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The underwater 10CrNi3MoV high-strength low-alloy steel thin-walled part with forming quality up to in-air laser deposition quality was successfully manufactured for the first time. The influencing mechanisms of complicated thermal history and water environment on microstructure evolution and mechanical properties of thin-walled part were researched. Due to austenitization and interlocking effect, the microstructure in the bottom, middle and top (below the 56th layer) areas of underwater sample and the middle area of in-air sample were composed of fine grain ferrite and granular bainite. With the increase of building height, the heat accumulation effect of underwater sample enhanced, resulting in small grain size (GS), high dislocation density, strong solution strengthening effect and low maximum texture strength at the bottom area, while the high proportion of high-angle grain boundaries (HAGBs) at the top area. These resulted in the greatest tensile strength (714 MPa) and microhardness (232 HV) at the bottom area and the highest elongation (11%) at the top area. Due to the cooling effect of water environment, the proportion of HAGBs reduced and there were oxides in fracture. As a result, the horizontal elongation of underwater sample was about 90.9% of in-air sample. Additionally, the GS reduced, and the dislocation density and solution strengthening effect increased, so the microhardness of underwater sample was slightly higher than that of in-air sample. However, due to some microscopic defects, the horizontal and vertical tensile strength of underwater sample were about 97.6% and 90.7% of in-air sample.

Abstract The Mg–9Gd–3Y–2Zn–0.5Zr alloy was studied for its long-term corrosion behavior in a simulated coastal storage environment. The results show that the Mg12 (Y, Gd) Zn phase in the Mg–9Gd–3Y–2Zn–0.5Zr alloy forms a galvanic couple with α-Mg, and the Mg12 (Y, Gd) Zn phase acts as a cathode to accelerate α-Mg during the corrosion initiation period. The corrosion of the anode is subsequently transformed into corrosive dissolution of the anode. With the dissolution of the Mg12 (Y, Gd) Zn phase, elements such as Gd and Y are gradually distributed into the entire corrosion product layer, improving the protective performance of the corrosion product layer by forming dense Gd2O3 and Y2O3.

Abstract Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry, especially in most breeds of obese type pigs. The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear. Lysine 2-hydroxyisobutyrylation (Khib), is a novel protein post-translational modification (PTM), which play an important role in transcription, energy metabolism and metastasis of cancer cells, but its role in adipogenesis and fat accumulation has not been shown. Results In this study, we first analyzed the modification levels of acetylation (Kac), Khib, crotonylation (Kcr) and succinylation (Ksu) of fibro-adipogenic progenitors (FAPs), myogenic precursors (Myo) and mesenchymal stem cells (MSCs) with varied differentiation potential, and found that only Khib modification in FAPs was significantly higher than that in MSCs. Consistently, in parallel with its regulatory enzymes lysine acetyltransferase 5 (KAT5) and histone deacetylase 2 (HDAC2) protein levels, the Khib levels increased quadratically (P

Abstract Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25–0.5 μg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.

Objective: To investigate the beneficial effects of phenolic extracts of Rosa roxburghii Tratt. on obese mice induced by a high-fat diet. Methods: The intervention involved administering polyphenol extract at a dose of 400 mg/kg body weight per day to mice on a high-fat diet. The mice were orally gavaged continuously for 4 weeks, and various parameters such as body weight, liver index, histomorphological changes in white fat and liver tissues, serum biochemical markers, organ antioxidant capacity, and intestinal barrier function were examined. Results: In comparison to control group (CON), the MODEL group (MODEL) exhibited significantly (P

Abstract In the third-generation (3G) gravitational-wave (GW) detector era, multi-messenger GW observation for binary neutron star (BNS) merger events can exert great impacts on exploring cosmic expansion history. In this work, we comprehensively explore the potential of 3G GW standard siren observations in cosmological parameter estimations by considering 3G GW detectors and the future short $$\gamma $$ γ -ray burst (GRB) detector THESEUS-like telescope joint observations. Based on a 10-year observation of different detection strategies, we predict that the numbers of detectable GW-GRB events are 334–674 with the redshifts $$z

Abstract Background The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. Methods Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. Results For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. Conclusions The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.

Ultra-intense, ultra-fast X-ray free-electron lasers (XFELs) enable the imaging of single protein molecules under ambient temperature and pressure. A crucial aspect of structure reconstruction involves determining the relative orientations of each diffraction pattern and recovering the missing phase information. In this paper, we introduce a predicted model-aided algorithm for orientation determination and phase retrieval, which has been tested on various simulated datasets and has shown significant improvements in the success rate, accuracy and efficiency of XFEL data reconstruction.

Study Design A retrospective cohort study. Purpose This study aimed to assess the reliability of quantitative computed tomography (QCT) in measuring bone mineral density (BMD) of instrumented vertebrae and investigate the effect of less paraspinal muscle damage on BMD changes after lumbar interbody fusion. Overview of Literature Patients always experience a decrease in vertebral BMD after lumbar interbody fusion. However, to the best of our knowledge, no study has analyzed the effect of paraspinal muscles on BMD changes. Methods This retrospective analysis included a total of 155 patients who underwent single-level lumbar fusion, with 81 patients in the traditional group and 74 patients in the Wiltse group (less paraspinal muscle damage). QCT was used to measure the volumetric BMD (vBMD), Hounsfield unit value, and cross-sectional area of the paraspinal muscles at the upper instrumented vertebrae (UIV), vertebrae one segment above the UIV (UIV+1), and the vertebrae one segment above the UIV+1 (UIV+2). Statistical analyses were performed. Results No significant differences in general data were observed between the two groups (p>0.05). Strong correlations were noted between the preoperative and 1-week postoperative vBMD of each segment (p0.05). Vertebral BMD loss was significantly higher in UIV+1 and UIV+2 in the traditional group than in the Wiltse group (−13.6%±19.1% vs. −4.2%±16.5%, −10.8%±20.3% vs. −0.9%±37.0%; p0.05). Conclusions QCT can reliably determine BMD in the instrumented spine after lumbar interbody fusion. With QCT, we found that reducing paraspinal muscle destruction through the Wiltse approach during surgery can help preserve the adjacent vertebral BMD; however, it does not help increase the BMD in the instrumented vertebrae.

