Intrinsic Activity Identification of Noble Metal Single-Sites for Electrocatalytic Chlorine Evolution.

Single-atom catalysts with maximal atom-utilization have emerged as promising alternatives for chlorine evolution reaction (CER) toward valuable Cl2 production. However, understanding their intrinsic CER activity have so far been plagued due to the lack of well-defined atomic structure controlling. Herein, we prepare and identify a series of atomically dispersed noble metals (e.g., Pt, Ir, Ru) in nitrogen-doped nanocarbons (M1-N-C) with an identical M-N4 moiety, which allows objective activity evaluation. Electrochemical experiments, operando Raman spectroscopy, and quasi-in situ electron paramagnetic resonance spectroscopy analyses collectively reveal that all the three M1-N-C proceed the CER via a direct Cl-mediated Vomer-Heyrovský mechanism with reactivity following the trend of Pt1-N-C > Ir1-N-C > Ru1-N-C. Density functional theory (DFT) calculations reveal that this activity trend is governed by the binding strength of Cl*-Cl intermediate (ΔGCl*-Cl) on M-N4 sites (Pt < Ir < Ru) featuring distinct d-band centers, providing a reliable thermodynamic descriptor for rational design of single metal sites toward Cl2 electrosynthesis.

Comparison of characteristics of children hospitalized for respiratory syncytial virus infection during the pre- and post-COVID-19 eras: a multicenter retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. METHODS: A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018-2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. RESULTS: A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January-April and October-December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P < 0.05). Furthermore, compared to the pre-COVID-19 group, the post-COVID-19 group displayed higher rates of SLRTI and mechanical ventilation, with a longer length of hospital stay (all P < 0.05). Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6 were the shared independent risk factors for RSV-related SLRTI in both pre- and post-COVID-19 groups, whereas seizures and co-infection were independently associated with SLRTI only in the post-COVID-19 group. CONCLUSIONS: An off-season RSV endemic was observed in Yunnan during the post-COVID-19 era, with changed clinical features and increased severity. Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6, seizures, and co-infection were the risk factors for RSV-related SLRTI in the post-COVID-19 era.

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. ß-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. ß-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

Nocardamine mitigates cellular dysfunction induced by oxidative stress in periodontal ligament stem cells.

BACKGROUND: The role of periodontal ligament stem cells (PDLSCs) in repairing periodontal destruction is crucial, but their functions can be impaired by excessive oxidative stress (OS). Nocardamine (NOCA), a cyclic siderophore, has been shown to possess anti-cancer and anti-bacterial properties. This study aimed to investigate the protective mechanisms of NOCA against OS-induced cellular dysfunction in PDLSCs. METHODS: The cytotoxicity of NOCA on PDLSCs was assessed using a CCK-8 assay. PDLSCs were then treated with hydrogen peroxide (H2O2) to induce OS. ROS levels, cell viability, and antioxidant factor expression were analyzed using relevant kits after treatment. Small molecule inhibitors U0126 and XAV-939 were employed to block ERK signaling and Wnt pathways respectively. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining of mineralized nodules. Expression levels of osteogenic gene markers and ERK pathway were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis. ß-catenin nuclear localization was examined by western blotting and confocal microscopy. RESULTS: NOCA exhibited no significant cytotoxicity at concentrations below 20 µM and effectively inhibited H2O2-induced OS in PDLSCs. NOCA also restored ALP activity, mineralized nodule formation, and the expression of osteogenic markers in H2O2-stimulated PDLSCs. Mechanistically, NOCA increased p-ERK level and promoted ß-catenin translocation into the nucleus; however, blocking ERK pathway disrupted the osteogenic protection provided by NOCA and impaired its ability to induce ß-catenin nuclear translocation under OS conditions in PDLSCs. CONCLUSIONS: NOCA protected PDLSCs against H2O2-induced OS and effectively restored impaired osteogenic differentiation in PDLSCs by modulating the ERK/Wnt signaling pathway.

Characterization of a novel SCN5A mutation associated with long QT syndrome and arrhythmogenic right ventricular cardiomyopathy in a family.

