Search

Abstract A common wisdom posits that transport of conserved quantities across clean nonintegrable quantum systems at high temperatures is diffusive when probed from the emergent hydrodynamic regime. We show that this empirical paradigm may alter if the strong interaction limit is taken. Using Krylov-typicality and purification matrix-product-state methods, we establish in short-to-intermediate time scales the following observations for the nonintegrable lattice model imitating the experimental Rydberg blockade simulator. Given the strict projection owing to the infinite density-density repulsion V, the Rydberg chain’s energy transport in the presence of a transverse field g is tentatively superdiffusive at infinite temperature featured by an anomalous scaling exponent $$\frac{3}{4}$$ 3 4 , indicating the potential existence of a novel dynamical universality class. Imposing, in addition, a growing longitudinal field h causes a putative superdiffusion-to-ballistic transport transition at h ≈ g. Interestingly, all the above results persist for large but finite interactions and temperatures, provided that the strongly interacting condition g, h ≪ k B T ≪ V is fulfilled. Our predictions are testable by current Rydberg quantum simulation facilities.

Abstract The astrocyte-to-neuron lactate shuttle model entails that, upon glutamatergic neurotransmission, glycolytically derived pyruvate in astrocytes is mainly converted to lactate instead of being entirely catabolized in mitochondria. The mechanism of this metabolic rewiring and its occurrence in human brain are unclear. Here by using immunohistochemistry (4 brains) and imaging mass cytometry (8 brains) we show that astrocytes of the adult human neocortex and hippocampal formation express barely detectable amounts of mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS). These data are corroborated by queries of transcriptomes (107 brains) of neuronal versus non-neuronal cells fetched from the Allen Institute for Brain Science for genes coding for a much larger repertoire of entities contributing to OXPHOS, showing that human non-neuronal elements barely expressed mRNAs coding for such proteins. With less OXPHOS, human brain astrocytes are thus bound to produce more lactate to avoid interruption of glycolysis.

Abstract Background The global prospective surveillance data showed the re-emergence of mycoplasma pneumoniae pneumonia (MPP) in Europe and Asia after the coronavirus disease 2019 pandemic. We sought to observe the effect of macrolide antibiotics in the treatment of MPP carrying a macrolide-resistant mutation gene and the potential of targeted next-generation sequencing (tNGS) as a front-line diagnostic in MPP patients. Methods The baseline characteristics of 91 children with MPP hospitalized from January to October 2023 were retrospectively analyzed. They were divided into two groups according to whether carrying the macrolide-resistant mutation or not. The logistic and linear regression analyses were used to determine whether the mutation was a standalone predictive predictor of the duration of fever and hospital length of stay. Results First, no patients had a fever for ≥ 7 days after macrolide treatment. But length of stay and hormone concentration were significantly different between the two groups (P

Abstract Holographic display offers the capability to generate high-quality images with a wide color gamut since it is laser-driven. However, many existing holographic display techniques fail to fully exploit this potential, primarily due to the system’s imperfections. Such flaws often result in inaccurate color representation, and there is a lack of an efficient way to address this color accuracy issue. In this study, we develop a color-aware hologram optimization approach for color-accurate holographic displays. Our approach integrates both laser and camera into the hologram optimization loop, enabling dynamic optimization of the laser’s output color and the acquisition of physically captured feedback. Moreover, we improve the efficiency of the color-aware optimization process for holographic video displays. We introduce a cascade optimization strategy, which leverages the redundant neighbor hologram information to accelerate the iterative process. We evaluate our method through both simulation and optical experiments, demonstrating the superiority in terms of image quality, color accuracy, and hologram optimization speed compared to previous algorithms. Our approach verifies a promising way to realize a high-fidelity image in the holographic display, which provides a new direction toward the practical holographic display.

Automatically and accurately identifying the deformation zone of coastal slope landslides is crucial for exploring the mechanism of landslides and predicting landslide disasters. To this end, this study proposes an integrated automatic recognition method combining Image Clipping (IC), Image Information Enhancement (IE), Adaptive K-means Clustering Segmentation (AKS), and Optimization (O): IC-IE-AKS-O, which achieves precise extraction of the deformation area in coastal slope landslide images. Firstly, due to the more complex natural environment of field slopes, to extend the monitoring duration, we introduce a hierarchical operation algorithm based on the HSV color model, which effectively mitigates the impact of sunlight, rain, and foggy weather on image recognition accuracy. Secondly, this study proposes a 2D landslide image segmentation technique that combines K-means clustering with global threshold segmentation for landslide images, enabling the segmentation of small image regions with precision. Finally, we combine image information enhancement technology with image segmentation technology. To verify its effectiveness, we identify a landslide image of a coastal slope in Pingtan. The method displays an average relative error of 5.20% and 5.14% in the X and Y directions, respectively. Its advantages are threefold: (1) The combination of image information enhancement and segmentation techniques can more accurately identify landslide areas that appear blurred in the image; (2) expanding the temporal dimension of coastal slope monitoring; (3) providing excellent boundary conditions and segmentation results. The practical application of this method ensures the stable and accurate operation of the coastal slope monitoring system, providing a safeguard for the sustainable development of marine safety.

Genomic instability is a core characteristic of cancer, often stemming from defects in DNA damage response (DDR) or increased replication stress. DDR defects can lead to significant genetic alterations, including changes in gene copy numbers, gene rearrangements, and mutations, which accumulate over time and drive the clonal evolution of cancer cells. However, these vulnerabilities also present opportunities for targeted therapies that exploit DDR deficiencies, potentially improving treatment efficacy and patient outcomes. The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality. This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway. Recent progress includes the development of inhibitors targeting other key DDR components such as DNA-PK, ATM, ATR, Chk1, Chk2, and Wee1 kinases. Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies.

