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Abstract CD8+ T cells are integral to the effective management of cancer and infectious diseases due to their cytotoxic functions. The efficacy of these cells is profoundly influenced by their metabolic state, which regulates their activation, differentiation, and longevity. Accordingly, the modulation of metabolic pathways within CD8+ T cells is crucial for enhancing the effectiveness of T cell-based immunotherapy. Precise metabolic control is paramount in optimizing therapeutic outcomes and minimizing potential toxicities associated with treatment. Importantly, the potential of exogenous metabolites to augment CD8+ T cell responses is critically evaluated, especially through in vivo evidence that underscores their therapeutic promise. This review also addresses current challenges, including the need for precise control of metabolic modulation to avoid adverse effects, the development of targeted delivery systems to ensure efficient metabolite delivery to CD8+ T cells, and the inherent variability of metabolic states among patients that may influence treatment outcomes. Addressing these hurdles will be crucial for the successful integration of metabolic interventions into established immunotherapeutic regimens.

Abstract The tumor microenvironment (TME) orchestrates a complex interplay between tumor cells and immune cells, crucially modulating the immune response. This review delves into the pivotal role of metabolic reprogramming in the TME, highlighting how tumor-derived metabolites influence T lymphocyte functionality and the efficacy of cancer immunotherapies. Focusing on the diverse roles of these metabolites, we examine how lactate, lipids, amino acids, and other biochemical signals act not only as metabolic byproducts but as regulatory agents that can suppress or potentiate T cell-mediated immunity. By integrating recent findings, we underscore the dual impact of these metabolites on enhancing tumor progression and inhibiting immune surveillance. Furthermore, we propose innovative therapeutic strategies that target metabolic pathways to restore immune function within the TME. The insights provided in this review pave the way for the development of metabolic interventions aimed at enhancing the success of immunotherapies in oncology, offering new hope for precision medicine in the treatment of cancer.

Abstract Impact ionization effect has been demonstrated in transistors to enable sub-60 mV dec−1 subthreshold swing. However, traditionally, impact ionization in silicon devices requires a high operation voltage due to limited electrical field near the device drain, contradicting the low energy operation purpose. Here, we report a vertical subthreshold swing device composed of a graphene/silicon heterojunction drain and a silicon channel. This structure creates a low voltage avalanche impact ionization phenomenon and leads to steep switching of the silicon-based device. Experimental measurements reveal a small average subthreshold swing of 16 µV dec−1 over 6 decades of drain current and nearly hysteresis-free, and the operating voltage at which a vertical subthreshold swing occurs can be as low as 0.4 V at room temperature. Furthermore, a complementary silicon-based logic inverter is experimentally demonstrated to reach a voltage gain of 311 at a supply voltage of 2 V.

Opioids abuse in adolescence is becoming a pressing public health issue. While evidence suggests that exposure to opioids during adolescence leads to lasting alterations in brain development, the long-term cognitive implications in adulthood remain uncertain. We developed a male mouse model of adolescent morphine exposure and used the 5-choice serial reaction time task (5‐CSRTT), along with the open field, novel object recognition, Y maze and Barnes maze tests, to assess changes in cognitive behavior. We found that exposure to morphine during adolescence led to deficits in multidimensional cognitive functions in mice, including attention, information processing speed, and behavior inhibition. Notable, these impairments persisted into adulthood. Furthermore, the morphine-exposed mice exhibited decreased learning efficiency and spatial memory. Adolescent morphine exposure also induced significant and persistent morphological changes and synaptic abnormalities in medial prefrontal cortex (mPFC) neurons, which may be responsible for cognitive impairments in adulthood. Together, our study suggests that opioid exposure during adolescence profoundly affects cognitive development and emphasizes that opioid-induced disruption of neurons in adolescence may link mPFC-associated cognitive impairments in adulthood.

BackgroundStudies on lower urinary tract symptoms (LUTS) in women, especially in relation to different modes of delivery, are limited. The relationship between the emergence of LUTS and the decline of pelvic muscle function after childbirth remains uncertain.Study designThis observational study was carried out at the Peking University First Hospital over a time span of 2019–2022. A total of 2,462 women were recruited and surveyed 6 weeks after delivery, utilizing questionnaires for data collection. Additionally, gynecological physical examinations and pelvic floor muscle screenings were conducted as part of the study. To assess individual LUTS and the level of discomfort caused by these symptoms, a modified Chinese version of the Bristol Female Lower Urinary Tract Symptoms questionnaire was employed. Data analysis methods such as descriptive statistics, χ2 tests, one-way ANOVAs, and multivariate logistic regressions were used to thoroughly examine the collected data.ResultsA high prevalence of LUTS was observed in the study participants, with 70.6% experiencing any symptoms. Storage symptoms were reported by 65.4%, while voiding symptoms were reported by 23.0%. Nocturia was the most commonly reported symptom (35.4%), followed by frequency (25.6%) and urgency (25.3%). Stress urinary incontinence (SUI) was reported by 20.8% of women. Interestingly, nocturia and frequency were generally perceived as less troublesome, with only a minority rating them as problematic. In contrast, urinary incontinence (UI) was frequently reported as highly bothersome, with SUI and urge urinary incontinence (UUI) accounting for significant proportions. Vaginal delivery (VD) and forceps delivery (FD) were identified as significant predictors of LUTS, with statistical significance observed (P

Objective: To investigate the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea (FHA).Methods: A retrospective cohort study was conducted to summarize the clinical and endocrine characteristics of 58 patients with FHA at initial diagnosis and to follow up the recovery of ovulation and spontaneous menstruation in the patients to investigate these biochemical indicators and their effects on recovery outcomes.Results: Among patients with FHA, 13.8% (8/58) and 15.5% (9/58) had above moderately severe depressive and severe anxiety symptoms respectively, and 25.9% (15/58) were at high risk for eating disorders. 34.5% (20/58) were included assessed as having recovered. The non-recovered group had higher scores on the Patient Health Questionnaire (PHQ-9) (p = .022) and higher scores on the Eating Attitude Test-26 (EAT-26) (p = .03) as well as bulimia and food preoccupation (p = .041). Follicle diameter >5 mm at initial diagnosis was an independent factor influencing recovery of reproductive axis function (odds ratio = 7.532; 95% confidence interval, 1.321–42.930; p = .023).Conculsions: Mood disorders and a certain risk of eating disorders were present in FHA.These, together with weight loss, endocrine and follicle size, could influence the outcome.

