is chilling sensitive and highly vulnerable to chilling injury (CI) during long-term inappropriate low temperature storage. The peach fruit show deterioration of quality of flesh leathery with texture elevated, occurrence of tissue woolliness, internal browning and loss of the inherent flavor which being the main risk of the sound development of peach industry. This article reviews the research progress of the mechanism on peach fruit chilling injury and summarizes the influence on change of cell membrane, cell wall metabolic, antioxidant system and arginine metabolism. In addition, the postharvest technologies to control chilling injury are also detailed, which would provide the foundation for the theoretical study and develop of applied techniques for storage and fresh-keeping after postharvest in peach.

Transcranial direct current stimulation (tDCS) has become a new method of rehabilitation treatment for stroke and is gradually gaining acceptance. However, the neurophysiological mechanisms of tDCS in the treatment of stroke still need to be further explored. In our research, we aimed to investigate the effects of tDCS on neural oscillation power and brain functional network (BFN) connectivity in stroke patients based on electroencephalogram (EEG). Fifteen patients with ischemic stroke attended two experimental sessions in a randomized crossover trial and received real and sham tDCS. Resting-state EEG signals were acquired before and after stimulation. First, the power of EEG delta, theta, alpha, beta, and gamma bands were analyzed before and after stimulation. Then, BFNs in different bands were constructed, and network characteristic parameters such as degree, clustering coefficient, characteristic path length, global efficiency, and small-world attribute were analyzed. The results showed that the delta power decreased significantly ( ${P}< {0.05}$ ) and the alpha power increased significantly ( ${P}< {0.05}$ ) after real tDCS, whereas the theta, beta, and gamma power did not change significantly ( ${P}>{0.05}$ ). The degree and global efficiency of the delta band BFN decreased significantly after real tDCS ( ${P}< {0.05}$ ), the characteristic path length increased significantly ( ${P}< {0.05}$ ), and the clustering coefficient and small-world attribute decreased but not statistically significant ( ${P}>{0.05}$ ). The degree, clustering coefficient, global efficiency, and small-world attribute of the alpha band BFN increased significantly after real tDCS ( ${P}< {0.05}$ ), and the characteristic path length decreased significantly ( ${P}< {0.05}$ ). The BFN characteristic parameters in theta, beta, and gamma bands did not change significantly after real tDCS ( ${P}>{0.05}$ ). There was no significant difference in sham tDCS group ( ${P}>{0.05}$ ). Our study found that the power of delta oscillations decreased and the global connectivity of delta band BFN weakened after tDCS in stroke patients, whereas the power of alpha oscillations increased and the global and local connectivity of alpha band BFN was enhanced. The findings implied that one of the neurophysiological mechanisms of tDCS treatment in stroke patients may be the modulation of the power of delta and alpha oscillations, as well as the improvement of the connectivity of delta and alpha oscillation networks.

Objectives: Thalassemia, the most common global monogenetic disorder, is highly prevalent in southern China. Epidemiological and molecular characterization of thalassemia is important for designing appropriate prevention strategies in high-risk areas, especially the border area of Guangxi-Yunnan-Guizhou province in southwestern China.Methods: We recruited 38812 reproductive age couples and screened them for thalassemia. Routine blood tests as well as hemoglobin components and levels were evaluated. In addition, suspected thalassemia were identified by gap polymerase chain reaction (Gap-PCR) and PCR-based reverse dot blot (PCR-RDB).Results: The overall prevalence of thalassemia was 26.76%. Specifically, incidences of α-thalassemia, β-thalassemia, and concurrent α- and β-thalassemia were 17.52%, 6.92%, and 2.32%, respectively. The diagnosed α-thalassemia anomalies were associated with six gene mutations and 25 genotypes. The β-thalassemia anomalies were associated with 12 gene mutations and 15 genotypes. Moreover, among the 1799 concurrent mutated α- and β-thalassemia genes, 95 different genotypes were identified. Couples in which both partners were positive for α-thalassemia and β-thalassemia isotypes were 8.80% and 2.08%, respectively. The proportion of couples at a risk of having children with thalassemia major or intermedia was high.Conclusions: This study elucidates on the prevalence and molecular characterization of thalassemia in the border area of Guangxi-Yunnan-Guizhou provinces. These findings provide valuable baseline data for genetic counseling and prenatal diagnosis, with the overarching goal of preventing and controlling severe thalassemia.

