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Abstract Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Abstract Load prediction tasks aim to predict the dynamic trend of future load based on historical performance sequences, which are crucial for cloud platforms to make timely and reasonable task scheduling. However, existing prediction models are limited while capturing complicated temporal patterns from the load sequences. Besides, the frequently adopted global weighting strategy (e.g., the self-attention mechanism) in temporal modeling schemes has quadratic computational complexity, hindering the immediate response of cloud servers in complex real-time scenarios. To address the above limitations, we propose a Wavelet decomposition-enhanced External Transformer (WETformer) to provide accurate yet efficient load prediction for cloud servers. Specifically, we first incorporate discrete wavelet transform to progressively extract long-term trends, highlighting the intrinsic attributes of temporal sequences. Then, we propose a lightweight multi-head External Attention (EA) mechanism to simultaneously consider the inter-element relationships within load sequences and the correlations across different sequences. Such an external component has linear computational complexity, mitigating the encoding redundancy prevalent and enhancing prediction efficiency. Extensive experiments conducted on Alibaba Cloud’s cluster tracking dataset demonstrate that WETformer achieves superior prediction accuracy and the shortest inference time compared to several state-of-the-art baseline methods.

Abstract Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

Objective To analyze the accuracy of the new generation intraocular lens (IOL) formula and the Wang-Koch (WK) adjustment in individuals with severe myopia undergoing combined anterior-posterior surgery. Methods A total of 100 patients (100 eyes) with axial length (AL) >26 mm undergoing combined anterior and posterior segment surgery in our department from June 2015 to June 2021 were enrolled in this study. Totally 13 IOL calculation formulas, such as Barrett Universal Ⅱ (BUⅡ), Emmetropia Verifying Optical (EVO), Kane, Haigis, Hoffer Q, Holladay, and SRK/T as well as the first generation linear WK eye axis optimization formula (Haigis-WK1, SRK/T-WK1, Hoffer Q-WK1, Holladay 1-WK1) and the second generation linear WK eye axis optimization formula (SRK/T-WK2, Holladay 1-WK2), were utilized to determine IOL diopter. The mean prediction error (ME), mean absolute error (MAE), median absolute error (MedAE), and percentage of prediction error within different refractive thresholds were calculated to assess the accuracy of each formula. In order to investigate the impact of AL on accuracy of IOL calculation, the patients were categorized into group A (38 eyes, 26.00 mm < AL≤28.00 mm), group B (28 eyes, 28.00 mm < AL≤30.00 mm), and group C (34 eyes, AL >30.00 mm). Additionally, the patients were also divided into silicone oil (63 eyes) and non-silicone oil (37 eyes) groups based on preoperative intraocular filling to determine the effect of intraocular filling on IOL calculation. Results The MedAE values of the new-generation IOL formulas (BUⅡ, EVO, and Kane) were significantly lower (0.34D, 0.31D, 0.35D) than those of traditional formulas (P < 0.05). Additionally, the percentage of prediction errors within ±0.25 D, ±0.50 D, ±0.75 D, and ±1.00 D were significantly higher with the new formulas when compared to traditional ones (P < 0.05). Traditional formulas exhibited a hyperopic deviation (0.35D~0.65 D), which could be corrected using the WK eye axis adjustment. WK2 was effective in improving the accuracy of calculation in SRK/T and Holladay 1 formulas, and there was no statistical difference in the MedAE values of SRK/T-WK2 and Holladay 1-WK2 formulas with the new-generation IOL formulas. When comparing the formulas across different axial eye length groups in terms of MedAE, the new IOL formulas (BUⅡ, kane and EVO) and WK-corrected formulas (Haigis-WK1, SRK/T-WK1, SRK/T-WK2, Hoffer Q-WK1, Holladay 1-WK1, Holladay 1-WK2) showed no significant differences among the different AL groups. However, there were significant differences in the MedAE values of traditional formulas among the different AL groups (P < 0.01), with group C displaying the largest MedAE values (Haigis: 0.84D, SRK/T: 1.10D, Hoffer Q: 1.23D, Holladay 1: 1.20D). Comparing the MedAE values of different formulas in various preoperative intraocular filling groups, it was observed that the MedAE values of the new-generation IOL formulas (BUⅡ, kane and EVO), Haigis, and SRK/T formulas were significantly higher in the silicone oil-filled eye group than the non-silicone oil-filled eye group (P < 0.05). Conclusion In patients with high myopia undergoing combined anterior and posterior segment surgery, the precision and consistency of the new-generation IOL formulas and the second-generation linear WK axis correction formula exhibit significant improvements when compared to traditional formulas.

Abstract Aiming at the problem of image classification with insignificant morphological structural features, strong target correlation, and low signal-to-noise ratio, combined with prior feature knowledge embedding, a deep learning method based on ResNet and Radial Basis Probabilistic Neural Network (RBPNN) is proposed model. Taking ResNet50 as a visual modeling network, it uses feature pyramid and self-attention mechanism to extract appearance and semantic features of images at multiple scales, and associate and enhance local and global features. Taking into account the diversity of category features, channel cosine similarity attention and dynamic C-means clustering algorithms are used to select representative sample features in different category of sample subsets to implicitly express prior category feature knowledge, and use them as the kernel centers of radial basis probability neurons (RBPN) to realize the embedding of diverse prior feature knowledge. In the RBPNN pattern aggregation layer, the outputs of RBPN are selectively summed according to the category of the kernel center, that is, the subcategory features are combined into category features, and finally the image classification is implemented based on Softmax. The functional module of the proposed method is designed specifically for image characteristics, which can highlight the significance of local and structural features of the image, form a non-convex decision-making area, and reduce the requirements for the completeness of the sample set. Applying the proposed method to medical image classification, experiments were conducted based on the brain tumor MRI image classification public dataset and the actual cardiac ultrasound image dataset, and the accuracy rate reached 85.82% and 83.92% respectively. Compared with the three mainstream image classification models, the performance indicators of this method have been significantly improved.

