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Abstract Background Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. Methods Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. Results Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. Conclusion This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

The deterioration of winding defects is one of the important causes of power transformer fires and even explosion failures. The change of leakage magnetic field distribution is the most direct response to winding defects. Currently there are few sensors suitable for online measurement of the internal magnetic field of transformers. Based on the Faraday magneto-optical effect, a magnetic field sensor with wide range and high sensitivity is proposed in this paper, which is suitable for the interior use of transformers. The straight-through optical structure with interior polarizer is adopted, and the sensor has a measurement range of 1.5 T and a sensitivity of 1 mT. It also possesses a small size, with a length of about 30 mm after encapsulation. The influence mechanism of vibration and temperature is revealed through theoretical analysis and numerical simulation. It is proposed to filter out the interference of vibration by characteristic frequency analysis and to compensate for temperature by a two-probe structure. An anti-interference test verifies the effectiveness of this method, and it can reduce the error from 80.56% to 2.63% under the combined interference of vibration and temperature.

Abstract Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

Abstract Background Mobility limitation—the loss of exercise capacity or independent living ability—is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled “A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)” to explore the effect of the MDT decision-making intervention for mobility limitation. Methods The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form − 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores. Conclusion Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life. Trial registration ChiCTR, ChiCTR2200056756, Registered 19 February 2022.

With the rapid development and widespread implementation of all types of ophthalmic surgery, more attention is being paid to the quality of post-operative vision. Dry eye is a common complication after ophthalmic surgery, often causing eye discomfort, blurred vision and other dry eye symptoms. Ophthalmic surgery-related dry eye is a common type of dry eye and is usually caused by a combination of surgical injury to the conjunctival tissue and nerves, destabilisation of the tear film, postoperative inflammatory reaction and perioperative topical medication. This article reviews the risk factors for ophthalmic surgery-related dry eye, the pathogenesis of dry eye due to different ophthalmic surgeries and the prevention of this type of dry eye, with the aim of reducing the occurrence and development of ophthalmic surgery-related dry eye and improving the quality of vision and life after ophthalmic surgery in the clinical setting.

Scientometric analysis is a useful tool that utilizes bibliometric data to measure scientific output of a disease or region in a particular field. In this report, we comprehensively provide bibliometric characteristics of all the papers on betel quid (BQ)-related cancer and precancerous lesions. There are 1403 papers on BQ-related cancer and precancerous lesions published until 2022 in the Scopus database. China (mainland and Taiwan region), India, United States, and United Kingdom contribute 1214 (86.5%) papers and 34,120 (91.9%) citations of all the papers. The number (457), citations (14,573), and h index (60) of the papers originated from Taiwan region stably remain in the first. The most frequent research keyword is arecoline, followed by drug, prevalence, metabolism, carcinogenesis, and pathology. Areca nut and BQ cessation program by Taiwan government has demonstrated a significant positive impact on oral cancer prevention. Collectively, the scientific output of BQ-related cancer and precancerous field represents distinct regional characteristic. BQ-related cancer prevention is still a long way off. Encouragingly, Taiwan region is well ahead in this way.

BackgroundThe CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS.MethodsWe prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients’ peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection.ResultsOf the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days.ConclusionWe identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

