The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice.

BACKGROUND: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes. RESULTS: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1. CONCLUSIONS: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.

Electrochemical Synthesis of Spirolactones from α-Tetralone Derivatives with Methanol as a C1 Source.

Spirolactones are widely found in pharmaceuticals and bioactive natural products. However, efficient and environmentally friendly approaches to accessing spirolactones are still highly desirable. Herein, a novel electrochemical synthesis of spirolactones from α-tetralone derivatives with methanol as a C1 source is described. This electrochemical reaction exhibits a high efficiency and good functional group tolerance.

Multi-Component Lithiophilic Alloy Film Modified Cu Current Collector for Long-Life Lithium Metal Batteries by a Novel FCVA Co-Deposition System.

Surface modification of Cu current collectors (CCs) is proven to be an effective method for protecting lithium metal anodes. However, few studies have focused on the quality and efficiency of modification layers. Herein, a novel home-made filtered cathode vacuum arc (FCVA) co-deposition system with high modification efficiency, good repeatability and environmental friendliness is proposed to realize the wide range regulation of film composition, structure and performance. Through this system, ZnMgTiAl quaternary alloy films, which have good affinity with Li are successfully constructed on Cu CCs, and the fully enhanced electrochemical performances are achieved. Symmetrical cells constructed with modified CCs maintained a fairly low voltage hysteresis of only 13 mV after 2100 h at a current density of 1 mA cm-2. In addition, the capacity retention rate is as high as 75.0% after 100 cycles in the full cells. The influence of alloy films on the dynamic evolution process of constructing stable artificial solid electrolyte interphase (SEI) layer is revealed by in situ infrared (IR) spectroscopy. This work provides a promising route for designing various feasible modification films for LMBs, and it displays better industrial application prospects than the traditional chemical methods owing to the remarkable controllability and scale-up capacity.

Joint effect of testosterone and neurofilament light chain on cognitive decline in men: The Shanghai Aging Study.

INTRODUCTION: The association of testosterone and cognitive decline is inconclusive, and its joint effect with neurofilaments light chain (NfL) remains largely unknown. METHODS: A total of 581 non-demented older men in the Shanghai Aging Study were included. Blood total testosterone (TT), free testosterone (FT), and NfL were measured at baseline. The relationships between TT, FT, TT/FT-NfL, and cognitive decline were explored by Cox regression models. RESULTS: During a median follow-up of 6.7 years, there was an inverse association between TT/FT and cognitive decline (TT, trend p = .004, Q1 vs Q4, hazard ratio [HR] = 4.39, 95% confidence interval [CI] = 1.60 to 12.04; FT, trend p = .002, Q1 vs Q4, HR = 5.29, 95% CI = 1.50 to 16.89). Compared to participants with high TT/FT-low NfL, those with low TT/FT-high NfL had significantly higher risks of cognitive decline (TT, HR = 5.10, 95% CI = 1.11 to 23.40; FT, HR = 6.14, 95% CI = 1.34 to 28.06). DISCUSSION: Our findings suggest that the combination of testosterone and neurodegenerative markers may provide reliable predictive insights into future cognitive decline. HIGHLIGHTS: Testosterone is inversely associated with cognitive decline in older men. There is a joint effect of testosterone and NfL on cognitive decline. Sex hormone and neurodegeneration may synergistically contribute to cognitive deterioration.

Adherence to guidelines and central line-associated bloodstream infection occurrence during insertion and maintenance of intravascular catheters: evidence from 20 tertiary hospitals.