Abstract Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.

AIM:To compare the corneal refractive power and visual quality after three kinds of corneal refractive surgery: laser subepithelial keratomileusis(LASEK), transepithelial photorefractive keratectomy(TransPRK)and femtosecond laser assisted in situ keratomileusis(FS-LASIK).METHODS: Retrospective study. A total of 232 patients(464 eyes)who underwent elective corneal refractive surgery in our hospital from January 2021 to December 2022 were selected as the study subjects. They were divided into the LASEK group of 70 cases(140 eyes), TransPRK group of 76 cases(152 eyes), and FS-LASIK group of 86 cases(172 eyes)according to the different surgical choices made by the patients. Uncorrected visual acuity(UCVA), visual quality, biomechanical stability, tear film break-up time(BUT), Schirmer Ⅰ test(SⅠt)and quality of life were compared among the three groups at 1 and 3 mo postoperatively.RESULTS: The UCVA of the three groups significantly improved at 1 and 3 mo postoperatively, the total high-order aberrations, spherical aberration, horizontal coma, and vertical coma of the entire cornea were significantly increased, while the biomechanical stability in all three groups were significantly reduced(all P0.05).CONCLUSION:In the treatment of ametropia, LASEK, TransPRK and FS-LASIK all have certain effects, and have similar results in improving UCVA and increasing visual quality. However, TransPRK and LASEK have more stable biomechanical properties than FS-LASIK, and have better efficacy in improving patients' quality of life.

The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.

High-pressure waterjet-assisted tunnel boring machine (WTBM) is an efficient method for improving the tunneling performance of a tunnel boring machine (TBM) and reducing the wear of its disc cutters in hard rock with high geostresses. Confining pressure directly affects the efficiency of rock breaking and the configuration of the disc cutters. In this study, we evaluated the effect of confining pressure on WTBM rock breaking by developing a self-designed and manufactured experimental system, including confining pressure loading, TBM disc-cutter penetration, and high-pressure waterjet. The macro fracture, acoustic emission (AE), peak normal force drop, and specific energy (SE) were analyzed for four different confining pressures (10, 20, 30, and 35 MPa). The results showed that the cutting depth of the waterjet increased linearly as the waterjet pressure increased and decreased with the gradual increase in the nozzle moving speed. The expansion and development of cracks formed rock debris, and the size of the rock fragments decreased with an increase in confining pressure. When the waterjet pressure was 280 MPa, the nozzle moving velocity was 800 mm/min and the kerf space was 75 mm, which indicated that the confining pressure, which was 23.16 MPa, minimized the cutting SE under this condition. However, regardless of the confining pressure, the maximum normal force of WTBM was less than that of a TBM, whereas the SE of WTBM was less than that of complete TBM cutting mode (CTCM). The average force drop and average drop rate of SE were approximately 25%, and 80%, respectively. The results of this study can inspire the design and mechanism of a TBM assisted by a high-pressure waterjet.

Objective: The aim of the present study is to explore the impact of the tet(A) type I variant (tetA-v1) on its fitness effect in Klebsiella pneumoniae. Methods: Clinical K. pneumoniae strains were utilized as parental strains to generate strains carrying only the plasmid vector (pBBR1MCS-5) or the tetA-v1 recombinant plasmid (ptetA-v1). Antimicrobial susceptibility testing was conducted to estimate the contribution of tetA-v1 to drug resistance. Plasmid stability was evaluated by serial passage over 10 consecutive days in the absence of tigecycline. Biological fitness was examined through growth curve analysis, in vitro competition assays and a neutropenic mouse thigh infection model. Results: A 2–4-fold increase in tigecycline MIC was observed following the acquisition of tetA-v1. Without tigecycline treatment, the stability of ptetA-v1 plasmids has been decreasing since day 1. The ptetA-v1 plasmid in Kp89, Kp91, and Kp93 exhibited a decrease of about 20% compared to the pBBR1MCS-5 plasmid. The acquisition of the tetA-v1 gene could inhibit the growth ability of K. pneumoniae strains both in vitro and in vivo. tetA-v1 gene imposed a fitness cost in K. pneumoniae, particularly in the CRKP strain Kp51, with a W value of approximately 0.56. Conclusion: The presence of tetA-v1 is associated with a significant fitness cost in K. pneumoniae in the absence of tigecycline, both in vitro and in vivo.

To investigate the effect of magnetic field on the electrochemical corrosion behavior of X70 pipeline steel and the effect of magnetic field on the corrosion behavior of X70 steel after immersed in Kuerle soil simulation solution, the electrochemical corrosion behavior of pipeline steel under different magnetic field strengths, directions and the presence or absence of product films was analyzed by electrochemical tests, immersion tests and metallographic analysis. Results showed that as the magnetic field strength increased, the corrosion rate of X70 steel first increased and then decreased. Changing the direction of the magnetic field had no significant effect on the electrochemical corrosion behavior of X70 steel. The corrosion trend of X70 pipeline steel was the same in both cases after immersed for 3 and 5 d, respectively, and the corrosion rate increased with the increase of external magnetic field. Moreover, the adsorption resistance of X70 steel with a product film on its surface was higher than that without a product film, and the X70 steel with the product film exhibited lower corrosion current density and lighter corrosion degree. However, different immersing times had little effect on the corrosion current density.

Abstract Background The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis. Methods Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1. Results UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis. Conclusions UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.