(1) Background: The effective selection of hyperspectral feature bands is pivotal in monitoring the nutritional status of intricate alpine grasslands on the Qinghai–Tibet Plateau. The traditional methods often employ hierarchical screening of multiple feature indicators, but their universal applicability suffers due to the use of a consistent methodology across diverse environmental contexts. To remedy this, a backward feature elimination (BFE) selection method has been proposed to assess indicator importance and stability. (2) Methods: As research indicators, the crude protein (CP) and chlorophyll (Chl) contents in degraded grasslands on the Qinghai–Tibet Plateau were selected. The BFE method was integrated with partial least squares regression (PLS), random forest (RF) regression, and tree-based regression (TBR) to develop CP and Chl inversion models. The study delved into the significance and consistency of the forage quality indicator bands. Subsequently, a path analysis framework (PLS-PM) was constructed to analyze the influence of grassland community indicators on SpecChl and SpecCP. (3) Results: The implementation of the BFE method notably enhanced the prediction accuracy, with ΔR2RF-Chl = 56% and ΔR2RF-CP = 57%. Notably, spectral bands at 535 nm and 2091 nm emerged as pivotal for CP prediction, while vegetation indices like the PRI and mNDVI were critical for Chl estimation. The goodness of fit for the PLS-PM stood at 0.70, indicating the positive impact of environmental factors such as grassland cover on SpecChl and SpecCP prediction (rChl = 0.73, rCP = 0.39). SpecChl reflected information pertaining to photosynthetic nitrogen associated with photosynthesis (r = 0.80). (4) Disscusion: Among the applied model methods, the BFE+RF method is excellent in periodically discarding variables with the smallest absolute coefficient values. This variable screening method not only significantly reduces data dimensionality, but also gives the best balance between model accuracy and variables, making it possible to significantly improve model prediction accuracy. In the PLS-PM analysis, it was shown that different coverage and different community structures and functions affect the estimation of SpecCP and SpecChl. In addition, SpecChl has a positive effect on the estimation of SpecCP (r = 0.80), indicating that chlorophyll does reflect photosynthetic nitrogen information related to photosynthesis, but it is still difficult to obtain non-photosynthetic and compound nitrogen information. (5) Conclusions: The application of the BFE + RF method to monitoring the nutritional status of complex alpine grasslands demonstrates feasibility. The BFE filtration process, focusing on importance and stability, bolsters the system’s generalizability, resilience, and versatility. A key research avenue for enhancing the precision of CP monitoring lies in extracting non-photosynthetic nitrogen information.

Abstract Background Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen–glucose deprivation (OGD). Methods We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. Results Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. Conclusions We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

Grassland, as a key component of the carbon cycle in terrestrial ecosystems, is vital in confronting global climate change. Characterising the carbon density of grassland ecosystems in the Longzhong Loess Plateau is important for accurately assessing the contribution of grasslands to global climate change and achieving the goal of “peak carbon” and “carbon neutral”. In this study, the Longzhong Loess Plateau was used as the research object to explore changes in the plant–soil system carbon density in two grassland types by analysing the aboveground vegetation biomass carbon density, belowground vegetation biomass carbon density, 0–100 cm soil carbon density, and ecosystem carbon density of temperate steppe and temperate desert. The results showed that the vegetation biomass (standing and living, litter, and belowground biomass), soil, and ecosystem carbon densities of the temperate steppe were significantly higher than those of the temperate desert (p < 0.05). Their carbon densities were 700.51, 7612.95, and 8313.45 g·m−2, respectively. The vertical distribution of belowground biomass and soil carbon density in the temperate steppe was significantly higher than that in the temperate desert. The overall trend of belowground biomass carbon density in the temperate steppe and temperate desert showed a gradual decrease, whereas soil carbon density showed a steady increase. More than 91% and 96% of the carbon was stored in soil in the temperate steppe and temperate desert, respectively, and the belowground biomass carbon stock accounted for more than 84% of the total biomass carbon pools in both temperate steppe and temperate desert. Temperate steppe has a significant effect in improving the carbon stock of grassland ecosystems, so ecological protection and restoration of grassland should be strengthened in the future to enhance the capacity of grassland to sequester carbon and increase sinks.

