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This study investigates the biomass and carbon fixation rate of Chlorella sp. by the main valuable elements in converter steel slag in F/2 seawater medium. The results indicate that Ca, Mg, P, Si, Fe, and Mn can increase the biomass and carbon fixation rate of Chlorella sp., while Cu, Zn, Cr, and Al can decrease the biomass and carbon fixation rate of Chlorella sp.. Three machine learning methods known as Back Propagation neural network (BPNN), decision tree (DT), and random forest (RF) were applied to construct the prediction model for the carbon fixation rate of Chlorella sp. based on real-life experimental data obtained from single factor experiments. The overall results exhibited that the BPNN model is better than the DT model and RF model to predict the carbon fixation rate of Chlorella sp.. Finally, the maximum carbon fixation rate for Chlorella sp. predicted by BPNN model is 50.86 mg/(L·d), which was 2.46 times that of the control group, under the optimum conditions of Ca 5.77 g/L, Mg 4.74 g/L, P 1.27 g/L, Si 6.31×10−1 g/L, Fe 6.50×10−4 g/L, Mn 5.00×10−5 g/L, Cu 2.51×10−6 g/L, Zn 4.98×10−6 g/L, Cr 0 g/L, and Al 0 g/L in F/2 seawater medium.

Abstract There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner

Abstract Recent studies indicate that Glypican 1 (GPC-1) is aberrantly expressed and plays a key role in certain cancers, but little is known in the hepatocellular carcinoma. Raw data from TCGA, GTEx and TIMER databases were utilized to comprehensively analyze GPC-1 expression landscape in pan-cancer, and the biological function of GPC-1 was investigated in liver cancer cells. The results revealed that GPC-1 is highly expressed in HCC, negatively correlated with survival, and also positively correlated with immune infiltration and clinical stage. Furthermore, GPC-1 promoted cell proliferation and inhibited apoptosis in the HCC cell lines. WGCNA analysis and HCCDB database revealed that Akt acted as a key molecule related to GPC-1, influencing biological functions and regulating cell malignant behaviors via the AKT signaling pathway. In conclusion, our findings provide a relatively comprehensive understanding of the oncogenic role of GPC-1 in HCC, implying that GPC-1 could serve as an innovative therapeutic target.

Abstract As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.

Abstract Background The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. Methods Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. Results (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P

Carbon dots (CDs) prepared from biomass usually produce poor quantum yield and reproducibility. A fine separation of raw materials may enhance the fluorescence performance. In this work, embryos of cumin seeds were precisely chosen as the carbon source to prepare (CDs) through hydrothermal method. The obtained product (CDs-E) possessed a higher quantum yield of 10.60 % than those synthesized with testas or whole seeds, which may be due to the relatively smaller particle size and more C-N functional groups. Rutin, as a common natural active component, could quench the fluorescence of CDs-E notably through internal filtering effect. Herein, a highly selective fluorescent sensor based on CDs-E for detecting rutin was proposed with a linearity range of 0.05 ∼ 30 μM and a detection limit of 0.015 μM obtained. Additionally, the developed method was successfully applied for the detection of rutin in Flos Sophorae, rutin tablets and capsules. This work showed the significance of fine classification for natural carbon source in preparation of CDs and provided a feasible method for quality monitoring of rutin-related pharmaceuticals, health care products and traditional Chinese medicinal materials.

In order to grasp the degradation of rolling bearings and prevent the failure of mechanical equipment, a remaining useful life (RUL) prediction method of rolling bearings based on degradation detection and deep bidirectional long short-term memory networks (BiLSTM) was proposed, considering the incomplete degradation feature extraction and low prediction accuracy of existing methods. By extracting the characteristics of time domain, frequency domain, and time-frequency domain of the full-life bearing vibration signal, the monotonicity, trend, and robustness measurement indexes of each feature were calculated. The best feature set that can fully reflect the degradation information was constructed by ranking the weighted comprehensive indexes of the features. A degradation detection strategy was used to determine the degradation starting time for setting piecewise linear network label. The RUL prediction model based on deep BiLSTM was established and optimized through Dropout technology and piecewise learning rate. The model was verified by the full-life data set of rolling bearings. The results showed that compared with the support vector machine (SVM), the traditional recurrent neural network (RNN), the single-layer BiLSTM, and long short-term memory networks (LSTM) model without Dropout, the proposed method fitted the degradation trend best, and the root mean square error (RMSE) was the smallest and only 0.0281, which improved the accuracy of RUL prediction of rolling bearings, helped prevent bearing failure, and ensured the safe and reliable operation of rotating machinery.

Introduction: Ovarian steroidogenesis not only affects the embryonic development and pregnancy outcome, but also associates with many diseases in mammals and women. Exploring the nutrients and mechanisms influencing ovarian steroidogenesis is critical to maintaining the optimal reproductive performance, as well as guaranteeing body health. Objectives: This research aimed to explore the effect of retinol metabolism on ovarian steroidogenesis and the underlying mechanisms. Methods: Comparative transcriptomic analysis of ovaries from normal and low reproductive performance sows were performed to identify the main causes leading to low fertility. The metabolites regulating steroid hormones synthesis were investigated in ovarian granulosa cells. Gene interference, overexpression, dual-luciferase reporter assays, chromatin immunoprecipitation and transcriptome analysis were further conducted to explore the underlying mechanisms of Aldh1a1 mediating ovarian steroidogenesis. Results: Transcriptome analysis of ovaries from normal and low reproductive performance sows showed the significant differences in both retinol metabolism and steroid hormones synthesis, indicating retinol metabolism probably influenced steroid hormones synthesis. The related metabolite retinoic acid was furtherly proven a highly active and potent substance strengthening estrogen and progesterone synthesis in ovarian granulosa cells. For the first time, we revealed that retinoic acid synthesis in porcine and human ovarian granulosa cells was dominated by Aldh1a1, and required the assistance of Aldh1a2. Importantly, we demonstrated that Aldh1a1 enhanced the proliferation of ovarian granulosa cells by activating PI3K-Akt-hedgehog signaling pathways. In addition, Aldh1a1 regulated the expression of transcription factor MESP2, which targeted the transcription of Star and Cyp11a1 through binding to corresponding promoter regions. Conclusion: Our data identified Aldh1a1 modulates ovarian steroidogenesis through enhancing granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway. These findings provide valuable clues for improving ovarian health in mammals.

