Hyperbaric oxygen for moderate-to-severe traumatic brain injury: outcomes 5-8 years after injury.

The use of hyperbaric oxygen (HBO 2 ) in the field of traumatic brain injury (TBI) is becoming more widespread and increasing yearly, however there are few prognostic reports on long-term functional efficacy. The aim of this study was to assess the functional prognosis of patients with moderate-to-severe TBI 5-8 years following HBO 2 treatments and to explore the optimal HBO 2 regimen associated with prognosis, using a retrospective study. Clinical data were retrospectively collected as a baseline for patients with moderate-to-severe TBI treated with HBO 2 during inpatient rehabilitation from January 2014 to December 2017. The primary outcome measure was the Disability Rating Scale (DRS) and the secondary outcome measure was the Glasgow Outcome Scale. A total of 133 patients enrolled, with 9 (6.8%) dying, 41 (30.8%) remaining moderately disabled or worse (DRS scores 4-29), 83 (62.4%) remaining partially/mildly disabled or no disability (DRS scores 0-3). Logistic regression analysis revealed that age at injury (odds ratio (OR), 0.96; 95% confidence interval (CI), 0.92-0.99), length of intensive care unit stay (OR, 0.94; 95% CI, 0.88-0.99), and HBO 2 sessions (OR, 0.97; 95% CI, 0.95-0.99) were variables that independently influenced long-term prognosis. Cubic fitting models revealed that 14 and 21.6 sessions of HBO 2 could be effective for moderate and severe TBI, respectively. This study highlighted that HBO 2 in moderate-to-severe TBI may contribute to minimize death and reduce overall disability in the long-term. However, clinicians should be cautious of the potential risk of adverse long-term prognosis from excessive HBO 2 exposure when tailoring individualized HBO 2 regimens for patients with moderate-to-severe TBI. The study was registered on ClinicalTrials.gov (NCT05387018) on March 31, 2022.

Behavior Change Techniques Used in Self-Management Interventions Based on mHealth Apps for Adults With Hypertension: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Hypertension has become an important global public health challenge. Mobile health (mHealth) intervention is a viable strategy to improve outcomes for patients with hypertension. However, evidence on the effect of mHealth app interventions on self-management in patients with hypertension is yet to be updated, and the active ingredients promoting behavior change in interventions remain unclear. OBJECTIVE: We aimed to evaluate the effect of mHealth app self-management interventions on blood pressure (BP) management and investigate the use of behavior change techniques (BCTs) in mHealth app interventions. METHODS: We conducted a literature search in 6 electronic databases from January 2009 to October 2023 for studies reporting the application of mHealth apps in self-management interventions. The Cochrane Risk of Bias (version 2) tool for randomized controlled trials was used to assess the quality of the studies. BCTs were coded according to the Taxonomy of BCTs (version 1). The extracted data were analyzed using RevMan5.4 software (Cochrane Collaboration). RESULTS: We reviewed 20 studies, of which 16 were included in the meta-analysis. In total, 21 different BCTs (mean 8.7, SD 3.8 BCTs) from 12 BCT categories were reported in mHealth app interventions. The most common BCTs were self-monitoring of outcomes of behavior, feedback on outcomes of behavior, instruction on how to perform the behavior, and pharmacological support. The mHealth app interventions resulted in a -5.78 mm Hg (95% CI -7.97 mm Hg to -3.59 mm Hg; P<.001) reduction in systolic BP and a -3.28 mm Hg (95% CI -4.39 mm Hg to -2.17 mm Hg; P<.001) reduction in diastolic BP. The effect of interventions on BP reduction was associated with risk factors, such as hypertension, that were addressed by the mHealth app intervention (multiple risk factors vs a single risk factor: -6.50 mm Hg, 95% CI -9.00 mm Hg to -3.99 mm Hg vs -1.54 mm Hg, 95% CI -4.15 mm Hg to 1.06 mm Hg; P=.007); the presence of a theoretical foundation (with vs without behavior change theory: -10.06 mm Hg, 95% CI -16.42 mm Hg to -3.70 mm Hg vs -4.13 mm Hg, 95% CI -5.50 to -2.75 mm Hg; P=.07); intervention duration (3 vs ≥6 months: -8.87 mm Hg, 95% CI -10.90 mm Hg to -6.83 mm Hg vs -5.76 mm Hg, 95% CI -8.74 mm Hg to -2.77 mm Hg; P=.09); and the number of BCTs (≥11 vs <11 BCTs: -9.68 mm Hg, 95% CI -13.49 mm Hg to -5.87 mm Hg vs -2.88 mm Hg, 95% CI -3.90 mm Hg to -1.86 mm Hg; P<.001). CONCLUSIONS: The self-management interventions based on mHealth apps were effective strategies for lowering BP in patients with hypertension. The effect of interventions was influenced by factors related to the study's intervention design and BCT.

