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Objective The liver plays a dual role in regulating temperature and immune responses. Examining the influence of heat stress (HS) on liver T cells contributes significantly to understanding the intricate interplay between the immune system and hepatic tissues under thermal stress. This study focused on investigating the characteristics of the T-cell receptor (TCR) β chain CDR3 repertoire in bovine liver samples under both HS and pair-fed (PF) environmental conditions. Methods Sequencing data from six samples sourced from the GEO database underwent annotation. Utilizing immunarch and VDJtool software, the study conducted comprehensive analyses encompassing basic evaluation, clonality assessment, immune repertoire comparison, diversity estimation, gene usage profiling, VJ gene segment pairing scrutiny, clonal tracking, and Kmers analysis. Results All four TCR chains, namely α, β, γ, and δ, were detected, with the α chains exhibiting the highest detection frequency, followed closely by the β chains. The prevalence of αβ TCRs in bovine liver samples underscored their crucial role in governing hepatic tissue’s physiological functions. The TCR β CDR3 repertoire showcased substantial inter-individual variability, featuring diverse clonotypes exhibiting distinct amino acid lengths. Intriguingly, HS cattle displayed heightened diversity and clonality, suggesting potential peripheral T cell migration into the liver under environmental conditions. Notably, differential VJ gene pairings were observed in HS cattle compared to the PF, despite individual variations in V and J gene utilization. Additionally, while most high-frequency amino acid 5-mers remained consistent between the HS and PF, GELHF, and YDYHF were notably prevalent in the HS group. Across all samples, a prevalent trend of high-frequency 5mers skewed towards polar and hydrophobic amino acids was evident. Conclusion This study elucidates the characteristics of liver TCR β chain CDR3 repertoire under HS conditions, enhancing our understanding of HS implications.

The abundance of molecules on early Earth likely enabled a wide range of prebiotic chemistry, with peptides playing a key role in the development of early life forms and the evolution of metabolic pathways. Among peptides, those with enzyme-like activities occupy a unique position between peptides and enzymes, combining both structural flexibility and catalytic functionality. However, their full potential remains largely untapped. Further exploration of these enzyme-like peptides at the nanoscale could provide valuable insights into modern nanotechnology, biomedicine, and even the origins of life. Hence, this review introduces the groundbreaking concept of “peptide nanozymes (PepNzymes)”, which includes single peptides exhibiting enzyme-like activities, peptide-based nanostructures with enzyme-like activities, and peptide-based nanozymes, thus enabling the investigation of biological phenomena at nanoscale dimensions. Through the rational design of enzyme-like peptides or their assembly with nanostructures and nanozymes, researchers have found or created PepNzymes capable of catalyzing a wide range of reactions. By scrutinizing the interactions between the structures and enzyme-like activities of PepNzymes, we have gained valuable insights into the underlying mechanisms governing enzyme-like activities. Generally, PepNzymes play a crucial role in biological processes by facilitating small-scale enzyme-like reactions, speeding up molecular oxidation-reduction, cleavage, and synthesis reactions, leveraging the functional properties of peptides, and creating a stable microenvironment, among other functions. These discoveries make PepNzymes useful for diagnostics, cellular imaging, antimicrobial therapy, tissue engineering, anti-tumor treatments, and more while pointing out opportunities. Overall, this research provides a significant journey of PepNzymes’ potential in various biomedical applications, pushing them towards new advancements.

Abstract To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.

Abstract The quality of Recombination signal sequences (RSSs), location, and genetics of mammalian V, D, and J genes synergistically affect the recombination frequency of genes; however, the specific regulatory mechanism and efficiency have not been elucidated. By taking advantage of single-cell RNA-sequencing (scRNA-seq) and high-throughput sequencing (HTS) to investigate V(D)J rearrangement characteristics in the CDR3 repertoire, we found that the distal and proximal V genes (or J genes) “to D” gene were involved in rearrangement significantly more frequently than the middle V genes (or J genes) in the TRB locus among various species, including Primates (human and rhesus monkey), Rodentia (BALB/c, C57BL/6, and Kunming mice), Artiodactyla (buffalo), and Chiroptera (Rhinolophus affinis). The RSS quality of the V and J genes affected their frequency in rearrangement to varying degrees, especially when the V-RSSs with recombination signal information content (RIC) score < -45 significantly reduced the recombination frequency of the V gene. The V and J genes that were “away from D” had the dual advantages of recombinant structural accessibility and relatively high-quality RSSs, which promoted their preferential utilization in rearrangement. The quality of J-RSSs formed during mammalian evolution was apparently greater than that of V-RSSs, and the D-J distance was obviously shorter than that of V-D, which may be one of the reasons for guaranteeing that the “D-to-J preceding V-to-DJ rule” occurred when rearranged. This study provides a novel perspective on the mechanism and efficiency of V-D-J rearrangement in the mammalian TRB locus, as well as the biased utilization characteristics and application of V and J genes in the initial CDR3 repertoire.

Abstract Background Telocytes (TCs) is a novel type of interstitial cells in many mammals organs, which participate in the organizational metabolism, mechanical support, immunomodulation and other aspects. The aim of this study was to explore the organizational chemical characteristics of TCs in pituitary gland and their changes in cryptorchid yaks. Methods Transmission electron microscopy (TEM), toluidine blue staining, immunofluorescence, qRT-PCR, and Western blotting may enable us to understand TCs distribution characteristics and biological functions. Result TEM confirmed the presence of TCs in the pituitary gland with small bodies and moniliform telopodes (Tps). The Tps extending out from the cell body to the peri-sinusoidal vessels spaces, the number of Tps is closely related to the morphology of the nucleus. The most obvious changes of TCs in the pituitary gland of cryptorchid yaks is the Tps are relatively shorter and decreased secretory vesicles. H.E. and toluidine blue staining revealed that TCs not only distributed between the sinusoidal blood vessels and the glandular cell clusters, but also present on the surface of vascular endothelial cells. The co-expression of TCs biomarkers, such as Vimentin/CD34, CD117/CD34 and α-SMA/CD34, were evaluated by immunofluorescence to further determine the phenotypic characteristics of TCs. Besides, we analyzed the mRNA and protein expression of these biomarkers to determine the characteristics of TCs changes and possible biological roles. Both the mRNA and protein expression of CD117 were significantly higher in the pituitary gland of cryptorchid yaks than in the normal (p 0.05), while the protein expression were significantly increased in the normal yaks (p

Abstract Telocytes (TCs) are a type of stromal cell discovered in the various organs of different animals and have many potential functions, including angiogenesis, signalling, and substance transport. However, the TCs have not been detected in the testis or epididymis of Tibetan sheep. This study investigated the position, characteristics, and distribution of TCs in the testis and epididymis of Tibetan sheep using transmission electron microscopy (TEM), toluidine blue staining, immunohistochemistry, and double immunofluorescence to elucidate their possible functions. TEM revealed that TCs were often found near basement membranes and capillaries and were characterised by large nuclei, elongated cytoplasmic protrusions, and many secretory vesicles. We also observed via toluidine staining that TCs were present near basement membrane and interstitial capillaries. Immunohistochemistry and double immunofluorescence revealed the positive expression of CD117, vimentin, platelet derived growth factor receptor α(PDGFRα), PDGFRα + CD117, and PDGFRα + vimentin in TCs. Additionally, we inferred that TCs participates in the formation of the blood–testis and blood–epididymis barriers, as well as in material transport and a stable microenvironment. This study presents the first evidence of the presence of TCs near the basement membrane and blood vessels in the testis and epididymis of Tibetan sheep. These findings provide new insights into the function of TCs in the reproductive systems of plateau animals.

