High-density mapping of durable and broad-spectrum stripe rust resistance gene Yr30 in wheat.

KEY MESSAGE: The durable stripe rust resistance gene Yr30 was fine-mapped to a 610-kb region in which five candidate genes were identified by expression analysis and sequence polymorphisms. The emergence of genetically diverse and more aggressive races of Puccinia striiformis f. sp. tritici (Pst) in the past twenty years has resulted in global stripe rust outbreaks and the rapid breakdown of resistance genes. Yr30 is an adult plant resistance (APR) gene with broad-spectrum effectiveness and its durability. Here, we fine-mapped the YR30 locus to a 0.52-cM interval using 1629 individuals derived from residual heterozygous F5:6 plants in a Yaco"S"/Mingxian169 recombinant inbred line population. This interval corresponded to a 610-kb region in the International Wheat Genome Sequencing Consortium (IWGSC) RefSeq version 2.1 on chromosome arm 3BS harboring 30 high-confidence genes. Five genes were identified as candidate genes based on functional annotation, expression analysis by RNA-seq and sequence polymorphisms between cultivars with and without Yr30 based on resequencing. Haplotype analysis of the target region identified six haplotypes (YR30_h1-YR30_h6) in a panel of 1215 wheat accessions based on the 660K feature genotyping array. Lines with YR30_h6 displayed more resistance to stripe rust than the other five haplotypes. Near-isogenic lines (NILs) with Yr30 showed a 32.94% higher grain yield than susceptible counterparts when grown in a stripe rust nursery, whereas there was no difference in grain yield under rust-free conditions. These results lay a foundation for map-based cloning Yr30.

Development and validation of risk prediction model for bacterial infections in acute liver failure patients.

Infections significantly increase mortality in acute liver failure (ALF) patients, and there are no risk prediction models for early diagnosis and treatment of infections in ALF patients. This study aims to develop a risk prediction model for bacterial infections in ALF patients to guide rational antibiotic therapy. The data of ALF patients admitted to the Second Hospital of Hebei Medical University in China from January 2017 to January 2022 were retrospectively analyzed for training and internal validation. Patients were selected according to the updated 2011 American Association for the Study of Liver Diseases position paper on ALF. Serological indicators and model scores were collected within 24 h of admission. New models were developed using the multivariate logistic regression analysis. An optimal model was selected by receiver operating characteristic (ROC) analysis, Hosmer-Lemeshow test, the calibration curve, the Brier score, the bootstrap resampling, and the decision curve analysis. A nomogram was plotted to visualize the results. A total of 125 ALF patients were evaluated and 79 were included in the training set. The neutrophil-to-lymphocyte ratio and sequential organ failure assessment (SOFA) were integrated into the new model as independent predictive factors. The new SOFA-based model outperformed other models with an area under the ROC curve of 0.799 [95% confidence interval (CI): 0.652-0.926], the superior calibration and predictive performance in internal validation. High-risk individuals with a nomogram score ≥26 are recommended for antibiotic therapy. The new SOFA-based model demonstrates high accuracy and clinical utility in guiding antibiotic therapy in ALF patients.

Estimated plasma volume status as a simple and accessible predictor of 28-day mortality in septic shock: insights from a retrospective study of the MIMIC-IV database.

Background: Assessing volume status in septic shock patients is crucial for tailored fluid resuscitation. Estimated plasma volume status (ePVS) has emerged as a simple and effective tool for evaluating patient volume status. However, the prognostic value of ePVS in septic shock patients remains underexplored. Methods: The study cohort consisted of septic shock patients admitted to the ICU, sourced from the MIMIC-IV database. Patients were categorized into two groups based on 28-day survival outcomes, and their baseline characteristics were compared. According to the ePVS (6.52 dL/g) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low ePVS groups. A multivariable Cox regression model was utilized to evaluate the association between ePVS and 28-day mortality rate. The Kaplan-Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test. Results: A total of 7,607 septic shock patients were included in the study, among whom 2,144 (28.2%) died within 28 days. A J-shaped relationship was observed between ePVS at ICU admission and 28-day mortality, with an increase in mortality risk noted when ePVS exceeded 6.52 dL/g. The high ePVS group exhibited notably higher mortality rates compared to the low ePVS group (28-day mortality: 26.2% vs. 30.2%; 90-day mortality: 35% vs. 42.3%). After adjustment for confounding factors, ePVS greater than 6.52 dL/g independently correlated with an increased risk of 28-day mortality (HR: 1.20, 95% CI: 1.10-1.31, p < 0.001) and 90-day mortality (HR: 1.25, 95% CI: 1.15-1.35, p < 0.001). Kaplan-Meier curves demonstrated a heightened risk of mortality associated with ePVS values exceeding 6.52 dL/g. Conclusion: A J-shaped association was observed between ePVS and 28-day mortality in septic shock patients, with higher ePVS levels associated with increased risk of mortality.