Abstract Wellen's syndrome, a STEMI equivalent, is associated with severe stenosis of the proximal left anterior descending (LAD) in a patient with chest pain who needs emergency coronary angiography with the possibility of intervention. Due to only T wave changes in the electrocardiograph (ECG), Wellen's syndrome was easily ignored. Moreover, it may progress to acute myocardial infarction or even cardiac arrest. Therefore, clinicians should improve their understanding of this ECG pattern and appropriately dilate the coronary angiography indication. In addition, more dangerous narrowing of a coronary artery, as in our case, the left main artery stenosis, should also be considered.

Background and purposeTo provide a comprehensive overview of epidemiological features and temporal trends of pancreatic cancer in urban Shanghai from 1973 to 2017.MethodsData on pancreatic cancer in urban Shanghai were obtained through the Shanghai Cancer Registry and the Vital Statistics System. Joinpoint analysis was used to describe the temporal trends and annual percent changes (APCs) and age-period-cohort analysis were used to estimate the effects of age, period, and birth cohort on pancreatic cancer.ResultsThere were a total of 29,253 cases and 27,105 deaths of pancreatic cancer in urban Shanghai over the 45-year study period. The overall average annual age-standardized incidence and mortality rates were 5.45/100,000 and 5.02/100,000, respectively. Both the incidence and mortality rates demonstrated fluctuating upward trends, with an average annual increase rate of 1.51% (APC = 1.51, P < 0.001) and 1.04% (APC = 1.04, P < 0.001), respectively. The upward trend in incidence was greater for females than for males, while the trend in mortality was seen in both sexes equally and continuously. In recent years (2013-2017), the age-specific incidence rates increased further than before, with statistically significant changes in the 35-year, 45- to 55-year and 70- to 85-year age groups (P < 0.05). The age-specific mortality rates also showed obvious upward trends, which in the 50- to 55-year, and 75- to 85-year age groups increased significantly. The results of the age-period-cohort analysis suggested significant effects of age, period, and cohort on the prevalence of pancreatic cancer.ConclusionThe prevalence of pancreatic cancer, dramatically influenced by socioeconomic development and lifestyles, demonstrated a significant upward trend from 1973 to 2017 in urban Shanghai and underscored the necessity and urgency for additional efforts in primary and secondary prevention measures.

Objective: We aimed to explore the relationship between peripheral blood circulating tumor cells (CTCs) and the expression of Claudin-4 in patients with breast cancer, and further explore the potential impact on clinical prognosis and risk assessment.Methods: We classified and enumerated circulating tumor cells in the blood of breast cancer patients by CTC-enriched in situ hybridization and the detection of Claudin-4 expression by immunohistochemistry. We carried out an analysis of the correlation between the two and the comparison of their impact on clinical parameters and prognosis.Results: There were 38 patients with a low expression of Claudin-4 and 27 patients with a high expression of Claudin-4. Compared with Claudin-4 low-expression patients, the number of CTCs was higher in patients with high Claudin-4 expression (11.7 vs. 7.4, p < 0.001). High Claudin-4 expression was associated with a lower count of epithelial CTCs (E-CTCs) (3.4 vs. 5.0, p = 0.033), higher counts of mesenchymal CTCs (M-CTC) (4.4 vs. 1.1, p < 0.001), and epithelial/mesenchymal CTCs (E/M-CTCs) (4.0 vs. 3.5, p = 0.021). The intensity of Claudin-4 was positively correlated with CTC (rs = 0.43, p = 0.001). Multivariate COX regression analysis showed that CTC counts (HR = 1.3, p < 0.001), Claudin-4 (HR = 4.6, p = 0.008), and Lymphatic metastasis (HR = 12.9, p = 0.001) were independent factors for poor prognosis. COX regression of CTC classification showed that epithelial/mesenchymal CTCs (E/M-CTC) (HR = 1.9, p = 0.001) and mesenchymal CTCs (M-CTC) (HR = 1.5, p = 0.001) were independent influencing factors of adverse reactions in breast cancer patients.Conclusion: The number of CTC in breast cancer is positively correlated with the expression of Claudin-4. High CTC counts and a high proportion of M-CTCs correlated with Claudin-4 expression. CTC counts and Claudin-4 expression were independent predictors of poor prognosis in breast cancer patients.