Abstract Efficient allocation of tasks and resources is crucial for the performance of heterogeneous cloud computing platforms. To achieve harmony between task completion time, device power consumption, and load balance, we propose a Graph neural network-enhanced Elite Particle Swarm Optimization (EPSO) model for collaborative scheduling, namely GraphEPSO. Specifically, we first construct a Directed Acyclic Graph (DAG) to model the complicated tasks, thereby using Graph Neural Network (GNN) to encode the information of task sets and heterogeneous resources. Then, we treat subtasks and independent tasks as basic task units while considering virtual or physical devices as resource units. Based on this, we exploit the performance adaptation principle and conditional probability to derive the solution space for resource allocation. Besides, we employ EPSO to consider multiple optimization objectives, providing fine-grained perception and utilization of task and resource information. It also increases the diversity of particle swarms, allowing GraphEPSO to adaptively search for the global optimal solution with the highest probability. Experimental results demonstrate the superiority of our proposed GraphEPSO compared to several state-of-the-art baseline methods on all evaluation metrics.

According to the convergence confinement theory, it is an effective measure to control the large deformation of high ground stress in fractured soft rock tunnels by using yielding support. The yielding support can be classified as either radial or circumferential yielding support. Circumferential yielding support is achieved by transforming radial displacement into circumferential tangential closure without compromising the support capacity of the primary lining support structure. Based on this, and inspired by the design principle of dampers, a yielding support structure system with spring damping elements as its core was developed, based on the connection characteristics of steel arches in highway tunnel, which can provide increasing support resistance in the yielding deformation section. Then the mechanical properties of spring damping elements were obtained through indoor axial pressure and flexural tests. In addition, according to these results with numerical calculations, the yielding support structure system with embedded spring damping elements can reduce the internal force of the support structure by approximately 10% and increase the area of the plastic zone of the surrounding rock by 11.23%, which can fully utilize the self-bearing capacity of surrounding rock and verify the effectiveness of circumferential yielding support. Finally, the spring damping support structure system was designed with reference to the construction process of the tunnel excavated by drilling and blasting method, and the transformation of the spring damping element to spring damping support structure was achieved. Based on field test results, surrounding ground pressure for the yielding support optimization scheme was reduced by 40% and more evenly distributed, resulting in the successful application and a reduction in the construction cost of large deformation tunnels in soft rock.

Abstract The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates’ local polarizabilities and observed enantio-selectivity were also revealed in three widely known asymmetric catalytic systems covering both reductions and oxidations. This broadly applicable polarizability-based electronic effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.

Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer, analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis. Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers. Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications. Based on the distribution characteristics of H3K27ac, the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored. The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses. Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues. Compared with normal gastric mucosa, the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer. A total of 8 847 enhancers with increased activity in intestinal type gastric cancer were identified, accounting for 8.3% of all enhancers, which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells. A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers, which was able to predict the overall survival of patients. Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer. These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC, E2F3 and other genes. A prognosis model based on enhancer target genes is constructed.

Abstract Background Ameloblastoma (AM) is the most common benign odontogenic tumor, which is more often detected in the mandible than maxilla, especially the mandibular body and mandibular angle. Pediatric AM is a rare disease, especially in patients aged 10 and younger. Compared with the mainstream osteotomy and reconstructive surgery for adult ameloblastoma, there is more room for discussion in the treatment of pediatric ameloblastoma. The postoperative functional and psychological influence can not be ignored. Especially for children in the period of growth and development, an osteotomy is often challenging to be accepted by their parents. We report two patients with ameloblastoma under 10 years old who are treated with curettage and fenestration, which is a beneficial method for children with ameloblastoma. Case presentation We present two cases of classic ameloblastoma in children. We describe in detail the patients’ characteristics, treatment processes, and follow-up result. The bone formation and reconstruction in the lesion area after fenestration decompression and curettage are recorded at every clinic review. The surgical details and principles of curettage and decompression are also described and discussed. The two patients have good bone shape recovery and no recurrence. Conclusions Children are in the growth and development period and possess an extremely strong ability of bone formation and reconstruction. Based on the principles of minimally invasive and functional preservation, we believe that curettage combined with decompression can be the first choice for treating AM in children, especially for mandibular lesions.

Abstract Arterial occlusion-induced ischemic stroke (IS) is a highly frequent stroke subtype. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that modulates antioxidant genes. Its role in IS is still unelucidated. The current study focused on constructing a transient middle cerebral artery occlusion (tMCAO) model for investigating the NRF2-related mechanism underlying cerebral ischemia/reperfusion (I/R) injury. Each male C57BL/6 mouse was injected with/with no specific NRF2 activator post-tMCAO. Changes in blood–brain barrier (BBB)-associated molecule levels were analyzed using western-blotting, PCR, immunohistochemistry, and immunofluorescence analysis. NRF2 levels within cerebral I/R model decreased at 24-h post-ischemia. NRF2 activation improved brain edema, infarct volume, and neurological deficits after MCAO/R. Similarly, sulforaphane (SFN) prevented the down-regulated tight junction proteins occludin and zonula occludens 1 (ZO-1) and reduced the up-regulated aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) after tMCAO. Collectively, NRF2 exerted a critical effect on preserving BBB integrity modulating ferroptosis and inflammation. Because NRF2 is related to BBB injury regulation following cerebral I/R, this provides a potential therapeutic target and throws light on the underlying mechanism for clinically treating IS.

IntroductionMesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.MethodsIn this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).ResultsThe median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.DiscussionThese finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

Summary: In this study, we obtained the whole genome sequence of GCRV-DY197 and investigated the localization, post-translational modifications, and host interactions of the 11 viral proteins encoded by GCRV-DY197 in grass carp ovary (GCO) cells. The whole genome sequence is 24,704 kb and contains 11 segments (S1–S11). Subcellular localization showed that the VP1, VP2, VP3, VP5, VP56, and VP35 proteins were localized in both cytoplasm and nucleus, whereas the NS79, VP4, VP41, VP6, and NS38 proteins were localized in the cytoplasm. The NS79 and NS38 proteins were phosphorylated, and the ubiquitination modification sites were identified in VP41 and NS38. An interaction network containing 9 viral proteins and 140 host proteins was also constructed. These results offer a theoretical basis for an in-depth understanding of the biochemical characteristics and pathogenic mechanism of GCRV-II.

