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Abstract Long-term continual straw return can enhance soil quality and increase crop yields by perpetually altering the soil environment. However, little is known about how different straw return methods affect soil physicochemical properties, enzymatic processes, and crop yields. The study aims to determine how different straw return practices improve soil structure, nutrients, enzyme activities, and maize yields. In this experiment, a field trial was conducted in 2021–2022 in the irrigated area of the Tumochuan Plain Irrigation District to determine the effects of four different straw returns on soil structure, nutrients, enzyme activities, soil quality, and maize yields. The four types of straw return included straw incorporation with deep tillage (DPR), straw incorporation with subsoiling (SSR), no-tillage mulching straw return, and farmer’s shallow rotation (CK). Our results showed that DPR and SSR enhanced water retention capacity by reducing the bulk weight of the 0–45 cm soil layer. DPR and SSR significantly increased soil organic C (12.76%), total nitrogen (25.32%), and available nutrients (i.e. AP, NO3 −–N) in the 0–45 cm soil layer compared to CK, whereas there were no differences between straw-returned treatments in the 0–15 cm soil layer. Finally, maize yield was significantly increased by 13.14% and 11.41% in the second year of DPR and SSR, respectively, compared to CK. This study demonstrated that DPR and SSR are effective at enhancing the agricultural utilization of crop residues and represent feasible strategies for improving physical, chemical, and biological processes in continuous maize cropping systems, leading to increased crop productivity.

Abstract Objective To construct a highly accurate and interpretable feeding intolerance (FI) risk prediction model for preterm newborns based on machine learning (ML) to assist medical staff in clinical diagnosis. Methods In this study, a sample of 350 hospitalized preterm newborns were retrospectively analysed. First, dual feature selection was conducted to identify important feature variables for model construction. Second, ML models were constructed based on the logistic regression (LR), decision tree (DT), support vector machine (SVM) and eXtreme Gradient Boosting (XGBoost) algorithms, after which random sampling and tenfold cross-validation were separately used to evaluate and compare these models and identify the optimal model. Finally, we apply the SHapley Additive exPlanation (SHAP) interpretable framework to analyse the decision-making principles of the optimal model and expound upon the important factors affecting FI in preterm newborns and their modes of action. Results The accuracy of XGBoost was 87.62%, and the area under the curve (AUC) was 92.2%. After the application of tenfold cross-validation, the accuracy was 83.43%, and the AUC was 89.45%, which was significantly better than those of the other models. Analysis of the XGBoost model with the SHAP interpretable framework showed that a history of resuscitation, use of probiotics, milk opening time, interval between two stools and gestational age were the main factors affecting the occurrence of FI in preterm newborns, yielding importance scores of 0.632, 0.407, 0.313, 0.313, and 0.258, respectively. A history of resuscitation, first milk opening time ≥ 24 h and interval between stools ≥ 3 days were risk factors for FI, while the use of probiotics and gestational age ≥ 34 weeks were protective factors against FI in preterm newborns. Conclusions In practice, we should improve perinatal care and obstetrics with the aim of reducing the occurrence of hypoxia and preterm delivery. When feeding, early milk opening, the use of probiotics, the stimulation of defecation and other measures should be implemented with the aim of reducing the occurrence of FI.

Abstract Color centers in silicon carbide (SiC) offer exciting possibilities for quantum information processing. However, the challenge of ionization during optical manipulation leads to charge variations, hampering the efficacy of spin-photon interfaces. Recent research predicted that modified divacancy color centers can stabilize their charge states, resisting photoionization. This study presents a method for precisely creating single divacancy arrays in 4H-SiC using a focused helium ion beam. Photoluminescence tests reveal consistent emission with minimal linewidth fluctuations (∼50 MHz over 3 h). By measuring the ionization rate for different polytypes of divacancies, we found that the modified divacancies are more robust against resonant excitation. Furthermore, angle-resolved photoluminescence excitation spectra unveil two resonant-transition lines with orthogonal polarizations. Enhanced optical and spin characteristics were notably observed in these color centers compared to those generated through carbon-ion and shallow implantation methods, positioning modified divacancies as promising contenders for advancing quantum networking.

Abstract We here report on the progress of the HHH Workshop, that took place in Dubrovnik in July 2023. After the discovery of a particle that complies with the properties of the Higgs boson of the Standard Model, all Standard Model (SM) parameters are in principle determined. However, in order to verify or falsify the model, the full form of the potential has to be determined. This includes the measurement of the triple and quartic scalar couplings. We here report on ongoing progress of measurements for multi-scalar final states, with an emphasis on three SM-like scalar bosons at 125 $$\,\text {Ge}\hspace{-.08em}\text {V}$$ Ge V , but also mentioning other options. We discuss both experimental progress and challenges as well as theoretical studies and models that can enhance such rates with respect to the SM predictions.

Abstract Background Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin and its biosynthesis occurs via ani gene cluster in Aspergillus nidulans NRRL8112. Strain improvement for industrial ECB production has mainly relied on mutation breeding due to the lack of genetic tools. Results Here, a CRISPR-base-editing tool was developed in A. nidulans NRRL8112 for simultaneous inactivation of the nkuA gene and two marker genes, pryoA and riboB, which enabled efficient genetic manipulation. Then, in-vivo plasmid assembly was harnessed for ani gene expression screening, identifying the rate-limiting enzyme AniA and a pathway-specific transcription factor AniJ. Stepwise titer enhancement was achieved by overexpressing aniA and/or aniJ, and ECB production reached 1.5 g/L during 5-L fed-batch fermentation, an increase of ~ 30-fold compared with the parent strain. Conclusion This study, for the first time, revealed the regulatory mechanism of ECB biosynthesis and harnessed genetic engineering for the development of an efficient ECB-producing strain.

Abstract With significant advances in classifying and cataloguing topological matter, the focus of topological physics has shifted towards quantum control, particularly the creation and manipulation of topological phases of matter. Floquet engineering, the concept of tailoring a system by periodic fields, offers a powerful tool to manipulate electronic properties of condensed systems, and even to create exotic non-equilibrium topological states that are impossibly present in equilibrium scenarios. In this perspective, we give a brief review of recent progress in theoretical investigations of Floquet engineering topological states from effective models towards realistic materials. We show that light irradiation can realize various desired topological states through the introduction of symmetry breaking, such as first- and higher-order Weyl fermions, quadrupole topological insulator with periodic driving and disorder, quantum anomalous Hall effects with a tunable Chern number, as well as beyond. Moreover, based on first-principles calculations and Floquet theorem, we show several realistic material candidates proposed as potential hosts for promising Floquet topological states, facilitating their verification in experiments. We believe that our perspective on Floquet engineering of topological states will advance further studies of rich exotic light-induced phenomena in condensed matter physics.

Abstract Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.