Abstract At the 3’ end of the C2 gene in the mammalian TRB locus, a distinct reverse TRBV30 gene (named TRBV31 in mice) has been conserved throughout evolution. In the fully annotated TRB locus of 14 mammals (including six orders), we observed noteworthy variations in the localization and quality of the reverse V30 genes and Recombination Signal Sequences (RSSs) in the gene trees of 13 mammals. Conversely, the forward V29 genes and RSSs were generally consistent with the species tree of their corresponding species. This finding suggested that the evolution of the reverse V30 gene was not synchronous and likely played a crucial role in regulating adaptive immune responses. To further investigate this possibility, we utilized single-cell TCR sequencing (scTCR-seq) and high-throughput sequencing (HTS) to analyze TCRβ CDR3 repertoires from both central and peripheral tissues of Primates (Homo sapiens and Macaca mulatta), Rodentia (Mus musculus: BALB/c, C57BL/6, and Kunming mice), Artiodactyla (Bos taurus and Bubalus bubalis), and Chiroptera (Rhinolophus affinis and Hipposideros armige). Our investigation revealed several novel observations: (1) The reverse V30 gene exhibits classical rearrangement patterns adhering to the ‘12/23 rule’ and the ‘D-J rearrangement preceding the V-(D-J) rearrangement’. This results in the formation of rearranged V30-D2J2, V30-D1J1, and V30-D1J2. However, we also identified ‘special rearrangement patterns’ wherein V30-D rearrangement preceding D-J rearrangement, giving rise to rearranged V30-D2-J1 and forward Vx-D2-J. (2) Compared to the ‘deletional rearrangement’ (looping out) of forward V1-V29 genes, the reverse V30 gene exhibits preferential utilization with ‘inversional rearrangement’. This may be attributed to the shorter distance between the V30 gene and D gene and the ‘inversional rearrangement’ modes. In summary, in the mammalian TRB locus, the reverse V30 gene has been uniquely preserved throughout evolution and preferentially utilized in V(D)J recombination, potentially serving a significant role in adaptive immunity. These results will pave the way for novel and specialized research into the mechanisms, efficiency, and function of V(D)J recombination in mammals.

Abstract Water quality in arid regions is a crucial determinant of sustainable social and economic development. Combining traditional hydrogeochemical methods with ordinary least squares (OLS) and geographically weighted regression modeling (GWR), the suitability of surface water irrigation in the summer irrigation period was investigated in the Tarim Basin. The results indicated that all water samples belonged to three types of water: SO4 Cl–Ca•Mg, SO4 Cl–Na, and HCO3–Ca Mg. A convergence phenomenon occurred under long-term irrigation conditions, showing a similarity between the salt composition of soils and surface irrigation waters. Although the current quality of surface water is generally suitable for irrigation, the process of reverse ion exchange has a more important effect on surface water bodies and soil salinity, thereby resulting in an increase in the Na-ion content of the soil and subsequently enhancing alkaline hazards. Both the OLS and GWR models unequivocally indicate that nitrate nitrogen primarily originates from natural weathering processes and that the sources of this material exhibit spatial heterogeneity across distinct regions. The construction of irrigation reservoirs to effectively deal with agricultural water shortages will lead to a deterioration in the quality of irrigation. The overall findings suggest that the water quality can meet the irrigation needs at present, but to ensure the sustainable use of water resources in arid regions, the increasing nitrogen concentration caused by human activities and the decline in water quality caused by reservoir construction need to be addressed in future irrigation management.

ObjectiveThis study initiated a preliminary computational fluid dynamics (CFD)-based study to investigate the relationship between quantitative hemodynamics of arteriovenous malformation (AVM) draining veins and rupture.MethodsThe quantitative hemodynamics of AVM draining veins were generated from computed tomography angiography (CTA)-based steady-state CFD models. Morphological and hemodynamic parameters were compared between the ruptured and unruptured groups. The boundary conditions of the drainage vein were obtained from quantitative digital subtraction angiography (QDSA). The draining veins were divided into 15 consecutive segments to analyze the spatial distribution of the hemodynamic parameters by linear regression analysis.ResultsFrom 11 AVMs, it was revealed that morphological parameters of drainage veins in ruptured and unruptured AVMs were similar. The intravascular pressure of the draining vein in the ruptured AVMs was significantly higher than those of the unruptured AVMs (pressure average: p = 0.006; pressure maximum: p = 0.045), and the WSS of the posterior segment was higher in ruptured AVMs (p = 0.045). WSS of draining veins in ruptured AVMs showed a linear increase trend with segmenting (R = 0.731, p

Many aerodynamic shape optimization methods often focus on utilizing the end-to-end relationship between design variables and aerodynamic performance to find the optimal design, while overlooking the exploration of geometric knowledge of the shape itself. To fully use geometric knowledge to improve optimization efficiency, this paper proposes an efficient method by exploring the potential correlation between geometric features and aerodynamic performance at a low cost. We use unsupervised isometric feature mapping in manifold learning to capture geometric features that can distinguish the aerodynamic performance of different airfoils without embedding any tags. Then a filter criterion is establish based on the geometric features. During the optimization process, airfoils that deliver poor aerodynamic performance can be filtered out with a high probability before being precisely evaluated through computational fluid dynamics simulations. This helps improve samples quality to enhance the optimization efficiency. We applied the proposed method to the unconstrained and constrained optimizations of the Royal Aircraft Establishment (RAE) 2822 airfoil to validate its performance. The results demonstrate that the proposed method can improve the efficiency of optimization by over 50% compared with the original evolutionary optimization algorithm. It performs well across various optimization problems, demonstrating high engineering practical value.

This paper considers Cyber-Physical Systems (CPSs) in the presence of Denial-of-Service (DoS) attacks, and investigates the networked control problem under data rate limitations. We develop a framework for CPSs in the presence of DoS attacks, and present a state-estimate control scheme for CPSs under DoS attacks. For the different communication status, the information on the plant state is transmitted to the controller by employing a different data rate in order to mitigate the influence of DoS attacks. Sufficient conditions on the data rate for mean square observability and stabilization of CPSs are derived by applying information theoretic tools of source coding. Our result is less conservative than some existing results. An illustrative example is given to demonstrate the effectiveness of the proposed quantization-coding scheme.

