High-performance thermoelectric fibers from metal-backboned polymers for body-temperature wearable power devices.

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric hybrid fiber. The obtained fiber demonstrated a power factor of 719.48 µW×m-1×K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the hybrid fiber shows simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

Diagnostic and predictive significance of the ferroptosis-related gene TXNIP in lung adenocarcinoma stem cells based on multi-omics.

BACKGROUND: Lung cancer stands as the foremost cause of cancer-related fatalities globally. The presence of cancer stem cells (CSCs) poses a challenge, rendering current targeted tumor therapies ineffective. This study endeavors to investigate a novel therapeutic approach focusing on ferroptosis and delves into the expression of ferroptosis-related genes within lung CSCs. METHODS: We systematically examined RNA-seq datasets derived from lung tumor cells (LTCs) and lung cancer stem cells (LSCs), as previously investigated in our research. Our focus was on analyzing differentially expressed genes (DEGs) related to ferroptosis. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), we conducted functional analysis of these ferroptosis-related DEGs. Additionally, we employed protein‒protein interaction networks to identify hub genes. LC‒MS/MS analysis of LTCs and LSCs was conducted to pinpoint the crucial ferroptosis-related gene-thioredoxin-interacting protein (TXNIP).Further, we delved into the immune cell infiltration landscape of LTCs and LSCs, examining the correlation between TXNIP and lung adenocarcinoma (LUAD) using data from The Cancer Genome Atlas (TCGA) database. To complement these findings, we measured the expression levels of TXNIP, glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4 (NCOA4) in LUAD tissues through immunohistochemistry (IHC) staining. RESULTS: A total of 651 DEGs were identified, with 17 of them being ferroptosis-related DEGs. These seventeen genes were categorized into four groups: driver genes, suppressor genes, unclassified genes, and inducer genes. Enrichment analysis revealed significant associations with oxidative stress, cell differentiation, tissue development, and cell death processes. The RNA-seq analysis demonstrated consistent gene expression patterns with protein expression, as evidenced by mass spectrometry analysis. Among the identified genes, SFN and TXNIP were singled out as hub genes, with TXNIP showing particularly noteworthy expression. The expression of the ferroptosis-related gene TXNIP exhibited correlations with the presence of an immunosuppressive microenvironment, TNM stages, and the degree of histological differentiation.Also, the ferroptosis-markers GPX4 and NCOA4 displayed correlations with LUAD. This comprehensive analysis underscores the significance of TXNIP in the context of ferroptosis-related processes and their potential implications in cancer development and progression. CONCLUSION: The investigation conducted in this study systematically delved into the role of the ferroptosis-related gene TXNIP in Lung CSCs. The identification of TXNIP as a potentially valuable biomarker in this context could have significant implications for refining prognostic assessments and optimizing therapeutic strategies for advanced lung cancer.

A case of excisionally remitted indolent NK-cell enteropathy in the oral cavity and a mini-review.

Benign natural killer cell enteropathy (NKCE) was first identified in the gastrointestinal (GI) tract. Notably, instances of NKCE have previously been observed at various sites other than the GI tract, including the gallbladder, lymph nodes, esophagus, and female genital tract. Typical NKCE manifests as an NK-cell immunohistological phenotype, with or without TCR rearrangement, and is characterized by the absence of Epstein-Barr virus (EBV) infection and protracted clinical progression. The misdiagnosis of NKT-cell lymphoma has resulted in some patients receiving chemotherapy, while in other instances, the patients' conditions resolved without treatment and showed no evidence of disease recurrence or progression during follow-up examinations. In this paper, we describe a unique case of EBV-negative NKCE occurring in the oral cavity, the first time such a case has been documented. The tumor completely resolved after an excisional biopsy, and subsequent follow-up did not reveal any signs of disease recurrence.

High-performance fibre battery with polymer gel electrolyte.