Abstract Background The host–microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, and microbial tryptophan metabolites are potent modulators of host physiology. However, whether and how these metabolites mediate host–microbiota interactions, particularly in terms of inter-microbial communication, remains unclear. Results Here, we have demonstrated that indole-3-lactic acid (ILA) is a key molecule produced by Lactobacillus in protecting against intestinal inflammation and correcting microbial dysbiosis. Specifically, Lactobacillus metabolizes tryptophan into ILA, thereby augmenting the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Notably, ILA, IPA, and IAA possess the ability to mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10−/− spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria (e.g., Clostridium), as well as the mRNA expression of acyl-CoA dehydrogenase and indolelactate dehydrogenase in vivo and in vitro, resulting in an augmented production of IPA and IAA. Furthermore, a mutant strain of Lactobacillus fails to protect against inflammation and producing other derivatives. ILA-mediated microbial cross-feeding was microbiota-dependent and specifically enhanced indole derivatives production under conditions of dysbiosis induced by Citrobacter rodentium or DSS, but not of microbiota disruption with antibiotics. Conclusion Taken together, we highlight mechanisms by which microbiome-host crosstalk cooperatively control intestinal homoeostasis through microbiota-derived indoles mediating the inter-microbial communication. These findings may contribute to the development of microbiota-derived metabolites or targeted “postbiotic” as potential interventions for the treatment or prevention of dysbiosis-driven diseases. Video Abstract

Abstract Visible‐infrared person re‐identification (VI‐ReID) aims to recognize images of the same person captured in different modalities. Existing methods mainly focus on learning single‐granularity representations, which have limited discriminability and weak robustness. This paper proposes a novel dual‐granularity feature fusion network for VI‐ReID. Specifically, a dual‐branch module that extracts global and local features and then fuses them to enhance the representative ability is adopted. Furthermore, an identity‐aware modal discrepancy loss that promotes modality alignment by reducing the gap between features from visible and infrared modalities is proposed. Finally, considering the influence of non‐discriminative information in the modal‐shared features of RGB‐IR, a greyscale conversion is introduced to extract modality‐irrelevant discriminative features better. Extensive experiments on the SYSU‐MM01 and RegDB datasets demonstrate the effectiveness of the framework and superiority over state‐of‐the‐art methods.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Abstract Objective To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). Methods This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1–3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded. Results A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = −0.413, p = 0.026) and NT-proBNP (r = −0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = −0.408, p = 0.028) and NT-proBNP (r = −0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95–52.36), MFI (OR 7.85, 95% CI 1.73–35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP. Conclusion SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.

Abstract Background Companion animals can contribute to the physical and mental health of people and often live in very close association with their owners. However, the antibiotic resistome carried by companion animals and the impact they have on their owners and living environment remain unclear. In this study, we compared the ARG profiles of cats, humans, and their living environments using metagenomic analysis to identify the core ARGs in the cat and human gut and explore the potential impact of cats on ARGs in the human gut through the environment. Results Results showed that the abundance of ARGs in the cat gut was significantly higher than that in the human gut (P 0.05). However, the abundance of aminoglycoside resistance genes including APH(2'')-IIa and AAC(6')-Im was significantly higher in cat owners than that in non-cat owners (P

Abstract Background Older people with hypertension may have more complex multisystem problems and a higher risk of morbidity and mortality. We aimed to examine the association of cognitive impairment (CI) and diabetes mellitus (DM) on all-cause mortality in the aged with hypertension (HTN). Methods This is a prospective cohort study with a sample of 1017 older people with hypertension aged 60 years or older who completed baseline examinations in 2009–2010 and followed up for ten years in 2020. The endpoint was death from any cause. Subjects were categorized as HTN only, HTN + DM, HTN + CI, and HTN + DM + CI. Cox regression model was used to determine the association of comorbidities on all-cause mortality. Results During the 10-year follow-up period, 196 deaths occurred. After adjusted for covariates, risk of death from any cause was significantly increased in the older people with increased comorbidities (P = 0.003). Compared with the HTN only, with HTN + CI, and HTN + DM + CI, the HRs (95% confidence intervals) for all-cause mortality were 1.61(1.13–2.30) and 1.79(1.07–2.99), respectively. In stratified analyses, the relationship between comorbidities level and the risk of all-cause mortality persisted. Conclusion All-cause mortality risks increased with increasing the comorbidities. This study emphasizes the importance of comprehensive management of the older people with HTN in clinical practice and public health policy.

Abstract Thermal homeostasis is vital for mammals and is controlled by brain neurocircuits. Yet, the neural pathways responsible for cold defense regulation are still unclear. Here, we found that a pathway from the lateral parabrachial nucleus (LPB) to the dorsomedial hypothalamus (DMH), which runs parallel to the canonical LPB to preoptic area (POA) pathway, is also crucial for cold defense. Together, these pathways make an equivalent and cumulative contribution, forming a parallel circuit. Specifically, activation of the LPB → DMH pathway induced strong cold-defense responses, including increases in thermogenesis of brown adipose tissue (BAT), muscle shivering, heart rate, and locomotion. Further, we identified somatostatin neurons in the LPB that target DMH to promote BAT thermogenesis. Therefore, we reveal a parallel circuit governing cold defense in mice, which enables resilience to hypothermia and provides a scalable and robust network in heat production, reshaping our understanding of neural circuit regulation of homeostatic behaviors.

Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial–mesenchymal transition (EMT) and mesothelial–mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

Extracting vanadium (V) from vanadium slag (VS) by the traditional roasting-leaching process has disadvantages of high energy consumption and high poisonous gases emission. In this work, a green and efficient route was developed to extract V from VS without roasting by electro-oxidation combined with ultrasound cavitation (EOUC) intensification in sulfuric acid solution. The leaching parameters (e.g., leaching temperature, sulfuric acid concentration, anodic current density, ultrasound power, liquid to solid ratio, leaching time and particle size) were optimized. The leaching mechanism was explored by comparing the leaching behavior and mineralogical evolution of the direct sulfuric acidic leaching (DSL), electro-oxidation-assisted sulfuric acidic leaching (EOSL), ultrasound cavitation-assisted sulfuric acidic leaching (UCSL) and EOUC methods. The results show that introducing electric field strengthens the ultrasound cavitation effect on slag particles in sulfuric acid solution. Under the optimum parameter of EOUC method, the leaching rate of V from VS is as high as 94.64 %. Using EOUC method can open the silicate-wrapped structure of the spinel, increase pore volume of VS from 0.00127 cm3 g−1 to 0.01124 cm3 g−1, decrease slag particle size from 26.8 μm to 16.4 μm and improve specific surface area from 0.508 m2 g−1 to 10.855 m2 g−1, which significantly accelerate V leaching process. The exposed spinel was oxidized by both electrochemical route and chemical route, forming a mixture of V3+ ion and VO2+ ion after leaching.