Abstract Background To compare and analyze clinical characteristics of patients undergoing two surgeries and multiple surgeries and explore relevant factors to lay the foundation for clinical prediction. Methods A retrospective analysis was conducted on clinical data from all patients who underwent twice and multiple strabismus surgeries at Tianjin Eye Hospital between October 2012 and September 2021. Patients were divided into Group A (two surgeries) and Group B (more than two surgeries) based on the cumulative number of surgeries performed. Clinical details at the first recurrence, including sex, age, native place, overall medical history, onset time, visual acuity, affected muscle(s), etc., were documented. Non-parametric tests and chi-square tests were used to analyze clinical characteristics in each group. Binary and ordered logistic regression analysis assessed parameters associated with multiple reoperations. A linear mixed-term model observed factors impacting affected muscle(s) during surgery. Researchers examined clinical traits related to secondary strabismus variables. Results Among the 910 included patients, 840 required two surgeries (Group A) and 70 underwent more than two surgeries (Group B). Significant differences were found in age, onset time, interval time, and secondary factors. Regression analysis highlighted the significant impact of interval time on the reoperation rate, effectively predicting outcomes in patients with concomitant strabismus. Other ophthalmoplegia and secondary factors significantly influenced reoperation rates in patients with non-concomitant strabismus. Interval time, esotropia, and exotropia were linked to concomitant secondary strabismus patients, while the number of surgeries, DVD, esotropia, exotropia, and esotropia V-pattern were associated with non-concomitant secondary strabismus patients. In a longitudinal study, patients with multiple surgeries showed a correlation between the vertical deviation angle magnitude and the number of involved extraocular muscles. Regression analysis revealed that in patients with concomitant strabismus, interval time, exotropia, and esotropia influenced the total number of muscles during surgery. For patients with non-concomitant strabismus, interval time, secondary factors, and SOP impacted the total number of muscles during surgery. Conclusions Interval time in patients with concomitant strabismus, as well as secondary and other ophthalmoplegia in non-concomitant strabismus, are the main factors for multiple reoperations.

Weiningbeishan is located in the eastern section of the North Qilian orogenic belt, which is one of the regions with the most favorable conditions for cobalt mineralization in Ningxia. Objective To understand the formation conditions and mineralization regularity of cobalt deposits in this area, Methods this paper summarizes the geological characteristics, controlling factors, and spatiotemporal distribution patterns of typical associated cobalt deposits in Weiningbeishan based on detailed field investigations and previous exploration results and proposes future exploration directions. Results Research has shown that the Datonggou copper cobalt deposit, Chaliangzi iron cobalt deposit, and Tuyao iron cobalt deposit are currently three representative associated cobalt deposits discovered in Weiningbeishan area. Among them, three copper cobalt ore bodies were discovered in Datonggou, with the highest Co grade of 0.06%. Cobalt-bearing minerals mainly include pyroxenite, cobalt-bearing pyrite and cobalt-bearing limonite. There are 4 ore belts and 8 iron cobalt ore bodies are distributed in Chaliangzi, with the highest Co grade of 0.03%. The cobalt-bearing minerals are mainly cobalt-bearing limonite. Only one iron cobalt ore body was found in Tuyao, with the highest Co grade of 0.20%. The cobalt-bearing minerals are similar to those of Chaliangzi. Cobalt mineralization is evidently controlled by faults, with the western cobalt deposit mainly controlled by east-west faults and their combined control with northeast faults, while the eastern cobalt deposits are mainly controlled by north-south faults. Cobalt ore are mainly found in the Upper Carboniferous Tupo Formation, which was the main source strata. Lithological control is mainly observed at the "silica-calcium interface" and the lithological combination interface with different competence, which controlled the mineral precipitation. The cobalt metallogenic era was the Indosinian. Cobalt was closely related to Cu, Au, Fe and Mn. Cobalt related to Cu and Au were mainly distributed in the west, while cobalt related to Fe and Mn were mainly distributed in the east. The diversity of mineral species in this region may be attributed to the multistage superimposition of structures and hydrothermal activity. Conclusion The most favourable locations for identifying cobalt deposits are the east-west faults and their intersections with the northeast faults in the western part, the north-south Carboniferous and Devonian interface faults in the eastern part, the " silica-calcium interface " within the Tupo Formation, and the lithological combination interfaces with different competence. Malachite alteration and ferritization are the most important prospecting indicators for copper cobalt deposits and iron cobalt deposits.

Optogenetics has revolutionized the landscape of research on neurological disorders by enabling high spatial specificity and millisecond-level temporal precision in neuroscience studies. In the field of traumatic brain injury (TBI), optogenetic techniques have greatly advanced our understanding of the pathological and physiological processes involved, providing valuable guidance for both monitoring and therapeutic interventions. This article offers a review of the latest research applications of optogenetics in the study of TBI.

Abstract Background Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML). Methods Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost). Results The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t 1, t 3/t max , t max , t 3/t 1, As, h f/3, t f/3/t max , t f/5, w and t f/3/t 1. Conclusion Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique.

Abstract Alcohol use disorder (AUD) is a profound psychiatric condition marked by disrupted connectivity among distributed brain regions, indicating impaired functional integration. Previous connectome studies utilizing functional magnetic resonance imaging (fMRI) have predominantly focused on undirected functional connectivity, while the specific alterations in directed effective connectivity (EC) associated with AUD remain unclear. To address this issue, this study utilized multivariate pattern analysis (MVPA) and spectral dynamic causal modeling (DCM). We recruited 32 abstinent men with AUD and 30 healthy controls (HCs) men, and collected their resting-state fMRI data. A regional homogeneity (ReHo)-based MVPA method was employed to classify AUD and HC groups, as well as predict the severity of addiction in AUD individuals. The most informative brain regions identified by the MVPA were further investigated using spectral DCM. Our results indicated that the ReHo-based support vector classification (SVC) exhibits the highest accuracy in distinguishing individuals with AUD from HCs (classification accuracy: 98.57%). Additionally, our results demonstrated that ReHo-based support vector regression (SVR) could be utilized to predict the addiction severity (alcohol use disorders identification test, AUDIT, R 2 = 0.38; Michigan alcoholism screening test, MAST, R 2 = 0.29) of patients with AUD. The most informative brain regions for the prediction include left pre-SMA, right dACC, right LOFC, right putamen, and right NACC. These findings were validated in an independent data set (35 patients with AUD and 36 HCs, Classification accuracy: 91.67%; AUDIT, R 2 = 0.17; MAST, R 2 = 0.20). The results of spectral DCM analysis indicated that individuals with AUD exhibited decreased EC from the left pre-SMA to the right putamen, from the right dACC to the right putamen, and from the right LOFC to the right NACC compared to HCs. Moreover, the EC strength from the right NACC to left pre-SMA and from the right dACC to right putamen mediated the relationship between addiction severity (MAST scores) and behavioral measures (impulsive and compulsive scores). These findings provide crucial evidence for the underlying mechanism of impaired self-control, risk assessment, and impulsive and compulsive alcohol consumption in individuals with AUD, providing novel causal insights into both diagnosis and treatment.

Abstract Citrullination plays an essential role in various physiological or pathological processes, however, whether citrullination is involved in regulating tumour progression and the potential therapeutic significance have not been well explored. Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Mechanistically, PADI4-mediated HIF-1αR698 citrullination blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation. We also show that citrullinated HIF-1αR698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumour tissues, suggesting a potential correlation between PADI4-mediated HIF-1αR698 citrullination and cancer development. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression.

