Antifouling and antimicrobial wearable electrochemical sweat sensors for accurate dopamine monitoring based on amyloid albumin composite hydrogels.

Wearable electrochemical sweat sensors are potentially promising for health monitoring in a continuous and non-invasive mode with high sensitivity. However, due to the complexity of sweat composition and the growth of skin bacteria, the wearable sweat sensors may gradually lose their sensitivity or even fail over time. To deal with this issue, herein, we proposed a new strategy to construct wearable sweat sensors with antifouling and antimicrobial capabilities. Amyloid albumin hydrogels (ABSAG) were doped with two-dimensional (2D) nanomaterial MXene and CeO2 nanorods to obtain the antifouling and antimicrobial amyloid albumin composite hydrogels (ABSACG, CeO2/MXene/ABSAG), and the wearable sensors were prepared by modifying flexible screen-printed electrodes with the ABSACG. Within this sensing system, the hydrophilic ABSAG possesses strong hydration capability, and it can form a hydration layer on the electrode surface to resist biofouling in sweat. The 2D nanomaterial MXene dispersed in the hydrogel endows the hydrogel with good conductivity and electrocatalytic capability, while the doping of CeO2 nanorods further improves the electrocatalytic performance of the hydrogel and also provides excellent antimicrobial capability. The designed wearable electrochemical sensors based on the ABSACG demonstrated satisfying antifouling and antimicrobial abilities, and they were capable of detecting dopamine accurately in human sweat. It is expected that wearable sensors utilizing the antifouling and antimicrobial ABSACG may find practical applications in human body fluids analysis and health monitoring.

Nanoparticles (NPs)-mediated lncMALAT1 silencing to reverse cisplatin resistance for effective hepatocellular carcinoma therapy.

Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles (e.g., nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino)ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor.

Nonlinear dynamic transfer partial least squares for domain adaptive regression.

Aiming to address soft sensing model degradation under changing working conditions, and to accommodate dynamic, nonlinear, and multimodal data characteristics, this paper proposes a nonlinear dynamic transfer soft sensor algorithm. The approach leverages time-delay data augmentation to capture dynamics and projects the augmented data into a latent space for constructing a nonlinear regression model. Two regular terms, distribution alignment regularity and first-order difference regularity, are introduced during data projection to address data distribution disparities. Laplace regularity is incorporated into the nonlinear regression model to ensure geometric structure preservation. The final optimization objective is formulated within the framework of partial least squares, and hyperparameters are determined using Bayesian optimization. The effectiveness of the proposed algorithm is demonstrated through experiments on three public datasets.

Preovulation body mass index and pregnancy after first frozen embryo transfer in patients with polycystic ovary syndrome and insulin resistance.

OBJECTIVE: To examine the association between preovulation body mass index and pregnancy outcomes after frozen embryo transfer in patients with polycystic ovary syndrome with insulin resistance. DESIGN: This was a single-center, retrospective cohort study. SUBJECTS: Women with infertility, diagnosed with polycystic ovary syndrome and insulin resistance, and treated at the Reproductive Medicine Center, Second People's Hospital of Nanning, China, between January 2020 and August 2023, were included. EXPOSURE: Patients were divided into four groups according to their body mass index (BMI): slim (<18.5 kg/m2), normal (18.5≤ BMI <24 kg/m2), overweight (24≤ BMI <28 kg/m2), or obese (≥28 kg/m2). MAIN OUTCOME MEASURES: The main pregnancy outcomes included rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy. RESULTS: In total, 282 eligible patients were included. A linear association was observed between the BMI and clinical pregnancy outcomes of the first frozen embryo transfer (P for nonlinearity>0.05). After accounting for all potential variables, each 1 kg/m2 increase in BMI was linked to a 2% decrease in the embryo implantation rate (P<0.05), 11% decrease in the frequency of biochemical pregnancy (P<0.05), and 9% decrease in the both clinical (P<0.05) and ongoing pregnancy rates. CONCLUSION: In patients with polycystic ovary syndrome and insulin resistance, a higher BMI was associated with lower rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy.

Psychological Distress and the Needs of Family Members of Critically Ill Patients in Emergency Departments During the COVID-19 Pandemic: A Cross-Sectional Study.