Multifunctional Buffer Layer Engineering for Efficient and Stable Wide-Bandgap Perovskite and Perovskite/Silicon Tandem Solar Cells.

Inverted perovskite solar cells (PSCs) are preferred for tandem applications due to their superior compatibility with diverse bottom solar cells. However, the solution processing and low formation energy of perovskites inevitably lead to numerous defects at both the bulk and interfaces. We report a facile and effective strategy for precisely modulating the perovskite by incorporating AlOx deposited by atomic layer deposition (ALD) on the top interface. We find that Al3+ can not only infiltrate the bulk phase and interact with halide ions to suppress ion migration and phase separation but also regulate the arrangement of energy levels and passivate defects on the perovskite surface and grain boundaries. Additionally, ALD-AlOx exhibits an encapsulation effect through a dense interlayer. Consequently, the ALD-AlOx treatment can significantly improve the power conversion efficiency (PCE) to 21.80 % for 1.66 electron volt (eV) PSCs. A monolithic perovskite-silicon TSCs using AlOx-modified perovskite achieved a PCE of 28.5 % with excellent photothermal stability. More importantly, the resulting 1.55 eV PSC and module achieved a PCE of 25.08 % (0.04 cm2) and 21.01 % (aperture area of 15.5 cm2), respectively. Our study provides an effective way to efficient and stable wide-band gap perovskite for perovskite-silicon TSCs and paves the way for large-area inverted PSCs.

Prospective Evaluation of the Peripheral Perfusion Index in Assessing the Organ Dysfunction and Prognosis of Adult Patients With Sepsis in the ICU.

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (ß -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (ß -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (ß -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (ß -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (ß -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (ß -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (ß -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research.

Preparation of a Novel Oat ß-Glucan-Chromium(III) Complex and Its Hypoglycemic Effect and Mechanism.

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.

Synergistic Effects of TiO2 and Carbon Black for Water Evaporation-Induced Electricity Generation.

Water evaporation-induced electricity generators (WEGs) have drawn widespread attention in the field of hydrovoltaic technology, which can convert atmospheric thermal energy into sustainable electric power. However, it is restricted in the wide application of WEGs due to the low power output, complex fabrication process, and high cost. Herein, we present a simple and effective approach to fabricate TiO2-carbon black film-based WEGs (TC-WEGs). A single TC-WEG device can sustainably output an open-circuit voltage of 1.9 V and a maximum power density of 40.9 µW/cm2. Moreover, it has been shown that TC-WEGs exhibit stable electrical energy output when operating in seawater, which can yield a short-circuit current of 1.2 µA. The superior electricity generation performance can be attributed to the intrinsic characteristics of the TC-WEGs, including hydrophilicity, porous structure, and electrical conductivity. This work provides an important reference for the constant harvesting of clean energy.

Persistent combined type sleep-related rhythmic movement disorder into adolescence: a case report.

SRMD is characterized by repetitive, stereotyped, rhythmic movements of large muscle groups, primarily occurring at the onset of sleep and during sleep. Common in infancy and early childhood, its persistence into adolescence or adulthood is rare. Combined type is rare. This article reviews and analyzes the diagnosis and treatment of a case with combined type SRMD persisting for 15 years aimed at enhancing the level of diagnosis and treatment of the disorder, and reducing misdiagnosis and missed diagnosis.