Abstract Pyroptosis is a kind of programmed cell death primarily mediated by gasdermin D (GSDMD) and shown to regulate multiple diseases. However, its contribution to liver regeneration, a fine‐tuned tissue repair process mediated primarily by hepatocytes after mass loss, remains unclear. Herein, we found that caspase‐11/GSDMD‐mediated pyroptosis was activated in regenerating liver after 70% partial hepatectomy. Impeding pyroptosis by deleting GSDMD significantly reduced liver injury and accelerated liver regeneration. Mechanistically, GSDMD deficiency up‐regulates the activation of hepatocyte growth factor/c‐Met and epidermal growth factor receptor mitogenic pathways at the initiation phase. Moreover, activin A and glypican 3 (GPC3), two terminators of liver regeneration, were inhibited when GSDMD was absent. In vitro study suggested the expressions of activin A and GPC3 were induced by interleukin (IL)–1β and IL‐18, whose maturations were regulated by GSDMD‐mediated pyroptosis. Similarly, pharmacologically inhibiting GSDMD recapitulates these phenomena. Conclusion: This study characterizes the role of GSDMD‐mediated pyroptosis in liver regeneration and lays the foundation for enhancing liver restoration by targeting GSDMD in liver patients with impaired regenerative capacity.

BackgroundIn China, involution, which means pressure to out-compete other group members, has attracted public attention on Weibo. The new online connotation of involution empowered group cohesion among youth. Dissimilar to other crises, this crise also closely relates to group cohesion concept. However, few previous group cohesion-related studies focus on this critical concept. This study explains why and how youth created group cohesion online when facing involution. First, by examining the relationship between involution and group cohesion. Second, by examining whether youth are united in the online discussion of involution by investigating the generational gap. Following this, this study analyzes the different opinions to identify why this group cohesion occurs, how youth think about involution, and why they regard “older adults” as others. Lastly, this study analyzes how youth use hashtags to attract more youth to voice their opinions, consequently leading to greater group cohesion.MethodsBy combining frontier computational methods with causation and axial coding, this study proposes a new way to in-depth analyze group cohesion on social media.ResultsThe results indicate that involution triggers poor online group cohesion, and online involution-related hot issues trigger identity-based group cohesion. Additionally, youth are significantly more negative than older adults, and their expressions are full of identity-based construction. By stressing the social roots and blaming the “other” (older adult group), youth united together online. These findings indicated that a generation gap does indeed exist and that youth unite on social media by posting related hashtags via “revealing social identity” and “positioning and becoming” strategies.ConclusionThe findings stress that involution is related to poor group cohesion and that social media offers a new way to face the involution crisis. Youth will use hashtags to unite and blame imagined enemies, such as older adults and the upper class. These findings might assist in understanding interventions that lead to more group cohesion.

Abstract Background Inflammatory myofibroblastic tumors in the head and neck (HNIMTs) sometimes show aggressive clinical features and can be diagnosed as HNIMT with malignant transformation. Methods The clinicopathological features of 45 HNIMTs with or without malignant transformation were retrospectively investigated. Logistic regression and receiver operating characteristic analysis were used to establish the predictive model. Results HNIMT with malignant transformation was associated with worse prognosis. HNIMT with a tumor size of >4.4 cm, tumors located in the maxillary sinus, or a preoperative neutrophil‐to‐lymphocyte ratio (NLR) greater than 1.958 were associated with higher chance of malignant transformation, with an AUC value of 0.9189. Postoperative radiotherapy could benefit HNIMT patients with high risk of malignant transformation. Conclusions HNIMT patients with a tumor size of >4.4 cm, tumors located in the maxillary sinus, and a preoperative NLR over 1.958 were associated with a higher risk of malignant transformation. These patients can benefit from postoperative radiotherapy.

Abstract Objective Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. Materials and methods The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. Results OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P