This paper investigates the state estimation problem for linear time-invariant systems where sensors and controllers are connected by a stationary memoryless digital communication channel. Time delay, packet dropout, and data rate limitation occur simultaneously in such a channel. We discuss observability of such systems under communication constraints. A real-time transport protocol (RTP) is used for data transmission. A quantization, coding, and control scheme on the basis of RTP is proposed in order to overcome such difficulties. Sufficient conditions for observability are provided in this case. Our result contains some existing results, and shows that there exists the inherent tradeoff between control and communication costs. Illustrative examples are given to demonstrate the effectiveness of the proposed quantization, coding, and control scheme.

ABSTRACTBackground Several studies indicate that the cystathionine β-synthase (CBS) gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region may be correlated with coronary artery disease (CAD) susceptibility, but the results have been inconsistent and inconclusive. Thus, a meta-analysis was conducted to provide a comprehensive estimate of these associations.Methods On the basis of searches in the PubMed, EMBASE, Cochrane Library, Wanfang, VIP, and CNKI databases, we selected 14 case – control studies including 2123 cases and 2368 controls for this meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated accordingly using a fixed-effect or random-effect model.Results The results indicated an increased risk between the CBS T833C gene polymorphisms and susceptibility to CAD under the dominant model (CC+CT vs. TT: OR = 1.92, 95% CI: 1.11 ~ 3.32), recessive model (CC vs. CT+TT: OR = 1.88, 95% CI: 1.17 ~ 3.03), and homozygous model (CC vs. TT: OR = 2.46, 95% CI: 1.04 ~ 5.83). In these three genetic models, no significant association was identified for CBS G919A (AA+AG vs. GG: OR = 1.48, 95% CI: 0.45 ~ 4.82),(AA vs. AG+GG: OR = 1.58, 95% CI: 0.93 ~ 2.70),(AA vs. GG: OR = 1.66, 95% CI: 0.40 ~ 6.92) or CBS 844ins68 (II+ID vs. DD: OR = 1.04, 95% CI: 0.80 ~ 1.35),(II vs. ID+DD: OR = 1.09, 95% CI: 0.51 ~ 2.36),(II vs. DD: OR = 1.10, 95% CI: 0.51 ~ 2.39).Conclusions This meta-analysis suggests that the CBS T833C gene polymorphism is significantly associated with the risk of CAD and it shows a stronger association in Asian populations. Individuals with the C allele of the CBS gene T833C polymorphism might be particularly susceptible to CAD.

Hepatic alveolar echinococcosis is a zoonotic disease with a high incidence in western China, particularly affecting plateau areas such as Qinghai, Tibet, and Xinjiang. Research has indicated the presence of neovascularization in the peripheral infiltration area of hepatic alveolar echinococcosis, with a strong correlation between angiogenesis and vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1-alpha (HIF-1α) overexpression. Given the similarities between hepatic alveolar echinococcosis and liver cancer, current research is focused on treating the disease by targeting related signaling pathways using molecular drugs used for liver cancer. This article aims to summarize the biological regulation of HIF-1α and VEGFA overexpression in angiogenesis related to hepatic alveolar echinococcosis, as well as the impact of the BMP9-ID1 signaling pathway on the expression levels of HIF-1α and VEGFA, providing new insights for potential treatment strategies.

Potentially toxic elements (PTEs) in surface water in arid areas pose a serious threat to environmental safety and human health within a basin. It is important to determine the factors controlling PTEs and to assess the likelihood that they will pose a risk to human health in order to support the development of environmental protection and risk management strategies. In this study, a structural equation model and Bayesian method were combined to discuss the distribution and probabilistic health risks of PTEs in surface water in arid area, and the Tarim River Basin was taken as a case study. The results show that the average concentrations of As, Co, Cu, and Ni in the surface water in the Tarim River Basin ranged from 0.04 to 2.92 μg/L, which do not exceed the international standard values. However, the maximum value of As (19.20 μg/L) exceeded both the recommended drinking water standards and the Chinese irrigation water standards. Spatially, the high As concentrations were distributed in the upper reaches of the Kashgar River, and the high Co, Cu and Ni concentrations were distributed in reservoirs and lakes on the main stream of the Tarim River. The concentrations of the PTEs in the surface water in the basin were not only affected by random anthropogenic factors such as traffic discharge, agricultural activities and mining industry, but were also directly and indirectly influenced by climatic factors. The results of the probabilistic health risk assessment showed that the 95th percentile the total hazard index for infants exceeded the allowable value of 1, and the total carcinogenic risk of PTEs exposure in four age groups was at the notable level. In this study, we conducted a comprehensive analysis of the controlling factors and health risks associated with PTEs in surface water in the Tarim River Basin, and the findings are expected to provide a scientific basis for regional water environment management and safety control.

As the largest organic carbon input in the agroecosystems, crop residues can increase soil carbon sequestration and crop production in greenhouse vegetable fields (GVFs). However, the soil microbiological mechanisms driving straw decomposition in GVFs under different incubation temperatures and fertilization treatments are not clear. Thus, soil samples were collected from a long-term field experiment included chemical fertilizer application alone (CF), 2/4 fertilizer N+2/4 organic fertilizer N (CM), 2/4 fertilizer N+1/4 organic fertilizer N+1/4 straw N (CMS), 2/4 fertilizer N+2/4 straw N (CS), and incubated with 13C-labeled straw at different temperatures (15, 25, and 35°C) for 60 days. Organic-amended treatments (CM, CMS, and CS), especially CMS treatment, increased soil bacterial Alpha diversity before and after straw addition. Straw decomposition process was dominated by soil Proteobacteria, Actinobacteria, and Firmicutes for each treatments. The effect of incubation temperature on soil microbial community composition was higher than that of fertilization treatments. Soil Alphaproteobacteria and Actinomycetia were the most predominant class involved in straw decomposition. Gammaproteobacteria (Pseudomonas, Steroidobacter, Acidibacter, and Arenimonas) were the unique and predominant class involved in straw decomposition at medium and high temperatures as well as in the straw-amended treatments. Organic-amended treatments, especially straw-amended treatments, increased the relative abundance of glycosyl transferases (GT) and auxiliary activities (AA). Alphaproteobacteria, Actinomycetia, and Gammaproteobacteria had higher relative contribution to carbohydrase genes. In summary, the long-term organic-amended treatments altered the structure of soil microbial communities and increased soil bacterial diversity, with the CMS having a greater potential to enhance resistance to external environmental changes. Soil Alphaproteobacteria and Actinomycetia were responsible for the dominance of straw decomposition, and Gammaproteobacteria may be responsible for the acceleration of straw decomposition. Fertilization treatments promote straw decomposition by increasing the abundance of indicator bacterial groups involved in straw decomposition, which is important for isolating key microbial species involved in straw decomposition under global warming.

