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The field of oncology has transformed in recent years, with treatments shifting from traditional surgical resection and radiation therapy to more diverse and customized approaches, one of which is immunotherapy. ICD (immunogenic cell death) belongs to a class of regulatory cell death modalities that reactivate the immune response by facilitating the interaction between apoptotic cells and immune cells and releasing specific signaling molecules, and DAMPs (damage-associated molecular patterns). The inducers of ICD can elevate the expression of specific proteins to optimize the TME (tumor microenvironment). The use of nanotechnology has shown its unique potential. Nanomaterials, due to their tunability, targeting, and biocompatibility, have become powerful tools for drug delivery, immunomodulators, etc., and have shown significant efficacy in clinical trials. In particular, these nanomaterials can effectively activate the ICD, trigger a potent anti-tumor immune response, and maintain long-term tumor suppression. Different types of nanomaterials, such as biological cell membrane-modified nanoparticles, self-assembled nanostructures, metallic nanoparticles, mesoporous materials, and hydrogels, play their respective roles in ICD induction due to their unique structures and mechanisms of action. Therefore, this review will explore the latest advances in the application of these common nanomaterials in tumor ICD induction and discuss how they can provide new strategies and tools for cancer therapy. By gaining a deeper understanding of the mechanism of action of these nanomaterials, researchers can develop more precise and effective therapeutic approaches to improve the prognosis and quality of life of cancer patients. Moreover, these strategies hold the promise to overcome resistance to conventional therapies, minimize side effects, and lead to more personalized treatment regimens, ultimately benefiting cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Cheng, Tan, Wang, Sun, Zhang and Wang.)

Vibration control is extremely important for countless mechanical systems. Inerter is a two-terminal dynamic element proposed in 2002, based on analogy between mechanical system and electric system. Dynamic characteristic of an ideal inerter is pure inertia. Force applied on each terminal of an inerter is directly proportional to relative acceleration of two terminals. Since inerter was put forward, it has made significant progress in vibration control systems. The paper is a review about physical realizations of inerter as well as inerter-based vibration control. Physical realizations and applications in vibration control of inerter are focused. First, the develop of inerter and typical physical realizations of inerter are introduced. The normative derivation processes based on Lagrange equation method of the dynamic relationships in the different inerters are summarized. And then, three categories of common inerter-based vibration control systems are explained. Finally, research trend of physical realizations of inerter are summarized, and the possible researches on inerter-based vibration control are discussed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Authors.)

Background: Brain inflammation plays a key role in ischemia/reperfusion (I/R) injury and is the main cause of "ineffective or futile recanalization" after successful mechanical thrombectomy (MT) in acute ischemic stroke (AIS). One of the primary sources of inflammatory cells after AIS are derived from the spleen. As an innovative and potential neuroprotective strategy after stroke, Remote Administration of Hypothermia (RAH) temporarily suppresses immune activities in the spleen, reduces the release of inflammatory cells and cytokines into blood, and thus reversibly diminishes inflammatory injury in the brain., Methods: This single-center, prospective, randomized controlled study (RCT) is proposed for AIS patients with anterior circulation large vessel occlusion (LVO). Subjects will be randomly assigned to either the control or intervention groups in a 1:1 ratio ( n  = 40). Participants allocated to the intervention group will receive RAH on the abdomen above the spleen prior to recanalization until 6 h after thrombectomy. All enrolled patients will receive standard stroke Guideline care. The main adverse events associated with RAH are focal cold intolerance and abdominal pain. The primary outcome will assess safety as it pertains to RAH application. The secondary outcomes include the efficacy of RAH on spleen, determined by spleen volumes, blood inflammatory factor (cells and cytokines), and on brain injury, determined by infarction volumes and poststroke functional outcomes., Discussion: This study aims to examine the safety and preliminary effectiveness of RAH over the spleen during endovascular therapy in AIS patients. The results of this study are expected to facilitate larger randomized clinical trials and hopefully prove RAH administration confers adjuvant neuroprotective properties in AIS treated with MT., Clinical Trial Registration: https://www.chictr.org.cn/. Identifier ChiCTR 2300077052., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Duan, Cheng, Geng, Rajah, Gao, Guo, Cai, Tong, Li, Jiang, Han and Ding.)

Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown. This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes. Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11-18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11-22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24-5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05). Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chronic obstructive pulmonary disease (COPD) is often associated with lung squamous cell carcinoma (LUSC), which has the same etiology (smoking, inflammation, oxidative stress, microenvironmental changes, and genetics). Smoking, inflammation, and airway remodeling are the most important and classical mechanisms of COPD comorbidity in LUSC patients. Cancer can occur during repeated airway damage and repair (airway remodeling). Changes in the inflammatory and immune microenvironments, which can cause malignant transformation of some cells, are currently being revealed in both LUSC and COPD patients. We obtained the GSE76925 dataset from the Gene Expression Omnibus database. Screening for possible COPD biomarkers was performed using the LASSO regression model and a random forest classifier. The compositional patterns of the immune cell fraction in COPD patients were determined using CIBERSORT. HTR2B expression was analyzed using validation datasets (GSE47460, GSE106986, and GSE1650). HTR2B expression in COPD cell models was determined via real-time quantitative PCR. Epithelial-mesenchymal transition (EMT) marker expression levels were determined after knocking down or overexpressing HTR2B. HTR2B function and mechanism in LUSC were analyzed with the Kaplan‒Meier plotter database. HTR2B expression was inhibited to detect changes in LUSC cell proliferation. A total of 1082 differentially expressed genes (DEGs) were identified in the GSE76925 dataset (371 genes were significantly upregulated, and 711 genes were significantly downregulated). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were mainly enriched in the p53 signaling and β-alanine metabolism pathways. Gene Ontology enrichment analysis indicated that the DEGs were largely related to transcription initiation from the RNA polymerase I promoter and to the regulation of mononuclear cell proliferation. The LASSO regression model and random forest classifier results revealed that HTR2B, DPYS, FRY, and CD19 were key COPD genes. Immune cell infiltration analysis indicated that these genes were closely associated with immune cells. Analysis of the validation sets suggested that HTR2B was upregulated in COPD patients. HTR2B was significantly upregulated in COPD cell models, and its upregulation was associated with increased EMT marker expression. Compared with that in bronchial epithelial cells, HTR2B expression was upregulated in LUSC cells, and inhibiting HTR2B expression led to the inhibition of LUSC cell proliferation. In conclusions, HTR2B might be a new biomarker and therapeutic target in COPD patients with LUSC., (© 2024. The Author(s).)