Abstract Purpose Malignant pleural effusion (MPE) is an adverse prognostic factor in patients with osteoblastic osteosarcoma; however, the cellular contexts of MPE are largely unknown. Experimental design We performed single‐cell RNA‐sequencing (scRNA‐seq) on 27 260 cells from seven MPE samples and 91 186 cells from eight osteosarcoma tissues, including one recurrent, one lung metastasis and six primary tumour (PT) samples, to characterize their tumour microenvironment. Results Thirteen main cell groups were identified in osteosarcoma tumour and MPE samples. Immune cells dominate the cellular contexts in MPE with more T/NK cells and less osteoclasts compared to PT samples. Of T/NK cells, CD8+GNLY+, CD8+KLRC2+ T cells and FCGR3A+NK cells were enriched in MPE but CD4+FOXP3+ Tregs were enriched in PT samples. Naïve IGHD+ B and immune regulatory IGHA1+ B cells were largely identified in MPE, whereas bone metabolism‐related CLEC11A+ B cells were significantly enriched in osteosarcoma PT. M2‐type TAMs, including CLEC11A_TAM, C1QC_TAM and Prolif_TAMs, among myeloid cells were enriched in PT, which may suppress cytotoxicity activities of T cells through multiple ligand–receptor interactions. Mature LAMP3+ DCs were transformed from CD1C+ DC and CLEC9A+ DC sub‐clusters when exposure to tumour alloantigens, which may improve T cell cytotoxicity activities on tumour cells under anti‐PD‐L1 treatments. In further, immune cells from MPE usually present up‐regulated glycolysis and down‐regulated oxidative phosphorylation and riboflavin metabolism activities compared to those in PT samples. Conclusions Our study provided a novel cellular atlas of MPE and PT in patients with advanced osteosarcoma, which may provide potential therapeutic targets in the future.

Sustainable structural materials with fully bio-based building blocks and great mechanical properties are vitally important for practical application. However, the challenges on how to evitable use petrochemical-based adhesive, improve their comprehensive mechanical strength, and reduce energy and time consumption still remain. Here, we report a robust and effective strategy with micro/nanoscale structure design to fabricate a mechanically strong and sustainable wood-derived structural material from fast-growing wood. Owing to the synergistic effect of aligned cellulose fiber, multi-layer structure, and hydrogen bonds, the obtained structural materials exhibited high mechanical properties of 158 MPa, high interfacial bonding strength of 1.13 MPa, and great Shore D hardness of 68.7. The role of hydrogen bonds in enhancing mechanical properties was also revealed. In addition, the adhesive and polymer are not used in the whole process, and the consumption of energy and time is reduced. The novel fully wood-derived materials provide more structural material selection and more micro/nanoscale structure design ideas.

ObjectiveMalnutrition is a nutritional disorder and common syndrome that has a high incidence and is easily ignored in hospitalized older patients. It can lead to multiple poor prognoses, such as frailty. Early identification and correct evaluation of possible malnutrition and frailty are essential to improve clinical outcomes in older patients. Therefore, our objective was to explore the applicability and effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) criteria for identifying malnutrition in older patients.MethodsIn total, 223 participants aged ≥60 years were involved. Nutrition was evaluated using the Mini Nutritional Assessment-Full Form (MNA-FF) and GLIM criteria, which adopt a two-step procedure. The first step was to use three different methods for the screening of nutritional risk: the Nutrition Risk Screening 2002, the Mini Nutritional Assessment Short Form (MNA-SF), and the Malnutrition Universal Screening Tool. The second step was to link a combination of at least one phenotypical criterion and one etiological criterion to diagnose malnutrition. The Clinical Frailty Scale was used to assess frailty. Sensitivity, specificity, Youden index, kappa values, and positive and negative predictive values were used to evaluate the validity of the GLIM criteria. Logistic regression models were used to assess whether there was a correlation between malnutrition, as defined by the GLIM criteria, and frailty.ResultsWe found that 32.3–49.8% of our patient sample were at risk of malnutrition based on the GLIM diagnosis and using the three different screening tools; 19.3–27.8% of the patients were malnourished. GLIM criteria with MNA-SF as a diagnostic validation and MNA-FF as a reference showed high consistency (K = 0.629; p < 0.001), sensitivity (90.5%), and specificity (86.4%). Logistic regression analysis showed that malnutrition, using MNA-SF with the GLIM criteria, was relevant for a higher likelihood of frailty (OR = 1.887; 95% CI 1.184–2.589).ConclusionsThe incidence of GLIM-defined malnutrition was 19.3–27.8% using different screening tools. The consistency between the GLIM criteria using the MNA-SF and the MNA methods was high. Malnutrition, as diagnosed by the GLIM criteria with MNA-SF, was significantly correlated with frailty. GLIM criteria with MNA-SF may be a more reliable malnutrition assessment process in older inpatients.