Discriminating strong aroma-type Baijiu (SAB) of different origins was significant for product quality control and origin protection. In this study, a 4×3 sensor array was constructed based on the Ag nanoprism (AgNPR) etching mechanism, in which four AgNPRs varying in shape and size were used as sensing materials, and two metal ions and one oxide anion were used as oxidation etchants. With this array, colorimetric reaction was conducted on 41 representative SAB samples from Sichuan, Jianghuai and North China. The obtained colorimetric signal values were subjected to linear discriminant analysis (LDA). Furthermore, some samples of unknown origin were selected to perform external validation on the discrimination model. Based on the results of colorimetric reaction mechanism, the samples could promote the etching effect of AgNPRs, which might be related to various organic acids contained in Baijiu. Sample discrimination showed that single array produced a comparatively low effect on samples of different origins. The combination of three arrays significantly improved the discrimination effect, whose rate of origin discrimination was up to 99% for 41 samples, and was up to 98% for 15 unknown samples. With combined array, the discriminant rates of 21 samples from 5 brands in Sichuan and 13 samples from 3 brands in Jianghuai could reach 99% and 100%, respectively, while all the discriminant rates could reach 100% for different grades of products from various manufacturers in Sichuan with single array. Being simple and fast, the nanocolorimetric sensing method adopted in this study is not only applicable to product identification and anti-counterfeiting, but also be auxiliarily used for quality control in production process, laying a research foundation for intelligent quality monitoring of Baijiu.

Abstract Since the basic rail of the switch needs to have a certain bending angle when the train changes direction, top bending is an important link in the production process of the basic rail. The three-point pressure top bending method is simple, flexible and widely used. In this study, the traditional three-point pressure bending is optimized, the influence of the pick width in the model is considered, a corresponding rebound model is established, and the model is applied to the pressure bending process of the basic rail. The bilinear strengthening model of the material was used to construct the bending moment expressions at different positions during the top bending process, and the relationship between the load and bending deflection in the elastic stage and elastic-plastic stage was obtained. The final top bending prediction model was obtained by combining the load-deflection model in the bending stage and the rebound stage. The correctness of the theoretical mathematical model was verified by establishing finite element simulations, and the theoretical calculation results were compared with the experimental results. The results showed that the top bend prediction optimization model established in this study had high feasibility and met the machining accuracy requirements.

Highlights The boosted heterogeneous interfaces in titanium nitride (TiN) nanotube/polydimethylsiloxane (PDMS) composite contributed to strong polarization loss relaxation ability. The TiN nanotubes/PDMS composite possessed both good impedance matching behavior and strong dielectric loss ability in wide temperature spectrum. The TiN nanotubes/PDMS composite exhibited excellent EMWA performances (effective absorption bandwidth value of 3.23 GHz and minimum reflection loss value of − 44.15 dB) at the varied temperature from 298 to 573 K.

Abstract Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single‐cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate‐limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti‐inflammatory polymorphonuclear myeloid‐derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research.

BackgroundBone metastases of lung cancer (BMLC) severely diminish patients’ quality of life due to bone-related events, and the lack of clear guidelines globally regarding medical and surgical treatment significantly reduces patient survival. While knowledge about BMLC has grown exponentially over the past two decades, a comprehensive and objective bibliometric analysis remains absent.MethodsA comprehensive bibliometric analysis was conducted on relevant literature on BMLC extracted from the Web of Science database from 2004 to 2023 by Biblioshiny, VOSviewer, Scimago Graphica, CiteSpace, and Microsoft Office Excel Professional Plus 2016 software. 936 papers related to BMLC were extracted from the Web of Science Core Collection (WoSCC). The number of publications, countries, institutions, global collaborations, authors, journals, keywords, thematic trends, and cited references were then visualized. Finally, the research status and development direction in the last 20 years were analyzed.ResultsThis study included a total of 936 papers on BMLC from 2004 to 2023. There has been a steady increase in global publications each year, peaking in 2021. China had the highest number of publications, followed by Japan and the United States. Additionally, China had the most citations with an H-index of 35, while the US followed with an H-index of 34, highlighting their significant contributions to the field. “Frontiers in Oncology” had the highest number of publications. CiteSpace analysis identified “lung cancer,” “bone metastasis,” and “survival” as the top high-frequency keywords, encapsulating the core research focus. Keyword clustering analysis revealed six main clusters representing the primary research directions. Burst analysis of keywords showed that “skeletal complications” had the highest burst intensity from 2005 to 2013, while recent research trends include “immunotherapy” and “denosumab,” with bursts from 2021 to 2023. Trend topic analysis indicated that “non-small cell lung cancer,” “immunotherapy,” and “immune checkpoint inhibitors” represent the cutting-edge research directions in this field.ConclusionThis article reveals the current status and trend of research on BMLC, which is increasing worldwide. China and the United States have contributed the most, but international cooperative research on BMLC should be strengthened. The pathogenesis, early prevention, and individualized treatment of BMLC need to be strengthened for further study, and immunotherapy is the next hotspot of lung cancer bone metastasis research.

Objective: The present investigation aimed to analyze the in vivo study in support with in silico molecular docking mechanism of natural phenolic compounds Syringic acid (SA), Resveratrol (RV), Gallic acid (GA) and combination (COMB) with SA + RV against Isoproterenol (ISO) in myocardial necrotic rats. Methods: The compounds were tested for in vivo and in silico lipid metabolism enzymes HMG-CoA reductase and lipoprotein lipase (LPL) regulatory activities. Rats were orally pretreated with 50 mg/ kg of each compounds SA, RV, GA and COMB (SA 25 mg/ kg + RV 25 mg/ kg) for 30 days. GA has taken as positive control. After the treatment period, ISO (50 mg/ kg) in sub-cutaneous route was administered to the rats for two consecutive days. Then the rats sacrificed and the cardiac tissues were used for enzyme inhibitory analysis. Results: SA, RV, GA and COMB exhibited HMG-CoA reductase enzyme inhibitory activity. Also, the compounds augmented the LPL enzyme activity in the rats administered with ISO. Furthermore, in silico molecular docking reports also supported to the activity of SA, RV, GA and COMB compounds towards the enzymes HMG-CoA reductase and LPL. Conclusion: This report for the first time indicates the potential of phenolic compounds SA, RV, GA and COMB as excellent natural compounds in the therapeutic treatment of lipid metabolism disorders.

In recent years, with the continuous development of molecular immunology, immune checkpoint inhibitors (ICIs) have also been widely used in the treatment of gastric cancer, but they still face some challenges: The first is that only some people can benefit, the second is the treatment-related adverse events (TRAEs) that occur during treatment, and the third is the emergence of varying degrees of drug resistance with long-term use. How to overcome these challenges, combined therapy based on ICIs has become one of the important strategies. This article summarizes the clinical application of ICIs combined with chemotherapy, targeted therapy, radiotherapy, photodynamic therapy, thermotherapy, immune adjuvant, and dual immunotherapy and discusses the mechanism, and also summarizes the advantages and disadvantages of the current combination modalities and the potential research value. The aim of this study is to provide more and more optimized combination regimen for ICI combined therapy in patients with advanced gastric cancer and to provide reference for clinical and scientific research.

