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Abstract Background This study aimed to design and develop a 5K low-density liquid chip for Hainan cattle utilizing targeted capture sequencing technology. The chip incorporates a substantial number of functional single nucleotide polymorphism (SNP) loci derived from public literature, including SNP loci significantly associated with immunity, heat stress, meat quality, reproduction, and other traits. Additionally, SNPs located in the coding regions of immune-related genes from the Bovine Genome Variation Database (BGVD) and Hainan cattle-specific SNP loci were included. Results A total of 5,293 SNPs were selected, resulting in 9,837 DNA probes with a coverage rate of 85.69%, thereby creating a Hainan cattle-specific 5K Genotyping by Target Sequencing (GBTS) liquid chip. Evaluation with 152 cattle samples demonstrated excellent clustering performance and a detection rate ranging from 96.60 to 99.07%, with 94.5% of SNP sites exhibiting polymorphism. The chip achieved 100% gender coverage and displayed a heterozygosity rate between 14.20% and 29.65%, with a repeatability rate of 99.65–99.85%. Analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed the potential regulatory roles of exonic SNPs in immune response pathways. Conclusion The development and validation of the 5K GBTS liquid chip for Hainan cattle represent a valuable tool for genome analysis and genetic diversity assessment. Furthermore, it facilitates breed identification, gender determination, and kinship analysis, providing a foundation for the efficient utilization and development of local cattle genetic resources.

This study aimed to evaluate the psychometric properties (factor structure, reliability and construct validity) of the Motivation of User-generated Technical Instructional Videos (MUTIV) scale. Employing a cross-sectional research design, two rounds of self-administered surveys were conducted in mainland China (N = 271/N = 318). Phase 1 involved item generation through both deductive methods (reviewing existing scales in the literature) and inductive methods (analyzing online discourse). Phase 2 focused on the scale development and questionnaire design. Five factors sixty items were extracted by Exploratory Factor Analysis (EFA; Principal Components Analysis) and confirmed by analysis of moment structures, forming the initial five-factor-16-item MUTIV scale. Phase 3 included the scale evaluation and validation assessment. All goodness of ft indices generated by Confirmatory Factor Analysis (CFA) were found satisfactory (χ2/df = 2.620, root mean square residual = 0.033, root-mean-square error of approximation = 0.076, incremental fit index = 0.934, Tucker-Lewis index = 0.915, comparative fit index = 0.933). Cronbach’s alpha value formed at α = 0.911. The five-factor-16-item MUTIV scale was successfully verified and developed. The MUTIV scale effectively assesses the motivation to produce user-generated technical instructional videos, identifying key factors such as sharing, membership, competence, autonomy, and reward. Technical and Vocation Education and Training (TVET) stakeholders and media platforms can use this tool to promote and assess motivation in educational contexts.

Summary: T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor γ t (RORγt) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORγt impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium. This indicates distinct RORγt roles in central nervous system pathogenesis versus gut-associated protective Th17 responses. Mechanically, RORγt/Runx1-dependent upregulation of galectin-3 (Lgals3) and chemokine receptor Ccr6 in CD4+ T cells is essential for EAE development but not for bacterial clearance. Moreover, Lgals3 is selectively required for recruiting macrophages to produce interleukin (IL)-1β, which in turn promotes Ccr6 expression on CD4+ T cells during EAE pathogenesis. Our findings highlight different RORγt-regulated Th17 pathways in autoimmunity and anti-bacterial immunity, with implications for therapies targeting Th17-mediated autoimmunity while preserving effective anti-bacterial responses.

Abstract Background China has thousands years of goat breeding and abundant goat genetic resources. Additionally, the Hainan black goat is one of the high-quality local goat breeds in China. In order to conserve the germplasm resources of the Hainan black goat, facilitate its genetic improvement and further protect the genetic diversity of goats, it is urgent to develop a single nucleotide polymorphism (SNP) chip for Hainan black goat. Results In this study, we aimed to design a 10K liquid chip for Hainan black goat based on genotyping by pinpoint sequencing of liquid captured targets (cGPS). A total of 45,588 candidate SNP sites were obtained, 10,677 of which representative SNP sites were selected to design probes, which finally covered 9,993 intervals and formed a 10K cGPS liquid chip for Hainan black goat. To verify the 10K cGPS liquid chip, some southern Chinese goat breeds and a sheep breed with similar phenotype to the Hainan black goat were selected. A total of 104 samples were used to verify the clustering ability of the 10K cGPS liquid chip for Hainan black goat. The results showed that the detection rate of sites was 97.34% -99.93%. 84.5% of SNP sites were polymorphic. The heterozygosity rate was 3.08%-36.80%. The depth of more than 99.4% sites was above 10X. The repetition rate was 99.66%-99.82%. The average consistency between cGPS liquid chip results and resequencing results was 85.58%. In addition, the phylogenetic tree clustering analysis verified that the SNP sites on the chip had better clustering ability. Conclusion These results indicate that we have successfully realized the development and verification of the 10K cGPS liquid chip for Hainan black goat, which provides a useful tool for the genome analysis of Hainan black goat. Moreover, the 10K cGPS liquid chip is conducive to the research and protection of Hainan black goat germplasm resources and lays a solid foundation for its subsequent breeding work.