Preparing for aging: Understanding middle-aged user acceptance of AI chatbots through the technology acceptance model.

Background: Preparing for aging with personalized technology is crucial due to the growing elderly population. Artificial Intelligence (AI), notably AI chatbots in healthcare, has transformed technology by simulating human-like conversations. Research on middle-aged adults' acceptance of AI chatbots is limited. Assessing middle-aged individuals' intentions to use AI is vital for enhancing AI competency among the elderly and guiding future interventions. Objective: This study aims to explore the acceptance of middle-aged individuals toward AI chatbots and influencing factors and verify the usability of Technology Acceptance Model 2 (TAM2) in the use of AI technology in middle-aged people, also to inspire the design of future intelligent systems and online interventions for improving the health and well-being of the aging population. Methods: A cross-sectional design and snowball sampling method were utilized to conduct an online questionnaire survey among middle-aged adults. The questionnaire was compiled based on TAM2 and was created using the online survey platform. SPSS 26.0 software was used for statistical analysis. Results: A total of 259 valid questionnaires were included in the final data analysis. The study reported the Cronbach's α of 0.94 for the questionnaire. We found that perceived ease of use, subjective norm, and user image significantly influence users' intention to use AI chatbots. Notably, perceived usefulness emerged as a complete mediator in the relationship between subjective norm and intention to use, highlighting its central role in shaping user perceptions. The study also revealed a moderate acceptance level among middle-aged adults, emphasizing the need for targeted interventions. Conclusions: This study emphasized the importance of customizing AI technology to improve its adoption among middle-aged adults, providing valuable guidance for developers and policymakers. The findings indicated the need for effective aging preparation that includes technological competency, suggesting that future planning should encompass comprehensive preparations for aging to enhance AI competency among the middle-aged population.

A Near-Infrared Retinomorphic Device with High Dimensionality Reservoir Expression.

Physical reservoir-based reservoir computing (RC) systems for intelligent perception have recently gained attention because they require fewer computing resources. However, the system remains limited in infrared (IR) machine vision, including materials and physical reservoir expression power. Inspired by biological visual perception systems, the study proposes a near-infrared (NIR) retinomorphic device that simultaneously perceives and encodes narrow IR spectral information (at ≈980 nm). The proposed device, featuring core-shell upconversion nanoparticle/poly (3-hexylthiophene) (P3HT) nanocomposite channels, enables the absorption and conversion of NIR into high-energy photons to excite more photo carriers in P3HT. The photon-electron-coupled dynamics under the synergy of photovoltaic and photogating effects influence the nonlinearity and high dimensionality of the RC system under narrow-band NIR irradiation. The device also exhibits multilevel data storage capability (≥8 levels), excellent stability (≥2000 s), and durability (≥100 cycles). The system accurately identifies NIR static and dynamic handwritten digit images, achieving recognition accuracies of 91.13% and 90.07%, respectively. Thus, the device tackles intricate computations like solving second-order nonlinear dynamic equations with minimal errors (normalized mean squared error of 1.06 × 10⁻3 during prediction).

Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Numerous studies have shown that metabolic reprogramming is crucial for the development of HCC. Carbamoyl phosphate synthase 1 (CPS1), a rate-limiting enzyme in urea cycle, is an abundant protein in normal hepatocytes, however, lacking systemic research in HCC. It is found that CPS1 is low-expressed in HCC tissues and circulating tumor cells, negatively correlated with HCC stage and prognosis. Further study reveals that CPS1 is a double-edged sword. On the one hand, it inhibits the activity of phosphatidylcholine-specific phospholipase C to block the biosynthesis of diacylglycerol (DAG), leading to the downregulation of the DAG/protein kinase C pathway to inhibit invasion and metastasis of cancer cells. On the other hand, CPS1 promotes cell proliferation by increasing intracellular S-adenosylmethionin to enhance the m6A modification of solute carrier family 1 member 3 mRNA, a key transporter for aspartate intake. Finally, CPS1 overexpressing adeno-associated virus can dampen HCC progression. Collectively, this results uncovered that CPS1 is a switch between HCC proliferation and metastasis by increasing intracellular aspartate level.

Involvement of BK Channels and Ryanodine Receptors in Salicylate-induced Tinnitus.

Neural hyperexcitability of the central auditory system is a key pathological characteristic of tinnitus, but its underlying molecular mechanisms remain elusive. The large-conductance Ca2+-activated K+ channel (BK) plays a crucial role in down- or upregulating neuronal activity. This study aims to investigate the role of BK channels in mediating tinnitus-associated neural hyperexcitability and elucidate the mechanisms behind it. Immunofluorescent staining revealed extensive expression of the BK channels on neurons within the central auditory system of rats. After long-term systemic administration of salicylate, a stable tinnitus inducer, we observed a significant change in the expression levels of BKα and ß4 subunits in the rat central auditory system. In addition, salicylate was found to enhance the outward potassium currents mediated by the BK channel when exogenously expressed in HEK293 cells. Interestingly, this effect could be blocked by ryanodine, a potent inhibitor of ryanodine receptors (RyRs). Molecular docking identified Gln4020 within the central domain of RyR as a key residue in RyR-salicylate interactions. The results indicated that salicylate might directly activate RyRs leading to Ca2+ release from endoplasmic reticulum, and increased BK currents subsequently. Systemic treatment with paxilline, a potent blocker of BK channel, selectively reversed the increased P4/P1 amplitude ratios in the frequency region of tinnitus perception induced by single-dose salicylate administration. These results suggest that BK channels and ryanodine receptors may play a selective role in salicylate-induced tinnitus.

High resistance of superconducting TiN thin films against environmental attacks.

Superconductors, an essential class of functional materials, hold a vital position in both fundamental science and practical applications. However, most superconductors, including MgB2, Bi2Sr2CaCu2O8+δ, and FeSe, are highly sensitive to environmental attacks (such as from water and moist air), hindering their wide applications. More importantly, the surface physical and chemical processes of most superconductors in various environments remain poorly understood. Here, we comprehensively investigate the high resistance of superconducting titanium nitride (TiN) epitaxial films against acid and alkali attacks. Unexpectedly, despite immersion in acid and alkaline solutions for over 7 days, the crystal structure and superconducting properties of TiN films remain stable, as demonstrated by high-resolution X-ray diffraction, electrical transport, atomic force microscopy, and scanning electron microscopy. Furthermore, combining scanning transmission electron microscopy analysis with density functional theory calculations revealed the corrosion mechanisms: acid corrosions lead to the creation of numerous defects due to the substitution of Cl ions for N anions, whereas alkaline environments significantly reduce the film thickness through the stabilization of OH* adsorbates. Our results uncover the unexpected stability and durability of superconducting materials against environmental attacks, highlighting their potential for enhanced reliability and longevity in diverse applications.

CD103+ cDC1 Dendritic Cell Vaccine Therapy for Osteosarcoma Lung Metastases.