Replacement of liquid electrolytes with polymer gel electrolytes is recognized as a general and effective way of solving safety problems and achieving high flexibility in wearable batteries1-6. However, the poor interface between polymer gel electrolyte and electrode, caused by insufficient wetting, produces much poorer electrochemical properties, especially during the deformation of the battery7-9. Here we report a strategy for designing channel structures in electrodes to incorporate polymer gel electrolytes and to form intimate and stable interfaces for high-performance wearable batteries. As a demonstration, multiple electrode fibres were rotated together to form aligned channels, while the surface of each electrode fibre was designed with networked channels. The monomer solution was effectively infiltrated first along the aligned channels and then into the networked channels. The monomers were then polymerized to produce a gel electrolyte and form intimate and stable interfaces with the electrodes. The resulting fibre lithium-ion battery (FLB) showed high electrochemical performances (for example, an energy density of about 128 Wh kg-1). This strategy also enabled the production of FLBs with a high rate of 3,600 m h-1 per winding unit. The continuous FLBs were woven into a 50 cm × 30 cm textile to provide an output capacity of 2,975 mAh. The FLB textiles worked safely under extreme conditions, such as temperatures of -40 °C and 80 °C and a vacuum of -0.08 MPa. The FLBs show promise for applications in firefighting and space exploration.

Evaluating the association between effort-reward imbalance and suboptimal health status among hospital nurses: a cross-sectional study.

OBJECTIVES: Occupational stress is a common complaint in nurses, who perceived more sense of effort-reward imbalance (ERI). Suboptimal health status (SHS) is a state between health and disease. However, the correlation between ERI and SHS is unclear. Therefore, the aim of this study was to examine the prevalence of SHS and ERI and evaluate the relationship between ERI and SHS in clinical nurses by a cross-sectional study. MATERIAL AND METHODS: The current cross-sectional study was conducted through an online survey at Dongping People's Hospital in China. A total of 633 completed surveys were received. Effort-reward imbalance was measured by subscales of the ERI questionnaire. SHS was measured by the Suboptimal Health Status Questionnaire - 25 (SHSQ-25). The relationship between ERI and SHS in nurses was subsequently assessed by Spearman's correlation coefficient and logistic regression model. RESULTS: The mean age of the optimal health status (OHS) group (M±SD 26.3±7.3 years) was younger than the SHS group (M±SD 30.3±6.9 years). The prevalence of SHS was 54.5% (345/633). Female nurses aged ≥30 years, a junior college or university graduate educational level, smokers, and nurses without regular exercise were at a higher risk of SHS. In Spearman's correlation analysis, ERI reflected by the effort-reward ratio was correlated with SHSQ-25 score (r = 0.662, p < 0.001). In logistic regression, ERI was strongly associated with SHS after potential confounding factors adjusting (OR 27.924, 95% CI 22.845-34.132). CONCLUSIONS: The prevalence of SHS was significantly high in clinical nurses. Administrators should pay more attention to health status of female nurses aged ≥30 years, with a junior college or bachelor's degree, smoking, and without regular exercise to reduce the SHS and ERI. Int J Occup Med Environ Health. 2024;37(2).

A radiomics model based on transrectal ultrasound for predicting prostate cancer.

AIM: Prostate cancer (PCa) is one of the most common neoplasms in men. However, the value of ultrasound-based radiomics for diagnosing PCa remains uncertain. MATERIAL AND METHODS: We retrospectively analyzed ultrasonic and clinical data from 373 patients. Patients were divided into two groups according to the pathological results. Radiomics features wereextracted from TRUS, and we screened the optimal features to construct radiomics models. Relationships between clinical characteristics and prostate lesions were identified by univariate and multivariate logistic regression analysis. Finally, a clinical-radiomics model was developed, and then visualized in the form of a nomogram. RESULTS: Of the 373 patients, 178 had benign disease and 195 had malignant disease. The support vector machine (SVM) classification model showed the best performance, while the diagnostic performance of the clinical model was poorer than that of the radiomics model (p<0.05) or the combined (clinical-radiomics) model (p<0.05). In general, the combined model demonstrated the highest AUC and proved to be more advantageous. CONCLUSION: The prediction model we constructed based on TRUS predicted PCa preoperatively with high efficiency. In addition, combining radiomics with clinical factors improved diagnostic accuracy.

Phosphatidic Acid Promoting the Generation of Interleukin-17A Producing Double-Negative T Cells by Enhancing mTORC1 Signaling in Lupus.