OBJECTIVE: To investigate adherence to intravascular catheter (IVC) insertion and maintenance guidelines in Chinese tertiary hospitals. METHODS: A cross-sectional questionnaire survey of adult inpatients with IVC placements was conducted from July to September 2022 in 20 tertiary hospitals in China. One clinical staff member from each department in each hospital was assigned to participate in the survey. Questionnaires were uniformly collected and reviewed after 3 months. RESULTS: This study included 1815 cases (62.69%) of central venous catheter, 471 cases (16.27%) of peripherally inserted central catheter, 461 cases (15.92%) of PORT, and 147 cases (5.08%) of haemodialysis catheter insertions. Statistically significant differences in compliance were observed across the four IVC types, specifically in relation to the insertion checklist, standard operating procedure, and insertion environment (P<0.05). Practice adherence during IVC maintenance differed significantly across the four IVC types in aspects such as availability of IVC maintenance verification forms, daily scrubbing of the catheterised patients, and catheter connection methods (P<0.05). A total of 386 (13.34%) patients developed fever, 1086 (37.53%) were treated with therapeutic antibiotics, 16 (0.55%) developed central line-associated bloodstream infections, two (0.07%) developed local skin infections, and six (0.21%) developed deep vein thrombosis. CONCLUSIONS: Adherence to guidelines regarding insertion and maintenance differed across the four IVC types; there is a gap between the recommended measures and the actual operation of the guideline. Therefore, it is necessary to further enhance training and develop checklists to prevent CLABSIs.

Effects of early nutritional intervention on oral mucositis and basic conditions in patients receiving radiotherapy for head and neck cancer: Randomized controlled trial (ChiCTR2000031418).

BACKGROUND & AIMS: This study aims to observe the effects of early nutritional intervention on radiation-induced oral mucositis (OM) and the nutritional status of patients with head and neck cancer (HNC) receiving radiotherapy. METHODS: Eligible patients receiving radiotherapy for HNC were randomly divided into an early nutritional intervention group (enteral nutritional intervention was administered at the beginning of radiotherapy) and a late nutritional intervention group (enteral nutritional intervention was administered at the beginning of eating restriction) in a 1:1 ratio. The primary endpoint was radiation-induced OM. Secondary endpoints included nutrition-related indicators, immune function, overall survival (OS), progression-free survival (PFS), quality of life, and other radiotherapy-induced adverse effects. RESULTS: A total of 100 patients were enrolled between 2020 and 2021, including 50 each in the early nutritional intervention group and in the late group. The incidence of Grade-III/IV OM was lower in the early treatment group than in the late treatment group (2% vs 14%, P = 0.059). By week 7 weight loss was significantly lower in the early group than in the late group (1.08 kg, 95% CI: 0.08-2.09, P = 0.035). Regarding the PG-SGA scores after receiving radiotherapy, the early group comprised more well-nourished and fewer malnourished patients than those in the late group (P = 0.002). The scores of the immune function indices of T cell CD3+, CD4+/CD8+, and B cell CD19+ were slightly higher in the early group than in the late group; however, the difference was not statistically significant (all P > 0.05). PFS and OS were better in the early group than in the late group; however, the differences were not statistically significant (P > 0.05). CONCLUSIONS: Early nutritional intervention can effectively improve the nutritional status and reduce the incidence of high-grade OM in patients with HNC receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry (http://www.chictr.org.cn). CHICTR-ID: ChiCTR2000031418.

Fluoride exposure during puberty induces testicular impairment via ER stress-triggered apoptosis in mice.

Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp78 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94, chop, Atf6, Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride.

Submucosal Trans-Septal Suturing Technique After a Septal Extension Graft with Porous High-Density Polyethylene: A Technical Report.