Abstract RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing RNA stability, functionality, and interactions. To date, over 170 distinct RNA chemical modifications and more than 100 RNA‐modifying enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has been made in understanding RNA modification, the regulatory mechanisms that govern RNA‐modifying proteins themselves remain insufficiently explored. Post‐translational modifications (PTMs) such as phosphorylation, ubiquitination, and acetylation are crucial in modulating the function and behavior of these proteins. However, the full extent of PTM influence on RNA‐modifying proteins and their role in disease development remains to be fully elucidated. This review addresses these gaps by offering a comprehensive analysis of the roles PTMs play in regulating RNA‐modifying proteins. Mechanistic insights are provided into how these modifications alter biological processes, contribute to cellular function, and drive disease progression. In addition, the current research landscape is examined, highlighting the therapeutic potential of targeting PTMs on RNA‐modifying proteins for precision medicine. By advancing understanding of these regulatory networks, this review seeks to facilitate the development of more effective therapeutic strategies and inspire future research in the critical area of PTMs in RNA‐modifying proteins.

Abstract Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as the hub of oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels a variety of cellular activities. Disruption in mitochondrial metabolism is a common feature in many diseases, including cancer, neurodegenerative conditions and cardiovascular diseases. Targeting tumor cell mitochondrial metabolism with multifunctional nanosystems emerges as a promising strategy for enhancing therapeutic efficacy against cancer. This review comprehensively outlines the pathways of mitochondrial metabolism, emphasizing their critical roles in cellular energy production and metabolic regulation. The associations between aberrant mitochondrial metabolism and the initiation and progression of cancer are highlighted, illustrating how these metabolic disruptions contribute to oncogenesis and tumor sustainability. More importantly, innovative strategies employing nanomedicines to precisely target mitochondrial metabolic pathways in cancer therapy are fully explored. Furthermore, key challenges and future directions in this field are identified and discussed. Collectively, this review provides a comprehensive understanding of the current state and future potential of nanomedicine in targeting mitochondrial metabolism, offering insights for developing more effective cancer therapies.

Abstract Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

BackgroundIn the era of the internet, individuals have increasingly accustomed themselves to gathering necessary information and expressing their opinions on public web-based platforms. The health care sector is no exception, as these comments, to a certain extent, influence people’s health care decisions. During the onset of the COVID-19 pandemic, how the medical experience of Chinese patients and their evaluations of hospitals have changed remains to be studied. Therefore, we plan to collect patient medical visit data from the internet to reflect the current status of medical relationships under specific circumstances. ObjectiveThis study aims to explore the differences in patient comments across various stages (during, before, and after) of the COVID-19 pandemic, as well as among different types of hospitals (children’s hospitals, maternity hospitals, and tumor hospitals). Additionally, by leveraging ChatGPT (OpenAI), the study categorizes the elements of negative hospital evaluations. An analysis is conducted on the acquired data, and potential solutions that could improve patient satisfaction are proposed. This study is intended to assist hospital managers in providing a better experience for patients who are seeking care amid an emergent public health crisis. MethodsSelecting the top 50 comprehensive hospitals nationwide and the top specialized hospitals (children’s hospitals, tumor hospitals, and maternity hospitals), we collected patient reviews from these hospitals on the Dianping website. Using ChatGPT, we classified the content of negative reviews. Additionally, we conducted statistical analysis using SPSS (IBM Corp) to examine the scoring and composition of negative evaluations. ResultsA total of 30,317 pieces of effective comment information were collected from January 1, 2018, to August 15, 2023, including 7696 pieces of negative comment information. Manual inspection results indicated that ChatGPT had an accuracy rate of 92.05%. The F1-score was 0.914. The analysis of this data revealed a significant correlation between the comments and ratings received by hospitals during the pandemic. Overall, there was a significant increase in average comment scores during the outbreak (P

Abstract Objectives To investigate the association of albumin-corrected anion gap (ACAG) with non-alcoholic fatty liver disease (NAFLD) and clinically significant fibrosis (CSF) defined by vibration-controlled transient elastography measurements. Methods This cross-sectional study including 4531 participants was conducted using the data from the NHANES database of cycles 2017–2018. The outcomes were set as NAFLD vs. non-NAFLD and NAFLD with CSF vs. NAFLD without CSF. The generalized additive model and restricted cubic spline analyses were used to assess the nonlinear relationship. The generalized linear models, logistic regression models, sensitivity analysis, P trend test, subgroup analysis, and mediation analysis were employed to analyze the association. Finally, an ACAG-based model was constructed and evaluated. Results A higher ACAG level was an independent risk factor for NAFLD (P 0.05). The sensitivity analysis and P trend test results substantiated the significantly positive relationship between ACAG and NAFLD (P

Abstract Background Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms. Methods First, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments. Results AXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1. Conclusions The present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.

Abstract This study aims to investigate the relationship between the healthy eating index (HEI) and the prevalence of stroke within a diverse United States population. Employing a cross-sectional design, we utilized data sourced from the National Health and Nutrition Examination Survey (NHANES). Dietary information was collected from participants and HEI scores were computed. NHANES employed stratified multistage probability sampling, with subsequent weighted analysis following NHANES analytical guidelines. Thorough comparisons were made regarding the baseline characteristics of individuals with and without stroke. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) methods were employed to ascertain the association between stroke risk and HEI, with LASSO regression utilized to identify dietary factors most closely linked to stroke risk. Additionally, we constructed a nomogram model incorporating key dietary factors and assessed its discriminatory capability using the receiver operating characteristic (ROC) curve. Our study encompassed 43,978 participants, representing an estimated 201 million U.S. residents. Participants with a history of stroke exhibited lower HEI scores than their non-stroke counterparts. Logistic regression analysis demonstrated a robust association between lower HEI scores and stroke, even after adjusting for confounding variables. RCS analysis indicated a nonlinear negative correlation between HEI and stroke risk. Furthermore, detailed subgroup analysis revealed a significant gender-based disparity in the impact of dietary quality on stroke risk, with females potentially benefiting more from dietary quality improvements. Sensitivity analysis using unweighted logistic regression yielded results consistent with our primary analysis. The nomogram model, based on key dietary factors identified through LASSO regression, demonstrated favorable discriminatory power, with an area under the curve (AUC) of 79.3% (95% CI 78.4–81.2%). Our findings suggest that higher HEI scores are inversely related to the risk of stroke, with potential greater benefits for women through dietary quality enhancement. These results underscore the importance of improving dietary quality for enhanced stroke prevention and treatment.