OBJECTIVE: The goal was to investigate the role and intracellular regulatory mechanisms of double-negative T (DNT) cells in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: DNT cells were assessed in murine models, patients with SLE, and controls using flow cytometry (FCM). DNT cells from either resiquimod (R848) or vehicle-treated C57BL/6 (B6) mice were cultured with B cells from R848-treated mice to explore functions. Differential mechanistic target of rapamycin (mTOR) pathway signaling in DNT cells measured using FCM and quantitative polymerase chain reaction was validated by rapamycin inhibition. Candidate lipid metabolites detected using liquid chromatography with electrospray ionization mass spectrometry/mass spectrometry were functionally assessed in DNT cell cultures. RESULTS: DNT cells were markedly increased in both spontaneous and induced mouse lupus models and in patients with SLE. Expanded DNT cells from R848-treated B6 mice produced elevated interleukin (IL)-17A and IgG with increased germinal center B (GCB) cells. Expansion of DNT cells associated with activation of mTORC1 pathway that both IL-17A levels and the number of DNT cells exhibited dose-dependent reduction with rapamycin treatment. Lipidomics studies revealed differential patterns of lipid metabolites in T cells of R848-treated mice. Among candidate metabolites, elevated phosphatidic acid (PA) that was partially controlled by phospholipase D2 increased the expression of the mTORC1 downstream target p-S6 and positively expanded IL-17A-producing DNT cells. Similarly, elevated proportions of circulating DNT cells in patients with SLE correlated with disease activity and proteinuria, and IL-17A secretion was elevated after in vitro PA stimulation. CONCLUSION: The accumulation of PA in T cells could activate the mTORC1 pathway, promoting DNT cell expansion and IL-17A secretion, resulting in GCB cell abnormalities in lupus.

Reduced mitochondrial-encoded NADH dehydrogenase 6 gene expression drives inflammatory CD4+T cells in patients with systemic lupus erythematosus.

Abnormal mitochondrial function has been implicated in the progression of systemic lupus erythematosus (SLE), the prototypical autoimmune disease, yet the underlying cause remains unclear. In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m6A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA antibodies. With the reduction of MT-ND6 levels, CD4+ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of reactive oxygen species (ROS) and mitochondrial ROS and insufficient ATP production. Accordingly, in vitro MT-ND6 silencing induced abnormalities in the above mitochondrial indicators in CD4+ T cells, and promoted the development of both transcription and inflammatory factors in these cells. In contrast, treatment with targeted mitochondrial antioxidants largely counteracted the silencing effect of MT-MD6. Thus, reduced MT-ND6 in SLE patients may lead to mitochondrial dysfunction through ROS overproduction, thereby promoting inflammatory CD4+ T cells.

Unveiling the link between systemic inflammation markers and cognitive performance among older adults in the US: A population-based study using NHANES 2011-2014 data.

PURPOSE: This study aimed to evaluate the association between systemic inflammation markers and cognitive performance among older US adults. METHODS: This cross-sectional study assessed 3,632 older participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). The main analysis included participants aged over 60 years. Systemic inflammation markers were quantified by calculating the composite inflammation indicators from the blood routine count, and cognitive performance was assessed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test (AFT), and Digit Symbol Substitution test (DSST). RESULTS: There were 2,743 individuals enrolled in the current analysis. The overall mean age was 64.9 years and 48.7 % were males. The levels of SIRI and PIV were significant negative associated with scores of CERAD, CERAD delayed recall, and DSST in the unadjusted models. Moreover, SII were significant negative associated with scores of CERAD and CERAD delayed recall. After adjusting the covariates of demographics, lifestyle factors, history of chronic diseases and BMI, significant negative association were observed between systematic inflammation markers and cognitive performance. Additionally, a progressive and significant decrease in the score of cognitive performance assessments with the increased levels of SIRI, SII, and PIV were respectively observed. Finally, the correlation between systemic inflammation markers and cognitive performance were evidenced in the sensitive analysis. CONCLUSION: Findings support a strong inverse correlation between systemic inflammation markers and cognitive performance, suggesting that addressing inflammation could be a promising avenue for enhancing cognitive health and mitigating age-related cognitive decline.

Golgi Protein 73 Promotes LPS-Induced Cardiac Dysfunction via Mediating Myocardial Apoptosis and Autophagy.

ABSTRACT: Sepsis-induced cardiac dysfunction represents a major cause of high mortality in intensive care units with limited therapeutic options. Golgi protein 73 (GP73) has been implicated in various diseases. However, the role of GP73 in lipopolysaccharide (LPS)-induced cardiac dysfunction is unclear. In this study, we established a sepsis-induced cardiac dysfunction model by LPS administration in wild-type and GP73 knockout ( GP73-/- ) mice. We found that GP73 was increased in LPS-treated mouse hearts and LPS-cultured neonatal rat cardiomyocytes (NRCMs). Knockout of GP73 alleviated myocardial injury and improved cardiac dysfunction. Moreover, depletion of GP73 in NRCMs relieved LPS-induced cardiomyocyte apoptosis and activated myocardial autophagy. Therefore, GP73 is a negative regulator in LPS-induced cardiac dysfunction by promoting cardiomyocyte apoptosis and inhibiting cardiomyocyte autophagy.