Sudden cardiac death represents a significant diagnostic challenge for forensic pathologists, particularly in inherited arrhythmia syndromes or cardiomyopathies resulting from genetic defects. Molecular autopsies can reveal the underlying molecular etiology in such cases. In this study, we investigated a family with a history of sudden cardiac death to elucidate the molecular basis responsible for sudden cardiac death. The proband underwent a comprehensive forensic examination. Family members received thorough clinical evaluations, including electrocardiogram, Holter monitoring, echocardiography, and cardiac magnetic imaging. Whole exome sequencing and genetic analysis were performed on the deceased and her parents. In addition, Western blotting and patch-clamp recordings were employed to evaluate the expression and function of the mutant protein in vitro. Forensic examination diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) as the cause of sudden death. Genetic analysis identified a novel missense mutation in SCN5A (p.V1323L), which was assessed as likely pathogenic by the ACMG guideline. Another family member carrying the mutation manifested long QT syndrome and mild cardiac fibrosis. The cellular electrophysiological study demonstrated that the mutation resulted in an enhanced late sodium current, suggesting it was a gain-of-function mutation. This study characterizes a novel SCN5A mutation that putatively causes long QT syndrome and may contribute to the development of ARVC. Our work expands the pathogenic spectrum of SCN5A variants and underscores the importance of molecular autopsy in sudden death cases, especially in those with suspected genetic disorders.

Distribution of Antibiotic-Resistant Genes in Intestines of Infants and Influencing Factors.

The objective of this study is to assess the prevalence of antibiotic-resistant genes (ARGs) in the intestines of infants and the factors affecting their distribution. Breast milk and infant stool samples were collected from nine full-term, healthy mother-infant pairs. The bacterial distribution and various types of ARGs present in the samples were analyzed using metagenomic next-generation sequencing. Over a period spanning from 2 to 240 d after birth, a total of 273 types of ARGs were identified in both infant feces and breast milk, exhibiting a trend of increasing prevalence over time. High concentrations of representative ARG populations were identified in the intestines of infants, especially at 12-15 d after birth. These populations included APH3-Ib, tetW/N/W, mphA, and Haemophilus influenzae PBP3, and multiple ARG Escherichia coli soxS that were resistant to common clinically used aminoglycoside, tetracycline, macrolide, and beta-lactam antibiotics. Gammaproteobacteria and Bacilli, especially Enterococcus, Staphylococcus, Acinetobacter, Streptococcus, and Escherichia were among the identified ARG carriers. Maternal age and body mass index (present and before pregnancy), infant sex, maternal consumption of probiotic yogurt during pregnancy, and lactation might be substantial factors influencing the occurrence of ARG-carrying bacteria and ARG distribution in the infant feces. These results indicate that environmental factors may influence the distribution of ARG-carrying bacteria and ARGs themselves in infants during early life. Providing appropriate recommendations regarding maternal age, body mass index during pregnancy, and use of probiotic products could potentially mitigate the transmission of antibiotic-resistant microbiota and ARGs, thereby diminishing the risk of antibiotic-resistant infections and safeguarding children's health.

Subsidence Characteristics in North Anhui Coal Mining Areas Using Space-Air-Ground Collaborative Observations.

To fully comprehend the patterns of land and ecological damage caused by coal mining subsidence, and to scientifically carry out ecological mine restoration and management, it is urgent to accurately grasp the information of coal mining, particularly in complex coaling areas, such as North Anhui, China. In this paper, a space-air-ground collaborative monitoring system was constructed for coal mining areas based on multi-source remote sensing data and subsidence characteristics of coaling areas were investigated in North Anhui. It was found that from 2019 to 2022, 16 new coal mining subsidence areas were found in northern Anhui, with the total area increasing by 8.1%. In terms of land use, water areas were increased by 101.9 km2 from 2012 to 2022, cultivated land was decreased by 99.3 km2, and residence land was decreased by 11.8 km2. The depth of land subsidence in the subsidence areas is divided into 307.9 km2 of light subsidence areas with a subsidence depth of less than 500 mm; 161.8 km2 of medium subsidence areas with a subsidence depth between 500 mm and 1500 mm; and 281.2 km2 of heavy subsidence areas with a subsidence depth greater than 1500 mm. The total subsidence governance area is 191.2 km2, accounting for 26.5% of the total subsidence area. From the perspective of prefecture-level cities, the governance rate reaches 51.3% in Huaibei, 10.1% in Huainan, and 13.6% in Fuyang. The total reclamation area is 68.8 km2, accounting for 34.5% of the subsidence governance area. At present, 276.1 km2 within the subsidence area has reached stable subsidence conditions, mainly distributed in the Huaibei mining area, which accounts for about 60% of the total stable subsidence area.

Foliar uptake screening: A promising strategy for identifying wheat varieties with low lead accumulation.

Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg-1) and field 2 (0.17 and 0.20 mg kg-1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.

Extrafibrillar demineralization: Yes or no?

