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Highlights A novel organohydrogel-based multimodal e-skin with excellent sensing performance for temperature, humidity, pressure, proximity, and NO2 is proposed for the first time, showing powerful sensing capabilities beyond natural skin. The developed multimodal e-skin exhibited extraordinary sensing performance at room temperature, including fast pressure response time (0.2 s), high temperature sensitivity (9.38% °C-1), a wide range of humidity response (22%–98% RH), high NO2 sensitivity (254% ppm-1), a low detection limit (11.1 ppb NO2) and the abilities to sense the proximity of objects accurately, which are yet achieved by previous e-skins. The multimodal e-skin was combined with the deep neural network algorithm and wireless alarm circuit to achieve zero-error classification of different objects and rapid response to NOx leak incidents, proving the feasibility of the e-skin-assisted rescue robot for post-earthquake rescue.

Abstract With the rapid development of the Internet of Things (IoTs), wearable sensors are playing an increasingly important role in daily monitoring of personal health and wellness. The signal-to-noise-ratio has become the most critical performance factor to consider. To enhance it, on the one hand, good sensing materials/devices have been employed; on the other hand, signal amplification and noise reduction circuits have been used. However, most of these devices and circuits work in an active sampling mode, requiring frequent data acquisition and hence, entailing high-power consumption. In this scenario, a flexible and wearable event-triggered sensor with embedded signal amplification without an external power supply is of great interest. Here, we report a flexible two-terminal piezotronic n-p-n bipolar junction transistor (PBJT) that acts as an autonomous and highly sensitive, current- and/or voltage-mediated pressure sensor. The PBJT is formed by two back-to-back piezotronic diodes which are defined as emitter-base and collector-base diodes. Upon force exertion on the emitter side, as a result of the piezoelectric effect, the emitter-base diode is forward biased while the collector-base diode is reverse biased. Due to the inherent BJT amplification effect, the PBJT achieves record-high sensitivities of 139.7 kPa-1 (current-based) and 88.66 kPa-1 (voltage-based) in sensing mode. The PBJT also has a fast response time of

Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive cancer characterized by a poor prognosis and resistance to chemotherapy. In this study, utilizing scRNA-seq, we discovered that the tetra-transmembrane protein mal, T cell differentiation protein 2 (MAL2), exhibited specific enrichment in ICC cancer cells and was strongly associated with a poor prognosis. The inhibition of MAL2 effectively suppressed cell proliferation, invasion, and migration. Transcriptomics and metabolomics analyses suggested that MAL2 promoted lipid accumulation in ICC by stabilizing EGFR membrane localization and activated the PI3K/AKT/SREBP-1 axis. Molecular docking and Co-IP proved that MAL2 interacted directly with EGFR. Based on constructed ICC organoids, the downregulation of MAL2 enhanced apoptosis and sensitized ICC cells to cisplatin. Lastly, we conducted a virtual screen to identify sarizotan, a small molecule inhibitor of MAL2, and successfully validated its ability to inhibit MAL2 function. Our findings highlight the tumorigenic role of MAL2 and its involvement in cisplatin sensitivity, suggesting the potential for novel combination therapeutic strategies in ICC.

Abstract Colorectal cancer (CRC) is a prevalent global health issue, with 5-fluorouracil (5-FU) being a commonly used chemotherapeutic agent for its treatment. However, the efficacy of 5-FU is often hindered by drug tolerance. Sodium butyrate (NaB), a derivative of intestinal flora, has demonstrated anti-cancer properties both in vitro and in vivo through pro-apoptotic effects and has shown promise in improving outcomes when used in conjunction with traditional chemotherapy agents. This study seeks to evaluate the impact and potential mechanisms of NaB in combination with 5-FU on CRC. We employed a comprehensive set of assays, including CCK-8, EdU staining, Hoechst 33258 staining, flow cytometry, ROS assay, MMP assay, immunofluorescence, and mitophagy assay, to detect the effect of NaB on the biological function of CRC cells in vitro. Western blotting and immunohistochemistry were used to verify the above experimental results. The xenograft tumor model was established to evaluate the in vivo anti-CRC activity of NaB. Subsequently, 16S rRNA gene sequencing was used to analyze the intestinal flora. The findings of our study demonstrate that sodium butyrate (NaB) exerts inhibitory effects on tumor cell proliferation and promotes tumor cell apoptosis in vitro, while also impeding tumor progression in vivo through the enhancement of the mitophagy pathway. Furthermore, the combined treatment of NaB and 5-fluorouracil (5-FU) yielded superior therapeutic outcomes compared to monotherapy with either agent. Moreover, this combination therapy resulted in the specific enrichment of Bacteroides, LigiLactobacillus, butyric acid-producing bacteria, and acetic acid-producing bacteria in the intestinal microbiota. The improvement in the intestinal microbiota contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Taken together, these findings indicate that NaB, a histone acetylation inhibitor synthesized through intestinal flora fermentation, has the potential to significantly enhance the therapeutic efficacy of 5-FU in CRC treatment and improve the prognosis of CRC patients.