Abstract Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

Abstract Objective To verify whether the bleeding risk assessment guidelines from the 9th American College of Chest Physicians (ACCP) are prognostic for respiratory intensive care unit (RICU) patients and to explore risk factors for hemorrhages, we conducted a secondary data analysis based on our previously published cohort study of venous thromboembolism. Patients and methods We performed a secondary data analysis on the single-center prospective cohort from our previous study. Patients admitted to the RICU at Beijing Chao-Yang Hospital from August 1, 2014 to December 31, 2020 were included and followed up until discharge. Results The study enrolled 931 patients, of which 715 (76.8%) were at high risk of bleeding, while the remaining were at low risk. Of the total, 9.2% (86/931) suffered major bleeding, and no significant difference was found between the two risk groups (p = 0.601). High-risk patients had poor outcomes, including higher mortality and longer stays. Independent risk factors for major bleeding were APACHE II score ≥ 15; invasive pulmonary aspergillosis; therapeutic dose of anticoagulants; extracorporeal membrane oxygenation; and continuous renal replacement therapy. Blood transfusion not related to bleeding appeared to be an independent protective factor for major bleeding (OR 0.099, 95% CI 0.045–0.218, p

Objective To explore the relationship between monocyte/high-density lipoprotein cholesterol ratio （MHR） and the progression and prognosis of type 2 diabetic kidney disease （DKD）. Methods From January 1， 2017 to December 31， 2022， 269 type 2 DKD patients were selected as DKD group while 269 healthy medical check-ups during the same period as healthy group. And the differences in MHR levels of two groups were compared. According to median MHR， DKD group were assigned into low-level MHR and high-level MHR sub-groups. General profiles， clinical data， the incidence rate of endpoint events and cumulative renal survival were compared two groups. Cox regression analysis was performed for exploring the independent risk factors for poor renal prognosis in DKD patients and drawing receiver operator characteristic curve （ROC） for exploring the diagnostic efficacy of MHR for poor prognosis of DKD. Results MHR level was higher in DKD group than that in healthy group [0.4918（0.3788，0.6818）×109/mmol vs 0.2984（0.1867，0.4112）×109/mmol] （P＜0.05）； high-level MHR group had higher levels of white blood cells （WBC） [7.70（6.40， 8.70）×109/L vs 6.50（5.40， 8.00）×109/L]， neutrophils （Ne） [4.60（3.60， 5.53）×109/L vs 3.99（3.18， 5.19）×109/L] and monocyte （Mono） [0.69（0.60， 0.70）×109/L vs 0.50（0.40， 0.60）×109/L]， urinary albumin to creatinine ratio （UACR） [1214.59（373.48， 3410.02）mg/g vs 1050.96（180.26， 3341.06） mg/g]， 24 h urine protein （24 hUP） [3.21（1.42， 5.51）g vs 2.66 （0.58， 4.56） g]， low-density lipoprotein cholesterol （LDL-C） [2.72（2.06， 3.40）mmol/L vs 2.23（1.63， 2.80）mmol/L]， serum creatinine （Scr） [152.10（95.20， 221.60）μmol/L vs 126.00（92.48， 186.55）μmol/L] than those in low-level MHR group； lymphocyte （Lym） [1.60（1.27， 2.20）×109/L vs 1.82（1.30， 2.40）×109/L]， high-density lipoprotein cholesterol （HDL-C） [0.94（0.83， 1.07）mmol/L vs 1.39（1.15， 1.65）mmol/L] and estimated glomerular filtration rate （eGFR） [39.69（25.19， 65.10）mL·min−1·（1.73 m²）−1 vs 47.12（28.86， 73.60）mL·min−1·（1.73 m²）−1] were lower than those in low-level MHR group； high-level MHR group had a cumulative kidney survival time and it was shorter than that in low level MHR group [63（39， 72）month vs 72（46， 72）month] （P＜0.05）； MHR was correlated positively with WBC， Ne， Mono， UACR， 24h UP， Scr and LDL-C （P＜0.05） and negatively with Lym， HDL-C， eGFR and cumulative renal survival time （P＜0.05）； the incidence of endpoint events was higher in high-level MHR group than that in low-level MHR group （52.59% vs 38.06%）（P＜0.05）； baseline MHR [0.5492（0.4030， 0.7235）×109/mmol vs 0.4255（0.3117， 0.5134）×109/mmol]， UACR [2062.65（752.80， 4234.80）mg/g vs 608.56（88.63. 1912.44）mg/g]， 24 hUP [3.79（2.54， 5.53）g vs 1.58（0.39， 4.85）g] and Scr [178.40（134.00， 234.23）μmol/L vs 100.95（74.25， 152.10）μmol/L] were higher than those in DKD patients without endpoint events； eGFR was lower than that in DKD patients without endpoint events [33.45（23.33， 46.41）mL·min−1·（1.73 m²）−1 vs 61.59（38.57， 95.98）mL·min−1·（1.73 m²）−1]（P＜0.05）. The results of Cox regression analysis indicated that MHR was an independent risk factor for a poor prognosis of DKD； The results of ROC curve showed that the area under the curve of MHR was 0.747 with a sensitivity of 0.820 and a specificity of 0.605. Conclusion DKD patients tend to have higher levels of MHR as compared with healthy individuals. As an independent risk for the progression of renal function in DKD patients， MHR has some diagnostic value for a poor prognosis of DKD. However， its specificity is not high.

Static air-gap eccentricity (SAGE) is a common fault in generators. Current researches primarily focus on the parallel SAGE types, while the inclined static air-gap eccentricity (ISAGE) has been rarely investigated. This paper proposes an improved air-gap eccentricity model and presents a study on the electromagnetic-mechanical properties in synchronous generators under typical ISAGE running conditions. Such electromagnetic-mechanical properties include not only the magnetic flux density (MFD) variations, but also the mechanical responses of the electromagnetic torque (EMT) and rotor unbalanced magnetic pulls (UMP). The typical ISAGE factors include: 1) a varied rotor inclined angle θ, and 2) different values of axial inclined distance z (indicates the offset combination case of the two rotor ends). This work is based on the MFD analysis calculation. Theoretical analysis, finite element analysis, and experimental study are carried out, respectively, by taking a 5 kVA two-pole prototype generator as the study object. It is shown that the electromagnetic-mechanical properties of the generator will change when the inclined eccentricity occurs. The EMT, and the rotor UMP as well as the vibrations will increase as the rotor inclined θ and z increase. Specifically, the 2nd harmonic has the most significant variation.