BackgroundOxidative stress is acknowledged as a pivotal factor in the intricate pathophysiological processes and pathogenesis of constipation. Modifying dietary patterns can elevate in vivo antioxidant biomarker levels, consequently mitigating oxidative stress. The Composite Dietary Antioxidant Index (CDAI) provides a dependable scoring mechanism for quantifying the potential antioxidant capacity of diets. The association between CDAI levels and the risk of constipation remains uncertain.PurposeTo investigate the potential correlation between CDAI and constipation, aiming to improve constipation management through dietary guidance.MethodsA total of 11,165 adults aged ≥20 years, drawn from the 2005–2010 National Health and Nutrition Examination Survey, were enrolled in this cross-sectional study. We evaluated the correlation between CDAI levels and the risk of constipation through three weighted logistic regression models. Restricted cubic spline (RCS) analysis was employed to assess nonlinear trends, and stratified analyses were conducted.ResultsAfter adjusting for all confounding variables, the findings revealed an association between CDAI and constipation [OR = 0.937; 95% CI (0.892, 0.984), p = 0.012]. Moreover, individuals in the highest quartile of CDAI demonstrated a 40.1% lower likelihood of experiencing constipation compared to those in the lowest quartile [OR = 0.599; 95% CI (0.382, 0.939), p = 0.027]. The RCS analysis indicated a linear relationship between CDAI and constipation (P-non-linear =0.1016). Subgroup analysis by gender revealed a negative correlation in the male population [OR = 0.871; 95% CI (0.801, 0.947), p = 0.002], with men in the highest CDAI quartile exhibiting a 59.8% lower likelihood of experiencing constipation compared to those in the lowest quartile [OR = 0.402; 95% CI (0.206, 0.787), p = 0.010]. Furthermore, alterations in selenium [OR = 0.997; 95% CI (0.995, 1.000), p = 0.039] per milligram were independently linked to constipation. In a gender subgroup analysis of a single antioxidant, changes per milligram of vitamin E [OR = 0.904; 95% CI (0.838 to 0.975), p = 0.011] among males were independently associated with constipation.ConclusionThe fully adjusted model showed a correlation between CDAI and constipation and a significant correlation in quartiles. Meanwhile, subgroup analysis by gender showed that CDAI was negatively associated with constipation in the male population. Moreover, the findings of this study imply that investigations into antioxidant diets should be contextualized within dietary patterns.

BackgroundThis study aimed to evaluate the effects of creatine monohydrate supplementation on cognitive function in adults and explore its potential role in preventing and delaying cognitive impairment-related diseases.MethodsFollowing the PRISMA 2020 guidelines, a systematic review with meta-analysis was conducted. Randomized controlled trials (RCTs) published between 1993 and 2024 were retrieved from PubMed, Scopus, and Web of Science databases. The study protocol was registered with PROSPERO (registration number: CRD42024533557). The impact of creatine supplementation on overall cognitive function, memory, executive function, attention, and information processing speed was assessed using standardized mean differences (SMD) and Hedge’s g with 95% confidence intervals (CI).ResultsSixteen RCTs involving 492 participants aged 20.8–76.4 years, including healthy individuals and patients with specific diseases, were selected. Creatine monohydrate was the form used in all included studies. Creatine supplementation showed significant positive effects on memory (SMD = 0.31, 95% CI: 0.18–0.44, Hedges’s g = 0.3003, 95% CI: 0.1778–0.4228) and attention time (SMD = −0.31, 95% CI: −0.58 to −0.03, Hedges’s g = −0.3004, 95% CI: −0.5719 to −0.0289), as well as significantly improving processing speed time (SMD = −0.51, 95% CI: −1.01 to −0.01, Hedges’s g = −0.4916, 95% CI: −0.7852 to −0.1980). However, no significant improvements were found on overall cognitive function or executive function. Subgroup analyses revealed that creatine supplementation was more beneficial in individuals with diseases, those aged 18–60 years, and females. No significant differences were found between short- (

Abstract Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer‐associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild‐hyperthermia photothermal therapy (mild‐PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)‐loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild‐PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)‐loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness‐mediated mild‐PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

ObjectiveThis study aimed to evaluate the feasibility of a hybrid Glubran-supported single-Proglide technique for large bore femoral access closure during percutaneous access endovascular aneurysm repair (EVAR).MethodsA retrospective cohort study was performed for all percutaneous EVARs at our center from January 2023 to June 2023. All patients received the hybrid Glubran-supported single-Proglide technique involving a mixture of surgical glue and Lipiodol injection after single suture placement for femoral access closure. Technical success was defined as achieving complete hemostasis without a bailout strategy. Vascular complications and bleeding were defined by Valve Academic Research Consortium-3 (VARC-3) criteria. Vascular access changes and 30-day mortality were recorded.ResultsThe technique success rate for the entire study population was 100% (55 femoral access in 37 patients; median age: 72; 78% males). The mean sheath size was 20.4 ± 2.3F. The mean manual compression time was 3.5 ± 1.4 min, the mean hemostasis time was 9.0 ± 2.5 min, and the mean procedural time was 103.9 ± 34.7 min. One patient (1.6%) developed an access site infection and recovered conservatively. No VARC-3 vascular complications and access changes were observed. No 30-day mortality happened.ConclusionsThe hybrid Glubran-supported single-Proglide technique is feasible for large bore access closure during EVAR and may be a viable alternative; however, larger prospective studies are required to confirm its efficacy.