【Objective】In order to provide a reference basis for the evaluation of soil environmental qualityand potential risks in the Illicium verum production areas, the heavy metal pollution levels of forest soil in the main production areas of I. verum in Yunnan were detected.【Method】The soil of I. verum forest land in seven counties of Wenshan County, Yunnan Province was studied. Eight heavy metal indexes of As, Cd, Cu, Cr, Pb, Hg, Zn and Ni were determined, and the pollution risks of soil heavy metals in forest land were evaluated by using individual and comprehensive pollution indexes.【Result】The coefficients of variation of heavy metals ranged from 7.11% to 18.75% in the test areas, and the average content of heavy metals Hg, As, Pb and Cr exceeded the background value of soil heavy metals in Yunnan Province, and that of As, Pb, and Cu exceeded the risk screening value. Pollution evaluation showed that the average value of single factor pollution index of As was 1.99, which was the alert level, and the Nemero comprehensive pollution index was evaluated as light pollution. The potential ecological risk factor and potential ecological risk index were both at low risk level, among which the ecological risk factor of Cd was the highest. The geological accumulation index values of Hg and As were between 1 and 2, and the pollution level was classified as moderate. Cluster analysis indicated that the soil heavy metals As, Pb, Cd, Cu, Zn, and Hg of the forest land were mainly influenced by soil parent matter and human activities, and the Cr and Ni were of similar sources, mainly from natural sources.【Conclusion】The contents of heavy metals of soil in I. verum planting area of Yunnan Province were significantly different, which were jointly influenced by human activities and soil parent matter, and part of heavy metals in some areas exceed the standard to a certain extent.

Abstract Background To evaluate the differences in pregnancy outcomes between assisted reproductive technology (ART) patients and natural pregnant women in Shanghai, China in the past 6 years objectively. And to assess the feasibility of the research method of registry-database linkage in mainland China. Methods This retrospective study was conducted using registry-database linkage. A total of 8102 pregnancies with ART and 8096 parturients with spontaneous conception (SC) from 10 reproductive centers and 111 hospitals composed our retrospective study. The primary outcomes were the rates of obstetric complications (pregnancy-induced hypertention [PIH], gestational diabetes mellitus [GDM], placenta previa, mode of delivery, preterm birth [PTB], low birth weight [LBW], and macrosomia). The prenatal outcomes were compared between ART and SC parturients, frozen-thawed embryo transfer (FET) and fresh embryo transfer, and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results The final matching rate of the target population was 92% by using registry linkage. ART resulted in a higher rate of multiple birth, PTB, LBW, cesarean section, placenta previa and GDM compared with SC in the singleton cohort. In ART patients, pregnant women with FET had a significantly higher risk of PIH than those with fresh embryo transfer (14.1% Vs 9.3%, AOR1.528, 95% CI 1.303–1.793), but there was no difference between IVF and ICSI. FET is also related to the severity of PIH. Conclusions ART increased the rate of complications during pregnancy, the risk and severity of PIH in patients with FET was higher than that in patients with fresh embryo transfer. The registry-database linkage study is an objective and feasible research method in mainland China.