Abstract Skull-base chordoma is a rare, aggressive bone cancer with a high recurrence rate. Despite advances in genomic studies, its molecular characteristics and effective therapies remain unknown. Here, we conduct integrative genomics, transcriptomics, proteomics, and phosphoproteomics analyses of 187 skull-base chordoma tumors. In our study, chromosome instability is identified as a prognostic predictor and potential therapeutic target. Multi-omics data reveals downstream effects of chromosome instability, with RPRD1B as a putative target for radiotherapy-resistant patients. Chromosome 1q gain, associated with chromosome instability and upregulated mitochondrial functions, lead to poorer clinical outcomes. Immune subtyping identify an immune cold subtype linked to chromosome 9p/10q loss and immune evasion. Proteomics-based classification reveals subtypes (P-II and P-III) with high chromosome instability and immune cold features, with P-II tumors showing increased invasiveness. These findings, confirmed in 17 paired samples, provide insights into the biology and treatment of skull-base chordoma.

Abstract Background Acinetobacter baumannii (AB) is a notable cause of hospital-acquired infections, with carbapenem-resistant Acinetobacter baumannii (CRAB) classified as a high-priority critical pathogen. Bacteriophage therapy is emerging as a promising alternative to combat drug-resistant bacterial infections. In this study, a lytic phage, HZY2308, was isolated from hospital sewage, and the biological properties, biosafety and anti-biofilm properties of phage HZY2308 were characterized and identified. Moreover, the antibacterial effect of phage HZY2308 in combination with antibiotics was investigated, and the apparent characteristics of phage-resistant strain AB48-R were demonstrated, which provided data support for further studies to elucidate the mechanism of generating phage resistance. Methods Phage HZY2308 was isolated by double agar plate method using clinical strain AB48 as the host bacterium. The morphology of phage HZY2308 was identified by transmission electron microscopy (TEM), and biological characteristics of phage HZY2308 were identified by host range, the efficiency of plating (EOP), sensitivity to temperature, pH, and chloroform, one-step growth curve, the optimal multiplicity of infection (MOI), and detection of endotoxin and cytotoxicity. Besides, the complete genome map of HZY2308 was constructed using CGview, and the phylogenetic tree of HZY2308 was constructed with MEGA. Additionally, the full genomic sequence of phage HZY2308 and the selected phage were compared using Easyfig. Checkerboard test of phage HZY2308 in combination with tigecycline (TGC) was performed to investigate their synergistic effect and bactericidal kinetics. The effect of HZY2308 on biofilm was investigated by semi-quantitative staining of biofilm with crystal violet, determination of bacterial activity in biofilm by 2,3-Bis (2-methoxy-4-nitro-5-sulfophenyl) -2 H-tetrazolium-5-carboxanilide (XTT) assay and observation of biofilm structure by fluorescence microscopy. Finally, Phage-resistant bacteria AB48-R were characterized by colony-forming capacity, morphology, growth curves, adsorption efficiency, and antibiotic susceptibility assays. Results A lytic phage, HZY2308, was isolated from hospital sewage, which exhibited advantageous traits such as a brief incubation period, large burst size, and robust stability. Safety assessments conducted at both genetic and cellular levels also have yielded positive outcomes. Besides, phage HZY2308 effectively inhibited AB biofilm formation and disrupted established biofilm structures. Furthermore, a synergistic antibacterial effect was noted when phage HZY2308 was combined with tigecycline. Interestingly, the phage-resistant strain, AB48-R was screened through natural selection. Compared to the wild strain AB48, the adsorption efficiency of the phage to AB48-R diminished. However, AB48-R’s sensitivity to antibiotics such as cefepime, gentamicin, amikacin, and tobramycin increased, indicating an evolutionary trade-off. Conclusions Phage HZY2308 shows strong antimicrobial potential, especially in combination with tigecycline, and the phage-resistant strain exhibits increased antibiotic sensitivity.

Abstract White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical ‘atrophy’ identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical ‘atrophy’ showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. 15 of the 20 loci regulated the expression of 54 genes in the cerebral cortex that, together with their co-expressed genes, were enriched in biological processes of axonal cytoskeleton and intracellular transport. The white matter hyperintensities-cortical thickness associations were most pronounced in cortical regions with higher expression of genes specific to excitatory neurons with long-range axons traversing through the white matter. The meta-GWAS-based polygenic risk score predicts vascular and all-cause dementia in an independent sample of 500,348 individuals. Thus, the genetics of white matter hyperintensities-related cortical atrophy involves vascular and neuronal processes and increases dementia risk.

Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown. Methods: In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted in vivo experiments to explore the role of CD73 in OA. Results: We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on NT5E (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus. Conclusions: The variants of SNP rs2229523 (base A to G) on NT5E were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix. The Translational Potential of this Article: This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA.

Abstract Background Cryptosporidium spp. are important zoonotic parasites that can cause moderate to severe diarrhea in humans and animals. Among the three Cryptosporidium species infecting the intestines of calves, Cryptosporidium parvum has a broad host range and causes severe diarrhea in calves, while Cryptosporidium bovis and Cryptosporidium ryanae mainly infect calves without obvious clinical symptoms. Comparative genomic analysis revealed differences in the copy number of genes encoding the nonfinancial disclosure quality (NFDQ) secretory protein family among the three species, suggesting that this protein family may be associated with the host range or pathogenicity of Cryptosporidium spp. To understand the function of cgd8_10 encoded NFDQ1, tagged and knockout strains were constructed and characterized in this study. Methods To determine the localization of NFDQ1, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to tag the C-terminus of NFDQ1 with three hemagglutinin epitopes (3 × HA). The tagged strain was constructed, and the genomic insertion was confirmed by polymerase chain reaction (PCR). Immunofluorescence assays were performed to observe the localization of NFDQ1 both in extracellular sporozoites and at various intracellular developmental stages. Immunoelectron microscopy was used to study the ultrastructural localization of NFDQ1. Then, the ΔNFDQ1 strain was generated by CRISPR/Cas9 and the in vitro growth assay on HCT-8 cells was used to analyze of phenotypic changes after knockout NFDQ1 in parasites. Results The NFDQ1 tagging and knockout stains were successfully constructed by CRISPR/Cas9 technology and the insertions of transgenic strains were validated by PCR. The expression of NFDQ1 was validated in parasite by western blot. Immunofluorescence and immune-electron microscopy assay showed that NFDQ1 expressed in both asexual and sexual stages of C. parvum, where it was localized to the cytoplasm of the parasite. Upon ablation of NFDQ1, the ΔNFDQ1 strain showed an apparent growth retardation during sexual replication in vitro. Conclusions NFDQ1 is a cytoplasmic protein without specific localization to secretory organelles, and it may participate in C. parvum growth during sexual reproduction. Future study should determine the role of NFDQ1 following C. parvum infection in vivo. Graphical Abstract

Abstract Background Activated regulatory T cells (aTregs) play a vital role in promoting a tumor immunosuppressive microenvironment in laryngeal squamous cell carcinoma (LSCC). However, the regulatory factors that induce the generation of aTregs are not clear. Herein, we investigated the effect of amphiregulin (AREG) on the production of aTregs in the tumor microenvironment of LSCC. Methods Immunohistochemical (IHC) analysis was conducted to examine the expression of AREG and FOXP3, and their association with clinical parameters and patient outcomes was demonstrated. The expression level of EGFRs in three functional subsets of Tregs was assessed, and the induction of CD4+ T cells into aTregs in the presence or absence of AREG or Gefitinib was analyzed using flow cytometry. Results Our results showed a higher expression level of AREG was significantly related to advanced clinical stage and worse survival, particularly with increased infiltration of Tregs in LSCC tumor tissue. The in vitro study showed that AREG significantly promoted the differentiation of aTregs, and enhanced the inhibitory effect of Tregs on T cell proliferation, which could be reversed by epidermal growth factor receptor (EGFR) inhibitors. In addition, we found that EGFR was highly expressed in aTregs, but not in other subsets of Tregs. It is suggested that AREG might induce aTregs, and enhance the immunosuppressive function of Tregs via the AREG/EGFR signal pathway. Conclusions Collectively, this study revealed the role and mechanism of AREG in negative immune regulation, and targeting AREG might be a novel immunotherapy for LSCC.