OBJECTIVE: Extrafibrillar demineralization is considered to be an ideal solution for addressing the durability of resin-dentin bonding interfaces. However, its theoretical basis is contradictory to ionization equilibrium of hydroxyapatite dissolution. In this study, various calcium chelators were selected as dentin conditioners to explore the essence of dentin demineralization with chelators and its effect on resin-dentin adhesion. METHODS: Polyethyleneimine grafted with EDTA and polyacrylic acid sodium (PAAN450k) larger than 40 kDa, as well as PAAN (PAAN3k) and EDTA smaller than 6 kDa, were prepared as dentin conditioners. The dentin powder was designed to characterize whether it would demineralize without contact with PAAN450k. Dentin demineralization effect with four conditioners was evaluated with field emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, atomic force microscopy and quantification of hydroxyproline concentration after enzymatic degradation. Micro-tensile bond strength (µTBS) test and failure mode analysis were employed to assess the bonding effect of the four chelators in both wet and dry bonding, with H3PO4 wet bonding serving as the control group. RESULTS: Demineralization occurs when PAAN450k was not in direct contact with the dentin powder. The extrafibrillar demineralization cannot be induced by any chelator regardless of its molecular weight. Complete demineralization including extrafibrillar and intrafibrillar demineralization would occur with sufficient interaction time. Moreover, chelators could not provide a reliable dentin bonding effect under a short interaction time. SIGNIFICANCE: From the perspective of theory and application, extrafibrillar demineralization is not a reliable strategy, which provides a reminder for exploring new strategies in the future.

Bottom-Up Assembling Hierarchical Enamel-Like Bulk Materials with Excellent Optical and Mechanical Properties for Tooth Restoration.

Enamel has good optical and mechanical properties because of its multiscale hierarchical structure. Biomimetic construction of enamel-like 3D bulk materials at nano-, micro-, mesh- and macro-levels is a challenge. A novel facile, cost-effective, and easy large-scale bottom-up assembly strategy to align 1D hydroxyapatite (HA) nanowires bundles to 3D hierarchical enamel structure with the nanowires bundles layer-by-layer interweaving orientation, is reported. In the strategy, the surface of oleate templated ultralong HA nanowires with a large aspect ratio is functionalized with amphiphilic 10-methacryloyloxydecyl dihydrogen phosphate (MDP). Furtherly, the MDP functionalized HA nanowire bundles are assembled layer-by-layer with oriented fibers in a single layer and cross-locked between layers at a certain angle at mesoscale and macroscale in the viscous bisphenol A-glycidyl methacrylate (Bis-GMA) ethanol solution by shear force induced by simple agitation and high-speed centrifugation. Finally, the excessive Bis-GMA and ethanol are removed, and (Bis-GMA)-(MDP-HA nanowire bundle) matrix is densely packed under hot pressing and polymerized to form bulk enamel-like materials. The composite has superior optical properties and comparable comprehensive mechanic performances through a combination of strength, hardness, toughness, and friction. This method may open new avenues for controlling the nanowires assembly to develop hierarchical nanomaterials with superior properties for many different applications.

Relationship between sarcopenia and fatty liver in middle-aged and elderly patients with type 2 diabetes mellitus.

OBJECTIVE: In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the prevention and treatment of sarcopenia. METHODS: A total of 282 patients diagnosed with T2DM aged 50 and older and were admitted to the Endocrinology Department of Xin Medical University First Affiliated Hospital between December 2021 and February 2023, were selected. Body mass index (BMI), and limb and trunk muscle mass of the patients were measured, and data were collected. Patients were grouped based on the sarcopenia diagnostic criteria. All study participants underwent the same physical examinations and laboratory tests. The relationship between the onset of sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with T2DM was then investigated using statistical analysis. RESULTS: Comparing the sarcopenia group to the non-sarcopenia group revealed statistically significant variations in gender, BMI, fatty liver prevalence rate, uric acid (UA), alanine aminotransferase (ALT), blood glucose, blood lipid associated indicators, and limb skeletal muscle content. There were, however, no statistically significant differences in age, disease duration, hypertension, smoking, or alcohol intake. There was a positive correlation between BMI, UA, fasting c-peptide, and Appendicular Skeletal Muscle Index (ASMI). Higher levels of BMI, ASMI, and UA were identified as protective variables against sarcopenia by multifactorial logistic regression analysis. CONCLUSION: Higher levels of BMI, ASMI, and UA can greatly reduce skeletal muscle atrophy in patients with T2DM. Patients with a fatty liver may be less vulnerable to sarcopenia. There is little evidence, however, that a fatty liver works as a preventive factor against sarcopenia.

Targeted genetic analysis in a cohort of sporadic death from spontaneous rupture of thoracic aortic dissection in Han Chinese population.