BackgroundDespite the long-lasting notion about the substantial contribution of intraoperative un-stabilization of homeostasis factors on the incidence on acute kidney injury (AKI), the possible influence of intraoperative glucose or lactate management, as a modifiable factor, on the development of AKI remains inconclusive.ObjectivesTo investigated the relationship between intraoperative hyperglycemia, hyperlactatemia, and postoperative AKI in cardiac surgery.MethodsA retrospective cohort study was conducted among 4,435 adult patients who underwent on-pump cardiac surgery from July 2019 to March 2022. Intraoperative hyperglycemia and hyperlactatemia were defined as blood glucose levels >10 mmol/L and lactate levels >2 mmol/L, respectively. The primary outcome was the incidence of AKI. All statistical analyses, including t tests, Wilcoxon rank sum tests, chi-square tests, Fisher's exact test, Kolmogorov-Smirnov test, logistic regression models, subgroup analyses, collinearity analysis, and receiver operating characteristic analysis, were performed using the statistical software program R version 4.1.1.ResultsAmong the 4,435 patients in the final analysis, a total of 734 (16.55%) patients developed AKI after on-pump cardiac surgery. All studied intraoperative metabolic disorders was associated with increased AKI risk, with most pronounced odds ratio (OR) noted for both hyperglycemia and hyperlactatemia were present intraoperatively [adjusted OR 3.69, 95% confidence intervals (CI) 2.68–5.13, p

Excessive iron intake is detrimental to human health, especially to the liver, which is the main organ for iron storage. Excessive iron intake can lead to liver injury. The gut-liver axis (GLA) refers to the bidirectional relationship between the gut and its microbiota and the liver, which is a combination of signals generated by dietary, genetic and environmental factors. Excessive iron intake disrupts the GLA at multiple interconnected levels, including the gut microbiota, gut barrier function, and the liver's innate immune system. Excessive iron intake induces gut microbiota dysbiosis, destroys gut barriers, promotes liver exposure to gut microbiota and its derived metabolites, and increases the pro-inflammatory environment of the liver. There is increasing evidence that excess iron intake alters the levels of gut microbiota-derived metabolites such as secondary bile acids (BAs), short-chain fatty acids, indoles, and trimethylamine N-oxide, which play an important role in maintaining homeostasis of the GLA. In addition to iron chelators, antioxidants, and anti-inflammatory agents currently used in iron overload therapy, gut barrier intervention may be a potential target for iron overload therapy. In this paper, we review the relationship between excess iron intake and chronic liver diseases, the regulation of iron homeostasis by the GLA, and focus on the effects of excess iron intake on the GLA. It has been suggested that probiotics, fecal microbiota transfer, farnesoid X receptor agonists, and microRNA may be potential therapeutic targets for iron overload-induced liver injury by protecting gut barrier function.

Abstract Left ventricular hypertrophy (LVH), the most common target organ damage in patients with hypertension, is closely related to excessive visceral adipose tissue (VAT) accumulation in the body. The hypertriglyceridemic waist (HTHW) phenotype can act as a surrogate marker of excessive VAT. However, the relationship between the HTHW phenotype and LVH in patients with hypertension remains unknown. The present study aimed to investigate whether the HTHW phenotype is associated with LVH, using echocardiography in a cross‐sectional study involving 4470 middle‐aged and older Chinese patients with hypertension. Logistic regression analysis revealed that patients with the HTHW phenotype were 1.52‐fold more likely to experience LVH than those with normal triglyceride levels and normal waist circumference. This association was independent of age, sex, and other potentially confounding factors. In the stratified analysis, a stronger correlation was found among women, people of at least 70 years of age, and people with hyperuricemia. These results suggest that distinguishing the HTHW phenotype in patients with hypertension could serve as a simple and effective screening strategy for identifying people with a higher risk of developing LVH.

Abstract Fatty acids are not only widely known as energy sources, but also play important roles in many metabolic pathways. The significance of fatty acids in modulating the reproductive potential of livestock has received greater recognition in recent years. Functional fatty acids and their metabolites improve follicular development, oocyte maturation and embryo development, as well as endometrial receptivity and placental vascular development, through enhancing energy supply and precursors for the synthesis of their productive hormones, such as steroid hormones and prostaglandins. However, many studies are focused on the impacts of individual functional fatty acids in the reproductive cycle, lacking studies involved in deeper mechanisms and optimal fatty acid requirements for specific physiological stages. Therefore, an overall consideration of the combination and synergy of functional fatty acids and the establishment of optimal fatty acid requirement for specific stages is needed to improve reproductive potential in livestock.

Abstract Background Abdominal obesity (AO) has been regarded as the most dangerous type of obesity. The Conicity-index (C-index) had a high ability to discriminate underlying AO. The purpose of this study was to determine the ability of C-index to predict all-cause mortality among non-cancer Chinese older people. Methods The participants were residents of the Wanshou Road community in Beijing, China. Receiver operating curve (ROC) curves were used to determine the sensitivity and specificity of the best cut-off values for different anthropometric measures for predicting all-cause mortality. The area under the curve (AUC) of the ROC curves were calculated to compare the relative ability of various anthropometric measures to correctly identify older people in the community where all-cause mortality occurs. Included subjects were grouped according to C-index tertiles. The association between C-index and all-cause mortality was verified using Kaplan–Meier survival analysis and different Cox regression models. Results During a mean follow-up period of 9.87 years, 1821 subjects completed follow-up. The average age was 71.21 years, of which 59.4% were female. The ROC curve results showed that the AUC of the C-index in predicting all-cause mortality was 0.633. Kaplan–Meier survival curves showed a clear dose–response relationship between C-index and all-cause mortality. With the increase of C-index, the survival rate of the study population showed a significant downward trend (P