BACKGROUND: Porous high-density polyethylene (pHDPE) is an alternative material for a septal extension graft (SEG) in oriental rhinoplasty when autologous cartilage is limited. Although nasal packing (NP) and trans-septal suturing (TSS) techniques are routine procedures to obviate the dead space after septoplasty, they are associated with certain discomforts and complications. OBJECTIVE: To investigate the application of a submucosal trans-septal suturing (STSS) technique after SEG with pHDPE. METHODS: A prospective study was conducted on 60 female participants who underwent SEG with pHDPE. The participants were randomly divided into the NP group and STSS group. The extra surgical duration of NP and STSS, pain, nasal obstruction, and sleeping disturbance as well as postoperative complications were recorded and compared between groups. RESULTS: No significant difference was found between group NP and group STSS in terms of mean age. The mean extra surgical duration of group STSS was significantly longer than group NP. There were significant higher pains of group NP at 24 hours and 48 hours postoperatively, compared with group STSS. The NP group also experienced significantly more nasal obstruction and sleep disturbance within 48h postoperatively compared to the STSS group. There was one infection in each group, minor bleeding in two NP patients, and one STSS patient. There was no major bleeding, hematoma, graft exposure, or septal perforation in both groups. CONCLUSION: Although STSS needs a longer extra surgical duration than NP, it significantly improves the patient's postoperative comfort with a faster return to normal respiration compared to NP. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) virus in a child in Shandong Province, China.

BACKGROUND: Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. METHODS: Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. RESULTS: RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). CONCLUSIONS: The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Periodic heat waves-induced neuronal etiology in the elderly is mediated by gut-liver-brain axis: a transcriptome profiling approach.

Heat stress exposure in intermittent heat waves and subsequent exposure during war theaters pose a clinical challenge that can lead to multi-organ dysfunction and long-term complications in the elderly. Using an aged mouse model and high-throughput sequencing, this study investigated the molecular dynamics of the liver-brain connection during heat stress exposure. Distinctive gene expression patterns induced by periodic heat stress emerged in both brain and liver tissues. An altered transcriptome profile showed heat stress-induced altered acute phase response pathways, causing neural, hepatic, and systemic inflammation and impaired synaptic plasticity. Results also demonstrated that proinflammatory molecules such as S100B, IL-17, IL-33, and neurological disease signaling pathways were upregulated, while protective pathways like aryl hydrocarbon receptor signaling were downregulated. In parallel, Rantes, IRF7, NOD1/2, TREM1, and hepatic injury signaling pathways were upregulated. Furthermore, current research identified Orosomucoid 2 (ORM2) in the liver as one of the mediators of the liver-brain axis due to heat exposure. In conclusion, the transcriptome profiling in elderly heat-stressed mice revealed a coordinated network of liver-brain axis pathways with increased hepatic ORM2 secretion, possibly due to gut inflammation and dysbiosis. The above secretion of ORM2 may impact the brain through a leaky blood-brain barrier, thus emphasizing intricate multi-organ crosstalk.

Investigating the role of green behavior and perceived benefits in shaping green car buying behavior with environmental awareness as a moderator.

As the planet faces the challenge of global warming, every individual and organization must adopt green practices to protect nature. The automobile industry is one of the primary industries which can contribute significantly towards sustainability. This study aims to examine the impact of green behavior and green perceived benefits on the green buying behaviors of automobiles. The research also explores the moderating influence of environmental awareness on the mechanism. The research is based on a quantitative method for which primary data was gathered from 406 respondents across Pakistan, China and Saudi Arabia via Quota-based purposive sampling. The gathered data was analyzed via SmartPLS. The results show that green behavior and perceived benefits positively and significantly influence green buying behavior. The findings also show the moderating role of environmental awareness on green behavior towards green buying and show no impact on the perceived benefits towards buying behavior. The study has practical and theoretical implications for managers, researchers, policymakers and institutions in the context of green automobile development and businesses. The study also contributes to the attainment of sustainable development goals.

Disposable Peptidoglycan-Specific Biosensor for Noninvasive Real-Time Detection of Broad-Spectrum Gram-Positive Bacteria in Exhaled Breath Condensates.

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Helical hollow channel waveguide in YAG fabricated by femtosecond laser enhanced wet etching.