The potentially lethal zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode larval stages of the tapeworm Echinococcus multilocularis . Metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular parasite-host interactions. The host has developed various ways to resist a parasitic infection, and the production of reactive oxygen species (ROS) is one of the most important strategies. Here, we found that scavenging of ROS reduced metacestode larval growth and germinative cell proliferation in in vivo models. Furthermore, using in vitro- cultured metacestode vesicles, we found that increased ROS levels enhanced metacestode growth and germinative cell proliferation, which was achieved by positively activating the ROS-EmERK-EmHIF1α axis. These results indicate that, beside its capacity to damage the parasite, ROS also play critical roles in metacestode growth and germinative cell proliferation. This study suggests that the effects of ROS on parasite may be bidirectional during AE infection, reflecting the parasite's adaptation to the oxidative stress microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Cheng, Ge, Xu, Wang, Li, Tian, Liu, Luo and Wang.)

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H 2 O 2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment., (© 2024 Wiley‐VCH GmbH.)

This study explored the relationship between the design of calf compression sleeves and the comfort of young women in long sitting and standing work environments. By studying the relationship between material elongation and comfort pressure, a prediction model was obtained. The characteristics of the calf models of 94 women were classified, and the influence of different calf characteristics on the pressure distribution and tensile value design was objectively analyzed through simulation tests. The samples were then produced based on the simulation results, and subjective and objective try-on tests and evaluations were carried out. The results show that the difference in the shape of the calf has a certain impact on the pressure distribution and comfort. The predicted value of the theoretical model is in good agreement with the actual test value. The sample can bring a suitable gradient pressure and meet the comfort requirements and safety standards.

Background: The performance of existing prognostic scores including the simplified Pulmonary Embolism Severity Index (sPESI) for short-term mortality of non-high-risk PE in Chinese population has not been widely validated., Methods: Non-high-risk patients were included from the prospective cohort of the China pUlmonary Thromboembolism REgistry Study (CURES). The sPESI, RIETE, Geneva, modified FAST, and Bova score were validated. The discriminatory performance was measured by the area under the curve (AUC). We also compared the sensitivity, odds ratio, specificity, positive predictive value and negative predictive value of these scores., Results: A total of 6,873 non-high-risk patients with acute PE were included and 241 (3.5 %) patients died within 30 days. Compared to the Geneva, modified FAST, and Bova score, the AUCs for predicting 30-day death of sPESI and RIETE score were higher at 0.712 (95 % CI, 0.680, 0.743) and 0.723 (95 % CI, 0.691, 0.755) respectively. The sPESI demonstrated the highest sensitivity at 0.809, while the RIETE score, Geneva, Modified FAST and BOVA score showed sensitivities of 0.622, 0.568, 0.477 and 0.502 respectively. A sPESI ⩾1 point was associated with a 4.7-fold increased risk of 30-day all-cause mortality (95 % CI, 3.427, 6.563, p < 0.001), while a RIETE score of ⩾1 point was associated with a 4.5-fold increased risk (95 % CI, 3.127, 6.341, p < 0.001). The Geneva score, modified FAST and Bova score showed inferior performance., Conclusions: The implementation of the fewer-parameter, easier-to-calculate sPESI in Chinese patients with PE can help to discriminate patients with extremely low risk of short-term mortality for home treatment or early discharge., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Electrical neuromodulation has achieved significant translational advancements, including the development of deep brain stimulators for managing neural disorders and vagus nerve stimulators for seizure treatment. Optoelectronics, in contrast to wired electrical systems, offers the leadless feature that guides multisite and high spatiotemporal neural system targeting, ensuring high specificity and precision in translational therapies known as "photoelectroceuticals". This Account provides a concise overview of developments in novel optoelectronic nanomaterials that are engineered through innovative molecular, chemical, and nanostructure designs to facilitate neural interfacing with high efficiency and minimally invasive implantation.This Account outlines the progress made both within our laboratory and across the broader scientific community, with particular attention to implications in materials innovation strategies, studying bioelectrical activation with spatiotemporal methods, and applications in regenerative medicine. In materials innovation, we highlight a nongenetic, biocompatible, and minimally invasive approach for neuromodulation that spans various length scales, from single neurons to nerve tissues using nanosized particles and monolithic membranes. Furthermore, our discussion exposes the critical unresolved questions in the field, including mechanisms of interaction at the nanobio interface, the precision of cellular or tissue targeting, and integration into existing neural networks with high spatiotemporal modulation. In addition, we present the challenges and pressing needs for long-term stability and biocompatibility, scalability for clinical applications, and the development of noninvasive monitoring and control systems.In addressing the existing challenges in the field of nanobio interfaces, particularly for neural applications, we envisage promising strategic directions that could significantly advance this burgeoning domain. This involves a deeper theoretical understanding of nanobiointerfaces, where simulations and experimental validations on how nanomaterials interact spatiotemporally with biological systems are crucial. The development of more durable materials is vital for prolonged applications in dynamic neural interfaces, and the ability to manipulate neural activity with high specificity and spatial resolution, paves the way for targeting individual neurons or specific neural circuits. Additionally, integrating these interfaces with advanced control systems, possibly leveraging artificial intelligence and machine learning algorithms and programming dynamically responsive materials designs, could significantly ease the implementation of stimulation and recording. These innovations hold the potential to introduce novel treatment modalities for a wide range of neurological and systemic disorders.

Objective: This network meta-analysis evaluates the efficacy and safety of tirzepatide compared to glucagon-like peptide-1 receptor agonists (GLP-1 RA) and other weight loss drugs in the treatment of overweight and obesity., Methods: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects., Results: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects., Conclusions: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity., (© 2024 The Obesity Society.)

Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. We evaluated the safety and feasibility of intravenous GTN in AIS patients. Subsequently, we conducted a secondary analysis to assess for possible efficacy of GTN as a neuroprotectant. We conducted a prospective, double-blind, randomized controlled trial in the Stroke Intervention & Translational Center (SITC) in Beijing Luhe Hospital, Capital Medical University (ChiCTR2100046271). AIS patients within 24 h of stroke onset were evenly divided into GTN or control groups (n = 20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110 mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin score (mRS) and the national institutes of health stroke score (NIHSS). Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and pre-mRS scores showed no significant difference between the groups. Safety measures of SBP<110 mmHg and headache occurrence were comparable. Overall, 90-day mRS (1 vs. 1) and NIHSS (1 vs. 1) did not significantly differ between groups. However, the GTN-treated group had a benefit in enhancing NIHSS recovery (△NIHSS 4.5 vs. 3, p = 0.028), indicating that GTN may augment recovery. Subgroup analyses revealed a benefit in the GTN group at the 90-day NIHSS score and △NIHSS follow up for non-thrombolysis patients (1 vs. 2, p = 0.016; 5 vs. 2, p = 0.001). Moreover, the GTN group may benefit mild stroke patients in NIHSS score at 90 day and △NIHSS observed at 90 days (1 vs. 1, p = 0.025; 3 vs. 2 p = 0.002). Overall, while preliminary data suggest GTN might aid recovery in NIHSS improvement, the evidence is tempered due to sample size limitations. The RIGID study confirms the safety and feasibility of intravenous GTN administration for AIS patients. Preliminary data also suggest that the GTN group may provide improvement in NIHSS recovery compared to the control group. Furthermore, a potential benefit for non-thrombolysis patients and those with mild stroke symptoms was identified, suggesting a possible potential role as a tailored intervention in specific AIS subgroups. Due to the limited sample size, further larger RCT will be necessary to replicate these results. TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2100046271., Competing Interests: Declaration of competing interest Research was conducted without any commercial or financial relationships that could be construed as conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The functional components in tartary buckwheat leaf powder can give flour products higher nutritional value. To comprehensively realize the high-value utilization of tartary buckwheat and its by-products, electric stone mill powder (EMP), ultra-fine mill powder (UMP), steel mill powder (SMP), and grain mill powder (GMP) from tartary buckwheat leaves were used in the preparation of wheat dough, and this was used to explore their effects on dough properties and protein microstructure. With an increase in tartary buckwheat leaf powder, the hydration characteristics, protein weakening rate, and starch gelatinization characteristics of the dough changed, and the water holding capacity and swelling capacity decreased. The retrogradation value increased, which could prolong the shelf life of related products. The water solubility of the dough showed an upward trend and was the lowest at 10% UMP. The addition of UMP produced a more uniform dough stability time and the lowest degree of protein weakening, which made the dough more resistant to kneading. An increasing amount of tartary buckwheat leaf powder augmented the free sulfhydryl content of the dough and decreased the disulfide bond content. The disulfide bond content of the dough containing UMP was higher than that of the other doughs, and the stability of the dough was better. The peaks of the infrared spectrum of the dough changed after adding 10% UMP and 20% EMP. The content of α-helical structures was the highest at 10% UMP, and the content of ordered structures was enhanced. The polymerization of low molecular weight proteins to form macromolecular polymers led to a reduction in surface hydrophobic regions and the aggregation of hydrophobic groups. The SEM results also demonstrated that at 10% tartary buckwheat leaf powder, the addition of UMP was significantly different from that of the other three leaf powders, and at 20%, the addition of EMP substantially altered the structure of the dough proteins. Considering the effects of different milling methods and different added amounts of tartary buckwheat leaf powder on various characteristics of dough, 10% UMP is the most suitable amount to add to the dough., Competing Interests: The authors declare no conflicts of interest.

Recent studies have uncovered that noncoding sequence variants may relate to Axenfeld-Rieger syndrome (ARS), a rare developmental anomaly with genetic heterogeneity. However, how these genomic regions are functionally and structurally associated with ARS is still unclear. In this study, we performed genome-wide linkage analysis and whole-genome sequencing in a Chinese family with ARS and identified a heterozygous deletion of about 570 kb (termed LOH-1) in the intergenic sequence between paired-like homeodomain transcription factor 2 (PITX2) and family with sequence similarity 241 member A. Knockout of LOH-1 homologous sequences caused ARS phenotypes in mice. RNA-Seq and real-time quantitative PCR revealed a significant reduction in Pitx2 gene expression in LOH-1-/- mice, while forkhead box C1 expression remained unchanged. ChIP-Seq and bioinformatics analysis identified a potential enhancer region (LOH-E1) within LOH-1. Deletion of LOH-E1 led to a substantial downregulation of the PITX2 gene. Mechanistically, we found a sequence (hg38 chr4:111,399,594-111,399,691) that is on LOH-E1 could regulate PITX2 by binding to RAD21, a critical component of the cohesin complex. Knockdown of RAD21 resulted in reduced PITX2 expression. Collectively, our findings indicate that a potential enhancer sequence that is within LOH-1 may regulate PITX2 expression remotely through cohesin-mediated loop domains, leading to ARS when absent.

Background: Portulacae Herba and Granati Pericarpium pair (PGP) is a traditional Chinese herbal medicine treatment for colitis, clinically demonstrating a relatively favorable effect on relieving diarrhea and abnormal stools. However, the underlying mechanism remain uncertain., Purpose: The present study intends to evaluate the efficacy of PGP in treating colitis in mice and investigate its underlying mechanism., Methods: The protective effect of PGP against colitis was determined by monitoring body weight, colon length, colon weight, and survival rate in mice. Colonic inflammation was assessed by serum cytokine levels, colonic H&E staining, and local neutrophil infiltration. The reversal of intestinal epithelial barrier damage by PGP was subsequently analyzed with Western blot and histological staining. Furthermore, RNA-seq analysis and molecular docking were performed to identify potential pathways recruited by PGP. Following the hints of the transcriptomic results, the role of PGP through the IL-6/STAT3/SOCS3 pathway in DSS-induced colitis mice was verified by Western blot., Results: DSS-induced colitis in mice was significantly curbed by PGP treatment. PGP treatment significantly mitigated DSS-induced colitis in mice, as evidenced by improvements in body weight, DAI severity, survival rate, and inflammatory cytokines levels in serum and colon. Moreover, PGP treatment up-regulated the level of Slc26a3, thereby increasing the expressions of the tight junction/adherens junction proteins ZO-1, occludin and E-cadherin in the colon. RNA-seq analysis revealed that PGP inhibits the IL-6/STAT3/SOCS3 pathway at the transcriptional level. Molecular docking indicated that the major components of PGP could bind tightly to the proteins of IL-6 and SOCS3. Meanwhile, the result of Western blot revealed that the IL-6/STAT3/SOCS3 pathway was inhibited at the protein level after PGP administration., Conclusion: PGP could alleviate colonic inflammation and reverse damage to the intestinal epithelial barrier in DSS-induced colitis mice. The underlying mechanism involves the inhibition of the IL-6/STAT3/SOCS3 pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis (E. multilocularis). Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitope peptides because of their unique structure and biocompatibility. In this study, four T-cells and four B-cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis., (© 2024 Wiley-VCH GmbH.)

It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection., (© 2024. The Author(s).)

Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.