Abstract Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Abstract Challenge 3 of the 2022 NIST additive manufacturing benchmark (AM Bench) experiments asked modelers to submit predictions for solid cooling rate, liquid cooling rate, time above melt, and melt pool geometry for single and multiple track laser powder bed fusion process using moving lasers. An in-house developed Additive Manufacturing Computational Fluid Dynamics code (AM-CFD) combined with a cylindrical heat source is implemented to accurately predict these experiments. Heuristic heat source calibration is proposed relating volumetric energy density (ψ) based on experiments available in the literature. The parameters of the heat source of the computational model are initially calibrated based on a Higher Order Proper Generalized Decomposition- (HOPGD) based surrogate model. The prediction using the calibrated heat source agrees quantitatively with NIST measurements for different process conditions (laser spot diameter, laser power, and scan speed). A scaling law based on keyhole formation is also utilized in calibrating the parameters of the cylindrical heat source and predicting the challenge experiments. In addition, an improvement on the heat source model is proposed to relate the Volumetric Energy Density (VEDσ) to the melt pool aspect ratio. The model shows further improvement in the prediction of the experimental measurements for the melt pool, including cases at higher VEDσ. Overall, it is concluded that the appropriate selection of laser heat source parameterization scheme along with the heat source model is crucial in the accurate prediction of melt pool geometry and thermal measurements while bypassing the expensive computational simulations that consider increased physics equations.

Abstract Background Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD. Methods Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603. Results HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-β1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-β1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-β1 induced cell migration. Conclusions These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-β1/Smad2/3 signalling pathway.

Abstract Industrial data trading can considerably enhance the economic and social value of abundant data resources. However, traditional data trading models are plagued by critical flaws in fairness, security, privacy and regulation. To tackle the above issues, we first proposed a distributed industrial data trading architecture based on blockchain and cloud for multiple data owners. Subsequently, we realized implemented distributed identity management by the distributed verifiable credentials scheme that possesses the desirable properties, i.e., selective disclosure, multi-show unlinkability, threshold traceability, and public verifiability. Finally, we presented a fair trading mechanism without trusted third parties based on smart contracts, and we employed blockchain and multi-signature to ensure data integrity during data storage and trading. The security and performance analysis shows that our proposal is feasible for sensitive data trading for multiple data owners and provides a useful exploration for future industrial data trading and management.

The squeezing effect and strike-induced vibration generated by pile driving pose a threat to adjacent structures. To mitigate the squeezing effect, open-ended pipe piles were implemented. However, this type of pile brings a degree of soil-plugging effect, particularly in sandy soil, which complicates the squeezing effect and the dynamic responses of the pile during pile driving. In this study, model experiments were conducted using both open-ended piles and open-ended piles with different fixed-length soil plugs to investigate the squeezing effect and dynamic responses of the piles. Moreover, spectrum analysis was performed to explore the patterns of vibration waves in the open-ended pipe pile during the striking process. For open-ended pipe piles, acceleration fluctuations were detectable solely when the pile reached the sensor depth and at the end of the pile driving process, which revealed that the hammering energy was mainly consumed by pile settlement and the formation of the soil plug. When the formation of the soil plug was completed, the majority of the energy was converted into propagating vibration, resulting in the emergence of another crest of acceleration. The spectrum analysis revealed that the maximum amplitude occurred when the penetration depth was equal to half of the pile length.

Abstract Aim To develop a comprehensive training course for training ICU nurses in prone positioning. Design A mixed study combining semi‐structured interviews and two rounds of Delphi surveys. Methods We constructed a questionnaire after collecting data through a literature review and semi‐structured interviews. We used the Delphi expert correspondence method to conduct two rounds of research among 17 experts in the field of critical illness. Data collection took place between May and August 2022. Results The effective questionnaire recovery rate was 88.2%. The expert authority coefficient was 0.876; the Kendall coordination coefficient was 0.402; the average importance score for each index ranged from 4.00 to 4.93; and the coefficient of variation for each index ranged from 0.05 to 0.19. We established 13 second‐level indicators and 41 third‐level indicators on prone position ventilation training according to three aspects: training contents, training methods and training assessment. The training system of prone mechanical ventilation for ICU nurses established in this study will provide an effective framework for training and evaluating the practical ability of prone mechanical ventilation for ICU nurses.

As network infrastructures continue to grow and traffic encryption technologies evolve at a rapid pace, the task of classifying encrypted traffic has become significantly more intricate. These emerging encryption methods render conventional approaches ineffectual in discerning traffic types, consequently posing novel challenges to network security and administration. Evidently, conventional traffic classification techniques are inadequate when it comes to encrypted traffic. Consequently, researchers have turned to machine learning and deep learning models to address this challenge, achieving remarkable results in this domain. Nonetheless, contemporary deep learning models exhibit a propensity to overly depend on self-attention mechanisms while processing 2D feature maps. This mechanism typically focuses only on individual query-key pairs, neglecting the rich contextual information among adjacent keys, thereby limiting their performance in encrypted traffic classification. To address this limitation, our study examines an innovative approach called CoTNet. The CoT module is integrated into the ResNet model to more comprehensively exploit the contextual associations among input keys. This innovation engenders a sturdier and more potent classification model, adept at comprehensively capturing the inherent patterns and correlated information within input features. The suggested method enhances the ResNet model by substituting the conventional 3x3 convolution operations with CoT modules, thereby more effectively harnessing the contextual associations among input keys. In particular, we integrate self-attention mechanisms at various model levels to more thoroughly capture the inherent patterns and correlated information within input features. Experimental results on two real-world datasets show that CoTNet outperforms multiple state-of-the-art methods in the encrypted traffic classification task.