Binocular image stereo matching is a key technology to realize autonomous obstacle avoidance and visual reconnaissance of unmanned auxiliary transport vehicles in coal mines. However, factors such as high dust and unstable lighting conditions in coal mines can lead to Salt-and-pepper noise in the images collected by the visual sensor, resulting in a high stereo matching error rate. Therefore, a Census stereo matching algorithm based on the combination of threshold and weight is proposed to reduce the impact of Salt-and-pepper noise on stereo matching. The main contributions include: ① threshold processing is carried out on the gray values of all pixels in the support window to remove the pixels with maximum and minimum gray values in the support window and solve the impact of outlier on the weighted fusion; ② the four diagonal pixels corresponding to the center point are weighted and fused to replace the center point pixel. Select pixel points along the four diagonal lines intersecting at the center pixel, with step sizes ranging from 1 to 3. According to the corresponding steps, weights of 0.7, 0.2, and 0.1 are assigned. Multiply the valid pixel points among these 12 points by their respective weights, then divide by the sum of the valid weights. This process yields the reference value of the center pixel point after weighted processing, addressing the issue of traditional algorithms' dependency on the center pixel of the Census transform window. Consequently, this approach enhances matching precision. The experimental results show that the average error rate calculated by the proposed algorithm is reduced by 5.64% compared to traditional Census algorithms, and reduced by 1.71% compared to the mean-based Census algorithm. What's more, the average error rate under different noise levels calculated by the proposed algorithm is reduced by 15.93% compared to the traditional Census algorithm, and reduced by 16.62% compared to the mean-based one. In non-occluded areas, the error matching rate of our algorithm is reduced by 17.19% compared to the traditional Census algorithm and 18.11% compared to the mean-based Census algorithm. The proposed Census stereo matching algorithm, which combines threshold and weight, effectively enhances the robustness against noise, reduces the error rate, and improves matching accuracy.

Abstract Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

Abstract Metallic structures produced with laser powder bed fusion (LPBF) additive manufacturing method (AM) frequently contain microscopic porosity defects, with typical approximate size distribution from one to 100 microns. Presence of such defects could lead to premature failure of the structure. In principle, structural integrity assessment of LPBF metals can be accomplished with nondestructive evaluation (NDE). Pulsed infrared thermography (PIT) is a non-contact, one-sided NDE method that allows for imaging of internal defects in arbitrary size and shape metallic structures using heat transfer. PIT imaging is performed using compact instrumentation consisting of a flash lamp for deposition of a heat pulse, and a fast frame infrared (IR) camera for measuring surface temperature transients. However, limitations of imaging resolution with PIT include blurring due to heat diffusion, sensitivity limit of the IR camera. We demonstrate enhancement of PIT imaging capability with unsupervised learning (UL), which enables PIT microscopy of subsurface defects in high strength corrosion resistant stainless steel 316 alloy. PIT images were processed with UL spatial–temporal separation-based clustering segmentation (STSCS) algorithm, refined by morphology image processing methods to enhance visibility of defects. The STSCS algorithm starts with wavelet decomposition to spatially de-noise thermograms, followed by UL principal component analysis (PCA), fine-tuning optimization, and neural learning-based independent component analysis (ICA) algorithms to temporally compress de-noised thermograms. The compressed thermograms were further processed with UL-based graph thresholding K-means clustering algorithm for defects segmentation. The STSCS algorithm also includes online learning feature for efficient re-training of the model with new data. For this study, metallic specimens with calibrated microscopic flat bottom hole defects, with diameters in the range from 203 to 76 µm, were produced using electro discharge machining (EDM) drilling. While the raw thermograms do not show any material defects, using STSCS algorithm to process PIT images reveals defects as small as 101 µm in diameter. To the best of our knowledge, this is the smallest reported size of a sub-surface defect in a metal imaged with PIT, which demonstrates the PIT capability of detecting defects in the size range relevant to quality control requirements of LPBF-printed high-strength metals.