Objective This study aimed to comprehensively analyze the detection capacity of non-invasive prenatal testing (NIPT) for chromosomal abnormalities of all 24 chromosomes, as well as high-risk indications for pregnancy and the fetal fraction, in a large cohort. Methods We retrospectively enrolled 118,969 pregnant women who underwent NIPT at Sichuan Provincial Maternity and Child Health Care Hospital from March 2019 to June 2022. The sensitivity, specificity, positive predictive value, negative predictive value, and positive chromosomal abnormality rate were calculated. The fetal fraction based on gestational age, maternal body mass index, and number was examined. Results NIPT demonstrated > 99% sensitivity and specificity for almost all of the common trisomies (T21, T18, and T13), sex chromosomal aneuploidies, rare autosomal trisomies, and microdeletion/microduplication syndromes. Positive predictive values varied from 12.0% to 89.6%. Advanced maternal age was associated with an increased risk of three major aneuploidies. The fetal fraction was positively correlated with gestational age and negatively correlated with the maternal body mass index. Conclusions NIPT can be used to effectively screen for chromosomal abnormalities across all 24 chromosomes. Advanced maternal age is a risk factor for high-risk pregnancy, and careful consideration of the fetal fraction is essential during NIPT.

Given the rapid development of the distributed energy resources (DER), involving DERs into the wholesale market under the market and renewable uncertainties to achieve economic benefits is necessary but challenging. In this work, an arbitraging strategy is proposed for DER aggregators that bridge DERs with the wholesale market through energy trading. Besides, a novel self-adaptive minimax regret (MMR)-based optimal offering model is proposed for the DER aggregator to handle the uncertainties in both renewable generations and market prices. Additionally, an exact and communication-free solution methodology is proposed to resolve the formulated optimization problem with high computational efficiency. In the numerical results, the proposed methods can achieve near-to-optimal profits. Moreover, the performance of the proposed approach remains satisfactory even if the environment becomes very volatile.

Knee medial compartment osteoarthritis is effectively treated by a medial open-wedge high tibial osteotomy (MOWHTO). The feasibility and safety of MOWHTO for mild lateral meniscal tears are unknown. This study examined the feasibility and safety of knee joint weight-bearing line ratio (WBLr) adjustment during MOWHTO with lateral meniscal injuries. We used a healthy adult male's lower extremities computed tomography scans and knee joint magnetic resonance imaging images to create a normal fine element (FE) model. Based on this model, we generated nine FE models for the MOWHTO operation (WBLr: 40–80%) and 15 models for various lateral meniscal injuries. A compressive load of 650N was applied to all cases to calculate the von Mises stress (VMS), and the intact lateral meniscus' maximal VMS at 77.5% WBLr was accepted as the corrective upper limit stress. Our experimental results show that mild lateral meniscal tears can withstand MOWHTO, while severe tears cannot. Our findings expand the use of MOWHTO and provide a theoretical direction for practical decisions in patients with lateral meniscal injuries.

Abstract The oncogenic role of circRNA in cancers including esophageal cancer (EC) has been well studied. However, whether and how circRNAs are involved in cancer cell metabolic processes remains largely unknown. Here, we reported that circRNA, circHIPK3, is highly expressed in ESCC cell lines and tissues. Knockdown of circHIPK3 significantly restrained cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, circHIPK3 was found to act as a ceRNA by sponging miR-637 to regulate FASN expression and fatty acid metabolism in ESCC cells. Anti-sense oligonucleotide (ASO) targeting circHIPK3 substantially inhibited ESCC both in vitro and in vivo. Therefore, these results uncover a modulatory axis constituting of circHIPK3/miR-637/FASN may be a potential biomarker and therapeutic target for ESCC in the clinic.

Osteonecrosis of the femoral head (ONFH) is a condition caused by a disruption or damage to the femoral head's blood supply, which causes the death of bone cells and bone marrow components and prevents future regeneration. Ferroptosis, a type of controlled cell death, is caused by iron‐dependent lipid peroxidation. Here, we identified ferroptosis‐related genes and infiltrating immune cells involved in ONFH and predicted the underlying molecular mechanisms. The GSE123568 dataset was subjected to differential expression analysis to identify genes related to ferroptosis. Subsequently, GO and KEGG pathway enrichment analyses, as well as protein–protein interaction (PPI) network analysis, were conducted. Hub genes involved in ferroptosis were identified using machine learning and other techniques. Additionally, immune infiltration analysis and lncRNA–miRNA‐mRNA network prediction analysis were performed. Finally, we determined whether ferroptosis occurred by measuring iron content. The hub genes were validated by ROC curve analysis and qRT–PCR. Four ferroptosis‐related hub genes (MAPK3, PTGS2, STK11, and SLC2A1) were identified. Additionally, immune infiltration analysis revealed a strong correlation among ONFH, hub genes, and various immune cells. Finally, we predicted the network relationship between differentially expressed lncRNAs and hub genes in the lncRNA–miRNA–mRNA network. MAPK3, PTGS2, STK11, and SLC2A1 have been identified as potential ferroptosis‐related biomarkers and drug targets for the diagnosis and prognosis of ONFH, while some immune cells, as well as the interaction between lncRNA, miRNA, and mRNA, have also been identified as potential pathogenesis markers and therapeutic targets.

In order to evaluate the impact of traffic emissions on urban air quality, an increasing number of cities have established near-road air quality monitoring stations (hereafter referred to as roadside stations). This study reviews the system of roadside stations, the data application, and the evolution of air pollutant concentrations in the traffic environment in typical cities, and proposes optimization suggestions roadside stations in the future. The results show a steady increase in publications on roadside stations over the years, with the annual average number of publications after 2020 being approximately 10 times the annual mean during 1994–2001. The literature mainly focused on ‘air pollution’, ‘particulate matter’, ‘emission’, etc., highlighting the impact of traffic emissions on urban air quality and human health. The purpose and principles of setting up roadside stations vary from country to country, but they are mainly used to assess the impact of vehicle emissions on air quality and to protect human health in the vicinity of roads. Over the past decade, near-road NO2 concentrations in typical cities have decreased by 30%–50%, although they remain higher than those observed in the urban atmosphere. The comprehensive analysis based on long-term data from roadside stations can provide insight into the effectiveness of vehicle emission control measures, and serve as a scientific basis for the formulation of future public health protection policies.