Abstract Ribosomal RNA (rRNA) modifications, essential components of ribosome structure and function, significantly impact cellular proteomics and cancer biology. These chemical modifications transcend structural roles, critically shaping ribosome functionality and influencing cellular protein profiles. In this review, the mechanisms by which rRNA modifications regulate both rRNA functions and broader cellular physiological processes are critically discussed. Importantly, by altering the translational output, rRNA modifications can shift the cellular equilibrium towards oncogenesis, thus playing a key role in cancer development and progression. Moreover, a special focus is placed on the functions of mitochondrial rRNA modifications and their aberrant expression in cancer, an area with profound implications yet largely uncharted. Dysregulation in these modifications can lead to metabolic dysfunction and apoptosis resistance, hallmark traits of cancer cells. Furthermore, the current challenges and future perspectives in targeting rRNA modifications are highlighted as a therapeutic approach for cancer treatment. In conclusion, rRNA modifications represent a frontier in cancer research, offering novel insights and therapeutic possibilities. Understanding and harnessing these modifications can pave the way for breakthroughs in cancer treatment, potentially transforming the approach to combating this complex disease.

ObjectiveThe structural response and dynamic structural collapse mode of a container ship in waves are studied by fully considering the effects of load nonlinearity and surface nonlinearity.MethodsFirst, a hydrodynamic model of a container ship is established based on the CFD platform, and the overset grid method is used to realize matching between the dynamic boundary grid of the hull hydrodynamic model and the Euler grid in the far-field fluid domain. The volume of fluid method is used to simulate the nonlinearity of the free surface in the whole fluid domain, and the N–S equations in three directions are solved in the whole flow field domain so as to solve the nonlinear wave load of the ship in real time. A nonlinear finite element model of the ship that can simulate its collapse behavior is then established, and the time-domain collapse response of the ship including plasticity and buckling is calculated based on the explicit dynamic nonlinear finite element method (FEM). Finally, the transmission of fluid pressure and node displacement between the hydrodynamic model and structural finite element model on the wet surface are realized, and two-way iterative coupling between the CFD solver and nonlinear finite element solver is carried out to calculate the nonlinear wave load and structural collapse response during the structural collapse of a 4600 TEU container ship in real time. ResultsUnder extreme waves, the upper to middle structures of the container ship are widely plastic, the main deck, side plate, deck longitudinal, side longitudinal and other components have typical yield instability under the action of wave loads, the deck longitudinal, side longitudinal and other structural members have serious lateral instability, and the hull structure loses its bearing capacity.ConclusionThe proposed CFD nonlinear FEM can accurately solve the structural response and dynamic collapse mode, making it viable as a new approach to studying the collapse response of ship structures.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors globally. Understanding the molecular basis of tumor progression and drug resistance can offer innovative strategies to enhance clinical outcomes for HNSCC patients. Methods The cytoskeletal remodeling genes associated with cisplatin resistance were screened using a PCR array. The role of alpha-actinin 1 (ACTN1) in modulating cisplatin resistance and tumorigenesis in HNSCC was evaluated both in vitro and in vivo. Co-immunoprecipitation (Co-IP), IP-mass spectrometry (MS), western blotting, dual-luciferase assay, and bioinformatics analysis were performed to elucidate the underlying mechanisms involved. Results Our study identifies ACTN1 as a crucial contributor to cisplatin resistance and tumorigenesis in HNSCC, as evidenced across cellular, animal, and patient-derived xenograft models. From a clinical perspective, overexpression of ACTN1 significantly correlates with a suboptimal response to neoadjuvant chemotherapy and reduced overall survival in HNSCC patients. Mechanistically, ACTN1 predominantly activates β-catenin-mediated signaling by promoting the interaction between myosin heavy chain 9 (MYH9) and GSK-3β, leading to the ubiquitin-dependent degradation of GSK-3β. ACTN1 also interacts with integrin β1, subsequently activating the FAK/PI3K/AKT pathway, providing an additional avenue for the activation of β-catenin signaling. Our study also unveils that the β-catenin/c-Myc axis transcriptionally regulates ACTN1, thereby creating a positive feedback loop promoting HNSCC tumorigenesis and drug resistance. Conclusions These insights underscore the novel mechanisms that highlight ACTN1's pivotal role in driving HNSCC progression and resistance to chemotherapy, suggesting ACTN1 as a promising therapeutic target in HNSCC management.

Abstract Background Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF. Methods We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese. We included controlled studies comparing HFNC with COT or NIV in patients with AHF. Primary outcomes included the intubation rate, respiratory rate (RR), heart rate (HR), and oxygenation status. Results From the 1288 original papers identified, 16 studies met the inclusion criteria, and 1333 patients were included. Compared with COT, HFNC reduced the intubation rate (odds ratio [OR]: 0.29, 95% CI: 0.14–0.58, P = 0.0005), RR (standardized mean difference [SMD]: -0.73 95% CI: -0.99 – -0.47, P

The DOF (DNA-binding with one finger) transcription factors are exclusive to plants and play crucial roles in plant growth, development, and environmental adaptation. Although extensive research has been conducted on the Dof gene family in Arabidopsis, maize, and Solanum, investigations concerning the role of this gene family in Liriodendron remain unreported, leaving its biological function largely unknown. In this study, we performed a comprehensive genome-wide identification of the Dof gene family based on the Liriodendron genome, resulting in the discovery of a total of 17 LcDof gene members. Based on the results of phylogenetic analysis, the 17 LcDof proteins were classified into eight subfamilies. The motif analysis revealed the diverse nature of motifs within the D1 subfamily, which includes a distinct type of Dof transcription factor known as CDF (Cycling Dof Factor). We further characterized the chromosomal distribution, gene structure, conserved protein motifs, and cis-elements in the promoter regions. Additionally, utilizing transcriptome data from Liriodendron hybrids and conducting RT-qPCR experiments, we investigated the expression patterns of LhDofs under various abiotic stresses such as drought, cold, and heat stress. Notably, we found that several LhDofs, particularly LhDof4 and LhDof6, were significantly upregulated in response to abiotic stress. Furthermore, we cloned LhDof4 and LhDof6 genes and found that its encoding protein was mainly located in the nucleus by transient transformation in Liriodendron hybrids protoplast. Subsequently, we used LhDof6-overexpressing Liriodendron hybrid seedlings. We found that overexpression of LhDof6 enhanced the cold tolerance of the plants, increasing their survival rate at −20 °C. This result was further validated by changes in physiological indicators.