PURPOSE: Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease that often results in sudden cardiac death (SCD). However, the genetic characteristics of individuals with TAD confirmed at autopsy have been rarely studied. Our objective was to determine the prevalence of pathogenic variants in TAD-associated genes in a cohort of sporadic deaths resulting from spontaneous rupture of TAD and identify relevant genotype-phenotype relationships in Han Chinese population. METHODS: We included sixty-one consecutive sporadic decedents whose primary cause of death was spontaneous rupture of TAD, and performed a whole exome sequencing based strategy comprising 26 known TAD-associated genes. RESULTS: We identified 7 pathogenic or likely pathogenic (P/LP) variants in 7 cases (11.48 %) and 22 variants of uncertain significance (VUS) in 22 cases (36.07 %). The FBN1 gene was found to be the major disease-causing gene. Notably, TAD decedents with P/LP variant exhibited significantly earlier mortality. Moreover, we reported for the first time that TAD decedents with P/LP variant had a shorter diagnosis and treatment time. CONCLUSION: Our study investigated the genetic characteristics of TAD individuals confirmed until autopsy in Han Chinese population. The findings enhanced the understanding of the genetic underpinnings of TAD and have significant implications for clinical management and forensic investigations.

Comparison of the effect of tea shoots during different seasons in Arma chinensis (Hemiptera: Pentatomidae) reared on Ectropis grisescens (Lepidoptera: Geometridae) pupae.

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

Activation of GPR81 by lactate drives tumour-induced cachexia.

Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate. Mechanistically, lactate/GPR81-induced cachexia occurs independently of the well-established protein kinase A catabolic pathway, but it is mediated by a signalling cascade sequentially activating Gi-Gßγ-RhoA/ROCK1-p38. These findings highlight the therapeutic potential of targeting GPR81 for the treatment of this life-threatening complication of cancer.

Bifunctional Electrocatalysts for Overall and Hybrid Water Splitting.

Electrocatalytic water splitting driven by renewable electricity has been recognized as a promising approach for green hydrogen production. Different from conventional strategies in developing electrocatalysts for the two half-reactions of water splitting (e.g., the hydrogen and oxygen evolution reactions, HER and OER) separately, there has been a growing interest in designing and developing bifunctional electrocatalysts, which are able to catalyze both the HER and OER. In addition, considering the high overpotentials required for OER while limited value of the produced oxygen, there is another rapidly growing interest in exploring alternative oxidation reactions to replace OER for hybrid water splitting toward energy-efficient hydrogen generation. This Review begins with an introduction on the fundamental aspects of water splitting, followed by a thorough discussion on various physicochemical characterization techniques that are frequently employed in probing the active sites, with an emphasis on the reconstruction of bifunctional electrocatalysts during redox electrolysis. The design, synthesis, and performance of diverse bifunctional electrocatalysts based on noble metals, nonprecious metals, and metal-free nanocarbons, for overall water splitting in acidic and alkaline electrolytes, are thoroughly summarized and compared. Next, their application toward hybrid water splitting is also presented, wherein the alternative anodic reactions include sacrificing agents oxidation, pollutants oxidative degradation, and organics oxidative upgrading. Finally, a concise statement on the current challenges and future opportunities of bifunctional electrocatalysts for both overall and hybrid water splitting is presented in the hope of guiding future endeavors in the quest for energy-efficient and sustainable green hydrogen production.

Ultrasound contrast-enhanced diagnosis of testicular Leydig cell tumor: A case report and literature review.

Leydig cell tumor (LCT) is a rare testicular tumor. We report a case of an elderly male patient who discovered a left testicular mass during a regular health examination four years ago. The patient did not experience any significant discomfort and opted for regular follow-up visits. During the most recent visit, we performed routine ultrasound and contrast-enhanced ultrasound (CEUS) examinations. By observing the lesion's location, echogenicity, margins, vascular distribution, as well as the rapid enhancement and slow washout characteristics on contrast-enhanced ultrasound, we arrived at a diagnosis of LCT. Subsequently, the patient underwent left inguinal orchiectomy. Postoperative pathology and immunohistochemistry confirmed the diagnosis of LCT. Additionally, we conducted a comprehensive review of LCT-related literature from PubMed and SCOPUS, summarizing the clinical features, follow-up duration, prognosis, and ultrasound characteristics associated with LCT.

Trimethylamine N-oxide impairs ß-cell function and glucose tolerance.

ß-Cell dysfunction and ß-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, ß-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on ß-cell function in vitro and in vivo. Additionally, long-term TMAO exposure promotes ß-cell ER stress, dedifferentiation, and apoptosis and inhibits ß-cell transcriptional identity. Inhibition of TMAO production improves ß-cell GSIS, ß-cell proportion, and glucose tolerance in both male db/db and choline diet-fed mice. These observations identify a role for TMAO in ß-cell dysfunction and maintenance, and inhibition of TMAO could be an approach for the treatment of T2D.