Abstract Background The immature neonatal fecal microbiota substantially impacts the development of gut health and greatly increases the risk of disease. Developing effective strategies to modulate the development of neonatal fecal microbiota has great significance. Herein, we investigated whether the maternal dietary supplementation and oral administration of Lactobacillus reuteri could effectively promote the development and maturation of the fecal microbiome in piglets from birth to weaning. Results Metagenomic analysis of colostrum showed that maternal dietary L. reuteri supplementation influenced the overall microbiota composition, decreased the abundance of the phylum Proteobacteria and increased that of the species Bifidobacterium choerinum. KEGG pathway analysis revealed that maternal L. reuteri supplementation enriched the lysine biosynthesis and glycolysis/gluconeogenesis pathways and downregulated the bacterial invasion of epithelial cells in the colostrum. In addition, L. reuteri supplementation significantly altered the metabolite features and modules in umbilical cord blood serum based on metabolomics. Further, a significant covariation was observed between these differential metabolites and the species in colostrum. Maternal dietary L. reuteri supplementation also significantly influenced the microbiota composition and increased the meconium abundance of beneficial bacteria (such as Romboutsia, Lactobacillus, Blautia, Butyricicoccus, and Ruminococcus), some of which were markedly associated with several differential metabolites in umbilical cord blood serum between two groups. Notably, both the maternal dietary supplementation and oral intake of L. reuteri had strong impacts on the overall microbial composition and maturation of fecal microbiota in piglets during early life, and these effects were dependent on the growth stage. Oral administration of L. reuteri promoted diarrhea resistance in neonates, while maternal supplementation of L. reuteri enhanced the abilities of antioxidants and decreased inflammation. Moreover, the administration of L. reuteri via both methods in combination improved the growth performances of piglets. Conclusion Overall, our data demonstrated that L. reuteri had the ability to modulate the composition of fecal microbiota in newborn piglets by influencing the microbial community and functional composition in the colostrum and by altering several key metabolites in the umbilical cord blood serum. Also, both the maternal dietary supplementation and oral administration of L. reuteri effectively promoted the development and maturation of the fecal microbiome in piglets during early life. Both the maternal dietary supplementation and oral administration of L. reuteri in combination optimized the growth performances of piglets. Video Abstract

Abstract Aims Esketamine upregulates Zn2+-dependent matrix metalloproteinase 9 (MMP9) and increases the neuronal apoptosis in retinal ganglion cell layer during the early development. We aimed to test whether albumin can alleviate esketamine-induced apoptosis through downregulating Zn2+-dependent MMP9. Methods We investigate the role of Zn2+ in esketamine-induced neuronal apoptosis by immunofluorescence. MMP9 protein expression and enzyme activity were investigated by zymography in situ., western blot and immunofluorescence. Whole-mount retinas from P7 Sprague-Dawley rats were used. Results We demonstrated that esketamine exposure increased Zn2+ in the retinal GCL during the early development. Zn2+-dependent MMP9 expression and enzyme activity up-regulated, which eventually aggravated apoptosis. Albumin effectively down-regulated MMP9 expression and activity via binding of free zinc, ultimately protected neurons from apoptosis. Meanwhile albumin treatment promoted activated microglia into multi-nucleated macrophagocytes and decreased the inflammation. Conclusion Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn2+ accumulation in GCL and downregulating Zn2+-dependent MMP9.

BackgroundThe fundus of the stomach is a challenging region for endoscopic resection of gastrointestinal stromal tumors (GISTs), especially in the anterior wall of the fornix at the side of the greater curvature. This study aimed to introduce the Forward-Return Way (FRW) technique in gastric fundus operations and provide evidence of its advantages. The FRW technique allows the gastroscope to access the stomach fornix without entering the gastric antrum after passing through the gastric cardia. Using FRW, the gastroscope body makes a forward return along the wall of the posterior wall of the upper gastric body and the wall of the greater curvature.MethodsThe clinical data of patients with stromal tumors in muscularis propria at the gastric fundus (STMF) at the Fourth Hospital of China Medical University between May 2020- March 2021 were reviewed. The novel FRW technique was used in the procedures, and the beneficial effects, suitability, applicable lesion site, and success rates of FRW were analyzed.ResultsA total of 10 cases were reviewed, and the FRW technique was successfully performed in 7 cases (70%). The gastroscope’s tip reached the area just below the gastric cardia, allowing endoscopists to successfully access all angles and sites of the stomach’s fundus in all seven patients. The lesion was easily accessed, and the gastroscope was stable with good left-right and forward-backwards movements.ConclusionThe FRW technique significantly facilitates the resection of the GISTs by aligning the endoscopy body movement direction with the observation direction. Gastrointestinal Stromal Tumor; forward-return of gastroscopy along the gastric body wall; muscularis propria; gastric fundus.

The air density in high altitude gas tunnel is small and the air supply is difficult. The jet tunnel ventilation is a common construction ventilation mode. In order to explore the pollutant distribution characteristics and the optimal ventilation length of tunnel ventilation in high altitude gas tunnel, Ningchan tunnel has been taken as the engineering background, the fluid dynamics software Fluent has been used to establish a three-dimensional model of jet tunnel ventilation, the distribution characteristics of methane, hydrogen sulfide and other harmful gas in the tunnel have been studied, and the optimal ventilation length of tunnel ventilation in high altitude gas tunnel degree has been explored. The results show that: the minimum ventilation length required in the existing technical specifications of gas tunnel is not reasonable, which leads to the existence of low-speed wind area in the tunnel, and harmful gas is easy to gather in the single head section, and the gas concentration can reach 0.59% at 2 m away from the working face; by reducing the ventilation length, the gas concentration in the single head section can be effectively reduced, and when the ventilation length is 1,200 m, the gas concentration at 2 m away from the working face will be reduced to 0.31%; setting local fan in front of the roadway can also significantly improve the accumulation degree of harmful gas in the single end section. The maximum gas concentration of working face reduced to 0.24%, and the average gas concentration of reduced to 0.15%. The results can provide reference for ventilation scheme of high altitude gas tunnel construction.

Abstract Background Increasing evidence suggests that aberrant methylation is involved in 5-fluorouracil (5-FU) resistance in gastric cancer (GC). Our previous work has identified that Methyl-CpG binding protein 2 (MeCP2) promotes GC progression by binding to the methylation sites of promoter regions of specific genes to affect the downstream signaling pathways. However, the function and molecular mechanisms of MeCP2 in GC 5-FU resistance remain unclear. Methods We detected the expression of MeCP2 in 5-FU-resistant GC cells and examined cell behaviors when MeCP2 was silenced. The molecular mechanisms were explored through chromatin immunoprecipitation (ChIP)-qRT-PCR, luciferase reporter assay, clinical tissue samples analysis, and in vivo tumorigenicity assay. Results MeCP2 was up-regulated in 5-FU-resistant GC cells. Knockdown of MeCP2 enhanced the sensitivity of the cells to 5-FU. Moreover, MeCP2 promoted NOX4 transcription in the cells by binding to the promoter of NOX4. Silencing NOX4 rescued the inductive effect of MeCP2 overexpression on 5-FU sensitivity of GC cells and reduced the expression of NOX4 and PKM2 in MeCP2 overexpressed 5-FU-resistant GC cells. In addition, our in vivo experiments demonstrated that MeCP2 knockdown enhanced 5-FU sensitivity in tumors. Conclusion MeCP2 confers 5-FU resistance in GC cells via upregulating the NOX4/PKM2 pathway, which may lead to a promising therapeutic strategy for GC.