Abstract Background The association between osteocalcin and mortality has been scantly studied. We aimed to investigate the association between osteocalcin along with its trajectories and mortality based on long-term longitudinal data. Methods We performed a retrospective cohort study of 9413 type 2 diabetic patients with at least three measurements of total serum osteocalcin within 3 years since their first inpatient diagnosis of type 2 diabetes. Baseline, mean values of osteocalcin levels and their trajectories were used as exposures. A multivariable-adjusted Cox proportional hazards model was used to estimate the association of osteocalcin levels and their trajectories with mortality. Results During a mean follow-up of 5.37 years, 1638 patients died, of whom 588 were due to cardiovascular events. Multivariable-adjusted hazard ratios (HRs) across quintiles of baseline osteocalcin levels were 2.88 (95% confidence interval (CI) 2.42–3.42), 1.65 (95% CI 1.37–1.99), 1.17 (95% CI 0.96–1.42), 1.00, and 1.92 (95% CI 1.60–2.30) for all-cause mortality, and 3.52 (95% CI 2.63–4.71), 2.00 (95% CI 1.46–2.73), 1.03 (95% CI 0.72–1.47), 1.00, 1.67 (95% CI 1.21–2.31) for CVD mortality, respectively. When we used the mean values of osteocalcin as the exposure, U-shaped associations were also found. These U-shaped associations were consistent among patients of different baseline characteristics. Patients with a stable or even increasing trajectory of osteocalcin may have a lower risk of both all-cause and CVD mortality. Conclusions A U-shape association between baseline osteocalcin and mortality was observed among patients with type 2 diabetes. Patients with lower levels of serum osteocalcin during follow-ups had higher risks for all-cause and cardiovascular mortality.

Background: Existing studies have already shown a connection between nitrogen dioxide (NO2) exposure and cerebrovascular mortality. However, the differential effects of NO2 on cerebrovascular disease and its subtypes remain unclear and require further exploration. Methods: Daily stroke mortality data between 2013 and 2021 in Shanghai, China were collected. Residential daily air pollution data for each decedent were predicted from a satellite model. An individual-level, time-stratified, case-crossover design was applied to examine the relationship between NO2 exposure and cerebrovascular mortality. A combination of conditional logistic regression and distributed lag models with a maximum lag of 7 days was used for data analysis. Results: A total of 219,147 cases of cerebrovascular mortality were recorded. Among them, the proportion of sequelae of cerebrovascular disease, hemorrhagic stroke and ischemic stroke was 50.7%, 17.1% and 27.5%, respectively. The monotonic increases in mortality risks of cerebrovascular diseases, sequelae of cerebrovascular disease and ischemic stroke were observed, without any discernible thresholds. Each 10 μg/m3 increase in NO2 concentration was associated with increments of 3.62% [95% confidence interval (CI): 2.56%, 4.69%] for total cerebrovascular mortality, 4.29% (95% CI: 2.81%, 5.80%) for sequelae of cerebrovascular disease mortality and 4.30% (95% CI: 2.30%, 6.33%) for ischemic stroke mortality. No positive associations between NO2 exposure and hemorrhagic stroke mortality were observed. A greater risk of NO2 was observed in the warm season, in patients with less than 9 years of education and in those with single marital status. The effects of NO2 were robust to mutual adjustment of co-pollutants. Conclusions: Short-term exposures to NO2 may increase the risk of cerebrovascular mortality, specifically for ischemic stroke and sequelae of cerebrovascular disease.