Dosage-sensitive and simultaneous detection of multiple small-molecule pollutants in environmental water and agriproducts using portable SERS-based lateral flow immunosensor.

The co-contamination of pesticide residues and mycotoxins in agricultural products is a global concern, with the potential for cumulative and synergistic damaging effects, imposing substantial health and economic burdens to the public. The dosage-sensitive and simultaneous detection of multiple pollutants, with a heightened sensitivity in real samples, poses a significant demand and challenge. Herein, we propose a portable detection method integrating surface-enhanced Raman scattering (SERS)-with lateral flow immunoassay (LFIA), offering high sensitivity and multiplex analysis capabilities. This approach enables the simultaneous detection of imidacloprid (IMI), pyraclostrobin (PYR) and aflatoxin B1 (AFB1) through a single test strip. Utilizing the immune-specific binding between antigen and antibodies, we immobilised antibody- conjugated SERS nanotags on three test lines of the strips to generate Raman signal amplification in the proposed biosensor. Accurate quantitative analysis was performed by measuring the SERS signal intensity on the test lines. The limits of detection were 8.6 pg/mL for IMI, 97.4 pg/mL for PYR and 8.9 pg/mL for AFB1, exhibiting sensitivities 12-fold, 102-fold and11-fold higher than the colorimetric signals, respectively. Importantly, the SERS-LFIA immunosensor demonstrated robust performance when applied to real samples, yielding recoveries ranging from 86.16 % to 115.0 %, with relative standard deviation values below 8.67 %. These results underscore the excellent stability, high selectivity and reliability the proposed SERS-LFIA immunosensor. Consequently, it holds promise for the detection of multiple pesticides and mycotoxins in both environmental and agricultural samples.

Blockade of Notch1 Signaling Alleviated Podocyte Injury in Lupus Nephritis Via Inhibition of NLRP3 Inflammasome Activation.

To explore the role of Notch1 pathway in the pathogenesis of podocyte injury, and to provide novel strategy for podocyte repair in lupus nephritis (LN). Bioinformatics analysis and immunofluorescence assay were applied to determine the expression and localization of Notch1 intracellular domain1 (NICD1) in kidneys of LN patients and MRL/lpr mice. The stable podocyte injury model in vitro was established by puromycin aminonucleoside (PAN) treatment. Expression of inflammasome activation related gene was detected by qPCR. The podocytes with PAN treatment were cultured with or without N-S-phenyl-glycine-t-butylester (DAPT), an inhibitor of Notch1 pathway. NICD1, Wilm'stumor1 (WT1), nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), and absent in melanoma-like receptors 2 (AIM2) were detected by western blot. In vivo, MRL/lpr mice were administrated with DAPT or vehicle. The LN symptoms were assessed. The podocyte injury was evaluated, and the NLRP3 in podocytes of mice was detected. Notch1 pathway was overactivated in glomeruli of LN patients. NICD1 was colocalized with podocytes of LN patients and MRL/lpr mice. The inflammasome-related genes were significantly increased in podocytes with PAN treatment. NICD1 and NLRP3 were significantly decreased, while WT1 was significantly increased in injured podocytes treated with DAPT in vitro. In vivo, lupus-like symptoms were alleviated in DAPT treatment group. Notch1 pathway was inhibited in kidneys of mice treated with DAPT. The renal inflammation was reduced and the podocyte injury was mitigated in DAPT treatment group. The NLRP3 was decreased in podocytes of mice treated with DAPT. Notch1 pathway was overactivated in podocytes of LN patients and MRL/lpr mice. Blockade of Notch1 pathway reduced renal inflammation and alleviated podocyte injury via inhibition of NLRP3 inflammasome activation in LN.

Synergistic Enhancement of Isoforskolin and Dexamethasone Against Sepsis and Acute Lung Injury Mouse Models.

Background: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation. Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR. Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2. Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.

Renomegaly and acute kidney injury as primary manifestations of non-Hodgkin's lymphoma: a report of three cases.

