Constructing novel hydrated metal molten salt with high self-healing as the anode material for lithium-ion batteries.

Lithium-ion batteries (LIBs) are greatly limited in their practical application because of their poor cycle performance, low conductivity and volume expansion. Herein, molten salts (MSs) FeCl3·6H2O-NMP with low temperature via simple preparation are used as the anode material of LIBs for the first time to break through the bottleneck of LIBs. The good fluidity and high self-healing of FeCl3·6H2O-NMP effectively avoid the collapse and breakage of the structure. Based on this feature, the initial discharge specific capacity reached 770.28 mA h g-1, which was more than twice that of the commercial graphite anode. After 200 cycles at a current density of 100 mA g-1, the specific capacity did not decrease rather it was found to be higher than the initial discharge specific capacity, reaching 867.24 mA h g-1. Besides, the good conductivity of MSs provides convenience for the removal and intercalation of Li+. The active H sites that can combine with lithium ions form LiH and provide capacity for LIBs. Density functional theory (DFT) calculation also provided theoretical proof for the mechanism of LIBs.

Characterising the changes in RSV epidemiology in Beijing, China during 2015-2023: results from a prospective, multi-centre, hospital-based surveillance and serology study.

Background: Respiratory syncytial virus (RSV) has posed substantial morbidity and mortality burden to young children and older adults globally. The coronavirus disease 2019 (COVID-19) pandemic was reported to have altered RSV epidemiology and could have important implications for RSV prevention and control strategies. We aimed to compare RSV epidemiology in different phases of the COVID-19 pandemic with the pre-pandemic period by leveraging epidemiological, molecular, and serological data collected from a prospective respiratory pathogen surveillance and serology study. Methods: This study was based on the data during July 1, 2015 to November 30, 2023 from the Respiratory Pathogen Surveillance System (RPSS), a sentinel-hospital based surveillance system of acute respiratory infections consisting of 35 hospitals that represent residents of all ages from all 16 districts in Beijing, China. RSV infection status was tested by RT-PCR and gene sequencing and phylogenetic analysis was conducted among the identified RSV strains. We further supplemented RPSS data with three serology surveys conducted during 2017-2023 that tested RSV IgG levels from serum specimens. RSV detection rate was calculated by calendar month and compared across RSV seasons (defined as the July 1 through June 30 of the following year). RSV IgG positivity proportion was calculated by quarter of the year and was correlated with quarterly aggregated RSV detection rate for understanding the relationship between infection and immunity at the population level. Findings: Overall, a total of 52,931 respiratory specimens were collected and tested over the study period. RSV detection rates ranged from 1.24% (94/7594) in the 2017-2018 season to 2.80% (219/7824) in the 2018-2019 season, and from 1.06% (55/5165) in the 2022-2023 season to 2.98% (147/4938) in the 2021-2022 season during the pre-pandemic and pandemic period, respectively. ON1 and BA9 remained the predominant genotypes during the pandemic period; no novel RSV strains were identified. RSV circulation followed a winter-months seasonal pattern in most seasons. One exception was the 2020-2021 season when an extensive year-round circulation was observed, possibly associated with partial relaxation of non-pharmaceutical interventions (NPIs). The other exception was the 2022-2023 season when very low RSV activity was observed during the usual winter months (possibly due to the concurrent local COVID-19 epidemic), and followed by an out-of-season resurgence in the spring, with RSV detection persisting to the end of the study period (November 2023). During the two seasons above, we noted an age-group related asynchrony in the RSV detection rate; the RSV detection rate in young children remained similar (or even increased with borderline significance; 43/594, 7.24%, and 42/556, 7.55% vs 292/5293, 5.52%; P = 0.10 and P = 0.06, respectively) compared with the pre-pandemic seasons whereas the detection rate in older adults decreased significantly (8/1779, 0.45%, and 3/2021, 0.15% vs 160/10,348, 1.55%; P < 0.001 in two comparisons). Results from serology surveys showed significantly declined RSV IgG positivity in the 2022-2023 season compared to the pre-pandemic seasons (9.32%, 29/311 vs 20.16%, 100/496; P < 0.001); older adults had significantly higher RSV IgG positivity than young children in both pre-pandemic and pandemic periods (P values < 0.001). Interpretation: Our study documented the trajectory of RSV detection along with the changes in the stringency of NPIs, measured IgG positivity, and local COVID-19 epidemics. The findings suggest the interplay between contact patterns, immunity dynamics, and SARS-CoV-2 infection in shaping the RSV epidemics of population of different ages. These findings provide novel insights into the potential drivers of RSV circulating patterns and have important implications for RSV prevention and control strategies. Funding: The High-qualified Public Health Professionals Development Project, Capital's Funds for Health Improvement and Research, and the Public Health Personnel Training Support Program.