Foodborne diseases are major public health problems globally. Metagenomics has emerged as a widely used tool for pathogen screening. In this study, we conducted an updated Tn5 transposase-assisted RNA/DNA hybrid co-tagmentation (TRACE) library construction approach. To address the detection of prevalent known foodborne viruses and the discovery of unknown pathogens, we employed both specific primers and oligo-T primers during reverse transcription. The method was validated using clinical samples confirmed by RT-qPCR and compared with standard RNA-seq library construction methods. The mapping-based approach enabled the retrieval of nearly complete genomes (>95%) for the majority of virus genome segments (86 out of 88, 97.73%), with a mean coverage depth of 21,494.53× (ranging from 77.94× to 55,688.58×). Co-infection phenomena involving prevalent genotypes of Norovirus with Astrovirus and Human betaherpesvirus 6B were observed in two samples. The updated TRACE-seq exhibited superior performance in viral reads percentages compared to standard RNA-seq library preparation methods. This updated method has expanded its target pathogens beyond solely Norovirus to include other prevalent foodborne viruses. The feasibility and potential effectiveness of this approach were then evaluated as an alternative method for surveilling foodborne viruses, thus paving the way for further exploration into whole-genome sequencing of viruses.

To study the influence of stone content on the stability of gravel soil slopes, static overload tests were carried out on slopes with different stone contents. By combining model tests combined with digital image correlation （DIC） technology, the deformation of the soil body in both the whole field and local field of the slope was analyzed. The findings indicated that the stone content had a significant controlling effect on the bearing capacity and deformation characteristics of gravel soil slope, and two threshold values of stone content, i.e. 20% and 70% were found based on the ultimate bearing capacity. Further analysis was conducted at the meso-scale to understand the deformation behaviour of local soil and the movement of gravel during the shearing process. The local soil was found to exhibit the shear dilatancy effect, resulting in a significant increase in porosity in the shear zone. By tracing the movement of gravel and its surrounding sand particles in the local soil, it was found that the gravel can affect the development of shear zone, and five modes of shear zone surrounding stone were summarized: unilateral rock bypass mode, bifurcation mode, crossing rock and bifurcation composite mode, bifurcation and unilateral rock bypass and crossing rock composite mode, and unilateral rock bypass and crossing rock composite mode. The research results provided a reference for further understanding the inherent mechanism of gravel soil slope instability.

Abstract Assessing long-term tumor survival rates is crucial for evaluating the effectiveness of tumor treatment and burden. However, timely assessment of long-term survival in patients with pancreatic cancer is lagging in China. In this study, we applied period analysis to estimate the long-term survival of pancreatic cancer patients using data from four population-based cancer registries in Taizhou city, eastern China. A total of 1121 patients diagnosed with pancreatic cancer between 2004 and 2018 were included. We assessed the 5-year relative survival (RS) using period analysis and further stratified by sex, age at diagnosis, and region. The 5-year RS during 2014–2018 overall reached 18.9% (14.7% for men and 23.3% for women, respectively). A decrease of the 5-year RS from 30.3% to 11.2% was observed in four diagnostic age gradients ( 74 years age groups). The 5-year RS was higher in urban (24.2%) than in rural (17.4%) areas. Moreover, the 5-year RS of pancreatic cancer patients showed an overall increasing trend for the three periods (2004–2008, 2009–2013, and 2014–2018). Our study, using period analysis for the first time in China, provides the latest estimates of the survival of patients with pancreatic cancer, which provides essential evidence for the prevention and intervention of pancreatic cancer. The results also indicate the importance of further applications of the period analysis for more up-to-date and accurate survival estimates.

Abstract Background Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. Methods In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. Results Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014–8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695–5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. Conclusions This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. Trial registration: ClinicalTrials.gov NCT01874691.

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR.Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury.Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered.Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.

The flammable gas volatilized from the storage medium in the tank will burn and explode under the action of an accidental ignition source. Tank explosions formed by the explosive shock wave, explosive debris will not only cause their own damage, but also on the safe operation of adjacent tanks to form a threat. Therefore, in this paper, the vertical dome roof tank is taken as the research object, the criteria of brittle fracture failure of tank materials are constructed, and the multi-field coupling calculation model of tank detonation based on TNT equivalent method is established, taking into account the fluid properties inside and outside the tank, the structure of implosion tank and adjacent tank. By analyzing the full time domain process of gas detonation in tanks under different influence factors, the response to implosion damage of tanks and adjacent tanks under the action of explosion shock wave overpressure and debris was obtained. With the increase of the liquid level, the overpressure and deformation of the shock wave of the detonation tank and adjacent tank decrease, and the type and number of fragments decrease. With the increase of the volume of the tank, the overpressure and stress of the shock wave become larger, the strain rate of the tank becomes larger, and brittle failure is more likely to occur. The types and number of fragments formed increase, but detonation fragments are not formed when the tank is full. The research results in this paper provide a theoretical basis and calculation method for preventing and controlling tank implosion accidents, as well as tank design and tank spacing layout.

ObjectiveThis study aims to investigate the relationship between taste dysfunction and depression among patients with schizophrenia, to achieve early detection of depression in clinical practice.MethodsFollowing PRISMA guidance, a comprehensive literature search was conducted globally, covering papers published from 1961 to June 2023. A total of 17 manuscripts were selected through meta-analysis and sensitivity analysis after examining available materials from seven databases to determine the correlation between depression and taste dysfunction.ResultsThe comparison of the 17 selected manuscripts revealed that individuals with gustatory dysfunction may be more likely to experience depressive symptoms (SMD, 0.51, 95% CI, 0.08 to 0.93, p = 0.02). Depression is associated with taste dysfunction in certain aspects, as indicated by the pleasantness ratings of sucrose solutions (SMD, -0.53, 95% confidence interval [CI] -1.11 to 0.05, p = 0.08), gustatory identification ability (SMD, 0.96, 95% CI, 0.03 to 1.89, p = 0.04), and the perception threshold of sweet taste (MD, 0.80, 95% CI, 0.79 to 0.81, p < 0.00001).ConclusionsDue to variations in the methods, designs, and selection criteria employed in the included studies, it is necessary to establish a feasible framework. Future research using detailed and targeted approaches can provide clearer and more unified conclusions on the relationship between taste dysfunction and depression. Moreover, further high-quality research is needed to obtain clearer conclusions and explore the potential of taste dysfunction as an effective tool for early screening of depression.Trial registrationThis review has been registered in the PROSPERO on April 2022 with the identifier CRD42023400172.

