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Amino oligosaccharides (AOs) possess various biological activities and are valuable in the pharmaceutical, food industries, and agriculture. However, the industrial manufacturing of AOs has not been realized yet, despite reports on physical, chemical, and biological approaches. In this study, the de novo production of chitin oligosaccharides (CHOS), a type of structurally defined AOs, was achieved in Escherichia coli through combinatorial pathway engineering. The most suitable glycosyltransferase for CHOS production was found to be NodCL from Mesorhizobium Loti. Then, by knocking out the nagB gene to block the flow of N-acetyl-d-glucosamine (NAG) to the glycolytic pathway in E. coli and adjusting the copy number of NodCL-coding gene, the CHOS yield was increased by 6.56 times. Subsequently, by introducing of UDP-N-acetylglucosamine (UDP-GlcNAc) salvage pathway for and optimizing fermentation conditions, the yield of CHOS reached 207.1 and 468.6 mg/L in shake-flask cultivation and a 5-L fed-batch bioreactor, respectively. Meanwhile, the concentration of UDP-GlcNAc was 91.0 mg/L, the highest level reported in E. coli so far. This study demonstrated, for the first time, the production of CHOS with distinct structures in plasmid-free E. coli, laying the groundwork for the biosynthesis of CHOS and providing a starting point for further engineering and commercial production.

Abstract Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects. We identified 32 rumen microbiota biomarkers including Bifidobacterium that were associated with FD-traits (Padj

This study develops a moderated mediation model that explores the link between empowering leadership and older teachers' knowledge-sharing behaviour by focusing on the mediating role of organization-based self-esteem and the moderating role of organizational status. Based on a two-wave survey of 204 older teachers in primary and secondary schools in China, the results indicate that principals' empowering leadership is positively related to older teachers' knowledge-sharing behaviour, and this relationship is mediated by organization-based self-esteem. Moreover, organizational status moderates the mediating role of organization-based self-esteem in transmitting the effect of empowering leadership to knowledge-sharing behaviour.

ABSTRACT Sheep are one of the globally significant livestock, providing meat, dairy products, and wool for human life, playing an indispensable role in human civilization. Despite significant advancements in microbiome research in recent years, most studies have focused solely on the rumen, lacking a comprehensive study covering the microbiome of different gastrointestinal tract (GIT) regions in sheep. In this study, we collected 338 samples from 10 different regions of the sheep GIT and systematically investigated their microbiome signatures, including community structure, enterotypes, interactions among taxa, and microbial community assembly. Our results showed that the bacterial diversity of sheep GIT exhibited a U-shaped pattern along the GIT, with the lowest diversity in the jejunum. The bacterial community composition and enterotype varied along the GIT, mainly divided into three distinct groups (four-chambered stomach, small intestine, and large intestine). The rumen had the highest total number of bacterial taxa, unique taxa, and unique functions, while the enterotypes were the same in the three regions of the large intestine. The bacterial co-occurrence networks differed greatly between different GIT regions, with more positive correlations than negative ones. Furthermore, we found that the assembly processes of bacterial communities in the four-chambered stomach and small intestine were mainly stochastic, while those in the large intestine were mainly shaped by deterministic processes, with a higher ecological niche width than other GIT regions. Our results reveal the spatial pattern of bacterial communities in the sheep GIT and the intrinsic mechanisms of bacterial community assembly, laying the foundation for microbial interventions to improve sheep productivity and sustainable farming.IMPORTANCESheep's gastrointestinal tract harbors a diverse microbial community crucial for immune system balance, nutrient digestion, and overall health. We explored the microbial community composition, community types (enterotypes), bacterial interactions, and ecological processes in 10 gastrointestinal regions of 36 six-month-old Hu sheep raised under same diets and environmental conditions. Our findings revealed a unique U-shaped pattern of bacterial diversity from the rumen to the rectum, with the lowest diversity in the jejunum. The composition and enterotypes of bacterial communities varied spatially along the gastrointestinal tract, primarily categorized into three distinct groups. The rumen exhibited the highest abundance of bacterial taxa, unique taxa, and unique functions, while the enterotypes in the three regions of the large intestine were consistent. We explored the assembly processes of bacterial communities, elucidating how they find their ecological niches based on their characteristics and environmental demands. The assembly processes in the four-chambered stomach and small intestine resembled random selection, where bacterial positioning depended on luck and chance, while in the large intestine, it appeared more deterministic, with specific bacteria likely selected based on their unique skills and environmental requirements. This study enhances our understanding of microbial coexistence and interactions in complex ecosystems, with implications for improving animal productivity, disease treatment, and the development of novel microbial formulations.