BACKGROUND: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. METHODS: A bilateral tumor model was used to assess cDCV therapy efficacy and systemic immunity induction. K7M3 cells were injected into mice bilaterally. Right-sided tumors received PBS (control) or cDCV. Left-sided tumors were untreated. Tumor growth was compared between the vaccine-treated and untreated tumor on the contralateral side and compared to the control group. The immune cell profiles of the tumors, and tumor-draining lymph nodes (TdLNs) and spleen were evaluated. To determine the efficacy of systemic cDCV therapy against established lung metastases, K7M3 cells were injected intratibially. Leg amputation was performed 5 weeks later. Mice were treated intravenously with PBS or cDCV and euthanized 6 weeks later. Lungs, TdLNs and spleen were collected. The number and size of the lung nodules were quantified. The immune cell profile of tumor, and lymph nodes and spleen were also evaluated. Using this same model, we evaluated the effect of cDCV + anti-CTLA-4. RESULTS: cDCV therapy inhibited the treated and untreated tumors and increased the number of T-cells in these tumors and the lymph nodes compared to control-treated mice. Systemic cDCV therapy administered following amputation decreased the size and number of lung metastases, and increased T-cell numbers in the tumor and lymph nodes. Combining anti-CTLA-4 with cDCV therapy increased cDCV efficacy against lung metastases. CONCLUSIONS: Intratumor cDCV generated a systemic immune response inhibiting the growth of both the treated and untreated tumors, with increased T-cells in the tumor and lymph nodes. Systemic cDCV was effective against established lung metastases. Efficacy was increased by anti-CTLA4. cDCVs may provide a novel therapeutic approach for relapsed/metastatic OS patients.

Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a devastating stroke, in which acidosis is one of detrimental complications. The extracellular pH reduction can activate G protein-coupled receptor 4 (GPR4) in the brain. Yet, the extent to which proton-activated GPR4 contributes to the early brain injury (EBI) post-SAH remains largely unexplored. Ferroptosis, iron-dependent programmed cell death, has recently been shown to contribute to EBI. We aimed to investigate the effects of GPR4 inhibition on neurological deficits and neuronal ferroptosis after SAH in rats. METHODS: A total 253 Sprague Dawley (SD) male rats (weighing 275-330g) were utilized in this study. SAH was induced by endovascular perforation. NE-52-QQ57 (NE), a selective antagonist of GPR4 was administered intraperitoneally 1-h post-SAH. To explore the mechanisms, RhoA activator U-46619 and YAP activator PY-60 were delivered intracerebroventricularly. Short- and long-term neurobehavior, SAH grading, Western blot assay, ELISA assay, immunofluorescence staining, and transmission electron microscopy was performed post-SAH. RESULTS: Following SAH, there was an upregulation of GPR4 expression in neurons. GPR4 inhibition by NE improved both short-term and long-term neurological outcomes post-SAH. NE also reduced neuronal ferroptosis, as evidenced by decreased lipid peroxidation products 4HNE and MDA levels in brain tissues, and reduced mitochondrial shrinkage, increased mitochondria crista and decreased membrane density. The application of either U-46619 or PY-60 partially offset the neuroprotective effects of NE on neuronal ferroptosis in SAH rats. CONCLUSIONS: This study demonstrated that acid-sensing receptor GPR4 contributed to neuronal ferroptosis after SAH via RhoA/YAP pathway, and NE may be a potential therapeutic strategy to attenuate GPR4 mediated neuronal ferroptosis and EBI after SAH.

Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.