Abstract Due to rapid homogenization in habitat types as a result of urbanization, some urban birds adapt their nesting strategies to changes in local habitat characteristics. Bird nesting decisions might have been mainly linked to resource constraints and ensuring reproductive success. In this study, we examined patterns of nesting behavior by spotted doves (Spilopelia chinensis) in a rapidly urbanizing area of Nanchang, China using ArcGIS 10.8, satellite tracking, camera traps, and field survey. To explore the mechanisms underlying nesting behavior in urban habitats, we assessed the correlations between nest reuse and reproductive success, and between nest reuse and nest predation. From December 2018 to December 2021, a total of 302 breeding nests were surveyed. The results revealed that the nest reuse rate was 38.08% (n = 115). Nests closer to trunk, with lower nest position and higher large‐scale urbanization score tended to have higher reuse rate. In addition, nests with the higher the nest height and percent of canopy cover, and the lower small‐scale urbanization score were more likely to reproduce successfully, and the reused nests also reproduce more successfully. The reproductive success associated with nest reuse was significantly higher than that associated with new nests (χ2 = 8.461, p = .004). High degree of urbanization promoted nest reuse of spotted doves (large‐scale urbanization score, z = 2.094, p = .036), which apparently enhanced their reproductive success (nest reuse, z = 2.737, p = .006). In conclusion, a nest structure with good permeability is the material basis for the nest reuse in spotted dove, while the relatively low risk of predation in urban habitat and the scarcity of nest site resources due to urbanization increase the tendency of birds to reuse old nests, which is associated with their reproductive success and evolutionary fitness.

The motivation for this research stems from the growing demand for solid-phase welding technology to join multilayers metals, particularly in green electric vehicles. Welding of foils and tabs inside battery is a challenging task due to poor joint formation at the interface and low strength. Ultrasonic welding is an efficient, reliable and environmentally friendly bonding method to firmly connect multi-layer copper foils and tabs. Therefore, this is used to achieve electrical bonding within the lithium-ion batteries. This is widely used in production of new energy vehicle batteries. In this work, 40 layers of copper foil were bonded to 0.3 mm nickel-plated copper tabs using ultrasonic metal welding technology. The effect of ultrasonic welding parameters on T-peel strength of joints was systematically investigated by orthogonal experimental design. The maximum T-peel strength of 359.17 N was obtained under optimal parameters (e.g., welding energy 600 J, pressure 0.3 MPa and amplitude 55 %). The variation of welding temperature and amplitude under different welding parameters was measured using infrared thermometer and laser vibrometer. Moreover, the surface, cross-sectional and failure fracture analysis and characterization of specimens with different weld qualities were performed using optical microscopy and scanning electron microscopy (SEM). In addition, the state of Ni layer in cross-section was analyzed using the energy dispersive spectroscopy (EDS) technique after ultrasonic welding. This approach can be straightforward and more appropriate to the development of solid-phase welding method for automotive industry.

Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Abstract Biominerals, the inorganic minerals of organisms, are known mainly for their physical property-related functions in modern living organisms. Our recent discovery of the enzyme-like activities of nanomaterials, coined as nanozyme, inspires the hypothesis that nano-biominerals might function as enzyme-like catalyzers in cells. Here we report that the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals. Through analyzing eighteen representative ferritins from three living kingdoms, we find that the iron core of prokaryote ferritin possesses higher superoxide-diminishing activity than that of eukaryotes. Further investigation reveals that the differences in catalytic capability result from the iron/phosphate ratio changes in the iron core, which is mainly determined by the structures of ferritins. The phosphate in the iron core switches the iron core from single crystalline to amorphous iron phosphate-like structure, resulting in decreased affinity to the hydrogen proton of the ferrihydrite-like core that facilitates its reaction with superoxide in a manner different from that of ferric ions. Furthermore, overexpression of ferritins with high superoxide-diminishing activities in E. coli increases the resistance to superoxide, whereas bacterioferritin knockout or human ferritin knock-in diminishes free radical tolerance, highlighting the physiological antioxidant role of this type of nanozymes.

Over the past decade, a growing number of studies have reported transcription factor-based in situ reprogramming that can directly convert endogenous glial cells into functional neurons as an alternative approach for neuroregeneration in the adult mammalian central nervous system. However, many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry. In addition, concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tracing mice. In this study, we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ectopic expression of the neural transcription factor NeuroD1 in both proliferating reactive astrocytes and lineage-traced astrocytes in the mouse cortex. Time-lapse imaging over several weeks revealed the step-by-step transition from a typical astrocyte with numerous short, tapered branches to a typical neuron with a few long neurites and dynamic growth cones that actively explored the local environment. In addition, these lineage-converting cells were able to migrate radially or tangentially to relocate to suitable positions. Furthermore, two-photon Ca2+ imaging and patch-clamp recordings confirmed that the newly generated neurons exhibited synchronous calcium signals, repetitive action potentials, and spontaneous synaptic responses, suggesting that they had made functional synaptic connections within local neural circuits. In conclusion, we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuroregeneration and neural circuit reconstruction.

Abstract Background Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys. Methods Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests. Results We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents. Conclusions This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.

Simulating wind turbine blade icing quickly is important for wind farms to issue early warnings and effectively deal with the adverse effects of cold weather. However, current numerical simulation methods suffer from high computational costs and lack straightforward acceleration techniques for practical ice prediction. Here, we developed a fast and simple blade icing simulation method via an integrated physical simulation and statistical analysis method. This method consists of two steps: firstly, numerical simulation with CFD, and secondly, table look-up calculations. Over 10,000 sets of wind turbine blade icing simulations based on FENSAP-ICE and an NACA64-A17 wing were conducted to develop this method and analyze the influences of environmental factors on blade icing. The results show that ice thickness generally increases with an increase in wind speed, a decrease in temperature, and an increase in liquid water content (LWC), but there is a nonlinear relationship between them. For example, ice thickness has a linear relationship with the LWC within a certain range but hardly changes with a LWC beyond that range. The validation results show that the fast simulation method established in this paper has good consistency with the original numerical simulation method. It can greatly improve the computational efficiency of icing simulations while retaining the accuracy of numerical simulations. It takes less than 1 s to complete over 1000 sets of icing simulations, which offers potential for the fast prediction of wind turbine blade icing in the future.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). However, whether LRRK2 mutations cause PD and degeneration of dopaminergic (DA) neurons via a toxic gain-of-function or a loss-of-function mechanism is unresolved and has pivotal implications for LRRK2-based PD therapies. In this study, we investigate whether Lrrk2 and its functional homolog Lrrk1 play a cell-intrinsic role in DA neuron survival through the development of DA neuron-specific Lrrk conditional double knockout (cDKO) mice. Unlike Lrrk germline DKO mice, DA neuron-restricted Lrrk cDKO mice exhibit normal mortality but develop age-dependent loss of DA neurons, as shown by the progressive reduction of DA neurons in the substantia nigra pars compacta (SNpc) at the ages of 20 and 24 months. Moreover, DA neurodegeneration is accompanied with increases in apoptosis and elevated microgliosis in the SNpc as well as decreases in DA terminals in the striatum, and is preceded by impaired motor coordination. Taken together, these findings provide the unequivocal evidence for the cell-intrinsic requirement of LRRK in DA neurons and raise the possibility that LRRK2 mutations may impair its protection of DA neurons, leading to DA neurodegeneration in PD.