ObjectiveThis study aims to evaluate inpatient services in 49 tertiary comprehensive hospitals using indicators from the diagnosis related groups (DRG) payment system.MethodDRG data from 49 tertiary comprehensive hospitals were obtained from the quality monitoring platform for provincial hospitals, and relevant indicators were identified. The analytic hierarchy process (AHP) was used to compute the weight of each indicator. The rank sum ratio method was used to calculate the weight rank sum ratio (WRSR) value and the corresponding probit value of each hospital. The hospitals were divided into four grades based on the threshold value: excellent, good, fair, and poor.ResultsEight indicators of the 49 hospitals were scored, and the hospital rankings of indicators varied. The No. 1 hospital ranked first in the indicators of “total number of DRG”, “number of groups”, and “proportion of relative weights (RW) ≥ 2”. The WRSR value of the No.1 hospital was the largest (0.574), and the WRSR value of the No. 44 hospital was the smallest (0.139). The linear regression equation was established: WRSRpredicted =-0.141+0.088*Probit, and the regression model was well-fitted (F = 2066.672, p < 0.001). The cut-off values of the three WRSRspredicted by the four levels were 0.167, 0.299, and 0.431, respectively. The 49 hospitals were divided into four groups: excellent (4), good (21), average (21), and poor (3). There were significant differences in the average WRSR values of four categories of hospitals (p < 0.05).ConclusionThere were notable variances in the levels of inpatient services among 49 tertiary comprehensive hospitals, and hospitals of the same category also showed different service levels. The evaluation results contribute to the health administrative department and the hospital to optimize the allocation of resources, improve the DRG payment system, and enhance the quality and efficiency of inpatient services.

BackgroundIn the context of increasing reports of co-infection with coronavirus disease 2019 (COVID-19), particularly with human herpes viruses (HHVs), it is important to consider the appropriate treatment options for HHVs that have been reactivated by COVID-19.Case presentationThis study presents two cases of severe COVID-19 with HHV co-infection. The first case involved a critically ill patient with COVID-19 co-infected with herpes simplex virus type 1, confirmed using metagenomic next-generation sequencing, and another patient with severe COVID-19 experiencing Epstein-Barr virus (EBV) reactivation, as evidenced by elevated EBV-DNA levels in the serum. Treatment included high-dose glucocorticoids and sivelestat sodium, with notable improvements observed after initiating ganciclovir anti-herpesvirus therapy.ConclusionThis study underscores the significance of recognizing HHV co-infections in severe COVID-19 cases and highlights the potential of combining anti-HHV treatment, increased glucocorticoid dosages, and anti-cytokine storm therapy to enhance prognosis.

Background: Little is known about the association between sarcopenia and multimorbidity among middle-aged and older adults. This study investigated whether sarcopenia is associated with multimorbidity in middle-aged and older Chinese individuals. Materials and methods: A total of 12,760 participants from China Health and Retirement Longitudinal Study (CHARLS) 2015, with data on 14 specified chronic diseases and sarcopenia status were included in the cross-sectional analysis. A total of 7345 participants without multimorbidity from the CHARLS 2015 were included and followed up in 2018 in the longitudinal analysis. Logistic regression models were used in a cross-sectional investigation to assess the association between sarcopenia status and multimorbidity. In a longitudinal analysis, the relationships between sarcopenia status and multimorbidity were investigated using Cox proportional hazards models. Results: Multimorbidity was prevalent in the no sarcopenia, possible sarcopenia, and sarcopenia groups at 38.8 % (3765/9713), 56.6 % (1199/2118), and 48.5 % (451/929), respectively. Multivariable regression revealed that both possible sarcopenia (β = 0.088, P

In view of the application of end slope shearer mining technology to recover a large amount of residual coal, the determination of reasonable width of supporting coal pillar is a key factor whether it can be safely and efficiently popularization and application, especially considering the influence of blasting vibration on the stability of supporting coal pillar. Based on the southern end slope at the open-pit coal mine of Pingshuo, field vibration test, theoretical analysis and numerical calculation were used to study the web pillar stability in open-pit highwall mining and its parameter design under the action of triangular load and blasting vibration on the side slope. Based on the theory of limit balance and the mutation theory, the stress distribution at the coal pillar was analyzed, combined with Mohr-Coulomb failure criterion. Besides, the ultimate strength function expression of coal pillar under the influence of mining height, mining width, load stress of overlying strata, cohesion and internal friction angle of coal pillar is established. The calculation formula of the maximum allowable plastic zone width and rational width of web pillar under different safety reserve factor conditions are established. The three-dimensional simple harmonic vibration response model of the supported coal pillar was established, and the blasting parameters such as the amount of single shot, elevation difference and horizontal distance of the blast center were studied on the response of the maximum instantaneous dynamic stress of the coal pillar, which revealed the influence mechanism of the blasting dynamic load effect on the width and stability of the plastic zone of the supported coal pillar and proposed the design method of the parameters of the supported coal pillar under the blasting dynamic load. The results show that the blasting vibration has a greater influence on the stability of coal pillar, and the instantaneous maximum dynamic stress response of coal pillar under the blasting dynamic load is positively correlated with the amount of single shot, and negatively correlated with the elevation difference and horizontal distance. With the increase of the maximum instantaneous dynamic stress response of coal pillar, the width of plastic zone of coal pillar increases proportionally, and the safety factor of coal pillar decays in an approximately linear pattern. The width of coal pillar under dynamic-static load is determined to be 5 m, and its reasonableness is verified by engineering practice.

Abstract Numerous users are experiencing unsafe communications due to the growth of big network mediums, where no node communication is detected in emergency scenarios. Many people find it difficult to communicate in emergency situations as a result of such communications. In this paper, a mobile cloud computing procedure is implemented in the suggested technique in order to prevent such circumstances, and to make the data transmission process more effective. An analytical framework that addresses five significant minimization and maximization objective functions is used to develop the projected model. Additionally, all mobile cloud computing nodes are designed with strong security, ensuring that all the resources are allocated appropriately. In order to isolate all the active functions, the analytical framework is coupled with a machine learning method known as Decision Tree. The suggested approach benefits society because all cloud nodes can extend their assistance in times of need at an affordable operating and maintenance cost. The efficacy of the proposed approach is tested in five scenarios, and the results of each scenario show that it is significantly more effective than current case studies on an average of 86%.

