Unraveling Stoichiometry Effect in Nickel-Tungsten Alloys for Efficient Hydrogen Oxidation Catalysis in Alkaline Electrolytes.

Anion-exchange membrane fuel cells provide the possibility to use platinum group metal-free catalysts, but the anodic hydrogen oxidation reaction (HOR) suffers from sluggish kinetics and its source is still debated. Here, over nickel-tungsten (Ni-W) alloy catalysts, we show that the Ni:W ratio greatly governs the HOR performance in alkaline electrolyte. Experimental and theoretical studies unravel that alloying with W can tune the unpaired electrons in Ni, tailoring the potential of zero charge and the catalytic surface to favor hydroxyl adsorption (OHad). The OHad species coordinately interact with potassium (K+) ions, which break the K+ solvation sheath to leave free water molecules, yielding an improved connectivity of hydrogen-bond networks. Consequently, the optimal Ni17W3 alloy exhibits alkaline HOR activity superior to the state-of-the-art platinum on carbon (Pt/C) catalyst and operates steadily with negligible decay after 10,000 cycles. Our findings offer new understandings of alloyed HOR catalysts and will guide rational design of next-generation catalysts for fuel cells.

MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A.

BACKGROUND: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission. AIM: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance. METHODS: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis. RESULTS: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target. CONCLUSION: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.

Comparison of left- and right-sided colorectal cancer to explore prognostic signatures related to pyroptosis.

Background: Colorectal cancer (CRC) is one of the most common malignancies, and pyroptosis exerts an immunoregulatory role in CRC. Although the location of the primary tumor is a prognostic factor for patients with CRC, the mechanisms of pyroptosis in left- and right-sided CRC remain unclear. Methods: Expression and clinical data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differences in clinical characteristics, immune cell infiltration, and somatic mutations between left- and right-sided CRC were then compared. After screening for differentially expressed genes, Pearson correlation analysis was performed to select pyroptosis-related genes, followed by a gene set enrichment analysis. Univariate and multivariate Cox regression analyses were used to construct and validate the prognostic model and nomogram for predicting prognosis. Collected left- and right-sided CRC samples were subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of key pyroptosis-related genes. Results: Left- and right-sided CRC exhibited significant differences in clinical features and immune cell infiltration. Five prognostic signatures were identified from among 134 pyroptosis-related differentially expressed genes to construct a risk score-based prognostic model, and adverse outcomes for high-risk patients were further verified using an external cohort. A nomogram was also generated based on three independent prognostic factors to predict survival probabilities, while calibration curves confirmed the consistency between the predicted and actual survival. Experiment data confirmed the significant differential expression of five genes between left- and right-sided CRC. Conclusion: The five identified pyroptosis-related gene signatures may be potential biomarkers for predicting prognosis in left- and right-sided CRC and may help improve the clinical outcomes of patients with CRC.

Accumulation patterns of tobacco root allelopathicals across different cropping durations and their correlation with continuous cropping challenges.

Introduction: Continuous cropping challenges have gradually emerged as pivotal factors limiting the sustainable development of agricultural production. Allelopathicals are considered to be the primary obstacles. However, there is limited information on allelopathic accumulation across various continuous cropping years and its correlation with the associated challenges. Methods: Tobacco was subjected to varying planting durations: 1 year (CR), 5 years (CC5), 10 years (CC10), and 15 years (CC15). Results: Our findings unveiled discernible disparities in tobacco growth patterns across diverse continuous cropping periods. Notably, the most pronounced challenges were observed in the CC5 category, characterized by yield reduction, tobacco black shank outbreaks, and a decline in beneficial flora. Conversely, CC15 exhibited a substantial reduction in challenges as the continuous cropping persisted with no significant differences when compared to CR. Within the tobacco rhizosphere, we identified 14 distinct allelopathic compounds, with 10 of these compounds displaying noteworthy variations among the four treatments. Redundancy analysis (RDA) revealed that eight allelopathic compounds exhibited autotoxic effects on tobacco growth, with MA, heptadecanoic acid, and VA ranking as the most potent inhibitors. Interaction network highlighted the pivotal roles of VA and EA in promoting pathogen proliferation and impeding the enrichment of 13 beneficial bacterial genera. Furthermore, a structural equation model elucidated that MA and EA primarily exert direct toxic effects on tobacco, whereas VA fosters pathogen proliferation, inhibits the enrichment of beneficial bacteria, and synergistically exacerbates the challenges associated with continuous cropping alongside EA. Discussion: These findings suggested discernible disparities in tobacco growth patterns across the various continuous cropping periods. The most pronounced challenges were observed in CC5, whereas CC15 exhibited a substantial reduction in challenges as continuous cropping persisted. VA may play a pivotal role in this phenomenon by interacting with pathogens, beneficial bacterial genera, and EA.