Abstract To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > − 2.0) and low BMD group (QCT Z-score ≤ − 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P

Abstract Background Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue. Methods Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques. Results Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group. Conclusions AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC.

Abstract Background Bacillus subtilis is widely used in industrial-scale riboflavin production. Previous studies have shown that targeted mutagenesis of the ribulose 5-phosphate 3-epimerase in B. subtilis can significantly enhance riboflavin production. This modification also leads to an increase in purine intermediate concentrations in the medium. Interestingly, B. subtilis exhibits remarkable efficiency in purine nucleoside synthesis, often exceeding riboflavin yields. These observations highlight the importance of the conversion steps from inosine-5’-monophosphate (IMP) to 2,5-diamino-6-ribosylamino-4(3 H)-pyrimidinone-5’-phosphate (DARPP) in riboflavin production by B. subtilis. However, research elucidating the specific impact of these reactions on riboflavin production remains limited. Result We expressed the genes encoding enzymes involved in these reactions (guaB, guaA, gmk, ndk, ribA) using a synthetic operon. Introduction of the plasmid carrying this synthetic operon led to a 3.09-fold increase in riboflavin production compared to the control strain. Exclusion of gmk from the synthetic operon resulted in a 36% decrease in riboflavin production, which was further reduced when guaB and guaA were not co-expressed. By integrating the synthetic operon into the genome and employing additional engineering strategies, we achieved riboflavin production levels of 2702 mg/L. Medium optimization further increased production to 3477 mg/L, with a yield of 0.0869 g riboflavin per g of sucrose. Conclusion The conversion steps from IMP to DARPP play a critical role in riboflavin production by B. subtilis. Our overexpression strategies have demonstrated their effectiveness in overcoming these limiting factors and enhancing riboflavin production.

Abstract Background Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. Methods We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8–11), moderate (4–7), and low (0–3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). Results The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I 2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger’s test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P

This paper proposes an assessment model of the regional rainstorm process based on the return period method, which is used to comprehensively assess the frequency and intensity of rainstorm processes. Based on the hourly rainfall data and rainstorm disaster data of 114 regional rainstorm processes in Chongqing from 2011 to 2021, the probabilistic fitting, return period calculation, correlation analysis and other methods are used to construct the return period assessment model of regional rainstorm processes, and the business verification is carried out. The results are as follows: (1) Using the return period calculation formula built in this study, the error between the return value and the original value of the rainstorm process characteristic quantity is less than 10%, suggesting a higher accuracy of the return period calculation. (2) The correlation coefficient between the constructed return period assessment model and direct economic loss is significant at the significance level of 0.001, which shows a 16% improvement compared to the current business index. (3) Historical backtracking and independent sample tests show that the grade consistency rate between the return period evaluation model and business index is 70%. The return period assessment model is stable and can reflect the frequency and intensity of events, which can provide a new idea for regional rainstorm process assessment.

Extreme urban heat poses significant challenges to the resilience and livability of cities. Urban squares are important open public spaces in cities, serving as main locations for residents' leisure and recreational activities and reflect the identity and cultural background of the cities. Improvement in thermal comfort in urban squares can improve the quality of the urban environment and help mitigate the urban heat island effect. This study developed 18 layout and landscape combination scenarios based on statistical analysis of data from 100 urban squares in regions with hot summers and cold winters. Further, the effectiveness of the proposed design solutions in improving the thermal environment was comprehensively analyzed. The results show that: 1) The block array layout with vegetation, water bodies, and permeable tiles is the most effective scenario, with a PET of 31.84 °C, approaching a comfortable level of heat stress; 2) Among the three layouts, the block array layout optimizes thermal comfort better than the main view entrance layout and main view center layout, and reduces physiological equivalent temperature by 10.51–10.77 °C compared with that of the other two layouts; 3) Scenarios incorporating water bodies provide better optimization effects than those with only trees, even when the total area covered by greenery remains unchanged; and 4) Permeable paving materials with high albedo more effectively improve the thermal comfort. Our results highlight a great potential of comprehensively using multiple landscape strategies to improve outdoor thermal comfort, and provides design basis for enhancing thermal comfort in similar sized urban squares in hot summer and cold winter areas.