INTRODUCTION: The literature highlights the importance of the needs of family members of critical patients in emergency departments. Understanding these needs helps to alleviate psychological distress and contribute to the patients' recoveries. This study aimed to examine the psychological distress and needs of family members of critical patients in emergency departments. METHODS: A cross-sectional design was used to collect data using the Depression, Anxiety, and Stress Scale-21, the Critical Care Family Needs Inventory for the Emergency Department, and the Needs Met Inventory questionnaire from a convenience sample of 170 family members of critical patients. Descriptive analysis and importance-performance analysis were applied to analyze the data. RESULTS: The results showed that 52.4% of family members reported mild to extremely severe levels of depression, 60% reported mild to extremely severe levels of anxiety, and 53.5% had mild to extremely severe levels of stress. Anxiety showed a significant negative correlation with comfort needs (r = -0.17) and support needs being met (r = -0.16). The importance-performance analysis showed that the coordinates for support needs were in quadrant IV, signifying a higher level of importance perceived by family members but a lower level of the needs being met. CONCLUSION: Providing the assessment and necessary support to alleviate psychological distress will help enhance the ability of the emergency department to meet families' needs.

Development and validation of novel interpretable survival prediction models based on drug exposures for severe heart failure during vulnerable period.

BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.

Synthesis of shape-controlled covalent organic frameworks for light scattering detection of iron and chromium ions.

Fabricating covalent organic frameworks with different morphologies based on the same structural motifs is both interesting and challenging. Here, a TTA-TFP-COF was synthesized by both solvothermal and room temperature methods, with 2,4,6-Tris(4-aminophenyl)-1,3,5-triazine (TTA) and 1,3,5-tris(4-formylphenyl)-benzene (TFP) as raw material. Using different synthesis conditions and adding aniline and benzaldehyde as regulators in the synthesis process, we found that these processes could slow down the reaction speed, increase the exchange and metathesis reactions of dynamic reversible reactions, and improve the reversibility of the reaction system. Thus, controllable synthesis of TTA-TFP-COF with different morphologies, including micro-particles, hollow tubes with controllable diameters, and micro-flowers was achieved. Our further study found that metal ions, Fe3+ and Cr3+ ions, could coordinate with N and O in TTA-TFP-COF and partially destroy the structure of TTA-TFP-COF. The particle size of the TTA-TFP-COF became smaller, thus resulting in the decrease of the light scattering intensity of the COF. An excellent linear relationship exists between the light scattering changes (ΔI) and metal ions concentration (c) from 2.0 to 350.0 µM for Fe3+ and 40.0-800.0 µM for Cr3+, respectively. Thus, rapid and selective analytical methods for detecting metal ions were developed by TTA-TFP-COF here.

Failure risk management: adaptive performance control and mission abort decisions.

The failure behavior of safety-critical systems typically depends on the system performance level, which offers opportunities to control system failure risk through dynamic performance adjustment. Moreover, mission abort serves as an intuitive way to mitigate safety hazards during mission execution. Our study focuses on systems that execute successive missions with random durations. To balance mission completion probability and system failure risk, we examine two decision problems: when to abort missions and how to select the performance level prior to mission abort. Our objective is to maximize the expected revenue through dynamic performance control and mission abort (PCMA) decisions. We consider condition-based PCMA decisions and formulate the joint optimization problem into a Markov decision process. We establish the monotonicity and concavity of the value function. Based on this insight, we show that optimizing the mission abort policy requires a series of control limits. In addition, we provide conditions under which the performance control policies are monotone. For comparative purposes, we analytically evaluate the performances of some heuristic policies. Finally, we present a case study involving unmanned aerial vehicles executing power line inspections. The results indicate the superiority of our proposed risk control policies in enhancing operational performance for safety-critical systems. Dynamic performance adjustment and mission abort decisions provide opportunities to reduce the failure risk and increase operational rewards of safety-critical systems.

Analysis of ventricular-vascular properties during preeclampsia: an echocardiography study.

