Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

miR-2467-3p/ABLIM1 Axis Mediates the Formation and Progression of Deep Vein Thrombosis by Regulating Inflammation and Oxidative Stress.

Deep vein thrombosis (DVT) is a common postoperative complication of orthopaedic surgery with a complex pathogenesis mechanism. The effect of the miR-2467-3p/acting-binding LIM protein 1 (ABLIM1) axis on thrombus formation and human vascular endothelial cells (HUVECs) progression was evaluated aiming to identify a novel potential biomarker of DVT. DVT rat models were established by inferior vena cava stenosis. The expression of the miR-2467-3p/ABLIM1 axis was analyzed by PCR. HUVECs were induced with oxidative low-density lipoprotein (ox-LDL). Cell growth and motility were assessed by cell counting kit 8 (CCK8) and Transwell assay. The inflammation and oxidative stress were estimated by proinflammatory cytokines and generation of MDA and reactive oxygen species (ROS). ABLIM1 was downregulated in DVT rats. Overexpressing ABLIM1 could suppress the formation of thrombosis and alleviate inflammation and oxidative stress. In HUVECs, ox-LDL induced significantly increased miR-2467-3p and decreased ABLIM1, and miR-2467-3p could negatively regulate ABLIM1. The knockdown of miR-2467-3p could alleviate the inhibited cell growth and motility by ox-LDL, and the inflammation and oxidative stress were also attenuated. While silencing could reverse the effect of miR-2467-3p on ox-LDL-induced HUVECs. The miR-2467-3p/ABLIM1 axis regulates the occurrence and development of DVT through modulating HUVECs inflammation and oxidative stress.

Naples Prognostic Score: A Novel Predictor of Survival in Patients with Triple-Negative Breast Cancer.

Purpose: This study investigated the correlation between the Naples prognostic score (NPS), clinicopathological traits, and the postoperative prognoses of patients with triple-negative breast cancer (TNBC). Based on NPS, a predictive nomogram was developed to estimate the long-term survival probabilities of patients with TNBC post-surgery. Patients and Methods: We retrospectively examined the clinical records of 223 women with TNBC treated at Ningbo Medical Center, Lihuili Hospital between January 1, 2016 and December 31, 2020. Blood tests and biochemical analyses were conducted before surgery. The prognostic nutritional index (PNI), controlling nutritional status (CONUT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and NPS were determined based on blood-related markers. A Kaplan-Meier survival analysis assessed the association between NPS, PNI, CONUT score, overall survival (OS), and breast cancer-specific survival (BCSS). Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and C index. The patients were randomly divided into the training and the validation group (6:4 ratio). A nomogram prediction model was developed and evaluated using the R Software for Statistical Computing (RMS) package. Results: NPS outperformed other scores in predicting inflammation outcomes. Patients with an elevated NPS had a poorer prognosis (P<0.001). Lymph node ratio (LNR), surgical method, postoperative chemotherapy, and NPS independently predicted OS, whereas M stage, LNR, and NPS independently predicted BCSS outcome. The OS and BCSS predicted by the nomogram model aligned well with the actual OS and BCSS. The decision curve analysis showed significant clinical utility for the nomogram model. Conclusion: In this study, NPS was an important prognostic indicator for patients with TNBC. The nomogram prognostic model based on NPS outperformed other prognostic scores for predicting patient prognosis. The model demonstrated a clear stratification ability for patient prognosis, which emphasized the potential benefits of early intervention for high-risk patients.

In this study, we aimed to understand how the Naples prognostic score (NPS) scoring system could predict the prognosis for patients with triple-negative breast cancer (TNBC). TNBC is a type of breast cancer that can be difficult to treat. Medical records of 223 women with TNBC were retrospectively analyzed. These women had their blood tested before surgery to check for certain markers related to nutrition and inflammation. NPS was used along with other scores to determine their accuracy in predicting survival. NPS was better at predicting outcomes than the other scores. The patients with higher NPS scores tended to have poorer outcomes. We also created a visual tool called a nomogram to help doctors predict patient outcomes based on the NPS scores. NPS can be a valuable tool for doctors treating patients with TNBC because it can help them predict how well a patient might do after surgery. This information could be used to tailor treatment plans for these patients. The nomogram provides a user-friendly way for doctors to use NPS in their practice. Overall, this study showed that NPS is a powerful tool for predicting outcomes for patients with TNBC, which could lead to better treatment decisions and improved outcomes for these patients.