Unraveling the prognostic significance of RGS gene family in gastric cancer and the potential implication of RGS4 in regulating tumor-infiltrating fibroblast.

Regulator of G-protein signaling (RGS) proteins are regulators of signal transduction mediated by G protein-coupled receptors (GPCRs). Current studies have shown that some molecules in the RGS gene family are related to the occurrence, development and poor prognosis of malignant tumors. However, the RGS gene family has been rarely studied in gastric cancer. In this study, we explored the mutation and expression profile of RGS gene family in gastric cancer, and evaluated the prognostic value of RGS expression. Then we established a prognostic model based on RGS gene family and performed functional analysis. Further studies showed that RGS4, as an independent prognostic predictor, may play an important role in regulating fibroblasts in the immune microenvironment. In conclusion, this study explores the value of RGS gene family in gastric cancer, which is of great significance for predicting the prognosis and guiding the treatment of gastric cancer.

Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer.

PURPOSE: The hyperactivation of epidermal growth factor receptor (EGFR) plays a crucial role in non-small cell lung cancer (NSCLC). Hedgehog (Hh) signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth. METHODS: Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 (CCK-8) and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting. RESULTS: Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth. CONCLUSION: Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.

Community coalescence and plant host filtering determine the spread of tetracycline resistance genes from pig manure into the microbiome continuum of the soil-plant system.

The spread of livestock manure-borne antibiotic resistance genes (ARGs) into agroecosystems through manure application poses a potential threat to human health. However, there is still a knowledge gap concerning ARG dissemination in coalescing manure, soil and plant microbiomes. Here, we examined the fate of tetracycline resistance genes (TRGs) originating from pig manure microbiomes and spread in the soil-A thaliana system and explored the effects of microbial functions on TRGs spread at different interfaces. Our results indicate that the TRGs abundances in all microbiome continuum of the soil-A. thaliana system were significantly increased with the application of a living manure microbiome, although the addition of manure with both an active and inactive microbiome caused a shift in the microbial community composition. This was attributed to the increasing relative abundances of tetA, tetL, tetM, tetO, tetW and tolC in the system. The application of living manure with DOX residues resulted in the highest relative abundance of total TRGs (3.30×10-3 copies/16S rRNA gene copies) in the rhizosphere soil samples. Community coalescence of the manure and soil microbiomes increased the abundance of Firmicutes in the soil and root microbiome, which directly explains the increase in TRG abundance observed in these interfaces. In contrast, the leaf microbiome differed markedly from that of the remaining samples, indicating strong plant host filtering effects on Firmicutes and TRGs from pig manure. The random forest machine learning model revealed microbial functions and their significant positive correlation with TRG abundance in the microbiome continuum of the system. Our findings revealed that community coalescence is the main driver of TRG spread from manure to the soil and root microbiomes. Plant host filtering effects play a crucial role in allowing certain microbial groups to occupy ecological niches in the leaves, thereby limiting the establishment of manure-borne TRGs in aboveground plant tissues.

Enhanced detection of ligand-PPARγ binding based on surface plasmon resonance through complexation with SRC1- or NCOR2-related polypeptide.

A previous study reported the use of a biosensing technique based on surface plasmon resonance (SPR) for the ligand binding detection of peroxisome proliferator activator receptor gamma (PPARγ). This detection was designed based on the structural properties of PPARγ. Because of cross-linked protein inactivation and the low molecular weight of conventional ligands, direct ligand binding detection based on SPR has low stability and repeatability. In this study, we report an indirect response methodology based on SPR technology in which anti-His CM5 chip binds fresh PPARγ every cycle, resulting in more stable detection. We developed a remarkable improvement in ligand-protein binding detectability in vitro by introducing two coregulator-related polypeptides into this system. In parallel, a systematic indirect response methodology can reflect the interaction relationship between ligands and proteins to some extent by detecting the changes in SA-SRC1 and GST-NCOR2 binding to PPARγ. Rosiglitazone, a PPARγ agonist with strong affinity, is a potent insulin-sensitizing agent. Some ligands may be competitively exerted at the same sites of PPARγ (binding rosiglitazone). We demonstrated using indirect response methodology that selective PPARγ modulator (SPPARM) candidates of PPARγ can be found by competing for the binding of the rosiglitazone site on PPARγ, although they may have no effect on polypeptides and PPARγ binding.