Abstract The goat, an early domesticated ruminant, is a reliable source of cashmere, meat and milk in global agricultural production. Despite this, the genome of cashmere-rich goats has yet to be characterized. Here, we assembled the nearly complete genome of a cashmere goat from a highly economically valuable Inner Mongolian Cashmere buck, utilizing a combination of PacBio HiFi, ONT ultra-long reads, and Hi-C technologies. The size of this genome is 2.76 Gb, with a contig N50 of 95.22 Mb. All assembled sequences were anchored onto 29 autosomes and both sex chromosomes, with only two gaps present on the X chromosome. We identified 1,333.29 Mb (48.26%) of repetitive sequences and predicted 22,480 protein-coding genes. Assembly quality assessment of the genome demonstrated that our assembled cashmere goat genome surpasses the continuity, completeness, and accuracy of other published goat genomes. Taken together, we provided the first cashmere goat assembly, bridging the gap in the genome of important economic breeds of domestic goats, and providing a valuable reference resource for goat genetics and genome research.

Abstract Since the United States Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell (CAR-T) therapy in 2017, it has marked a major breakthrough in cancer treatment, leading to a surge in global research and applications in this field. In recent years, China has made rapid progress, quickly catching up through heavy investment in CAR-T construction, preparation processes, and treatment strategies. China’s CAR-T therapy market is driven by substantial pharmaceutical investment targeting its vast population, yet high therapy costs remain uncovered by basic medical insurance. In November 2023, FDA issued a warning about the risk of secondary cancers in patients undergoing CAR-T therapy, sparking global concern. In fact, the China National Medical Products Administration (NMPA) preemptively implemented a series of measures to address the safety concerns of CAR-T therapy, emphasizing the risk of secondary cancers and advising lifelong monitoring as part of the approval process for CAR-T products. Nevertheless, additional regulatory measures are needed to address emerging risks, particularly the threat of secondary cancers. The authors believe that raising the standards for Investigational New Drug (IND) approval and establishing a dynamic reporting and feedback system based on real-world data will strengthen regulatory oversight and support the sustainable growth of the CAR-T industry in China.

Abstract Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.

Abstract The current selection of ligands for both proteins of interest (POI) and E3 ubiquitin ligase significantly restricts the scope of targeted protein degradation (TPD) technologies. This study introduces cell-penetrating peptide-induced chimera conjugates (cp-PCCs) targeting the DHHC3 enzyme involved in PD-L1 palmitoylation. This approach disrupts PD-L1’s immunosuppressive function, enhancing anti-tumor immunity. We developed cp-PCCs to degrade DHHC3, directly linking DHHC3-mediated PD-L1 palmitoylation to PD-L1 stability on tumor cells. Our research utilized both in vitro assays and in vivo experiments in immune checkpoint blockade-resistant mouse models. We focused on a CRBN-based cp-PCC named PCC16, which demonstrated a DC50 of 102 nmol for DHHC3 degradation and significantly reduced PD-L1 levels. In resistant models, PCC16 not only robustly downregulated PD-L1 but also exhibited substantial anti-tumor activity in vivo without significant toxicity. This outperformed traditional inhibitors, showcasing the potential of cp-PCC technology to bypass current PROTAC limitations. Our findings suggest that cp-PCCs offer a promising method for targeting PD-L1 through DHHC3 inhibition and support their continued exploration as a versatile tool in cancer immunotherapy, especially for tumors resistant to standard treatments.

Abstract Diseases of the female reproductive system, especially malignant tumors, pose a serious threat to women’s health worldwide. One of the key factors limiting research progress in this area is the lack of representative models. Organoid technology, especially tumor organoids, has been increasingly applied in the study of female reproductive system tumors due to their high heterogeneity, close resemblance to the physiological state, easy acquisition and cultivation advantages. They play a significant role in understanding the origin and causes of tumors, drug screening, and personalized treatment and more. This article reviews the organoid models for the female reproductive system, focusing on the cancer research advancements. It discusses the methods for constructing tumor organoids of the female reproductive tract and summarizes the limitations of current research. The aim is to offer a reference for future development and application of these organoid models, contributing to the advancement of anti-tumor drugs and treatment strategies for female reproductive tract cancer patients.

Abstract Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer’s disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.

Abstract Transition-metal dichalcogenide monolayers possess large exciton binding energy and a robust valley degree of freedom, making them a viable platform for the development of spintronic devices capable of operating at room temperature. The development of such monolayer TMD-based spintronic devices requires strong spin-dependent interactions and effective spin transport. This can be achieved by employing exciton-polaritons. These hybrid light-matter states arising from the strong coupling of excitons and photons allow high-speed in-plane propagation and strong nonlinear interactions. Here, we demonstrate the operation of all-optical polariton spin switches by incorporating a WS2 superlattice into a planar microcavity. We demonstrate spin-anisotropic polariton nonlinear interactions in a WS2 superlattice at room temperature. As a proof-of-concept, we utilize these spin-dependent interactions to implement different spin switch geometries at ambient conditions, which show intrinsic sub-picosecond switching time and small footprint. Our findings offer new perspectives on manipulations of the polarization state in polaritonic systems and highlight the potential of atomically thin semiconductors for the development of next generation information processing devices.

Abstract This article studies the feedback stabilization problem of an impulsive switched linear system whose feedback loop is closed over a digital network. Particularly, the combined effects of mode switches, impulses, quantization, network delay and external disturbances on the stability of that system are investigated. By extending the previous delay‐free and impulse‐free methods of reachable‐set approximation and propagation, some novel communication and control policies are designed to stabilize the concerned switched system with both network delay and impulses. In order to save the occupied network bandwidth, some event‐triggered control policies are proposed. To handle the effects of the mode switches and the impulse, we design event‐triggering conditions for both the case with no switch and no impulse on an inter‐event interval and the case with one switch or one impulse on an inter‐event interval. Note that the occurrence of a mode switch or an impulse leads to the switch of the event‐triggering conditions. Under the event‐triggered control policies, a stabilizing bit rate condition is derived. It is proven that even under impulses and network delay, the event‐triggered control policies can stabilize the switched system at a lower bit rate than earlier works based on conventional time‐triggered control policies.