CD40, a novel immunomodulatory cancer therapy target, is expressed by B cells, macrophages, and dendritic cells (DCs) and mediates cytotoxic T cell priming through the CD40 ligand. Some tumors show promising responses to monotherapy or combination therapy with agonistic anti-CD40 antibodies. The development of improved anti-CD40 antibodies makes CD40 activation an innovative strategy in cancer immunotherapy. In this review, we trace the history of CD40 research and summarize preclinical and clinical findings. We emphasize the ongoing development of improved anti-CD40 antibodies and explore strategies for effective combination therapies. Guided by predictive biomarkers, future research should identify patient populations benefiting the most from CD40 activation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Thermal management is critical in contemporary electronic systems, and integrating diamond with semiconductors offers the most promising solution to improve heat dissipation. However, developing a technique that can fully exploit the high thermal conductivity of diamond, withstand high-temperature annealing processes, and enable mass production is a significant challenge. In this study, the successful transfer of AlGaN/GaN/3C-SiC layers grown on Si to a large-size diamond substrate is demonstrated, followed by the fabrication of GaN high electron mobility transistors (HEMTs) on the diamond. Notably, no exfoliation of 3C-SiC/diamond bonding interfaces is observed even after annealing at 1100 °C, which is essential for high-quality GaN crystal growth on the diamond. The thermal boundary conductance of the 3C-SiC-diamond interface reaches ≈55 MW m -2  K -1 , which is efficient for device cooling. GaN HEMTs fabricated on the diamond substrate exhibit the highest maximum drain current and the lowest surface temperature compared to those on Si and SiC substrates. Furthermore, the device thermal resistance of GaN HEMTs on the diamond substrate is significantly reduced compared to those on SiC substrates. These results indicate that the GaN/3C-SiC on diamond technique has the potential to revolutionize the development of power and radio-frequency electronics with improved thermal management capabilities., (© 2023 Wiley‐VCH GmbH.)

The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H 2 O 2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), β-lapachone (a DNA topoisomerase inhibitor with H 2 O 2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H 2 O 2 ). HBGL can achieve rapid, continuous, and massive H 2 O 2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The coupled transport of charge and heat provide fundamental insights into the microscopic thermodynamics and kinetics of materials. We describe a sensitive ac differential resistance bridge that enables measurements of the temperature difference on two sides of a coin cell with a resolution of better than 10 μK. We use this temperature difference metrology to determine the ionic Peltier coefficients of symmetric Li-ion electrochemical cells as a function of Li salt concentration, solvent composition, electrode material, and temperature. The Peltier coefficients Π are negative, i.e. , heat flows in the direction opposite to the drift of Li ions in the applied electric field, large, -Π > 30 kJ mol -1 , and increase with increasing temperature at T > 300 K. The Peltier coefficient is approximately constant on time scales that span the characteristic time for mass diffusion across the thickness of the electrolyte, suggesting that heat of transport plays a minor role in comparison to the changes in partial molar entropy of Li at the interface between the electrode and electrolyte. Our work demonstrates a new platform for studying the non-equilibrium thermodynamics of electrochemical cells and provides a window into the transport properties of electrochemical materials through measurements of temperature differences and heat currents that complement traditional measurements of voltages and charge currents.

Background: High myopia (HM) refers to an eye refractive error exceeding -5.00 D, significantly elevating blindness risk. The underlying mechanism of HM remains elusive. Given the extensive genetic heterogeneity and vast genetic base opacity, it is imperative to identify more causative genes and explore their pathogenic roles in HM., Methods: We employed exome sequencing to pinpoint the causal gene in an HM family. Sanger sequencing was used to confirm and analyse the gene mutations in this family and 200 sporadic HM cases. Single-cell RNA sequencing was conducted to evaluate the gene's expression patterns in developing human and mouse retinas. The CRISPR/Cas9 system facilitated the gene knockout cells, aiding in the exploration of the gene's function and its mutations. Immunofluorescent staining and immunoblot techniques were applied to monitor the functional shifts of the gene mutations at the cellular level., Results: A suspected nonsense mutation (c.C172T, p.Q58X) in CCDC66 was found to be co-segregated with the HM phenotype in the family. Additionally, six other rare variants were identified among the 200 sporadic patients. CCDC66 was consistently expressed in the embryonic retinas of both humans and mice. Notably, in CCDC66-deficient HEK293 cells, there was a decline in cell proliferation, microtube polymerisation rate and ace-tubulin level. Furthermore, the mutated CCDC66 failed to synchronise with the tubulin system during Hela cell mitosis, unlike its wild type counterpart., Conclusions: Our research indicates that the CCDC66 variant c.C172T is associated with HM. A deficiency in CCDC66 might disrupt cell proliferation by influencing the mitotic process during retinal growth, leading to HM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Steatotic liver disease poses a serious threat to human health and has emerged as one of the most significant burdens of chronic liver disease worldwide. Currently, the research mechanism is not clear, and there is no specific targeted drug for direct treatment. Phosphorylation is widely regarded as the most common type of protein modification, closely linked to steatotic liver disease in previous studies. However, there is no systematic review to clarify the relationship and investigate from the perspective of phosphorylation. Phosphorylation has been found to mainly regulate molecule stability, affect localization, transform molecular function, and cooperate with other protein modifications. Among them, adenosine 5'-monophosphate-activated protein kinase (AMPK), serine/threonine kinase (AKT), and nuclear factor kappa-B (NF-kB) are considered the core mechanisms in steatotic liver disease. As to treatment, lifestyle changes, prescription drugs, and herbal ingredients can alleviate symptoms by influencing phosphorylation. It demonstrates the significant role of phosphorylation as a mechanism occurrence and a therapeutic target in steatotic liver disease, which could be a new star for future exploration., (© 2024. The Author(s).)

Heat dissipation plays a crucial role in the performance and reliability of high-power GaN-based electronics. While AlN transition layers are commonly employed in the heteroepitaxial growth of GaN-on-SiC substrates, concerns have been raised about their impact on thermal transport across GaN/SiC interfaces. In this study, we present experimental measurements of the thermal boundary conductance (TBC) across GaN/SiC interfaces with varying thicknesses of the AlN transition layer (ranging from 0 to 73 nm) at different temperatures. Our findings reveal that the addition of an AlN transition layer leads to a notable increase in the TBC of the GaN/SiC interface, particularly at elevated temperatures. Structural characterization techniques are employed to understand the influence of the AlN transition layer on the crystalline quality of the GaN layer and its potential effects on interfacial thermal transport. To gain further insights into the trend of TBC, we conduct molecular dynamics simulations using high-fidelity deep learning-based interatomic potentials, which reproduce the experimentally observed enhancement in TBC even for atomically perfect interfaces. These results suggest that the enhanced TBC facilitated by the AlN intermediate layer could result from a combination of improved crystalline quality at the interface and the "phonon bridge" effect provided by AlN that enhances the overlap between the vibrational spectra of GaN and SiC.

Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa&#95;circ&#95;0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa&#95;circ&#95;0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa&#95;circ&#95;0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa&#95;circ&#95;0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma., (© 2024. The Author(s).)

