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Abstract This survey explores the transformative impact of foundation models (FMs) in artificial intelligence, focusing on their integration with federated learning (FL) in biomedical research. Foundation models such as ChatGPT, LLaMa, and CLIP, which are trained on vast datasets through methods including unsupervised pretraining, self-supervised learning, instructed fine-tuning, and reinforcement learning from human feedback, represent significant advancements in machine learning. These models, with their ability to generate coherent text and realistic images, are crucial for biomedical applications that require processing diverse data forms such as clinical reports, diagnostic images, and multimodal patient interactions. The incorporation of FL with these sophisticated models presents a promising strategy to harness their analytical power while safeguarding the privacy of sensitive medical data. This approach not only enhances the capabilities of FMs in medical diagnostics and personalized treatment but also addresses critical concerns about data privacy and security in healthcare. This survey reviews the current applications of FMs in federated settings, underscores the challenges, and identifies future research directions including scaling FMs, managing data diversity, and enhancing communication efficiency within FL frameworks. The objective is to encourage further research into the combined potential of FMs and FL, laying the groundwork for healthcare innovations.

Nanocomposite-coatings were fabricated on the Ti6Al4V titanium alloy plates via plasma electrolyte oxidation (PEO) with the addition of ZrO2 nanoparticles (NPs), followed by low surface energy modification. Effects of ZrO2 NPs concentrations on microstructure, adhesive strength, wear resistance, hydrophobic property and corrosion resistance of the PEO coatings were investigated, and corresponding influence mechanisms were revealed. The dual-layered nanocomposite-PEO coatings consisting of anatase, rutile, TiP2O7, m-ZrO2, t-ZrO2, ZrTiO4 and Zr3(PO4)4 were formed, and ZrO2 NPs were incorporated into the coatings via both inertia and reactive modes. Both the average pore size and porosity were reduced with ZrO2 NPs addition. The adhesive strength of the PEO coatings was promoted via the addition of ZrO2 NPs. An enhancement in wear resistance was achieved for the PEO coatings with ZrO2 NPs due to the lower COF, higher microhardness and denser microstructure than that without NPs addition. The hydrophobic property was enhanced for the low surface energy modified PEO coatings with ZrO2 NPs. A significant enhancement in the corrosion resistance was achieved for the PEO coatings with the addition of ZrO2 NPs. The PEO coatings with ZrO2 NPs in 6 g/L exhibited a higher corrosion inhibition efficiency and a higher charge transfer resistance than that in other concentrations and without ZrO2 NPs addition, respectively. The enhancement in corrosion resistance for the PEO coatings with ZrO2 NPs in 6 g/L were due to the formation of corrosion-resistant phases including ZrO2 and ZrTiO4, and denser microstructure with better hydrophobic properties compared with that in other concentrations.

Abstract Early disease diagnosis hinges on the sensitive detection of signaling molecules. Among these, hydrogen sulfide (H2S) has emerged as a critical player in cardiovascular and nervous system signaling. On-chip immunoassays, particularly nanoarray-based interfacial detection, offer promising avenues for ultra-sensitive analysis due to their confined reaction volumes and precise signal localization. Beyond the DNA or protein biomolecules array, this work presents a promising hybrid small molecule nano-array for H2S detection, using the power of dual molecules: a dye for fluorescence emission and a quencher with specific H2S reactivity. Upon H2S interaction, the quenched fluorescence reignites, creating an easily detectable array of bright spots. The molecule nano-array sensor shows exceptional responses to H2S over 8 magnitudes of dynamic range from 1 fM to 0.1 μM, with a remarkable detection limit of 1 fM, just using a 10 μL solution. This H2S detection method has the potential to significantly improve bioassay platforms, and the hybrid small-molecule nano-arrays we developed could be a valuable tool for advancing signaling molecule detection.

A novel dissimilar resistance spot welding of Ti6Al4V alloy and 316L stainless steel was performed via copper as interlayer by using optimal electrodes. A significant improvement in nugget morphology being of less defects was achieved with increasing the copper interlayer thickness from 50 μm to 400 μm. Thinner interfacial reaction layers at both the nugget/titanium interface and the nugget/stainless steel interface and finer equiaxed dendritic grained structure at the inner nugget were formed with copper interlayer thickness of 300 μm compared with those without interlayer. The formation of TiCu and Ti2Cu was facilitated with the incorporation of Cu into the nugget, which effectively inhibited the formation of the brittle Ti–Fe intermetallic compounds including Fe2Ti. The nugget in the welded joint with copper interlayer in 300 μm thickness exhibited a far lower microhardness than that of the interlayer-free welded joint, and the average microhardness reduced to 604 HV in the inner nugget, which was about 36% lower than that of the interlayer-free welded joint. The tensile shear load of the welded joint exhibited an increased tendency with increasing interlayer thicknesses from 50 μm to 300 μm, and the maximum tensile shear load of 6.3 kN was obtained with the interlayer thickness of 300 μm, which was ∼97% higher than that of the interlayer-free welded joint. The welded joint with copper interlayer exhibited hybrid ductile and fragile fractured characteristics. The work would provide a facile and cost-effective method to achieve a reliable welded joint of Ti alloy and stainless steel.

Dissimilar materials of TC4 titanium alloy and 316L stainless steel were joined by means of resistance spot welding with nickel interlayer in different thicknesses. A significant enhancement in terms of nugget morphology quality with less defects was achieved for the welded joints with nickel interlayer compared with that without interlayer. With increasing the nickel interlayer thickness from 50 μm to 300 μm, the effective nugget diameter increased gradually from ∼4.8 mm to ∼5.2 mm, which was lower than that of the interlayer-free welded joint being ∼5.9 mm. A thinner intermetallic compound layer with dual-layered structure features with thickness of ∼11 μm was formed at the nugget/titanium interface in the welded joint with nickel interlayer compared with that of the interlayer-free welded joint, meanwhile an intermetallic compound layer with thickness of ∼3 μm was formed at the nugget/stainless steel interface, which exhibited serrated structure features. The introduction of nickel interlayer in the welded joint could suppress the formation of the brittle Ti–Fe intermetallics such as Fe2Ti, and facilitate the formation of TiNi, Ti2Ni and TiNi3. A more homogeneous current density distribution and a lower peak temperature (1809 °C) during welding were achieved via employing nickel interlayer. With increasing nickel interlayer thickness from 0 μm to 300 μm, the tensile shear load of welded joints experienced an increased tendency first and then decreased, meanwhile the maximum tensile shear load of 3.7 kN was obtained with the interlayer thickness of 200 μm, which was 61% higher than that of the interlayer-free welded joint.