Acute kidney injury in critical care: complications of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic inflammatory reactions and multiple-organ failure, including renal involvement. HLH can be classified as primary or secondary, with primary HLH associated with genetic mutations affecting cell degranulation capacity, and secondary HLH often linked to infections, tumors, and autoimmune diseases. The pathogenesis of HLH is not fully understood, but primary HLH is typically driven by genetic defects, whereas secondary HLH involves the activation of CD8+ T cells and macrophages, leading to the release of inflammatory cytokines and systemic inflammatory response syndrome (SIRS). The clinical presentation of HLH includes non-specific manifestations, making it challenging to differentiate from severe sepsis, particularly secondary HLH due to infections. Shared features include prolonged fever, hepatosplenomegaly, hematopenia, hepatic dysfunction, hypertriglyceridemia, and hypofibrinogenemia, along with histiocytosis and hemophagocytosis. However, distinctive markers like dual hemocytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated sCD25 levels may aid in differentiating HLH from sepsis. Indeed, no singular biomarker effectively distinguishes between hemophagocytic lymphohistiocytosis and infection. However, research on combined biomarkers provides insights into the differential diagnosis. Renal impairment is frequently encountered in both HLH and sepsis. It can result from a systemic inflammatory response triggered by an influx of inflammatory mediators, from direct damage caused by these factors, or as a consequence of the primary disease process. For instance, macrophage infiltration of the kidney can lead to structural damage affecting various renal components, precipitating disease. Presently, tubular necrosis remains the predominant form of renal involvement in HLH-associated acute kidney injury (HLH-AKI). However, histopathological changes may also encompass interstitial inflammation, glomerular abnormalities, microscopic lesions, and thrombotic microangiopathy. Treatment approaches for HLH and sepsis diverge significantly. HLH is primarily managed with repeated chemotherapy to eliminate immune-activating stimuli and suppress hypercellularity. The treatment approach for sepsis primarily focuses on anti-infective therapy and intensive symptomatic supportive care. Renal function significantly influences clinical decision-making, particularly regarding the selection of chemotherapy and antibiotic dosages, which can profoundly impact patient prognosis. Conversely, renal function recovery is a complex process influenced by factors such as disease severity, timely diagnosis, and the intensity of treatment. A crucial aspect in managing HLH-AKI is the timely diagnosis, which plays a pivotal role in reversing renal impairment and creating a therapeutic window for intervention, may have opportunity to improve patient prognosis. Understanding the clinical characteristics, underlying causes, biomarkers, immunopathogenesis, and treatment options for hemophagocytic lymphohistiocytosis associated with acute kidney injury (HLH-AKI) is crucial for improving patient prognosis.

A composite enzyme derived from papain and chymotrypsin reduces the Allergenicity of Cow's Milk allergen casein by targeting T and B cell epitopes.

Casein, the major allergen in cow's milk, presents a significant challenge in providing nutritional support for children with allergies. To address this issue, we investigated a composite enzyme, comprising papain and chymotrypsin, to reduce the allergenicity of casein. Enzymatic hydrolysis induced substantial structural changes in casein, diminishing its affinity for specific IgE and IgG antibodies. Additionally, in a BALB/c mouse model, casein hydrolysate alleviated allergic symptoms, evidenced by lower serum IgE and IgG levels, reduced plasma histamine, and decreased Th2 cytokine release during cell co-culture. Peptidomic analysis revealed a 52.38% and 60% reduction in peptides containing IgE epitopes in casein hydrolyzed by the composite enzyme compared to papain and chymotrypsin, respectively, along with a notable absence of previously reported T cell epitopes. These results demonstrate the potential of enzyme combinations to enhance the efficiency of epitope destruction in allergenic proteins, providing valuable insights into the development of hypoallergenic dairy products.

Evaluating eDNA and eRNA metabarcoding for aquatic biodiversity assessment: From bacteria to vertebrates.

The monitoring and management of aquatic ecosystems depend on precise estimates of biodiversity. Metabarcoding analyses of environmental nucleic acids (eNAs), including environmental DNA (eDNA) and environmental RNA (eRNA), have garnered attention for their cost-effective and non-invasive biomonitoring capabilities. However, the accuracy of biodiversity estimates obtained through eNAs can vary among different organismal groups. Here we evaluate the performance of eDNA and eRNA metabarcoding across nine organismal groups, ranging from bacteria to terrestrial vertebrates, in three cross-sections of the Yangtze River, China. We observe robust complementarity between eDNA and eRNA data. The relative detectability of eNAs was notably influenced by major taxonomic groups and organismal sizes, with eDNA providing more robust signals for larger organisms. Both eDNA and eRNA exhibited similar cross-sectional and longitudinal patterns. However, the detectability of larger organisms declined in eRNA metabarcoding, possibly due to differential RNA release and decay among different organismal groups or sizes. While underscoring the potential of eDNA and eRNA in large river biomonitoring, we emphasize the need for differential interpretation of eDNA versus eRNA data. This highlights the importance of careful method selection and interpretation in biomonitoring studies.