Accurate estimation of the State of Health (SOH) of batteries is important for intelligent battery management in energy storage systems. To solve the problems of poor quality of data features as well as the difficulty of model parameter adjustment, this study proposes a method for estimating the SOH of lithium batteries based on denoising battery health features and an improved Long Short-Term Memory (LSTM) neural network. First, in this study, three health features related to SOH decrease were selected from the battery charge/discharge data, and the singular value decomposition technique was applied to the noise reduction of the features to improve their correlation with the SOH. Then, the whale optimization algorithm is improved using cubic chaotic mapping to enhance its global optimization-seeking capability. Then, the Improved Whale Optimization Algorithm (IWOA) is used to optimize the model parameters of LSTM, and the IWOA-LSTM model is applied to the battery SOH estimation. Finally, the model proposed in this research is validated against the Center for Advanced Life Cycle Engineering (CALCE) battery dataset. The experimental results show that the prediction error of battery SOH by the method proposed in this study is less than 0.96%, and the prediction error is reduced by 49.42% compared to its baseline model. The method presented in the article achieves accurate estimation of the SOH, providing a reference for practical engineering applications.

Energy storage batteries still have usable capacity after retirement, with excellent secondary utilization value. Estimating the state of health (SOH) of retired batteries is critical to ensure their reuse. As the battery first reaches the end of its useful life, its performance degradation pattern significantly differs from that in service, increasing the difficulty of accurate SOH estimation. This study developed a SOH estimation method for retired batteries based on battery positive, negative, and center temperature data from 80% to 50% of retired battery health. The variational mode decomposition technique divides the temperature signal into multiple trends representing different battery aging mechanisms. The decomposed modes are given a physical meaningfulness, providing a new perspective to monitor battery health. In addition, this study proposes a multi-task learning framework that realizes the parallel processing of two tasks under this framework. On the one hand, the gated recurrent unit is used to estimate the relationship between the battery baseline temperature and SOH, which captures macro-degradation trends of the battery. On the other hand, the transformer network is responsible for analyzing short-term battery health fluctuations caused by subtle temperature changes. This multi-task approach can simultaneously process and analyze both macro-degradation trends and micro-fluctuations in battery degradation, estimating that the root mean square error of battery health is 5.22 × 10−5. Compared to the existing techniques, this study shows potential applications in the retired battery state of health assessment.

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

Abstract Background We aim to compare and assess the surgical parameters and follow-up information of one-hole split endoscopic discectomy (OSE) and microendoscopic discectomy (MED) in the treatment of LDH. Methods This study included 154 patients with degenerative lumbar disk disease. Sixty-eight patients underwent OSE and 86 patients MED. The VAS score for lower back and lower limb radiation pain, ODI score, modified MacNab score, estimated blood loss (EBL), length of the incision, amount of C-reactive protein, and recurrence and complication rates were examined as indicators for clinical outcomes and adverse events. Results After surgery, the VAS and ODI scores in the two groups significantly decreased. On the third day after surgery, the VAS and ODI scores of the OSE group were significantly better than those of the MED group. The VAS and ODI scores preoperatively and at 1 month, 3 months, 6 months, and 12 months following the procedure did not substantially vary between the two groups. There was less EBL and a shorter incision with OSE than with MED. There was no significant difference in the rate of complications between the two groups. Conclusion Compared with MED, OSE is a new alternative option for LDH that can achieve similar and satisfactory clinical outcomes. Furthermore, OSE has many advantages, including less EBL and a smaller incision. Further clinical studies are needed to confirm the effectiveness of OSE.