ABSTRACT Importance Aicardi–Goutières syndrome (AGS) is a rare genetic disorder mainly affecting the central nervous system and autoimmunity. However, research on AGS among Chinese patients is limited. Objective To summarize the neurologic phenotypes and genetic causes in pediatric AGS patients, providing insights for early recognition and diagnosis in the Chinese population. Methods Clinical features and neuroimaging results of the patients diagnosed with AGS from Beijing Children's Hospital between January 2018 and January 2022 were collected. Whole exome sequencing was used for genetic analysis. Results A total of 15 patients was included, all presenting with various neurological symptoms, including developmental delay (100%), motor skill impairment (100%), language disability (78.6%), dystonia (93.3%), microcephaly (73.3%), sleep disorders (26.7%), regression (20.0%), vessel disease (6.7%), and epilepsy (6.7%). Neuroimaging revealed intracranial calcification (86.7%), cerebral atrophy (73.3%), and leukodystrophy (73.3%). Seven genes were identified, with TREX1 being the most common (40.0%, 6/15), followed by IFIH1 (20.0%, 3/15). Variant c.294dupA (p.C99Mfs*3) was detected in four unrelated patients, accounting for 66.7% (4/6) patients with the TREX1 variant. A literature review showed that TREX1 gene mutations in 35.6% (21/59) of AGS patients among the Chinese population. Interpretation Neurological symptoms are the most prevalent and severe presentation of AGS. Diagnosis may be considered when symptoms such as developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy emerge. TREX1 mutations are predominant in the Chinese population.

Expressway weaving areas meet dissipative structure characteristics. When traffic states reach a certain range, they exhibit self-organising criticality, and slight changes may trigger unpredictable congestion. This paper examines the correlation between the dissipative structure of the weaving area and key traffic parameters. The range of dissipative structure states in the weaving area is defined through the dissipative structure concept with three-phase traffic flow theory and real traffic data. Based on the fundamental diagram and measured traffic data, the weaving area dissipative structure model characterising the relationship between critical state changes in traffic volume is constructed and validated. Finally, the Cell Transmission Model simulation was used to examine the characteristic relationship between the weaving area dissipative structure state duration, the weaving area length and the weaving flow ratio. The results show that the length of the dissipative structure state is maintained when the traffic flow is self-organised into a free-flow or a congested state positively correlates with the length of the weaving area. Higher weaving flow ratios lead to shorter dissipative structure state durations during congestion formation, and the exact opposite during congestion evacuation. This paper is important for analysing the congestion mechanism and managing congestion.

Abstract Background Woven coronary artery (WCA) is a rare and underdiagnosed congenital anomaly that involves multiple thin and tortuous epicardial arterial conduits reassembling distally into a single lumen. Recanalized thrombus may present as woven-like coronary arteries, appearing similar to WCA on angiographic images. Case presentation A 58-year-old female patient with intermittent chest pain for 5 years and polycythaemia vera (PV) for 8 years. The left anterior descending artery was presented like WCA on coronary angiography and finally confirmed as recanalized thrombus by optical coherence tomography(OCT), which might have been caused by PV. Given the patient’s high thrombotic risk of PV and thrombotic changes in the left circumflex artery (LCX), we ultimately chose a conservative treatment without stenting. Conclusions OCT would be needed for the diagnosis and differential diagnosis of woven-like coronary arteries. And physicians should take an appropriate treatment in a personalized way in patients with PV.

【Objective】Hibiscus rosa-sinensis L. has high ornamental value due to rich flower colors and is widely used in urban greening and landscape architecture in South China. In order to provide theoretical and technical support for in-depth excavation of variety characteristics and flower color directional breeding technology, the characteristic differences of types and contents of anthocyanin in different flower colors were detected, and the specificity and common characteristics of different varieties of H. rosa-sinensis L. were analyzed.【Method】The anthocyanin composition and content of different petal tissues of white (W), red (R) and yellow (Y) flowers were determined by targeted metabolomics. Functional annotation, identification and analysis of metabolites were performed by using pathway enrichment analysis and multivariate statistical methods.【Result】The results showed that a total of 90 metabolites were detected in W, R and Y colors of H. rosa-sinensis L., among which 78 were differential metabolites, including cyanidin (41.11%), delphinidin (20.00%), peonidin (13.33%), and etc. There were 62 (Y vs R), 50 (Y vs W) and 65 (R vs W) differential metabolites among different flower colors, with a total of 22 common differential metabolites. Comprehensively considering the significance and absolute contents of differences in different comparative combinations, it was found thta the cyanidin-3-O-sambubioside-glucoside, pelargonidin-3-O-sophoroside, cyanidin-3-O-gentiobioside and peonidin-3-O-glucoside were relatively high in red flower; the delphinidin-3-O-(6''-O-tartaryl) glucoside, procyanidin B4 and procyanidin B3 were relatively high in yellow flower. KEGG metabolic pathways analysis revealed that differential metabolites were significantly enriched in different flower color tissues.【Conclusion】The cyanidin-3-O-sambubioside-glucoside, pelargonidin-3-O-sophoroside, cyanidin-3-O-gentiobioside and peonidin-3-O-glucoside were important metabolites determining the flower red color, while procyanidin B3 was an important metabolite determining the flower yellow color. This result preliminary revealed the differences in metabolites among different colors of H. rosa-sinensis L., which could provide theoretical references for the mechanism of color formation and color improvement for H. rosa-sinensis L..

Abstract Diabetic cardiomyopathy (DCM), a severe complication of diabetes, is characterized by mitochondrial dysfunction, oxidative stress, and DNA damage. Despite its severity, the intrinsic factors governing cardiomyocyte damage in DCM remain unclear. It is hypothesized that impaired iron–sulfur (Fe–S) cluster synthesis plays a crucial role in the pathogenesis of DCM. Reduced S‐sulfhydration of cysteine desulfurase (NFS1) is a novel mechanism that contributes to mitochondrial dysfunction and PARthanatos in DCM. Mechanistically, hydrogen sulfide (H2S) supplementation restores NFS1 S‐sulfhydration at cysteine 383 residue, thereby enhancing Fe–S cluster synthesis, improving mitochondrial function, increasing cardiomyocyte viability, and alleviating cardiac damage. This study provides novel insights into the interplay between Fe–S clusters, mitochondrial dysfunction, and PARthanatos, highlighting a promising therapeutic target for DCM and paving the way for potential clinical interventions to improve patient outcomes.

The water quality health of the farm ponds in the small watersheds of the Three Gorges Reservoir Area is critical to maintaining agricultural productivity. The main challenge in managing the water quality is predicting and controlling the release of total phosphorus (TP) from endogenous pollution in the substrate. Numerous studies have shown that endogenous pollution release from large water bodies like lakes is influenced by factors such as temperature and pH. However, knowledge about the response mechanisms in smaller water bodies, such as farm ponds, is still lacking. This study focuses on TP, using indoor simulation tests and orthogonal tests to investigate the transport and transformation of TP in four representative farm ponds located in Ruxi Town, at the heart of the Three Gorges Reservoir Area. Results showed that seasonal variations led to temperature changes thereby significantly affect TP release, with the highest release rates occurring in summer when the temperature was highest. The farm ponds demonstrated a significant annual cycle in phosphorus source-sink dynamics. Furthermore, factors including pH and water depth influenced the release rates; acidic conditions promoted phosphorus release from the substrate more effectively than alkaline conditions. Additionally, disturbances at lower intensities were observed to inhibit TP release. Building on these findings, this study further explored the advantages and limitations of using multiple regression analysis and BP Neural Network models for modeling phosphorus release and predicting annual TP release. Ultimately, the study proposes measures to reduce and control endogenous pollution, laying a foundation for managing eutrophication and protecting aquatic health in farm ponds.