This study reported a case of MELAS syndrome presenting as the initial imaging characteristics of Fahr’s syndrome with “near” sudden unexpected death in epilepsy (SUDEP) and lateralized periodic discharges (LPD). The patient, a young boy, experienced loss of consciousness 2 days prior, which was followed by two limb and facial convulsions. He was later found in cardiac arrest during hospitalization, but regained consciousness gradually after receiving cardiopulmonary resuscitation and tracheal intubation. The patient exhibited short stature, intellectual disability, poor sports abilities, and academic performance since childhood, but had no family history. Emergency head computed tomography (CT) revealed high density calcification in bilateral caudate nucleus, lentiform nucleus, thalamus, and dentate nucleus with evidence of an acute process. The patient was transferred to the neurology department where he continued to recover consciousness, though he experienced dysarthria, left limb hemiplegia, and hemiparesthesia. Changes in head magnetic resonance imaging (MRI) findings were noted at admission, 1 month later, and 6 months later. LPD were observed in his video electroencephalogram. The CT urography indicated a narrow left ureteropelvic junction with left hydronephrosis, which was suggestive of ureteropelvic junction obstruction. Ultimately, a diagnosis of near-SUDEP was suspected in this patient, indicating a rare case of MELAS syndrome with near-SUDEP and LPD. The gene tests results revealed the presence of the mitochondrial DNA A3243G mutation, leading to the final diagnosis of MELAS syndrome. This case expands the clinical disease spectrum of the MELAS syndrome.

Introduction Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%–6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy.Methods and analysis This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable.Ethics and dissemination The study protocol has been approved by the ethics committees of the Sixth People’s Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences.Trial registration number ChiCTR2300073864.

Abstract Heterogeneous organ‐specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single‐cell profiling using formalin‐fixed paraffin‐embedded (FFPE) materials. In this study, single‐cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ‐specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single‐cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ‐specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ‐specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM‐3. This study originally deciphers the single‐cell landscape of the organ‐specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ‐specific treatment approaches.

Aims: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. Methods and results: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. Conclusions: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

Introduction and Objectives: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. Materials and Methods: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. Results: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). Conclusions: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Abstract Background Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis’s mechanism. Results Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis. Conclusions Our findings suggest that PKM2 may be a tumor’s promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.

Abstract In recent years, there has been a global trend of aging, which has resulted in significant changes to the burden of gastritis and duodenitis (GD). Using the global burden of disease (GBD) database spanning 1990 to 2019, we evaluated the temporal trends of age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized disability-adjusted life years (AS-DALYs) for GD using estimated annual percentage changes (EAPC). Additionally, we examined the burden of GD across various strata, including social demographic index (SDI), age, and sex. Finally, the risk factors linked to the incidence and mortality of GD, utilizing Pearson correlation analysis. In 2019, there were 31 million GD patients globally, a notable increase of 12 million from 1990, while the ASIR, ASDR, and AS-DALYs for GD all showed a decrease. Correlation analysis showed a significant negative relationship between ASIR and SDI. Factors like hand hygiene and vitamin A deficiency had significant positive correlations with ASIR and ASDR in 2019. Over the past thirty years, the burden of GD has increased alongside global population aging. Future efforts should focus on exploring prevention for GD, with special attention to the elderly population in low SDI regions.

Abstract Background The increasing number of sequential treatments complicates the evaluation of overall survival (OS) in clinical trials for hepatocellular carcinoma (HCC), therefore, reliable surrogate endpoints (SEs) are required. This study aimed to evaluate the surrogacy of progression-free survival (PFS) and one-year (1-yr) milestone survival for OS in HCC trials. Methods We systematically searched databases for randomized clinical trials that evaluated systemic treatments for advanced HCC. Individual patient data were reconstructed to calculate the 1-yr survival rate. We adopted a two-stage meta-analytic validation model to evaluate the correlation between SEs and OS, and the correlation between treatment effects on SEs and OS. The hazard ratio (HR) was calculated to assess the treatment effects on PFS and OS, and the 1-yr survival ratio was calculated to evaluate the treatment effects on the 1-yr milestone survival. Results Thirty-two HCC trials involving 13,808 patients were included. A weak correlation was detected between the median PFS and median OS (R2 = 0.32), whereas the correlation improved between PFS HR and OS HR (R2 = 0.58). We identified strong correlations between the 1-yr survival rate and median OS and between the 1-yr survival ratio and OS HR (R2 = 0.74 and 0.65, respectively). In subgroup analyses, PFS HR strongly correlated with OS HR in trials relevant to immune checkpoint inhibitors (ICIs). Although the correlation remained weak between PFS and OS even in trials with PFS HR ≤ 0.6, the 1-yr survival rate and 1-yr survival ratio were strong surrogates for median OS and OS HR, respectively (R2 = 0.77 and 0.75). Conclusions One-year milestone survival outperformed PFS as a SE for OS in HCC, indicating the application of 1-yr survival as a secondary endpoint. In particular, PFS HR was a potential SE for OS HR in the ICI trials.