Global prevalence of erectile dysfunction and its associated risk factors among men with type 1 diabetes: a systematic review and meta-analysis.

Various observational studies have examined the prevalence and determinants of erectile dysfunction (ED) in men with type 1 diabetes across different geographical areas. Nevertheless, a comprehensive systematic review and meta-analysis to consolidate the worldwide prevalence and risk factors remains lacking. Hence, the primary study objective was to perform an extensive systematic review and meta-analysis that specifically examined ED prevalence and determinants in men with type 1 diabetes. A thorough exploration was conducted by examining electronic databases, such as PubMed, Embase, and Web of Science. The general ED prevalence and a 95% confidence interval (CI) in men with type 1 diabetes were summarized. The relevant risk factors were analyzed by deriving a comprehensive odds ratio (OR) from merging the ORs using fixed- or random-effects models. The sources of heterogeneity were investigated using subgroup analyses and meta-regression. This systematic review and meta-analysis included 19 articles involving 3788 men with type 1 diabetes. The meta-analysis revealed that men with type 1 diabetes had a combined ED prevalence of 42.5% (95% CI: 34.3%-50.8%). This prevalence showed significant heterogeneity (I2 = 96.2%, P < 0.01). Meta-regression revealed that age (P = 0.016) and type 1 diabetes duration (P = 0.004) were significant causes of heterogeneity. Furthermore, the ED risk in men with type 1 diabetes was significantly influenced by age, type 1 diabetes duration, body mass index, glycated hemoglobin (HbA1c), retinopathy, and smoking habits (all P < 0.05). In summary, this systematic review and meta-analysis revealed a significant prevalence of ED in men with type 1 diabetes, highlighting the importance of clinicians addressing concerns regarding ED in this specific group of individuals.

CD4+ T cell immunity is dependent on an intrinsic stem-like program.

CD4+ T cells are central to various immune responses, but the molecular programs that drive and maintain CD4+ T cell immunity are not entirely clear. Here we identify a stem-like program that governs the CD4+ T cell response in transplantation models. Single-cell-transcriptomic analysis revealed that naive alloantigen-specific CD4+ T cells develop into TCF1hi effector precursor (TEP) cells and TCF1-CXCR6+ effectors in transplant recipients. The TCF1-CXCR6+CD4+ effectors lose proliferation capacity and do not reject allografts upon adoptive transfer into secondary hosts. By contrast, the TCF1hiCD4+ TEP cells have dual features of self-renewal and effector differentiation potential, and allograft rejection depends on continuous replenishment of TCF1-CXCR6+ effectors from TCF1hiCD4+ TEP cells. Mechanistically, TCF1 sustains the CD4+ TEP cell population, whereas the transcription factor IRF4 and the glycolytic enzyme LDHA govern the effector differentiation potential of CD4+ TEP cells. Deletion of IRF4 or LDHA in T cells induces transplant acceptance. These findings unravel a stem-like program that controls the self-renewal capacity and effector differentiation potential of CD4+ TEP cells and have implications for T cell-related immunotherapies.

Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape.

Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor-ß (TGF-ß) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy.

Detection and quantification of etomidate and metomidate in human hairs by ultraperformance liquid chromatography with triple quadrupole mass spectrometry (UPLC-MS/MS).