Abstract In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin–eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia–reperfusion injury.

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Skeletal muscle atrophy was one of main complications of type 2 diabetes mellitus. Hydrogen sulfide (H2S) is involved in various physiological functions, such as anti-hypertension and anti-oxidant. Skeletal muscle atrophy caused by type 2 diabetes could lead to the regeneration of muscle fibers. Wnt signaling pathway plays a crucial important role in this process. H2S maybe regulate the Wnt signaling pathway to alleviate skeletal muscle atrophy, however, this role has not been clarified. The aim of this study is to investigate the potential regulatory role of H2S in the Wnt signaling pathway. C2C12 myoblasts treated with 500 μmol palmitate as an in vitro model. Western blot was used to detect the levels of CSE, PKM1, β-catenin, MuRF1, MYOG, MYF6 and MYOD1. In addition, MuRF1 was mutated at Cys44 and MuRF1 S-sulfhydration was detected by biotin switch assay. The interaction between PKM1 and MuRF1 was assessed via Co-immunoprecipitation. Differentiation of C2C12 myoblasts was evaluated using LAMININ staining. These data showed the levels of CSE, β-catenin, PKM1, MYOG, MYF6 and MYOD1 were decreased in pal group, compared with control and pal + NaHS groups. MuRF1 Cys44 mutants increased the protein levels of β-catenin, MYOG, MYF6 and MYOD1 in pal group. Our results suggest that H2S regulates the S-sulfhydration levels of MuRF1 at Cys44, influencing the ubiquitination levels of PKM1 and ultimately promoting myoblast differentiation.

Background In patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens.Methods In a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes.Results Of the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of −5.2% and −3.3%; both were >−10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1–3 severity.Conclusions Zuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL.Trial registration number Chinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.

BackgroundPulmonary Artery in situ Thrombosis (PAIST) refers to a thrombus forming within the pulmonary arterial system, distinct from an embolus originating from elsewhere in the body (e.g., the deep veins of the lower extremities) and traveling to the lungs where it lodges and forms.Case presentationWe present a case of PAIST caused by the arterial ductus arteriosus. The patient primarily presented with dyspnea, and the chest pain dichotomy Computed Tomography Angiography(CTA) suggested that a nodular low-density filling defect was seen in the lumen of the left pulmonary artery trunk. Initially, pulmonary embolism (PE) was suspected. However, upon reevaluation of the imaging, it became apparent that the patient's pulmonary artery obstruction was closely associated with the ductus arteriosus. After admission, the patient was treated with sodium ampicillin (2.0 g Q12H) for infection, heparin sodium (5,000 IU Q12H) for anticoagulation, and metoprolol succinate extended-release tablets (23.75 mg QD) to correct cardiac remodeling, among other treatments. Subsequently, the patient underwent a cardiac surgery involving the ligation of the arterial duct, resection of pulmonary artery lesions, and open-heart surgery with extracorporeal circulation support. Postoperative examination of the pulmonary artery mass indicated coagulation tissue. The final diagnosis was “PAIST”.ConclusionBoth PAIST and PE manifest as low-density filling defects in the pulmonary arteries. However, due to the relative unfamiliarity with PAIST, such findings are often initially attributed to PE.

Customer Relationship Management (CRM) is vital in modern business, aiding in the management and analysis of customer interactions. However, existing methods struggle to capture the dynamic and complex nature of customer relationships, as traditional approaches fail to leverage time series data effectively. To address this, we propose a novel GWO-attention-ConvLSTM model, which offers more effective prediction of customer churn and analysis of customer satisfaction. This model utilizes an attention mechanism to focus on key information and integrates a ConvLSTM layer to capture spatiotemporal features, effectively modeling complex temporal patterns in customer data. We validate our proposed model on multiple real-world datasets, including the BigML Telco Churn dataset, IBM Telco dataset, Cell2Cell dataset, and Orange Telecom dataset. Experimental results demonstrate significant performance improvements of our model compared to existing baseline models across these datasets. For instance, on the BigML Telco Churn dataset, our model achieves an accuracy of 95.17%, a recall of 93.66%, an F1 score of 92.89%, and an AUC of 95.00%. Similar results are validated on other datasets. In conclusion, our proposed GWO-attention-ConvLSTM model makes significant advancements in the CRM domain, providing powerful tools for predicting customer churn and analyzing customer satisfaction. By addressing the limitations of existing methods and leveraging the capabilities of deep learning, attention mechanisms, and optimization algorithms, our model paves the way for improving customer relationship management practices and driving business success.

BackgroundKlebsiella pneumoniae is a major cause of hospital-acquired infections (HAIs), primarily spread through environmental contamination in hospitals. The effectiveness of current chemical disinfectants is waning due to emerging resistance, which poses environmental hazards and fosters new resistance in pathogens. Developing environmentally friendly and effective disinfectants against multidrug-resistant organisms is increasingly important.MethodsThis study developed a bacteriophage cocktail targeting two common carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, ST11 KL47 and ST11 KL64. The cocktail was used as an adjunctive disinfectant in a hospital’s respiratory intensive care unit (RICU) via ultrasonic nebulization. Digital PCR was used to quantify CRKP levels post-intervention. The microbial community composition was analyzed via 16S rRNA sequencing to assess the intervention’s impact on overall diversity.ResultsThe phage cocktail significantly reduced CRKP levels within the first 24 hours post-treatment. While a slight increase in pathogen levels was observed after 24 hours, they remained significantly lower than those treated with conventional disinfectants. 16S rRNA sequencing showed a decrease in the target pathogens’ relative abundance, while overall species diversity remained stable, confirming that phages selectively target CRKP without disrupting ecological balance.DiscussionThe findings highlight the efficacy and safety of phage-based biocleaners as a sustainable alternative to conventional disinfectants. Phages selectively reduce multidrug-resistant pathogens while preserving microbial diversity, making them a promising tool for infection control.

Objective Tread defects are a primary manifestation of wheel failures in high-speed railway EMU (electrical multiple unites) trains, significantly impacting both EMU train operation safety and passenger ride comfort. Wheel tread defects are predominantly concentrated on front and rear cars, which may result from a combination of various factors, requiring predictive method that comprehensively integrate various influencing factors. Method Based on the wheel reprofiling maintenance data of EMU train operated by a railway bureau, the dataset sample consists of 10 features (including 4 nominal and 6 continuous features) and the data are preprocessed. By treating the imbalanced dataset through synthetic minority over-sampling technique (SMOTE), a standardized dataset is constructed. A DNN (deep neural network) model is established to combine the underlying features and form a high-level abstract representation of the features. The optimal learning performance of the model is achieved through network structure adjustment and hyperparameter optimization. The model is trained and tested to verify its prediction effect. Result & Conclusion The data-driven prediction method for wheel tread defects of front and rear cars demonstrates high-predictive accuracy and relatively excellent comprehensive performance, achieving a precision rate of 92.5%. Thus the probability of wheel tread damage of front and rear cars can be effectively predicted.