Contrast-enhanced ultrasound for the preoperative prediction of pathological characteristics in breast cancer.

Objective: We aimed to investigate the value of contrast-enhanced ultrasound (CEUS) in the preoperative prediction of the histological grades and molecular subtypes of breast cancer. Methods: A total of 183 patients with pathologically confirmed breast cancer were included. Contrast enhancement patterns and quantitative parameters were compared in different groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of CEUS in the preoperative prediction of pathological characteristics, including histologic grade and molecular subtypes. Results: Heterogeneous enhancement, perfusion defects, and peripheral radial vessels were mostly observed in higher histologic grade (grade III) breast cancer. Heterogeneous enhancement and perfusion defect were the most effective indicators for grade III breast cancer, with the areas under the ROC curve of 0.768 and 0.756, respectively. There were significant differences in the enhancement intensity, post-enhanced margin, perfusion defects, and peripheral radial vessel among the different molecular subtypes of breast cancer (all P < 0.01). Perfusion defects and clear edge after enhancement were the best qualitative criteria for the diagnosis of HER-2 overexpressed and triple-negative breast cancers, and the corresponding areas under the ROC curves were 0.804 and 0.905, respectively. There were significant differences in PE, WiR, WiPI, and WiWoAUC between grade III vs grade I and II breast cancer (P < 0.05). PE, WiR, WiPI, and WiWoAUC had good efficiency in the diagnosis of high-histologic-grade breast cancer. PE had the highest diagnostic efficiency in Luminal A, while WiPI had the highest diagnostic efficiency in Luminal B subtype breast cancer, and the areas under the ROC curve were 0.825 and 0.838, respectively. WiWoAUC and WiR were the most accurate parameters for assessing triple-negative subtype breast cancers, and the areas under the curve were 0.932 and 0.922, respectively. Conclusion: Qualitative and quantitative perfusion analysis of contrast-enhanced ultrasound may be useful in the non-invasive prediction of the histological grade and molecular subtypes of breast cancers.

[Blocking Effects of Foliar Conditioners on Cadmium, Arsenic, and Lead Accumulation in Wheat Grain in Compound-contaminated Farmland].

Heavy metal contamination of soil has become a hot issue of social concern due to its impact on the safety of agricultural products in recent years. Wheat is one of the most dominant staple food crops worldwide and has become a major source of toxic metals in human diets. Foliar application was considered to be a more efficient and economical method of heavy metal remediation. Field experiments were carried out in Cd-, As-, and Pb-contaminated farmland soils. The effects of foliar conditioners on the accumulation of Cd, As, and Pb in wheat grains were investigated after being sprayed with Zn (0.2% ZnSO4), Mg (0.4% MgSO4), and Mn (0.2% MnSO4) separately and in combination. Thus, the effective foliar conditioners were selected to block the accumulation of Cd, As, and Pb in wheat grains grown in combined heavy metal-contaminated farmland in north China. The results showed that, compared with that in the control, the Cd, As, and Pb contents in wheat grains of the Zn+Mg+Mn foliar treatment were significantly decreased by 18.96%, 23.87%, and 51.31%, respectively, and TFgrain/straw decreased by 14.62%, 27.73%, and 47.70%, respectively. Thus, spraying the compound foliar conditioner of Zn+Mg+Mn could effectively reduce heavy metal accumulation in wheat grains through inhibition translocation of those metals from stem leaves to grain. In addition, the results indicated that Cd and As were mainly distributed at the central endosperm (34.08%-37.08%), whereas Pb was primarily distributed at the pericarp and seed coat (27.78%) of the wheat grain. Compared with that in the control, spraying the compound foliar conditioner of Zn+Mg+Mn extremely decreased Cd and As accumulation in the aleurone layer of the wheat grain by 81.10% and 82.24%, respectively. Except for the pericarp, seed coat, and central endosperm layers, the Pb content in each grain layer was dramatically decreased by 42.85% to 91.15%. There was only a significant negative correlation between heavy metal content and Zn content in the aleurone layer (P2) of wheat flour. In summary, the accumulation of Cd, As, and Pb in wheat grains, especially in the aleurone layer, could be effectively reduced by foliar conditioner application at the jointing, booting, and early filling stages of wheat, separately. Furthermore, besides the foliar treatment, removing wheat bran to reduce Cd contamination in wheat grains is highly recommended to ensure the safe production of wheat.