PURPOSE: Intravenous narcotic agents, such as etomidate and metomidate, has been widely spread and abused in the world, including in Korea and China; thus, it is important to establish validated and sensitive analytical method for these compounds. Human hair as a biological sample has various advantages, including a wide detection window of drugs, compared to other typical samples, such as urine and blood in investigation. The purpose of this communication is to develop a reliable and useful method for the simultaneous detection and quantification of etomidate and metomidate in human hair samples by ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry (UPLC-MS/MS), and to apply it for authentic samples in abuse cases. METHODS: The hair samples were washed with a detergent solution, followed by with water and acetone. After drying, they were cut into approximately 2 mm sections and then ground to powder by a low-temperature grinder. The 20 mg of hair powder plus internal standard in 1 mL of methanol was vortexed and then centrifuged to obtain the supernatant layer, followed by subjecting to analysis. RESULTS: The coefficient of determination (r2) values of the calibration curves of etomidate and metomidate in the hair samples were both more than 0.99 in the range of 1-500 ng/mg and 1-500 pg/mg, respectively. The limits of detection and lower limits of quantification were 0.5 and 1 pg/mg, respectively, for the both target compounds. Other tested validation data were all satisfactory. Etomidate and metomidate could be detected in the all hair samples and cigarette oil, which were seized by the police. The concentrations of etomidate and metomidate obtained from 10 samples from suspects were 5.48-45.7 ng/mg and 3.60-377 pg/mg, respectively. The concentrations of etomidate and metomidate in the cigarette oil were 95.8 µg/mg and 2.8 µg/mg, respectively. CONCLUSIONS: In this study, a simple and reliable analytical method for etomidate and metomidate in the human hair has been established. To the best of our knowledge, this is the first report to establish a method for the simultaneous detection and quantification of etomidate and metomidate in the human hair, and to apply it to authentic samples seized in authentic cases.

Direct visualization of immune status for tumor-infiltrating lymphocytes by rolling circle amplification.

The immune status of tumor-infiltrating lymphocytes (TILs) is essential for the effectiveness of cancer immunotherapies. However, due to the diversity of immune status in TILs, cellular heterogeneity, and the applicability to the clinic, it is still lacking effective strategies to meet clinical needs. We developed a novel immuno-recognition-induced method based on rolling circle amplification (RCA), namely immunoRCA, to in situ visualize the immune status of TILs in actual clinical samples. This developed immunoRCA method, in which, feature mRNAs were used as the biomarkers for the immune status of TILs, has a low fluorescence background, high sensitivity, and specificity. The immunoRCA was able to efficiently evaluate the immune status of CD8+ T cells regulated by activating or inhibiting factors, track the T cell type and immune status during in vitro expansion, and in situ visualize the number, location, and immune status of TILs in clinical specimens.

Colorectal liver metastases: Correlations of contrast-enhanced ultrasound features with tumor clinicopathological factors and clinical outcomes following conversion therapy.

OBJECTIVE: To explore the prognostic impact of contrast-enhanced ultrasound (CEUS) features for initially unresectable colorectal liver metastases (CLMs) in a clinical setting of conversion therapy. METHODS: Between March 2015 and November 2020, consecutive patients with CLMs who received conversion treatment were prospectively enrolled. All participants underwent liver CEUS at baseline. The primary endpoint was conversion resection rate (R0 and overall resection). Secondary endpoints were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS: 104 participants who completed conversion treatment were included. CEUS enhancement pattern was correlated with index lesion (size and echogenicity), primary (site, differentiation, perineural invasion, and RAS genotype) and serum (CA19-9 level) characteristics (P = <0.001-0.016). CEUS enhancement pattern was significantly associated with R0 resection rate, ORR, PFS, and OS (P = 0.001-0.049), whereas enhancement degree was associated with PFS and OS (P = 0.043 and 0.045). Multivariate analysis showed that heterogeneous enhancement independently predicted R0 and overall resection (P = 0.028 and 0.024) while rim-like enhancement independently predicted ORR and OS (P = 0.009 and 0.026). CONCLUSION: CEUS enhancement pattern was significantly associated with tumor characteristics and clinical outcomes following conversion therapy, and thus might be of prognosis impact for initially unresectable CLMs.

High-quality 3D printing of ethylene vinyl acetate with direct pellet-based FDM for medical applications: Mechanical analysis, energy absorption and recovery evaluation.