Immune checkpoint blockades (ICBs) have revolutionized cancer therapy through unleashing anti-tumor adaptive immunity. Despite that, they are usually effective only in a small subset of patients and relapse can occur in patients who initially respond to the treatment. Recent breakthroughs in this field have identified innate immune checkpoints harnessed by cancer cells to escape immunosurveillance from innate immunity. MHC1 appears to be such a molecule expressed on cancer cells which can transmit a negative signal to innate immune cells through interaction with leukocyte immunoglobulin like receptor B1 (LILRB1). The review aims to summarize the current understanding of MHC1/LILRB1 axis on mediating cancer immune evasion with an emphasis on the therapeutic potential to block this axis for cancer therapy. Nevertheless, one should note that this field is still in its infancy and more studies are warranted to further verify the effectiveness and safety in clinical as well as the potential to combine with existing immune checkpoints.

Abstract Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade and difficulty in stable proliferation and differentiation of NSCs limit its application and translation. Here, a novel physico‐chemical bifunctional neural stem cells delivery system containing magnetic nanoparticles (MNPs and methylprednisolone (MP) is designed to repair SCI, the former regulates NSCs differentiation through magnetic mechanical stimulation in the chronic phase, while the latter alleviates inflammatory response in the acute phase. The delivery system releases MP to promote microglial M2 polarization, inhibit M1 polarization, and reduce neuronal apoptosis. Meanwhile, NSCs tend to differentiate into functional neurons with magnetic mechanical stimulation generated by MNPs in the static magnetic field, which is related to the activation of the PI3K/AKT/mTOR pathway. SCI mice achieve better functional recovery after receiving NSCs transplantation via physico‐chemical bifunctional delivery system, which has milder inflammation, higher number of M2 microglia, more functional neurons, and axonal regeneration. Together, this bifunctional NSCs delivery system combined physical mechanical stimulation and chemical drug therapy is demonstrated to be effective, which provides new treatment insights into clinical transformation of SCI repair.

Abstract Macrophage/microglia polarization acts as an important part in regulating inflammatory responses in spinal cord injury (SCI). However, the regulation of inflammation of Schwann cell-derived exosomes (SCDEs) for SCI repair is still unclear. Therefore, we intend to find out the effect of SCDEs on regulating the inflammation related to macrophage polarization during the recovery of SCI. Firstly, the thesis demonstrated that SCDEs could attenuate the LPS- inflammation in BMDMs by suppressing M1 polarization and stimulating M2 polarization. Similarly, SCDEs improved functional recovery of female Wistar rats of the SCI contusion model according to BBB (Basso, Beattie, and Bresnahan) score, electrophysiological assay, and the gait analysis system of CatWalk XT. Moreover, MFG-E8 was verified as the main component of SCDEs to improve the inflammatory response by proteomic sequencing and lentiviral transfection. Improvement of the inflammatory microenvironment also inhibited neuronal apoptosis. The knockout of MFG-E8 in SCs can reverse the anti-inflammatory effects of SCDEs treatment. The SOCS3/STAT3 signaling pathway was identified to participate in upregulating M2 polarization induced by MFG-E8. In conclusion, our findings will enrich the mechanism of SCDEs in repairing SCI and provide potential applications and new insights for the clinical translation of SCDEs treatment for SCI.

Accurate estimation of battery health is an effective means of improving the safety and reliability of electrical equipment. However, developing data-driven models to estimate battery state of health (SOH) is challenging when the amount of data is restricted. In this regard, this study proposes a method for estimating the SOH of lithium batteries based on sample data generation and a temporal convolutional neural network. First, we analyzed the charge/discharge curves of the batteries, from which we extracted features that were highly correlated with the SOH decay. Then, we used a Variational Auto-Encoder (VAE) to learn the features and distributions of the sample data to generate highly similar data and enrich the number of samples. Finally, a temporal convolutional neural network (TCN) was built to mine the nonlinear relationship between features and SOH by combining the source and extended domain data to realize SOH estimation. The experimental results show that the proposed method in this study has less than 2% error in SOH estimation, which improves the accuracy by 64.9% based on its baseline model. The feasibility of using data-driven models for battery health management in data-constrained application scenarios is demonstrated.

Mycoplasma capricolum subsp. Capricolum (Mcc) is an important member of the Mycoplasma mycoides cluster (Mm cluster) and causes caprine contagious agalactia. Mcc can infect goats of all age groups, especially pregnant ewes and kids. It can cause the abortion in pregnant ewes and the death of goat kids, leading to enormous losses in the goat breeding industry. To date, the prevalence of epidemic Mcc strains on Hainan Island, China, remains unclear. This study aimed to isolate and identify Mcc strains endemic to Hainan Island, China. Genome sequencing and comparative genomic analysis were performed to reveal the molecular characteristics and evolutionary relationships of the isolated strain. Mcc HN-B was isolated and identified in Hainan Island, China. The Mcc HN-B genome consists of a 1,117,925 bp circular chromosome with a 23.79% G + C content. It contains 912 encoding genes, 3 gene islands, and 14 potential virulence genes. The core genome with the features of the Mm cluster and the specific genes of Mcc HN-B were identified by comparative genomic analysis. These results revealed the evolutionary relationship between Mcc HN-B and other members of the Mm cluster. Our findings provide a reference for further studies on the pathogenic mechanism and local vaccine development of Mcc.