Three-dimensional optical waveguides with hollow channels have many advantages, such as strong mode confinement and excellent dispersion control ability. Femtosecond laser enhanced wet etching is widely used to fabricate hollow channel waveguides in transparent dielectric materials. We propose a method for fabricating hollow channel waveguides in YAG using femtosecond laser enhanced wet etching with a simpler fabrication process and shorter etching time compared with the previous work. After 90 h of etching, a series of helical hollow channel waveguides with a length of 5 mm and a radius of 32 µm were successfully fabricated. At a pitch of 3 µm, the waveguide exhibited a loss (including coupling loss and transmission loss) as low as 0.68 dB at 1030 nm. The helical hollow channel waveguide also exhibited exceptional isotropic light confinement capability and remarkable supercontinuum-generating properties. Moreover, helical hollow channel waveguides with a radius of 2 µm were successfully fabricated. According to simulations, waveguides of such size can effectively control dispersion. Our work presents, to our knowledge, a novel approach to fabricating hollow channel waveguides with arbitrary lengths using femtosecond laser-enhanced wet etching.

DenseNet model incorporating hybrid attention mechanisms and clinical features for pancreatic cystic tumor classification.

PURPOSE: The aim of this study is to develop a deep learning model capable of discriminating between pancreatic plasma cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN) by leveraging patient-specific clinical features and imaging outcomes. The intent is to offer valuable diagnostic support to clinicians in their clinical decision-making processes. METHODS: The construction of the deep learning model involved utilizing a dataset comprising abdominal magnetic resonance T2-weighted images obtained from patients diagnosed with pancreatic cystic tumors at Changhai Hospital. The dataset comprised 207 patients with SCN and 93 patients with MCN, encompassing a total of 1761 images. The foundational architecture employed was DenseNet-161, augmented with a hybrid attention mechanism module. This integration aimed to enhance the network's attentiveness toward channel and spatial features, thereby amplifying its performance. Additionally, clinical features were incorporated prior to the fully connected layer of the network to actively contribute to subsequent decision-making processes, thereby significantly augmenting the model's classification accuracy. The final patient classification outcomes were derived using a joint voting methodology, and the model underwent comprehensive evaluation. RESULTS: Using the five-fold cross validation, the accuracy of the classification model in this paper was 92.44%, with an AUC value of 0.971, a precision rate of 0.956, a recall rate of 0.919, a specificity of 0.933, and an F1-score of 0.936. CONCLUSION: This study demonstrates that the DenseNet model, which incorporates hybrid attention mechanisms and clinical features, is effective for distinguishing between SCN and MCN, and has potential application for the diagnosis of pancreatic cystic tumors in clinical practice.

Integration of single-cell RNA sequencing of endothelial cells and proteomics to unravel the role of ICAM1-PTGS2 communication in apical periodontitis: A laboratory investigation.

AIM: Endothelial cells (EDs) play a key role in angiogenesis and are associated with granulomatous lesions in patients with chronic apical periodontitis (CAP). This study aimed to investigate the diversity of EDs using single-cell ribonucleic acid sequencing (scRNA-seq) and to evaluate the regulation of intercellular adhesion molecule 1 (ICAM1) on the ferroptosis-related protein, prostaglandin-endoperoxide synthase 2 (PTGS2), in CAP. METHODOLOGY: EDs from the uploaded scRNA-seq data of five CAP samples (GSE181688 and GSE197680) were categorized using distinct marker genes. The interactions between vein EDs (veinEndo) and other cell types were analysed using CellPhoneDB. Differentially expressed proteins in the proteomics of human umbilical vein EDs (HUVECs) and THP-1-derived macrophages infected with Porphyromonas gingivalis were compared with the differentially expressed genes (DEGs) of VeinEndo in scRNA-seq of CAP versus healthy control periodontal tissues. The protein-protein interaction of ICAM1-PTGS2 in macrophages and HUVECs was validated by adding recombinant ICAM1, ICAM1 inhibitor and PTGS2 inhibitor using real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence staining. RESULTS: EDs in patients with CAP were divided into eight subclusters: five vein ED, capillaries, arterials and EC (PLA). There were 29 mutually upregulated DEGs and two mutually downregulated DEGs in vein cells in the scRNA-seq data, as well as differentially expressed proteins in the proteomics of HUVECs. Real-time PCR and immunofluorescence staining showed that ICAM1 and PTGS2 were highly expressed in CAP, infected HUVECs, and macrophages. Recombinant protein ICAM1 may improve PTGS2 expression, reactive oxygen species (ROS), and Fe2+ levels and decrease glutathione peroxidase 4 (GPX4) and SLC7A11 protein levels. ICAM1 inhibitor may inverse the above changes. CONCLUSIONS: scRNA-seq revealed the diversity of EDs in CAP and identified the possible regulation of ICAM1 by the ferroptosis-related protein, PTGS2, in infected HUVECs and macrophages, thus providing a basis for therapeutic approaches that target the inflammatory microenvironment of CAP.