Traditional Chinese medicine (TCM) formulas, including the Er-Long-Zuo-Ci pill, Tong-Qiao-Er-Long pill, and Er-Long pill, have long been utilized in China for managing age-related hearing loss (ARHL). However, the specific bioactive compounds, pharmacological targets, and underlying mechanisms remain elusive. This study aims to find the shared bioactive ingredients among these three formulas, uncover the molecular pathways they regulate, and identify potential therapeutic targets for ARHL. Furthermore, it seeks to validate the efficacy of these major components through both in vivo and in vitro experiments. Common bioactive ingredients were extracted from the TCMSP database, and their putative target proteins were predicted using the Swiss Target Prediction database. ARHL-related target proteins were collected from GeneCards and OMIM databases. Our approach involved constructing drug-target networks and drug-disease-specific protein-protein interaction networks and conducting clustering, topological property analyses, and functional annotation through GO and KEGG enrichment analysis. Molecular docking analysis was utilized to delineate interaction mechanisms between major bioactive ingredients and key target proteins. Finally, in vivo and in vitro experiments involving ABR recording, immunofluorescent staining, HE staining, and quantitative PCR were conducted to validate the treatment effects of flavonoids on the declining auditory function in DBA/2 J mice. We identified 11 common chemical compounds across the three formulas and their associated 276 putative targets. Additionally, 3350 ARHL-related targets were compiled. As an intersection of the putative targets of the common compounds and ARHL-related proteins, 145 shared targets were determined. Functional enrichment analysis indicated that these compounds may modulate various biological processes, including cell proliferation, apoptosis, inflammatory response, and synaptic connections. Notably, potential targets such as TNFα, MAPK1, SRC, AKT, EGFR, ESR1, and AR were implicated. Flavonoids emerged as major bioactive components against ARHL based on target numbers, with molecular docking demonstrating diverse interaction models between these flavonoids and protein targets. Furthermore, baicalin could mitigate the age-related cochlear damage and hearing loss of DBA/2 J mice through its multi-target and multi-pathway mechanism, involving anti-inflammation, modulation of sex hormone-related pathways, and activation of potassium channels. This study offers an integrated network pharmacology approach, validated by in vivo and in vitro experiments, shedding light on the potential mechanisms, major active components, and therapeutic targets of TCM formulas for treating ARHL.

Associations between metabolic overweight/obesity phenotypes and mortality risk among patients with chronic heart failure.

Background: Metabolic disorders and overweight or obesity are highly prevalent and intricately linked in patients with chronic heart failure (CHF). However, it remains unclear whether there is an interactive effect between these conditions and the prognosis of heart failure, and whether such an interaction is influenced by stratification based on age and sex. Methods: A total of 4,955 patients with CHF were enrolled in this study. Metabolic status was assessed according to the presence or absence of metabolic syndrome (MetS). BMI categories included normal weight and overweight or obesity (BMI < 24, ≥ 24 kg/m2). Patients were divided into four phenotypes according to their metabolic status and BMI: metabolically healthy with normal weight (MHNW), metabolically unhealthy with normal weight (MUNW), metabolically healthy with overweight or obesity (MHO), and metabolically unhealthy with overweight or obesity (MUO). The incidence of primary outcomes, including all-cause and cardiovascular (CV) death, was recorded. Results: During a mean follow-up of 3.14 years, a total of 1,388 (28.0%) all-cause deaths and 815 (16.4%) CV deaths were documented. Compared to patients with the MHNW phenotype, those with the MUNW (adjusted hazard ratio [aHR], 1.66; 95% confidence interval [CI], 1.38-2.00) or MUO (aHR, 1.42 [95% CI, 1.24-1.63]) phenotypes had a greater risk of all-cause death, and those with the MHO phenotype (aHR, 0.61 [95% CI, 0.51-0.72]) had a lower risk of all-cause death. Moreover, the above phenomenon existed mainly among males and elderly females (aged ≥ 60 years). In nonelderly females (aged < 60 years), the detrimental effects of MetS were lower (aHR, 1.05 [95% CI, 0.63-1.75] among MUNW group and aHR, 0.52 [95% CI, 0.34-0.80] among MUO group), whereas the protective effects of having overweight or obesity persisted irrespective of metabolic status (aHR, 0.43 [95% CI, 0.26-0.69] among MHO group and aHR, 0.52 [95% CI, 0.34-0.80] among MUO group). Similar results were obtained in the Cox proportional risk analysis of the metabolic overweight/obesity phenotypes and CV death. Conclusions: In male and elderly female patients with CHF, the detrimental effects of MetS outweighed the protective benefits of having overweight or obesity. Conversely, in nonelderly females, the protective effects of having overweight or obesity were significantly greater than the adverse impacts of MetS.