Ethylene Vinyl Acetate (EVA) is a biocompatible and non-toxic copolymer known for its applications in medicine, drug delivery systems, and energy absorption. This paper presents a novel method for 3D printing EVA using the Fused Deposition Modeling (FDM) technique. By directly utilizing pellet-form EVA material and employing pneumatic pressure for extrusion, we addressed the issue of filament buckling commonly encountered in traditional filament-based printing. A custom-made pellet printer enabled direct feeding of polymer pellets. The mechanical properties, microstructure of the printed EVA parts was analyzed to evaluate the suitability of the direct pellet printing technique for producing high-quality EVA components. The results showed acceptable printing quality and favorable mechanical properties (about 1000% elongation at break and 6.59 MPa tensile strength). Additionally, a cyclic compression test was conducted, subjecting specimens to various strains (30%,80% and 120%) and assessing their compressive and energy absorption properties undergoing significant deformations. Observations reveal a noticeable decline in the mechanical properties after the first compression cycle. The mechanical properties tend to stabilize and reach a steady state from the second cycle onwards until the sixth cycle. Furthermore, a compression cyclic test with various strain rates conducted, investigated the functional performance of the printed EVA components in engineering and biomedical applications, considering the impact of strain rate. Observations indicate that lower strain rates tend to enhance the material's ability to withstand deformation before yielding. This study contributes to expanding the potential of EVA in additive manufacturing, particularly in biomedical and energy absorption systems.

The transcription factor IRF4 determines the anti-tumor immunity of CD8+ T cells.

Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into effector T cell states. As a result, IRF4-engineered anti-tumor T cells exhibited significantly improved anti-tumor efficacy, and inhibited tumor growth either alone or in combination with PD-L1 blockade. These findings identify IRF4 as a crucial cell-intrinsic driver of T cell infiltration and function in tumors, emphasizing the potential of IRF4-engineering as an immunotherapeutic approach.

Vitrectomy for retinal detachment associated with macular hole: Prognostic factor analysis under different axial length conditions.

PURPOSE: To identify prognostic factors for complete anatomical success (CAS) under different axial length (AL) conditions after vitrectomy plus internal limiting membrane (ILM) peeling for retinal detachment associated with macular hole (MHRD). METHODS: This retrospective study included 243 patients (251 eyes) with MHRD who underwent primary vitrectomy plus ILM peeling. Multivariate logistic regression explored prognostic factors for CAS in AL <30 mm and ≥ 30 mm groups. RESULTS: Overall, 113 eyes (45.0% of 251) exhibited complete CAS after initial surgery. Eyes with CAS had greater best-corrected visual acuity improvement than eyes without CAS (p < 0.001). CAS was more common in eyes with AL < 30 mm (50.3% of 155) than in eyes with AL ≥ 30 mm (36.5%, 35/96; p = 0.032). In the AL < 30 mm group, CAS was associated with ILM insertion (odds ratio [OR], 2.824, 95% confidence interval [CI], 1.189-6.710; p = 0.019), silicone oil (SO)/perfluoropropane (C3F8) tamponade (SO: OR, 0.408, 95% CI, 0.191-0.873; C3F8: OR, 2.448, 95% CI, 1.145-5.234; p = 0.021) and staphyloma (OR, 0.318, 95% CI, 0.143-0.707; p = 0.005). In the AL ≥30 mm group, CAS was associated with ILM insertion (OR, 11.621, 95% CI, 2.557-52.813; p = 0.001), SO /C3F8 tamponade (SO: OR, 5.305, 95% CI, 1.206-23.334; C3F8: OR, 0.188, 95% CI, 0.043-0.829; p = 0.027) and age (OR, 0.928, 95% CI, 0.876-0.983; p = 0.011). CONCLUSION: Vitrectomy plus ILM peeling can effectively treat MHRD but has limited efficacy in eyes with AL ≥ 30 mm. ILM insertion was associated with more frequent CAS at any AL. C3F8 tamponade yielded better outcomes with AL < 30 mm; SO tamponade yielded better outcomes with AL ≥ 30 mm.

Reusable, Stable, Efficient and Multifunctional Superhydrophobic and Oleophilic Polyurethane Sponge for Oil-Water Separation Prepared Using Discarded Composite Insulator.