Abstract The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

ABSTRACTDeposition path patterns play an important role in controlling residual stresses and deformation in direct energy deposition-arc (DED-arc) process. In this paper, the effects of various path patterns on the evolution of the temperature history, residual stress distribution, and substrate deformations are investigated through experiments and finite element analysis. The predicted results of temperature fields and substrate deformations are verified experimentally by the infrared thermal imager and the laser profile scanner, respectively. It is found that the path patterns have significant effects on the stress distribution in the first few layers, and the minimum substrate deformation is obtained by the zigzag path along the short edge of the block. The proposed finite element method and measuring method are confirmed to be effective and feasible, providing valuable insight into the residual stresses and deformations control in the DED-arc process.

Abstract The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. The scRNA‐seq and bulk RNA‐seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single‐cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan‐cancer patients. The proportion of APOE+ macrophages is higher in ICI non‐responders of triple‐negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real‐world immunotherapy data accurately predicts the ICI response of pan‐cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells.

Abstract Contact resistance has become one of the main bottlenecks that hinder further improvement of mobility and integration density of organic field‐effect transistors (OFETs). Much progress has been made in reducing contact resistance by modifying the electrode/semiconductor interface and decreasing the crystal thickness, however, the development of new organic semiconductor materials with low contact resistance still faces many challenges. Here, 2,6‐bis‐phenylethynyl‐anthracene (BPEA) is found, which is a material that combines high mobility with low contact resistance. Single‐crystal BEPA OFETs with a thickness of ≈20 nm demonstrated high mobility of 4.52 cm2 V−1 s−1, contact resistance as low as 335 Ω cm, and band‐like charge transport behavior. The calculated compatibility of the EHOMO of BPEA with the work function of the Au electrode, and the decreased |EHOMO‐ΦAu| with the increase of external electric field intensity from source to gate both contributed to the efficient charge injection and small contact resistance. More intriguingly, p‐type BPEA as a buffer layer can effectively reduce the contact resistance, improve the mobility, and meanwhile inhibit the double‐slope electrical behavior of p‐channel 2,6‐diphenyl anthracene (DPA) single‐crystal OFETs.

Introduction: IL4I1, also known as Interleukin-4-induced gene 1, is an enzyme that can modulate the immune system by acting as a L-amino acid oxidase. Nevertheless, a precise understanding of the correlation of IL4I1 with immunological features and immunotherapy efficacy in bladder cancer (BLCA) remains incomplete.Methods: We analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) to investigate the immune function and prognostic importance of IL4I1 across different cancer types. We further examined the TCGA-BLCA cohort for correlations between IL4I1 and various immunological characteristics of tumor microenvironment (TME), such as cancer immune cycle, immune cell infiltration, immune checkpoint expression and T cell inflamed score. Validation was conducted using two independent cohort, GSE48075 and E-MTAB-4321. Finally, RNA sequencing data from the IMvigor210 cohort and immunohistochemistry assays were employed to validate the predictive value of IL4I1 for the TME and immunotherapy efficacy.Results: In our findings, a positive correlation was observed between IL4I1 expression and immunomodulators expression, immune cell infiltration, the cancer immune cycle, and T cell inflamed score in BLCA, suggesting a significant link to the inflamed TME. In addition, studies have shown that IL4I1 elevated levels of individuals tend to be more performance for basal subtype and exhibit enhanced response rates to diverse treatment modalities, specifically immunotherapy. Clinical data from the IMvigor 210 cohort confirmed a higher rate of response to immunotherapy and better survival benefits in patients with high IL4I1 expression.Discussion: To summarize, our research showed that elevated IL4I1 levels are indicative of an inflamed TME, the basal subtype, and a more favorable response to various treatment methods, especially immune checkpoint blockade therapy in BLCA.

ABSTRACTPortal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn’s disease and thyroid diseases. Graves’ disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

Objectives: To enhance the ability of predicting self-harm behaviors through multidimensional data and machine learning methods, and provide a foundation for future comprehensive interventions. Methods: One hundred and twelve young adults aged 18-22 years with self-harm behaviors participated in this study as an experimental group, 98 in the control group. Eighty-three social-demographic and genetic features were collected and analyzed by an extreme gradient boosting (XGBoost) approach. Results: We found significant differences in social-demographic and genetic features between the self-harm and control groups (p

Abstract This paper is devoted to the distributed demand response (DR) charging control of plug‐in electric vehicles (PEVs) for frequency regulation in power systems in terms of load following service. Specifically, PEVs are divided into different clusters according to their parking place under different energy management systems. Each EV cluster is modelled by a transport‐based load aggregate model with the input being the charging rate, and the output is the aggregate power. Based on the aggregate charging control model, a novel dynamic real‐time distributed pinning control algorithm is proposed to coordinate the charging rates such that the aggregate charging power of PEVs can follow a given reference power trajectory. The theoretical analysis shows that if the reference power profile is in the trackable area of all PEVs' charging power and the ramping rate is restrained by a predefined bounded constraint, then the demand response charging tracking control is solvable. Finally, simulation results on an EV system with twelve PEV clusters are presented to show the effectiveness of the proposed demand response control algorithm.