Introduction Significant numbers of patients undergoing minimally invasive lung surgery develop chronic symptoms such as chronic pain and chronic cough after surgery, which may lead to a reduced quality of life (QoL). Despite this, there remains a dearth of high-quality prospective studies on this topic. Therefore, our study aims to systematically investigate the incidence and progression of long-term chronic symptoms following minimally invasive lung surgery, as well as changes in patient’s psychological status and long-term QoL.Methods This is a single-centre, observational, prospective study that included patients with stage I non-small cell lung cancer or benign lesions. Prior to surgery, patients’ baseline levels of chronic pain, chronic cough and sleep will be documented. Anxiety, depression and QoL assessments will be conducted using the Hospital Anxiety and Depression Scale (HADS) and the European Organisation for Research and Treatment of Cancer (EORTC) 30-item QoL Questionnaire (QLQ-C30). Following surgery, pain and cough will be evaluated during the initial 3 days using the Numeric Pain Rating Scale and Visual Analogue Scale score, with assessments performed thrice daily. Additionally, sleep status will be recorded daily during this period. Subsequently, postoperative chronic symptoms and QoL will be assessed at weeks 1, 2, 4, 12, 26 and 52. Chronic cough will be evaluated using the Leicester Cough Questionnaire, chronic pain will be assessed via the Brief Pain Inventory and McGill Pain Questionnaire while the EORTC QLQ-C30 questionnaire and HADS will provide continuous monitoring of QoL, anxiety and depression statuses. Data will also include the timing of chronic symptom onset, predisposing factors, as well as aggravating and relieving factors.Ethics and dissemination Ethical approval was obtained from the Ethics Committees of Fujian Medical University Union Hospital. The findings will be disseminated in peer-reviewed publications.Trial registration number NCT06016881.

With the rapid development of distributed generation, represented by photovoltaic power, the access of a large number of distributed generation poses threats to the security and reliable operation of islanded distribution networks. However, relying on the distributed energy storage system can stabilize the island power supply, which can effectively improve the reliability of the island distribution network. To this end, under the premise of knowing photovoltaic output and load forecast curve, this paper proposes a distributed energy storage optimization configuration method in the active islanding operation mode of multi-source distribution network, which satisfies the “N-1″ safety criterion. First, this paper establishes an optimization configuration model for distributed energy storage with multiple objectives, including minimizing the load shedding in the non-fault loss of power zone, the initial investment cost of distributed energy storage, the node voltage deviation and the system frequency offset. Then, aiming at the islanded power flow calculation process mentioned above, an improved trust region algorithm is proposed, and integrating this method with the harmony search algorithm and ”N-1″ safety criterion solves the model. Finally, the IEEE 33-node distribution system is used to test the performance of the proposed algorithm. The results show that the proposed improved trust region algorithm has the advantages of fast convergence speed and short time-consumption compared with the traditional trust region algorithm. And the proposed optimization configuration scheme for distributed energy storage can satisfy the “N-1″ safety criterion of the distribution network under different fault scenarios.

Abstract Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota‐derived 3‐hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6‐mediated radiation damage. Irradiated cell‐fecal microbiota co‐culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43‐mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut‐immune axis in radiation pathophysiology, with potential therapeutic applications.

IntroductionOmega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized.MethodsMendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR–Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates.ResultsWe found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (p = 8 × 10−4), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (p = 2 × 10−2), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (p = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (p = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases.ConclusionThis study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.

IntroductionEpilepsy is a common neurological condition that affects a large number of individuals worldwide. One of the primary challenges in epilepsy is the accurate and timely detection of seizure. Recently, the graph regularized broad learning system (GBLS) has achieved superior performance improvement with its flat structure and less time-consuming training process compared to deep neural networks. Nevertheless, the number of feature and enhancement nodes in GBLS is predetermined. These node settings are also randomly selected and remain unchanged throughout the training process. The characteristic of randomness is thus more easier to make non-optimal nodes generate, which cannot contribute significantly to solving the optimization problem.MethodsTo obtain more optimal nodes for optimization and achieve superior automatic detection performance, we propose a novel broad neural network named self-adaptive evolutionary graph regularized broad learning system (SaE-GBLS). Self-adaptive evolutionary algorithm, which can construct mutation strategies in the strategy pool based on the experience of producing solutions for selecting network parameters, is incorporated into SaE-GBLS model for optimizing the node parameters. The epilepsy seizure is automatic detected by our proposed SaE-GBLS model based on three publicly available EEG datasets and one private clinical EEG dataset.Results and discussionThe experimental results indicate that our suggested strategy has the potential to perform as well as current machine learning approaches.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167–7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922–41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374–12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780–10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771–0.894) and 0.821 (95 % CI 0.720–0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

Abstract The development of highly active, reusable catalysts for aqueous‐phase reactions is challenging. Herein, metallic nickel is encapsulated in a nitrogen‐doped carbon–silica composite (SiO2@Ni@NC) as a catalyst for the selective hydrogenation of vanillin in aqueous media. The constructed catalyst achieved 99.8% vanillin conversion and 100% 4‐hydroxymethyl‐2‐methoxyphenol selectivity at room temperature. Based on combined scanning transmission electron microscopy, X‐ray photoelectron spectroscopy, and Raman analyses, the satisfactory catalytic performance is attributed to the composite structure consisting of an active metal, carbon, and silica. The hydrophilic silica core promoted dispersion of the catalyst in aqueous media. Moreover, the external hydrophobic NC layer has multiple functions, including preventing oxidation or leaching of the internal metal, acting as a reducing agent to reduce the internal metal, regulating the active‐site microenvironment by enriching the concentrations of H2 and organic reactants, and modifying the electronic structure of the active metal via metal–support interactions. Density functional theory calculations indicated that NC facilitates vanillin adsorption and hydrogen dissociation to promote aqueous‐phase hydrogenation. This study provides an efficient strategy for constructing encapsulated Ni‐based amphiphilic catalysts to upgrade biomass‐derived compounds.