BackgroundIn hospital settings, malnutrition affects 30–50% of aged inpatients and is related to a higher risk of hospital complications and death. This study aims to demonstrate the effectiveness of a tailored optimum nutritional therapy in malnourished, elderly inpatients based on multidisciplinary team recommendations in hopes of decreasing the incidence of deleterious clinical outcomes.Methods and DesignThis trial will be a multicenter, open-label, randomized control trial conducted in the geriatric wards of at least five hospitals in five different regions. We aim to include 500 inpatients over the age of 60 with or at risk of malnutrition based on a Mini Nutritional Assessment Short-Form (MNA-SF) score of ≤ 11 points and the Global Leadership Initiative on Malnutrition with an expected length of stay of ≥ 7 days. Eligible inpatients will be randomized into a 1:1 ratio, with one receiving a multidisciplinary team intervention and the other receiving standard medical treatment or care alone. A structured comprehensive assessment of anthropometry, nutritional status, cognition, mood, functional performance, and quality of life will be conducted twice. These assessments will take place on the day of group allocation and 1 year after discharge, and a structured screening assessment for elderly malnutrition will be conducted at 3 and 6 months after discharge using the MNA-SF. The primary outcome will be nutritional status based on changes in MNA-SF scores at 3, 6 months, and 1 year. The secondary outcome will be changes in cognition, mood, functional status, length of hospital stay, and all-cause mortality 1 year after discharge.DiscussionGuided by the concept of interdisciplinary cooperation, this study will establish a multidisciplinary nutrition support team that will develop an innovative intervention strategy that integrates nutritional screenings, evaluations, education, consultation, support, and monitoring. Moreover, nutritional intervention and dietary fortification will be provided to hospitalized elderly patients with or at risk of malnutrition. The nutrition support team will formulate a clinical map for malnutrition in elderly patients with standardized diagnosis and treatment for malnutrition in this population.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2200055331].

ObjectiveTo realize the three-dimensional visual output of surgical navigation information by studying the cross-linking of mixed reality display devices and high-precision optical navigators.MethodsApplying quaternion-based point alignment algorithms to realize the positioning configuration of mixed reality display devices, high-precision optical navigators, real-time patient tracking and calibration technology; based on open source SDK and development tools, developing mixed reality surgery based on visual positioning and tracking system. In this study, four patients were selected for mixed reality-assisted tumor resection and reconstruction and re-examined 1 month after the operation. We reconstructed postoperative CT and use 3DMeshMetric to form the error distribution map, and completed the error analysis and quality control.ResultsRealized the cross-linking of mixed reality display equipment and high-precision optical navigator, developed a digital maxillofacial surgery system based on mixed reality technology and successfully implemented mixed reality-assisted tumor resection and reconstruction in 4 cases.ConclusionsThe maxillofacial digital surgery system based on mixed reality technology can superimpose and display three-dimensional navigation information in the surgeon's field of vision. Moreover, it solves the problem of visual conversion and space conversion of the existing navigation system. It improves the work efficiency of digitally assisted surgery, effectively reduces the surgeon's dependence on spatial experience and imagination, and protects important anatomical structures during surgery. It is a significant clinical application value and potential.

Osteosarcoma (OS) is the most common malignant bone tumor. However, treatment strategies have not changed over the past 30 years. The relationship between OS and the immune microenvironment may provide a basis for the establishment of novel therapeutic targets. In this study, a large-scale gene expression dataset (GSE42352) was used to identify key genes in OS. A Target-OS dataset from the Cancer Genome Atlas was used as a validation set. Ecotropic viral integration site 2B (EVI2B) was significantly upregulated in OS tumor samples. Differentially expressed genes (DEGs) were identified between samples with high and low EVI2B expression in both the test and validation cohorts. The top three functions of DEGs determined by a gene set enrichment analysis (GSEA) were chemokine signaling, cytokine–cytokine receptor interaction, and Human T-cell leukemia virus 1 infection. A prognostic prediction model including EVI2B, DOCK2, and CD33 was constructed by a Cox regression analysis. This model indicated that EVI2B is an independent protective prognostic marker in OS. An analysis of immune infiltration further showed that high EVI2B expression levels were correlated with high levels of macrophage infiltration. Protein expression data derived from the Human Protein Atlas suggested EVI2B to be highly expressed in monocytes. Finally, we validated the elevated expression of EVI2B in OS cell lines and OS tissue samples; these results were consistent with those of the analyses of the GSE42352 and Target-OS datasets. Our integrative bioinformatics analysis and experimental results provide clear evidence for the prognostic value of EVI2B in OS and its close relationship with monocyte and macrophage infiltration.