BackgroundEvidence on the association between cognitive activities and mortality among older adults with cognitive impairment is limited. Therefore, the study aimed to assess the association and examine whether baseline cognitive function mediates the association.MethodsA total of 10477 older participants with cognitive impairment (median age: 95.0 [IQR: 88.0-100.0], males: 27.9%, Mini-Mental State Examination score ≤24 points) from the Chinese Longitudinal Healthy Longevity Survey conducted between 1998 and 2014 were included, with follow-up until 2018. Exposures were three prevalent cognitive activities among older adults in China: reading books/newspapers, playing cards/mah-jong, and watching TV or listening to radio, and the outcome was all-cause mortality within a 10-year follow-up period. We evaluated the association between these activities and mortality using Cox regression models and also conducted a mediation analysis to examine the role of baseline cognitive function in this association.ResultsDuring a follow-up period of totaling 33632.1 person-years, there were 8763 recorded deaths (83.6%). For each cognitive activity, the risk of mortality decreased with an increased frequency of engagement in these activities. Moreover, the risk of mortality significantly decreased with a greater number of cognitive activities. With zero activities as reference, adjusted hazard ratios were 0.83 (95% CI: 0.79-0.87) for one activity, 0.76 (95% CI: 0.69-0.83) for two activities, and 0.67 (95% CI: 0.53-0.86) for three activities, respectively. Stratified and sensitivity analyses confirmed the robustness of these findings. Additionally, baseline cognitive function partially mediated the association between cognitive activities and mortality; compared to zero activities, the mediated proportions were 15.2% (95% CI: 10.9%-22.4%) for one activity, 13.4% (95% CI: 8.9%-21.3%) for two activities, and 9.3% (95% CI: 4.2%-23.4%) for three activities, respectively.ConclusionsAmong older adults with cognitive impairment in China, the risk of all-cause mortality significantly decreased as both the frequency and number of cognitive activities increased. Baseline cognitive function only mediated a small proportion of the benefits of cognitive activities in longevity.

ObjectiveThe relationship between small subcortical ischemic infarction remains poorly characterized. Therefore, the present study aimed to investigate the association between artery-to-artery embolization and small subcortical infarctions.MethodsThis retrospective observational cross-sectional study enrolling 230 patients with acute middle cerebral artery (MCA) stroke classified into the microembolic signals-positive (MES+) and MES-negative (MES−) groups. The diffusion weighted imaging (DWI) infarction patterns in the MCA were divided into the territorial, border zone (BZ), cortical, and subcortical infarcts. We set the standard of small subcortical infarction (SCI) into two levels: < 10 mm diameter and

Jixian seismic station is the only bedrock outcrop in the Tianjin area, with two sets of VP broadband inclinometers installed in Xinshan cave and Xiaoxinzhuang cave respectively. Through comparative analysis of the intrinsic quality, co-seismic response, environmental impact, and instrument maintenance of two sets of VP broadband inclinometers at Jixian station, the following conclusions are drawn. Taking 2023 as an example, the continuity and completeness of the VP broadband inclinometer in Xiaoxinzhuang cave at Jixian station were high, but the completeness of the VP broadband inclinometer in Xinshan cave was relatively low due to human interference and instrument maintenance. The tidal factor stability of both instruments is good, but due to pendulum system failure, the NS accuracy of the Xinshandong cave VP broadband inclinometer is relatively poor. By comparing from 2018 to 2023, the VP broadband inclinometer in Xiaoxinzhuang cave had a clear annual variation pattern, while the VP broadband inclinometer in Xinshan cave had an inconspicuous annual variation pattern, which may be related to the relatively fragmented geological conditions of the regional structure in Xinshan cave. Natural environmental changes such as heavy rainfall and strong winds can have a certain impact on the observation of the two sets of instruments. The Xinshan cave is significantly affected by the pumping around the station. VP broadband inclinometers have a strong ability to record earthquakes, and can clearly record periodic surface waves of several seconds to tens of seconds for far-field earthquakes. For near-field strong earthquakes, they can clearly record the initial arrival of P-waves, but subsequent seismic phase identification is more difficult. A maintenance process was summarized to provide reference for the operation and maintenance of similar instruments, in response to the occasional sudden jumping errors in the EW direction of the Xinshan cave VP broadband inclinometer.