Identification of a Novel Antiviral Lectin against SARS-CoV-2 Omicron Variant from Shiitake-Mushroom-Derived Vesicle-like Nanoparticles.

Lectins are a class of carbohydrate-binding proteins that may have antiviral activity by binding to the glycans on the virion surface to interfere with viral entry. We have identified a novel lectin (named Shictin) from Shiitake mushroom (Lentinula edodes)-derived vesicle-like nanoparticles (VLNs, or exosomes) that exhibits strong activity against the SARS-CoV-2 Omicron variant with an IC50 value of 87 nM. Shictin contains 298 amino acids and consists of two unique domains (N-terminal and C-terminal domain). The N-terminal domain is the carbohydrate-binding domain (CBD) that is homologous with CBDs of other lectins, suggesting that Shictin inhibits SARS-CoV-2 infection by binding to the glycans on the virion surface to prevent viral entry. This finding demonstrates that exosomes of vegetables are a valuable source for the identification of antiviral lectins. Therefore, it is believed that lectins from vegetable VLNs have potential as antiviral therapeutic agents.

Carbon Ink Enhanced Calcium Alginate-Based Hydrogel with Response Surface Methodology Optimized for Solar-Driven Salt-Tolerant Desalination.

The global shortage of freshwater resources is becoming more and more serious; therefore, it is necessary to obtain freshwater by desalinating seawater resources. Solar-driven interfacial photothermal evaporation, which is an environmentally friendly and energy-efficient technology, has been used to desalinate seawater for water purification and production. Herein, the IPCA hydrogel with abundant pores consisting of carbon ink as a photothermal conversion material and PU sponge loaded with calcium alginate as a water transport medium was successfully prepared and used to obtain portable water. The parameters of the synthesized IPCA are optimized by Response Surface Methodology analysis, and it was found that the IPCA exhibits a high evaporation efficiency of 3.779 kg m-2 h-1 and up to 95.98% of photothermal conversion capacity under one solar intensity. It maintains a high evaporation efficiency and salt resistance after 10 cycles of evaporation in actual seawater. Moreover, IPCA shows a high removal of various organic dye pollutants in wastewater. The results suggest a new approach for the preparation of simple, efficient, and green solar evaporators in practical application.

Reinforcement Learning-Based Nonautoregressive Solver for Traveling Salesman Problems.

The traveling salesman problem (TSP) is a well-known combinatorial optimization problem (COP) with broad real-world applications. Recently, neural networks (NNs) have gained popularity in this research area because as shown in the literature, they provide strong heuristic solutions to TSPs. Compared to autoregressive neural approaches, nonautoregressive (NAR) networks exploit the inference parallelism to elevate inference speed but suffer from comparatively low solution quality. In this article, we propose a novel NAR model named, which incorporates a specially designed architecture and an enhanced reinforcement learning (RL) strategy. To the best of our knowledge, is the first TSP solver that successfully combines RL and NAR networks. The key lies in the incorporation of NAR network output decoding into the training process. efficiently represents TSP-encoded information as rewards and seamlessly integrates it into RL strategies, while maintaining consistent TSP sequence constraints during both training and testing phases. Experimental results on both synthetic and real-world TSPs demonstrate that outperforms five state-of-the-art (SOTA) models in terms of solution quality, inference speed, and generalization to unseen scenarios.

Simultaneous targeting of TGF-ß1/PD-L1 via a hydrogel-nanoparticle system to remodel the ECM and immune microenvironment for limiting adhesion formation.