Abstract Background The first local outbreak of Delta Variant B.1.617.2 COVID-19 of China occurred in Guangzhou city, south China, in May 2021. This study analyzed the transmission chains and local cluster characteristics of this outbreak, intended to provide information support for the development and adjustment of local prevention and control strategies. Methods The transmission chains and local cluster characteristics of 161 local cases in the outbreak were described and analyzed. Incubation period, serial interval and generation time were calculated using the exact time of exposure and symptom onset date of the cases. The daily number of reported cases and the estimated generation time were used to estimate the effective reproduction number (Rt). Results We identified 7 superspreading events who had more than 5 next generation cases and their infected cases infected 70.81%(114/161) of all the cases transmission. Dining and family exposure were the main transmission routes in the outbreak, with 29.19% exposed through dining and 32.30% exposed through family places. Through further analysis of the outbreak, the estimated mean incubation period was 4.22 (95%CI: 3.66–4.94) days, the estimated mean generation time was 2.60 (95%CI: 1.96–3.11) days, and the estimated Rt was 3.29 (95%CI: 2.25–5.07). Conclusions Classification and dynamically adjusted prevention and control measures had been carried out according to analysis of transmission chains and epidemical risk levels, including promoting nucleic acid screening at different regions and different risk levels, dividing closed-off area, controlled area according to the risk of infection, raising the requirements of leaving Guangzhou. By the above control measures, Guangzhou effectively control the outbreak within 28 days without implementing a large-scale lockdown policy.

Abstract To assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p

Abstract Background As global aging intensifies, older adults with chronic diseases are of increasing concern. Home and community-based services (HCBSs) have been proven to promote self-rated health (SRH) in older adults, but no research explored the associations between the use of overall HCBSs, three different types of HCBSs (health care, daily care, and social support services) and SRH among older adults with chronic diseases. Consequently, this study applies a national publicly available database to examine these associations among older adults with chronic diseases. Methods 8,623 older adults with chronic diseases (≥ 60 years old) were included in this study. SRH was evaluated applying a concise question with a 1 − 5 scale. HCBSs utilization was assessed through the question, “What kind of HCBSs were used in the community?”. Univariate general linear regression models aimed to compare the mean values of SRH in terms of HCBSs utilization in each group. This study is a cross-sectional study design and the relationship between HCBSs utilization and SRH was assessed by multilevel linear regression. Results The mean score for SRH among the respondents was 3.19, of whom 20.55% used one or more HCBSs, 19.47% utilized health care services, 2.44% utilized social support services, and only 0.55% utilized daily care services. The use of HCBSs was found to be linked to SRH among older adults with chronic diseases (β = 0.085, SE = 0.025, p

In this study, the structural characters, antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides (HRPs) obtained by the commonly used hot water (HRP-W), pressurized hot water (HRP-H), ultrasonic (HRP-U), acid (HRP-C) and alkali (HRP-A) assisted extraction methods were investigated. The results demonstrated that extraction methods had significant effects on extraction yield, monosaccharide composition, molecular weight, particle size, triple-helical structure, and surface morphology of HRPs except for the major linkage bands. Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability. The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities. Moreover, the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network (HRP-C, HRP-W and HRP-U), which exhibited stronger bile acid binding capacity. The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Submergence stress challenges direct seeding in rice cultivation. In this study, we identified a heat shock protein, NAL11, with a DnaJ domain, which can regulate the length of rice coleoptiles under flooded conditions. Through bioinformatics analyses, we identified cis-regulatory elements in its promoter, making it responsive to abiotic stresses, such as hypoxia or anoxia. Expression of NAL11 was higher in the basal regions of shoots and coleoptiles during flooding. NAL11 knockout triggered the rapid accumulation of abscisic acid (ABA) and reduction of Gibberellin (GA), stimulating rice coleoptile elongation and contributes to flooding stress management. In addition, NAL11 mutants were found to be more sensitive to ABA treatments. Such knockout lines exhibited enhanced cell elongation for coleoptile extension. Quantitative RT-PCR analysis revealed that NAL11 mediated the gluconeogenic pathway, essential for the energy needed in cell expansion. Furthermore, NAL11 mutants reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde under submerged stress, attributed to an improved antioxidant enzyme system compared to the wild-type. In conclusion, our findings underscore the pivotal role of NAL11 knockout in enhancing the tolerance of rice to submergence stress by elucidating its mechanisms. This insight offers a new strategy for improving resilience against flooding in rice cultivation.

The enantioselective mechanism of the esterase QeH against the two enantiomers of quizalofop–ethyl (QE) has been primitively studied using computational and experimental approaches. However, it is still unclear how the esterase QeH adjusts its conformation to adapt to substrate binding and promote enzyme–substrate interactions in the catalytic kinetics. The equilibrium processes of enzyme–substrate interactions and catalytic dynamics were reproduced by performing independent molecular dynamics (MD) runs on the QeH-(R)/(S)-QE complexes with a newly developed residue-specific force field (RSFF2C). Our results indicated that the benzene ring of the (R)-QE structure can simultaneously form anion–π and cation–π interactions with the side-chain group of Glu328 and Arg384 in the binding cavity of the QeH-(R)-QE complex, resulting in (R)-QE being closer to its catalytic triplet system (Ser78-Lys81-Tyr189) with the distances measured for the hydroxyl oxygen atom of the catalytic Ser78 of QeH and the carbonyl carbon atom of (R)-QE of 7.39 Å, compared to the 8.87 Å for (S)-QE, whereas the (S)-QE structure can only form an anion–π interaction with the side chain of Glu328 in the QeH-(S)-QE complex, being less close to its catalytic site. The computational alanine scanning mutation (CAS) calculations further demonstrated that the π–π stacking interaction between the indole ring of Trp351 and the benzene ring of (R)/(S)-QE contributed a lot to the binding stability of the enzyme–substrate (QeH-(R)/(S)-QE). These results facilitate the understanding of their catalytic processes and provide new theoretical guidance for the directional design of other key enzymes for the initial degradation of aryloxyphenoxypropionate (AOPP) herbicides with higher catalytic efficiencies.