The aim of the study is to analyze ventricular-vascular properties with different ventricular-arterial coupling (VAC) ratio in the preeclamptic women. Seventy-seven pregnant women with preeclampsia and eighty-nine with normal pregnancy were performed echocardiography. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees). Using the VAC value of 0.8 as the cut-off near uncoupling, the preeclampsia cases were divided into two subgroups: VAC ratio ≥ 0.8 and <0.8. Cardiac structure and function, VAC properties, as well as four components of the LV pressure-strain loop, including global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were determined. The preeclampsia with VAC ≥ 0.8 had an enlarger indexed ventricular volume and a thicker relative ventricular wall than the VAC < 0.8. The Ees significantly increased in the subgroup with VAC < 0.8 and decreased in the VAC ≥ 0.8, while the Ea increased in both of them. The preeclampsia with VAC ≥ 0.8 showed an obvious augmentation in GWI, GCW and GWE, along with a similar GWW compared to those with VAC < 0.8. There were variable relationships between the LV pressure-strain components and VAC properties. Thus, the preeclampsia with VAC ≥ 0.8 undergoes a more adverse remodeling and a greater impact on cardiac contractility. The increased stiffness of the heart and arterial system, and increased resistance of peripheral vessels net lead to the deteriorative ventricular efficiency with elevated myocardial oxygen consumption during a preeclampsia pregnancy.

Gut microbiota as a residual risk factor causally influencing cardiac structure and function: Mendelian randomization analysis and biological annotation.

Background: The gut microbiota (GM) is widely acknowledged to have a significant impact on cardiovascular health and may act as a residual risk factor affecting cardiac structure and function. However, the causal relationship between GM and cardiac structure and function remains unclear. Objective: This study aims to employ a two-sample Mendelian randomization (MR) approach to investigate the causal association between GM and cardiac structure and function. Methods: Data on 119 GM genera were sourced from a genome-wide association study (GWAS) meta-analysis (13,266 European participants) conducted by the MiBioGen consortium, while data on 16 parameters of cardiac structure and function were obtained from the UK Biobank's GWAS of cardiac magnetic resonance imaging (up to 41,135 European participants). Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for causal association assessments, with sensitivity analyses conducted to reinforce the findings. Finally, biological annotation was performed on the GWAS data of GM and cardiac phenotypes with causal associations to explore potential mechanisms. Results: The MR analysis, predominantly based on the IVW model, revealed 93 causal associations between the genetically predicted abundance of 44 GM genera and 16 cardiac structure and function parameters. These associations maintained consistent directions in MR-Egger and WM models, with no evidence of pleiotropy detected. Biological annotations suggest that GM may influence cardiac structure and function through pathways involved in myocardial cell development, cardiac contractility, and apoptosis. Conclusion: The MR analysis supports a causal association between certain abundances of genetically predicted GM and cardiac structure and function, suggesting that GM could be a residual risk factor impacting cardiac phenotypes.

[Report of a child with Bainbridge-Ropers syndrome due to a novel variant of ASXL3 gene and a literature review].

OBJECTIVE: To explore the clinical phenotype and genetic basis of a child with Bainbridge-Ropers syndrome (BRPS). METHODS: A child with BRPS who had visited Nanjing Children's Hospital on June 26, 2019 was selected as the study subject. Clinical data of the child was reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was a 6-month-old girl with peculiar facial features, feeding difficulties, malnutrition, global developmental delay, hypotonia, mildly elevated aminotransferase and ulnar deviation. Results of WES showed that she has harbored a c.1533_1534del variant of the ASXL3 gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. No similar case had been retrieved from the HGMD and ClinVar databases. No frequency for this variant among Asian populations was available in the ExAC, 1000 Genomes, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1533_1534del variant of the ASXL3 gene was determined to be likely pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The ASXL3 gene c.1533_1534del variant probably underlay the BRPS in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling for children with similar disorders.

HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China.

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.

Monocarboxylate transporter 4 facilitates Mycobacterium tuberculosis survival through NF-κB p65-mediated interleukin-10 production.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

Scalable Multi-FPGA HPC Architecture for Associative Memory System.

Associative memory is a cornerstone of cognitive intelligence within the human brain. The Bayesian confidence propagation neural network (BCPNN), a cortex-inspired model with high biological plausibility, has proven effective in emulating high-level cognitive functions like associative memory. However, the current approach using GPUs to simulate BCPNN-based associative memory tasks encounters challenges in latency and power efficiency as the model size scales. This work proposes a scalable multi-FPGA high performance computing (HPC) architecture designed for the associative memory system. The architecture integrates a set of hypercolumn unit (HCU) computing cores for intra-board online learning and inference, along with a spike-based synchronization scheme for inter-board communication among multiple FPGAs. Several design strategies, including population-based model mapping, packet-based spike synchronization, and cluster-based timing optimization, are presented to facilitate the multi-FPGA implementation. The architecture is implemented and validated on two Xilinx Alveo U50 FPGA cards, achieving a maximum model size of 200×10 and a peak working frequency of 220 MHz for the associative memory system. Both the memory-bounded spatial scalability and compute-bounded temporal scalability of the architecture are evaluated and optimized, achieving a maximum scale-latency ratio (SLR) of 268.82 for the two-FPGA implementation. Compared to a two-GPU counterpart, the two-FPGA approach demonstrates a maximum latency reduction of 51.72× and a power reduction exceeding 5.28× under the same network configuration. Compared with the state-of-the-art works, the two-FPGA implementation exhibits a high pattern storage capacity for the associative memory task.