Abstract Background Aberrant alternative splicing (AS) is a pervasive event during colorectal cancer (CRC) development. SF3B3 is a splicing factor component of U2 small nuclear ribonucleoproteins which are crucial for early stages of spliceosome assembly. The role of SF3B3 in CRC remains unknown. Methods SF3B3 expression in human CRCs was analyzed using publicly available CRC datasets, immunohistochemistry, qRT-PCR, and western blot. RNA-seq, RNA immunoprecipitation, and lipidomics were performed in SF3B3 knockdown or overexpressing CRC cell lines. CRC cell xenografts, patient-derived xenografts, patient-derived organoids, and orthotopic metastasis mouse models were utilized to determine the in vivo role of SF3B3 in CRC progression and metastasis. Results SF3B3 was upregulated in CRC samples and associated with poor survival. Inhibition of SF3B3 by RNA silencing suppressed the proliferation and metastasis of CRC cells in vitro and in vivo, characterized by mitochondria injury, increased reactive oxygen species (ROS), and apoptosis. Mechanistically, silencing of SF3B3 increased mTOR exon-skipped splicing, leading to the suppression of lipogenesis via mTOR-SREBF1-FASN signaling. The combination of SF3B3 shRNAs and mTOR inhibitors showed synergistic antitumor activity in patient-derived CRC organoids and xenografts. Importantly, we identified SF3B3 as a critical regulator of mTOR splicing and autophagy in multiple cancers. Conclusions Our findings revealed that SF3B3 promoted CRC progression and metastasis by regulating mTOR alternative splicing and SREBF1-FASN-mediated lipogenesis, providing strong evidence to support SF3B3 as a druggable target for CRC therapy.

Purpose – The safety and reliability of high-speed trains rely on the structural integrity of their components and the dynamic performance of the entire vehicle system. This paper aims to define and substantiate the assessment of the structural integrity and dynamical integrity of high-speed trains in both theory and practice. The key principles and approaches will be proposed, and their applications to high-speed trains in China will be presented. Design/methodology/approach – First, the structural integrity and dynamical integrity of high-speed trains are defined, and their relationship is introduced. Then, the principles for assessing the structural integrity of structural and dynamical components are presented and practical examples of gearboxes and dampers are provided. Finally, the principles and approaches for assessing the dynamical integrity of high-speed trains are presented and a novel operational assessment method is further presented. Findings – Vehicle system dynamics is the core of the proposed framework that provides the loads and vibrations on train components and the dynamic performance of the entire vehicle system. For assessing the structural integrity of structural components, an open-loop analysis considering both normal and abnormal vehicle conditions is needed. For assessing the structural integrity of dynamical components, a closed-loop analysis involving the influence of wear and degradation on vehicle system dynamics is needed. The analysis of vehicle system dynamics should follow the principles of complete objects, conditions and indices. Numerical, experimental and operational approaches should be combined to achieve effective assessments. Originality/value – The practical applications demonstrate that assessing the structural integrity and dynamical integrity of high-speed trains can support better control of critical defects, better lifespan management of train components and better maintenance decision-making for high-speed trains.

Abstract This study aims to explore the relationship between traffic flow states and crash type/severity in the scenarios of normal crashes, primary crashes, and secondary crashes using the association rules mining approach. The crash data and real‐time traffic data were collected from the I‐880 freeway for five years in California, USA. The secondary crashes were identified using a speed contour plot approach. Traffic flow states were identified by the three‐phase flow theory. The results showed that the free flow is associated with the proportion of the sideswipe normal crash, the hit object primary crash, and the injury primary crash. The synchronized flow, the wide moving jams, and the transitional state from synchronized flow to wide moving jams are associated with the proportion of the rear‐end secondary crash. The transitional state from synchronized flow to free flow is associated with the proportion of the rear‐end primary crash and the property damage only primary crash. In addition, the unsafe speed behaviour can increase the proportion of the rear‐end normal, primary, and secondary crashes. The unsafe lane change behaviour can increase the proportion of the sideswipe normal, primary, and secondary crashes. These results have the potential to reduce the secondary crash probability.

Abstract Introduction The pericapsular nerve group (PENG) block has been shown to be an effective approach to alleviating pain and reducing the need for opioids among older adults following hip surgery, with possible motor-sparing effects. No reports to date, however, have described appropriate ropivacaine volumes for use in the context of PENG block. The present prospective randomized controlled study was thus developed to assess the quadriceps muscle strength and analgesic efficacy associated with PENG block performed using three different volumes of 0.33% ropivacaine following general anesthesia in older adults undergoing hip arthroplasty. Methods In this prospective randomized double-blind controlled clinical study, 60 patients were assigned at random to undergo ultrasound-guided PENG block for hip arthroplasty using different volumes of ropivacaine. Specifically, these patients were administered 10 ml (Group A, n = 20), 20 ml (Group B, n = 20), or 30 ml (Group C, n = 20) of 0.33% ropivacaine. Quadriceps muscle strength was evaluated at 6 h post-surgery. Visual analog scale (VAS) scores at rest and with movement were assessed at 4, 6, 12, and 24 h post-surgery. Block duration, adverse event incidence, and patient satisfaction were evaluated at 24 h post-surgery. Results Quadriceps motor block incidence rates at 6 h post-surgery in the 10 ml, 20 ml, and 30 ml groups were 5%, 20%, and 75%, respectively. Quadriceps muscle weakness at 6 h post-surgery was significantly more common in the 30 ml group relative to the others (p

Abstract The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient’s prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.

In order to solve the problems such as small influence range, fast decay rate, difficulty in gas disaster control and long treatment period of gas extraction drilling in Hebi Mining Area, a technological process of coordinated stamping operation was put forward, and the technical mode of drilling and stamping coordinated operation with automatic drilling rig group drilling - temporary sealing hole pre-pumping - stamping joint operation after pre-pumping is formed, and industrial test is carried out in Hebi No.6 Coal Mine for industrial trials, the field application results show that: the technology mode gives full play to the advantages of automatic drilling rig continuous drilling, fast operation, reducing staff and improving efficiency, realizes the specialization, continuity and scale of gas extraction drilling construction operation and hydraulic stamping coordinated penetration operation, and makes the construction work efficiency of construction of penetration drilling in the bottom rock tunnel for gas treatment increase by 48% under the same geological conditions; meanwhile, the at the same time, after the construction of extraction holes by automatic drilling rig is completed, the temporary sealing of the extraction holes is carried out, so that the free gas in the holes is greatly reduced after extraction, which greatly reduces the frequency of gas overrunning accidents in the roadway during the construction of hydraulic measures and effectively guarantees the safety of construction; the average gas extraction concentration of the test borehole is 1.31 times of that of the conventional hydraulic ramming measure, and the average daily pure extraction volume of the test unit borehole is 1.79 times of that of the conventional hydraulic ramming measure.

The high-amplitude and high-frequency wheel–rail impacts excited by wheel flat result in severe contact friction in axle-box bearing (ABB), and the friction can cause a temperature rise or even structural damage of ABB. To this end, a thermal analysis model considering the vehicle operation environment is proposed to analyze the temperature characteristics of ABB. Various coupling dynamics effects between the vehicle–track system and ABB are synergistically integrated. The heat conduction, convection, and radiation between the various components of ABB are also integrated into the thermal analysis modeling. By the field tests, the accuracy of the ABB thermal model is validated. The results obtained through the model simulation show that the ABB temperature increases with vehicle speed and wheel flat length, and the ABB temperature at the outside row is higher than that at the inside row. Moreover, the temperature of the roller, cage, inner ring, outer ring, and axle box increases following an ascending order. Specifically, the temperature at the small end of the roller is higher than that at the large end. The findings of this study can provide engineering guidelines for the condition monitoring of ABBs.