This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan–Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients.

Abnormalities in pulmonary vasculature or technical issues during lung procurement can lead to an insufficient left atrial (LA) cuff in donors. However, surgeons frequently need to reconfigure these less-than-ideal lungs for transplantation. This case report introduces a novel technique for such reconstruction. The patient was a 35-year-old male diagnosed with pneumoconiosis for over a year. Due to progressive worsening dyspnoea leading to respiratory failure on multiple occasions, he was deemed a candidate for lung transplantation. While obtaining the donor's lung, an inadvertent short cut of the LA cuff around the left inferior pulmonary vein orifice resulted in the residual vein retracting into the pulmonary hilum. To overcome this, we employed the aortic arch for reconstruction, enabling the successful completion of the lung transplantation. On post-transplantation day 2, extracorporeal membrane oxygenation was no longer required. Mechanical ventilation ceased after 13 days, with the subsequent removal of a tracheostomy. The patient spent 35 days in the intensive care unit and 58 days in the hospital. Post-transplantation complications included primary graft dysfunction, acute kidney failure, pneumothorax in the transplanted lung, the clots in the inferior vena cava, and pneumonia. Remarkably, over a year of follow-up (19 months after lung transplantation), the patient reported no adverse events and had successfully returned to work. In this case, the aortic arch is an alternative for reconstructing an insufficient LA cuff.

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

BackgroundPost-thrombectomy intraparenchymal hyperdensity (PTIH) in patients with acute anterior circulation large vessel occlusion is a common CT sign associated with a higher incidence of futile reperfusion (FR). We aimed to develop a nomogram to predict FR specifically in patients with PTIH.MethodsWe retrospectively collected information on patients with acute ischemic stroke who underwent endovascular thrombectomy (EVT) at two stroke centers. A total of 398 patients with PTIH were included to develop and validate the nomogram, including 214 patients in the development cohort, 92 patients in the internal validation cohort and 92 patients in the external validation cohort. The nomogram was developed according to the independent predictors obtained from multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images within half an hour after EVT. The performance of the nomogram was evaluated with integrated discrimination improvement (IDI), category-free net reclassification improvement (NRI), the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analyses for discrimination, calibration ability, and clinical net benefits, respectively.ResultsOur nomogram was constructed based on three clinical factors (age, NIHSS score and ASPECT score) and two CT texture features (entropy and kurtosis), with AUC-ROC of 0.900, 0.897, and 0.870 in the development, internal validation, and external validation cohorts, respectively. NRI and IDI further validated the superior predictive ability of the nomogram compared to the clinical model. The calibration plot revealed good consistency between the predicted and the actual outcome. The decision curve indicated good positive net benefit and clinical validity of the nomogram.ConclusionThe nomogram enables clinicians to accurately predict FR specifically in patients with PTIH within half an hour after EVT and helps to formulate more appropriate treatment plans in the early post-EVT period.

The limited osteointegration often leads to the failure of implant, which can be improved by fixing bioactive molecules onto the surface, such as arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. Metal-Phenolic Networks (MPNs) have garnered increasing attention from different disciplines in recent years due to their simple and rapid process for depositing on various substrates or particles with different shapes. However, the lack of cellular binding sites on MPNs greatly blocks its application in tissue engineering. In this study, we present a facile and efficient approach for producing PC/Fe@c(RGDfc) composite coatings through the conjugation of c(RGDfc) peptides onto the surface of PC/Fe-MPNs utilizing thiol-click reaction. By combined various techniques (ellipsometry, X-ray photoelectron spectroscopy, Liquid Chromatography-Mass Spectrometry, water contact angle, scanning electronic microscopy, atomic force microscopy) the physicochemical properties (composition, coating mechanism and process, modulus and hydrophilicity) of PC/Fe@c(RGDfc) surface were characterized in detail. In addition, the PC/Fe@c(RGDfc) coating exhibits the remarkable ability to positively modulate cellular attachment, proliferation, migration and promoted bone-implant integration in vivo, maintaining the inherent features of MPNs: anti-inflammatory, anti-oxidative properties, as well as multiple substrate deposition. This work contributes to engineering MPNs-based coatings with bioactive molecules by a facile and efficient thiol-click reaction, as an innovative perspective for future development of surface modification of implant materials.

Objectives This study measures the differences in inpatient performance after a points-counting payment policy based on diagnosis-related group (DRG) was implemented. The point value is dynamic; its change depends on the annual DRGs’ cost settlements and points of the current year, which are calculated at the beginning of the following year.Design A longitudinal study using a robust multiple interrupted time series model to evaluate service performance following policy implementation.Setting Twenty-two public general hospitals (8 tertiary institutions and 14 secondary institutions) in Wenzhou, China.Intervention The intervention was implemented in January 2020.Outcome measures The indicators were case mix index (CMI), cost per hospitalisation (CPH), average length of stay (ALOS), cost efficiency index (CEI) and time efficiency index (TEI). The study employed the means of these indicators.Results The impact of COVID-19, which reached Zhejiang Province at the end of January 2020, was temporary given rapid containment following strict control measures. After the intervention, except for the ALOS mean, the change-points for the other outcomes (p0.05), the uptrend of the CEI mean in tertiary institutions alleviated (p0.05).Conclusions This study showed a positive effect of the DRG policy in Wenzhou, even during COVID-19. The policy can motivate public general hospitals to improve their comprehensive capacity and mitigate discrepancies in treatment expenses efficiency for similar diseases. Policymakers are interested in whether the reform successfully motivates hospitals to strengthen their internal impetus and improve their performance, and this is supported by this study.

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.