In this study, we sequenced the complete mitochondrial genome of the shield-faced leaf-nosed bat (Hipposideros lylei Thomas, 1914) using the Illumina platform. The mitochondrial genome of H. lylei is 16,856 bp in length, encoding 37 genes, which include 13 protein-coding genes, 22 tRNA genes, two rRNA genes, one replication start, and one non-coding control region (D-loop) of 417 bp in length. It has a G + C content of 42.0%, lower than the A + T content, indicating an obvious AT base preference. Phylogenetic analyses revealed that H. lylei clusters with three species of the genus Hipposideros in one branch and is relatively closely related to H. armiger and H. larvatus.

In order to explore the characteristics of the mitochondrial genome sequence of Pratt’s leaf-nosed bat (Hipposideros pratti Thomas 1891) and understand their phylogenetic status in Chiroptera, this study determined the mitochondrial genome sequences of H. pratti from five regions in China using high-throughput sequencing technology, sequence assembly, and genome annotation. The results showed that these sequences contained 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 non-coding region, all exhibiting a significant AT bias. Based on the phylogenetic tree constructed using 13 protein-coding genes from 15 Chiroptera species, the study found that H. pratti from the five regions clustered together, and then clustered with H. lylei into a single clade. Meanwhile, H. pratti from Jiangxi, Fujian, and Guangdong regions of China showed closer genetic relationships, while H. pratti from Yunnan and Henan regions of China exhibited closer genetic relationships. This study not only supplemented the mitochondrial genome database of H. pratti but also laid a foundation for genetic variation, molecular classification, and evolutionary studies of H. pratti.

Abstract Comprehensive functional genome annotation is crucial to elucidate the molecular mechanisms of agronomic traits in livestock, yet systematic functional annotation of the sheep genome is lacking. Here, we generated 92 transcriptomic and epigenomic data sets from nine major tissues, along with whole‐genome data from 2357 individuals across 29 breeds worldwide, and 4006 phenotypic data related to tail fat weight. We constructed the first multi‐tissue epigenome atlas in terms of functional elements, chromatin states, and their functions and explored the utility of the functional elements in interpreting phenotypic variation during sheep domestication and improvement. Particularly, we identified a total of 753,723 nonredundant functional elements, with over 60% being novel. We found tissue‐specific promoters and enhancers related to sensory abilities and immune response that were highly enriched in genomic regions influenced by domestication, while longissimus dorsi tissue‐specific active enhancers and tail fat tissue‐specific active promoters were highly enriched in genomic regions influenced by breeding and improvement. Notably, a variant, Chr13:51760995A>C, located in an enhancer region, was identified as a causal variant for tail fat deposition based on multi‐layered data sets. Overall, this research provides foundational resources and a successful case for future investigations of complex traits in sheep through the integration of multi‐omics data sets.

As a crucial economic trait, fat deposition is directly related to carcass quality and feed efficiency in sheep. The purpose of this study was to investigate the polymorphisms of the FGB gene related to fat deposition and detect the expression features of the FGB gene in different adipose tissues of sheep by using Sanger sequencing, MassARRAY® SNP technique, and quantitative real-time PCR (qRT-PCR). Results showed that in the intron region of the FGB gene, a SNP g. 3378953 A > T has been identified, and significant association was found between perirenal fat weight, perirenal fat relative weight, mesenteric fat weight, and mesenteric fat relative weight (P

Scrotal circumference is an important reproductive index of breeding rams, which has a high genetic correlation with ejaculation volume and semen quality. In this study, the scrotal circumference of 1353 male Hu sheep at different stages of development was measured and descriptive statistical analysis was performed. The results showed that the coefficient of variation of scrotal circumference at each stage was greater than 10%, and its heritability were moderately to high, ranging from 0.318 to 0.719. We used PCR amplification and Sanger sequencing to scan the polymorphisms of the IGFALS gene, and performed association analysis with the circumference of the scrotum at different stages. We identified a synonymous mutation g.918 G > C in exon 1 of the IGFALS gene, and this mutation was significantly associated with scrotal circumference at 100, 120, 140, 160 and 180 days (p

Abstract Background Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey. Methods A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival. Results During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80–0.87) for the pre-frailty group, 0.68 (95% CI: 0.64–0.72) for the mild frailty group, and 0.52 (95% CI: 0.48–0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82–0.85). Stratified and sensitivity analyses suggested the robustness of the results. Conclusions The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.