Oil spills and chemical leakages are a serious source of pollution in oceans and rivers, and have attracted worldwide attention. Many scientists are currently engaged in the development of oil-water separation technology. In this study, the umbrella skirt of a discarded silicone rubber insulator was utilized as feedstock, and polydimethylsiloxane (PDMS) was employed to immobilize the prepared powder (FXBW) onto a polyurethane (PU) sponge skeleton. Without any modifications using chemical reagents, a novel oil-water separation material, FXBW-PU, was developed, with a water contact angle of 155.3°. The FXBW-PU sponge exhibited an absorption capacity ranging from 11.79 to 26.59 g/g for various oils and organic solvents, while maintaining an excellent selective adsorption performance, even after undergoing ten compression cycles, due to its exceptional chemical and mechanical stability. With the assistance of a vacuum pump, the FXBW-PU sponge was utilized in a continuous separation apparatus, resulting in a separation efficiency exceeding 98.6% for various oils and organic solvents. The separation efficiency of n-hexane remains as high as 99.2% even after 10 consecutive separation cycles. Notably, the FXBW-PU sponge also separated the dichloromethane-in-water emulsions, which achieved the effect of purifying water. In summary, FXBW-PU sponge has great potential in the field of cleaning up oil/organic solvent contamination due to its low preparation cost, environmental friendliness and excellent performance.

Limb Reconstruction System Assisted Reduction and Internal Fixation for Intra-Articular Calcaneal Fractures: A New Application.

BACKGROUND: Minimally invasive reduction and fixation of intra-articular calcaneal fractures poses great challenges for orthopaedic surgeons. The aim of the present study was to report the technical points, evaluate the efficacy of minimally invasive reduction and internal fixation assisted by the temporary limb reconstruction system (LRS) external fixator for intra-articular calcaneal fractures, and propose the indications of our protocol. METHODS: In this retrospective study, a series of 34 consecutive closed and displaced intra-articular calcaneal fractures involving the articular surface were treated by this technology between June 2016 and April 2018. X-ray and computed tomography (CT) scans were performed before and after surgery to measure Bohler's angle; the length, height, and width of the calcaneus; and the mechanical axis of the hindfoot. Postoperative complications were recorded. Imaging and clinical outcomes were comprehensively evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot-ankle scoring system. After testing the normality of the data, Bohler's angle and the length of calcaneus were compared using the Wilcoxon signed-rank test. The height, width of the calcaneus, and the mechanical axis of the hindfoot were compared using the Paired-Samples t-test. RESULTS: Thirty-two fractures were followed up for an average of 20.66 months (from 12 to 32 months). All fractures achieved stable reduction and bony union. The articular surface was reduced and fixed with direct vision through the sinus tarsi incision. No failure of internal fixation or loss of reduction was detected during follow-up. There were no soft tissue complications. Bohler's angle; the length, height, and width of the calcaneus; and the mechanical axis of the hindfoot improved significantly. The AOFAS scores averaged 84.12 points; seven cases were rated excellent, 20 good, four fair, and one poor. CONCLUSIONS: For intra-articular calcaneal fractures, minimally invasive surgery assisted with temporary LRS external fixation can reconstruct the calcaneal shape and the sub-talar articular surface. This simple surgical modality with limited complications may be helpful in the surgical treatment of most type II and III calcaneal fractures except comminuted fractures of the calcaneal tuberosity.

Efficient NH3-Tolerant Nickel-Based Hydrogen Oxidation Catalyst for Anion Exchange Membrane Fuel Cells.

Converting hydrogen chemical energy into electrical energy by fuel cells offers high efficiencies and environmental advantages, but ultrapure hydrogen (over 99.97%) is required; otherwise, the electrode catalysts, typically platinum on carbon (Pt/C), will be poisoned by impurity gases such as ammonia (NH3). Here we demonstrate remarkable NH3 resistivity over a nickel-molybdenum alloy (MoNi4) modulated by chromium (Cr) dopants. The resultant Cr-MoNi4 exhibits high activity toward alkaline hydrogen oxidation and can undergo 10,000 cycles without apparent activity decay in the presence of 2 ppm of NH3. Furthermore, a fuel cell assembled with this catalyst retains 95% of the initial peak power density even when NH3 (10 ppm)/H2 was fed, whereas the power output reduces to 61% of the initial value for the Pt/C catalyst. Experimental and theoretical studies reveal that the Cr modifier not only creates electron-rich states that restrain lone-pair electron donation but also downshifts the d-band center to suppress d-electron back-donation, synergistically weakening NH3 adsorption.