BACKGROUND: In adults with non-Hodgkin's lymphoma, renal enlargement and acute kidney injury occur infrequently at first presentation, especially in T lymphocytic lymphomas. CASE PRESENTATION: We report three cases of non-Hodgkin's lymphoma with acute renal injury and bilateral renal enlargement. At diagnosis, one patient presented with an adrenal mass, one patient's lymph node biopsy was consistent with a renal biopsy, and one patient had primary renal lymphoma with no extrarenal disease. Assessment of renal pathology in Case 2 and Case 3 showed interstitial lymphocyte infiltration; the pathological types were non-Hodgkin's diffuse large B lymphoma originating from activated B cells outside germinal centers and non-Hodgkin's T-lymphoblastic lymphoma/leukemia, respectively. Case 1 did not receive anti-lymphoma therapy and died from infection and multiple organ failure within 1 month of hospitalization. Case 2 received eight courses of R-CHOP; her lymphoma recurred 2 years after diagnosis and she died from severe pulmonary infection 3 years after diagnosis. Case 3 received hyper-CVAD regularly and achieved stable renal function; this patient remains under follow-up. CONCLUSIONS: Renal lymphoma may have diverse manifestations, especially primary renal lymphoma without extrarenal involvement. Nephrologists should pay careful attention to these manifestations to ensure accurate diagnosis.

MST1/2 in inflammation and immunity.

The mammalian Sterile 20-like kinase 1/2 (MST1/2) belongs to the serine/threonine (GC) protein kinase superfamily. Collective studies confirm the vital role MST1/2 in inflammation and immunity. MST1/2 is closely related to the progress of inflammation. Generally, MST1/2 aggravates the inflammatory injury through MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, as well as several regulatory factors such as tumor necrosis factor-α (TNF-α), mitochondrial extension factor 1 (MIEF1), and lipopolysaccharide (LPS). Moreover, MST1/2 is also involved in the regulation of immunity to balance immune activation and tolerance by regulating MST1/2-Rac, MST1-Akt1/c-myc, MST1-Foxos, MST1-STAT, Btk pathways, and lymphocyte function-related antigen 1 (LFA-1), which subsequently prevents immunodeficiency syndrome and autoimmune diseases. This article reviews the effects of MST1/2 on inflammation and immunity.

Effect of Modified Cellulose Nanocrystals on the Structure of Calcium Silicate Hydrate Studied by Molecular Dynamics Simulation and Experiment.

The interfacial bonding of the four cellulose nanocrystals (CNCs) and calcium silicate hydrate (C-S-H) in vacuum and solution conditions was analyzed by molecular dynamics simulation. The binding energies were calculated, and the sources of interface strength were analyzed by the formation and lifetime of hydrogen bonds. The adsorption between CNC/C-S-H was characterized by the movement of interfacial atoms and CNC's adsorption conformation. The types of the functional group determine the bonding of the CNC/C-S-H, and the interface adsorption in two simulation conditions both followed: CNC-C (carboxyl) > CNC-O (hydroxyl) > CNC-N (amino) > CNC-S (sulfonic). The bonding of the interface affects the load transferred between the matrix and CNC, which can be reflected in the overall mechanical properties of the mortar. The mechanical strength of the mortar is in line with the simulation results. CNC-C has the strongest reinforcement effect, while CNC-S has the weakness effect. In the solution simulation, there is almost no chemical adsorption between C-S-H and CNC-S; instead, CNC-S decreased the bonding between the matrix and reduced the strength of the sample. Scanning electron microscopy found that CNC was interspersed in the matrix, riveting the matrix and enhanced the stability of the mortar structure. The influence of CNC on the mortar structure was analyzed by the calcium to silicon ratio (C/S) and it was showed that CNC-C, CNC-O, and CNC-N have an enhancement effect, while CNC-S decreased the coherence of the cement matrix. Durability and nuclear magnetic resonance tests further verified the effect of the four CNCs on the structure of mortar, and results indicated that CNC-C, CNC-O, and CNC-N can control the growth of hydration crystals, fill the cracks, and reduced porosity of samples, while CNC-S reduces the compactness of hydration products and ultimately decreased the mechanical and durability properties of the mortar.

Early C-reactive Protein Kinetics Predict Response to Immune Checkpoint Blockade in Unresectable Hepatocellular Carcinoma.