Fertilization can improve soil nutrition and increase the yield of Sapindus mukorossi, but the response of soil microbial communities to fertilization treatments and their correlation with soil nutrition and Sapindus mukorossi yield are unclear. In order to investigate the characteristics of soil physicochemical qualities and the bacterial community, we carried out a field experiment comparing various quantities of nitrogen (N), phosphorus (P), and potassium (K) fertilizers to the unfertilized control treatments and the yield of Sapindus mukorossi in raw material forests in response to different applications of fertilizers and to try to clarify the interrelation among the three. Results showed that (1) there are significant differences in the effects of different fertilization treatments on the soil properties of Sapindus mukorossi raw material forests. The increase in the application rates of nitrogen or phosphorus fertilizers significantly reduced the soil pH value. (2) Compared with control, the α-diversity of bacterial communities was significantly lower in N3P2K2 and N1P1K2 treatments. Among the dominant groups of soil bacteria at the phylum level, the relative abundance of Chloroflexi showed an increase and then a decrease trend with the increase in N application. The relative abundance of Firmicutes, Bacteroidota, and Fusobacteriota was positively correlated with the application of P and K fertilizers, while the relative abundance of Acidobacteriota and Verrucomicrobiota decreased with the increase in P and K fertilizers. (3) The N2P2K2 treatment produced the highest sapindus yield (1464.58 kg/ha), which increased by 258.67% above the control. (4) Redundancy analysis (RDA) showed that the primary determinants of bacterial community structure were soil pH, total K, and effective P concentration. (5) Structural equation modeling (SEM) showed that soil nutrient content was the main direct factor driving the yield of Sapindus mukorossi, whereas the bacterial community attributes (e.g., diversity and structure) had minor effects on the yield. In summary, the rational use of formulated fertilization can change the bacterial community structure, improve the bacterial diversity, and increase the soil nutrient content, with the latter exerting a significant effect on the improvement of the yield of Sapindus mukorossi.

The normalized operation of 30,000-ton heavy-haul trains is of significant importance for enhancing the transportation capacity of heavy-haul railways. However, with the increase in train formation size, traditional braking strategies result in excessive longitudinal impulse when combined pneumatic and electric braking is applied on long, steep gradients. This presents a serious challenge to the braking safety of the train. To this end, this paper establishes a longitudinal dynamic model of a 30,000-ton heavy-haul train based on vehicle system dynamics theory, and validates the model’s effectiveness through line test data. On this basis, the influence of two braking parameters, namely, the distribution of the magnitude of the electric braking force and the matching time of pneumatic braking and electric braking, on the longitudinal dynamic behavior of heavy-haul trains is studied. Thereby, an optimized combined pneumatic and electric braking strategy is formulated to reduce the longitudinal impulse of the trains. The results show that setting reasonable braking parameters can effectively reduce the longitudinal impulse, with the braking matching time having a significant impact on the longitudinal impulse. Specifically, when using a strategy where the electric braking forces of three locomotives are set to 90 kN, 300 kN, and 300 kN, with a 30 s delay in applying the electric braking force, a better optimization effect is achieved. The two proposed braking strategies reduce the maximum longitudinal forces by 20.27% and 47.83%, respectively, compared to conventional approaches. The research results provide effective methods and theoretical guidance for optimizing the braking strategy and ensuring the operational safety of 30,000-ton heavy-haul trains.

Signal retiming is the most cost-efficient measure to reduce vehicle delay and alleviate congestion on urban roads. Previous studies have explored the potential of using connected vehicle data for signal retiming specifically under the current low-penetration environment, which will significantly reduce the cost and increase the productivity of signal retiming. However, the existing methods are mostly deterministic and do not well consider the uncertainty in both traffic demand and capacity. This compromises their robustness in a real application. In this study, a novel traffic state measure—queue service time (QST)—is introduced and used as the only input to generate a robust signal plan at isolated intersections for a time-of-day period. First, a Bayesian-based model is proposed to estimate the QST distribution by collectively using the lower and upper boundary observations reported by connected vehicles. Then, a goal programming-based signal optimization model is formulated using quantiles of QST as input, which accounts for the combined uncertainty in both traffic demand and capacity. Simulation experiments validate the effectiveness and robustness of the proposed method. It is shown that the proposed QST estimation model is reliable to use under a penetration rate as low as 0.05 and can effectively estimate the actual distribution in both under- and oversaturation conditions. Compared with a demand-based method that only accounts for uncertainty in traffic demand, the proposed QST-based signal timing optimization method shows its superiority in reducing the occurrence of oversaturation or phase failure, as well as enhancing performance against the worst cases.

The sampled-data asynchronous control problem for T-S fuzzy systems is investigated in this paper. Firstly, a new fuzzy Lyapunov functional that contains the fuzzy line integral function and an improved looped functional is constructed, in which two new system state integral terms and some augmented terms are involved. Secondly, the asynchronous issue of premise variables is considered by taking some reasonable restrictions on the membership functions. Thirdly, based on the constructed fuzzy Lyapunov functional, with the help of some zero equations, new stability and stabilization conditions are established. Especially, the case of linear systems is presented to further illustrate the effectiveness of the constructed looped functional. Finally, two examples are given to show the superiority of this work.

Abstract Background Diabetic cardiomyopathy, a distinctive complication of diabetes mellitus, has been correlated with the presence of intracellular lipid deposits. However, the intricate molecular mechanisms governing the aberrant accumulation of lipid droplets within cardiomyocytes remain to be comprehensively elucidated. Methods Both obese diabetic (db/db) mice and HL‐1 cells treated with 200 μmol/L palmitate and 200 μmol/L oleate were used to simulate type 2 diabetes conditions. Transmission electron microscopy is employed to assess the size and quantity of lipid droplets in the mouse hearts. Transcriptomics analysis was utilized to interrogate mRNA levels. Lipidomics and ubiquitinomics were employed to explore the lipid composition alterations and proteins participating in ubiquitin‐mediated degradation in mice. Clinical data were collected from patients with diabetes‐associated cardiomyopathy and healthy controls. Western blot analysis was conducted to assess the levels of proteins linked to lipid metabolism, and the biotin‐switch assay was employed to quantify protein cysteine S‐sulfhydration levels. Results The administration of H2S donor, NaHS, effectively restored hydrogen sulfide levels in both the cardiac tissue and plasma of db/db mice (+7%, P

A blood glucose concentration and temperature sensor with a balloon-shaped single-mode fiber (SMF) based on a core-offset structure is proposed and experimentally demonstrated. The balloon-shaped SMF is created by offset-fusing a straight-line SMF between two other SMFs, thereby forming a Mach–Zehnder interferometer (MZI). The core-offset structure can effectively excite higher-order cladding modes. The experimental results showed that the maximum sensitivity of blood glucose concentration was 0.331 nm/(mmol/l) and the maximum sensitivity of temperature was 0.216 nm/°C when the offset distance was 10 μm. Dual-parameter measurement was achieved through a dual-parameter matrix. In addition, the sensor has characteristics such as simple structure, low cost, good stability, and electromagnetic interference resistance, making it potentially valuable for diagnosing high blood glucose and related conditions.