Abstract Background There is no evidence to determine the association between the lactate dehydrogenase to albumin ratio (LAR) and the development of sepsis-associated acute kidney injury (SAKI). We aimed to investigate the predictive impact of LAR for SAKI in patients with sepsis. Methods A total of 4,087 patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC IV) database were included. Logistic regression analysis was used to identify the association between LAR and the risk of developing SAKI, and the relationship was visualized using restricted cubic spline (RCS). The clinical predictive value of LAR was evaluated by ROC curve analysis. Subgroup analysis was used to search for interactive factors. Results The LAR level was markedly increased in the SAKI group (p

Abstract Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates of patients with dilated DCM have greatly improved in recent decades. Nevertheless, the clinical prognosis for DCM patients remains unfavorable. The primary driving factors underlying the pathogenesis of DCM remain incompletely understood. The present study aimed to identify driving factors underlying the pathogenesis of DCM from the perspective of gene regulatory networks. Single-cell RNA sequencing data and bulk RNA data were obtained from the Gene Expression Omnibus (GEO) database. Differential gene analysis, single-cell genomics analysis, and functional enrichment analysis were conducted using R software. The construction of Gene Regulatory Networks was performed using Python. We used the pySCENIC method to analyze the single-cell data and identified 401 regulons. Through variance decomposition, we selected 19 regulons that showed significant responsiveness to DCM. Next, we employed the ssGSEA method to assess regulons in two bulk RNA datasets. Significant statistical differences were observed in 9 and 13 regulons in each dataset. By intersecting these differentiated regulons and identifying shared targets that appeared at least twice, we successfully pinpointed three differentially expressed targets across both datasets. In this study, we assessed and identified 19 gene regulatory networks that were responsive to the disease. Furthermore, we validated these networks using two bulk RNA datasets of DCM. The elucidation of dysregulated regulons and targets (CDKN1A, SAT1, ZFP36) enhances the molecular understanding of DCM, aiding in the development of tailored therapies for patients.

Abstract Purpose Symptom assessment is central to appropriate adenomyosis management. Using a WeChat mini-program-based portal, we aimed to establish a valid symptom assessment scale of adenomyosis (AM-SAS) to precisely and timely identify needs of symptom management and ultimately, to alert disease recurrence. Methods A combination of intensive interviews of patients with adenomyosis and natural language processing on WeChat clinician-patient group communication was used to generate a pool of symptom items-related to adenomyosis. An expert panel shortened the list to form the provisional AM-SAS. The AM-SAS was built in a Wechat mini-programmer and sent to patients to exam the psychotically validity and clinical applicability through classic test theory and item response theory. Results Total 338 patients with adenomyosis (29 for interview, 179 for development, and 130 for external validation) and 86 gynecologists were included. The over 90% compliance to the WeChat-based symptom evaluate. The AM-SAS demonstrated the uni-dimensionality through Rasch analysis, good internal consistency (all Cronbach’s alphas above 0.8), and test-retest reliability (intraclass correlation coefficients ranging from 0.65 to 0.84). Differences symptom severity score between patients in the anemic and normal hemoglobin groups (3.04 ± 3.17 vs. 5.68 ± 3.41, P

Abstract Topological phases in photonic systems have garnered significant attention, often relying on precise structural design for generating non-trivial topological phases. However, this dependency on fixed structures limits their adaptability. This study systematically explores incident angle-induced topological phase transitions in a one-dimensional photonic crystal (PC). Both TE and TM polarized modes undergo topological phase transitions at the same critical transition angles. Additionally, the TM-polarized mode undergoes a unique topological phase transition at the Brewster angle. When these two kinds of transition angles coincide, even if the band structure of the TM-polarized mode undergoes an open-close-reopen process, the topological properties of the corresponding bandgap remain unchanged. Based on theoretical analysis, we design the composite PCs comprising two interfaced PCs having common bandgaps but different topological properties. By tuning the incident angle, we theoretically and experimentally achieve TE-TM splitting of topological interface states in the visible region, which may have potential applications in optical communications, optical switching, photonic integrated circuits, and so on.

Abstract Background Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. Methods In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. Results Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. Conclusions The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. Trial registration All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

The high morbidity and mortality rate of individuals with human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS) coinfected with Mycobacterium tuberculosis (MTB) is a tough challenge for current global tuberculosis prevention and control efforts. HIV/MTB coinfection is more complex than a single infection, and the interaction between the two diseases aggravates the deterioration caused by the disease, resulting in increased hospitalizations and deaths. Rapid screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals, thereby reducing transmission and the incidence of adverse prognoses. To date, pathogenic detection has remained the gold standard for diagnosing tuberculosis, but its sensitivity and specificity are greatly affected by the body's immune status, which limits its application in the diagnosis of HIV/MTB coinfection. Recently, immunology and molecular detection technology has developed rapidly. New detection technologies, such as interferon-γ release assays, interferon-gamma inducible protein 10, and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods, significantly improved the sensitivity and specificity of tuberculosis diagnosis, and brought new hope to the detection of HIV/MTB coinfection. In this article, the principle, scope of application, and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.

Abstract Background Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved. Methods C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM. Results Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1β. Conclusion These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.

Abstract Artificial intelligence (AI) telephone is reliable for the follow‐up and management of hypertensives. It takes less time and is equivalent to manual follow‐up to a high degree. We conducted a reliability study to evaluate the efficiency of AI telephone follow‐up in the management of hypertension. During May 18 and June 30, 2020, 350 hypertensives managed by the Pengpu Community Health Service Center in Shanghai were recruited for follow‐up, once by AI and once by a human. The second follow‐up was conducted within 3–7 days (mean 5.5 days). The mean length time of two calls were compared by paired t‐test, and Cohen's Kappa coefficient was used to evaluate the reliability of the results between the two follow‐up visits. The mean length time of AI calls was shorter (4.15 min) than that of manual calls (5.24 min, P

Abstract Baricitinib is approved for the treatment of rheumatoid arthritis (RA) in more than 70 countries, and juvenile idiopathic arthritis (JIA) in the European Union. Population pharmacokinetic (PK) models were developed in a phase 3 trial to characterize PK in pediatric patients with JIA and identify weight‐based dosing regimens. The phase 3, randomized, double‐blind, placebo‐controlled withdrawal, efficacy and safety trial, JUVE‐BASIS, enrolled patients (aged 2 to