Efficient and Stable Inverted Perovskite Solar Modules Enabled by Solid-Liquid Two-Step Film Formation.

A considerable efficiency gap exists between large-area perovskite solar modules and small-area perovskite solar cells. The control of forming uniform and large-area film and perovskite crystallization is still the main obstacle restricting the efficiency of PSMs. In this work, we adopted a solid-liquid two-step film formation technique, which involved the evaporation of a lead iodide film and blade coating of an organic ammonium halide solution to prepare perovskite films. This method possesses the advantages of integrating vapor deposition and solution methods, which could apply to substrates with different roughness and avoid using toxic solvents to achieve a more uniform, large-area perovskite film. Furthermore, modification of the NiOx/perovskite buried interface and introduction of Urea additives were utilized to reduce interface recombination and regulate perovskite crystallization. As a result, a large-area perovskite film possessing larger grains, fewer pinholes, and reduced defects could be achieved. The inverted PSM with an active area of 61.56 cm2 (10 × 10 cm2 substrate) achieved a champion power conversion efficiency of 20.56% and significantly improved stability. This method suggests an innovative approach to resolving the uniformity issue associated with large-area film fabrication.

Focus on oliguria during renal replacement therapy.

Oliguria is a clinical symptom characterized by decreased urine output, which can occur at any stage of acute kidney injury and also during renal replacement therapy. In some cases, oliguria may resolve with adjustment of blood purification dose or fluid management, while in others, it may suggest a need for further evaluation and intervention. It is important to determine the underlying cause of oliguria during renal replacement therapy and to develop an appropriate treatment plan. This review looks into the mechanisms of urine production to investigate the mechanism of oliguria during renal replacement therapy from two aspects: diminished glomerular filtration rate and tubular abnormalities. The above conditions all implying a renal oxygen supply-demand imbalance, which is the signal of worsening kidney injury. It also proposes a viable clinical pathway for the treatment and management of patients with acute kidney injury receiving renal replacement therapy.

A Novel Nomogram to Predict Prognosis of Advanced Hepatocellular Carcinoma Treated with Intensity-Modulated Radiotherapy Plus Anti-PD1.

Purpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1. Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC). Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3-4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3-4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1-3 years AUROC of 78.7, 78.6, and 93.5, respectively. Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.

The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti­PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3­4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3­4 weeks after IMRT initiation demonstrated good reliability.

Echocardiographic features of right ventricle in septic patients with elevated central venous pressure.

BACKGROUND: Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. METHODS: We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. RESULTS: Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302-0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007-1.903, p = 0.045) were independently associated with 30-day mortality. CONCLUSIONS: Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.

Boosting oxygen reduction durability by embedding Co9S8 nanoparticles into Co single atoms anchored porous carbon frameworks.

Developing an efficient and low-cost oxygen reduction electrocatalyst is essential for the application of aqueous zinc-air batteries (ZABs). Herein, we report a facile adsorption-confined pyrolysis strategy to fabricate the hybrid electrocatalyst (denoted as Co9S8/CoSA-PC) by embedding Co9S8 nanoparticles into Co single atoms (Co-SAs) anchored porous carbon sheets for boosting oxygen reduction reaction (ORR) durability. In this strategy, the Co2+ ions are first absorbed into oxygen-rich porous carbon nanosheets and further form the Co-SAs with the help of thiourea in the following pyrolysis procedure, which is believed to be able to confine the generated Co9S8 nanoparticles into carbon frameworks due to their interface interaction. Benefiting from the synergistic effect of different components, the obtained Co9S8/CoSA-PC electrocatalyst for ORR exhibits outstanding catalytic activity with a half-wave potential of 0.82 V and a distinguished long-term durability with a current retention of 80 % after cycling 80 h under alkaline conditions, which is superior to commercial Pt/C. Moreover, the assembled ZABs with Co9S8/CoSA-PC as cathodic catalyst deliver a high specific capacity of 764 mAh gZn-1 at 10 mA cm-2 and the outstanding peak power density of up to 221.4 mW cm-2. This work provides a novel structure design strategy to prepare transition metal sulfide-based electrocatalysts with superior durability for ORR.