High efficiency Hg(II) electrochemical detection based on the number of defect engineering on MoS2: Insight in synergistic action of sulfur vacancies and undercoordinated Mo.

Defects on nanomaterials can effectively enhance the performance of electrochemical detection, but an excessive number of defects may have an adverse effect. In this study, MoS2 nanosheets were synthesized using a hydrothermal synthesis method. By controlling the calcination temperature, MoS2-7H, calcined at 700 °C under H2/Ar2, exhibited an optimal ratio of "point" defects to "plane" defects, resulting in excellent detection performance for mercury ions (Hg(II)). In general, the sulfur vacancies (SV) and undercoordinated Mo generated after calcination of MoS2 significantly promotes the adsorption process and redox of Hg(II) by increasing surface chemical activity, providing additional adsorption sites and adjusting surface charge status to accelerate the catalytic redox of Hg(II). The prepared MoS2-7H-modified electrode showed a sensitivity of 18.25 µA µM-1 and a low limit of detection (LOD) of 6.60 nM towards Hg(II). MoS2-7H also demonstrated a good anti-interference, stability, and exhibited a strong current response in real water samples. The modulation to obtain appropriate number of defects in MoS2 holds promise as a prospective electrode modification material for the electroanalysis.

Extraction Optimization of Phenolic Compounds from Triadica sebifera Leaves: Identification, Characterization and Antioxidant Activity.

Triadica sebifera (T. sebifera) has attracted much attention because of the high oil content in its seeds, but there are few systematic studies on the phenolic compounds of T. sebifera leaves (TSP). In this study, the extraction process of TSP was optimized by response surface methodology. The phenolic components of these extracts were analyzed by high-performance liquid chromatography (HPLC). Moreover, the effects of hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activity and characterization of T. sebifera leaf extract (TSLE) were evaluated. Under the conditions of ethanol concentration 39.8%, liquid-solid ratio (LSR) 52.1, extraction time 20.2 min and extraction temperature 50.6 °C, the maximum TSP yield was 111.46 mg GAE/g dw. The quantitative analysis and correlation analysis of eight compounds in TSP showed that the type and content of phenolic compounds had significant correlations with antioxidant activity, indicating that tannic acid, isoquercitrin and ellagic acid were the main components of antioxidant activities. In addition, through DPPH and ABTS determination, VD-TSLE and FD-TSLE showed strong scavenging ability, with IC50 values of 138.2 µg/mL and 135.5 µg/mL and 73.5 µg/mL and 74.3 µg/mL, respectively. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) infrared spectroscopy revealed small differences in the extracts of the three drying methods. This study lays a foundation for the effective extraction process and drying methods of phenolic antioxidants from T. sebifera leaves, and is of great significance for the utilization of T. sebifera leaves.

scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

Three-dimensional lattice Boltzmann model with self-tuning equation of state for multiphase flows.

In this work, the recent lattice Boltzmann (LB) model with self-tuning equation of state (EOS) [Huang et al., Phys. Rev. E 99, 023303 (2019)2470-004510.1103/PhysRevE.99.023303] is extended to three dimensions for the simulation of multiphase flows, which is based on the standard three-dimensional 27-velocity lattice and multiple-relaxation-time collision operator. To achieve the self-tuning EOS, the equilibrium moment is devised by introducing a built-in variable, and the collision matrix is improved by introducing some velocity-dependent nondiagonal elements. Meanwhile, the additional cubic terms of velocity in recovering the Newtonian viscous stress are eliminated to enhance the numerical accuracy. For modeling multiphase flows, an attractive pairwise interaction force is introduced to mimic the long-range molecular interaction, and a consistent scheme is proposed to compensate for the ɛ^{3}-order discrete lattice effect. Thermodynamic consistency in a strict sense is established for the multiphase LB model with self-tuning EOS, and the wetting condition is also treated in a thermodynamically consistent manner. As a result, the contact angle, surface tension, and interface thickness can be independently adjusted in the present theoretical framework. Numerical tests are first performed to validate the multiphase LB model with self-tuning EOS and the theoretical analyses of bulk and surface thermodynamics. The collision of equal-sized droplets is then simulated to demonstrate the applicability and effectiveness of the present LB model for multiphase flows.