Abstract Background Diabetes is a common chronic metabolic disease. The progression of the disease promotes vascular inflammation and the formation of atherosclerosis, leading to cardiovascular disease. The coronary artery perivascular adipose tissue attenuation index based on CCTA is a new noninvasive imaging biomarker that reflects the spatial changes in perivascular adipose tissue attenuation in CCTA images and the inflammation around the coronary arteries. In this study, a radiomics approach is proposed to extract a large number of image features from CCTA in a high-throughput manner and combined with clinical diagnostic data to explore the predictive ability of vascular perivascular adipose imaging data based on CCTA for coronary heart disease in diabetic patients. Methods R language was used for statistical analysis to screen the variables with significant differences. A presegmentation model was used for CCTA vessel segmentation, and the pericoronary adipose region was screened out. PyRadiomics was used to calculate the radiomics features of pericoronary adipose tissue, and SVM, DT and RF were used to model and analyze the clinical data and radiomics data. Model performance was evaluated using indicators such as PPV, FPR, AAC, and ROC. Results The results indicate that there are significant differences in age, blood pressure, and some biochemical indicators between diabetes patients with and without coronary heart disease. Among 1037 calculated radiomic parameters, 18.3% showed significant differences in imaging omics features. Three modeling methods were used to analyze different combinations of clinical information, internal vascular radiomics information and pericoronary vascular fat radiomics information. The results showed that the dataset of full data had the highest ACC values under different machine learning models. The support vector machine method showed the best specificity, sensitivity, and accuracy for this dataset. Conclusions In this study, the clinical data and pericoronary radiomics data of CCTA were fused to predict the occurrence of coronary heart disease in diabetic patients. This provides information for the early detection of coronary heart disease in patients with diabetes and allows for timely intervention and treatment.

Abstract Autism Spectrum Disorders (ASD) are neurodevelopmental disorders that cause people difficulties in social interaction and communication. Identifying ASD patients based on resting-state functional magnetic resonance imaging (rs-fMRI) data is a promising diagnostic tool, but challenging due to the complex and unclear etiology of autism. And it is difficult to effectively identify ASD patients with a single data source (single task). Therefore, to address this challenge, we propose a novel multi-task learning framework for ASD identification based on rs-fMRI data, which can leverage useful information from multiple related tasks to improve the generalization performance of the model. Meanwhile, we adopt an attention mechanism to extract ASD-related features from each rs-fMRI dataset, which can enhance the feature representation and interpretability of the model. The results show that our method outperforms state-of-the-art methods in terms of accuracy, sensitivity and specificity. This work provides a new perspective and solution for ASD identification based on rs-fMRI data using multi-task learning. It also demonstrates the potential and value of machine learning for advancing neuroscience research and clinical practice.

Abstract Background Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo polarization to M1/M2-like phenotype under stress stimulation, which mediates intracellular inflammatory response. β-elemene is a natural sesquiterpene and possesses potent anti-inflammatory activity. This study aimed to investigate the anti-inflammatory efficacy and mechanism of β-elemene in ischemic stroke from the perspective of balancing microglia M1/M2-like polarization. Methods The middle cerebral artery occlusion (MCAO) model and photothrombotic stroke model were established to explore the regulation effect of β-elemene on the cerebral ischemic injury. The LPS and IFN-γ stimulated BV-2 cells were used to demonstrate the anti-inflammatory effects and potential mechanism of β-elemene regulating M1/M2-like polarization in vitro. Results In C57BL/6 J mice subjected to MCAO model and photothrombotic stroke model, β-elemene attenuated neurological deficit, reduced the infarction volume and neuroinflammation, thus improving ischemic stroke injury. β-elemene promoted the phenotype transformation of microglia from M1-like to M2-like, which prevented neurons from oxygen and glucose deprivation/reoxygenation (OGD/R) injury by inhibiting inflammatory factor release, thereby reducing neuronal apoptosis. Mechanically, β-elemene prevented the activation of TLR4/NF-κΒ and MAPK signaling pathway and increased AKT/mTOR mediated-autophagy, thereby promoting M2-like polarization of microglia. Conclusions These results indicated that β-elemene improved cerebral ischemic injury and promoted the transformation of microglia phenotype from M1-like to M2-like, at least in part, through AKT/mTOR-mediated autophagy. This study demonstrated that β-elemene might serve as a promising drug for alleviating ischemic stroke injury.

Abstract Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function. The reduced expression of HNF1α is a critical event in the development of HCC, but the underlying mechanism for its degradation remains elusive. In this study, we discovered that the expression of TRIM8 was upregulated in HCC tissues, and was positively correlated with aggressive tumor behavior of HCC and shorter survival of HCC patients. Overexpression of TRIM8 promoted the proliferation, colony formation, invasion, and migration of HCC cells, while TRIM8 knockdown or knockout exerted the opposite effects. RNA sequencing revealed that TRIM8 knockout suppresses several cancer-related pathways, including Wnt/β-catenin and TGF-β signaling in HepG2 cells. TRIM8 directly interacts with HNF1α, promoting its degradation by catalyzing polyubiquitination on lysine 197 in HCC cells. Moreover, the cancer-promoting effects of TRIM8 in HCC were abolished by the HNF1α-K197R mutant in vitro and in vivo. These data demonstrated that TRIM8 plays an oncogenic role in HCC progression through mediating the ubiquitination of HNF1α and promoting its protein degradation, and suggests targeting TRIM8-HNF1α may provide a promising therapeutic strategy of HCC.