Artificial sweeteners (AS) are extensively utilized as sugar substitutes and have been recognized as emerging environmental contaminants. While the effect of AS on aquatic organisms has garnered recent attention, their effects on soil invertebrates and gut microbial communities remain unclear. To address this knowledge gap, we exposed springtails (Folsomia candida) to both single and combined treatments of four typical AS (sucralose [SUC], saccharin [SAC], cyclamate [CYC], and acesulfame [ACE]) at environmentally relevant concentrations of 0.01, 0.1 and 1 mg kg−1 in soil. Following the first-generational exposure, the reproduction of juveniles showed a significant increase under all the AS treatments of 0.1 mg kg−1. The transcriptomic analysis revealed significant enrichment of several Kyoto Encyclopedia of Gene and Genome pathways (e.g., glycolysis/gluconeogenesis, pentose and glucuronate interconversions, amino sugar, and nucleotide sugar metabolism, ribosome, and lysosome) in springtails under all AS treatments. Analysis of gut bacterial microbiota indicated that three AS (SUC, CYC, and ACE) significantly decreased alpha diversity, and all AS treatments increased the abundance of the genus Achromobacter. After the sixth-generational exposure to CYC, weight increased, but reproduction was inhibited. The pathways that changed significantly (e.g., extracellular matrix-receptor interaction, amino sugar and nucleotide sugar metabolism, lysosome) were generally similar to those altered in first-generational exposure, but with opposite regulation directions. Furthermore, the effect on the alpha diversity of gut microbiota was contrary to that after first-generational exposure, and more noticeable disturbances in microbiota composition were observed. These findings underscore the ecological risk of AS in soils and improve our understanding of the toxicity effects of AS on living organisms.

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Abstract Objectives The incidence of multiple primary lung cancer (MPLC) has increased in recent years. The risk factors of MPLC are not well studied, especially in the Asian population. This case-control study investigated the association between a family history of cancer and MPLC risk. Methods We used data from people who surgically confirmed MPLC with at least 2 nodes of Fujian Medical University Union Hospital and matched 1:2 normal individuals as controls between 2016 and 2017. Information on age, sex, lifestyle, personal history, and family history of cancer was collected using a self-administered questionnaire, and odds ratios (OR) were estimated using unconditional logistic regression. Results We included 2 104 patients. In total, 321 patients with histologically confirmed MPLC and 642 healthy controls were studied. The significantly higher ratio of current smokers was observed for the cases than the controls (54.1% vs. 30.0%). A family history of LC in first-degree relatives of the cases reported a significantly higher proportion than in the controls (15.3% vs. 8.6%). Family history of all cancers and LC significantly increased the risk of MPLC (OR = 1.64, P = 0.009 and OR = 2.59, P = 0.000, respectively). The multivariate analysis identified a significantly increased risk of MPLC (OR = 2.45, P = 0.000) associated with parents and siblings influenced by LC history. The younger age (aged

Abstract Background Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. MicroRNA‐1301‐3p (miR‐1301‐3p) plays vital roles in a majority of malignancies. The aim of this study was to investigate the role of miR‐1301‐3p/NBL1 axis on ESCA cell invasion, migration, epithelial‐mesenchymal transition (EMT) process, as well as its association with prognosis of ESCA patients. Methods The expression levels of miR‐1301‐3p and NBL1 were predicted by bioinformatics and further verified by RT‐qPCR assays. Kaplan–Meier (K–M) plotter analysis and univariate and multivariate Cox analyses were used to evaluate the relationship between miR‐1301‐3p and clinicopathological variables and prognosis. The role of miR‐1301‐3p on cell invasion, migration was detected by transwell invasion, and wound healing assays, respectively. The EMT‐related proteins were detected by western blot. The target genes and the target binding sites were predicted by bioinformatics and further determined by RT‐qPCR assay. Results MiR‐1301‐3p was remarkably upregulated in ESCA tissues and cells, and its high expression was associated with poor prognosis of ESCA. Overexpression of miR‐1301‐3p promoted ESCA cell invasion, migration and mediated EMT process in vitro, whereas knockdown of miR‐1301‐3p showed the opposite effects. Moreover, NBL1 was predicted as a target gene of miR‐1301‐3p. NBL1 was lowly expressed in ESCA cells and significantly decreased after upregulation of miR‐1301‐3p. Meanwhile, we found that low expression of NBL1 was significantly associated with poor prognosis of ESCA patients. Conclusion MiR‐1301‐3p is a potential biomarker for predicting the prognosis of ESCA patients. It may promote ESCA invasion, migration and EMT progression by regulating NBL1 expression.

Abstract Background Indeterminate pulmonary nodules (IPNs) are common after surgery for esophageal cancer. The paucity of data on postoperative IPNs for esophageal cancer causes a clinical dilemma. Objective The aim of this study was to identify the characteristics and clinical significance of IPNs after radical esophagectomy for metastatic esophageal cancer, determine the risk factors for pulmonary metastasis, and construct a risk score model to standardize the appropriate time to either follow up or treat the patient. Methods All consecutive patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between 2013 and 2016 were included in this retrospective study. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop risk score models. Results A total of 816 patients were enrolled in the study. During a median follow-up period of 45 months, IPNs were detected in 221 (27.1%) patients, of whom 66 (29.9%) were diagnosed with pulmonary metastases. The following five variables maintained prognostic significance after multivariate analyses: the pathologic N category, number of IPNs, shape of IPNs, time of detection of IPNs, and size of IPNs. The Pulmonary Metastasis Prediction Model (PMPM) scale ranges from 0 to 15 points, and patients with higher scores have a higher probability of pulmonary metastases. The Hosmer–Lemeshow test showed a good calibration performance of the clinical prediction model (χ 2 = 8.573, P = 0.380). After validation, the PMPM scale showed good discrimination with an AUC of 0.939. Conclusion A PMPM scale for IPNs in patients who underwent esophagectomy for ESCC may be clinically useful for diagnostic and therapeutic decision-making.