Acupoints catgut embedding recovers leptin resistance via improving autophagy progress mediated by AMPK-mTOR signaling in obese mice.

Purpose: Leptin resistance represents a primary pathological manifestation in obesity. Investigating potential treatments and associated mechanisms to restore leptin sensitivity is crucial for effective obesity management. This study aimed to explore the therapeutic potential of acupoints catgut embedding (ACE) in addressing obesity and its associated leptin resistance. Methods: A simple obesity model was established by subjecting C57 male mice to a high-fat diet (HFD) for 12 weeks, followed by ACE treatment administered to half of the obese mice for a duration of 4 weeks. The levels of leptin and its receptor-lepRb, were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. Autophagy progression markers were evaluated through quantitative polymerase chain reaction (qPCR) and Western blot analysis. Also, the liver autophagosomes were photographed using electron microscopy. The role of autophagy in regulating leptin resistance was elucidated using an autophagy suppression model. Results: Comparative analyses demonstrated that ACE treatment resulted in a significant reduction in body weight and blood lipid levels compared to the HFD group. Furthermore, serum leptin levels decreased, while liver lepRb expression increased following ACE treatment. The mRNA and protein expression levels of autophagy in liver were adjusted by ACE treatment. Interestingly, the beneficial effects of ACE were attenuated upon the administration of an autophagy inhibitor. Additionally, ACE treatment led to the activation of the AMPK-mTOR signaling pathway, a crucial regulator of autophagy. Conclusion: These findings suggest that ACE therapy holds promise for recovering leptin resistance by enhancing autophagy progression, mediated via the AMPK-mTOR signaling pathway in liver.

Analysis of widely targeted metabolites of quinoa sprouts (Chenopodium quinoa Willd.) under saline-alkali stress provides new insights into nutritional value.

Quinoa sprouts are a green vegetable rich in bioactive chemicals, which have multiple health benefits. However, there is limited information on the overall metabolic profiles of quinoa sprouts and the metabolite changes caused by saline-alkali stress. Here, a UHPLC-MS/MS-based widely targeted metabolomics technique was performed to comprehensively evaluate the metabolic profiles of quinoa sprouts and characterize its metabolic response to saline-alkali stress. A total of 930 metabolites were identified of which 232 showed significant response to saline-alkali stress. The contents of lipids and amino acids were significantly increased, while the contents of flavonoids and phenolic acids were significantly reduced under saline-alkali stress. Moreover, the antioxidant activities of quinoa sprouts were significantly affected by saline-alkali stress. The enrichment analysis of the differentially accumulated metabolites revealed that flavonoid, amino acid and carbohydrate biosynthesis/metabolism pathways responded to saline-alkali stress. This study provided an important theoretical basis for evaluating the nutritional value of quinoa sprouts and the changes in metabolites in response to saline-alkali stress.

A Novel Prolene Suture Pull-out Technique Combined with Anchor Technique for the Treatment of Tendinous Mallet Finger.

Background: Mallet finger deformity is a prevalent disability that causes discomfort and inconvenience to the patients. Despite the existence of various surgical approaches, surgical management remains a controversial subject. Methods: We retrospectively analyzed the clinical data of 26 patients with isolated tendinous mallet fingers who were admitted between January 2021 and June 2022. Among them, there were 18 men and eight women, aged between 20 and 56 years, with an average age of 38 years. The causes of injury were cutting injuries (15 cases), sports impact injuries (nine cases), and sprains (two cases). The time interval between injury and surgery ranged from 2 hours to 48 days, with an average of 12 days. During the surgical procedure, the distal interphalangeal joint was fixed in a mild dorsiflexion position using Kirschner wire. Absorbable anchors were used to assist in the reconstruction of the insertion point of the finger extensor tendon. Additionally, a 4-0 Prolene suture was used for reinforcement. Results: All 26 patients were followed up for a period ranging from 6 to 24 months, with an average follow-up duration of 9 months. The function of distal interphalangeal joint was preserved. According to the Crawford functional evaluation criteria, the function of the affected fingers was excellent in 15 cases, good in eight cases, fair in three cases, and poor in no cases. Conclusions: A novel Prolene suture pull-out technique is an effective approach to repair tendon mallet finger and reconstruct the tendon-bone anatomical unit. This treatment option provides favorable outcomes, with high rates of excellent and good functional results.