Abstract Infants conceived with in vitro fertilization (IVF) are exposed to underlying infertility and the IVF process. High risks of adverse birth outcomes (ABOs) were observed among these infants, including preterm birth, low birth weight, macrosomia, being large/small for gestational age (LGA/SGA). It is unclear whether the specific etiology of the rise of ABOs among IVF infants is IVF technology itself or underlying infertility. A total of 9,480 singletons conceived with IVF and 1,952,419 singletons from the general population were obtained in this study. Multivariable logistic regression model was used to assess variations in risk of ABOs according to causes of infertility. Poisson distributions were applied to calculate standardized risk ratios of IVF infants vs. general population after controlling the causes of infertility. Higher risk of preterm birth and low birth weight were observed among parents with polycystic ovary syndrome, endometriosis, uterine and semen abnormalities. Compared to the general population, after excluding the influence of infertility causes, singletons conceived with IVF were at higher risk of macrosomia (SRR = 1.28, 95% CI 1.14–1.44) and LGA (SRR = 1.25, 95% CI 1.15–1.35). The higher risk of ABOs in IVF was driven by both IVF treatments and infertility, which is important for improving IVF treatments and the managing pregnancies and child development.

Abstract. Background:. Little was known about the association among time in range (TIR), time above range (TAR), time below range (TBR), and cancer mortality among patients with type 2 diabetes. We aimed to investigate the association among TIR, TAR, TBR, and the risk of cancer mortality among patients with type 2 diabetes. Methods:. A total of 6225 patients with type 2 diabetes were prospectively recruited in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline and was defined as the average percentage of time in the target glucose range during a 24 h period. Cox proportion hazard regression analysis was used to determine the association between TIR and the risk of cancer mortality. Results:. During a mean follow-up of 7.10 years, we confirmed 237 death events related to cancer. The multivariable-adjusted hazard ratio (HR) for cancer mortality was 1.32 (95% confidence interval [CI]: 1.01–1.75) in patients with TIR ≤70% compared with those with TIR >70%. When TIR was considered as a continuous variable, the multivariable-adjusted HR for cancer mortality associated with each 10% decrease in TIR was 1.07 (95% CI: 1.02–1.14). In the site-specific analysis, a significant association between TIR as a continuous variable and the risk of hepatocellular cancer was found (HR: 1.24; 95% CI: 1.09–1.41). However, no relationship between hemoglobin A1c and cancer mortality was observed (HR: 1.04; 95% CI: 0.97–1.10). Conclusions:. The present study found an inverse association of TIR with the risk of cancer mortality among patients with type 2 diabetes. New evidence of TIR was added into the clinical practice that TIR may be an optimal target of glycemic control among patients with type 2 diabetes.

IntroductionIn an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant.MethodsFive isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days.ResultsThe results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1β/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson’s correlation.DiscussionTaken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.

Objectives: Baise, a multiethnic inhabited area of southwestern China, is a historical malaria-endemic area with a high prevalence of G6PD deficiency. However, few studies of G6PD deficiency have been conducted in this region. Therefore, we performed a genetic analysis of G6PD deficiency in the Baise population from January 2020 to June 2021.Methods: A SNPscan assay was developed to simultaneously detect 33 common Chinese G6PD mutations. 30 G6PD-deficient samples were used for the method’s validation. Then, a total of 709 suspected G6PD-deficient samples collated from the Baise population were evaluated for G6PD status, type of mutation and effect of mutations.Results: The SNPscan test had a sensitivity of 100% [95% confidence interval (CI): 94.87%–100%] and a specificity of 100% (95% CI: 87.66%–100%) for identifying G6PD mutations. A total of fifteen mutations were identified from 76.72% (544/709) of the samples. The most common mutation was discovered to be G6PD Kaiping (24.12%), followed by G6PD Canton (17.91%), and G6PD Gaohe (11.28%). We compared the G6PD mutation spectrum among Zhuang, Han and other Southeast Asian populations, and the Zhuang population’s mutation distribution was quite similar to that in the Han population.Conclusion: This study provided a detailed G6PD mutation spectrum in Baise of southwestern China and will be valuable for the diagnosis and research of G6PD deficiency in this area. Furthermore, the SNPscan assay could be used to quickly diagnose these G6PD mutations accurately.