ABSTRACTThe emergence and re-emergence of abundant viruses from bats that impact human and animal health have resulted in a resurgence of interest in bat immunology. Characterizing the immune receptor repertoire is critical to understanding how bats coexist with viruses in the absence of disease and developing new therapeutics to target viruses in humans and susceptible livestock. In this study, IGH germline genes of Chiroptera including Rhinolophus ferrumequinum, Phyllostomus discolor, and Pipistrellus pipistrellus were annotated, and we profiled the characteristics of Rhinolophus affinis (RA) IGH CDR3 repertoire. The germline genes of Chiroptera are quite different from those of human, mouse, cow, and dog in evolution, but the three bat species have high homology. The CDR3 repertoire of RA is unique in many aspects including CDR3 subclass, V/J genes access and pairing, CDR3 clones, and somatic high-frequency mutation compared with that of human and mouse, which is an important point in understanding the asymptomatic nature of viral infection in bats. This study unveiled a detailed map of bat IGH germline genes on chromosome level and provided the first immune receptor repertoire of bat, which will stimulate new avenues of research that are directly relevant to human health and disease.IMPORTANCEThe intricate relationship between bats and viruses has been a subject of study since the mid-20th century, with more than 100 viruses identified, including those affecting humans. While preliminary investigations have outlined the innate immune responses of bats, the role of adaptive immunity remains unclear. This study presents a pioneering contribution to bat immunology by unveiling, for the first time, a detailed map of bat IGH germline genes at the chromosome level. This breakthrough not only provides a foundation for B cell receptor research in bats but also contributes to primer design and sequencing of the CDR3 repertoire. Additionally, we offer the first comprehensive immune receptor repertoire of bats, serving as a crucial library for future comparative analyses. In summary, this research significantly advances the understanding of bats’ immune responses, providing essential resources for further investigations into viral tolerance and potential zoonotic threats.

Study region: The Issyk-Kul Basin, Central Asia. Study focus: Currently, there is a scarcity of in-depth evaluations of the progression and factors that affect the intensification of the water cycle at the basin level, given the increased fluctuations in the global hydrological cycle. In this study, a water cycle intensity (WCI) indicator based on the terrestrial water balance equation was used to assess basin-scale water cycle characteristics from 1982 to 2017, and the Bayesian estimator algorithm (BEAST) and wavelet transform coherence (WTC) were used to analyse the temporal evolution characteristics and factors influencing the intensity of the water cycle. New hydrological insights for the region: The WCI of the Issyk-Kul Basin (ISKB) undergoes an abrupt change and displays an intensified trend with a clear time-scale effect in the trend change following the global warming hiatus. In terms of forcing factors, the interannual variability in the WCI was driven by the Tibetan Plateau Index_B (TPI) and the North Atlantic Oscillation (NAO) until 1998, while afterwards it was driven by the Antarctic Oscillation (AAO). The alteration in the forcing relationship was a significant contributor to the sudden shift observed in the WCI in 1998. This study improves the comprehension of basin-scale alterations in the intensity of the water cycle and their driving mechanisms under climate change, with practical implications for the management of water resources in arid Central Asia.

Abstract It is imperative to develop practicable pathogenic bacteria detection methods. We devised a biosensor for the ultrasensitive detection of Salmonella typhimurium (S. typhi), termed as SCOUT‐dCas9 (ultrasensitive, cross‐validating, on‐site, and dUal‐mode test using CRISPR/dCas9). Simply, the species‐specific invA gene of S. typhi was amplified using loop‐mediated isothermal amplification with a biotinylated primer, which can be specifically “pulled down” by “antibody‐like” dCas9‐single guide RNA to form a ternary complex. SYBR Green I and streptavidin‐modified alkaline phosphatase were used to functionalize them to generate fluorescent and colorimetric signals, respectively. With this strategy, the target could be dexterously converted into bimodal signals that were cross‐validated to afford more reliable results. For both modes, SCOUT‐dCas9 was able to detect as low as 1 CFU/mL with a dynamic range from 1 to 109 CFU/mL. Lastly, SCOUT‐dCas9 had satisfactory selectivity and was capable of detecting S. typhi‐contaminated real food samples. SCOUT‐dCas9 provides a robust platform for bacterial detection.

Abstract Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

Abstract In complex high in-situ stress conditions, how to achieve the ideal rock blasting effect through effective methods is often a difficult point of blasting operations. This paper analyzes the influence of guide holes on blasting effect by adding guide holes to the rock pre-treatment method. Based on the particle expansion method to carry out double-hole blasting experiments, the influence of the blasthole spacing and ground stress on the blasting effect is investigated from the levels of macroscopic cracking effect, microscopic particle contact and so on. The study shows that: (i) the setting of empty holes between the gun holes can enhance the crack penetration effect, and the penetration effect is more obvious when the distance between the gun holes and the empty holes is less than 2.5 times the radius of the crushed zone. (ii) At the level of contact force chain, when the distance between blastholes and empty holes is less than 2.5 times the radius of the crushing zone. The compressive stress in the direction perpendicular to the direction of the blasthole line inhibits crack development, and the tensile stress in the direction parallel to the blasthole line promotes crack development. The main stress direction is perpendicular to the direction of the blasthole line. (iii) As the distance between the blastholes increases, the effect of crack suppression by stresses in the vertical direction decreases, and the main force direction is parallel to the direction of the blasthole line.

To address the issue of intelligent optimization algorithms being prone to local optima, resulting in insufficient feature extraction and low fault-type recognition rates when optimizing Variational Mode Decomposition and Support Vector Machine parameters, this paper proposes a fault diagnosis method based on an improved Artificial Gorilla Troops Optimization algorithm. The Artificial Gorilla Troops Optimization algorithm was enhanced using Logistic chaotic mapping, a linear decreasing weight factor, the global exploration strategy of the Osprey Optimization Algorithm, and the Levy flight strategy, improving its ability to escape local optima, adaptability, and convergence accuracy. This algorithm was used to optimize the parameters of Variational Mode Decomposition and Support Vector Machine for fault diagnosis. Experiments on fault diagnosis with two datasets of different sample sizes showed that the proposed method achieved a diagnostic accuracy of no less than 98% for samples of varying sizes, with stable and reliable results.