Abstract Objectives To evaluate the potential connections between marginal cord insertion during the first trimester and furcate cord insertion later in pregnancy. Methods This is a prospective study of screening data on the cord insertion site in 3178 singleton pregnancies. The cord insertion site was examined in two stages. The first stage was screening for the cord insertion site between 10–13 weeks of gestation, the purpose is to determine the category of umbilical cord insertion. The second stage, performed at 22–28 weeks of gestation, was to follow up on the relationship between the cord insertion site and the placenta and to identify any changes in the category of umbilical cord insertion. This was performed to diagnose or exclude furcate cord insertion by identifying whether the umbilical cord trunk separated or branched before it reached the placenta. Factors influencing progression to furcate cord insertion and perinatal complications were assessed. Results Fourteen cases (0.44%) with progression to furcate cord insertion, all of which showed marginal cord insertion on ultrasound in the first trimester (p

Abstract The authors propose a novel object detection algorithm for identifying bird nests in medium voltage power line aerial images, which is crucial for ensuring the safe operation of the power grid. The algorithm utilises an improved Swin Transformer as the main feature extraction network of Fast R‐CNN, further enhanced with a channel attention and modified binary self‐attention mechanism to improve the feature representation ability. The proposed algorithm is evaluated on a newly constructed image dataset of medium voltage transmission lines containing bird nests, which are annotated and classified. Experimental results show that the proposed algorithm achieves satisfied accuracy and robustness in recognising bird nests compared to traditional algorithms.

Abstract Background The World Health Organization urged governments to prioritize the health and work well-being of nursing staff by promoting a positive working environment. A safe and healthy physical and psychosocial work environment is a basic human right for nurses. Job crafting is a necessary skill when facing challenging working conditions. Objectives This cross-sectional correlational research based on the Job Demands-Resources Model aimed to explore the correlation between psychosocial work environment and work well-being among nurses working in the intensive care unit (ICU) and determine whether personal perceived health could mediate the relationship and whether job crafting can moderate the mediating effect. The study hypothesized that: 1. The psychosocial work environment would impact nurses' work well-being; 2. Personal perceived health would play a role as a mediator in the relationship between psychosocial work environment and work well‐being; 3. Job crafting would moderate the relationship between personal perceived health and work well‐being. Methods A total of 655 registered nurses (RNs) from 7 ICUs in a teaching hospital in Beijing participated in this study. The RNs completed a battery questionnaire measuring their health, psychosocial work environment, well-being, and job crafting. PROCESS macros analysis was used to test mediating and moderating effects. Results Personal perceived health mediated the relationship between psychosocial work environment and work well-being (b = 0.012, 95% CI [0.008, 0.016]). The moderated mediated analysis revealed that job crafting moderated perceived health’s impact on work well-being (b = -0.007, 95% CI [− 0.010, − 0.003]). Conclusion A better psychosocial work environment with well-designed work organization and job content through job crafting could positively impact nurses’ health and work well-being.

Abstract Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs

Abstract Background Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development. Methods Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs. Results Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis. Conclusion This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes—PFDN4, CEMIP, and BTBD10—may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.

Abstract Background To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. Methods Data were obtained from the 2019–2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. Results A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203–1.787; P

Objective Postoperative coronal decompensation and less fusion level are dilemmas and the proper selective posterior fusion (SPF) strategy should be investigated. We proposed a parameter, modified S‐line, and aimed to investigate if the modified S‐line could predict postoperative coronal decompensation in patients with Lenke 5C adolescent idiopathic scoliosis (AIS). Methods This is a retrospective radiographic study and Lenke 5C AIS patients undergoing SPF during the period from September 2017 to June 2021 were included. The modified S‐line was defined as the line linking the centers of the concave‐side pedicles of the upper end vertebra (UEV) and lower end vertebra (LEV) at baseline. A modified S‐line tilt to the right is established as modified S‐line+ (UEV being to the right of the LEV). The patients were further categorized into two groups: the Cobb to Cobb fusion group and the Cobb‐1 to Cobb fusion group. Outcomes including thoracic Cobb angle, TL/L Cobb angle, coronal balance, upper instrumented vertebra (UIV) translation, lower instrumented vertebra (LIV) translation, UIV tilt, LIV tilt, LIV disc angle, thoracic apical vertebral translation, lumbar apical vertebral translation (L‐AVT), L‐T AVT ratio, L‐T Cobb were measured at baseline, immediately after surgery, and the last follow‐up. Radiographic parameters and the incidence of both proximal and distal decompensation between the two groups were compared by chi‐square test. Results Among 92 patients, 48 were modified S‐line+ and 44 were modified S‐line−. Modified S‐line+ status was identified as a risk factor for postoperative proximal decompensation (p = 0.005) during follow‐up. In Cobb to Cobb group, a higher occurrence of proximal decompensation in individuals with modified S‐line+ status (p = 0.001) was confirmed. Also, in the Cobb to Cobb group with baseline modified S‐line+ status, patients presenting decompensation showed a significantly larger baseline of the UIV tilt and postoperative disc angle below the lower instrumented vertebra. However, In Cobb‐1 group, the incidence of decompensation after surgery showed no association with baseline modified S‐line tilt status (p = 0.815 and 0.540, respectively). Conclusion The modified S‐line could serve as an important parameter in surgical decision‐making for Lenke 5C AIS patients. Cobb to Cobb SPF is not recommended with a modified S‐line+ status, and the Cobb‐1 to Cobb fusion may serve as a potential alternative.