Objective: To study the optimal process conditions of flash extraction and antioxidant activity of American ginseng flower polysaccharides (AGFPs). Methods: American ginseng flower (AGF) as the raw material, the effects of extraction voltage, liquid-material ratio, and extraction time on the yield of AGFPs were explored. The flash extraction process of AGFPs was improved by response surface methodology. The scavenging effect on DPPH and hydroxy free radicals and total reduction capacity of AGFPs were determined to assess the antioxidant activity of AGFPs. Results: The optimal extraction conditions were determined as 130 V of extraction voltage, 30:1 mL/g of liquid-material ratio, and 100 s of extraction time, resulting in an AGFPs yield of 11.12%±0.23%, which agreed with the model prediction. The AGFPs exhibited significant scavenging effects on DPPH and hydroxyl radicals, with IC50 values of 1.34 mg/mL and 1.42 mg/mL, respectively, and had a certain reducing power. Conclusion: These results suggested that flash extraction was an efficient and rapid method for obtaining AGFPs from AGF, and that AGFPs had promising antioxidant potential for further applications. This study can provide a theoretical basis for the development and application of AGF.

Salt stress is a vital environmental stress that severely limits plant growth and productivity. Prohexadione-calcium (Pro-Ca) has been extensively studied to regulate plant growth, development, and stress responses. However, the constructive role of Pro-Ca in alleviating damages and enhancing rice tillers’ morph-physiological characteristics under salt stress remains largely unknown. The results showed that Pro-Ca significantly improved Changmaogu’s (CMG’s) productive tillering rate and the total yield per plant by 17.1% and 59.4%, respectively. At tillering stage, the results showed that Pro-Ca significantly improved the morph-physiological traits, i.e., leaf area, and photosynthetic traits of the rice variety with salt tolerance, under NaCl stress. Pro-Ca significantly increased the seedling index of the main stem and tiller by 10.3% and 20.0%, respectively. Pro-Ca significantly increased the chlorophyll a (chl a), chlorophyll b (chl b) and carotenoid contents by 32.8%, 58.4%, and 33.2%, respectively under NaCl stress. Moreover, Pro-Ca significantly enhanced the net photosynthetic rate (A) by 25.0% and the non-photochemical (NPQ) by 9.0% under NaCl stress. Furthermore, the application of Pro-Ca increased the activities of antioxidant enzymes by 7.5% and 14.7% in superoxide dismutase (SOD), 6.76% and 18.0% in peroxidase (POD), 26.4% and 58.5% in catalase (CAT), 11.0% and 15.9% in ascorbate peroxidase (APX), and Pro-Ca reduced the membrane damage index by 10.8% and 2.19% in malondialdehyde (MDA) content, respectively, for main stem and tiller leaves under NaCl stress. Pro-Ca significantly enhanced the soluble protein content of the main stem and tiller leaves by 2.60% and 6.08%, respectively. The current findings strongly suggested that exogenous application of Pro-Ca effectively alleviated the adverse impact of NaCl stress on the main stem and tillers by enhancing the photosynthetic capacity and antioxidant enzyme activity, and ultimately increased the productive tillering rate and grain yield.