Adhesion seriously affects the recovery of tendon gliding function. Our group previously found that inhibition of TGF-ß1, which is closely related to adhesion formation, effectively attenuated adhesions but did not eliminate them, suggesting that there may be other mechanisms involved in adhesion formation. In this study, we considered that uncontrolled and excessively proliferating fibroblasts undergo immune escape, which aggravates the deposition of extracellular matrix during the adhesion formation. We found that the expression of the immune checkpoint PD-L1 was significantly elevated after injury and may be involved in adhesion formation. Therefore, we intended to silence both TGF-ß1 and PD-L1 to improve the immune advantage in the microenvironment after flexor tendon injury to further reduce adhesion. We constructed the nanoparticle/TGF-ß1 or/and PD-L1 siRNA complexes and verified their high biocompatibility and high transfection efficiency. We found that CD8+ T cells had a greater killing effect on the excessively proliferating cells that were transfected with nanoparticle/TGF-ß1 or/and PD-L1 siRNAs. The hydrogel-nanoparticle/TGF-ß1 or/and PD-L1 siRNA system could effectively improve the gliding function of the tendons without weakening the mechanical properties in injured rat FDL tendon and chicken FDP tendon models. In addition, the potential of CD8+ T cells to encircle the adhesion cells on the tendon surface was observed, which resulted in increased levels of cell apoptosis. Thus, our study confirmed that combined knockdown of TGF-ß1 and PD-L1 could activate immunodominance after flexor tendon repair and provided a potential treatment to limit adhesion formation and improve gliding function. STATEMENT OF SIGNIFICANCE: Adhesion seriously affects the recovery of tendon gliding function. TGF-ß1 is related to adhesion formation as it regulates the production of extracellular matrix. We found that excessively proliferated fibroblasts might undergo immune escape, which aggravated the deposition of extracellular matrix. Therefore, we constructed a hydrogel-nanoparticle/TGF-ß1 and PD-L1 siRNAs system for silencing TGF-ß1 and PD-L1 to improve the immune advantage in the microenvironment after tendon injury. This system could improve the gliding function of tendons without weakening the mechanical property and increase the killing effect of CD8+ T cells. Combined knockdown of TGF-ß1 and PD-L1 could activate immunodominance after tendon repair and provide a potential treatment to limit adhesion formation.

Synthesis of 6-oxa-Spiro[4.5]decane Derivatives by Merging Ring-Opening of Benzo[c]oxepines and Formal 1,2-Oxygen Migration.

A facile one-pot synthetic method has been developed for constructing 6-oxa-spiro[4.5]decane skeletons by merging the ring-opening of benzo[c]oxepines and formal 1,2-oxygen migration reactions. More than 30 examples of the 6-oxa-spiro[4.5]decane derivatives have been synthesized under transition-metal-free conditions.

An Antagonistic Photovoltaic Memristor for Bioinspired Active Contrast Adaptation.

Machine vision systems that consist of cameras and image-processing components for visual inspection and identification tasks play a critical role in various intelligent applications, including pilotless vehicles and surveillance systems. However, current systems usually possess a limited dynamic range and fixed photoresponsivity, restricting their capability of gaining high-fidelity images when encoding a high-contrast scene. Here, it is shown that a photovoltaic memristor incorporating two antagonistic photovoltaic junctions can autonomously adjust its response to varying light stimuli, enabling the amplification of shadows and inhibition of highlight saturation. Due to the dynamic photodoping effect at the p-n junction with an asymmetrical profile, the photocurrent polarities of the antagonistic memristor can be changed as the light intensity increases. The light-intensity-dependent switchable photovoltaic behaviors match Weber's law where photosensitivity is inversely proportional to the light stimuli. An 11 × 11 memristor array is used to detect a high-contrast scene with light intensities ranging from 1 to 5 × 104 µW cm-2, achieving a similar active contrast adaptation performance compared with the human visual systems (less than 1.2 s at 94 dB). This work paves the way for innovative neuromorphic device designs and may lead to the development of state-of-the-art active visual adaptation photosensors.

Clinical implications of the latest advances in gastrointestinal tumor research.