Osteoporosis-related bone fracture and falls have a severe impact on patients’ daily lives. Osteoblasts are bone-building cells that play a vital role in bone formation and remodeling. Imbalanced osteoblast differentiation could lead to osteoporosis. GPR39 is an orphan G protein-coupled receptor that mediates metabolic pathways. In this study, we show that GPR39 is expressed in MC3T3-E1 cells. Osteoblast differentiation culture media induces GPR39, suggesting that GPR39 is a differentiation-responsive factor. Activation of GPR39 using its selective agonist TC-G 1008 induces alkaline phosphatase (ALP), osteocalcin (OCN), and type I collagen (Col-I) expression, and increases cellular ALP activity and calcium deposition, implying that GPR activation promotes cells toward osteoblast differentiation. Treatment with TC-G 1008 also increases Runx-2 expression and AMPK activation. However, the inhibition of AMPK by Compound C abolished TC-G 1008-mediated ALP, OCN, and Col-I induction, and reduces ALP activity and cellular calcium deposition as well as Runx-2 induction. These data indicate that TC-G 1008-mediated GPR39 activation involves AMPK-mediated Runx-2 induction. In summary, our study uncovers a new role of GPR39 activation in osteoblast differentiation, implying that GPR39 could be a promising therapeutic target for osteoporosis.

The labyrinth-honeycomb seals have been widely used in aero-engine. However, radial cracks appear on labyrinth seal fins of shrouded turbine blade in use. To clarify the rubbing mode of radial crack initiation, a high-speed rubbing test bench was designed. The effects of five rubbing modes on crack initiation were studied. Through the test, it is found that cracks would be formed at the junction of the fin tip and side of the labyrinth seal fins under all five modes. When two successive rubbing modes are different, the temperature of the last rubbing can be lower than that of it alone rubbing, and simultaneous radial and axial rubbing can inhibit each other. Radial rubbing mainly affects the initiation of cracks on fin tip, while axial rubbing mainly affects the initiation of cracks on the side. Moreover, the rubbing temperature is mainly affected by radial force.

In order to reduce the oil consumption, the vehicle in the process of in-situ shift should be quick enough, but the vibration and shock of the vehicle will be deteriorate. Then the effect of a novel semi-active hydraulic damping strut (HDS) on vehicle shock and vibration in the process of in-situ shift quickly in this study is analyzed. Firstly, the shift shock is analyzed from the driver system, and the powertrain mounting system (PMS) is regarded as the object to be optimized in this study. Then the 13 degree of freedoms (DOFs) vehicle dynamic model (VDM) with semi-active HDS is presented in this paper. The excitation force in the process of quick in-situ shift is identified, and the evaluation indexes (EIs) are reduced with semi-active HDS introduced. Finally, the experiments are carried out to validate the effect of the semi-active HDS on vehicle longitudinal vibration and shock in the process of quick in-situ shift, and the results show that the acceleration of the seat rail and steering wheel are reduced to a great extent. Different shift time is discussed and the results show that we can reduce the shift time to save the oil with semi-active HDS introduced.

Pasteurella multocida (Pm) infection causes severe respiratory disease in goats. We investigated the effects of the Pm infection intratracheally on the histopathology, miRNA and mRNA expression dynamics in the lung of goats infected for 1, 2, 5 and 7 days. Pm infection caused fever, which significantly (p < 0.05) increased the body temperature of the goats from day 1 to 5. Haemotoxylin–eosin staining of the infected lung tissue showed characteristics of suppurative pneumonia with inflammatory cells infiltration and the lung structure destruction. During the Pm infection of the goats, compared with the control group, there were 3080, 3508, 2716 and 2675 differentially expressed genes and 42, 69, 91 and 108 significantly expressed miRNAs (|log2Fold Change| > 1, p < 0.05) in the Pm_d1, Pm_d2, Pm_d5 and Pm_d7 groups, respectively. Five miRNAs and nine immune-related genes were selected for confirmation by reverse transcription–polymerase chain reaction. The results indicated that the expression patterns of the miRNAs and genes were consistent with those determined by next-generation sequencing. The differentially expressed genes were enriched in cytokine–cytokine receptor interaction, cell adhesion molecules, complement and coagulation cascades, tight junction and phagosome Kyoto Encyclopedia of Genes and Genomes pathways and cytokine production, leukocyte migration, myeloid leukocyte migration, cell periphery, plasma membrane, extracellular region part, extracellular region and other Gene Ontology terms. The differentially expressed genes were mapped to marker genes in human and mouse lung cells. The results showed the presence of some marker genes of the immune cells. Compared with the CK group, five miRNAs and 892 common genes were differentially expressed in the Pm_d1, Pm_d2, Pm_d5 and Pm_d7 groups. The target relationships between the common 5 miRNAs and 892 differentially expressed genes were explored and the miRNAs involved in the host immune reaction may act through the target genes. Our study characterized goats’ reaction in the lung from histopathological and molecular changes upon Pm infection, which will provide valuable information for understanding the responses in goats during Pm infection.