Introduction: Despite the high morbidity and mortality, the effective therapies for heart failure with preserved fraction (HFpEF) are limited as the poor understand of its pathophysiological basis., Objective: This study was aimed to characterize the cellular heterogeneity and potential mechanisms of HFpEF at single-cell resolution., Methods: An HFpEF mouse model was induced by a high-fat diet with N-nitro-L-arginine methyl ester. Cells from the hearts were subjected to single-cell sequencing. The key protein expression was measured with Immunohistochemistry and immunofluorescence staining., Results: In HFpEF hearts, myocardial fibroblasts exhibited higher levels of fibrosis. Furthermore, an increased number of fibroblasts differentiated into high-metabolism and high-fibrosis phenotypes. The expression levels of genes encoding certain pro-angiogenic secreted proteins were decreased in the HFpEF group, as confirmed by bulk RNA sequencing. Additionally, the proportion of the endothelial cell (EC) lineages in the HFpEF group was significantly downregulated, with low angiogenesis and high apoptosis phenotypes observed in these EC lineages. Interestingly, the fibroblasts in the HFpEF heart might cross-link with the EC lineages via over-secretion of ANGPTL4, thus displaying an anti-angiogenic function. Immunohistochemistry and immunofluorescence staining then revealed the downregulation of vascular density and upregulation of ANGPTL4 expression in HFpEF hearts. Finally, we predicted ANGPTL4as a potential druggable target using DrugnomeAI., Conclusion: In conclusion, this study comprehensively characterized the angiogenesis impairment in HFpEF hearts at single-cell resolution and proposed that ANGPTL4 secretion by fibroblasts may be a potential mechanism underlying this angiogenic abnormality., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Antineutrophil cytoplasmic antibody vasculitis-associated interstitial lung disease (AAV-ILD) is a potentially life-threatening disease. However, very little research has been done on the condition's mortality risk. Hence, our objective is to find out the factors influencing the prognosis of AAV-ILD and employ these findings to create a nomogram model. Patients with AAV-ILD who received treatment at the First Affiliated Hospital of Zhengzhou University during the period from March 1, 2011, to April 1, 2022 were selected for this research. The development of nomogram entailed a synergistic integration of univariate, Lasso, and multivariate Cox regression analyses. Internal validation ensued through bootstrap techniques involving 1000 re-sampling iterations. Discrimination and calibration were assessed utilizing Harrell's C-index, receiver operating characteristic (ROC) curve, and calibration curve. Model performance was evaluated through integrated discrimination improvement (IDI), net reclassification improvement (NRI), and likelihood ratio test. The net benefit of the model was evaluated using decision curve analysis (DCA). A cohort comprising 192 patients was enrolled for analysis. Throughout observation period, 32.29% of the population died. Key factors such as cardiac involvement, albumin, smoking history, and age displayed substantial prognostic relevance in AAV-ILD. These factors were incorporated to craft a predictive nomogram. Impressively, the model exhibited robust performance, boasting a Harrell's C index of 0.826 and an AUC of 0.940 (95% CI 0.904-0.976). The calibration curves depicted a high degree of harmony between predicted outcomes and actual observations. Significantly enhancing discriminative ability compared to the ILD-GAP model, the nomogram was validated through the IDI, NRI, and likelihood ratio test. DCA underscored the superior predictive value of the predictive model over the ILD-GAP model. The internal validation further affirmed this efficacy, with a mean Harrell's C-index of 0.815 for the predictive model. The nomogram model can be employed to predict the prognosis of patients with AAV-ILD. Moreover, the model performance is satisfactory. In the future, external datasets could be utilized for external validation., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lung cancer is one of the leading causes of death worldwide and early detection is crucial to reduce the mortality. A reliable computer-aided diagnosis (CAD) system can help facilitate early detection of malignant nodules. Although existing methods provide adequate classification accuracy, there is still room for further improvement. This study is dedicated to investigating a new CAD scheme for predicting the malignant likelihood of lung nodules in computed tomography (CT) images in light of a deep learning strategy. Conceived from the residual learning and selective kernel, we investigated an efficient residual selective kernel (RSK) block to handle the diversity of lung nodules with various shapes and obscure structures. Founded on this RSK block, we established a multiview RSK network (MRSKNet), to which three anatomical planes in the axial, coronal, and sagittal directions were fed. To reinforce the classification efficiency, seven handcrafted texture features with a filter-like computation strategy were explored, among which the homogeneity (HOM) feature maps are combined with the corresponding intensity CT images for concatenation input, leading to an improved network architecture. Evaluated on the public benchmark Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) challenge database with ten-fold cross validation of binary classification, our experimental results indicated high area under receiver operating characteristic (AUC) and accuracy scores. A better compromise between recall and specificity was struck using the suggested concatenation strategy comparing to many state-of-the-art approaches. The proposed pulmonary nodule classification framework exhibited great efficacy and achieved a higher AUC of 0.9711. The association of handcrafted texture features with deep learning models is promising in advancing the classification performance. The developed pulmonary nodule CAD network architecture is of potential in facilitating the diagnosis of lung cancer for further image processing applications., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Introduction: Diabetes is a worldwide chronic disease. The incidence rate of this disease is high, and it is a common disease in clinics. At present, the incidence rate of diabetes patients is increasing year by year due to the increasing work pressure, the accelerated pace of life, the change of diet, the reduction of labor, and the acceleration of aging., Evidence Acquisition: The computer retrieves four databases to obtain random controlled trials on the influence of resistance exercise and aerobic exercise on type 2 diabetes. After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software., Evidence Synthesis: Ten studies were ultimately included in this meta-analysis. 10 studies reported the HbA1c of the test group and the control group, which was no significant statistical significance (SMD: -0.01; 95% CI: -0.20,0.19; P=0.959) than the control group, HOMA-IR (SMD: 0.02; 95% CI: -0.65,0.69; P=0.954), SBP (SMD: 3.92; 95% CI: -0.92,8.75; P=0.112), DBP (SMD: 0.67; 95% CI: -3.66,5.01; P=0.761), HDL (SMD: -0.08; 95% CI: -2.79,2.64; P=0.955), TG (SMD: -7.51; 95% CI: -21.25,6.22; P=0.284) and TC (SMD: 9.10; 95% CI: -13.43,31.62; P=0.428)., Conclusions: The results of this study suggest that both resistance exercise and aerobic exercise may be effective on patients with type 2 diabetes, as evidenced by HbA1c, HOMA-IR, SBP, DBP, HDL, TG and TC. There is no significant difference in their impact on type 2 diabetes patients, and the above conclusions need to be verified by more high-quality studies.