Diagnostic value of one-step nucleic acid amplification for sentinel lymph node metastasis in cytokeratin 19-positive tumors: evidence from bioinformatics and meta-analysis.

Background: The status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database. Methods: Two researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection. Results: After literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/µl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/µl. Discussion: OSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers.

ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion.

Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.

Impact of MSMEG5257 Deletion on Mycolicibacterium smegmatis Growth.

Mycobacterial membrane proteins play a pivotal role in the bacterial invasion of host cells; however, the precise mechanisms underlying certain membrane proteins remain elusive. Mycolicibacterium smegmatis (Ms) msmeg5257 is a hemolysin III family protein that is homologous to Mycobacterium tuberculosis (Mtb) Rv1085c, but it has an unclear function in growth. To address this issue, we utilized the CRISPR/Cas9 gene editor to construct Δmsmeg5257 strains and combined RNA transcription and LC-MS/MS protein profiling to determine the functional role of msmeg5257 in Ms growth. The correlative analysis showed that the deletion of msmeg5257 inhibits ABC transporters in the cytomembrane and inhibits the biosynthesis of amino acids in the cell wall. Corresponding to these results, we confirmed that MSMEG5257 localizes in the cytomembrane via subcellular fractionation and also plays a role in facilitating the transport of iron ions in environments with low iron levels. Our data provide insights that msmeg5257 plays a role in maintaining Ms metabolic homeostasis, and the deletion of msmeg5257 significantly impacts the growth rate of Ms. Furthermore, msmeg5257, a promising drug target, offers a direction for the development of novel therapeutic strategies against mycobacterial diseases.

Thickness- and Field-Dependent Magnetic Domain Evolution in van der Waals Fe3GaTe2.

The discovery of room-temperature ferromagnetism in van der Waals (vdW) materials opens new avenues for exploring low-dimensional magnetism and its applications in spintronics. Recently, the observation of the room-temperature topological Hall effect in the vdW ferromagnet Fe3GaTe2 suggests the possible existence of room-temperature skyrmions, yet skyrmions have not been directly observed. In this study, real-space imaging was employed to investigate the domain evolution of the labyrinth and skyrmion structure. First, Néel-type skyrmions can be created at room temperature. In addition, the influence of flake thickness and external magnetic field (during field cooling) on both labyrinth domains and the skyrmion lattice is unveiled. Due to the competition between magnetic anisotropy and dipole interactions, the specimen thickness significantly influences the density of skyrmions. These findings demonstrate that Fe3GaTe2 can host room-temperature skyrmions of various sizes, opening up avenues for further study of magnetic topological textures at room temperature.

Maternal PFOS exposure in mice induces hepatic lipid accumulation and inflammation in adult female offspring: Involvement of microbiome-gut-liver axis and autophagy.

Perfluorooctane sulfonates (PFOS) are the persistent organic pollutants. In the present study, 0, 0.3, or 3-mg/kg PFOS were administered to pregnant mice from GD 11 to GD 18. The histopathology of liver and intestine, serum and hepatic lipid levels, lipid metabolism related genes, and gut microbiota were examined in adult female offspring. The results suggested that maternal PFOS exposure increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and induced F4/80+ macrophage infiltration in adult female offspring, in addition to the elevation of TNF-α and IL-1ß mRNA levels in low-dose and high-dose groups, respectively. Furthermore, maternal exposure to PFOS increased serum triglyceride (TG) and hepatic total cholesterol (TC) levels, which was associated with the alteration of the process of fatty acid transport and ß-oxidation, TG synthesis and transport, cholesterol synthesis and excretion in the liver. The AMPK/mTOR/autophagy signaling was also inhibited in the liver of adult female offspring. Moreover, changes in gut microbiota were also related to lipid metabolism, especially for the Desulfovibrio, Ligilactobacillus, Enterorhabdus, HT002 and Peptococcaceae_unclassified. Additionally, maternal exposure to PFOS decreased mRNA expressions of the tight junction protein and AB+ goblet cells in the colon, while increasing the overproduction of lipopolysaccharides (LPS) and F4/80+ macrophage infiltration. Collectively, maternal PFOS exposure induced liver lipid accumulation and inflammation, which strongly correlated with the disruption of the gut-liver axis and autophagy in adult female offspring, highlighting the persistent adverse effects in offspring exposed to PFOS.