Abstract It has been reported that double-stranded break (DSB)-induced small RNAs (diRNAs) are generated via the RNA-directed DNA methylation pathway and function in DSB repair in Arabidposis. However, important questions remain regarding the biogenesis and function of diRNAs. Here, we used CRISPR/Cas9- or TALEN-triggered DSBs to characterize diRNAs in Arabidopsis and rice. We found that 21-nt diRNAs were generated from a 35S promoter::GU-US reporter transgene targeted by CRISPR/Cas9. Unexpectedly, Pol II transcription of the transgene was required for efficient diRNA production and the level of diRNA accumulation correlated with the expression level of the transgene. diRNAs were not detected from CRISPR/Cas9- or TALEN-induced DSBs within the examined endogenous genes in Arabidopsis or rice. We also found that DCL4 and RDR6 that are known to be involved in posttranscriptional gene silencing were required to generate diRNAs. Our results suggest that DSBs are necessary but not sufficient for efficient diRNA generation and a high level of diRNAs is not necessary for DSB repair.

Recurrent somatic mutations in spliceosome factor 3b subunit 1 (SF3B1) are identified in hematopoietic malignancies, with SF3B1-K700E being the most common one. Here, we show that regulatory T cell (Treg)-specific expression of SF3B1-K700E (Sf3b1K700Efl/+/Foxp3YFP-Cre) results in spontaneous autoimmune phenotypes. CD4+ T cells from Sf3b1K700Efl/+/Foxp3YFP-Cre mice display defective Treg differentiation and inhibitory function, which is demonstrated by failed prevention of adoptive transfer colitis by Sf3b1K700Efl/+/Foxp3YFP-Cre Tregs. Mechanically, SF3B1-K700E induces an aberrant splicing event that results in reduced expression of a cell proliferation regulator Anapc13 due to the insertion of a 231-base pair DNA fragment to the 5' untranslated region. Forced expression of the Anapc13 gene restores the differentiation and ability of Sf3b1K700Efl/+/Foxp3YFP-Cre Tregs to prevent adoptive transfer colitis. In addition, acute myeloid leukemia grows faster in aged, but not young, Sf3b1K700Efl/+/Foxp3YFP-Cre mice compared to Foxp3YFP-Cre mice. Our results highlight the impact of cancer-associated SF3B1 mutation on immune responses, which affect cancer development. [ABSTRACT FROM AUTHOR]

T cell activation stimulates substantially increased protein synthesis activity to accumulate sufficient biomass for cell proliferation. The protein synthesis is fueled by the amino acids transported from the environment. Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. Here, we show that SRC2 recruited by c-Myc enhances CD4+ T cell activation to stimulate immune responses via upregulation of amino acid transporter Slc7a5. Mice deficient of SRC2 in T cells (SRC2fl/fl/CD4Cre) are resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and susceptible to Citrobacter rodentium (C. rodentium) infection. Adoptive transfer of naive CD4+ T cells from SRC2fl/fl/CD4Cre mice fails to elicit EAE and colitis in Rag1/recipients. Further, CD4+ T cells from SRC2fl/fl/CD4Cre mice display defective T cell proliferation, cytokine production, and differentiation both in vitro and in vivo. Mechanically, SRC2 functions as a coactivator to work together with c-Myc to stimulate the expression of amino acid transporter Slc7a5 required for T cell activation. Slc7a5 fails to be up-regulated in CD4+ T cells from SRC2fl/fl/CD4Cre mice, and forced expression of Slc7a5 rescues proliferation, cytokine production, and the ability of SRC2fl/fl/CD4Cre CD4+ T cells to induce EAE. Therefore, SRC2 is essential for CD4+ T cell activation and, thus, a potential drug target for controlling CD4+ T cell-mediated autoimmunity. [ABSTRACT FROM AUTHOR]