Enhanced Electrochemical Performance and Cycling Stability of the (NH4)8[VIV12VV7O41(OH)9]·11H2O Cathode in Aqueous Zinc Ion Batteries.

Although vanadium-based compounds possess several advantageous characteristics, such as multivalency, open structure, and high theoretical specific capacity, which render them highly promising candidates for cathode materials in aqueous zinc ion batteries (AZIBs), their large-scale application still necessitates addressing the challenges posed by slow kinetics resulting from low conductivity and capacity degradation caused by material dissolution. Therefore, we have successfully synthesized high-purity mixed multivalent (NH4)8[VIV12VV7O41(OH)9]·11H2O (NVO) crystalline materials via a liquid-phase precipitation modulation method and employed it as an innovative AZIB cathode material for the first time. It exhibits a remarkable reversible specific capacity of 240 and 102.2 mAh g-1 after undergoing 1000 cycles at current densities of 1 and 5 A g-1, respectively, highlighting its exceptional cycling stability and electrochemical performance. The results from cyclic voltammetry (CV) and GITT tests demonstrate that the dominant factor influencing the charge storage is the pseudocapacitive behavior, which is accompanied by an exceptionally high diffusion coefficient of Zn2+ at a rate of 10-10 cm2 s-1. The highly reversible intercalation-deintercalation of Zn2+ in NVO/Zn cells is demonstrated through ex-situ TEM, XRD, and XPS analyses. This work provides a benchmark for the development of high-performance POV electrode materials.

Enhancing Oxygen Activation Ability by Composite Interface Construction over a 2D Co3O4-Based Monolithic Catalyst for Toluene Oxidation.

Developing robust metal-based monolithic catalysts with efficient oxygen activation capacity is crucial for thermal catalytic treatment of volatile organic compound (VOC) pollution. Two-dimensional (2D) metal oxides are alternative thermal catalysts, but their traditional loading strategies on carriers still face challenges in practical applications. Herein, we propose a novel in situ molten salt-loading strategy that synchronously enables the construction of 2D Co3O4 and its growth on Fe foam for the first time to yield a unique monolithic catalyst named Co3O4/Fe-S. Compared to the Co3O4 nanocube-loaded Fe foam, Co3O4/Fe-S exhibits a significantly improved catalytic performance with a temperature reduction of 44 °C at 90% toluene conversion. Aberration-corrected scanning transmission electron microscopy and theoretical calculation suggest that Co3O4/Fe-S possesses abundant 2D Co3O4/Fe3O4 composite interfaces, which promote the construction of active sites (oxygen vacancy and Co3+) to boost oxygen activation and toluene chemisorption, thereby accelerating the transformation of reaction intermediates through Langmuir-Hinshelwood (L-H) and Mars-van Krevelen (MvK) mechanisms. Moreover, the growth mechanism reveals that 2D Co3O4/Fe3O4 composite interfaces are generated in situ in molten salt, inducing the growth of 2D Co3O4 onto the surface lattice of 2D Fe3O4. This study provides new insights into enhancing oxygen activation and opens an unprecedented avenue in preparing efficient monolithic catalysts for VOC oxidation.

Design of eco-friendly antifreeze peptides as novel inhibitors of gas-hydration kinetics.