As an important indicator of urban development capacity, vitality can be affected by the human perception of street views, which is a dynamic sensory process that can differ greatly according to different transportation modes, due to their different travel speeds, distances, and routes. However, few studies have evaluated how the dynamic spatial perceptions differ between different travel modes and how these differences can affect vitality differently, due to the limitation of city-scale quantitative data on the dynamic perception of urban scenes. To fill the gap, we propose a “dynamic through-movement perception” (DTMP) measure which integrates a streetscape quality evaluation model with a network-based movement potential model. We measure the streetscape qualities from Baidu street-view images (SVI) and compare the spatial perceptions of drivers and pedestrians in central Guangzhou, China. First, more than twenty visual elements were classified from SVIs to predict human perceptions collected from visual surveys. Second, the through-movement probability of driving and walking were calculated based on classic natural movement theory in space syntax and measured as the angular betweenness for the two travel modes. Third, we accumulate the multipliers of visual perception and through-movement probability of driving and walking as the DTMP for both modes. Lastly, the DTMPs of both modes were fitted into linear regression models to explain street vitality, which is measured using Baidu mobile phone check-in data, when other control variables such as functional density, functional diversity and amenity clustering reachability are accounted for. The results show that the dynamic perception of driving overall shows a stronger correlation with street vitality, while perceived richness is significantly positive in both travel modes. This study provides the first quantitative evidence to reveal how the movement probability of different travel modes can significantly influence people’s sense of place, while in turn increasing street vitality. Our results can explain how different types of street commerce (i.e., pedestrian-oriented, and auto-oriented) aggregate spontaneously due to the dynamic movement potential, which provides an important reference for urban planners and decision makers for improving street vitality when making urban revitalization policies.

Abstract Purpose We report our experience of intensity‐modulated proton and carbon‐ion radiotherapy (IMPT/IMCT) for head and neck sarcomas (HNS). Methods and Materials An analysis of the ongoing prospective data registry from the Shanghai Proton and Heavy Ion Center (SPHIC) for patients with HNS was conducted. The 12‐ and 24‐month rates of local recurrence‐free, overall, distant metastasis‐free, progression‐free survival (LRFS, OS, DMFS, and PFS), and acute/late toxicities were calculated. The prognostic factors for the effectiveness of the treatment were also analyzed. Results Between 7/2014 and 5/2018, 51 consecutive patients with HNS received definitive doses of IMCT (41 cases), IMPT (two cases), or their combination (eight cases). One patient had R0 resection and another treated on the Chinese Food and Drug Administration registration trial received IMPT only. Twenty‐seven patients were treated according to various dose escalation trials or institutional protocols using IMCT or IMPT + IMCT boost. Twenty‐two patients with locoregional recurrence (10 and four patients failed surgery or surgery followed by radiotherapy, respectively) or radiation‐induced second primary sarcomas (eight patients) received salvage particle radiotherapy. With a median follow‐up time of 15.7 months, four patients with second primary sarcoma died. The 1‐ and 2‐year OS, PFS, LRFS, and DMFS rates for the entire cohort were 92.9% vs 90%, 73.6% vs 57.4%, 88.4% vs 78.9%, and 84.6% vs 76.5%, respectively. Those rates for patients without prior radiotherapy were 100% vs 100%, 82.1% vs 65.8%, 93.6% vs 85.3%, and 88.4% vs 79.5%, respectively. Multivariate analyses revealed that re‐irradiation was an independent prognostic factor for both LRFS and PFS (P = 0.015 and 0.037, respectively). In addition, gross tumor volume (GTV) was an independent prognostic factor for PFS (P = 0.048). One patient experienced Grade 3 acute toxicity (oral mucositis); another experienced Grade 4 acute event (hemorrhage) which required embolization. He lately died from hemorrhage (Grade 5) at 3.4 months after the completion of treatment. No patient experienced radiation‐induced acute/late toxicity of ≥ Grade 2 otherwise. Conclusion With few observed acute/late toxicities, IMPT/IMCT provided effective short‐term tumor control in our patients with HNS. Further investigations, preferably in a prospective fashion, will be required to confirm the efficacy and toxicities of IMPT/IMCT in this group of patients.