Giant vesicles form in physiological saline and encapsulate pDNA by the modified electroformation method.

Giant vesicles (GVs) are used to study the structures and functions of cells and cell membranes. Electroformation is the most commonly used method for GV preparation. However, the electroformation of GVs is hindered in highly concentrated ionic solutions, limiting their application as cell models for research under physiological conditions. In this study, giant multilayer vesicles were successfully generated in physiological saline using a modified electroformation device by adding an insulating layer between the two electrode plates. The influence of the electric frequency and strength on the electroformation of GVs in physiological saline was explored, and a possible mechanism for this improvement was assessed. It has been shown that an insulating layer between the two electrodes can improve the electroformation of GVs in physiological saline by increasing the electrical impedance, which is weakened by the saline solution, thereby restoring the reduced effective electric field strength. Furthermore, macromolecular plasmid DNA (pDNA) was successfully encapsulated in the electroformed GVs of the modified device. This modified electroformation method may be useful for generating eukaryotic cell models under physiological conditions.

Effect of subanesthetic dose of esketamine on postoperative pain in elderly patients undergoing laparoscopic gastrointestinal tumor Surgery:A prospective, double-blind, randomized controlled trial.

Purpose: Postoperative pain is prevalent and severe complication in elderly surgical patients. Multiple studies propose that a small dose of esketamine administered intraoperatively can alleviate postoperative pain and curtail opioid usage. We aimed to evaluate the impact of esketamine on postoperative acute pain among elderly patients with gastrointestinal tumors. Patients and methods: This is a prospective, parallel-group, randomized controlled trial. Ninety patients aged 60 and above, undergoing resection of gastrointestinal tumors, were randomly assigned to two groups: esketamine group (Group S, a single dose of 0.25 mg/kg and 0.1 mg/kg/h infusion) and control group (Group C, saline). Visual Analogue Scale (VAS) pain scores were the primary outcome. Remifentanil consumption, instances of rescue analgesia, delirium, sleep quality, postoperative recovery quality, serum levels of inflammatory cytokines, and adverse events within 72 h post-surgery were secondary outcomes, respectively. Results: Data of 87 of 99 eligible patients were analyzed. VAS scores at rest in Group S were lower than those in Group C at 6 h [1.2 (0.6, 1.6) vs 1.6 (1.0, 2.0), P = 0.003], 12 h [1.4 (1.0, 2.0) vs 2.0 (1.5, 2.0), P < 0.001], and 24 h [1.8 (1.3, 2.0) vs 2.2 (1.6, 2.6), P < 0.001] postoperatively. At 6 h post-surgery, VAS score during coughing was lower in Group S than Group C [2.0 (2.0, 2.3) vs 2.0 (2.0, 3.0), P = 0.009]. The instances of rescue analgesia were fewer in group S compared to group C (P = 0.007). Furthermore, the esketamine group showed improved sleep quality and QoR-15 score (P < 0.05) postoperatively. Conclusion: Intravenous administration of esketamine as an adjunct to general anesthesia can decrease the intensity of pain for 24 h without additional adverse effects after laparoscopic gastrointestinal tumor surgery.

Bayesian mixed model inference for genetic association under related samples with brain network phenotype.

Genetic association studies for brain connectivity phenotypes have gained prominence due to advances in noninvasive imaging techniques and quantitative genetics. Brain connectivity traits, characterized by network configurations and unique biological structures, present distinct challenges compared to other quantitative phenotypes. Furthermore, the presence of sample relatedness in the most imaging genetics studies limits the feasibility of adopting existing network-response modeling. In this article, we fill this gap by proposing a Bayesian network-response mixed-effect model that considers a network-variate phenotype and incorporates population structures including pedigrees and unknown sample relatedness. To accommodate the inherent topological architecture associated with the genetic contributions to the phenotype, we model the effect components via a set of effect network configurations and impose an inter-network sparsity and intra-network shrinkage to dissect the phenotypic network configurations affected by the risk genetic variant. A Markov chain Monte Carlo (MCMC) algorithm is further developed to facilitate uncertainty quantification. We evaluate the performance of our model through extensive simulations. By further applying the method to study, the genetic bases for brain structural connectivity using data from the Human Connectome Project with excessive family structures, we obtain plausible and interpretable results. Beyond brain connectivity genetic studies, our proposed model also provides a general linear mixed-effect regression framework for network-variate outcomes.

Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging.

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia. Participants underwent [18F]MK6240 tau-PET, were assigned a PET-based Braak stage at baseline and were followed for a mean (SD) of 1.97 (0.66) years. Functional performance was evaluated with the Functional Activities Questionnaire, Everyday Cognition and functional Clinical Dementia Rating sum of boxes. Multiple linear regressions assessed the association of PET-based Braak stages with baseline functionality and with the longitudinal rate of change in functional scores, adjusting for age, sex and amyloid-ß load. We employed voxel-based regression models to investigate the association between functionality and tau-PET signal and assessed the voxel overlap with Braak regions of interest. We included 291 individuals (181 cognitively unimpaired, 56 amyloid-ß+ mild cognitive impairment and 54 amyloid-ß+ Alzheimer's disease) aged 70.60 (7.48) years. At baseline, PET-based Braak stages III-IV (ß = 0.43, P = 0.03) and V-VI (ß = 1.20, P < 0.0001) showed associations with poorer Functional Activities Questionnaire scores. Similarly, stages III-IV (ß = 0.43, P = 0.02) and V-VI (ß = 1.15, P < 0.0001) were associated with worse Everyday Cognition scores. Only stages V-VI were associated with higher functional Clinical Dementia Rating sum of boxes (ß = 1.17, P < 0.0001) scores. Increased tau-PET signals in all Braak regions of interest were linked to worse performance in all tools. The voxelwise analysis showed widespread cortical associations between functional impairment and tau-PET and high voxel overlap with Braak regions of interest. Baseline PET-based Braak stages V-VI predicted significant longitudinal functional decline as assessed by the Functional Activities Questionnaire (ß = 1.69, P < 0.0001), the Everyday Cognition (ß = 1.05, P = 0.001) and the functional Clinical Dementia Rating sum of boxes (ß = 1.29, P < 0.0001). Our results suggest that functional impairment increases with the severity of tau accumulation. These findings also indicate that PET-based Braak staging is a good predictor of functional impairment in the Alzheimer's disease continuum. Finally, our study provides evidence for the clinical significance of the PET-based Braak staging framework.

Identification of novel protein biomarkers from the blood and urine for the early diagnosis of bladder cancer via proximity extension analysis.

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.

A hydrogel-based ratiometric fluorescent sensor relying on rhodamine B labelled AIE-featured hyperbranched poly(amido amine) for heparin detection.

The fluorescent flexible sensor for point-of-care quantification of clinical anticoagulant drug, Heparin (Hep), is still an urgent need of breakthrough. In this research, a hyperbranched poly(amido amine) (HPA) was decorated with tetraphenylethene (TPE) and Rhodamine B (RhB), constructing a ratiometric fluorescent sensor (TR-HPA) for Hep. When the sensor was exposed to Hep, the TPE units within the probe skeleton would aggregate, resulting in an increasing fluorescent emission at 483 nm. The 580 nm of fluorescence came from RhB enhance, simultaneously, due to the fluorescence resonance energy transfer. As a result, there are two good linear correlation between the fluorescence emission ratio (E483/E580) of TR-HPA and the Hep concentration over a range of 0-1.0 µM, with a low limit of detection of 3.0 nM. Furthermore, we incorporate the TR-HPA probe into a polyvinyl alcohol (PVA) hydrogel matrix to create a flexible fluorescent sensing system platform, denoted as TR-HPA/PVA. This approach offers a straightforward visual detection method by causing a fluorescence color change from pink to blue when trace amounts of Hep are present. The hydrogel-based fluorescent sensor streamlines the detection procedures for Hep in biomedical applications. It shows great potential in rapid and point-of-care human blood clotting condition monitoring, making it suitable for next-generation wearable medical devices.

DNA hypomethylation of Syk induces oxidative stress and apoptosis via the PKCß/P66shc signaling pathway in diabetic kidney disease.