4,4-Difluoro-4-bora-3a,4a-diaza-sindacene (BODIPY) is a sort of photofunctional dye which possesses advantages including strong light-capturing property, high photon-resistance, etc. Meso-N substituted aza-BODIPY is a crucial derivative of BODIPY scaffold that has the favorable optical properties and a significant spectral redshift. The photophysical properties can be tuned by molecular design, and the attenuation path of the excited state energy release of absorbed light energy can be well controlled via structural modifications, enabling tailored application. It has been extensively employed in life medicine fields including fluorescence imaging diagnosis, photodynamic therapy photosensitizer and photothermal therapy reagent and so forth. Extensive research and review have been performed in these areas. However, BODIPYs/aza-BODIPYs have a significant role in energy, catalysis, optoelectronics, photo-responsive materials and other fields. Nevertheless, there are relatively few studies and reviews in these fields on the modification and application based on BODIPY/aza-BODIPY scaffold. Herein, in this review we summarized the application of BODIPY/aza-BODIPY in the aforementioned fields, with the molecular regulation of dye as the foundation and the utilization in the above fields as the objective, in the intention of providing inspiration for the exploration of innovative BODIPY/aza-BODIPY research in the field of light resource conversion and functional materials.

Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties. In this study, we found that AcbE from Actinoplanes sp. SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towards α-amylase than acarbose. Recombinant AcbE mainly catalyzed the formation of two new compounds, namely acarstatins A and B, using acarbose as substrate. Using high-resolution mass spectrometry, nuclear magnetic resonance, and glycosidase hydrolysis, we elucidated their chemical structures as O-α-d-maltosyl-(1 → 4)-acarbose and O-α-d-maltotriosyl-(1 → 4)-acarbose, respectively. Acarstatins A and B exhibited 1584- and 1478-fold greater inhibitory activity towards human salivary α-amylase than acarbose. Furthermore, both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis. Therefore, acarstatins A and B have great potential as candidate therapeutic agents for T2DM.

In this paper, the radial basis function (RBF) neural network was modified by data assimilation method to improve the modeling accuracy of high-dimensional aerodynamics. A correction factor γ was introduced into the kernel function of the traditional RBF neural network. The correction factor was corrected by using the EnKF data assimilation algorithm, and it was applied to the high-dimensional aerodynamic modeling prediction of the CRA309 rotor airfoil. The data assimilation method adopts a non-intrusive method to correct only the correction factor of the kernel function without destroying the overall architecture of the neural network, which greatly reduces the optimization parameters and variables, and significantly improves the modeling accuracy and efficiency of the RBF neural network. The modified RBF neural network model was then applied to high-dimensional aerodynamic modeling, and the aerodynamic parameters were predicted by simulation data instead. The design results verify the feasibility of the prediction model. In the case of less wind tunnel test data, it has certain engineering practical value to improve the utilization efficiency of test data.

This study investigated the influence of Sb addition on the microstructure, thermal behavior, mechanical properties, and interfacial evolution of SAC305-2Bi-xSb/Cu solder joints. Compared with the SAC305-2Bi alloy, the melting temperature and pasty range slightly increased with the increasing of Sb content from 0.2 to 2.0 wt.%, while the undercooling temperature decreased. The research revealed that with the addition of Sb element, the grain size of β-Sn is refined. When the content of Sb is 0.5 wt.%, the grain size of β-Sn reached minimum (19.91 μm). Compared to the SAC305-2Bi alloy, the ultimate tensile strength of SAC305-2Bi–2Sb alloy is increased by 30.10%, contributed to the Sb solid solution strengthening effect and the refinement of β-Sn. With the addition of Sb, the thickness and growth rate of the interface is reduced gradually. The uniform solution of Sb and Sn can significantly inhibit the diffusion rate of Cu atoms and Sn atoms at the interface. The SAC305-2Bi-xSb alloy system has low melting temperature, superior mechanical properties, and reliable solder joints for service. Therefore, it is a potentially reliable lead-free solder for high-stability connections in automotive electronics, communications electronics, and medical devices.

Objectives. Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. Methods. We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. Results. The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48). Conclusion. We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Abstract Protein ubiquitination regulates a wide range of cellular processes. The degree of protein ubiquitination is determined by the delicate balance between ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase (DUB)-mediated deubiquitination. In comparison to the E3-substrate interactions, the DUB-substrate interactions (DSIs) remain insufficiently investigated. To address this challenge, we introduce a protein sequence-based ab initio method, TransDSI, which transfers proteome-scale evolutionary information to predict unknown DSIs despite inadequate training datasets. An explainable module is integrated to suggest the critical protein regions for DSIs while predicting DSIs. TransDSI outperforms multiple machine learning strategies against both cross-validation and independent test. Two predicted DUBs (USP11 and USP20) for FOXP3 are validated by “wet lab” experiments, along with two predicted substrates (AR and p53) for USP22. TransDSI provides new functional perspective on proteins by identifying regulatory DSIs, and offers clues for potential tumor drug target discovery and precision drug application.