Gastric cancer (GC) is one of the most common types of human cancers worldwide. However, the detail mechanisms underlying GC progression remained to be investigated. The present study identified 2823 differently expressed mRNAs and 441 differently expressed lncRNAs in GC. WGCNA was conducted to identify highly correlated lncRNAs and mRNAs. Bioinformatics analysis observed that these dysregulated lncRNAs were significantly associated with the regulation of angiogenesis, cell division, cell-cell adhesion, blood vessel development, adaptive immune response, gastric acid secretion, immune response. Co-expression analysis identified ILF3-AS1 was a key lncRNA involved in regulating GC progression. Loss of function assays showed that knockdown of ILF3-AS1 significantly suppressed GC cell proliferation and metastasis. Mechanically, the results indicate that ILF3-AS1 could enhance PTBP3 expression as an miR-29a sponge, thereby promoting the proliferation and metastasis of GC cells. Our work suggests that the ILF3-AS1/miR-29a/PTBP3 axis may be a potential target for the clinical diagnosis and treatment of GC.

The temperature field of FeCrNiCu alloy forming layers of continuous wave(CW) and pulsed laser remanufacture was analyzed using the non-contact infrared thermometer.The general rule of temperature field distribution of molten pool and heat-affected zone of the two modes was obtained. The pulsed laser process superiority in heat input, forming deformation control and reducing the temperature in molten pool and heat-affected zone was vilidated. The results show that during pulsed laser forming the peak temperature in the heat-affected zone is 730.4-810.5℃,the peak temperature in the molten pool is 998.7-1383.4℃,which are all obviously lower than the same process of the CW mode; the temperature-rise rate and cooling rate of pulsed laser are higher, which is helpful to the forming of fine grain structures and good mechanical performance; the forming experiment also further verifies more narrow heat-affected zone in pulsed laser process.

Transcription from chromosomes is regulated by posttranslational modifications to histones, such as methylation and ubiquitination. Monoubiquitination of histones H2A and H2B influences H3 methylation to reinforce the activation or repression of gene expression. Here, we provide evidence that H3 polyubiquitination represses transcription of fetal and cell-cycle genes in postnatal mouse liver by crosstalk with H3K9 methylation. We found that the CRL4 ubiquitin ligase targets H3 for polyubiquitination at K79 via the DCAF8 substrate receptor in hepatocytes. Genetic inactivation of DCAF8 and overexpression of an H3K79 mutant in cells or inducible deletion of CRL4 in mouse liver abrogates H3 ubiquitination, reactivates the expression of fetal liver and cell-cycle genes by interfering with methylated H3K9 occupancy, and leads to cell senescence. Restoring CRL4DCAF8 expression in cells with decreased H3 ubiquitination reinstates the epigenetic gene silencing. Our results suggest that progressive H3 ubiquitination plays an important role in postnatal liver maturation.