Recent research emphasised the indispensable role of histone lactylation in the activation of hepatic stellate cells. The VHL mutation is extremely common in clear cell renal cell carcinoma, which normally causes a metabolic shift in cancer cells and increases lactate production, eventually creating a lactate-enriched tumour microenvironment. Cancer-associated fibroblasts (CAFs) promote tumour progression, which is also vital in clear cell renal cell carcinoma. Therefore, this study investigated histone lactylation in CAFs and its impact on patient survival. Multiomics technology was employed to determine the role of histone lactylation-related genes in the evolution of CAFs which correlated with the function and molecular signatures of CAFs. The results suggested that TIMP1 was the hub gene of histone lactylation-related genes in clear cell renal cell carcinoma.

Viscoelastic plastic solutions for tunnel excavation in strain-softening rock mass and tunnel-rock interaction are proposed based on the Mohr-Coulomb and the Generalized Zhang-Zhu (GZZ) strength criterion considering stress path. The solutions are verified by numerical simulations, results show that the theoretical solutions are close to the simulated data. The evolutions of rock stresses, strains, displacements and support pressure were investigated and the influences of residual strength parameter, support stiffness, support timing, initial support pressure and viscosity coefficient on the rock deformation and the support pressure are discussed by proposed solution. It is found that strain-softening results in large deformation and high support pressure, with stiffer support and a larger viscosity coefficient contributing to even greater support pressure. Ductile support is recommended at the first stage to release the energy and reduce the support pressure by allowing a relatively large deformation. The support pressure, especially the additional support pressure at the second stage will be much smaller if a higher initial support pressure is applied at the first stage. This can not only control the displacement rate of surrounding rock and improve the tunnel stability at the first stage by exerting sufficient support pressure immediately after tunnel excavation, but also greatly reduce the pressure acted on permanent support and improve the structure stability at the second stage. Therefore, to avoid the instability of support structure, ductile support, which could not only deform continuously but also provide sufficient high support pressure, is recommended at the first stage.

Quantitative Real-time PCR (qRT-PCR) is one of the most widely used methods for gene quantification because it is extremely sensitive, can be highly sequence specific, and has high precision while being easily reproducible in samples. The stability of the reference genes used for data normalization is crucial for exact experimental results and conclusions. In this study, qRT-PCR was used to analyze the expression of eight candidate reference genes including β-actin (ACTB), α-tubulin (TUBA), Elongation factor-1-α (EF1A), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH1, GAPDH2), Hypoxanthine guanine phosphoribosyl transferase1 (HPRT), Ribosomal protein L7 (RPL7), and RNA polymerase II (RNA PoL Ⅱ) in largemouth bass. The expression and stability of above genes were evaluated among eight tissues with or without largemouth bass virus (LMBRaV) infection and assessed using BestKeeper, GeNorm, NormFinder statistical softwares and comparative Ct method, and then analyzed the comprehensive ranking by ReFinder. Our results showed that ACTB was identified as the most suitable genes of different tissues, while TUBA was ranked as the best reference gene in tissues infection with LMBRaV. To verify the screened reference genes, the expression pattern of IFN in spleen during LMBRaV infection was examined. This study provides useful information for gene expression characterization using qRT-PCR, which will benefit for future studies of gene regulation in largemouth bass.

High-entropy alloy (HEA) coatings have demonstrated great potential in anti-wear applications. To further improve the mechanical and tribo-corrosion properties of the HEA coatings, the VAlTiMoSi, (VAlTiMoSi)80C20, and (VAlTiMoSi)60C40 coatings were successfully deposited by DC magnetron sputtering. The microstructure, mechanical, and tribo-corrosion properties of as-deposited and heat-treated coatings were analyzed. All the as-deposited HEA coatings were BCC + amorphous phases. The thermal effect promoted the formation of intermetallic compounds, and the C inhibited the formation of Mo3Si and Ti5Si4. The hardness and elastic modulus of the heat-treated VAlTiMoSi coating were 20.1 and 294.0 GPa, respectively. The heat-treated (VAlTiMoSi)60C40 coating showed the lowest wear rate, namely 5.2 × 10−14 m3·Nm−1, and the best formation ability of passive film in 3.5 wt% NaCl solution.

BackgroundA common sense is that lower serum cholesterol levels are better. However, a growing number of researches have questioned this especially for the oldest old. The current study was to assess the association between total cholesterol and all-cause mortality in a group of people aged 85 years old and over.MethodsWe selected 903 Chinese old participants who aged ≥85 years from the Chinese Longitudinal Healthy Longevity Survey(CLHLS) at baseline in 2012. The participants were followed up until death or until December 31, 2014. The outcome was all-cause mortality. The univariate and multivariate Cox regression analyses were used to estimate risk levels of all-cause mortality. We stratified the participants into three groups (

As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of β2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of β2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the sh-β2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between β2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-β2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting β2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