Against the backdrop of a changing global climate, the soil environment may undergo significant changes, directly affecting agricultural productivity and exacerbating global food security issues. Three different substrates were set up in this study, namely, S (high sand and low nutrient content), T (medium sand and medium nutrient content), and TT (low sand and high nutrient content). The results showed that the root/shoot ratio increased as the sand content increased (nutrient content decreased). Rice in different substrates had various degrees of dependence on antioxidant enzymes and antioxidants. For example, seedlings in TT treatment may depend more on ascorbic acid (AsA) compared to T. In addition, compared with S and T, the photosynthetic activity of rice in the optimized substrate (TT) was the highest; the net photosynthetic rate (Pn) of TT seedlings was significantly higher than that of T. This study also detected that the change in substrates affected the gas exchange parameters of rice leaves. The transpiration rate (Tr) and stomatal conductance (Gs) of the TT treatment were higher than those of the T treatment. The results of this study may provide a scientific basis for formulating agricultural management strategies.

IntroductionSalt stress is a major abiotic stress that affects crop growth and productivity. Choline Chloride (CC) has been shown to enhance salt tolerance in various crops, but the underlying molecular mechanisms in rice remain unclear.MethodsTo investigate the regulatory mechanism of CC-mediated salt tolerance in rice, we conducted morpho-physiological, metabolomic, and transcriptomic analyses on two rice varieties (WSY, salt-tolerant, and HHZ, salt-sensitive) treated with 500 mg·L-1 CC under 0.3% NaCl stress.ResultsOur results showed that foliar application of CC improved morpho-physiological parameters such as root traits, seedling height, seedling strength index, seedling fullness, leaf area, photosynthetic parameters, photosynthetic pigments, starch, and fructose content under salt stress, while decreasing soluble sugar, sucrose, and sucrose phosphate synthase levels. Transcriptomic analysis revealed that CC regulation combined with salt treatment induced changes in the expression of genes related to starch and sucrose metabolism, the citric acid cycle, carbon sequestration in photosynthetic organs, carbon metabolism, and photosynthetic antenna proteins in both rice varieties. Metabolomic analysis further supported these findings, indicating that photosynthesis, carbon metabolism, and carbon fixation pathways were crucial in CC-mediated salt tolerance.DiscussionThe combined transcriptomic and metabolomic data suggest that CC treatment enhances rice salt tolerance by activating distinct transcriptional cascades and phytohormone signaling, along with multiple antioxidants and unique metabolic pathways. These findings provide a basis for further understanding the mechanisms of metabolite synthesis and gene regulation induced by CC in rice in response to salt stress, and may inform strategies for improving crop resilience to salt stress.

Abstract Chitobiose (COS2) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS2 can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS2 involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS2 administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob−/− mice. Moreover, the hypolipidemic effect of COS2 and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS2 in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver–gut axis signaling. Graphical Abstract

Objective: To explore the treatment effect and potential mechanism on gut microbiota, nutrition, and metabolism of Fufang Duzheng Tablet (DZGP) on rheumatoid arthritis (RA). Methods: Collagen-induced arthritis rats’ models were established and divided into three groups: model control group (FK), DZGP group (FZ, 0.45 g/kg/d), and methotrexate group (FM, 1.35 mg/kg), which were treated by gavage for 28 days. The physiopathologic changes of joints and body weight in each group were recorded; the morphology of synovial and ankle tissues was observed by hematoxylin-eosin staining, and the level of serum TNF-α and IL-1β was tested by ELISA. UPLC/MS-MS and network pharmacological analysis were used to identify the serum components, and 16S rDNA sequencing analysis was applied to the intestinal contents of rats. Results: DZGP treatment significantly alleviated arthritis symptoms, pathological manifestations, toe thickness, and TNF-α and IL-1β levels in RA rats. We identified 105 metabolites and 18 components in the serum of DZGP-group rats. The main therapeutic targets of DZGP for anti-RA were TP53, epidermal growth factor receptor, and AKT1. Molecular docking showed that there was good binding efficiency between core components and main targets. 16S rDNA sequencing showed that DZGP treatment regulated the structure of the gut microbiota. Conclusion: DZGP showed a good anti-inflammatory effect on RA and played an important role in improving the structure of the gut microbiota in RA rats.