Programmed death ligand 1 (PD-L1) functions as a key immune inhibitory factor by binding with its receptor, programmed death 1 (PD-1), to induce immune cell dysfunction and escape of the immune system. However, the mechanisms of PD-L1 expression under growth factor stimulation are not well characterized. Here, we demonstrate a novel role for glial cell line-derived neurotrophic factor (GDNF) in upregulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). The expression and correlation of PD-L1, GDNF and perineural invasion (PNI) status were evaluated by bioinformatics analysis of TCGA database and IHC assays from 145 HNSCC patients. PD-L1 expression was investigated by flow cytometry, Western blot and real-time PCR analyses in HNSCC cells after GNDF incubation. The cell signaling pathways activated by GDNF were analyzed with an antibody array and blocked by specific signaling inhibitors in cancer cell lines. PD-L1 expression was significantly higher in cancer cells that exhibited PNI in the HNSCC specimens, and elevated PD-L1 expression was significantly correlated with GDNF levels. GDNF not only enhanced cancer cell PNI in a co-culture of dorsal root ganglions and cancer cells but also had a potent role in inducing PD-L1 expression through the JAK2-STAT1 signaling pathway. Moreover, a JAK2 inhibitor attenuated GDNF-induced PD-L1 and enhanced tumor cell susceptibility to NK cell killing. Our findings provide clinically novel evidence that nerve-derived GDNF can increase PD-L1 levels in cancer cells around the perineural niche and that regulatory signaling is critical for cancer cell escape from immune surveillance in the nerve-cancer microenvironment.

Neck dissection is the most definitive and effective treatment for head and neck cancer. This systematic review aims to compare the efficacy and surgical outcomes of neck dissection between the harmonic scalpel and conventional surgical techniques and conduct a quantitative meta-analysis of the randomized trials.Randomized controlled trials (RCTs) were identified from the major electronic databases (MEDLINE, EMBASE and Cochrane Library) using the keywords ''harmonic scalpel'' and ''neck dissection,'' and a quantitative meta-analysis was conducted. The operative time and intraoperative bleeding were the primary outcome measures, and other parameters assessed included the drainage fluid volume and length of hospital stay.Seven trials that met the inclusion criteria included 406 neck dissection cases (201 in the harmonic scalpel group). Compared with conventional surgical techniques, the HS group had an operative time that was significantly reduced by 29.3 minutes [mean difference: -29.29; 95% CI = (-44.26, -14.32); P=0.0001], a reduction in intraoperative bleeding by 141.1 milliliters [mean difference: -141.13; 95% CI = (-314.99, 32.73); P=0.11], and a reduction in drainage fluid volume by 64.9 milliliters [mean difference: -64.86; 95% CI = (-110.40, -19.32); P=0.005] , but it is not significant after removal of studies driving heterogeneity. There was no significant difference in the length of the hospital stay [mean difference: -0.21; 95% CI = (-0.48, 0.07); P=0.14].This systematic review showed that using the harmonic scalpel for neck dissection significantly reduces the operative time and drainage fluid volume and that it is not associated with an increased length of hospital stay or perioperative complications. Therefore, the harmonic scalpel method is safe and effective for neck dissection. However, the statistical heterogeneity was high. Further studies are required to substantiate our findings.

BACKGROUND: Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. METHODOLOGY AND FINDINGS: 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non-neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p

Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsisassociated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS. [ABSTRACT FROM AUTHOR]

Abstract Our understanding of drought evolution and land-atmosphere interactions under climate mitigation scenarios remains limited. Here, we analyzed future drought under net-zero and net-negative emission scenarios using the Community Earth System Model version 2, particularly focusing on three atmospheric CO2 states: linearly increases, decreases, and a return to the initial state. Interestingly, results revealed that net-zero emissions are more effective for drought mitigation than net-negative targets. Drying trends and drought characteristics — such as the duration, frequency, intensity, and area expansion are prominently increased under net-negative emissions due to higher potential evapotranspiration (PET). This is because the soil moisture and temperature couplings are stronger over drought regions and years, especially under net-negative forcing, with notable impacts in Central Africa and South Asia. Nevertheless, both target scenarios offer regional benefits, such as weakened dryness. This suggests that mitigating CO2 alone may not be sufficient to manage future droughts, highlighting the need for advanced water management strategies.