Cognitive load in tele-robotic surgery: a comparison of eye tracker designs.

PURPOSE: Eye gaze tracking and pupillometry are evolving areas within the field of tele-robotic surgery, particularly in the context of estimating cognitive load (CL). However, this is a recent field, and current solutions for gaze and pupil tracking in robotic surgery require assessment. Considering the necessity of stable pupillometry signals for reliable cognitive load estimation, we compare the accuracy of three eye trackers, including head and console-mounted designs. METHODS: We conducted a user study with the da Vinci Research Kit (dVRK), to compare the three designs. We collected eye tracking and dVRK video data while participants observed nine markers distributed over the dVRK screen. We compute and analyze pupil detection stability and gaze prediction accuracy for the three designs. RESULTS: Head-worn devices present better stability and accuracy of gaze prediction and pupil detection compared to console-mounted systems. Tracking stability along the field of view varies between trackers, with gaze predictions detected at invalid zones of the image with high confidence. CONCLUSION: While head-worn solutions show benefits in confidence and stability, our results demonstrate the need to improve eye tacker performance regarding pupil detection, stability, and gaze accuracy in tele-robotic scenarios.

Associations between blood manganese levels and sarcopenia in adults: insights from the National Health and Nutrition Examination Survey.

Background: While increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population. Objective: This study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults. Methods: In our study, we evaluated 8,135 individuals aged 18-59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia. Results: After adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 µg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups. Conclusion: Our results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 µg/L.

A single-cell profile reveals the transcriptional regulation responded for Abelmoschus manihot (L.) treatment in diabetic kidney disease.

BACKGROUND: Huangkui capsule (HKC), as an ethanol extract of Abelmoschus manihot (L.), has a significant efficacy in treatment of the patients with diabetic kidney disease (DKD). The bioactive ingredients of HKC mainly include the flavonoids such as rutin, hyperoside, hibifolin, isoquercetin, myricetin, quercetin and quercetin-3-O-robinobioside. PURPOSE: To explore the molecular mechanisms of A. manihot in treatment of DKD. STUDY DESIGN: A single-cell RNA sequencing analysis of kidneys in db/db mice with and without HKC administration. METHODS: Urinary biochemical and histopathological examination in C57BL/6 and db/db mice of DKD and HKC groups was done. Single-cell RNA sequencing pipeline was then performed. The regulatory mechanisms of seven flavonoids in HKC were revealed by cell communication, prediction of transcription factor regulatory network, and molecular docking. RESULTS: By constructing ligand-receptor regulatory network and performing molecular docking between 75 receptors with different activities and seven flavonoids. 11 key receptors in 4 cell types (segment 3 proximal convoluted tubular cell, ascending limbs of the loop of Henle, distal convoluted tubule, and T cell) in kidneys were found to be directly interacted with HKC. The interactions regulated 8 downstream regulons. The docking receptors in T cell led to transcriptional event differences in the regulons such as Cebpb, Rel, Tbx21 and Klf2 and consequently affected the activation, differentiation, and infiltration of T cell, while the receptors Tgfbr1 and Ldlr in stromal cells of kidneys were closely associated with the downstream transcriptional events of renal injury and proteinuria in DKD. CONCLUSION: The current study provides novel information of the key receptors and regulons in renal cells for a better understanding of the cell type specific molecular mechanisms of A. manihot in treatment of DKD.