Innovative prognostic modeling in ESCC: leveraging scRNA-seq and bulk-RNA for dendritic cell heterogeneity analysis.

Background: Globally, esophageal squamous cell carcinoma (ESCC) stands out as a common cancer type, characterized by its notably high rates of occurrence and mortality. Recent advancements in treatment methods, including immunotherapy, have shown promise, yet the prognosis remains poor. In the context of tumor development and treatment outcomes, the tumor microenvironment (TME), especially the function of dendritic cells (DCs), is significantly influential. Our study aims to delve deeper into the heterogeneity of DCs in ESCC using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis. Methods: In the scRNA-seq analysis, we utilized the SCP package for result visualization and functional enrichment analysis of cell subpopulations. CellChat was employed to identify potential oncogenic mechanisms in DCs, while Monocle 2 traced the evolutionary trajectory of the three DC subtypes. CopyKAT assessed the benign or malignant nature of cells, and SCENIC conducted transcription factor regulatory network analysis, offering a preliminary exploration of DC heterogeneity. In Bulk-RNA analysis, we constructed a prognostic model for ESCC prognosis and immunotherapy response, based on DC marker genes. This model was validated through quantitative PCR (qPCR) and immunohistochemistry (IHC), confirming the gene expression levels. Results: In this study, through intercellular communication analysis, we identified GALECTIN and MHC-I signaling pathways as potential oncogenic mechanisms within dendritic cells. We categorized DCs into three subtypes: plasmacytoid (pDC), conventional (cDC), and tolerogenic (tDC). Our findings revealed that pDCs exhibited an increased proportion of cells in the G2/M and S phases, indicating enhanced cellular activity. Pseudotime trajectory analysis demonstrated that cDCs were in early stages of differentiation, whereas tDCs were in more advanced stages, with pDCs distributed across both early and late differentiation phases. Prognostic analysis highlighted a significant correlation between pDCs and tDCs with the prognosis of ESCC (P< 0.05), while no significant correlation was observed between cDCs and ESCC prognosis (P = 0.31). The analysis of cell malignancy showed the lowest proportion of malignant cells in cDCs (17%), followed by pDCs (29%), and the highest in tDCs (48%), with these results being statistically significant (P< 0.05). We developed a robust ESCC prognostic model based on marker genes of pDCs and tDCs in the GSE53624 cohort (n = 119), which was validated in the TCGA-ESCC cohort (n = 139) and the IMvigor210 immunotherapy cohort (n = 298) (P< 0.05). Additionally, we supplemented the study with a novel nomogram that integrates clinical features and risk assessments. Finally, the expression levels of genes involved in the model were validated using qPCR (n = 8) and IHC (n = 16), thereby confirming the accuracy of our analysis. Conclusion: This study enhances the understanding of dendritic cell heterogeneity in ESCC and its impact on patient prognosis. The insights gained from scRNA-seq and Bulk-RNA analysis contribute to the development of novel biomarkers and therapeutic targets. Our prognostic models based on DC-related gene signatures hold promise for improving ESCC patient stratification and guiding treatment decisions.

Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.

Global burden of head and neck cancers from 1990 to 2019.

Head and neck cancer (HNC) exerts a significant healthcare burden worldwide. Insufficient data impedes a comprehensive understanding of its global impact. Through analysis of the 2019 Global Burden of Disease (GBD) database, our secondary investigation unveiled a surging global incidence of HNC, yet a decline in associated mortality and disability-adjusted life years (DALYs) owing to enhanced prognosis. Particularly noteworthy is the higher incidence of escalation among females compared to males. Effective resource allocation, meticulous control of risk factors, and tailored interventions are imperative to curtail mortality rates among young individuals afflicted with HNC in underprivileged regions, as well as in elderly individuals grappling with thyroid cancer.