To provide the necessary theoretical models of sphere–soil interaction for the structural design, motion control, and simulation of spherical robots, this paper derives analytical expressions for traction force and driving torque when spherical robots slide and sink into sandy terrain, based on terramechanics and multibody dynamics. Furthermore, orthogonal experimental analysis identifies the load, joint angular acceleration, and maximum joint angular velocity of spherical robots as influencing factors, highlighting that the load significantly affects their longitudinal motion performance. Experimental results indicate that rolling friction and additional resistance on sandy terrain cannot be ignored. The corrected theoretical model effectively replicates the temporal variation of driving torque exerted by spherical robots on sandy terrain. Numerical computations and experimental analyses demonstrate that increasing the radius of the sphere shell, the load, and the slip ratio all lead to increased traction force and driving torque. However, traction force and driving torque begin to decrease once the slip ratio reaches approximately 0.5. Therefore, in the design of spherical robot structures and control laws, appropriate parameters such as load and slip ratio should be chosen based on the established sphere–soil interaction theoretical model to achieve high-quality longitudinal motion performance on sandy terrain.

Human milk oligosaccharides (HMOs) are very distinctive components in human milk and are beneficial for infant health. Lacto-N-biose I (LNB) is the core structural unit of HMOs, which could be used for the synthesis of other HMOs. In this study, an ATP-free in vitro synthetic enzymatic biosystem contained four thermostable enzymes (alpha-glucan phosphorylase from Thermococcus kodakarensis, UDP-glucose-hexose-1-phosphate uridylyltransferase from Thermotoga maritima, UDP-glucose 4-epimerase from T. maritima, lacto-N-biose phosphorylase from Clostridium thermobutyricum) were constructed for the biosynthesis of LNB from starch and N-acetylglucosamine (GlcNAc). Under the optimal conditions, 0.75 g/L and 2.23 g/L LNB was produced from 1.1 g/L and 4.4 g/L GlcNAc and excess starch, with the molar yield of 39% and 29% based on the GlcNAc concentration, respectively, confirming the feasibility of this in vitro synthetic enzymatic biosystem for LNB synthesis and shedding light on the biosynthesis of other HMOs using LNB as the core structural unit from low cost polysaccharides.

The results showed that the precipitation in the study area was mainly in a downward trend before the mid-1930s, and then turned upward. In the 1950s, the precipitation generally showed a distribution of rising in the west and falling in the east, and this trend continued until the early 21st century. By 2007, except for the central part of the Continental Basin, the overall trend was mainly upward. In this study, 65 El Niño Southern Oscillation (ENSO) events were identified, including 24 El Niño events and 41 La Niña events. The precipitation was generally less when ENSO occurred. However, there were differences in the type and intensity of the event. For example, El Niño had a greater impact on precipitation than La Niña did, and extremely strong or strong El Niño/La Niña events had a more significant impact than moderate, weak, or extremely weak ones. The correlation between precipitation and El Niño or La Niña events had some similarities and differences. For example, precipitation was mainly negatively correlated with El Niño and La Niña at the same time, and both correlations were proportional to intensity, but the correlation between precipitation and El Niño was significantly stronger than that of La Niña. HIGHLIGHTS Most of the studies classified the types of ENSO based on the location, and this paper classified it by intensity.; Most of the studies were carried out on the seasonal scale, the annual scale is still relatively lacking.; Most studies focused on the qualitative relationship between precipitation and ENSO, this paper quantified the relationship.; The study area in this paper was wider, and the results were more representative.;

Abstract Allelic exclusion, one lymphocyte expresses one antigen receptor, is a fundamental mechanism of immunological self-tolerance and highly specific immune responses to pathogens. However, the phenomenon of V(D)J allelic inclusion (incomplete allelic exclusion or allelic escape) rearrangement and dual TCR T cells have been discovered by multiple laboratories. Despite continuous new discoveries, the proportion and underlying mechanism of dual TCR has been puzzling immunologists. In this study, we observed the presence of single T cells expressing multiple TCR chains in all samples, with the proportion of 15%, 10%, and 20% in the human thymus, human peripheral blood, and mouse lymphoid organs, respectively. The proportion of T cells possessing multiple T-cell receptors (TCR) varied significantly in different physiological states and developmental stages. By analyzing RSS category, RSS direction, and V(D)J gene position at TR locus of T cells which contain multiple TCR chains, we creatively found that one of TCR β (or TCR α) should originate from the transcription of V(D)J combination in T-cell receptor excision circle (TREC) formed after the twice successful rearrangement in the same chromosome. Moreover, human V30 (or mouse V31) gene may participate in reverse recombination and transcription to prevent allelic exclusion. In general, high proportion of T cells with multiple TCR at the transcriptome level was first made public, and we proposed a novel mechanism of secondary (or more) TCR rearrangement on a single chromosome. Our findings also indicated that the single-cell sequencing data should be classified according to the single, multiple, and abnormal TCR when analyzing the T-cell repertoire.

This study has investigated the effect of ultrasound (US) as an emerging non-thermal sterilization technique on microbial growth and quality changes in three freshly squeezed pumpkin juices (Cucurbita maxima Duchesne, Cucurbita moschata Duchesne, and Cucurbita pepo L.).The three pumpkin juices were ultrasonicated at different ultrasonic power (0–400 W), time (0–20 min), and temperature (0–30 °C), and the total colony counts of the treated pumpkin juices were less than 5 log CFU/mL, which complied with the food safety and consumption standards. Based on these results, we further investigated the effects of different ultrasonic power (25 kHz, 10 min, 20 °C, 0–400 W) on the physicochemical properties and sensory quality of the three pumpkin juices. The physicochemical properties (color, sugar content, organic acid content, soluble solids, and carotenoids) of treated pumpkin juice were retained or improved to some extent. The antioxidant capacity was also increased by 9.09%, 10.25%, and 16.9% compared to the untreated group. During sonication, the particle size of all samples decreased significantly, the microstructure broke down significantly, and the sensory qualities of pumpkin juice were well preserved after sonication.

Purpose: Over the past decade, digital labor platforms (DLP) have emerged as a new trend and are major components of the platform economy. Crowdsourcing is being used in an innovative way to allow firms to outsource tasks to individuals with access to DLP. Apart from paid crowdsourcing, unpaid crowdsourcing has also emerged, where crowdsourced volunteers are recruited to contribute to crowdsourcing tasks available on the platform. Integrating perspectives from the public services motivation, uses and gratification theory and self-determination theory, this paper investigates the motives and underlying needs behind participation in the crowdsourcing of translation tasks. Design/methodology/approach: Interviews were conducted with 21 volunteer crowdsourced volunteers from a voluntary global crowdsourcing community to understand the factors driving them to spend time and effort contributing to the community. Content analysis methods were utilized to analyze the text data. Findings: The results indicated that the autonomy, competence and relatedness needs were the underlying needs of the crowdsourced volunteers. Furthermore, we found diverse motives consisting of both intrinsic and extrinsic motivations driving users to contribute voluntarily. Originality: While prior research efforts have clarified many issues related to participation in DLP, the reasons behind volunteers' participation in DLP are still unexplored. The findings of the present study contribute to a better understanding of the motives underlying volunteers’ participation in the crowdsourcing tasks on DLP.