A comparative study on cadmium tolerance and applicability of two Solanum lycopersicum L. cultivars.

Solanum lycopersicum L. can be classified into low Cd-accumulating and high Cd-accumulating types based on their accumulation characteristics of cadmium (Cd). There are many common S. lycopersicum varieties available in the market, but their specific Cd tolerance and enrichment abilities are not well understood. This article uses two S. lycopersicum cultivars, Yellow Cherry and Yellow Pearl, as experimental materials. The experimental method of soil pot planting was adopted, and Cd concentrations in the soil were added at 0, 0.6, 1.5, 2.5, 5, and 10 mg/kg. The changes in Cd content, biomass, photosynthetic pigment content, and photosynthetic parameters of the two S. lycopersicum cultivars were analyzed to screen for low-accumulation S. lycopersicum cultivars. The results showed that S. lycopersicum are Cd-sensitive plants. The Cd accumulation, photosynthetic parameters, and other basic indicators of Yellow Cherry basically showed significant differences when the soil Cd concentration was 0.6 mg/kg, and the biomass showed significant differences when the soil Cd concentration was 1.5 mg/kg. Except for the Cd accumulation in the roots and leaves of Yellow Pearl, which showed significant differences at a soil Cd concentration of 0.6 mg/kg, the other indicators basically showed significant differences when the soil Cd concentration was 1.5 mg/kg. When the soil Cd concentration was 0.6 mg/kg, the Cd accumulation in the fruit of Yellow Pearl was 0.04 mg/kg, making it a low-accumulation S. lycopersicum variety suitable for promoting cultivation in Cd-contaminated soil at 0.6 mg/kg. In conclusion, the Cd accumulation in the fruit of Yellow Pearl is significantly lower than that of Yellow Cherry and even below the Cd limit value for fresh vegetables specified in GB2762-2017. Therefore, Yellow Pearl can be grown as edible crops in soils with Cd concentrations ≤0.6 mg/kg. Furthermore, Yellow Cherry demonstrate strong Cd tolerance and can be used for the remediation of Cd-contaminated soils.

CD276 Promotes an Inhibitory Tumor Microenvironment in Hepatocellular Carcinoma and is Associated with Poor Prognosis.

Background: CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME). Methods: The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system. Results: CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8+ T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1-derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration. Conclusion: CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.

Osteoblasts are induced into cancer-associated osteoblasts to promote tumor progression in head and neck squamous cell carcinoma.

Bone invasion by head and neck squamous cell carcinoma (HNSCC) significantly impacts tumor staging, treatment choice, prognosis, and quality of life. While HNSCC is known to cause osteolytic bone invasion, we found that specific HNSCC subtypes can induce osteogenic bone destruction at the tumor-bone interface. This destruction mode significantly correlated with reduced patient survival rates and increased neck lymph node metastasis. Further in vivo and in vitro experiments indicated that HNSCC cells triggered abnormal phenotypic changes in osteoblasts to remodel the tumor-bone microenvironment, facilitating tumor lymphatic metastasis. Through transcriptome analysis, we identified three genes-osteopontin (SPP1), chemokine (C-X-C motif) ligand 1 (CXCL1), and matrix metalloprotein (MMP)9 (MMP9) linked to a poorer prognosis. We discovered osteoblasts with abnormal phenotypes at the tumor-bone interface exhibiting high SPP1, MMP9, and CXCL1 expressions. Based on these characteristics, we identified this osteoblast subpopulation as "cancer-associated osteoblasts (CAOs)." HNSCC cells activated the TNF-α/NF-κB signaling pathway in osteoblasts, transforming them into "CAOs." These CAOs significantly contributed to the progression of tumor-induced bone invasion, facilitating cancer growth and metastasis. We first provided clinical data and in vivo and in vitro evidence that HNSCC cells can promote tumor progression by manipulating osteoblasts into "CAOs" in the bone invasion.

Protective effects of patchouli alcohol against DSS-induced ulcerative colitis.

Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.

Multi-Omics analysis elucidates tumor microenvironment and intratumor microbes of angiogenesis subtypes in colon cancer.