Abstract Objectives The proper procedure for inferior pulmonary ligament (IPL) during upper lobectomy remains a topic of debate. To address this matter, we carried out a trial comparing the clinical outcomes of IPL preservation versus IPL dissection during thoracoscopic upper lobectomy (TUL). Methods Patients undergoing thoracoscopic left/right upper lobectomy (TLUL/TRUL) were assigned to either the dissection group (Group D) or the preservation group (Group P). Our primary objective was to quantify and compare the alterations in postoperative residual bronchial angle and lung volume changes between the two groups. Our secondary objective encompassed the assessment of various other intraoperative and postoperative outcomes. Results Following adherence to the inclusion and exclusion criteria, we enrolled 100 patients (41 left and 59 right) in Group P and 108 patients (41 left and 67 right) in Group D for the study. Our findings revealed that in TLUL, Group P was able to reduce the degree of postoperative residual bronchial angle change (P 0.05) with regard to alterations in lung volume or the occurrence of postoperative complications—except for the duration of postoperative hospital stay (P

To address challenges in locating high-impedance grounding faults (HIGFs) and isolating fault areas in resonant grounding systems, this paper proposes a novel fault identification method based on coordinating a Peterson coil and a resistance grounding system. This method ensures power supply reliability by extinguishing the fault arc during transient faults with the Peterson coil. When a fault is determined to be permanent, the neutral point switches to a resistance grounding mode, ensuring regular distribution of zero-sequence currents in the network, thereby addressing the challenges of HIGF localization and fault area isolation. Fault calibration and nature determination rely on recognizing neutral point displacement voltage waveforms and dynamic characteristics, eliminating interference from asymmetric phase voltage variations. Fault area identification involves assessing the polarity of zero-sequence current waveforms attenuation during grounding mode switching, preventing misjudgments in grounding protection due to random initial fault angles and Peterson coil compensation states. Field experiments validate the feasibility of this fault location method and its control strategy.

Abstract Background Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC. Methods All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2–3 N0 M0 or T2–3 N + M0 will be included. A total of 25 patients are to be recruited for the study. Twelve patients will be recruited in phase I, with at least two achieving major pathological response (MPR) before entering phase II. They will be treated with radical surgery within 4–8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after 12 patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission. Discussion We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC. Trial registration This trial protocol has been registered on the NIH Clinical Trials database ( www.clinicaltrials.gov/ , NCT05176002. Registered on 2022/01/04). The posted information will be updated as needed to reflect protocol amendments and study progress.

Abstract Background Osteoarthritis is a very common clinical disease in middle-aged and elderly individuals, and with the advent of ageing, the incidence of this disease is gradually increasing. There are few studies on the role of basement membrane (BM)-related genes in OA. Method We used bioinformatics and machine learning methods to identify important genes related to BMs in OA patients and performed immune infiltration analysis, lncRNA‒miRNA-mRNA network prediction, ROC analysis, and qRT‒PCR. Result Based on the results of machine learning, we determined that LAMA2 and NID2 were the key diagnostic genes of OA, which were confirmed by ROC and qRT‒PCR analyses. Immune analysis showed that LAMA2 and NID2 were closely related to resting memory CD4 T cells, mast cells and plasma cells. Two lncRNAs, XIST and TTTY15, were simultaneously identified, and lncRNA‒miRNA‒mRNA network prediction was performed. Conclusion LAMA2 and NID2 are important potential targets for the diagnosis and treatment of OA.

Abstract Mitochondrial dysfunction has been suggested to contribute to Parkinson’s disease pathogenesis, though an understanding of the extent or exact mechanism of this contribution remains elusive. This has been complicated by challenging nature of pathway-based analysis and an inability simultaneously study multiple related proteins within human brain tissue. We used imaging mass cytometry (IMC) to overcome these challenges, measuring multiple protein targets, whilst retaining the spatial relationship between targets in post-mortem midbrain sections. We used IMC to simultaneously interrogate subunits of the mitochondrial oxidative phosphorylation complexes, and several key signalling pathways important for mitochondrial homoeostasis, in a large cohort of PD patient and control cases. We revealed a generalised and synergistic reduction in mitochondrial quality control proteins in dopaminergic neurons from Parkinson’s patients. Further, protein-protein abundance relationships appeared significantly different between PD and disease control tissue. Our data showed a significant reduction in the abundance of PINK1, Parkin and phosphorylated ubiquitinSer65, integral to the mitophagy machinery; two mitochondrial chaperones, HSP60 and PHB1; and regulators of mitochondrial protein synthesis and the unfolded protein response, SIRT3 and TFAM. Further, SIRT3 and PINK1 did not show an adaptive response to an ATP synthase defect in the Parkinson’s neurons. We also observed intraneuronal aggregates of phosphorylated ubiquitinSer65, alongside increased abundance of mitochondrial proteases, LONP1 and HTRA2, within the Parkinson’s neurons with Lewy body pathology, compared to those without. Taken together, these findings suggest an inability to turnover mitochondria and maintain mitochondrial proteostasis in Parkinson’s neurons. This may exacerbate the impact of oxidative phosphorylation defects and ageing related oxidative stress, leading to neuronal degeneration. Our data also suggest that that Lewy pathology may affect mitochondrial quality control regulation through the disturbance of mitophagy and intramitochondrial proteostasis.