Objective: We aim to assess the incidence and impact of in-hospital medical complications (MCs) on clinical outcomes in acute ischemic stroke (AIS) patients after endovascular therapy (EVT)., Methods: AIS patients who underwent EVT were consecutively recruited from January 2019 to July 2022. The primary outcome was a poor 3-month functional outcome, defined as a modified Rankin Scale score (mRS) of 3-6. The safety variables were symptomatic intracerebral hemorrhage and mortality at 7 and 30 days., Results: A total of 306 (50.1%) patients experienced at least one of the MCs. The most common MC was pneumonia (42.6%). Multivariate analysis revealed that the setting of MCs was an independent predictor of a poor 3-month functional outcome (adjusted odds ratio [aOR] 4.40, 95% confidence interval [CI] 3.01-6.42; P < 0.001). In the subgroup analysis, this trend was significant, especially in the patients aged 60-75 years (aOR 5.87, 95% CI 3.45-9.97; P < 0.001) or with baseline NIHSS (≤16) (aOR 5.05, 95% CI 2.84-9.01; P < 0.001). For individuals, cardiac events (aOR 8.56, 95% CI 4.05-18.09; P < 0.001), pneumonia (aOR 5.08, 95% CI 3.42-7.55; P < 0.001), and gastrointestinal bleeding (GIB) (aOR 6.12, 95% CI 3.40-11.01; P < 0.001) were independently associated with the poor 3-month outcome. The setting of MCs was independently associated with symptomatic intracerebral hemorrhage (aOR 2.11, 95% CI 1.22-3.64; P = 0.007) and mortality at 30 days (aOR 2.11, 95% CI 1.22-3.64; P = 0.007) after adjustment, but not with mortality at 7 days., Conclusions: MCs in AIS patients after EVT have a high incidence, despite successful reperfusion, adversely affecting clinical outcomes and increasing short-term mortality., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aim to elucidate the contribution of early dynamic changes in the neutrophil-to-lymphocyte ratio (NLR) to poor clinical outcomes in acute ischemic stroke patients after endovascular treatment (EVT)., Methods: Acute ischemic stroke patients who underwent EVT were consecutively recruited from January 2019 to July 2022. Blood cell counts were sampled at admission and at following 24 hours after EVT. Clinical outcome measures included 3-month functional dependence (modified Rankin scale of 3-6), symptomatic intracranial hemorrhage, and mortality at 7 days and 30 days. Multinomial logistic regressions were used to evaluate the association of changes in the NLR with unfavorable outcomes., Results: A total of 590 patients were included in the final analysis. The multinomial logistic model indicated that the increasing changes in the NLR after EVT was an independent factor for poor outcomes; the adjusted odds ratio was 1.06 (95% confidence interval [CI] 1.03-1.10; P < 0.001) at poor 3-month functional outcomes, 1.07 (95% CI 1.04-1.10; P < 0.001) at symptomatic intracranial hemorrhage, 1.08 (95% CI 1.05-1.12; P < 0.001) at mortality at 7 days, and 1.04 (95% CI 1.02-1.07; P = 0.001) at mortality at 30 days. Areas under the curve of changes in NLR to discriminate adverse outcomes were 0.725, 0.687, 0.664, and 0.659, respectively. The optimal cutoff values were 5.77 (56.6% sensitivity, 81.0% specificity), 6.92 (60.0% sensitivity, 77.0% specificity), 8.64 (51.0% sensitivity, 82.0% specificity), and 8.64 (48.7% sensitivity, 83.0% specificity), respectively., Conclusions: The NLR in acute ischemic stroke patients increased remarkably independent of successful reperfusion. Elevated changes in the NLR might predict malignant hemorrhagic transformation, adverse functional outcomes, and short-term mortality., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: ARLs, which are a class of small GTP-binding proteins, play a crucial role in facilitating tumor tumorigenesis and development. ARL4C, a vital member of the ARLs family, has been implicated in the progression of tumors, metastatic dissemination, and development of resistance to therapeutic drugs. Nevertheless, the precise functional mechanisms of ARL4C concerning tumor prognosis and immunotherapy drug susceptibility remain elusive. Methods: By combining the GTEx and TCGA databases, the presence of ARL4C was examined in 33 various types of cancer. Immunohistochemistry and immunofluorescence staining techniques were utilized to confirm the expression of ARL4C in particular tumor tissues. Furthermore, the ESTIMATE algorithm and TIMER2.0 database were utilized to analyze the tumor microenvironment and immune infiltration associated with ARL4C. The TISCH platform facilitated the utilization of single-cell RNA-seq datasets for further analysis. ARL4C-related immune escape was investigated using the TISMO tool. Lastly, drug sensitivity analysis was conducted to assess the sensitivity of different types of tumors to compounds based on the varying levels of ARL4C expression. Results: The study found that ARL4C was highly expressed in 23 different types of cancer. Moreover, the presence of high ARL4C expression was found to be associated with a poor prognosis in BLCA, COAD, KIRP, LGG, and UCEC. Notably, ARL4C was also expressed in immune cells, and its high expression was found to be correlated with cancer immune activation. Most importantly, the drug sensitivity analysis revealed a positive correlation between ARL4C expression and the heightened sensitivity of tumors to Staurosporine, Midostaurin, and Nelarabine. Conclusion: The findings from our study indicate that the expression level of ARL4C may exert an influence on cancer development, prognosis, and susceptibility to immunotherapy drugs. In addition, the involvement of ARL4C in the tumor immune microenvironment has expanded the concept of ARL4C-targeted immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Yang, Yue, Chen, Cheng, Sun and Song.)

Aerobic glycolysis is a pivotal hallmark of cancers, including colorectal cancer. Evidence shows glycolytic enzymes are regulated by post-translational modifications (PTMs), thereby affecting the Warburg effect and reprograming cancer metabolism. Lysine lactylation is a PTM reported in 2019 in histones. In this study, we identified protein lactylation in FHC cells and SW480 colon cancer cells through mass spectrometry. Totally, 637 lysine lactylation sites in 444 proteins were identified in FHC and SW480 cells. Lactylated proteins were enriched in the glycolysis pathway, and we identified lactylation sites in phosphofructokinase, platelet (PFKP) lysine 688 and aldolase A (ALDOA) lysine 147. We also showed that PFKP lactylation directly attenuated enzyme activity. Collectively, our study presented a resource to investigate proteome-wide lactylation in SW480 cells and found PFKP lactylation led to activity inhibition, indicating that lactic acid and lactylated PFKP may form a negative feedback pathway in glycolysis and lactic acid production., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The electrode/electrolyte interfaces play an important role in the electrochemical reaction kinetics to alleviate the severe polarization and voltage hysteresis in lithium primary batteries. Herein, C 5 F 5 N is proposed as an electrolyte additive to tune the characteristics of the electrode/electrolyte interfaces. The Li/CF x primary battery with C 5 F 5 N additive exhibits an excellent discharge-specific capacity of 981.4 mAh g -1 (0.1 C), a remarkable high-rate capability of 598 mAh g -1 (15 C), and an outstanding energy/power density of 1068.7 Wh kg -1 /24362.5 W kg -1 . It also shows remarkable storage performance with 717.2 mAh g -1 at 0.1 C after storage at 55 °C for 2 months. The excellent performance of the Li/CF x batteries is closely related to the improved and stable Li 3 N/LiF-rich homogeneous interfaces induced by the C 5 F 5 N additive, which results in uniform distribution of Li + flux, facilitated electrochemical kinetics, and increased rate capability of Li/CF x battery. Therefore, C 5 F 5 N is expected to be a promising electrolyte additive, and the related electrode/electrolyte interface engineering provides an effective and facile strategy to increase the performance of the lithium primary battery., (© 2023 Wiley-VCH GmbH.)