Graphidessa jinfoensis sp. nov. is described from Chongqing and Guizhou in Southwest China. The diagnostic morphological characters of the new species are described and illustrated in color plates. The distribution of all species of the genus Graphidessa Bates, 1884 is mapped and the key to all species of this genus is updated. The COI gene sequence of the new species is also provided.

Abstract Background Lifestyle change plays a crucial role in the prevention and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). In recent years, diet soft drinks that emphasize “zero sugar and zero calories” have become all the rage, but whether diet soft drink consumption is associated with MASLD is not clear. Methods This study included data from the National Health and Nutrition Examination Surveys (NHANES) in 2003–2006. The assessment of MASLD status primarily relied on the Fatty Liver Index (FLI). Weighted multiple Logistic regression models were constructed to evaluate the association between diet soft drink consumption and MASLD. Additionally, mediation analysis was performed to examine the mediating effect of body mass index (BMI). Results A total of 2,378 participants were included in the study, among which 1,089 individuals had MASLD, and the weighted prevalence rate was 43.64%. After adjusting for variables related to demographic, lifestyle, and metabolic syndrome, excessive diet soft drink consumption (the “always” frequency) remained significantly associated with the occurrence of MASLD (OR = 1.98, 95%CI = 1.36–2.89, P = 0.003). It was estimated that 84.7% of the total association between diet soft drink consumption and MASLD was mediated by BMI (P

Abstract Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Abstract Objectives To investigate the optimal parameters of spectral CT for preferably visualizing the periprosthetic vasculature and metal artifact reduction (MAR) in total hip arthroplasty (THA). Methods A total of 34 THA of 30 patients were retrospectively included. Image reconstructions included conventional image (CI), CI combined with MAR (CIMAR), and virtual monoenergetic images (VMI) combined with MAR (VMIMAR) at 50–120 keV. The attenuation and standard deviation of the vessel and artifact, and the width of artifact were measured. Qualitative scoring was evaluated including the vascular contour, the extent of artifact, and overall diagnostic evaluation. Results The attenuation, noise of the vessel and artifact, and the width of artifact decreased as the energy level increased (p

Abstract Linear biometric measurements on magnetic resonance images are important for the assessment of fetal brain development, which is expert knowledge dependent and laborious. This study aims to construct a segmentation-based method for automatic two-dimensional biometric measurements of fetal brain on magnetic resonance images that provides a fast and accurate measurement of fetal brain. A total of 268 volumes (5360 images) magnetic resonance images of normal fetuses were included. The automatic method involves two steps. First, the fetal brain was segmented into four parts with a deep segmentation network: cerebrum, cerebellum, and left and right lateral ventricles. Second, the measurement plane was determined, and the corresponding biometric parameters were calculated according to clinical guidelines, including cerebral biparietal diameter (CBPD), transverse cerebellar diameter (TCD), left and right atrial diameter (LAD/RAD). Pearson correlation coefficient and Bland–Altman plots were used to assess the correlation and agreement between computer-predicted values and manual measurements. Mean differences were used to evaluate the errors quantitatively. Analysis of fetal cerebral growth based on the automatic measurements was also displayed. The experiment results show that correlation coefficients for CBPD, TCD, LAD and RAD were as follows: 0.977, 0.990, 0.817, 0.719, mean differences were − 2.405 mm, − 0.008 mm, − 0.33 mm, − 0.213 mm, respectively. The correlation between the errors and gestational age was not statistically significant (p values were 0.2595, 0.0510, 0.1995, and 0.0609, respectively). The proposed automatic method for linear measurements on fetal brain MRI achieves excellent performance, which is expected to be applied in clinical practice and be helpful for prenatal diagnosis and clinical work efficiency improvement.