Abstract Background As the phenomenon of ageing continues to intensify, home and community-based services (HCBSs) have been increasingly important in China. However, the association between HCBSs utilization and depressive symptoms in older adults in China is unclear. Consequently, this study aimed to examine the association between HCBSs utilization and depressive symptoms in Chinese older adults. Methods This study included 7,787 older adults (≥ 60 years old) who were recruited within the framework of the 2018 China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale (CES-D-10). HCBSs utilization was assessed via the question, “What kind of HCBSs were being utilized in their community?”. Data were analyzed using binary logistic regression models and generalized hierarchical linear models (GHLM). Results Of the 7,787 participants, 20.0% (n = 1,556) reported that they utilized HCBSs, and 36.7% (n = 2,859) were evaluated that they had depressive symptoms. After adjusting for individual- and province-level covariates, the HCBSs utilization was found to be associated with depressive symptoms (OR = 1.180, 95% CI: 1.035–1.346, p

Objective: Segmentectomy as a parenchymal-sparing surgical approach has been recommended over lobectomy in select patients with early-stage non–small cell lung cancer. This study aimed to address 3 aspects of segmentectomy (“patient indication”; “segmentectomy approaches”; “lymph node assessment”) where there is limited clinical guidance. Methods: A modified Delphi approach comprising 3 anonymous surveys and 2 expert discussions was used to establish consensus on the aforementioned topics among 15 thoracic surgeons (2 Steering Committee; 2 Task Force; 11 Voting Experts) from Asia who have extensive segmentectomy experience. Statements were developed by the Steering Committee and Task Force based on their clinical experience, published literature (rounds 1-3), and comments received from Voting Experts through surveys (rounds 2-3). Voting Experts indicated their agreement with each statement on a 5-point Likert scale. Consensus was defined as ≥70% of Voting Experts selecting either “Agree”/“Strongly Agree” or “Disagree”/“Strongly Disagree.” Results: Consensus from the 11 Voting Experts was reached on 36 statements (11 “patient indication” statements; 19 “segmentation approaches” statements; 6 “lymph node assessment” statements). In rounds 1, 2, and 3, consensus was reached on 48%, 81%, and 100% of drafted statements, respectively. Conclusions: A recent phase 3 trial reported significantly improved 5-year overall survival rates for segmentectomy compared with lobectomy, proposing thoracic surgeons to consider segmentectomy as a surgical option in suitable patients. This consensus serves as a guidance to thoracic surgeons considering segmentectomy in patients with early non–small cell lung cancer, outlining key principles that surgeons should consider in surgical decision-making.

Background: Whether minimally invasive esophagectomy (MIE) is superior to open esophagectomy (OE) in the treatment of esophageal squamous cell carcinoma (ESCC) is still uncertain. Therefore, this multicenter prospective study aimed to compare MIE with OE in postoperative parameters and long-term survival. Methods: All hospitalized patients with cT1b-3N0–1M0 thoracic ESCC treated by MIE or OE were enrolled from 19 selected centers from April 1, 2015 to December 31, 2018. The propensity score matching (PSM) was performed to minimize the selection bias. The basic clinicopathological characteristics and 3-year overall survival (OS) as well as disease-free survival (DFS) of two groups were compared by R version 3.6.2. Results: MIE were performed in 1,387 patients and OE in 335 patients. 335 cases in each group were finally matched by PSM, and no significant differences in the essential demographic characteristics were observed between the MIE and OE groups after PSM. Compared with OE, MIE had significantly less intraoperative bleeding, less total drainage volume, shorter postoperative hospital stay, and harvested significantly more lymph nodes (LNs) (all P < 0.001). There were no significant differences in the major postoperative complications and death rates between MIE and OE. The 3-year OS and DFS were 77.0% and 68.1% in the MIE group versus 69.3% and 60.9% in the OE group (OS: P = 0.03; DFS: P = 0.09), and the rates were 75.1% and 66.5% in the MIE group versus 66.9% and 58.6% in the OE group for stage cII patients (OS: P = 0.04, DFS: P = 0.09), respectively. Conclusions: Compared with OE, MIE is a safe and effective treatment approach with similar mortality and morbidity. It has the advantages in harvesting more LNs, improving postoperative recovery and survival of stage cII ESCC patients.

The CBF (C-repeat binding factors) genes play important roles in response to abiotic stress and environmental changes. In the present study, a total of 18 CBF genes were identified from a grapevine. Their domains, phylogenetics, and collinearity were analysed. The results revealed, that 18 VviCBF genes were distributed on 10 chromosomes unevenly in the grape genome. Promoter data analysis showed that the CBF gene has many cis-acting elements related to plant growth and development, light response, hormone, and abiotic stress response. We found that six VviCBF genes including, VviCBF5, VviCBF13, VviCBF14, VviCBF15, VviCBF16, and VviCBF18 differentially expressed during fruit developmental stages. Furthermore, four VviCBF genes including, VviCBF1, VviCBF3, VviCBF6, and VviCBF11 were expressed at the early stage of bud dormancy, whereas, nine VviCBF genes were expressed at the bud dormancy-breaking stage. Additionally, various VviCBFs genes respond to different abiotic and biotic stress. These findings will lay a foundation for further study of the CBF genes in bud dormancy, downy mildew, and abiotic and biotic stresses.

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1’s target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function and the broader role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.

Introduction Oesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour regression observed in a proportion of patients after treatment, but prognostic improvement remains limited. Immunotherapy in combination with chemotherapy (CT) has been shown to be efficacious as the first-line treatment of advanced OC and neoadjuvant therapy. Therefore, we conducted a prospective, two-arm, randomised, unblinded phase II study to explore the efficacy of camrelizumab in combination with CT versus chemoradiotherapy for the conversion of unresectable advanced OSCC.Methods and analysis All participants meeting the inclusion criteria will be enrolled after signing an informed consent form. Patients with clinically cT4b or spread to at least one group of lymph nodes with possible invasion of surrounding organs and unresectable locally advanced squamous carcinoma of the thoracic segment of the oesophagus will be included in the study. Patients with suspected distant metastases on the preoperative examination will be excluded from this study. Patients eligible for enrolment will be grouped by centre randomisation according to the study plan. Patients will undergo radical surgery after completion of two cycles of chemotherapy (CT) combined with camrelizumab induction therapy or concurrent chemoradiotherapy if assessed to be operable. Patients evaluated as inoperable will be scheduled for a multidisciplinary consultation to determine the next treatment option. The primary endpoint is the R0 resection rate in patients undergoing surgery after treatment. Secondary endpoints are the rate of major pathological remission, pathological complete response rate, overall survival, progression-free survival and adverse events for all patients.Ethics and dissemination Ethical approval was obtained from the ethics committees of Fujian Medical University Union Hospital (No. 2022YF039-02). The findings will be disseminated in peer-reviewed publications.Trial registration number NCT05821452.