Human activity and hydroclimate change greatly influence the environment in a lake and its catchment, particularly in areas with fragile ecosystems, such as arid Central Asia. In this study, lipid biomarkers (n-alkanes and n-fatty acids) were measured in a 210Pb- and 137Cs-dated sediment core from Lake Balkhash to determine their environmental significance and infer the history of environmental change over the last ~200 years. The terrestrial origin of long-chain n-alkanes and the aquatic origin of both n-fatty acids and mid-/short-chain n-alkanes were inferred from molecular distributions and diagnostic ratios. Three major environmental phases were identified over the past two centuries based on stratigraphic shifts in biomarker indicators. During 1800-1860 AD, the lake exhibited a high-water level with abundant submerged/floating macrophytes and limited phytoplankton, as suggested by multiple indicators, e.g., high proportions of aquatic macrophytes (Paq) and long-chain n-fatty acids (L-FAs). Overall, minor terrestrial inputs were revealed by low concentrations of long-chain n-alkanes (L-ALKs), suggesting dense vegetation cover in the catchment. The lake environment experienced a pronounced change in the subsequent phase from 1860–1930 AD, during which the cover of submerged/floating macrophytes gradually diminished, as revealed by the decreasing trend of aquatic proxies, e.g., L-FAs and Paq. In contrast, the number of emergent plants and terrestrial inputs increased, as suggested by the decreased Paq values. A great variation in water levels likely resulted in the shrinkage of the submerged/floating macrophyte cover. During 1930-2017 AD, anthropogenic impacts began to appear on the sediment profile. The highest terrestrial inputs, as revealed by the maximum L-ALK abundance on record, indicated intensive exploitation of the catchment during 1935-1959 AD. The lowest L-FA and Paq values suggested that submerged/floating macrophytes were at the lowest levels during this phase, possibly in response to the decreased water levels and increasing salinity. Increased human-induced nutrient loading coupled with elevated regional temperature prompted the lake to become an increasingly productive lake system, especially in more recent decades, as indicated by the highest levels of short-chain lipids. These results highlight the important role of hydrological variation and human activity in the environmental evolution of the Ili-Balkhash Basin.

Abstract Background Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain. Methods Single‐cell Cytometry by Time‐of‐Flight (CyTOF) technology was employed to profile the single‐cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression. Results Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up‐regulated in T cells, B cells and monocytes from the controls but down‐regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti‐inflammatory functional molecules (IL‐4 and IL‐10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out‐of‐bag errors). Conclusion These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.

The exponential growth of human activities has resulted in a substantial increase in land use practices that not only modify the characteristics of landscape patterns but also pose significant landscape ecological risk (LER), with the latter being pivotal for ecosystem conservation and sustainable social development. However, research on LER and driving factors of Irtysh River Basin (IRB) are limited. Objectively assessing the LER of the high latitudes within Central Asia (Irtysh River Basin) and quantitatively identifying the environmental factors driving its changes holds significant research value for ensuring the ecological security of human habitation amidst global change. In this study, the spatial autocorrelation analysis method and geographically weighted regression (GWR) and geographical detector (Geo-Detector) models were utilized to reveal the spatiotemporal changes in LER based on land use/land cover (LULC) changes in the IRB from 1992 to 2020. The findings indicate that (1) the temporal scale reveals a slight increasing trend in LER within the IRB. (2) The spatial distribution is characterized by a dominance of lower- and medium-risk regions, with evident positive spatial autocorrelation. (3) The spatial pattern of LER is influenced by various factors, with a significant impact from temperature in the geo-detector model. In addition, the spatial heterogeneity of the effects of major factors was further obtained using the GWR model. The findings presented herein can serve as scientific references for the development of sustainability and ecological safety management in global arid zones and high-latitude cold regions, thus promoting environmental protection in various countries, enhancing consensus on ecological protection and facilitating international cooperation on conservation.

Through the pendulum mechanism inside the spherical shell, the centroid can be varied circumferentially, enabling the spherical robot to achieve omnidirectional flexible movement. Additionally, the radial variation ability of the centroid enables spherical robots to adopt two distinct driving modes: the traditional lower pendulum driving mode and the inverted pendulum driving mode. There are two manifestations of radial variation in the centroid: having different radial positions of the centroid and achieving radial movement of the centroid. Focusing on these two manifestations, experimental data are obtained through different motion velocities and different motion slopes to conduct research on the influence of radial variation in the centroid on the motion of spherical robots. Based on the experimental data, multiple indicators are analyzed, including response speed, convergence speed, stability, and overshoot, as well as steering ability, climbing ability, and output power. The impact of the radial variation ability of the centroid on the control performance, locomotion capability, and energy consumption of spherical robots is summarized, and the correlation model relating the motion requirements to the radial position of the centroid is established, providing a theoretical basis for the selection of driving modes and centroid positions for spherical robots facing complex task requirements.

Mathematical models of prediction provide theoretical support for basic rail automation. The three-point bending method for basic rails is characterized by its simplicity and flexibility, and, as such, it is widely used in bending processes. However, due to the significant curvature changes that occur after bending, it is not suitable for scenarios requiring large arc bending, and its range of achievable deflections is limited. This study focuses on four-point bending, dividing the bending process into three stages and using a power-law material hardening model to establish different bending moment expressions for each stage. We derived the relationships between curvature, elastic zone ratio, load, and deflection, ultimately creating a load–deflection model. Based on the simple springback law, we developed the final bending prediction model. Finite element simulations were conducted to simulate the bending process under various conditions, using top punch distances ranging from 200 mm to 400 mm and die distances ranging from 600 mm to 1000 mm. These simulations validated the advantages and accuracy of the four-point bending prediction model in large arc bending. Additionally, a four-point bending experimental setup was established under specified conditions. The experimental results were compared with the theoretical model calculations, showing errors within 0.2 mm and thus verifying the accuracy of the four-point bending prediction model. The mathematical model developed in this study provides theoretical support for the automation of basic rail bending.

The optimal designing of the hybrid energy system (HES) is a challenging task due to the multiple objectives and various uncertainties. Especially for HES, primarily powered by solar energy, the reference solar radiation data directly impact the result of the optimization design. To incorporate the stochastic characteristics of solar radiation into the sizing process, a data-driven stochastic modeling method for solar radiation is proposed. The method involves two layers of stochastic processes that capture the intraday variation and daily evolution of solar radiation. First, the clearness index (CI) is introduced to describe the radiation intensity at different times. Then, the daily clearness state (DCS) is proposed, based on the statistical indicators of the intraday CI. The Markov model is used to describe the stochastic evolutionary characteristics between different DCSs. The probabilistic distribution of the CI under different DCS is obtained based on the diffusion kernel density estimation (DKDE), which is used for the stochastic generation of the CI at various times of the day. Finally, the radiation profile required for the optimal design is obtained by the stochastic generation of the DCS sequences and the intraday clearness index under corresponding states. A case study of an off-grid solar-powered HES is provided to illustrate this methodology.