Abstract The triglyceride glucose (TyG) index was regarded as a simple surrogate marker of insulin resistance (IR). It is confirmed that IR was significantly associated with hyperuricemia, and obesity was the risk factor for IR and hyperuricemia. However, the relationship between the TyG index and hyperuricemia and the potential role of obesity in Han Chinese hypertension are not entirely elucidated. A community‐based cross‐sectional study was conducted in 4551 hypertension patients aged 40–75 years with clinical and biochemical data. The TyG index was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. Hyperuricemia was determined as serum uric acid ≥357μmol/L (6 mg/dl) for females and ≥417μmol/L (7 mg/dl) for males. Our study suggested that the TyG index was higher in patients with hyperuricemia than in those without (8.99±0.61, 8.70±0.59, p

Abstract Background In patients with diabetes and hypertension, proteinuria is independently associated with all-cause death. However, in the general population, urinary albumin to creatinine ratio (UACR) is less used to predict all-cause mortality. When the urinary albumin to creatinine ratio is within the normal range (UACR 30 mg/g). We used Kaplan-Meier survival analysis and Cox regression model to verify the relationship between UACR and all-cause mortality. Results At an average follow-up of 9.87 years (718,407.3 years), the total mortality rate were 183.4/1000. In the Cox proportional hazards model, after adjusting for possible confounders, those with normal high-value UACR (group 2) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.289, 95% confidence interval (CI) 1.002 ~ 1.659 for all-cause mortality]. Those with proteinuria (group 3) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.394, 95% confidence interval (CI) 1.020 ~ 1.905 for all-cause mortality]. Conclusion Urinary albumin to creatinine ratio is an important risk factor for all-cause death in community population. Even if it is within the normal range (UACR

Abstract Background This study aimed to assess the relationship of a new anthropometric index with left ventricular hypertrophy (LVH) in hypertensive patients among the Han Chinese. Methods The study is a community-based cross-sectional study that included 4639 patients with hypertension and integrated clinical and echocardiographic data. Left ventricular (LV) mass was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of left ventricular mass indexed (LVMI) over 49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Quartiles of a body shape index (ABSI), body roundness index (BRI), waist circumference (WC), and body mass index (BMI) were used regarding LVH prevalence. The logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CI) of the new anthropometric index and LVH. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the obesity indices for LVH risk. Results The prevalence of LVH increased across quartiles for ABSI, BRI, BMI, and WC. Comparing the lowest with the highest quartile, adjusted OR (95% CI) for LVH were significantly different for BRI 3.86 (3.12–4.77), BMI 3.54 (2.90–4.31), and WC 2.29 (1.88–2.78). No association was observed for ABSI. According to ROC analysis, the area under the curve (AUC) of BRI was (AUC: 0.653, 95% CI 0.637–0.669), BMI (AUC: 0.628, 95% CI 0.612–0.644), WC (AUC: 0.576, 95% CI 0.559–0.593), ABSI (AUC: 0.499, 95% CI 0.482–0.516). Conclusions This study shows that LVH prevalence increased per quartile across the Han Chinese population with hypertension for ABSI, BRI, BMI, and WC. There is a significant association between BRI and LVH in hypertensive people, while ABSI was not. BRI showed potential for use as an alternative obesity measure in the assessment of LVH.

BackgroundThe association between intraoperative hyperglycemia (IH) and postoperative infections in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) is inadequately studied.MethodsA total of 3,428 patients who underwent cardiac surgery with CPB at our institution between June 1, 2019 and July 30, 2021 were enrolled to evaluate the association of IH (blood glucose ≥ 180 mg/dL) with postoperative infection in patients. The new onset of any type of infection and the optimal cutoff values of intraoperative glucose to predict in-hospital infection were determined.ResultsThe composite outcome occurred in 497 of 3,428 (14.50%) patients. IH was associated with an increased risk of postoperative composite infection [adjusted odds ratio: 1.39, (95% confidence interval), 1.06–1.82, P = 0.016]. Restricted cubic splines were applied to flexibly model and visualize the association of intraoperative peak glucose with infection, and a J-shaped association was revealed. Besides, it was demonstrated that the possibility of infection was relatively flat till 150 mg/dL glucose levels which started to rapidly increase afterward.ConclusionWe summarize that IH is associated with an elevated risk of postoperative new-onset composite infections and perioperative blood glucose management should be more stringent, i.e., lesser than 150 mg/dL in patients undergoing cardiac surgery.

Abstract The strategy of combining immune checkpoint inhibitors (ICIs) with anthracycline is recommended by clinical guidelines for the standard‐of‐care treatment of triple‐negative breast cancer (TNBC). Nevertheless, several fundamental clinical principles are yet to be elucidated to achieve a great therapeutic effect, including cancer‐homing delivery efficiency and ordinal‐interval regime. Tumor‐derived extracellular vesicles (TDEVs), as vectors for intratumoral intercellular communication, can encapsulate therapeutic agents and home tumors. However, PD‐L1 overexpression in TDEVs leads to systemic immunosuppression during in vivo circulation, ultimately inhibiting intratumoral T activity. In this study, CRISPR/Cas9‐edited Pd‐l1KO TDEV‐fusogenic anthracycline doxorubicin (DOX) liposomes with high drug encapsulation (97%) are fabricated, which homologously deliver DOX to breast cancer cells to intensify the immunogenic response and induce PD‐L1 overexpression in the tumor. By setting the stage for sensitizing tumors to ICIs, sequential treatment with disulfide‐linked PD1‐cross‐anchored TDEVs nanogels at one‐day interval could sustainably release PD1 in the tumor, triggering a high proportion of effector T cell‐mediated destruction of orthotopic and metastatic tumors without off‐target side effects in the 4T1‐bearing TNBC mouse model. Such a TDEV‐tandem‐augmented chemoimmunotherapeutic strategy with efficient cancer‐homing delivery capacity and optimized ordinal‐interval regime provides a solid foundation for developing chemoimmunotherapeutic formulations for TNBC therapy at the clinical level.