ABSTRACT: Salmonella, which is widely distributed in nature, is an important zoonotic pathogen affecting humans, livestock, and other animals. Salmonella infection not only hinders the development of livestock and poultry-related industries but also poses a great threat to human health. In this study, we collected 1,537 samples including weak chicks, dead embryos, fecal samples and environmental samples from 2020 to 2023 (for a period of 1 to 2 months per year) to keep a long-term monitor the prevalence of Salmonella in an intensive laying hen farm, 105 Salmonella strains were isolated with an isolation rate of 6.83% (105/1,537). It revealed a significant decrease in prevalence rates of Salmonella over time (P < 0.001). Before 2020, the predominant serotype was S. Enteritidis. S. Kentucky was first detected in November 2020 and its proportion was gradually found to exceed that of S. Enteritidis since then. S. Kentucky isolates were distributed in various links of the four regions in the poultry farm. A total of 55 S. Kentucky strains, were assigned to ST198 based on whole genome sequencing. Among them, 54 strains were resistant to 12 to 16 antibiotics, indicating that they were extensively drug-resistant (XDR). Seventeen antimicrobial resistance genes were detected in 55 S. Kentucky isolates. For most of these isolates, antibiotic resistance phenotypes were concordant with their genotypes. All S. Kentucky strains isolated from this farm in 2020 to 2023 showed a high similarity based on their core-genome SNP-based phylogeny. The traceability analysis revealed that S. Kentucky was introduced to the farm through newly purchased flocks. The long-term existence of XDR S. Kentucky ST198 poses a substantial risk because of the multiage management and circulation of workers in this poultry farm. Thus, this study is the first to report extensively drug-resistant S. Kentucky ST198 detected in this intensive poultry farm in China.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease, and quality of life of COPD patients can be severely impaired with increasing severity of disease. As a kind of exercise in Traditional medicine, Baduanjin Qigong is an aerobic exercise which is suitable for elderly patients. It can improve the cardiopulmonary function of patients and is conducive to the rehabilitation of COPD. This article summarized the effective intervention of Baduanjin Qigong exercise therapy on elderly patients with COPD in stable stage, and provided reference for modify the exercise prescription for elderly patients with CODP. (慢性阻塞性肺疾病(COPD)是临床老年患者常见呼吸系统疾病, 严重影响老年患者的生活质量。八段锦动作柔和缓慢, 属于有氧运动, 且不受场地限制, 适用于老年患者, 可改善其心肺功能, 有利于COPD的康复。本研究从老年COPD稳定期患者开展八段锦运动锻炼的效果、作用机制及运动方案进行综述, 以期为老年COPD患者运动处方的修订提供参考。)

Although Federated Deep Learning (FDL) enables distributed machine learning in the Internet of Vehicles (IoV), it requires multiple clients to upload model parameters, thus still existing unavoidable communication overhead and data privacy risks. The recently proposed Swarm Learning (SL) provides a decentralized machine learning approach for unit edge computing and blockchain-based coordination. A Swarm-Federated Deep Learning framework in the IoV system (IoV-SFDL) that integrates SL into the FDL framework is proposed in this paper. The IoV-SFDL organizes vehicles to generate local SL models with adjacent vehicles based on the blockchain empowered SL, then aggregates the global FDL model among different SL groups with a credibility weights prediction algorithm. Extensive experimental results show that compared with the baseline frameworks, the proposed IoV-SFDL framework reduces the overhead of client-to-server communication by 16.72%, while the model performance improves by about 5.02% for the same training iterations.

This paper was mainly concerned with the stability analysis of a class of fractional-order neural networks with S-type distributed delays. By using the properties of Riemann-Liouville fractional-order derivatives and integrals, along with the additivity of integration intervals and initial conditions, fractional-order integrals of the state function with S-type distributed delays were transformed into fractional-order integrals of the state function without S-type distributed delays. By virtue of the theory of contractive mapping and the Bellman-Gronwall inequality, the sufficient conditions for finite-time stability and global Mittag-Leffler stability were obtained when certain conditions were satisfied. Moreover, the correctness and realizability of the conclusion were verified through the presentation of two illustrative numerical simulation examples.

Abstract Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant soft-tissue tumor that originates from the skin. It has a slow onset in the early stages, non-specific clinical symptoms, low specificity, and can easily be overlooked, missed, or misdiagnosed by clinicians and pathologists. In addition, DFSP is prone to recurrence after local surgical treatment; however, distant metastasis, especially abdominal metastasis, is rare, which is also a challenge for the accurate diagnosis of DFSP when it progresses distantly. Now a case of abdominal metastasis of DFSP is reported. The patient has been treated with imatinib for ten years, and the lesion has shrunk, but because the patient has been receiving imatinib treatment, his abdominal lesion was once misdiagnosed as gastrointestinal stromal tumor. Therefore, we report on this case to enhance the understanding of the diagnosis and treatment of DFSP, and to provide reference for the pathological diagnosis and precise treatment of such patients.

Abstract Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

BackgroundThe very small-angle neutron scattering (VSANS) spectrometer is currently being constructed at the China spallation neutron source (CSNS). The neutron detector plays a key role in meeting the detection requirements of the spectrometer.PurposeThis study aims to achieve accurate measurement of neutron diffraction in the small angle scattering mode which requires the position resolution of the neutron detector to be ≤2 mm, and the detection efficiency to be ≥60%@0.4 nm.MethodsA large-area position-sensitive neutron scintillator detector mainly composed of 6LiF/ZnS(Ag) scintillation screen, wavelength shift fiber (WLSF), and a silicon photomultiplier (SiPM) was designed and developed to achieve high efficiency and high-resolution real-time detection of thermal neutrons. The optical transmission performance of the 0.5-mm-diameter wavelength shift fiber was investigated in detail. The gain and the thermal noise characteristics of various SiPMs were examined. Finally, a 300 mm×300 mm engineering prototype of the detector was developed and tested by experiments. The detection efficiency was calculated with comparison of the incident neutron counts of the stander 3He tube whilst the detector's position resolution was tested using a boron-doped aluminum plate with a narrow slit bearing the label 'CSNS'.ResultsThe neutron beam test results show that the position resolution of the detector is 1.2 mm×1.2 mm and that the neutron detection efficiency is (61.8±0.2)%@0.4 nm.ConclusionsThe high-resolution neutron scintillator detector developed in this study satisfies the engineering design target, and meets the neutron scintillator detector meets the neutron diffraction measurement needs for the VSANS spectrometer of the CSNS.