Abstract Background Feline blood transfusion is required for the treatment of various illnesses in cats, and the safety of donor cats is vital. Donor adverse reactions can include cardiorespiratory, venepuncture‐related, and behavioral abnormalities. Hypothesis/Objectives To describe a large number of feline blood donation events and document use of sedation and anxiolysis, record volume of blood collected and describe the frequency, type, and risk factors for, adverse reactions. Animals The study included 7812 individual cats and 29 201 donation events at a blood banking center over 5 years. Methods Retrospective analysis of donation event records with signalment, donation volume, sedation status, donation number, and adverse reactions (acute and caregiver reported) recorded. Risk factors for adverse reactions were examined by stratifying data according to groups exposed to relevant predictors and calculating odds ratios with 95% and 99% confidence intervals (CIs). Results Adverse reactions were uncommon (0.29%, 2.88/1000 donor events) and most commonly were cardiorespiratory (0.08%, 0.75/1000 donor events) or behavioral (0.06%, 0.62/1000 donor events). The only risk factor significantly associated with adverse reactions was conscious donation, with conscious donors 4.4 times more likely to have an adverse reaction (95% CI, 2.5‐7.9, P ≤ .0001). Conclusions and Clinical Importance Feline blood donation is associated with a low rate of adverse reactions. Sedation should be considered to reduce adverse reactions, and the environment and interactions optimized to reduce donor stress. Caregiver education on care postdonation could reduce behavioral adverse reactions.

The genus Coccinella is reviewed with seven species found in Pakistan: C. luteopicta (Mulsant, 1866), C. marussii Kapur, 1973, C. iranica Dobzhansky, 1926, C. transversalis Fabricius, 1781, C. septempunctata Linnaeus, 1758, C. transversoguttata transversoguttata Faldermann, 1835 and C. undecimpunctata Linnaeus, 1758. Information on prey, host plants, distribution and an identification key for Coccinella species in Pakistan is provided. Additionally, newly-sequenced partial COI (cytochrome-c-oxidase subunit I) for C. luteopicta and C. marussii were used to determine their phylogenetic positions within the genus Coccinella.This study comprehensively reviews the genus Coccinella in Pakistan and highlights Coccinella luteopicta as a new country record. Morphological features of adults, including male genital characters and an identification key to known species in Pakistan are presented. Records of prey, host plants and distributions for all identified species are included. The new data (COI-barcode) shows that C. luteopicta (Mulsant, 1866) was recorded first in Pakistan.

Abstract Background The global incidence of frozen shoulder (FS) (2% ~ 5%) and osteoporosis (OP) is high (9.1%-12.1%). Clinically, postmenopausal women are particularly at risk for both diseases. The main objective of this current research is to investigate the pathogenesis mechanism of FS and explore the connection between FS and OP. Methods We obtained FS and OP datasets from GEO and identified crosstalk genes. Following KEGG and GO enrich analysis, the p38 MAPK signaling pathway was focused and the specific p38α inhibitor TAK715 was screened out. We conducted flow cytometry, western blot, and PCR analyses to assess the treatment effect of TAK715 on FS synovium fibroblasts at different concentrations. Additionally, we employed SD rats to validate the treatment effects of TAK715 in vivo. Results TAK715 was useful in reversing fibrosis at the concentration of 1 μM, 5 μM and 10 μM. The unbalanced apoptosis process in frozen shoulder cell and the activation of osteoclast were inhibited at the concentration of 5 μM by TAK715. Then we successfully established a FS and OP rat model, with the FS with OP rat displaying less range of motion (ROM) and thicker shoulder capsule. In FS rat that was treated with TAK715, the frozen shoulder side was corrected in ROM and bone loss. Conclusions The frozen shoulder with osteoporosis may exhibit more severe symptoms, and TAK715 is effective in protecting fibrosis and osteoporosis both in vitro and vivo. The therapy to correct FS and OP simultaneously by TAK715 provides novel approach in FS treatment and study.

Abstract Due to global climate anomalies, the intensity and spatial extent of weather and climate extremes have increased notably. Therefore, extreme events must be studied to ensure agricultural production. In this study, the growing season accumulated temperature above 10 °C (GSAT10) was used as the climate regionalization index for maize in the Songliao Plain region, and the study area was divided into three climate zones. The standardized precipitation requirement index (SPRI) and standardized temperature index (STI) were introduced to analyze the spatial and temporal patterns of drought, waterlogging, and heat during the maize growing season from May to September using meteorological station data from the Songliao Plain between 1991 and 2020. The compound event magnitude indices were constructed by modeling the marginal distribution to detect the patterns of compound drought and heat events (CDHEs) and compound waterlogging and heat events (CWHEs), and to assess their potential impacts on maize production. The results show that: (1) The major meteorological disasters in the Songliao Plain region were drought and heat. The areas with prolonged high temperatures were similar to the areas with higher severity of temperature extremes, and were mainly concentrated in the central and southern parts of the study area (Zone 3). (2) The CWHEs mainly occurred in the northern part of the study area (Zones 1 and 2), and the CDHEs predominantly occurred in the central and southern parts of the study area. (3) For most sites on the Songliao Plain, the duration, severity, and intensity of compound extreme events were positively correlated with relative meteorological yield (Y w). Maize yield reduction was significantly affected by the CDHEs.

Abstract Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer’s disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.) strain that highly expressed a gene encoding a putative adhesin containing Rib repeats (Ribhigh-L.m.) particularly enriched in 5XFAD transgenic mice. Mechanistically, Ribhigh-L.m. adherence to the gut epithelia upregulated fecal metabolites, among which lactate ranked as the top candidate. Excess lactate stimulated the epithelial production of serum amyloid A (SAA) in the gut via the GPR81-NFκB axis, contributing to peripheral Th1 activation. Moreover, GV-971 disrupted the adherence of Ribhigh-L.m. to gut epithelia via direct binding to Rib, which corrected the excess lactate, reduced SAA, and alleviated Th1-skewed inflammation. Together, we gained further insights into the molecular link between gut bacteria and AD progression and the mechanism of GV-971 in treating AD.

Abstract Halomonas species are renowned for their production of organic compatible solutes, particularly ectoine. However, the identification of key regulatory genes governing ectoine production in Halomonas remains limited. In this study, we conducted a combined transcriptome-proteome analysis to unveil additional regulatory genes influencing ectoine biosynthesis, particularly under ultraviolet (UV) and salt conditions. NaCl induction resulted in a 20-fold increase, while UV treatment led to at least 2.5-fold increases in ectoine production. The number of overlapping genes between transcriptomic and proteomic analyses for three comparisons, i.e., non-UV with NaCl (UV0-NaCl) vs. non-UV without NaCl (UV0), UV strain 1 (UV1-NaCl) vs. UV0-NaCl, and UV strain 2 (UV2-NaCl) vs. UV0-NaCl were 137, 19, and 21, respectively. The overlapped Gene Ontology (GO) enrichments between transcriptomic and proteomic analyses include ATPase-coupled organic phosphonate, phosphonate transmembrane transporter activity, and ATP-binding cassette (ABC) transport complex in different comparisons. Furthermore, five common genes exhibited different expression patterns at mRNA and protein levels across the three comparisons. These genes included orf01280, orf00986, orf01283, orf01282 and orf01284. qPCR verification confirmed that three of the five common genes were notably under-expressed following NaCl and UV treatments. This study highlighted the potential role of these five common genes in regulating ectoine production in Halomonas strains.