Abstract Background The Mini-Mental State Examination (MMSE) is the most widely used instrument to test cognitive functioning. The present study prospectively investigated the association between MMSE scores, MMSE domains, and all-cause mortality. Methods A total of 2134 participants aged 60 years or over, selected from one urban community-dwelling population in China, were enrolled in the study. The cognitive test was performed by use of the MMSE at baseline, and covariates were recorded simultaneously. Cox regression models were used for examining the cognitive function, expressed by different MMSE transformations, and all-cause mortality. After followed up for a median of 10.8 years (ranging from 1.0 to 11.3 years), loss to follow-up was 13.1% and 1854 individuals were finally included in the analyses. Results The subjects had the mean (SD) age of 71.01 (7.00) years, and 754 (40.67%) of them were women. Per point increase on MMSE scores was associated a 4% decreased risk of all-cause mortality [hazard ratio (HR): 0.96; 95%confidence interval (CI): 0.93–0.98]; compared to MMSE scores of ≥24, MMSE scores of

Abstract Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9–1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40–75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Our study suggested that the ABI was higher in patients with LVH than in those without (1.13±0.11, 1.11±0.11, p

Abstract Background Metabolic reprogramming sustains tumorigenesis and aggressiveness of neuroblastoma (NB), the most common extracranial malignancy in childhood, while underlying mechanisms and therapeutic approaches still remain elusive. Methods Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation (ChIP) sequencing, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by ChIP, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA-encoded protein and its partners on the lipid metabolism, mitochondrial activity, growth, invasion, and metastasis of NB cells. Results A novel 113-amino acid protein (p113) of CUT-like homeobox 1 (CUX1) was identified in NB cells treated by serum deprivation. Further validating studies revealed that nuclear p113 was encoded by circRNA of CUX1, and promoted the lipid metabolic reprogramming, mitochondrial activity, proliferation, invasion, and metastasis of NB cells. Mechanistically, p113 interacted with Zuotin-related factor 1 (ZRF1) and bromodomain protein 4 (BRD4) to form a transcriptional regulatory complex, and mediated the transactivation of ZRF1/BRD4 in upregulating ALDH3A1, NDUFA1, and NDUFAF5 essential for conversion of fatty aldehydes into fatty acids, fatty acid β-oxidation, and mitochondrial complex I activity. Administration of an inhibitory peptide blocking p113-ZRF1 interaction suppressed the tumorigenesis and aggressiveness of NB cells. In clinical NB cases, high expression of p113, ZRF1, or BRD4 was associated with poor survival of patients. Conclusions These results indicate that p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation.

BackgroundAnkle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are both important indicators of arterial stiffness and vascular injury. At present, most studies on the relationship between ABI and baPWV and all-cause mortality in community-based elderly are analyzing ABI or baPWV alone, and will focus on a single special population such as diabetes and stroke. The purpose of this study was to evaluate the relationship between ABI and baPWV in a Chinese community-based elderly population, and to analyze their impact on all-cause mortality in a community-based population through a follow-up of nearly 10 years.MethodsParticipants were residents of the Wanshou Road community in Beijing, China. A total of 2,162 people in the community were included, with an average age of 71.48 years. During a mean follow-up period of 9.87 years, 1,826 subjects completed follow-up. Kaplan-Meier survival analysis and different Cox regression models were used to verify the association of ABI and baPWV with all-cause mortality. The selected subjects were divided into two groups according to ABI and baPWV, and ABI was divided into two groups with 0.90 as the cut-off point (group 1: 0.9 < ABI ≤ 1.3; group 2: ABI ≤ 0.9); according to the level of baPWV, they were divided into three groups (Tertile 1: baPWV

Esophageal carcinoma (EC) is recognized as one of the most frequently occurring malignancies worldwide, and its high morbidity rate motivates efforts to identify potential therapeutic targets. Notably, forkhead box (FOX) family genes are highlighted as possible biomarkers for diagnostics, prognostics, and therapeutics of various malignancies, including EC. Our present study was performed to investigate the underlying mechanism of FOXO6 on the development of EC. We observed a significant upregulation of FOXO6 in EC tissues, contributing to the migration and proliferation in EC cells through gain- and loss-of-function assays. FOXO6 directly interacted with the ubiquitin-specific processing protease 7 (USP7) gene promoter and enhanced its transcriptional activity, which resulted in suppressed cancer cell apoptosis as revealed by chromatin immunoprecipitation (ChIP)-qPCR. USP7 enhanced the ubiquitination of Jumonji domain-containing protein D3 (JMJD3), elevated JMJD3-promoted growth of EC cells, and transcriptionally activated clusterin (CLU) expression at the promoter region via histone H3 lysine 27 tri-methyl (H3K27me3) demethylation, according to immunoprecipitation and ubiquitination assays. Finally, we verified that FOXO6 mediated effects on the USP7/JMJD3/CLU axis to exert an oncogenic role in vivo, which was blocked by USP7 and JMJD3 inhibitor. Our findings demonstrate an important role of the FOXO6/USP7/JMJD3/CLU pathway in EC progression and thus provide attractive potential therapeutic targets for EC patients.

BackgroundTo explore the relationship between weight-adjusted-waist index (WWI) and the risk of all-cause mortality in one urban community-dwelling population in China.MethodsThis is a prospective cohort study with a sample of 1,863 older adults aged 60 years or over in Beijing who completed baseline examinations in 2009–2010 and a 10-year follow-up in 2020. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Cox regression analysis was performed to investigate the significance of the association of WWI with all-cause mortality. The area under the receiver operating characteristic (ROC) curves were used to compare the ability of each obesity index to predict mortality.ResultsDuring a median follow-up of 10.8 years (1.0 to 11.3 years), 339 deaths occurred. After adjusted for covariates, the hazard ratios (HRs) for all-cause mortality progressively increased across the tertile of WWI. Compared with the lowest WWI category (tertile1

N6-methyladenosine (m6A) is the most common and conserved internal eukaryotic mRNA modification. m6A modification is a dynamic and reversible post-transcriptional regulatory modification, initiated by methylase and removed by RNA demethylase. m6A-binding proteins recognise the m6A modification to regulate gene expression. Recent studies have shown that altered m6A levels and abnormal regulator expression are crucial in the ageing process and the occurrence of age-related diseases. In this review, we summarise some key findings in the field of m6A modification in the ageing process and age-related diseases, including cell senescence, autophagy, inflammation, oxidative stress, DNA damage, tumours, neurodegenerative diseases, diabetes, and cardiovascular diseases (CVDs). We focused on the biological function and potential molecular mechanisms of m6A RNA methylation in ageing and age-related disease progression. We believe that m6A modification may provide a new target for anti-ageing therapies.