Enhancing residents’ purchasing intention of prepared dishes is crucial for the sustainable development of the prepared dishes industry. Understanding how residents’ cognition influences their continuous purchasing intention can provide valuable insight for developing and refining company strategies, thereby reducing industry development obstacles. Based on the theory of distributed cognition, this study utilizes questionnaire data from urban residents in Beijing and Shanghai, and employs Structural Equation Modeling to explore the influence of cognition on the continuous purchasing intention of Chinese urban residents towards prepared dishes. The study results reveal that: (1) Individual power and geographical power have a significant positive effect on residents’ continuous purchasing intention for prepared dishes, while cultural power does not have a significant effect. (2) Risk perception partially mediates the effect of individual power and geographical power on continuous purchasing intention and fully mediates the effect of cultural power on continuous purchasing intention. Recommendations include: (1) The government should enhance standardization and supervision to create a favorable consumption environment; (2) Enterprises should provide more objective and transparent information to improve residents’ knowledge of prepared dishes and establish a good reputation.

With the continuous development of information technology, the information environment while driving is constantly being enriched, and driver information processing and application are also dynamically evolving. Analysing information processing and application can better provide information services and is particularly important for traffic safety. Based on VOSviewer bibliometric software, this paper explores the research hotspots and future development trends of the driver information processing and application fields using the Web of Science (WoS) core collection as the data source. The results show that the field has a long history and has grown steadily in recent years. The United States, China and Germany are the top three countries in terms of the number of published articles. “Situational awareness and visual load”, “route selection under variable information signs”, “en-route information and behaviour” and “new information technology attitudes” are important knowledge bases for driver information processing and application. En-route information sources, human-computer interaction, and autonomous vehicle information are the research trends of the driver information processing and application field. The results of this research can help people comprehensively and systematically understand the current situation of driver information processing and application research, provide directions for future driver information processing and application research, and promote the engineering application of such research.

Abstract Excessive ROS accumulation contributes to cardiac injury in type 2 diabetes mellitus. Hydrogen sulfide (H2S) is a vital endogenous gasotransmitter to alleviate cardiac damage in diabetic cardiomyopathy (DCM). However, the underlying mechanisms remain unclear. In this study, we investigated the effects of NaHS administration in db/db mice via intraperitoneal injection for 20 weeks and the treatment of high glucose (HG), palmitate (PA) and NaHS in HL-1 cardiomyocytes for 48 h, respectively. H2S levels were decreased in hearts of db/db mice and HL-1 cardiomyocytes exposed to HG and PA, which were restored by NaHS. Exogenous H2S activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/glutathione (GSH) pathway, suppressed ferroptosis and mitigated mitochondrial apoptosis in db/db mice. However, these effects were abrogated after Nrf2 knockdown. NaHS treatment elevated the ubiquitination level of Kelch-like ECH-associated protein (Keap1) by preserving its E3 ligase synoviolin (Syvn1), resulting in Nrf2 nuclear translocation. H2S facilitated the sulfhydration of Syvn1-cys115 site, a post-translational modification. Transfecting Syvn1 C115A in cardiomyocytes exposed to HG and PA partially attenuated the effects of NaHS on Nrf2 and cell death. Our findings suggest that exogenous H2S regulates Nrf2/GPx4/GSH pathway by promoting the Syvn1-Keap1 interaction to reduce ferroptosis and mitochondrial apoptosis in DCM.

Abstract Background Myocardial ischemia reperfusion injury (MIRI), the tissue damage which is caused by the returning of blood supply to tissue after a period of ischemia, greatly reduces the therapeutic effect of treatment of myocardial infarction. But the underlying functional mechanisms of MIRI are still unclear. Methods We constructed mouse models of MIRI, extracted injured and healthy myocardial tissues, and performed transcriptome sequencing experiments (RNA-seq) to systematically investigate the dysregulated transcriptome of MIRI, especially the alternative splicing (AS) regulation and RNA binding proteins (RBPs). Selected RBPs and MIRI-associated AS events were then validated by RT-qPCR experiments. Results The differentially expressed gene (DEG) analyses indicated that transcriptome profiles were changed by MIRI and that DEGs’ enriched functions were consistent with MIRI’s dysregulated pathways. Furthermore, the AS profile was synergistically regulated and showed clear differences between the mouse model and the healthy samples. The exon skipping events significantly increased in MIRI model samples, while the opposite cassette exon events significantly decreased. According to the functional analysis, regulated alternative splicing genes (RASGs) were enriched in protein transport, cell division /cell cycle, RNA splicing, and endocytosis pathways, which were associated with the development of MIRI. Meanwhile, 493 differentially expressed RBPs (DE RBPs) were detected, most of which were correlated with the changed ratios of AS events. In addition, nine DE RBP genes were validated, including Eif5, Pdia6, Tagln2, Vasp, Zfp36l2, Grsf1, Idh2, Ndrg2, and Uqcrc1. These nine DE RBPs were correlated with RASGs enriched in translation process, cell growth and division, and endocytosis pathways, highly consistent with the functions of all RASGs. Finally, we validated the AS ratio changes of five regulated alternative splicing events (RASEs) derived from important regulatory genes, including Mtmr3, Cdc42, Cd47, Fbln2, Vegfa, and Fhl2. Conclusion Our study emphasized the critical roles of the dysregulated AS profiles in MIRI development, investigated the potential functions of MIRI-associated RASGs, and identified regulatory RBPs involved in AS regulation. We propose that the identified RASEs and RBPs could serve as important regulators and potential therapeutic targets in MIRI treatment in the future.

Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Abstract Background Disparities in COVID-19 outcomes exist on the basis of ethnicity and comorbidities. Minority ethnic groups in the UK are known to have poorer COVID-19 outcomes, but also an increased prevelance of certain comorbidities associated with severe outcomes. Additionally, despite the prevalence of certain psychiatric disorders there is a lack of research establishing their relationship with COVID-19 outcomes. Methods We used UK Biobank data, involving 472,182 participants, to test for an association between comorbidities and COVID-19 diagnosis (n = 30,901); and to test for an association between comorbidities and severe COVID-19 (n = 3182). This was done by performing univariable and multivariable logistic regression analysis, estimating odds ratios (ORs) and their 95% confidence intervals (95% CIs). The comorbidities studied were coronary heart disease (CHD), hypertension, type II diabetes mellitus (T2DM), obesity, chronic kidney disease (CKD), depression and anxiety. Multivariable models were adjusted for various socioeconomic, demographic and health-related confounders. We then performed sub-group analysis by common UK ethnic groups (White, South Asian, and Black). Results Increased prevalence of all studied comorbidities was seen in both outcomes, compared to the rest of the cohort. All studied comorbidities were associated with an increased risk of COVID-19 infection and severity across all models. For example, the adjusted ORs (95% CI) for depression were 1.112 (1.083 – 1.161) for COVID-19 diagnosis and 2.398 (2.163 – 2.658) for severe COVID-19. Sub-group analysis revealed stronger associations of COVID-19 diagnosis and severe COVID-19 for South-Asian participants for CHD (OR 1.585 [95% CI 1.194–2.105] for COVID-19 diagnosis and 3.021 [1.683–5.390] for severe COVID-19), hypertension (1.488 [1.231–1.799]; 3.399 [1.862–6.206]) and T2DM (1.671 [1.346–2.076]; 5.412 [3.130–9.357]) compared to White participants (1.264 [1.195–1.336] and 1.627 [1.441–1.837] for CHD; 1.131 [1.097–1.116] and 2.075 [1.885–2.284] for hypertension; 1.402 [1.331–1.476] and 2.890 [2.596–3.216] for T2DM). Similar results were seen for Black participants with CKD and hypertension. Conclusion Specific comorbidities are risk factors for poorer COVID-19 outcomes, supporting targeted interventions and policy aimed at individuals with these comorbidities. Although further research is required, there’s also a need for targeted policies for ethnic minorities assessing the unique reasons they are at greater risk of poor COVID-19 outcomes.