ObjectiveUlcerative colitis (UC) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely intertwined; however, the precise molecular mechanisms governing their coexistence remain unclear.MethodsWe obtained UC (GSE75214) and MASLD (GSE151158) datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired by the ‘edgeR’ and ‘limma’ packages of R. We then performed functional enrichment analysis of common DEGs. Hub genes were selected using the cytoHubba plugin and validated using GSE87466 for UC and GSE33814 for MASLD. Immunohistochemistry was employed to validate the hub genes’ expression in clinical samples. Immune infiltration and gene set enrichment analyses of the hub genes were performed. Finally, we estimated the Spearman’s correlation coefficients for the clinical correlation of the core genes.ResultsWithin a cohort of 26 differentially regulated genes in both UC and MASLD, pathways involving cytokine-mediated signaling, cell chemotaxis, and leukocyte migration were enriched. After further validation, CXCR4, THY1, CCL20, and CD2 were identified as the hub genes. Analysis of immune infiltration patterns highlighted an association between elevated pivotal gene expression and M1 macrophage activation. Immunohistochemical staining revealed widespread expression of pivotal genes in UC- and MASLD-affected tissues. Furthermore, significant correlations were observed between the increased expression of hub genes and biochemical markers, such as albumin and prothrombin time.ConclusionThis bioinformatics analysis highlights CXCR4, THY1, CCL20, and CD2 as crucial genes involved in the co-occurrence of UC and MASLD, providing insights into the underlying mechanisms of these two conditions.

Unmanned aerial vehicles (UAVs) have been generally applied in the field of communication due to their small size, flexible mobility, and convenient deployment. As a mobile base station, the UAV node can quickly establish a line-of-sight link with the ground node, thereby improving communication performance. In this paper, we study a multi-UAV assisted data collecting system. Specifically, in the case of limited system energy consumption, UAV flight energy consumption and ground node data transmission energy consumption are considered as an general limitation, and considering the channel interference between nodes, a multi-UAV assisted data collection model is studied. An non-convex problem that maximizes the minimum amount of data collected from ground nodes is further formulated. Since the original optimization problem is non-convex that difficult to solve directly, the problem is first decomposed into four sub-problems, and then the solution of each sub-problem is obtained by using successive convex approximation and block coordinate descent method. Finally, based on the solution of the four subproblems, an iterative algorithm for joint optimization of data transmission planning, transmission power, UAV trajectory and mission time is proposed. Simulation experiments show that the proposed algorithm can obtain more transmission data than the baseline algorithms.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Abstract Biomass‐based hydrogel is a promising flame‐retardant material and has a high potential for applications in transportation, aerospace, building and electrical engineering, and electronics. However, rapid vat photopolymerization (VP) 3D printing of biomass‐based hydrogels, especially that of all‐natural ones, is still rare. Herein, a new class of VP 3D‐printed hydrogels with strong covalent networks, fabricating using fully biomass materials and a commercial liquid crystal display (LCD) printer assembled with low‐intensity visible light is presented. Encouragingly, the highly ordered layer‐by‐layer packing structures provided by VP 3D printing technology endow these hydrogels with remarkable flame retardancy, exceptional temperature resistance, advantageous combustion behaviors, and favorable mechanical strength, in particular, giving them a better limit oxygen index (83.5%) than various biomass‐based hydrogels. The proposed approach enables the green design as well as the precise and efficient preparation for flame‐retardant materials, paving the way for the future flame‐retardant materials toward attaining green sustainability.

IntroductionVisual hallucination is a prevalent psychiatric disorder characterized by the occurrence of false visual perceptions due to misinterpretation in the brain. Individuals with Parkinson’s disease often experience both minor and complex visual hallucinations. The underlying mechanism of complex visual hallucinations in Parkinson’s patients is commonly attributed to dysfunction in the visual pathway and attention network. However, there is limited research on the mechanism of minor hallucinations.MethodsTo address this gap, we conducted an experiment involving 13 Parkinson’s patients with minor hallucinations, 13 Parkinson’s patients without hallucinations, and 13 healthy elderly individuals. We collected and analyzed EEG and MRI data. Furthermore, we utilized EEG data from abnormal brain regions to train a machine learning model to determine whether the abnormal EEG data were associated with minor hallucinations.ResultsOur findings revealed that Parkinson’s patients with minor hallucinations exhibited excessive activation of cortical excitability, an imbalanced interaction between the attention network and the default network, and disruption in the connection between these networks. These findings is similar to the mechanism observed in complex visual hallucinations. The visual reconstruction of one patient experiencing hallucinations yields results that differ from those observed in subjects without such symptoms.DiscussionThe visual reconstruction results demonstrated significant differences between Parkinson’s patients with hallucinations and healthy subjects. This suggests that visual reconstruction techniques may offer a means of evaluating hallucinations.