Background: We have reported a positive correlation between S100 calcium-binding protein (S100) A8/S100A9 and sepsis-induced lung damage before. However, limited knowledge exists concerning the biological role of S100A8/A9 in pulmonary vascular endothelial barrier dysfunction, as well as the diagnostic value of S100A8/A9 in sepsis., Methods: Sepsis was induced in C57BL/6J mice and S100A9-knockout (KO) mice through the cecal ligation and puncture (CLP). Pulmonary vascular leakage was determined by measuring extravasated Evans blue (EB). Reverse transcription polymerase chain reaction and the histological score were used to evaluate inflammation and lung injury, respectively. Recombinant S100A8/A9 (rhS100A8/A9) was used to identify the effects of S100A8/A9 on endothelial barrier dysfunction in human umbilical vein endothelial cells (HUVECs). Additionally, the diagnostic value of S100A8/A9 in sepsis was assessed using receiver operating characteristic., Results: S100A8/A9 expression was up-regulated in the lungs of CLP-operated mice. S100A9 KO significantly reversed CLP-induced hypothermia and hypotension, resulting in an improved survival rate. S100A9 KO also decreased the inflammatory response, EB leakage, and histological scores in the lungs of CLP-operated mice. Occludin and VE-cadherin expressions were decreased in the lungs of CLP-operated mice; However, S100A9 KO attenuated this decrease. Moreover, CLP-induced signal transducer and activator of transcription 3 (STAT3) and p38/extracellular signal-regulated kinase (ERK) signalling activation and apoptosis were mitigated by S100A9 KO in lungs. In addition, rhS100A8/A9 administration significantly decreased occludin and VE-cadherin expressions, increased the phosphorylated (p)-ERK/ERK, p-p38/p38, and B-cell leukaemia/lymphoma 2 protein (Bcl-2)-associated X protein/Bcl-2 ratios in HUVECs., Conclusion: The present study demonstrated S100A8/A9 aggravated sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Moreover, S100A8/A9 showed the potential as a biomarker for sepsis diagnosis., (© 2023. The Author(s).)

Identifying the individual and combined hydrological response of land use landscape pattern and climate changes is key to effectively managing the ecohydrological balance of regions. However, their nonlinearity, effect size, and multiple causalities limit causal investigations. Therefore, this study aimed to establish a comprehensive methodological framework to quantify changes in the landscape pattern and climate, evaluate trends in streamflow response, and analyze the attribution of streamflow events in five basins in Beijing from the past to the future. Future climate projections were based on three general circulation models (GCMs) under two shared socioeconomic pathways (SSPs). Additionally, the landscape pattern in 2035 under a natural development scenario was simulated by the patch-generating land use simulation (PLUS). The Soil and Water Assessment Tool (SWAT) was applied to evaluate the streamflow spatial and temporal dynamics over the period 2005-2035 with multiple scenarios. A bootstrapping nonlinear regression analysis and boosted regression tree (BRT) model were used to analyze the individual and combined attribution of landscape pattern and climate changes on streamflow, respectively. The results indicated that in the future, the overall streamflow in the Beijing basin would decrease, with a slightly reduced peak streamflow in most basins in the summer and a significant increase in the autumn and winter. The nonlinear quadratic regression more effectively explained the impact of landscape pattern and climate changes on streamflow. The trends in the streamflow change depended on where the relationship curve was in relation to the threshold. In addition, the impacts of landscape pattern and climate changes on streamflow were not isolated but were joint. They presented a nonlinear, non-uniform, and coupled relationship. Except for the YongDing River Basin, the annual streamflow change was influenced more by the landscape pattern. The dominant factors and the critical pair interactions varied from basin to basin. Our findings have implications for city planners and managers for optimizing ecohydrological functions and promoting sustainable development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.The financial support was provided by the National Key Research and Development Program of China (No. 2019YFD11004021)., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The application of nanomaterials in healthcare has emerged as a promising strategy due to their unique structural diversity, surface properties, and compositional diversity. In particular, nanomaterials have found a significant role in improving drug delivery and inhibiting the growth and metastasis of tumor cells. Moreover, recent studies have highlighted their potential in modulating the tumor microenvironment (TME) and enhancing the activity of immune cells to improve tumor therapy efficacy. Various types of nanomaterials are currently utilized as drug carriers, immunosuppressants, immune activators, immunoassay reagents, and more for tumor immunotherapy. Necessarily, nanomaterials used for tumor immunotherapy can be grouped into two categories: organic and inorganic nanomaterials. Though both have shown the ability to achieve the purpose of tumor immunotherapy, their composition and structural properties result in differences in their mechanisms and modes of action. Organic nanomaterials can be further divided into organic polymers, cell membranes, nanoemulsion-modified, and hydrogel forms. At the same time, inorganic nanomaterials can be broadly classified as nonmetallic and metallic nanomaterials. The current work aims to explore the mechanisms of action of these different types of nanomaterials and their prospects for promoting tumor immunotherapy., (© 2023 Wiley-VCH GmbH.)

Although endovascular therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. This study aimed to evaluate the safety, feasibility, and preliminary efficacy of intra-arterial administration of glyceryl trinitrate (GTN) after endovascular recanalization for neuroprotection. This is a prospective randomized controlled study. Eligible patients were randomized to receive 800 μg GTN or the same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (ICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NO x ). A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. Additionally, no significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends, while non-significant, were noted in both outcome and imaging for functional independence at 90 days and reduction in final infarct volume (75.0% vs 65.0%; 33.2 vs 38.9 ml) for the GTN group. Moreover, the concentration of blood NO x in the GTN group was significantly higher than in the control group at 2 h after GTN administration (26.2 vs 18.0 μmol/l, p < 0.05). The AGAIN study suggests intra-arterial administration of GTN post-endovascular therapy is safe and feasible and GTN successfully raised NO x levels over controls at 2 h. A multi-center randomized controlled trial with a larger sample size is warranted to determine GTN neoadjuvant efficacy., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)