Corn straw-based board has great potential for the protection of forest resources, waste recycling, and sustainable economic development. However, corn stalk-based board has poor mechanical properties due to its short fiber length and poor water resistance because of the presence of numerous hydrophilic hydroxyl functional groups in its structure. Natural mycelium originating from waste Pleurotus ostreatus substrate is a hydrophobic bio-adhesive. In the present study, formaldehyde-free corn stalk/P. ostreatus substrate bio-composites were prepared using the hot-pressing technique without the addition of any chemical adhesive. The mechanical properties and water resistance of the prepared bio-composites were excellent. The highest internal bonding strength (IBS) of 2.16 MPa and the minimum thickness swelling (TS) of 18.3% were observed, which are beyond the national standards for particleboard in China. These bio-composites were prepared using a simple, green, and convenient manufacturing method to promote their popularization and application. The method may, therefore, be used as a novel technical measure to resolve the problem of overuse of forestry resources and waste disposal.

Abstract Background Glehnia littoralis is a medicinal and edible plant species having commercial value and has several hundred years of cultivation history. Polyploid breeding is one of the most important and fastest ways to generate novel varieties. To obtain tetraploids of G. littoralis in vitro, colchicine treatment was given to the seeds and then were screened based on morphology, flow cytometry, and root tip pressing assays. Furthermore, transcriptome analysis was performed to identity the differentially expressed genes associated with phenotypic changes in tetraploid G. littoralis. Results The results showed that 0.05% (w/v) colchicine treatment for 48 h was effective in inducing tetraploids in G. littoralis. The tetraploid G. littoralis (2n = 4x = 44) was superior in leaf area, leaf thickness, petiole diameter, SPAD value (Chl SPAD), stomatal size, epidermal tissues thickness, palisade tissues thickness, and spongy tissues thickness to the diploid ones, while the stomatal density of tetraploids was significantly lower. Transcriptome sequencing revealed, a total of 1336 differentially expressed genes (DEGs) between tetraploids and diploids. Chromosome doubling may lead to DNA content change and gene dosage effect, which directly affects changes in quantitative traits, with changes such as increased chlorophyll content, larger stomata and thicker tissue of leaves. Several up-regulated DEGs were found related to growth and development in tetraploid G. littoralis such as CKI, PPDK, hisD and MDP1. KEGG pathway enrichment analyses showed that most of DEGs were enriched in metabolic pathways. Conclusions This is the first report of the successful induction of tetraploids in G. littoralis. The information presented in this study facilitate breeding programs and molecular breeding of G. littoralis varieties.

Abstract Background Mammary Pathogenic Escherichia coli (MPEC) is an important pathogen that can escape the attack of the host immune system through biofilm formation and proliferate in the mammary gland continuously, resulting in mastitis in cows and causing enormous economic losses. As an effector of AI-2 quorum sensing, LsrR extensively affects the expression levels of hundreds of genes related to multiple biological processes in model E. coli strain. However, the regulatory role of LsrR in MPEC and whether it is involved in pathogenesis has been seldom reported. Results In this study, the function of LsrR in strain MPEC5, obtained from a milk sample in dairy cows with mastitis, was investigated by performing high-throughput sequencing (RNA-seq) assays. The results revealed that LsrR down-regulated the transcript levels of fimAICDFGH (encoding Type 1 pili), which have been reported to be associated with biofilm formation process. Biofilm assays confirmed that deletion of lsrR resulted in a significant increase in biofilm formation in vitro. In addition, electrophoretic mobility shift assay (EMSA) provided evidence that LsrR protein could directly bind to the promoter regions of fimAICDFGH in a dose-dependent manner. Conclusions These results indicate that LsrR protein inhibits the biofilm formation ability of MPEC5 by directly binding to the fimAICDFGH promoter region. This study presents a novel clue for further exploration of the prevention and treatment of MPEC.

A novel Zr–Ti conversion coating (ZrTiCC) was fabricated on 6016 aluminum alloy. The coating thickness was evaluated, and the corrosion resistance of the coating was investigated through CuSO4 drop experiments to determine the optimum process. Potentiodynamic polarization results revealed the corrosion current density of ZrTiCC (4.821 μA/cm2) was lower than that of bare specimen (12.263 μA/cm2), and the δE of ZrTiCC (0.752V) was significantly lower than bare specimen (0.087 V). Scanning electron microscope and energy dispersive spectrometer was used to characterize the morphology and composition changes of the coating during its growth. The coating was proved to have a double-layer structure, and cracks appeared when the coating thickness continued to increase, which reduced the corrosion resistance. The growth mechanism of the coating was explained in detail. X-ray photoelectron spectroscopy was used to determine the components of the coating, which comprised Al2O3 at the base, with TiO2, AlF3, and ZrF4 at the top and ZrO2 evenly distributed throughout. Bode diagram revealed the impedance modulus of the coating at low frequency was increased to 8.6 × 104 Ω/cm2 after five days immersion in 0.5 M NaCl. The coating's self-sealing behavior and active protection may relate to the formation of SiO2, as well as the dissolution and regeneration of the upper coating (AlF3 and ZrF4) on 6016 aluminum alloy.