Abstract Aim Patients with chronic liver disease (CLD), especially cirrhosis, are at a high risk of severe illness or death from coronavirus disease‐2019 (COVID‐19) and may have a suboptimal immune response to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine. This study aimed to evaluate the safety and immunogenicity of the COVID‐19 booster vaccination in patients with CLD. Methods The study protocol was prospectively registered at ClinicalTrials.gov (No. NCT05204602) after approval by the Ethics Committee. Adult participants with CLD were enrolled in this multicenter prospective study. They completed two doses of the inactivated COVID‐19 vaccine and received booster doses at least 6 months later. Adverse reactions were recorded within 14 days after the booster dose. Serum samples of the enrolled patients were collected before and after booster vaccination and tested for SARS‐CoV‐2 receptor‐binding domain (RBD) immunoglobulin G and neutralizing antibodies. The chi‐squared or Fisher's exact test was used to compare categorical data, and the Mann–Whitney U test was used to compare continuous variables. Two‐sided p

Abstract The association between specific genetic mutations and immunotherapy benefits has been widely known, while such studies in pan-cancer are still limited. SPEN, mainly involved in X chromosome inactivation (XCI), plays an essential in tumorigenesis and sex differences in cancer. Thus, we firstly analyzed the potential role of SPEN in the TCGA pan-cancer cohort and clinical samples. Bioinformatics analysis and immunohistochemistry (IHC) staining confirm that the expression of SPEN is significantly different in various cancers and may involve RNA splicing and processing via enrichment analysis. Then, our data further revealed that those patients with SPEN mutation could predict a better prognosis in pan-cancer and had distinct immune signatures, higher tumor mutation burden (TMB), and microsatellite instability (MSI) in common cancer types. Finally, the cancer patients from 9 studies treated with immune checkpoint inhibitors were included to investigate the efficacy of immunotherapy. The results further showed that SPEN mutation was associated with better clinical outcomes (HR, 0.74; 95%CI, 0.59–0.93, P = 0.01), and this association remained existed in female patients (HR, 0.60; 95%CI, 0.38–0.94 P = 0.024), but not in male patients (HR, 0.82; 95%CI, 0.62–1.08 P = 0.150). Our findings demonstrated that SPEN mutation might strongly predict immunotherapy efficacy in pan-cancer.

Abstract Timely and remote biomarker detection is highly desired in personalized medicine and health protection but presents great challenges in the devices reported so far. Here, we present a cost-effective, flexible and self-powered sensing device for H2S biomarker analysis in various application scenarios based on the structure of galvanic cells. The sensing mechanism is attributed to the change in electrode potential resulting from the chemical adsorption of gas molecules on the electrode surfaces. Intrinsically stretchable organohydrogels are used as solid-state electrolytes to enable stable and long-term operation of devices under stretching deformation or in various environments. The resulting open-circuit sensing device exhibits high sensitivity, low detection limit, and excellent selectivity for H2S. Its application in the non-invasive halitosis diagnosis and identification of meat spoilage is demonstrated, emerging great commercial value in portable medical electronics and food security. A wireless sensory system has also been developed for remote H2S monitoring with the participation of Bluetooth and cloud technologies. This work breaks through the shortcomings in the traditional chemiresistive sensors, offering a direction and theoretical foundation for designing wearable sensors catering to other stimulus detection requirements.

Objective: A method for simultaneous determination of 17 β-receptor agonists in meat was established by QuEChERS EMR-Lipid with isotope dilution-ultra performance liquid chromatography-tandem mass spectrometry. Methods: The samples were added to ammonium acetate buffer solution (pH5.2) and enzymatic hydrolyzed by β-glucuronidase and arysulfatase. The hydrolysates were extracted by acetonitrile containing 5% formic acid, and purified by QuEChERS EMR-Lipid. The analyses were separated by CORTECS™ UPLC® C18 chromatographic column with gradient elution using 0.1% formic acid and methanol as the mobile phase. The target compounds were monitored in scheduled MRM mode. Then the internal standard method was used for quantitative analysis. Results: The linear regression correlation coefficients for the 17 β-receptor agonists were all higher than 0.99 in the range from 0 ng/mL to 20 ng/mL. The limits of detection were 0.01~0.09 μg/kg and the limits of quantification were 0.05~0.31 μg/kg. The average recoveries at three spiked levels of 0.5, 2.0 and 5.0 μg/kg ranged from 81.7% to 111.8% with the relative standard deviations of 0.8%~10.3% (n=6). No β-receptor agonists were detected in 100 batches of fresh meat. Conclusion: The method has the advantages of simple pretreatment steps and good purification effect. It shortened enzymolysis time, improved sample detection efficiency. The internal standard method was accurate and reliable. It was suitable for simultaneous determination of β-receptor agonists in a large number of meat samples.