The liquefied natural gas (LNG) fuel tank in a large container ship is loaded with liquid LNG at an ultra-low temperature (-163°C), there is a significant temperature difference in the cargo hold area where the entire fuel tank is located, which will have an important impact on the steel grade design and structural safety of the cargo tank in container ship. This paper develops two heat transfer models using Computational Fluid Dynamics method (CFD method) and an analytical method to analyze the temperature distribution in a large container ship equipped with Type-B LNG fuel tank. These models incorporate the arrangement and heat transfer characteristics of LNG fuel tanks. The temperature field analysis is conducted under typical the environmental conditions specified in the Code for the Construction and Equipment of Ships Transporting Liquefied Gas in Bulk (IGC Code) and the United States Coast Guard Code (USCG Code), based on the CFD method and the analytical method, and the results of temperature field distribution are compared. Additionally, a parametric analysis of the hull temperature field is further carried out, the results show that the thermal conductivity of the insulation layer in LNG storage tanks and the types of the loaded liquid cargo have a limited impact on the final temperature field distribution in hull structure. However, the selection of steel grade in the local structure of the cargo hold, especially in the inner hull part, may lead to significant changes.

Abstract Background Few studies have investigated healthy female individuals (HFI) and those with obstructed defecation syndrome associated with moderate rectocele in women (MRW), identified using three-dimensional high-resolution anorectal manometry (3D HRAM) parameters that correlate with age stratification. Objective We aimed to explore the clinical diagnostic values of the MRW and HFI groups using 3D HRAM parameters related to age stratification. Methods A prospective non-randomized controlled trial involving 128 cases from the MRW (treatment group, 68 cases) and HFI (control group, 60 cases) groups was conducted using 3D HRAM parameters at Tianjin Union Medical Center between January 2017 and June 2022, and patients were divided into two subgroups based on their ages: the ≥50 and < 50 years subgroups. Results Multivariate binary logistic regression analysis showed that age (P = 0.024) and rectoanal inhibitory reflex (P = 0.001) were independent factors affecting the disease in the MRW group. Compared to the HFI group, the receiver operating characteristic (ROC) curve demonstrated that the 3D HRAM parameters exhibited a higher diagnostic value for age (Youden index = 0.31), urge to defecate (Youden index = 0.24), and rectoanal pressure differential (Youden index = 0.21) in the MRW group. Conclusions Compared to the HFI group, the ROC curve of the 3D HRAM parameters suggests that age, urge to defecate, and rectoanal pressure differential in the MRW group have a significant diagnostic value. Because the Youden index is lower, 3D HRAM cannot be considered the gold standard method for diagnosing MRW.

Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells.

Abstract Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor β (IR-β), and loss of BACH1 reduces the interaction between PTP1B and IR-β upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis.

With the increasing proportion of people with lower limb dysfunction in the population, lower limb exoskeleton, mainly in the form of physical assisted therapy, has become a research hotspot in the field of rehabilitation. In this study, a wearable lower limb exoskeleton prototype model is proposed and its motion performance is studied. Firstly, the corresponding relation between human lower limbs and exoskeleton is established. Secondly, the standard D-H method is used to build the exoskeleton kinematics mathematical model, the forward and inverse kinematics is solved through the homogeneous transformation matrix, and the correctness of the model and the solving equation is verified. Finally, the man-machine coupling model is simulated based on the gait characteristics of human lower limbs. The goodness of curve fitting shows that the exoskeleton runs smoothly, and has good compatibility and tracking performance. The joint curve data provides the data basis for the formulation of the control strategy of the lower limb exoskeleton.

Recently, regime-switching option pricing based on fractional diffusion models has been used, which explains many significant empirical facts about financial markets better. There are many methods to solve the problem, but to the best of our knowledge, effective preconditioners for the second-order schemes have not been proposed. Thus, in this article, an implicit numerical scheme is developed for a regime-switching European option pricing problem under a multi-state tempered fractional model. The scheme is proven to be unconditionally stable and converges quadratically in space and linearly in time. Besides, the resulting linear system is solved using an iterative method, and a preconditioner is proposed to accelerate the rate of convergence. The preconditioner is constructed through circulant approximations to the Toeplitz blocks due to the coefficient matrix, which is is a block matrix with Toeplitz blocks. The spectral analysis of the preconditioned matrix is given, which demonstrates that the spectrum of the preconditioned matrix is clustered around 1. Numerical examples show the efficiency of the proposed method, and an empirical study is also provided.

Abstract Carbapenem-resistant Enterobacterales (CRE) has emerged as a worldwide spread nosocomial superbug exhibiting antimicrobial resistance (AMR) to all current antibiotics, leaving limited options for treating its infection. To discovery novel antibiotics against CRE, we designed and synthesized a series of 14 isothiazol-3(2H)-one analogues subjected to antibacterial activity evaluation against Escherichia coli (E. coli) BL21 (NDM-1) and clinical strain E. coli HN88 for investigating their structure–activity relationships (SAR). The results suggested that 5-chloroisothiazolone core with an N-(4-chlorophenyl) substitution 5a was the most potent antibacterial activity against the E. coli BL21 (NDM-1) with MIC value of less than 0.032 μg/mL, which was at least 8000-fold higher than the positive control Meropenem (MRM). It also displayed 2048-fold potent than the positive control MRM against E. coli HN88. Additionally, SAR analysis supported the conclusion that compounds with a chloro-group substituted on the 5-position of the heterocyclic ring was much more potent than other positions. The board spectrum analysis suggested that compound 5a showed a promising antimicrobial activity on MRSA and CRE pathogens. Meanwhile, cytotoxicity study of compound 5a suggested that it had a therapeutic index value of 875, suggesting future therapeutic potential. In vivo efficacy study declared that compound 5a could also protect the BALB/c mice against American type culture collection (ATCC) 43,300. Further screening of our compounds against a collection of CRE strains isolated from patients indicated that compound 5 g displayed much stronger antibacterial activity compared with MRM. In conclusion, our studies indicated that isothiazolones analogues could be potent bactericidal agents against CRE and MRSA pathogens.