Spinal cord injury (SCI) is a severely disabling and catastrophic condition that poses significant global clinical challenges. The difficulty of SCI repair results from the distinctive pathophysiological mechanisms, which are characterised by limited regenerative capacity and inadequate neuroplasticity of the spinal cord. Additionally, the formation of cystic cavities and astrocytic scars after SCI further obstructs both the ascending and descending neural conduction pathways. Consequently, the urgent challenge in post-SCI recovery lies in repairing the damaged spinal cord to reconstruct a functional and intact neural conduction circuit. In recent years, significant advancements in biological tissue engineering technology and novel therapies have resulted in a transformative shift in the field of SCI repair. Currently, SCI treatment primarily involves drug therapy, stem cell therapy, the use of biological materials, growth factors, and other approaches. This paper comprehensively reviews the progress in SCI research over the years, with a particular focus on the concept of ''Spinal Cord Fusion'' as a promising technique for SCI reconstruction. By discussing this important research progress and the neurological mechanisms involved, our aim is to help solve the problem of SCI repair as soon as possible and to bring new breakthroughs in the treatment of paraplegia after SCI.

Objective: Follicular lymphoma (FL) is an indolent B-cell lymphoproliferative disorder, characterized by a lymphoid follicular pattern of growth. PFI-1 or CPI-203 has been known to effectively promote the inhibition of primary effusion lymphoma progression. This study aimed at investigating the anti-tumor properties of PFI-1 and CPI-203 on FL cells and uncover the underlying mechanism of action. Methods: FL cells were treated with PFI-1 and CPI-203, and the treated cells were evaluated for their cell viability, cell cycle and apoptosis using CCK8, flow cytometry, and Western blot assays. A xenograft mouse model was used for assessing the in vivo effects of CPI-203 on tumorigenesis. Results: PFI-1 or CPI-203 showed potential inhibitory effects on the cell viability of DOHH2 and RL cells in a dose-response-dependent manner. Furthermore, PFI-1 and CPI-203 inhibited cell growth, induced apoptosis of FL cells in vitro, and facilitated the translocation of β-catenin into cytoplasm both in vitro and in vivo. After engrafted with FL cells, CPI-203-treated mice got a longer duration of survival and a smaller tumor size than control mice. Mechanistically, PFI-1 and CPI-203 impede the activity of β-catenin and its downstream molecules by regulating the DVL2/GSK3β axis. Conclusion: In conclusion, PFI-1 and CPI-203 may serve as potential anti-tumor inhibitors for the therapy of FL.

We study the disorder-induced crossover between the two recently discovered thermalization slowing-down universality classes, characterized by long- and short-range coupling, in classical unitary-circuit maps close to integrability. We compute Lyapunov spectra, which display qualitatively distinct features depending on whether the proximity to the integrable limit is short or long range. For sufficiently small nonlinearity, translationally invariant systems fall into the long-range class. Adding disorder to such a system triggers a transition to the short-range class, implying a breaking of this invariance, and in the very limit of vanishing nonlinearity Anderson localization emerges. The crossover from the long- to the short-range class is attained by tuning the localization length ξ from ξ≈N to ξ≪N, where N is the system size. As a consequence, the Lyapunov spectrum becomes exponentially suppressed, depending on the extent to which its translational invariance is destroyed. We expect that this disorder-induced crossover will lead to prethermalized phases and, following quantization, to many-body localization.

Pre-eclampsia (PE), a major cause of perinatal morbidity and mortality, accounts for up to 14 % mortality of maternal and 18 % of fetal or infant mortalities. However, the pathogenesis process of PE remains unclear. The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the peripheral blood exosomes of early-onset PE patients versus healthy pregnant women using high-throughput sequencing, and to find candidate miRNAs as molecular markers. Methods: Peripheral blood samples were collected from five preeclamptic patients and five healthy women. Exosomal miRNAs were sequenced using the Illumina HiSeq4000 sequencing platform. The target gene prediction, biological function enrichment, and signaling pathway prediction of the miRNAs with significant differences were carried out using the Starbase database software, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. Our results showed 65 significantly differentially expressed miRNAs in the exosomes of early-onset PE patients compared to control group, with 17 up-regulated and 48 down-regulated (P

【Objective】Barthea barthei (Hance ex Benth.) Krass. is a unique shrub of the genus Barthea in Melastomataceae in China, which has important ornamental value. However, it is mainly distributed in the wild, and its artificial cultivation technology system has not been fully established, which greatly limits its application potential as a landscape plant. In this study, by comparing the effects of different types in nutrients and different application concentrations on the growth and root indexes of the seedlings, the main nutrient dosage affecting the growth of the seedlings was determined, providing a scientific basis for the cultivation of the seedlings.【Method】The tissue culture seedlings of B. barthei were used as materials, and they were transplanted into the seedling cups with yellow soil as the cultivation substrate. After 3 months' culture, 6 kinds of N nutrients (Glutamic acid, Alanine, Aspartic acid, Compound fertilizer, Urea, Controlled-released fertilizer) and 3 kinds of application amount (0.7, 1.4 and 2.8 mg/plant) were applied respectively. The seedling height and chlorophyll content of B. barthei were measured monthly, and the root indexes of B. barthei was measured after the experiment.【Result】Nutrient type and application amount had significant effects on the early growth and development of B. barthei seedlings. The highest increment of seedling height was 5.18±0.13 cm after 1 month of treatment with T9 (Aspartic acid, 2.8 mg/plant). The increment became smaller after 4~5 months. The seedling height increment of seedlings treated with T5 (Alanine, 1.4 mg/plant) was not significantly different from that of the control in the first 2 months, but it was much higher than that of the control after the 4th and 5th months. The increment of seedling height of T18 (Controlled-released fertilizer, 2.8 mg/plant) was the largest after 4 and 5 months. The root biomass of T14 (Urea, 1.4 mg/plant), T9 (Aspartic acid, 2.8 mg/plant) and T15 (Urea, 2.8 mg/plant) were the largest, which were 0.71 (±0.40) g, 0.65 (±0.21) g and 0.64 (±0.24) g, respectively. The root surface area with diameter less than or equal to 2 mm under T9 treatment was 273.63 cm2, which was significantly higher than that under other treatments.【Conclusion】Considering the seedling height and root index of root surface area with diameter ≤ 2 mm, the best nutrient for the early stage of B. barthei growth was Aspartic acid with the amount of 2.8 mg/plant.