Abstract The preoperative distinguishment of lymph nodes (LN) with metastasis plays a pivotal role in guiding the surgical extension for gastric cancer (GC). We aim to identify the preparative risk factors for LN metastasis in GC patients. We retrospectively reviewed 424 patients who underwent radical GC resection in our medical center between Jan 2011 and Dec 2018. Multivariate logistic regression was employed to identify risk factors for LN metastasis, while multivariate COX regression was utilized to evaluate prognostic factors. The median overall survival of patients with or without LN metastases was 31 and 58 months, respectively. In multivariate analysis, lower albumin (OR = 0.512; P = 0.004) and prealbumin (OR = 0.367, P = 0.001) and higher CEA (OR = 3.178, P

Abstract The therapeutic efficacy of adoptive T cell therapy is largely restricted by reduced viability and dysfunction of CD8+ T cells. Continuous antigen stimulation disrupts the expansion, effector function, and metabolic fitness of CD8+ T cells, leading to their differentiation into an exhausted state within the tumor microenvironment (TME). While the function of the cell cycle negative regulator p16 in senescent cells is well understood, its role in T cell exhaustion remains unclear. In this study, we demonstrated that TCR stimulation of CD8+ T cells rapidly upregulates p16 expression, with its levels positively correlating with TCR affinity. Chronic TCR stimulation further increased p16 expression, leading to CD8+ T cell apoptosis and exhaustion differentiation, without inducing DNA damage or cell senescence. Mechanistic investigations revealed that p16 downregulates mTOR, glycolysis, and oxidative phosphorylation (OXPHOS) associated gene expression, resulting in impaired mitochondrial fitness, reduced T cell viability, and diminished effector function. Furthermore, the deletion of p16 significantly enhances the persistence of CD8+ T cells within tumors and suppresses the terminal exhaustion of tumor-infiltrating T cells. Overall, our findings elucidate how increased p16 expression reshapes T cell intracellular metabolism, drives T cell apoptosis and exhaustion differentiation, and ultimately impairs T cell anti-tumor function.

Abstract This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p

Abstract The complete compound of gefitinib is effective in the treatment of lung adenocarcinoma. However, the effect on lung adenocarcinoma (LUAD) during its catabolism has not yet been elucidated. We carried out this study to examine the predictive value of gefitinib metabolism-related long noncoding RNAs (GMLncs) in LUAD patients. To filter GMLncs and create a prognostic model, we employed Pearson correlation, Lasso, univariate Cox, and multivariate Cox analysis. We combined risk scores and clinical features to create nomograms for better application in clinical settings. According to the constructed prognostic model, we performed GO/KEGG and GSEA enrichment analysis, tumor immune microenvironment analysis, immune evasion and immunotherapy analysis, somatic cell mutation analysis, drug sensitivity analysis, IMvigor210 immunotherapy validation, stem cell index analysis and real-time quantitative PCR (RT-qPCR) analysis. We built a predictive model with 9 GMLncs, which showed good predictive performance in validation and training sets. The calibration curve demonstrated excellent agreement between the expected and observed survival rates, for which the predictive performance was better than that of the nomogram without a risk score. The metabolism of gefitinib is related to the cytochrome P450 pathway and lipid metabolism pathway, and may be one of the causes of gefitinib resistance, according to analyses from the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Immunological evasion and immunotherapy analysis revealed that the likelihood of immune evasion increased with risk score. Tumor microenvironment analysis found most immune cells at higher concentrations in the low-risk group. Drug sensitivity analysis found 23 sensitive drugs. Twenty-one of these drugs exhibited heightened sensitivity in the high-risk group. RT-qPCR analysis validated the characteristics of 9 GMlncs. The predictive model and nomogram that we constructed have good application value in evaluating the prognosis of patients and guiding clinical treatment.

To study temperature and rate-dependent behaviors of molybdenum-rhenium (Mo–Re) alloys, compressive tests at variable temperatures and strain rates were conducted. After the same machining and thermal annealing processes, fully recrystallization happens in Mo and Mo–Re alloys with low Re content (5 wt %), while recovery occurs in Mo–Re alloys with high Re content (14 wt% and 42 wt %). The strength increases as Re content rises at all temperatures (300 °C, 600 °C and 1200 °C), meaning sufficient strengthening effect of Re. The rate-dependent behaviors, however, show different trends between Mo and Mo–Re alloys. Positive strain rate sensitivity is detected in Mo and low Re Mo–Re alloys in all temperatures, which is consistent to other research. While, near zero strain rate sensitivity is found in high Re Mo–Re alloys at 600 °C. Such an unusual phenomenon may be contributed to high stored dislocation density during mechanical processes. The stored dislocations are activated at a proper temperature to accommodate plastic flow, which weakens the influence of strain rate on strength.

This study aims to understand and enhance the indicative significance of convective initiation (CI) products from Fengyun-4A (FY-4A) satellite for summer precipitation over the Qinghai-Tibet Plateau. Using the convective initiation (CI) products of FY-4A and precipitation data from the Global Precipitation Measurement Program (GPM), and based on the correspondence between the CI samples identified by the FY-4A CI product and the actual observed precipitation one hour after identifying the CI in the Qinghai-Tibet Plateau region from June to August 2022, three categories of the CI samples, including no precipitation CI, weak precipitation CI, and strong precipitation CI, were divided. Then a CI class recognition model was established and the model performance testing was conducted by combining atmospheric convective parameters and geographic location information, two machine learning methods, decision tree and random forest. The results show that there are significant regional differences in the precipitation situation within one hour after the occurrence of CI in the Qinghai Tibet Plateau region, with a higher proportion of no precipitation in the northwest region and a higher proportion of precipitation in the southeast region. By utilizing atmospheric convective parameters such as lift index, total cloud water, wind shear, middle and low level humidity, cloud bottom height, zero degree layer height and so on, it is possible to better distinguish whether there is precipitation and the strength of precipitation after the appearance of CI in the Qinghai Tibet Plateau. The random forests identify model have better performance for CI classification than decision tree, and the use of random forests identify model can more effectively classify summer CI on the Qinghai Tibet Plateau according to precipitation intensity.