The core protein allosteric modulators (CpAMs) have shown great potential as highly effective antiviral drugs against hepatitis B virus (HBV) in preclinical studies and clinical trials. In this study, we evaluated a small molecule compound called QL-007, which could potentially influence capsid assembly, using HBV replicated and susceptible cell models as well as mice infected with rAAV-HBV. QL-007 significantly inhibited HBV replication in a dose-dependent manner both in vitro and in vivo, resulting in significant decreases in HBV DNA, 3.5 kb HBV RNA and HBeAg. Furthermore, QL-007 not only induced the formation of misshaped Cp149 capsids but also possessed the capability to disassemble HBV capsids. It is noteworthy that QL-007 effectively reduced cccDNA biosynthesis in de novo infections. Mechanistically, QL-007 blocked the encapsidation of pgRNA and induced aberrant polymers assembly at concentrations ≥100 nM, while having no impact on the stability of core proteins. In conclusion, our findings underscore the potential of QL-007 as an effective agent against HBV replication and introduce it as a novel CpAM for the antiviral treatment of chronic hepatitis B., Competing Interests: Declaration of competing interest Jingyuan Xi, Zhiqiang Gu, Zimin Chen, Ting Zhang, Ran Chen, Tianyu Liu, Hao Liao, Jun Zou, Danli Yang, Qiang Xu, Jie Wang, Guochao Wei, Fengmin Lu and Xiangmei Chen declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Chunyan Sun and Zhe Cheng are employees of Qilu Pharmaceutical Co, Ltd., (Copyright © 2023. Published by Elsevier B.V.)

The use of bioelectronic devices relies on direct contact with soft biotissues. For transistor-type bioelectronic devices, the semiconductors that need to have direct interfacing with biotissues for effective signal transduction do not adhere well with wet tissues, thereby limiting the stability and conformability at the interface. We report a bioadhesive polymer semiconductor through a double-network structure formed by a bioadhesive brush polymer and a redox-active semiconducting polymer. The resulting semiconducting film can form rapid and strong adhesion with wet tissue surfaces together with high charge-carrier mobility of ~1 square centimeter per volt per second, high stretchability, and good biocompatibility. Further fabrication of a fully bioadhesive transistor sensor enabled us to produce high-quality and stable electrophysiological recordings on an isolated rat heart and in vivo rat muscles.

Background: Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity., Methods: Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively., Results: RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide., Conclusion: Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Soft and stretchable electronics have emerged as highly promising tools for biomedical diagnosis and biological studies, as they interface intimately with the human body and other biological systems. Most stretchable electronic materials and devices, however, still have Young's moduli orders of magnitude higher than soft bio-tissues, which limit their conformability and long-term biocompatibility. Here, we present a design strategy of soft interlayer for allowing the use of existing stretchable materials of relatively high moduli to versatilely realize stretchable devices with ultralow tissue-level moduli. We have demonstrated stretchable transistor arrays and active-matrix circuits with moduli below 10 kPa-over two orders of magnitude lower than the current state of the art. Benefiting from the increased conformability to irregular and dynamic surfaces, the ultrasoft device created with the soft interlayer design realizes electrophysiological recording on an isolated heart with high adaptability, spatial stability, and minimal influence on ventricle pressure. In vivo biocompatibility tests also demonstrate the benefit of suppressing foreign-body responses for long-term implantation. With its general applicability to diverse materials and devices, this soft-interlayer design overcomes the material-level limitation for imparting tissue-level softness to a variety of bioelectronic devices., (© 2023. The Author(s).)

This paper presents a gel-based three-dimensional (3D) substrate for surface-enhanced Raman spectroscopy (SERS) mediated by photonic nanojets (PNJs) to enhance the sensitivity of SERS detection. The porous structure of the gel-based substrate allowed small molecules to diffuse into the substrate, while the placement of silica beads on the substrate surface resulted in the generation of photonic nanojets during SERS measurements. Because the gel-based SERS substrate had electromagnetic (EM) hot spots along the Z -direction for several tens of microns, the focuses of the PNJs, which were located a few microns away from the substrate surface, could excite the EM hot spots located within the substrate. Our objective was to maximize SERS signal intensity by coating the substrate with a close-packed array of silica beads to enable the generation of multiple PNJs. The bead array was formed using an optical fiber decorated with gold nanorods (AuNRs) to create a temperature gradient in a mixture containing silica beads, thereby enabling their arrangement and deposition in arbitrary locations across the substrate. In experiments, the Raman enhancement provided by multiple PNJs significantly exceeded that provided by single PNJs. The proposed PNJ-mediated SERS method reduced the limit of detection for malachite green by 100 times, compared to SERS results obtained using the same substrate without beads. The proposed enhancement scheme using a gel-based 3D SERS substrate with a close-packed array of silica beads could be utilized to achieve high-sensitivity SERS detection for a variety of molecules in a diverse range of applications.

Aim: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action., Methods: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury., Results: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury., Conclusion: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage., Competing Interests: Declaration of Competing Interest No conflict of interest, (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Dielectric elastomer actuators (DEAs) are widely exploited for actuating soft machines and granting soft robots with capability to operate in both underwater and on-land environments is important to make them adapt to more complex situations. Here, a DEA-driven, highly robust, amphibious imperceptible soft robot (AISR) based on an all-environment stable ionic conductive material is presented. A soft, self-healable, all-environment stable ionic conductor is developed by introducing cooperative ion-dipole interactions to provide underwater stability as well as efficient suppression of ion penetration. By tuning molecular structures of the material, a 50-time device lifetime increase compared with unmodified [EMI][TFSI]-based devices and excellent underwater actuating performance is achieved. With the synthesized ionic electrode, the DEA-driven soft robot exhibits amphibious functionality to traverse hydro-terrestrial regions. When encountering damage, the robot shows good resilience and can self-heal underwater and it also exhibits imperceptibility to light, sound, and heat., (© 2023 Wiley-VCH GmbH.)

The emergence of wide and ultrawide bandgap semiconductors has revolutionized the advancement of next-generation power, radio frequency, and opto- electronics, paving the way for chargers, renewable energy inverters, 5G base stations, satellite communications, radars, and light-emitting diodes. However, the thermal boundary resistance at semiconductor interfaces accounts for a large portion of the near-junction thermal resistance, impeding heat dissipation and becoming a bottleneck in the devices' development. Over the past two decades, many new ultrahigh thermal conductivity materials have emerged as potential substrates, and numerous novel growth, integration, and characterization techniques have emerged to improve the TBC, holding great promise for efficient cooling. At the same time, numerous simulation methods have been developed to advance the understanding and prediction of TBC. Despite these advancements, the existing literature reports are widely dispersed, presenting varying TBC results even on the same heterostructure, and there is a large gap between experiments and simulations. Herein, we comprehensively review the various experimental and simulation works that reported TBCs of wide and ultrawide bandgap semiconductor heterostructures, aiming to build a structure-property relationship between TBCs and interfacial nanostructures and to further boost the TBCs. The advantages and disadvantages of various experimental and theoretical methods are summarized. Future directions for experimental and theoretical research are proposed.