AbstractAn outbreak of a disease with a high mortality rate occurred in a Chinese Softshell Turtle (Pelodiscus sinensis) farm in Hubei Province. This study isolated a highly pathogenic Bacillus cereus strain (Y271) from diseased P. sinensis. Y271 has β hemolysis, containing both Hemolysin BL (hblA, hblC, and hblD), Non-hemolytic enterotoxin, NHE (nheA, nheB, and nheC), and Enterotoxin FM (entFM) genes. Y271 is highly pathogenic against P. sinensis with an LD50 = 6.80 × 103 CFU/g weight. B. cereus was detected in multiple tissues of the infected P. sinensis. Among them, spleen tissue showed the highest copy number density (1.54 ± 0.12 × 104 copies/mg). Multiple tissues and organs of diseased P. sinensis exhibited significant pathological damage, especially the spleen, liver, kidney, and intestine. It showed obvious tissue structure destruction, lesions, necrosis, red blood cells, and inflammatory cell infiltration. B. cereus proliferating in the spleen, liver, and other tissues was observed. The intestinal microbiota of the diseased P. sinensis was altered, with a greater abundance of Firmicutes, Fusobacterium, and Actinomyces than in the healthy group. Allobaculum, Rothia, Aeromonas, and Clostridium abundance were higher in the diseased group than in the healthy group. The number of unique microbial taxa (472) in the disease group was lower than that of the healthy group (705). Y271 was sensitive to multiple drugs, including florfenicol, enrofloxacin, neomycin, and doxycycline. B. cereus is the etiological agent responsible for the massive death of P. sinensis and reveals its potential risks during P. sinensis cultivation.

Abstract Background Heat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress. Results Rice plants were pretreated with distilled water, 50 μM ABA and 10 μM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2 – and H2O2) by 15.0–25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4–16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress. Conclusion Taken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

Mangroves are among the most carbon-rich ecosystems in the world. However, they have experienced widespread loss due to climate change and have been reclaimed for coastal cropland and aquaculture ponds. Studying the impact of climate change on the potential distribution and carbon benefits of mangroves is crucial for their conservation and restoration. Currently, there is limited research on the potential distribution of mangroves in China under future climate change scenarios using ensemble models. Furthermore, there is a relative scarcity of studies that apply simulation results to the restoration and protection of mangroves. Therefore, based on 15 dominant mangrove species, we constructed high-precision species distribution models to simulate the potential distribution of mangroves in China during the current period (1981–2010) and predicted their potential distribution under three climate scenarios (SSP1-2.6, SSP3-7.0, and SSP5-8.5) in the late 21st century (2071–2100). Our study showed that 1) the four most crucial drivers of mangrove suitability in China are: air temperature in the coldest quarter, sea surface temperature range, isothermality, and annual precipitation amount. 2) mangroves tend to expand northward by 2–2.5 degrees of latitude in the end of the 21st century. Meanwhile, the potential distribution of Spartina alterniflora is expected to expand rapidly and pose a significant competitive threat to native mangrove species; 3) by restoring coastal cropland and aquaculture ponds to mangroves in the potential mangrove distribution area, the potential carbon stocks of mangroves would increase by 178.22–296.44 % and 170.31–277.13 % compared to the current carbon stocks of mangroves, the annual blue carbon would increase by 242.64–262.70 % compared to the current blue carbon of mangroves. Our research could provide valuable information for the future conservation and restoration of mangroves in China.

Metallic sodium (Na) serving as anode for sodium-based batteries (SBBs) has caught much attention, owning to its low electrode potential and high theoretical capacity. However, the notorious Na dendrites severely restrict its practical application in Na metal batteries (SMBs). Herein, the hybrid artificial layer (Na/VN-S) composed of sodium sulfide, vanadium nitride and metal vanadium are constructed on Na anode via pretreatment metallic Na with vanadium nitride and vanadium sulfide powders. The obtained Na/VN-S electrode presents superior electrolyte wettability, high sodiophilicity, low activation energy barrier and high Young’s modulus, leading to homogeneous distribution of Na ions and even Na deposition, so that the Na dendrite growth can be suppressed. Owing to these virtues, the Na/VN-S symmetrical cells present a long cycle life of 1400 h at 0.5 mA cm−2 with 1 mAh cm−2, and can stably cycle at a higher current density of 4 mA cm−2. Moreover, when the commercial Na3V2(PO4)3 (NVP) cathodes are coupled with the Na/VN-S anodes, the Na/VN-S||NVP full cells display a prolonged life of 1900 cycles at 5 C with an outstanding capacity retention of 84.2%. This work contributes to the advancement of Na metal anode in high performance SBBs.

ABSTRACT: Salmonellosis in poultry is detrimental to the advancement of the breeding industry and poses hazards to human health. Approximately 2,600 Salmonella varieties exist, among which S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis are prevalent serotypes in the poultry industry in recent years. They can also infect humans by contaminating poultry eggs and meat. Therefore, identifying these serotypes is crucial for successful preventive and control interventions. The White–Kauffmann–Le Minor scheme is time-consuming and requires expensive reagents. Whole-genome sequencing (WGS) and other molecular biology techniques require skilled technical staff. In comparison, the polymerase chain reaction (PCR) is more accurate, rapid, and inexpensive, thus proving suitable for widespread application in the poultry industry. Here, we selected 4 specific primers: lygD, mdh, ipaJ, and SIN_02055, which correspond to detecting S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, respectively. They were integrated into a 1-step multiplex PCR method. We optimized the PCR method by utilizing specificity test results to determine the optimal annealing temperature (57°C). The PCR method exhibited excellent sensitivity for genomic DNA and bacterial cultures. We used the developed method to determine 157 clinical Salmonella isolates from various stages of the poultry production chain. The results aligned with serotype data generated via WGS analysis, demonstrating the method's excellent accuracy. In conclusion, this study developed a 1-step multiplex PCR method that simultaneously identifies S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, allowing routine mass detection in the grass-root poultry industry.