BackgroundIn some MMD patients, the digital subtraction angiography (DSA) examination found, occlusion in the ipsilateral internal carotid artery or middle cerebral artery, accompanied by the formation of numerous moyamoya vessels. Conversely, the contralateral internal carotid artery or middle cerebral artery shows signs of stenosis without the presence of moyamoya vessels. Notably, cerebral perfusion studies reveal a similar or even more severe reduction in perfusion on the occluded side compared to the stenotic side. Importantly, clinical symptoms in these patients are typically attributed to ischemia caused by the stenotic side. This condition is referred to as unstable moyamoya disease (uMMD).ObjectiveThis clinical research focuses on evaluating risk factors related to MMD and developing strategies to minimize postoperative complications. The study aims to analyze vascular characteristics and identify potential risk factors in patients with uMMD.MethodsThe authors reviewed consecutive cases with complete clinical and radiological documentation of patients who underwent surgery between January 2018 and June 2023. Univariate analysis and multivariate logistic regression analysis were employed to understand the risk factors and prognosis of postoperative complications in uMMD.ResultsPostoperative complications were retrospectively analyzed in 1481 patients (aged 14 to 65). Among them, 1,429 patients were assigned to the conventional treatment group, while 52 were in the unstable moyamoya disease group. The uMMD treatment group showed a significantly higher incidence of early postoperative complications such as RIND, cerebral infarction, and cerebral hemorrhage (p

Abstract How to establish a self‐equilibrium configuration is vital for further kinematics and dynamics analyses of tensegrity mechanism. In this study, for investigating tensegrity form‐finding problems, a concise and efficient dynamic relaxation‐noise tolerant zeroing neural network (DR‐NTZNN) form‐finding algorithm is established through analysing the physical properties of tensegrity structures. In addition, the non‐linear constrained optimisation problem which transformed from the form‐finding problem is solved by a sequential quadratic programming algorithm. Moreover, the noise may produce in the form‐finding process that includes the round‐off errors which are brought by the approximate matrix and restart point calculating course, disturbance caused by external force and manufacturing error when constructing a tensegrity structure. Hence, for the purpose of suppressing the noise, a noise tolerant zeroing neural network is presented to solve the search direction, which can endow the anti‐noise capability to the form‐finding model and enhance the calculation capability. Besides, the dynamic relaxation method is contributed to seek the nodal coordinates rapidly when the search direction is acquired. The numerical results show the form‐finding model has a huge capability for high‐dimensional free form cable‐strut mechanisms with complicated topology. Eventually, comparing with other existing form‐finding methods, the contrast simulations reveal the excellent anti‐noise performance and calculation capacity of DR‐NTZNN form‐finding algorithm.

In order to study the effects of deep-sea complex and severe working conditions on the power device of deep-sea wading equipment, taking the contacting mechanical seal for deep-sea propeller as the research object, a two-dimensional axisymmetric finite element model is established. The influence of alternating conditions on the temperature rise of seal face is explored. The pseudo-real condition test of the mechanical seal is conducted on a self-built test rig, and the temperature rise of seal face is monitored. The surface morphology and wear characteristics are measured and analyzed. The results show that the alternating conditions have a significant influence on the temperature field of the seal ring, and the temperature rise of seal face shows an obvious alternating transient characteristic. After the alternating condition test, the end face roughness of the rotating ring increases significantly. The transient working condition makes the contact state between the seal faces unstable. Abrasive wear occurs on the end face, with obvious pits and densely distributed furrows of different depths. The alternating speed has a greater influence on the temperature rise and wear of the end face than that of the alternating medium pressure. The numerical simulation results are in good agreement with the experimental results, which provides a necessary theoretical guidance and experimental basis for the structural design of the mechanical seal of the deep-sea propeller.

Abstract Background Heritable rumen microbiota is an important modulator of ruminant growth performance. However, no information exists to date on host genetics-rumen microbiota interactions and their association with phenotype in sheep. To solve this, we curated and analyzed whole-genome resequencing genotypes, 16S rumen-microbiota data, and longitudinal body weight (BW) phenotypes from 1150 sheep. Results A variance component model indicated significant heritability of rumen microbial community diversity. Genome-wide association studies (GWAS) using microbial features as traits identified 411 loci-taxon significant associations (P < 10−8). We found a heritability of 39% for 180-day-old BW, while also the rumen microbiota likely played a significant role, explaining that 20% of the phenotypic variation. Microbiota-wide association studies (MWAS) and GWAS identified four marker genera (Bonferroni corrected P < 0.05) and five novel genetic variants (P < 10−8) that were significantly associated with BW. Integrative analysis identified the mediating role of marker genera in genotype influencing phenotype and unravelled that the same genetic markers have direct and indirect effects on sheep weight. Conclusions This study reveals a reciprocal interplay among host genetic variations, the rumen microbiota and the body weight traits of sheep. The information obtained provide insights into the diverse microbiota characteristics of rumen and may help in designing precision microbiota management strategies for controlling and manipulating sheep rumen microbiota to increase productivity. Video Abstract