Abstract To safely and efficiently recover trapped coal under final endwalls in open cut mines, theoretical analysis and numerical calculation were used to study the stability of web pillar during auger mining. The partial ordered set (poset) evaluation model was used to develop a risk assessment methodology, and auger mining at Pingshuo Antaibao open cut coal mine was used as a field example for validation. Based on the catastrophe theory, the failure criterion of web pillar was established. From the limit equilibrium theory, the maximum allowable plastic yield zone width and minimum web pillar width were proposed under various Factor of Safety (FoS) thresholds. This in turn provides a new method for web pillar design. Based on the poset theory and combining with the risk evaluation and proposed hazard levels, input data were standardized and weighted. Subsequently, the comparison matrix, HASSE matrix and HASSE diagram were established. The study shows that: when the width of the plastic zone of web pillar exceeds 88% of the total width, web pillar may be unstable. Based on the calculation formula for the required width of web pillar, the required pillar width was 4.93 m and it was deemed as “mostly stable”. This was consistent with the field condition on site. Such that this method was validated.

Abstract Cloud Mobile Ad-hoc Networks (Cloud-MANETs) is a framework that can access and deliver cloud services to MANET users through their smart devices. MANETs is a pool of self-organized mobile gadgets that can communicate with each other with no support from a central authority or infrastructure. The main advantage of MANETs is its ability to manage mobility while data communication between different users in the system occurs. In MANETs, clustering is an active technique used to manage mobile nodes. The security of MANETs is a key aspect for the fundamental functionality of the network. Addressing the security-related problems ensures that the confidentiality and integrity of the data transmission is secure. MANETs are highly prone to attacks because of their properties.In clustering schemes, the network is broken down to sub-networks called clusters. These clusters can have overlapping nodes or be disjointed. An enhanced node referred to asthe Cluster Head (CH) is chosen from each set to overseetasks related to routing. It decreases the member nodes’ overhead and improvesthe performance of the system. The relationship between the nodes and CH may vary randomly, leading to re-associations and re-clustering in a MANET that is clustered. An efficient and effective routing protocol is required to allow networking and to find the most suitable paths between the nodes. The networking must be spontaneous, infrastructure-less, and provide end-to-end interactions. The aim of routing is the provision of maximum network load distribution and robust networks. This study focused on the creation of a maximal route between a pair of nodes, and to ensure the appropriate and accurate delivery of the packet. The proposed solution ensured that routing can be carried out with the lowest bandwidth consumption. Compared to existing protocols, the proposed solution had a control overhead of 24, packet delivery ratio of 81, the lowest average end-to-end delay of 6, and an improved throughput of 80,000, thereby enhancing the output of the network. Our result shows that multipath routing enables the network to identify alternate paths connecting the destination and source. Routing is required to conserve energy and for optimum bandwidth utilization.

Thioredoxin (TRX) is a small protein with REDOX activity that plays a crucial role in a plant’s growth, development, and stress resistance. The TRX family has been extensively studied in Arabidopsis, rice, and wheat, and so it is likely that its members have similar biological functions in Liriodendron that have not been reported in Liriodendron. In this study, we performed the genome-wide identification of the TRX gene family based on the Liriodendron chinense genome, leading to a total of 42 LcTRX gene members. A phylogenetic analysis categorized these 42 LcTRX proteins into 13 subfamilies. We further characterized their chromosome distributions, gene structures, conserved protein motifs, and cis-elements in the promoter regions. In addition, based on the publicly available transcriptome data for Liriodendron hybrid and following RT-qPCR experiments, we explored the expression patterns of LhTRXs to different abiotic stressors, i.e., drought, cold, and heat stress. Notably, we found that several LhTRXs, especially LhTRX-h3, were significantly upregulated in response to abiotic stress. In addition, the subcellular localization assay showed that LhTRX-h3 was mainly distributed in the cytoplasm. Subsequently, we obtained LhTRX-h3 overexpression (OE) and knockout (KO) callus lines in Liriodendron hybrid. Compared to the wild type (WT) and LhTRX-h3-KO callus proliferation of LhTRX-h3-OE lines was significantly enhanced with reduced reactive oxygen species (ROS) accumulation under drought stress. Our findings that LhTRX-h3 is sufficient to improve drought tolerance. and underscore the significance of the TRX gene family in environmental stress responses in Liriodendron.

Background: Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1) protein is important for synaptic remodeling and is highly expressed in the amygdala, an important brain region involved in various emotional behaviors. We examined whether SLITRK1 protein in the amygdala participates in NPP and comorbid ADD. Methods: A chronic NPP mouse model was constructed by L5 spinal nerve ligation; changes in chronic pain and ADD-like behaviors were measured in behavioral tests. Changes in SLITRK1 protein and excitatory synaptic functional proteins in the amygdala were measured by immunofluorescence and Western blot. Adeno-associated virus was transfected into excitatory synaptic neurons in the amygdala to up-regulate the expression of SLITRK1. Results: Chronic NPP-related ADD-like behavior was successfully produced in mice by L5 ligation. We found that chronic NPP and related ADD decreased amygdalar expression of SLITRK1 and proteins important for excitatory synaptic function, including Homer1, postsynaptic density protein 95 (PSD95), and synaptophysin. Virally-mediated SLITRK1 overexpression in the amygdala produced a significant easing of chronic NPP and ADD, and restored the expression levels of Homer1, PSD95, and synaptophysin. Conclusion: Our findings indicated that SLITRK1 in the amygdala plays an important role in chronic pain and related ADD, and may prove to be a potential therapeutic target for chronic NPP-ADD comorbidity.