In this editorial, we provide commentary on six articles recently published in the World Journal of Gastrointestinal Oncology. These articles collectively present the latest findings in the field of gastric and colorectal cancer (CRC) research. The global incidence of gastric cancer varies based on geographical location, age, and sex. The disease predominantly affects middle-aged and elderly individuals, with a slightly higher prevalence in men than in women. CRC is characterized by a low 5-year survival rate and high mortality rate. It primarily affects individuals over the age of 50, and the risk of disease increases with age. Both gastric and CRC pose significant health threats, thus requiring more effective diagnostic, therapeutic, and supportive care strategies to improve patient outcomes. The articles discussed in this editorial encompass topics such as screening, diagnosis, mechanisms of progression, and postoperative recovery in gastric and CRC, and the findings offer valuable insights for clinical decision-making in the diagnosis, treatment, and prognosis of gastrointestinal cancers.

Intramolecular/Intermolecular Sequential Cyclization Accompanied by Double C-F Bond Cleavage: Access to Tricyclic Fluorine-Containing Pyrano[3,2-c]chromenes.

Defluorinative cyclization of CF3-alkenes has emerged as a reliable strategy for crafting intricate polycyclic frameworks. In this study, a facile defluorinative bicyclization approach was developed for the construction of 4H,5H-pyrano[3,2-c]chromenes under mild conditions involving a sequence of intramolecular cyclization and intermolecular defluoroheterocyclization. A variety of polysubstituted 4H,5H-pyrano[3,2-c]chromenes featuring C2-fluorine could be synthesized in good yields with excellent tolerance toward various functional groups. Moreover, the introduction of a C-F bond provides additional possibilities for further modification of this skeleton. The product features aggregation-induced emission (AIE) characteristics after simple modification, which is promising for chemical and biomedical imaging.

A novel long non-coding RNA connects obesity to impaired adipocyte function.

BACKGROUND: Long non-coding RNAs (lncRNAs) can perform tasks of key relevance in fat cells, contributing, when defective, to the burden of obesity and its sequelae. Here, scrutiny of adipose tissue transcriptomes before and after bariatric surgery (GSE53378) granted identification of 496 lncRNAs linked to the obese phenotype. Only expression of linc-GALNTL6-4 displayed an average recovery over 2-fold and FDR-adjusted p-value <0.0001 after weight loss. The aim of the present study was to investigate the impact on adipocyte function and potential clinical value of impaired adipose linc-GALNTL6-4 in obese subjects. METHODS: We employed transcriptomic analysis of public dataset GSE199063, and cross validations in two large transversal cohorts to report evidence of a previously unknown association of adipose linc-GALNTL6-4 with obesity. We then performed functional analyses in human adipocyte cultures, genome-wide transcriptomics, and untargeted lipidomics in cell models of loss and gain of function to explore the molecular implications of its associations with obesity and weight loss. RESULTS: The expression of linc-GALNTL6-4 in human adipose tissue is adipocyte-specific and co-segregates with obesity, being normalized upon weight loss. This co-segregation is demonstrated in two longitudinal weight loss studies and two cross-sectional samples. While compromised expression of linc-GALNTL6-4 in obese subjects is primarily due to the inflammatory component in the context of obesity, adipogenesis requires the transcriptional upregulation of linc-GALNTL6-4, the expression of which reaches an apex in terminally differentiated adipocytes. Functionally, we demonstrated that the knockdown of linc-GALNTL6-4 impairs adipogenesis, induces alterations in the lipidome, and leads to the downregulation of genes related to cell cycle, while propelling in adipocytes inflammation, impaired fatty acid metabolism, and altered gene expression patterns, including that of apolipoprotein C1 (APOC1). Conversely, the genetic gain of linc-GALNTL6-4 ameliorated differentiation and adipocyte phenotype, putatively by constraining APOC1, also contributing to the metabolism of triglycerides in adipose. CONCLUSIONS: Current data unveil the unforeseen connection of adipocyte-specific linc-GALNTL6-4 as a modulator of lipid homeostasis challenged by excessive body weight and meta-inflammation.