PurposeTo investigate the differences of retinal thickness (RT) and superficial vascular density (SVD) between patients with Sjogren's syndrome (SS) and healthy controls (HCs) using optical coherence tomography angiography (OCTA).MethodsIndividuals with SS and healthy controls were enrolled (n = 12 per group). An en-face OCTA scan was performed on each eye. Images were segmented into 9 subregions and macular RT and SVD were measured and compared between the 2 groups.ResultsVisual acuity (VA) differed significantly between patients with SS (24 eyes) and controls (24 eyes) (p < 0.001). In patients with SS, inner RT was reduced in the inner superior region, outer RT was reduced in the outer nasal (ON) region, and full RT was reduced in the ON region compared with the control group (p < 0.05). RT was negatively correlated with serum IgG level in the outer and full retina at ON regions (p < 0.05). SVD in the inner nasal, ON, and inner temporal regions was significantly lower in patients with SS than in control subjects (p < 0.05). SVD was positively correlated with full RT in the ON region in patients with SS (p < 0.05). The areas under the receiver operating characteristic (ROC) curves for the diagnostic sensitivity of outer RT and full RT in the ON region for SS were 0.828 (95% CI: 0.709–0.947) and 0.839 (95% CI: 0.715–0.963), respectively.ConclusionsIn patients with SS, retinal thinning in the macular area—which affects vision—can also reflect the severity of dry eyes in SS and has clinical value for assisted imaging diagnosis.

N-methylation of amines and imines with formic acid as C1 source by easily prepared Pt NPs as heterogeneous catalyst is reported here. Primary, secondary amines and imines were successfully methylated in good to excellent yields under mild conditions. Both aromatic and aliphatic amines could be applied as substrates. Meanwhile, the heterogeneous Pt NPs were capable to be recylcled and reused for 7 times without significant decrease of reactivity. This protocol provided an indirect utilization pathway of CO2 by using formic acid as C1 source.

Left ventricular hypertrophy (LVH) has been classified separately as an independent risk factor for hypertension. However, comparisons between different body size indices and left ventricular hypertrophy (LVH) in hypertensive populations have not been reported yet. In this study, we enrolled 4,639 hypertensive patients from rural China. Anthropometric indices and cardiovascular disease risk factor variables were measured and analyzed using Spearman’s correlation, logistic regression, and receiver operating characteristic (ROC) curve analyses. Patients in the highest quartile of body size indices were more likely to have left ventricular hypertrophy than those in the lowest quartile; these indices were BMI (adjusted OR: 3.55, 95% CI: 2.90; 4.35), WC (adjusted OR: 2.23, 95% CI: 1.84; 2.70), WHR (adjusted OR: 1.44, 95% CI: 1.18; 1.75), and WHtR (adjusted OR: 3.23, 95% CI: 2.62; 3.99). The areas under the ROC curves of BMI (AUC: 0.628, 95% CI: 0.612; 0.644), WHtR (AUC: 0.628, 95% CI: 0.560; 0.593), WHR (AUC: 0.530, 95% CI: 0.513; 0.547), and WC (AUC: 0.576, 95% CI: 0.513; 0.547) were all above 0.5, which indicated that the four anthropometric indicators may be associated with LVH. The four anthropometric indicators of obesity were identified as risk factors for LVH. Weight control might help reduce the risk of left ventricular hypertrophy.

Purpose: To evaluate the conjunctival and fundus retinal vessel density in patients with systemic lupus erythematosus (SLE) with optical coherence tomography angiography (OCTA), and to investigate the relationship between vessel density and clinical indicators.Methods: Twelve patients with SLE (24 eyes) and 12 healthy controls (24 eyes) were recruited. OCTA was used to examine the superficial retina layer (SRL) and deep retina layer (DRL) in the macular retina and conjunctival capillary plexus of each eye. We calculated the density of the temporal conjunctival vessels, fundus microvascular (MIR), macrovascular (MAR) and total MIR(TMI) and compared the results in both groups. We used annular partitioning (C1–C6), hemispheric quadrants, and Early Treatment Diabetic Retinopathy Study partitioning (ETDRS) to analyze changes in the retinal vascular density. Correlation analysis was used to investigate the association between blood capillary density and clinical indicators.Results: OCTA results showed significant differences in the conjunctival microvascular density (p < 0.001). There was no significant difference in MIR, TMI, and MAR in the superficial layers between the SLE and healthy group (p > 0.05). The DRL and DTMI (Deeper TMI) densities were decreased in the macular regions of SLE patients (p < 0.05). In the hemispheric segmentation analysis, the superficial MIR was significantly decreased in the IL (inferior left) region of the SLE patients (p < 0.05), and the deep MIR in the IR (inferior right) region was significantly reduced (p < 0.05). In the ETDRS partitioning analysis, the superficial MIR in the inferior, right, and left subdivisions was significantly decreased in the SLE patients (p < 0.05). In the circular segmentation analysis, the deep MIR in the C1 and C3 regions was significantly reduced in SLE patients (p < 0.05), while the superficial MIR density was decreased only in the C3 region (p < 0.05). The conjunctival vascular density was negatively correlated with the STMI (Superficial TMI) (r = −0.5107; p = 0.0108) and DTMI (r = −0.9418, p < 0.0001). There was no significant correlation between vascular density and SLEDAI-2k (Systemic Lupus Erythematosus Disease Activity Index−2000) (P > 0.05).Conclusion: Clinically, patients with SLE and patients suspected of SLE should receive OCTA examination in a comprehensive eye examination to detect changes in ocular microcirculation at an early stage.

Abstract Background As a metabolic reprogramming feature, cancer cells derive most of their energy from aerobic glycolysis, while its regulatory mechanisms and therapeutic strategies continue to be illusive. Methods Integrative analysis of publically available expression profile datasets was used to identify critical transcriptional regulators and their target glycolytic enzymes. The functions and acting mechanisms of transcriptional regulators in cancer cells were investigated by using in vitro and in vivo assays. The Kaplan–Meier curve and log‐rank assay were used to conduct the survival study. Results Salmonella pathogenicity island 1 (SPI1/PU.1), a haematopoietic transcription factor, was identified to facilitate glycolytic process, tumourigenesis, invasiveness, as well as metastasis of colon cancer cells, which was interplayed by tumour‐associated neutrophils. Mechanistically, neutrophils delivered SPI1 mRNA via extracellular vesicles, resulting in enhanced SPI1 expression of cancer cells. Through physical interaction with SPI1‐related protein (SPIB), SPI1 drove expression of glycolytic genes within cancer cells, which in turn induced polarization of neutrophils via glycolytic metabolite lactate. Depletion of neutrophils or SPIB–SPI1 interaction in cancer cells significantly inhibited glycolytic process, tumourigenesis and aggressiveness. Upregulation of SPI1 or SPIB was found to be associated with poor prognosis in patients suffering from colon cancer. Conclusions Therapeutic targeting of SPIB/SPI1‐facilitated interplay of cancerous cells and neutrophils suppresses aerobic glycolysis and progression of cancer.