BACKGROUND: Angiogenesis plays an important role in colon cancer (CC) progression. AIM: To investigate the tumor microenvironment (TME) and intratumor microbes of angiogenesis subtypes (AGSs) and explore potential targets for antiangiogenic therapy in CC. METHODS: The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. K-means clustering was used to construct the AGSs. The prognostic model was constructed based on the differential genes between two subtypes. Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC, which was validated by immunofluorescence. Its biological functions were further explored in HUVECs. RESULTS: CC samples were grouped into two AGSs (AGS-A and AGS-B) groups and patients in the AGS-B group had poor prognosis. Further analysis revealed that the AGS-B group had high infiltration of TME immune cells, but also exhibited high immune escape. The intratumor microbes were also different between the two subtypes. A convenient 6-gene angiogenesis-related signature (ARS), was established to identify AGSs and predict the prognosis in CC patients. SLC2A3 was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs. CONCLUSION: Our study identified two AGSs with distinct prognoses, TME, and intratumor microbial compositions, which could provide potential explanations for the impact on the prognosis of CC. The reliable ARS model was further constructed, which could guide the personalized treatment. The SLC2A3 might be a potential target for antiangiogenic therapy.

Advances in immune regulation of the G protein-coupled estrogen receptor.

Estrogen and related receptors have been shown to have a significant impact on human development, reproduction, metabolism and immune regulation and to play a critical role in tumor development and treatment. Traditionally, the nuclear estrogen receptors (nERs) ERα and ERß have been thought to be involved in mediating the estrogenic effects. However, our group and others have previously demonstrated that the G protein-coupled estrogen receptor (GPER) is the third independent ER, and estrogen signaling mediated by GPER is known to play an important role in normal physiology and a variety of abnormal diseases. Interestingly, recent studies have progressively revealed GPER involvement in the maintenance of the normal immune system, abnormal immune diseases, and inflammatory lesions, which may be of significant clinical value primarily in the immunotherapy of tumors. In this article, we review current advances in GPER-related immunomodulators and provide a theoretical basis and potential clinical targets to ameliorate immune-related diseases and immunotherapy for tumors.

Triple-negative breast cancer survival prediction: population-based research using the SEER database and an external validation cohort.

Introduction: Triple-negative breast cancer (TNBC) is linked to a poorer outlook, heightened aggressiveness relative to other breast cancer variants, and limited treatment choices. The absence of conventional treatment methods makes TNBC patients susceptible to metastasis. The objective of this research was to assess the clinical and pathological traits of TNBC patients, predict the influence of risk elements on their outlook, and create a prediction model to assist doctors in treating TNBC patients and enhancing their prognosis. Methods: We included 23,394 individuals with complete baseline clinical data and survival information who were diagnosed with primary TNBC between 2010 and 2015 based on the SEER database. External validation utilised a group from The Affiliated Lihuili Hospital of Ningbo University. Independent risk factors linked to TNBC prognosis were identified through univariate, multivariate, and least absolute shrinkage and selection operator regression methods. These characteristics were chosen as parameters to develop 3- and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) nomogram models. Model accuracy was assessed using calibration curves, consistency indices (C-indices), receiver operating characteristic curves (ROCs), and decision curve analyses (DCAs). Finally, TNBC patients were divided into groups of high, medium, and low risk, employing the nomogram model for conducting a Kaplan-Meier survival analysis. Results: In the training cohort, variables such as age at diagnosis, marital status, grade, T stage, N stage, M stage, surgery, radiation, and chemotherapy were linked to OS and BCSS. For the nomogram, the C-indices stood at 0.762, 0.747, and 0.764 in forecasting OS across the training, internal validation, and external validation groups, respectively. Additionally, the C-index values for the training, internal validation, and external validation groups in BCSS prediction stood at 0.793, 0.755, and 0.811, in that order. The findings revealed that the calibration of our nomogram model was successful, and the time-variant ROC curves highlighted its effectiveness in clinical settings. Ultimately, the clinical DCA showcased the prospective clinical advantages of the suggested model. Furthermore, the online version was simple to use, and nomogram classification may enhance the differentiation of TNBC prognosis and distinguish risk groups more accurately. Conclusion: These nomograms are precise tools for assessing risk in patients with TNBC and forecasting survival. They can help doctors identify prognostic markers and create more effective treatment plans for patients with TNBC, providing more accurate assessments of their 3- and 5-year OS and BCSS.

Ginsenoside Rg1 mitigates cerebral ischaemia/reperfusion injury in mice by inhibiting autophagy through activation of mTOR signalling.