BackgroundThe relation between circulating homocysteine (hcy) and folate concentrations and risk of type 2 diabetes mellitus (T2DM) has been evaluated in several observational studies with inconsistent results; and it is unclear about their causal relationships. Our aim was to assess the causality association between circulating hcy or folate concentrations and the development of T2DM using Mendelian randomization (MR) analysis, based on results of an observational study in Chinese adults.MethodsWe conducted an observational study of 370 patients with T2DM and 402 controls after routine physical examination who consulted at the Zhongnan Hospital of Wuhan University between March 2021 and December 2021. Correlations between hcy and folate and the incidence of T2DM were quantified using logistic regression models. Two-sample MR analysis was conducted using summary statistics of genetic variants gained from 2 genome-wide association studies (GWAS) on circulating hcy and folate concentrations in individuals of European ancestry and from an independent GWAS study based on DIAMANTE meta-analysis.ResultsIn the observational study, after logistic regression with multiple adjustment, lower hcy and higher folate levels were identified to be associated with the risk of T2DM, with OR (95% CI) for hcy of 1.032 (1.003–1.060); while 0.909 (0.840–0.983) for folate. In the MR analysis, the OR for T2DM was 1.08 (95% CI: 0.95, 1.21; P = 0.249) for each SD unit increase in genetically predicted homocysteinemia and the OR for T2DM per SD increase in genetically predicted folate elevation was 0.80 (95% CI: 0.60, 1.00, P = 0.026).ConclusionsWe discovered that high circulating hcy and low folate concentrations were related with an increased risk of developing T2DM in Chinese adults. Moreover, MR analysis provided genetic evidence for a possible causal relationship between serum folate and the risk of T2DM.

Abstract Background The de Winter ECG pattern was described by upsloping ST‐segment depression in leads V1‐V6, tall and symmetrical T waves in precordial leads. The ECG pattern is regarded to be associated with occlusion of the left anterior descending (LAD) artery. Methods One patient with de Winter ECG pattern was included. The 12‐lead ECG of patients with chest pain showed upsloping ST‐segment depression up to 3 mm at the J point in leads V2‐V6; tall symmetrical T waves in leads V2‐V4; 1mm J point elevation in lead aVR; ST‐segment depression 1mm in I, aVL leads and inverted T waves in the inferior leads. The ECG was showed the de Winter pattern. Results The ECG was showed the de Winter pattern. CAG was performed, which showed the normal left main; 60%‐80% LAD stenosis; 50%‐60% ostial right coronary artery(RCA) stenosis; and 90% stenosis of the vessel at middle segment. Both proximal and middle RCA vascular lesions were dilated and successfully inserted with drug‐eluting stents, respectively. Conclusion Our case the ECG was showed horizontal ST depression with tall T waves in leads V2‐V4 (maximal ST depression in lead V4) while only ST depression in leads V5‐V6, which may result from multivessel disease.

The research on the remote control of manipulators based on flexible sensor technology is gradually extensive. In order to achieve stable, accurate, and efficient control of the manipulator, it is necessary to reasonably design the structure of the sensor with excellent tensile strength and flexibility. The acquisition of manual information by high-performance sensors is the basis of manipulator control. This paper starts with the manufacturing of materials of the flexible sensor for the manipulator, introduces the substrate, sensor, and flexible electrode materials, respectively, and summarizes the performance of different flexible sensors. From the perspective of manufacturing, it introduces their basic principles and compares their advantages and disadvantages. Then, according to the different ways of wearing, the two control methods of data glove control and surface EMG control are respectively introduced, the principle, control process, and detection accuracy are summarized, and the problems of material microstructure, reducing the cost, optimizing the circuit design and so on are emphasized in this field. Finally, the commercial application in this field is explained and the future research direction is proposed from two aspects: how to ensure real-time control and better receive the feedback signal from the manipulator.