Abstract Background COVID-19 manifests with huge heterogeneity in susceptibility and severity outcomes. UK Black Asian and Minority Ethnic (BAME) groups have demonstrated disproportionate burdens. Some variability remains unexplained, suggesting potential genetic contribution. Polygenic Risk Scores (PRS) can determine genetic predisposition to disease based on Single Nucleotide Polymorphisms (SNPs) within the genome. COVID-19 PRS analyses within non-European samples are extremely limited. We applied a multi-ethnic PRS to a UK-based cohort to understand genetic contribution to COVID-19 variability. Methods We constructed two PRS for susceptibility and severity outcomes based on leading risk-variants from the COVID-19 Host Genetics Initiative. Scores were applied to 447,382 participants from the UK-Biobank. Associations with COVID-19 outcomes were assessed using binary logistic regression and discriminative power was validated using incremental area under receiver operating curve (ΔAUC). Variance explained was compared between ethnic groups via incremental pseudo-R2 (ΔR2). Results Compared to those at low genetic risk, those at high risk had a significantly greater risk of severe COVID-19 for White (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42–1.74), Asian (OR 2.88, 95% CI 1.63–5.09) and Black (OR 1.98, 95% CI 1.11–3.53) ethnic groups. Severity PRS performed best within Asian (ΔAUC 0.9%, ΔR2 0.98%) and Black (ΔAUC 0.6%, ΔR2 0.61%) cohorts. For susceptibility, higher genetic risk was significantly associated with COVID-19 infection risk for the White cohort (OR 1.31, 95% CI 1.26–1.36), but not for Black or Asian groups. Conclusions Significant associations between PRS and COVID-19 outcomes were elicited, establishing a genetic basis for variability in COVID-19. PRS showed utility in identifying high-risk individuals. The multi-ethnic approach allowed applicability of PRS to diverse populations, with the severity model performing well within Black and Asian cohorts. Further studies with larger sample sizes of non-White samples are required to increase statistical power and better assess impacts within BAME populations.

Abstract Background This retrospective study aimed to compare the outcomes of toric implantable collamer lens (TICL) surgery with those of implantable collamer lens (ICL) implantation combined with limbal relaxing incision (LRI) in patients with low myopia and astigmatism. Methods A total of 40 eyes of 28 patients who underwent TICL implantation and 40 eyes of 27 patients who underwent ICL implantation combined with manually LRI between 2021 and 2022 were included. Primary outcomes were manifest sphere and cylinder, intraocular pressure, visual acuity, and astigmatism parameters at 1 day, 1 week, and 1, 3, and 6 months postoperatively. Results The two surgeries showed comparable effects on manifest sphere and cylinder, intraocular pressure, and visual acuity (all p > 0.1). Surgery-induced astigmatism (SIA) was maintained as stable in the TICL group (1.73 to 1.68, p = 0.420), but was significantly reduced in the ICL/LRI group (1.74 to 1.17, p = 0.001) from preoperative to postoperative 6 months. The TICL group displayed significantly higher SIA and correction index at postoperative 1, 3, and 6 months than the ICL/LRI group (at 6 months: SIA, 1.68 (1.26, 1.96) vs., 1.17 (1.00, 1.64), p = 0.010; CI: 0.98 (0.78, 1.25) vs. 0.80 (0.61, 1.04), p = 0.018). No complications occurred during follow-up. Conclusions The effects of ICL/LRI are comparable to those of TICL in correcting myopia. TICL implantation displays better astigmatism correction than ICL/LRI.

Abstract Background Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease, the pathogenesis of which is not clear. Clinical remission, or decreased disease activity, is the aim of treatment for RA. However, our understanding of disease activity is inadequate, and clinical remission rates for RA are generally poor. In this study, we used multi-omics profiling to study potential alterations in rheumatoid arthritis with different disease activity levels. Methods Fecal and plasma samples from 131 rheumatoid arthritis (RA) patients and 50 healthy subjects were collected for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing, and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The PBMCS were also collected for RNA sequencing and whole exome sequencing (WES). The disease groups, based on 28 joints and ESR (DAS28), were divided into DAS28L, DAS28M, and DAS28H groups. Three random forest models were constructed and verified with an external validation cohort of 93 subjects. Results Our findings revealed significant alterations in plasma metabolites and gut microbiota in RA patients with different disease activities. Moreover, plasma metabolites, especially lipid metabolites, demonstrated a significant correlation with the DAS28 score and also associations with gut bacteria and fungi. KEGG pathway enrichment analysis of plasma metabolites and RNA sequencing data demonstrated alterations in the lipid metabolic pathway in RA progression. Whole exome sequencing (WES) results have shown that non-synonymous single nucleotide variants (nsSNV) of the HLA-DRB1 and HLA-DRB5 gene locus were associated with the disease activity of RA. Furthermore, we developed a disease classifier based on plasma metabolites and gut microbiota that effectively discriminated RA patients with different disease activity in both the discovery cohort and the external validation cohort. Conclusion Overall, our multi-omics analysis confirmed that RA patients with different disease activity were altered in plasma metabolites, gut microbiota composition, transcript levels, and DNA. Our study identified the relationship between gut microbiota and plasma metabolites and RA disease activity, which may provide a novel therapeutic direction for improving the clinical remission rate of RA.

Abstract DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 μg/mL against G. zeae, EC50 = 1.01 μg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 μg/mL against A. alternata, EC50 = 0.20 μg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.

Objective To explore the effect of online and offline collaborative and integrated mode (Internet + blood donation souvenirs), and develop diversified scientific ways of caring for voluntary blood donors in combination with the potential expectation of the target population, ao as to recruit and retain more blood donors. Methods A total of 4 000 blood donors from Yichang Central Blood Station from January 1 to June 30, 2022 were selected, and they could collect souvenirs from online and offline. The intelligent platform V9.5 of modern blood station management information system of Qiao Technology was used to classify the data of online and offline souvenir distribution, and digital intelligent comparison and analysis on age, occupation, education, type (first-time blood donors or repeat blood donors), region (main urban districts of Yichang and other counties and suburban districts) and gender were carried out. Results A total of 1 400 blood donors chose online souvenirs, who were mainly under 25 years old, students, female, college education or above, urban areas and regular donors; 2 600 chose offline souvenirs, who were mainly over 25 years old, male, junior college degree or below, occupations other than students (medical workers, educators, etc.), counties and suburban districts, and first-time blood donors. The collaborative and integrated mode of the two distribution methods were complementary and had a good incentive effect on blood donor recruitment. Conclusion The online and offline collaborative and integrated mode demonstrates a good effect and meets the needs of different population. Digital intelligence system is helpful to develop diversified and scientific ways of caring for voluntary blood donors, recruit and retain more blood donors, achieve high-quality development of blood collection and supply, therefore guarantee the increasing demand for clinical blood use.