Background: The accuracy of decoding fine motor imagery (MI) tasks remains relatively low due to the dense distribution of active areas in the cerebral cortex. Methods: To enhance the decoding of unilateral fine MI activity in the brain, a weight-optimized EEGNet model is introduced that recognizes six types of MI for the right upper limb, namely elbow flexion/extension, wrist pronation/supination and hand opening/grasping. The model is trained with augmented electroencephalography (EEG) data to learn deep features for MI classification. To address the sensitivity issue of the initial model weights to classification performance, a genetic algorithm (GA) is employed to determine the convolution kernel parameters for each layer of the EEGNet network, followed by optimization of the network weights through backpropagation. Results: The algorithm’s performance on the three joint classification is validated through experiment, achieving an average accuracy of 87.97%. The binary classification recognition rates for elbow joint, wrist joint, and hand joint are respectively 93.92%, 90.2%, and 94.64%. Thus, the product of the two-step accuracy value is obtained as the overall capability to distinguish the six types of MI, reaching an average accuracy of 81.74%. Compared to commonly used neural networks and traditional algorithms, the proposed method outperforms and significantly reduces the average error of different subjects. Conclusions: Overall, this algorithm effectively addresses the sensitivity of network parameters to initial weights, enhances algorithm robustness and improves the overall performance of MI task classification. Moreover, the method is applicable to other EEG classification tasks; for example, emotion and object recognition.

Abstract Background Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 and triggers the expression of NF-κB and NLRP3 inflammasomes, inducing pyroptosis and inflammatory response. However, whether mtDNA induces NPC pyroptosis via the TLR9-NF-κB-NLRP3 axis and promotes IVDD remains uncertain. Methods We constructed an in vitro NPC oxidative stress injury model to clarify the mechanism of mtDNA release, TLR9-NF-κB signaling pathway activation, and NPC injury. We further verified the mechanism of action underlying the inhibition of mtDNA release or TLR9 activation in NPC injury in vitro. We then constructed a rat punctured IVDD model to understand the mechanism inhibiting mtDNA release and TLR9 activation in IVDD. Results We used human NP specimen assays to show that the expression levels of TLR9, NF-κB, and NLRP3 inflammasomes correlated with the degree of IVDD. We demonstrated that mtDNA mediated TLR9-NF-κB-NLRP3 axis activation in oxidative stress-induced human NPC pyroptosis in vitro. Oxidative stress can damage the mitochondria of NPCs, causing the opening of the mitochondrial permeability transition pores (mPTP) and leading to the release of mtDNA into the cytosol. Furthermore, inhibition of mPTP opening or TLR9 activation blocked TLR9-NF-κB-NLRP3 axis activation and thereby mediated NPC pyroptosis and IVDD. Conclusion mtDNA plays a key role in mediating NPC pyroptosis and IVDD via the TLR9-NF-κB-NLRP3 axis. Our findings provide new potential targets for IVDD.

Abstract Background Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the diagnosis and treatment of rmTBI are quite limited. Methods We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery efficiency and specific target of IgG while reducing the effective therapeutic dose of the drug. Results Our results demonstrated that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also effectively inhibit the activation of microglia and the release of inflammatory factors. Conclusions In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG.

Highlights A systematic summary of the research progress of hydrogel-based gas and humidity sensors is presented. The sensing mechanism of hydrogel-based gas and humidity sensors is elaborated. The potential of hydrogel-based vapor sensors in different fields of application is demonstrated.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is highly aggressive with a significant tropism of lymph nodes, which restricts treatment options and negatively impacts patient outcomes. Although progress has been made in understanding the molecular mechanisms underlying lymphatic metastasis (LM), these mechanisms remain elusive. ANXA6 is a scaffold protein that participates in tumor pathogenesis and autophagy regulation; however, how ANXA6 affects autophagy and LM in HNSCC cells remains unknown. Methods RNA sequencing was performed on HNSCC clinical specimens with or without metastasis as well as on The Cancer Genome Atlas dataset to investigate ANXA6 expression and survival. Both in vitro and in vivo studies were performed to investigate the role of ANXA6 in the regulation of LM in HNSCC. The molecular mechanism by which ANXA6 interacts with TRPV2 was examined at the molecular level. Results ANXA6 expression was significantly upregulated in HNSCC patients with LM and higher expression was associated with poor prognosis. ANXA6 overexpression promoted the proliferation and mobility of FaDu and SCC15 cells in vitro; however, ANXA6 knockdown retarded LM in HNSCC in vivo. ANXA6 induced autophagy by inhibiting the AKT/mTOR signaling pathway in HNSCC, thereby regulating the metastatic capability of the disease. Furthermore, ANXA6 expression positively correlated with TRPV2 expression both in vitro and in vivo. Lastly, TRPV2 inhibition reversed ANXA6-induced autophagy and LM. Conclusions These results indicate that the ANXA6/TRPV2 axis facilitates LM in HNSCC by stimulating autophagy. This study provides a theoretical basis for investigating the ANXA6/TRPV2 axis as a potential target for the treatment of HNSCC, as well as a biomarker for predicting LM.