Purpose: In recent years, a new therapeutic approach, known as immune checkpoint blockade (ICB), has been proposed as approach to improve outcomes in patients with intermediate stage (Barcelona Clinic Liver Cancer, BCLC B) or advanced stage (BCLC C) hepatocellular carcinoma (HCC). Unfortunately, only a select patients can benefit from ICB. Hence, biomarkers that can predict the success and survival of treatment are still necessary. Patients and Methods: Between 2018 to 2021, 132 patients received ICB treatment for intermediate or advanced stage HCC. Based on the early kinetics of C-reactive protein (CRP), the patients were classified into three groups. The study endpoints were progression-free survival (PFS) and overall survival (OS). Results: Our findings support the predictive power of early CRP kinetics in determining immunotherapy response for intermediate or advanced HCC. Objective response rates (ORR) were found in 41.2% of CRP flare-responders, 13.3% of CRP responders, and 3.5% of CRP non-responders (p<0.001). Disease control rates (DCR) in the three groups were substantially different (p<0.001). The improved PFS and OS were strongly correlated with the early kinetics of CRP. Compared to CRP non-responders, CRP responders, especially CRP flare-responders, had significantly longer PFS (median PFS: CRP flare-responders: 11.6 months vs CRP responders: 5.2 months vs CRP non-responders: 2.3 months, p<0.001). Conclusion: The CRP flare response robustly predicts the immunotherapy response and outcomes in patients with HCC. Early CRP kinetics may be an inexpensive, easily implemented and non-invasive biomarker to anticipate response to ICB therapy in intermediate or advanced HCC, with the potential to optimize treatment monitoring.

Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα). Plk-1 inhibition impeded NF-κB signal pathway activation in LPS-treated mouse hearts and NRCMs. Augmented Plk-1 is thus essential for the development of SIMD and is a druggable target for SIMD.

Efficacy and safety of totally laparoscopic gastrectomy with uncut Roux-en-Y for gastric cancer: a dual-center retrospective study.

BACKGROUND: Uncut Roux-en-Y (URY) effectively alleviates the prevalent complexities connected with RY, such as Roux-en-Y stasis syndrome (RSS). Nevertheless, for gastric cancer (GC) patients, it is still controversial whether URY has an impact on long-term prognosis and whether it has fewer afferent loop recanalization. Therefore, compare whether URY and RY have differences in prognosis and long-term complications of GC patients undergoing totally laparoscopic gastrectomy (TLG). METHODS: We analyzed the data of patients who underwent TLG combined with digestive tract reconstruction from dual-center between 2016 and 2022. Only patients undergoing URY and RY were selected for analysis. Relapse-free survival (RFS) and overall survival (OS) were estimated. Bias between the groups was reduced by propensity score matching (PSM). The Cox proportional hazard regression model was used to further analyze the influence of URY on prognosis. RESULTS: Two hundred forty two GC patients were enrolled. The URY had significantly shorter operation time, liquid food intake time, and in-hospital stays than the RY (P < 0.001). The URY had fewer long-term and short-term postoperative complications than the RY, especially with regard to RSS, reflux esophagitis, and reflux gastritis. The 3-year and 5-year OS of the URY group and the RY group before PSM: 87.5% vs. 65.6% (P < 0.001) and 81.4% vs. 61.7% (P = 0.001). PSM and Cox multivariate analysis confirmed that compared to RY, URY can improve the short-term and long-term prognosis of GC patients. CONCLUSION: TLG combined with URY for GC, especially for advanced, older, and poorly differentiated patients, may promote postoperative recovery and improve long-term prognosis.

Atomistic Study of the Effect of Hydrogen on the Tendency toward Slip Planarity in Bcc Iron.

H-enhanced slip planarity is generally explained in terms of H-reducing stacking fault energy in fcc systems. Here, we showed that H-decreasing dislocation line energies can enhance the tendency toward slip planarity in bcc Fe through systematically studying the interaction between H and 1/2 <111> {110} dislocations using the EAM potential for Fe-H systems. It was found that the binding energy of H, the excess H in the atmosphere, and the interaction energy of H increased with edge components, leading to larger decrements in the line energies of the edge and increased mixed dislocations than those of a screw dislocation. The consequence of such interaction patterns is an increment in the energy change in the system when the edge and mixed dislocations are converted to screw dislocations as compared to the H-free cases. The cross-slip in bcc Fe is thus suppressed by H, increasing the tendency toward slip planarity.