ObjectiveBreast cancer is one of the most common causes of death among women. Statins, typically used for cholesterol management, have been hypothesized to reduce recurrence and mortality rates in breast cancer. However, this association remains a subject of debate. This study evaluates the potential impact of statins on breast cancer recurrence and mortality.MethodsA comprehensive search was conducted in the PubMed, EMBASE, and Cochrane databases for articles published up to June 2023. These articles examined the effect of statins on breast cancer recurrence and mortality both before and after diagnosis. The analysis was performed using random-effects models, calculating pooled hazard ratios (HR) and their 95% confidence intervals (CI).ResultsA total of 31 cohort studies, involving 261,834 female breast cancer patients, were included in this analysis. It was found that statin use prior to diagnosis was associated with a decrease in overall mortality (HR, 0.8; 95% CI, 0.69–0.93; I2 = 77.6%; P = 0.001) and breast cancer-specific mortality (HR, 0.76; 95% CI, 0.67–0.87; I2 = 72.7%; P = 0.005). Additionally, statin use after diagnosis was observed to reduce the recurrence of breast cancer (HR, 0.71; 95% CI, 0.61–0.82; I2 = 60%; P = 0.003), overall mortality (HR, 0.81; 95% CI, 0.70–0.92; I2 = 80.7%; P < 0.001), and breast cancer-specific mortality (HR, 0.76; 95% CI, 0.67–0.86; I2 = 74.5%; P < 0.001).ConclusionsThe findings of this study indicate that statin usage, both before and after breast cancer diagnosis, may be associated with reduced risks of overall and breast cancer-specific mortality, as well as lower recurrence rates.

BackgroundBreast cancer (BC) is one of the females’ most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies.MethodsA combined significance (pcombined) was calculated for each gene by Fisher’s method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a pcombined< 0.01 were subjected to univariate cox and Lasso regression, whereby an RS signature was established. The predicted performance of the RS signature would be assessed in GSE7390 and GSE20685, and emphatically analyzed in triple-negative breast cancer (TNBC) patients, while the expression of immune checkpoints and drug sensitivity were also examined. GSE176078, a single-cell dataset, was used to validate the differences in cellular composition in tumors between TNBC patients with different RS.ResultsThe RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment.ConclusionThe six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.

Background: Exosomes and cancer immunology are both important areas of research for cancer treatment. As much effort has been made to explore the relationship between exosomes and cancer immunology, exosomes in cancer immunology have become a hotspot in medical research. Methods: We retrieved all relevant publications between 2011 and 2021 from the Web of Science and utilized Microsoft Excel 365, Citespace, Online Analysis Platform of Literature Metrology ( http://bibliometric.com/ ) and software including VOS viewer to analyze and visualize the research result. Results: Of the 820 studies included, China published the most articles, followed by the USA. Cooperation between countries has progressed over the past decade. Shanghai Jiao Tong University and Oncotargets and Therapy were the institution and journal that published the most articles respectively. The most frequently cited article in this field, titled “Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver,” was published in Nature Cell Biology . Keywords were divided into three: Mechanism research, treatment application research, and diagnosis and prognosis research of which the latter was the newest cluster. “Microenvironment,” “PD-L1” and “M2 macrophage” were representative new keywords while “tumor suppressor” was the keyword cited most frequently. Conclusion: The publication trend shows that cooperation between different countries and institutions contributes to the development of this field. Researchers should continue to extend collaborations for further advances. The rising relative research interest indicated that this is a hot topic with great research potential. Macrophages polarization and PD-L1 application in tumor immunotherapy are worthy of further research. Hotspots will likely transfer from mechanistic research to clinical research, particularly for methods to increase the survival rate and improve the prognosis of cancer patients.

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0–1 versus 2–3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow‐up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high‐UA‐level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197–1.804]) and medium‐UA‐level group (adjusted HR, 1.478 [95% CI, 1.012–2.160]), compared with the low‐UA‐level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence‐based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.

Objective: To evaluate the effects of pelvic floor muscle training (PFMT) and perineal massage during late pregnancy on postpartum pelvic floor function in nulliparas. Design: Randomised controlled trial. Setting: The Peking University First Hospital, a teaching hospital in China. Participants: Two-hundred nulliparas were included. Interventions: Nulliparas were randomised into four groups in a 1:1:1:1 ratio. Group A, control; group B, perineal massage; group C, pelvic floor muscle training (PFMT); group D, perineal massage and PFMT. The intervention group received the corresponding intervention from 34 weeks of gestation until delivery. Measurements: Changes in pelvic floor function from 34 weeks of gestation to 6 weeks postpartum were assessed using pelvic floor electromyography (EMG), pelvic organ prolapse quantitation (POP-Q), and pelvic floor distress inventory-20 (PFDI-20). Results: Those with PFMT (groups C and D) had a smaller decline in pelvic floor EMG of fibre II than those without PFMT (groups A and B) [− 0.2 (− 7.1, 11.3) µV vs 6.1 (− 0.2, 15.2) µV, P = 0.040]. The same scenario was observed in the pelvic floor EMG of fibre I. The Aa point measurement differences of those with PFMT (groups C and D) were smaller than those without PFMT (groups A and B) [0.0 (0.0, 2.0) cm vs 1.0 (0.0, 3.0) cm, P = 0.006]. The same result was observed for point Ba. No difference was observed in EMG and POP-Q in nulliparas with (groups B and D) or without perineal massage (groups A and C). No differences were observed in PFDI-20 scores. Key conclusions: PFMT during late pregnancy enhanced pelvic floor EMG, while perineal massage alone or PFMT combined with perineal massage did not. Implications for practice: PFMT in late pregnancy enhances pelvic floor function.

Abstract Mesenchymal stem cell-based therapy has become an effective therapeutic approach for bone regeneration. However, there are still limitations in successful clinical translation. Recently, the secretome of mesenchymal stem cells, especially exosome, plays a critical role in promoting bone repair and regeneration. Exosomes are nanosized, lipid bilayer-enclosed structures carrying proteins, lipids, RNAs, metabolites, growth factors, and cytokines and have attracted great attention for their potential application in bone regenerative medicine. In addition, preconditioning of parental cells and exosome engineering can enhance the regenerative potential of exosomes for treating bone defects. Moreover, with recent advancements in various biomaterials to enhance the therapeutic functions of exosomes, biomaterial-assisted exosomes have become a promising strategy for bone regeneration. This review discusses different insights regarding the roles of exosomes in bone regeneration and summarizes the applications of engineering exosomes and biomaterial-assisted exosomes as safe and versatile bone regeneration agent delivery platforms. The current hurdles of transitioning exosomes from bench to bedside are also discussed.