Epigenetic alterations, especially DNA methylation, have been shown to play a role in the pathogenesis of diabetes mellitus (DM) and its complications, including diabetic kidney disease (DKD). Spleen tyrosine kinase (Syk) is known to be involved in immune and inflammatory disorders. We, therefore, investigated the possible involvement of Syk promoter methylation in DKD, and the mechanisms underlying this process. Kidney tissues were obtained from renal biopsies of patients with early and advanced DKD. A diabetic mouse model (ApoE-/- DM) was generated from ApoE knockout (ApoE-/-) mice using a high-fat and high-glucose diet combined with low-dose streptozocin intraperitoneal injection. We also established an in vitro model using HK2 cells. A marked elevation in the expression levels of Syk, PKCß, and P66shc in renal tubules was observed in patients with DKD. In ApoE-/- DM mice, Syk expression and the binding of Sp1 to the Syk gene promoter were both increased in the kidney. In addition, the promoter region of the Syk gene exhibited hypomethylation. Syk inhibitor (R788) intervention improved renal function and alleviated pathologic changes in ApoE-/- DM mice. Moreover, R788 intervention alleviated oxidative stress and apoptosis and downregulated the expression of PKCß/P66shc signaling pathway proteins. In HK2 cells, oxLDL combined with high-glucose stimulation upregulated Sp1 expression in the nucleus (compared with control and oxLDL groups), and this was accompanied by an increase in the binding of Sp1 to the Syk gene promoter. SP1 silencing downregulated the expression of Syk and inhibited the production of reactive oxygen species and cell apoptosis. Finally, PKC agonist intervention reversed the oxidative stress and apoptosis induced by Syk inhibitor (R406). In DKD, hypomethylation at the Syk gene promoter was accompanied by an increase in Sp1 binding at the promoter. As a consequence of this enhanced Sp1 binding, Syk gene expression was upregulated. Syk inhibitors could attenuate DKD-associated oxidative stress and apoptosis via downregulation of PKCß/P66shc signaling pathway proteins. Together, our results identify Syk as a promising target for intervention in DKD.

Spatially resolved transcriptome of the aging mouse brain.

Brain aging is associated with cognitive decline, memory loss and many neurodegenerative disorders. The mammalian brain has distinct structural regions that perform specific functions. However, our understanding in gene expression and cell types within the context of the spatial organization of the mammalian aging brain is limited. Here we generated spatial transcriptomic maps of young and old mouse brains. We identified 27 distinguished brain spatial domains, including layer-specific subregions that are difficult to dissect individually. We comprehensively characterized spatial-specific changes in gene expression in the aging brain, particularly for isocortex, the hippocampal formation, brainstem and fiber tracts, and validated some gene expression differences by qPCR and immunohistochemistry. We identified aging-related genes and pathways that vary in a coordinated manner across spatial regions and parsed the spatial features of aging-related signals, providing important clues to understand genes with specific functions in different brain regions during aging. Combined with single-cell transcriptomics data, we characterized the spatial distribution of brain cell types. The proportion of immature neurons decreased in the DG region with aging, indicating that the formation of new neurons is blocked. Finally, we detected changes in information interactions between regions and found specific pathways were deregulated with aging, including classic signaling WNT and layer-specific signaling COLLAGEN. In summary, we established a spatial molecular atlas of the aging mouse brain (http://sysbio.gzzoc.com/Mouse-Brain-Aging/), which provides important resources and novel insights into the molecular mechanism of brain aging.

A comprehensive review of various carbonaceous materials for anodes in lithium-ion batteries.

With the advent of lithium-ion batteries (LIBs), the selection and application of electrode materials have been the subject of much discussion and study. Among them, graphite has been widely investigated for use as electrode materials in LIBs due to its abundant resources, low cost, safety and electrochemical diversity. While it is commonly recognized that conventional graphite materials utilized for commercial purposes have a limited theoretical capacity, there has been a steady emergence of new and improved carbonaceous materials for use as anodes in light of the progressive development of LIBs. In this paper, the latest research progress of various carbon materials in LIBs is systematically and comprehensively reviewed. Firstly, the rocking chair charging and discharging mechanism of LIBs is briefly introduced in this paper, using graphite anodes as an example. After that, the general categories of carbonaceous materials are highlighted, and the recent research on the recent progress of various carbonaceous materials (graphite-based, amorphous carbon-based, and nanocarbon-based) used in LIB anodes is presented separately based on the classification of the structural morphology, emphasizing the influence of the morphology and structure of carbon-based materials on the electrochemical performance of the batteries. Finally, the current challenges of carbonaceous materials in LIB applications and the future development of other novel carbonaceous materials are envisioned.