In this study, peptides designed using fragments of an antifreeze protein (AFP) from the freeze-tolerant insect Tenebrio molitor, TmAFP, were evaluated as inhibitors of clathrate hydrate formation. It was found that these peptides exhibit inhibitory effects by both direct and indirect mechanisms. The direct mechanism involves the displacement of methane molecules by hydrophobic methyl groups from threonine residues, preventing their diffusion to the hydrate surface. The indirect mechanism is characterized by the formation of cylindrical gas bubbles, the morphology of which reduces the pressure difference at the bubble interface, thereby slowing methane transport. The transfer of methane to the hydrate interface is primarily dominated by gas bubbles in the presence of antifreeze peptides. Spherical bubbles facilitate methane migration and potentially accelerate hydrate formation; conversely, the promotion of a cylindrical bubble morphology by two of the designed systems was found to mitigate this effect, leading to slower methane transport and reduced hydrate growth. These findings provide valuable guidance for the design of effective peptide-based inhibitors of natural-gas hydrate formation with potential applications in the energy and environmental sectors.

Pan­cancer analysis on the role of KMT2C expression in tumor progression and immunotherapy.

Histone lysine N-methyltransferase 2C (KMT2C) is involved in transcriptional regulation and DNA damage repair. Mutations in KMT2C have been implicated in the progression, metastasis, and drug resistance of multiple cancer types. However, the roles of KMT2C in the regulation of tumor prognosis, immune cell infiltration and the immune microenvironment in these multiple cancer types remain unclear. Therefore, in the present study, data from The Cancer Genome Atlas and Genotype-Tissue Expression databases were used for KMT2C expression analyses. Kaplan-Meier and univariate Cox regression analyses were also performed to investigate the prognostic role of KMT2C. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to study the KMT2C-related signaling pathways. Tumor immune estimation resource 2 and single-sample GSEA were conducted to investigate the correlation between KMT2C expression and immune cell infiltrations, and Spearman's analysis was conducted to study the correlations among KMT2C, tumor mutational burden, microsatellite instability, immune regulators, chemokines and immune receptors. Immunohistochemistry of patient kidney tumor samples was performed to verify the correlation between KMT2C and programmed death-ligand 1 (PD-L1) expression. Finally, RNA interference, wound healing and colony formation assays were conducted to evaluate the effects of KMT2C expression on cell proliferation and metastasis. The results of the present study demonstrated that KMT2C was highly expressed in multiple cancer types, was a protective factor in kidney renal clear cell carcinoma and ovarian serous cystadenocarcinoma, and a risk factor for lung squamous cell carcinoma and uveal melanoma. In addition, KMT2C levels were negatively correlated with immune-activated pathways and the infiltration of immune cells, and positively correlated with inhibitory immune factors and tumor angiogenesis. Patients with low KMT2C expression had higher objective response rates to immunotherapy, and drug sensitivity analysis indicated that topoisomerase, histone deacetylase, DOT1-like histone H3K79 methyltransferase and G9A nuclear histone lysine methyltransferase inhibitors could potentially be used to treat tumors with high KMT2C expression levels. Finally, the KMT2C and PD-L1 expression levels were shown to be positively correlated, and KMT2C knockdown markedly promoted the proliferation and invasion capacities of A549 cells. In conclusion, the present study revealed that low KMT2C expression may be a promising biomarker for predicting the response of patients with cancer to immunotherapy. Conversely, high KMT2C expression was shown to promote tumor angiogenesis, which may contribute to the formation of the immunosuppressive tumor microenvironment.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis.

BACKGROUND: Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide. Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy (PTCSL). AIM: To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation (PTOBF) technique guided by three-dimensional (3D) visualization. METHODS: This was a retrospective, single-center study analyzing, 140 patients who, between October 2016 and October 2023, underwent one-step PTCSL for hepatolithiasis. The patients were divided into two groups: The 3D-PTOBF group and the PTOBF group. Stone clearance on choledochoscopy, complications, and long-term clearance and recurrence rates were assessed. RESULTS: Age, total bilirubin, direct bilirubin, Child-Pugh class, and stone location were similar between the 2 groups, but there was a significant difference in bile duct strictures, with biliary strictures more common in the 3D-PTOBF group (P = 0.001). The median follow-up time was 55.0 (55.0, 512.0) days. The immediate stone clearance ratio (88.6% vs 27.1%, P = 0.000) and stricture resolution ratio (97.1% vs 78.6%, P = 0.001) in the 3D-PTOBF group were significantly greater than those in the PTOBF group. Postoperative complication (8.6% vs 41.4%, P = 0.000) and stone recurrence rates (7.1% vs 38.6%, P = 0.000) were significantly lower in the 3D-PTOBF group. CONCLUSION: Three-dimensional visualization helps make one-step PTCSL a safe, effective, and promising treatment for patients with complicated primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis. This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.