Abstract Background Zika virus (ZIKV) primarily spreads through mosquito bites and can lead to microcephaly in infants and Guillain-Barre syndrome in adults. It is noteworthy that ZIKV can persist in the semen of infected males for extended periods and can be sexually transmitted. Infection with ZIKV has severe pathological manifestations on the testicular tissues of male mice, resulting in reduced sperm motility and fertility. However, there are no approved prophylactic vaccines or therapeutics available to treat Zika virus infection. Methods Using a male type I and II interferon receptor-deficient (ifnar1(-/-) ifngr1(-/-)) C57BL/6 (AG6) mouse model infected with ZIKV as a representative model, we evaluated the degree of testicular damage and viral replication in various organs in mice treated with EVs derived from MSC-stimulated with IFN-β (IFNβ-EVs) and treated with controls. We measured testicle size, detected viral load in various organs, and analyzed gene expression to assess treatment efficacy. Results Our findings demonstrated that intravenous administration of IFNβ-EVs effectively suppressed ZIKV replication in the testes. Investigation with in-depth RNA sequencing analysis found that IFN-β treatment changed the cargo miRNA of EVs. Notably, miR-431-5p was identified to be significantly enriched in IFNβ-EVs and exhibited potent antiviral activity in vitro. We showed that CD95 was a direct downstream target for miR-431-5p and played a role in facilitating ZIKV replication. miR-431-5p effectively downregulated the expression of CD95 protein, consequently promoted the phosphorylation and nuclear localization of NF-kB, which resulted in the activation of anti-viral status, leading to the suppression of viral replication. Conclusions Our study demonstrated that the EVs produced by IFNβ-treated MSCs could effectively convey antiviral activity.

Abstract The L-shell x-ray emission of tellurium induced by H2 + ions impact is investigated in an energy range of 150–300 keV. The blue shifts of various L-subshell x rays and the enhancement of the relative intensity ratios of Lι, Lβ to Lα x ray are observed and interpreted by the multiple ionization of outer-shell electrons. The new experimental x-ray production cross sections, which almost correspond to those of protons with half of the original energy, are extracted and compared with various theoretical estimations. The correction effects of the united atom approximation and the multiple ionization atomic parameters are compared, and the influence of atomic parameters from different databases on the simulations is discussed. Overall, the ECUSAR-MI calculations using theoretical atomic parameters present the best agreement with the experiment results.

Abstract Urinary incontinence (UI) in females is a prevailing condition that affects individuals across various age groups and is not limited to older females. The presence of serum alpha-Klotho (α-klotho) serves as a reliable biomarker to indicate the effects of antiaging. Nevertheless, the scientific research on the association between α-klotho and UI remains limited. Therefore, the purpose of this study is to investigate and evaluate the connection between α-klotho levels and the UI among females in the US. We utilized data from the National Health and Nutrition Examination Survey 2007–2016 to investigate the potential connection between α-klotho levels and the UI among females aged 40 to 79. Weighted linear regression models and sensitivity tests were conducted to explore the correlation. 2628 females were involved in this study, representing 22,492,348 non-institutionalized residents in the US. The mean age was 53.9 ± 0.2 years and the mean level of α-klotho was 873.0 ± 8.9 pg/mL. After adjusting for relevant covariables, weighted linear regression models revealed that individuals with severe UI exhibited significantly lower serum α-klotho levels (β = − 100.66; 95% CI: − 156.31, − 45.01; P

Abstract The purpose of this study was to examine the effects of different dryland warm-up protocols on knee isokinetic strength, vertical jumping, and sprint performance in competitive swimmers. Twenty-four male swimmers were randomly assigned to the FIFA 11 + group (n = 12) or the post-activation performance enhancement (PAPE) group (n = 12). The FIFA 11 + group performed the FIFA 11 + warm-up program three times per week for 6 weeks, whereas the PAPE group consisted of performing general activities and three sets of five drop jumps. Performance test included concentric (con) and eccentric (ecc) isokinetic strength of the quadriceps (Q) and hamstrings (H) of the dominant (DL) and non-dominant (NDL) limbs at three angular velocities, countermovement jump (CMJ), squat jump (SJ) and a 50-m time trial. The conventional (Hcon: Qcon) and functional (Hecc: Qcon) ratios were calculated pre- and post- intervention. The FIFA 11 + group showed a significant increase in DL-Hcon (p

Abstract This study aims to explore the interplay between locomotor demands and goal differentials to better understand their combined influence on overall success. Spanning three competitive seasons within the male Turkish Super League, this study analyzed all participating teams across 124 matches. Locomotor demands, including total distance (m) covered (TD), distances covered (m) at different speed thresholds (0.21–2.0 m/s; 2.01–4.0 m/s; 4.01–5.5 m/s; and 5.5–7.7 m/s), and the number of accelerations in range of 5.5–7.0 m/s (n), were quantified using an optical tracking system. Subsequently, regression models were employed to predict the total points earned by all teams over the three seasons. The logistic regression model, tailored to predict team categorization as high-points earners (HPE) or low-points earners (LPE) based on locomotor variables, exhibited a mean accuracy of 74%. Notably, total distance covered, running speed intervals between 4.4 and 5.5 m/s, and the number of accelerations in range of 5.5–7.0 m/s emerged as significant predictors of team success. Our findings highlight the pivotal role of running speed (4.01–5.5 m/s), number of accelerations, and total distance in predicting success for high-performing teams. Coaches can leverage these insights to refine training programs, thereby optimizing team performance, and fostering success in competitive environments.

Abstract For the blasting scenario, our research develops an emulsion explosive grasping and filling system suitable for tunnel robots. Firstly, we designed a system, YOLO-SimAM-GRCNN, which consists of an inference module and a control module. The inference module primarily consists of a blast hole position detection network based on YOLOv8 and an explosive grasping network based on SimAM-GRCNN. The control module plans and executes the robot’s motion control based on the output of the inference module to achieve symmetric grasping and filling operations. Meanwhile, The SimAM-GRCNN grasping network model is utilized to carry out comparative evaluated on the Cornell and Jacquard dataset, achieving a grasping detection accuracy of 98.8% and 95.2%, respectively. In addition, on a self-built emulsion explosive dataset, the grasping detection accuracy reaches 96.4%. The SimAM-GRCNN grasping network model outperforms the original GRCNN by an average of 1.7% in accuracy, achieving a balance between blast holes detection, grasping accuracy and filling speed. Finally, experiments are conducted on the Universal Robots 3 manipulator arm, using distributed deployment and manipulator arm motion control mode to achieve an end-to-end grasping and filling process. On the Jetson Xavier NX development board, the average time consumption is 119.67 s, with average success rates of 87.1% for grasping and 79.2% for filling emulsion explosives.