Reperfusion injury, which is distinct from ischaemic injury, occurs when blood flow is restored in previously ischaemic brain tissue, further compromising neurons and other cells and worsening the injury. There is currently a lack of pharmaceutical agents and therapeutic interventions that specifically mitigate cerebral ischaemia/reperfusion (I/R) injury. Ginsenoside Rg1 (Rg1), a protopanaxatriol-type saponin isolated from Panax ginseng C. A. Meyer, has been found to protect against cerebral I/R injury, but its intricate protective mechanisms remain to be elucidated. Numerous studies have shown that autophagy plays a crucial role in protecting brain tissue during the I/R process and is emerging as a promising therapeutic strategy for effective treatment. In this study, we investigated whether Rg1 protected against I/R damage in vitro and in vivo by regulating autophagy. Both MCAO and OGD/R models were established. SK-N-AS and SH-SY5Y cells were subjected to OGD followed by reperfusion with Rg1 (4-32 µM). MCAO mice were injected with Rg1 (30 mg·kg-1·d-1. i.p.) for 3 days before and on the day of surgery. Rg1 treatment significantly mitigated ischaemia/reperfusion injury both in vitro and in vivo. Furthermore, we demonstrated that the induction of autophagy contributed to I/R injury, which was effectively inhibited by Rg1 in both in vitro and in vivo models of cerebral I/R injury. Rg1 inhibited autophagy through multiple steps, including impeding autophagy initiation, inducing lysosomal dysfunction and inhibiting cathepsin enzyme activities. We revealed that mTOR activation was pivotal in mediating the inhibitory effect of Rg1 on autophagy. Treatment with Torin-1, an autophagy inducer and mTOR-specific inhibitor, significantly reversed the impact of Rg1 on autophagy, decreasing its protective efficacy against I/R injury both in vitro and in vivo. In conclusion, our results suggest that Rg1 may serve as a promising drug candidate against cerebral I/R injury by inhibiting autophagy through activation of mTOR signalling.

Taohong Siwu decoction alleviates cognitive impairment by suppressing endoplasmic reticulum stress and apoptosis signaling pathway in vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (TSD), a classic traditional Chinese medicine formula, is used for the treatment of vascular diseases, including vascular dementia (VD). However, the mechanisms remain unclear. AIM OF STUDY: This study aimed to investigate whether TSD has a positive effect on cognitive impairment in VD rats and to confirm that the mechanism of action is related to the Endoplasmic Reticulum stress (ERs) and cell apoptosis signaling pathway. MATERIALS AND METHODS: A total of 40 male adult Sprague-Dawley rats were divided into four groups: sham-operated group (Sham), the two-vessel occlusion group (2VO), the 2VO treated with 4.5 g/kg/d TSD group (2VO + TSD-L), the 2VO treated with 13.5 g/kg/d TSD group (2VO + TSD-H). The rats underwent either 2VO surgery or sham surgery. Postoperative TSD treatment was given for 4 consecutive weeks. Behavioral tests were initiated at the end of gastrulation. Open-field test (OFT) was used to detect the activity level. The New Object Recognition test (NOR) was used to test long-term memory. The Morris water maze (MWM) test was used to examine the foundation of spatial learning and memory. As a final step, the hippocampus was taken for molecular testing. The protein levels of GRP78 (Bip), p-PERK, PERK, IRE1α, p-IRE1α, ATF6, eIF2α, p-eIF2α, ATF4, XBP1, Bcl-2 and Bax were determined by Western blot. Immunofluorescence visualizes molecular expression. RESULTS: In the OFT, residence time in the central area was significantly longer in both TSD treatment groups compared to the 2VO group. In the NOR, the recognition index was obviously elevated in both TSD treatment groups. The 2VO group had a significantly longer escape latency and fewer times in crossing the location of the platform compared with the Sham group in MWM. TSD treatment reversed this notion. Pathologically, staining observations confirmed that TSD inhibited hippocampal neuronal loss and alleviated the abnormal reduction of the Nissl body. In parallel, TUNEL staining illustrated that TSD decelerated neuronal apoptosis. Western Blot demonstrated that TSD reduces the expression of ERs and apoptotic proteins. CONCLUSION: In this study, the significant ameliorative effect on cognitive impairment of TSD has been determined by comparing the behavioral data of the 4 groups of rats. Furthermore, it was confirmed that this effect of TSD was achieved by suppressing the ERs-mediated apoptosis signaling pathway.

Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.