Background: The population of older adults is growing rapidly with the increasing pace of aging worldwide. The triglyceride glucose (TyG) index has been a convenient and reliable surrogate marker of insulin resistance (IR). This study aimed to determine the association between the TyG index and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) in Chinese older adults.Methods: A total of 2,035 participants aged 60 years or above were enrolled. Demographic, anthropometric, and cardiovascular risk factors were collected. TyG index was calculated using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Arterial stiffness was measured using baPWV.Results: The participants, with the mean [standard deviation (SD)] age of 71.32 (6.75) years, the female proportion of 39.65%, the mean (SD) baPWV of 1,998 (437) cm/s, and the mean (SD) TyG index of 8.86 (0.54), were divided into four groups according to TyG index quartiles. Age-adjusted baPWV presented an increasing trend according to TyG index quartiles. In the fully adjusted linear regression model, the baPWV increased 49 cm/s, with the 95% confidence interval (CI) from 24 to 75 cm/s, per-SD increase in the TyG index. In the fully-adjusted logistic regression model, the odds ratio (95% CI) of high baPWV (>75th percentile) was 1.32 (1.09, 1.60) for each SD increase in the TyG index. The generalized additive model analysis also confirmed the significant association of the TyG index with baPWV and high baPWV.Conclusion: The TyG index is significantly associated with arterial stiffness assessed by baPWV in Chinese older adults.

Fatty acids play important roles in maintaining ovarian steroidogenesis and endometrial receptivity. Porcine primary ovarian granulosa cells (PGCs) and endometrial epithelial cells (PEECs) were treated with or without medium- and short-chain fatty acids (MSFAs) for 24 h. The mRNA abundance of genes was detected by fluorescence quantitative PCR. The hormone levels in the PGCs supernatant and the rate of adhesion of porcine trophoblast cells (pTrs) to PEECs were measured. Sows were fed diets with or without MSFAs supplementation during early gestation. The fecal and vaginal microbiomes were identified using 16S sequencing. Reproductive performance was recorded at parturition. MSFAs increased the mRNA abundance of genes involved in steroidogenesis, luteinization in PGCs and endometrial receptivity in PEECs (p < 0.05). The estrogen level in the PGC supernatant and the rate of adhesion increased (p < 0.05). Dietary supplementation with MSFAs increased serum estrogen levels and the total number of live piglets per litter (p < 0.01). Moreover, MSFAs reduced the fecal Trueperella abundance and vaginal Escherichia-Shigella and Clostridium_sensu_stricto_1 abundance. These data revealed that MSFAs improved pregnancy outcomes in sows by enhancing ovarian steroidogenesis and endometrial receptivity while limiting the abundance of several intestinal and vaginal pathogens at early stages of pregnancy.

Objective: Resistance to anticancer agents ensures a poor prognosis in patients with lung cancer. Metformin could enhance the anticancer effects of standard antineoplastic agents [traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)]; however, it is unclear whether metformin can be combined with antineoplastic agents in the treatment of lung cancer. To explore the efficacy of combinational strategies, we performed a systematic review and meta-analysis for diabetic and non-diabetic patients with lung cancer.Method: An electronic literature search was performed to obtain relevant randomized controlled trials (RCTs) and observational cohort studies. Hazard ratios (HR) with 95% confidence intervals (CI) of overall survival (OS) and progression-free survival (PFS) outcomes were extracted. Subgroup analysis by antineoplastic agents, study type, histology and clinical stage were investigated.Results: 14 studies (three RCTs and eleven observational cohort studies) consisting 3,856 patients were included in the meta-analysis. Compared to standard antineoplastic agents alone (traditional chemotherapy drugs, EGFR-TKIs or ICIs), the antineoplastic agents combined with metformin significantly improved OS (HR 0.73, 95% CI 0.66–0.81, p < 0.00001) and PFS (HR 0.72, 95% CI 0.59–0.88, p = 0.001); a similar association was found in observational evidence. Limited data from RCTs showed no differences in OS or PFS.Conclusion: Metformin plus antineoplastic agents may improve survival outcomes of patients with lung cancer. Further investigation is needed.

Abstract Background Primary periodic paralysis is characterized by recurrent quadriplegia typically associated with abnormal serum potassium levels. The molecular diagnosis of primary PP previously based on Sanger sequencing of hot spots or exon-by-exon screening of the reported genes. Methods We developed a gene panel that includes 10 ion channel-related genes and 245 muscular dystrophy- and myopathy-related genes and used this panel to diagnose 60 patients with primary periodic paralysis and identify the disease-causing or risk-associated gene mutations. Results Mutations of 5 genes were discovered in 39 patients (65.0%). SCN4A, KCNJ2 and CACNA1S variants accounted for 92.5% of the patients with a genetic diagnosis. Conclusions Targeted next-generation sequencing offers a cost-effective approach to expand the genotypes of primary periodic paralysis. A clearer genetic profile enables the prevention of paralysis attacks, avoidance of triggers and the monitoring of complications.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep–wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep–wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

Due to the special mechanical properties of macker rock, problems may be caused easily if the pressure of the surrounding rock calculated from the standard empirical equation is used in the structural design of tunnel support, such as obviously insufficient bearing capacity of the support structure, large deformation, and collapse. Taking the Jiangluling Macker Tunnel in Gonghe-Yushu Highway as an example, the distribution pattern of plastic zone of the surrounding rock and the calculation method and reasonable values of pressure of the surrounding rock are studied in this paper, by means of theoretical analysis, numerical computation, and field measurement data. The results show that the elastic-plastic analysis method is suitable for the pressure of the surrounding rock of macker tunnel. The influence radius of the plastic zone of the surrounding rock can be 32 m, and the lateral pressure of the surrounding rock of the tunnel is equivalent to the vertical pressure. In the absence of test conditions and measured data, the pressure of the surrounding rock can be approximately 0.83 MPa for the purpose of design of tunnel support structure. This conclusion provides technical support for projects in similar conditions.