Abstract In response to the weakened capability of feature transfer and parameter distribution alignment across domains due to significant differences in data distribution collected by different devices, this paper constructs a motor bearing fault diagnosis model based on multi-adversarial domain adaptation. Initially, an improved residual network is employed as the feature extraction module to enhance feature extraction capabilities. It then incorporates a Selective Kernel Network (SKNet) to implement attention mechanisms on convolutional kernels, and a Global Context Network (GCNet) to effectively utilize global contextual information for re-weighting across different channels. Additionally, the model uses a multi-kernel maximum mean discrepancy to measure the distribution between domains and classes, establishing a dynamic adjustment factor in conjunction with multiple domain discriminators to modulate the importance of marginal and conditional distributions. Ultimately, the proposed model was applied to transfer experiments across different operating conditions and devices, demonstrating excellent diagnostic results.

Abstract Background Vascular calcification is a crucial pathophysiological process associated with age-related cardiovascular diseases. Elabela, a recently identified peptide, has emerged as a significant player in the regulation of cardiovascular function and homeostasis. However, the effects and underlying mechanisms of Elabela on age-related vascular calcification remain largely unexplored. Methods In-vivo vascular calcifications of C57BL/6J mice (8-week-old) and young (8-week-old) or aged (72-week-old) SD rats were injected with vitamin D3 (VitD3) or saline, respectively. Furthermore, the VitD3-overloaded mice received Elabela (1 mg/kg/d), peroxisome proliferators-activated receptor-γ (PPAR-γ) activator Rosiglitazone (5 mg/kg/d) or copper-ionophore Elesclomol (20 mg/kg/d), respectively. As for in-vitro studies, primary rat vascular smooth muscle cells (VSMCs) were isolated from aortas and cultured for explore the role and underlying mechanism of Elabela in vascular calcification. Results There were marked increases in FDX1 and Slc31a1 levels in both aortas and VSMCs during vascular calcification, coinciding with a rise in copper levels and a decrease in Elabela levels. Alizarin red and von-Kossa staining indicated that the administration of Elabela effectively hindered the progression of vascular cuproptosis and arterial calcification in VitD3-overloaded mice and rat arterial rings models. Moreover, Elabela significantly suppressed osteogenic differentiation and calcium deposition in VSMCs and strikingly reversed high phosphate-induced augmentation of FDX1 expression, DLAT aggregation as well as intracellular copper ion levels. More importantly, Elabela exhibited remarkable abilities to prevent mitochondrial dysfunctions in primary rat VSMCs by maintaining mitochondrial membrane potential, inhibiting mitochondrial division, reducing mitochondrial ROS production and increasing ATP levels. Interestingly, Elabela mitigated cellular senescence and production of pro-inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-18 and TNF-α, respectively. Furthermore, Elabela upregulated the protein levels of PPAR-γ in VitD3-overloaded mice. Administrating PPAR-γ inhibitor GW9662 or blocking the efflux of intracellular copper abolished the protective effect of Elabela on vascular calcification by enhancing levels of FDX1, Slc31a1, Runx2, and BMP2. Conclusion Elabela plays a crucial role in protecting against vascular cuproptosis and arterial calcification by activating the PPAR-γ /FDX1 signaling. Elabela supplementation and cuproptosis suppression serve as effective therapeutic approaches for managing vascular calcification and related cardiovascular disorders.

Abstract Background Increasing evidence suggests a link between the enzyme cathepsin S (CTSS) and tumour development. However, the potential involvement and molecular functions of CTSS in clear cell renal cell carcinoma (ccRCC) remain unclear. Methods We downloaded original data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated them using R. Kaplan–Meier plots of integrated expression scores were used to analyse survival outcomes. Additionally, we investigated mRNA expression, clinicopathological features, immune infiltrates, and single-cell sequencing analysis of CTSS in ccRCC. In vitro experiments were conducted with qRT-PCR and IHC staining. Results CTSS transcriptomic and proteomic levels were higher in ccRCC than in para-cancerous tissues. Low CTSS expression was correlated with poor prognosis in patients with ccRCC. Our data demonstrated that the expression of CTSS was strongly correlated with immune cell infiltration levels and gene markers of immune cells, chemokines, and receptors. Single-cell sequencing analysis demonstrated that CTSS expression was detectable in monocytes/macrophages. Finally, certain chemicals were confirmed to affect CTSS expression. Conclusion Our findings indicate that CTSS offers promise as a prognostic biomarker and novel immune-related therapeutic target for ccRCC.

Abstract Activating mutations in NRAS account for 15–20% of melanoma, yet effective anti-NRAS therapies are still lacking. In this study, we unveil the casein kinase 1δ (CK1δ) as an uncharacterized regulator of oncogenic NRAS mutations, specifically Q61R and Q61K, which are the most prevalent NRAS mutations in melanoma. The genetic ablation or pharmacological inhibition of CK1δ markedly destabilizes NRAS mutants and suppresses their oncogenic functions. Moreover, we identify USP46 as a bona fide deubiquitinase of NRAS mutants. Mechanistically, CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity towards NRAS mutants, thus promoting oncogenic NRAS-driven melanocyte malignant transformation and melanoma progression in vitro and in vivo. Our findings underscore the significance of the CK1δ-USP46 axis in stabilizing oncogenic NRAS mutants and provide preclinical evidence that targeting this axis holds promise as a therapeutic strategy for human melanoma harboring NRAS mutations.

Abstract Surface charge patchiness of different charge types can influence the solution behaviours of colloidal particles and globular proteins. Herein, coiled-coil ‘bundlemer’ nanoparticles that display only a single type of surface charge (SC) are computationally designed to compare their solution behaviours to mixed charge-type (MC) counterparts with both positively and negatively charged side chains. Nematic and columnar liquid crystal phases are discovered in low concentrations of SC particles, indicative of particle end-to-end stacking into columns combined with lateral electrostatic repulsion between columns, while MC particles with the same net charge and particle shape produced only amorphous, soluble aggregates. Similarly, porous lattices are formed in mixtures of SC/MC particles of opposite charges while MC/MC mixtures of opposite charges produce only amorphous aggregates. The lattice structure is inferred with a machine learning optimization approach. The differences between SC and MC particle behaviours directly show the importance of surface electrostatic patchiness.

Abstract African swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase (vRNAP), temporally expressed transcription factors and transcript associated proteins, facilitating cross-species transmission via intermediate host. The protein composition of the virion and the presence of transcription factors in virus genome suggest existence of distinct transcription systems during viral infection. However, the precise mechanisms of transcription regulation remain elusive. Through analyses of dynamic transcriptome, vRNAP-associated components and cell-based assay, the critical role of M1249L in viral transcription regulation has been highlighted. Atomic-resolution structures of vRNAP-M1249L supercomplex, exhibiting a variety of conformations, have uncovered the dual functions of M1249L. During early transcription, M1249L could serve as multiple temporary transcription factors with C-terminal domain acting as a switcher for activation/inactivation, while during late transcription it aids in the packaging of the transcription machinery. The structural and functional characteristics of M1249L underscore its vital roles in ASFV transcription, packaging, and capsid assembly, presenting novel opportunities for therapeutic intervention.