Objective: For the extraction of polysaccharides from American ginseng fruits, the extraction process was optimized in combination with response surface methodology, and to investigate whether polysaccharides from American ginseng fruits had antioxidant activity in vitro. Methods: In this study, polysaccharides were extracted from fresh American ginseng fruits by water extraction and alcohol precipitation method. The extraction process was optimized using single factor tests as well as response surface methodology. In vitro antioxidant activity studies of polysaccharides from American ginseng fruits were conducted from three aspects: DPPH radical scavenging rate, hydroxyl radical scavenging rate as well as reducing power. Results: The optimal process parameters were as follows: the extraction time was 2.5 h, the concentration of ethanol was 80%, the feed to liquid ratio of 1:16 g/mL, and the measured average value of polysaccharide yield was 29.47%±0.65%, which was comparable to the model predicted value. In vitro antioxidant activities of polysaccharides from American ginseng fruits were examined in the following three aspects. When the concentration of polysaccharides was 3.4 mg/mL, the DPPH radical scavenging rate was 75.14%±0.65%, and IC50 value was 0.71 mg/mL. When the concentration of polysaccharide was 3.4 mg/mL, the scavenging rate against hydroxyl radicals could reach 71.82%±1.43%, and IC50 value was 0.87 mg/mL. When the concentration of polysaccharides was 1.0 mg/mL, the total reducing power reached 0.730, and its in vitro antioxidant capacity was enhanced with increasing concentrations of polysaccharides from American ginseng fruits. Conclusion: The experimental results of antioxidant activities illustrated that polysaccharides from American ginseng fruits had better antioxidant activities. This study may provide a theoretical basis for further development and utilization of polysaccharides from American ginseng fruits, and ensure that traditional Chinese medicine resources can be fully utilized.

In Northeast China’s black soil rice cropping area, nitrogen (N) application is lower than in the south, yet excessive N fertilizer use persists, particularly in base fertilizers. This study aimed to assess the impact of reduced N and increased planting density on rice yields and photosynthetic matter production. From 2019 to 2020, a field split-plot experiment was conducted with two N rates (conventional N, CN: 120 kg ha−1 and reduced basal N, RN: 108 kg ha−1) and two planting densities (D1: 33.3 × 104 hills ha−1 and D2: 27.8 × 104 hills ha−1) using the rice varieties Kongyu131 (KY131) and Kendao24 (KD24). The results showed that RN increased the effective panicle formation rate but decreased the tiller numbers, dry matter accumulation, stems/sheaths transport capacity, leaf photosynthetic capacity, and yield by 2.67% compared to CN. D1 significantly boosted the dry matter accumulation, stems/sheaths transport, effective panicles, grains per square meter, and yield by 8.26% compared to D2. Interaction analysis revealed that RN under D2 conditions reduced the effective panicle percentage, harvest index, filled grain number, leaf area index (LAI), crop growth rate (CGR), and net assimilation rate (NAR) but increased the seed setting rate and 1000-grain weight. Under D1, RN reduced the LAI, CGR, and NAR at the tillering and heading stages but increased the NAR post-heading. Compared to CND2, RND1 increased the biomass, stems/sheaths transport, LAI, CGR, NAR, seed setting rate, 1000-grain weight, panicle numbers, and filled grains per square meter, compensating for the lower harvest index and effective panicle rate, achieving a 5.36% yield increase. KD24 outperformed KY131 in yield improvement. In summary, using 108 kg ha−1 with a planting density of 33.3 × 104 hills ha−1 promotes tillering, enhances photosynthetic substance production stems/sheaths dry matter transport, and increases rice yields.

The uncontrolled bacterial infection-induced cytokine storm and sequential immunosuppression are commonly observed in septic patients, which indicates that the activation of phagocytic cells and the efficient and timely elimination of bacteria are crucial for combating bacterial infections. However, the role of dysregulated immune cells and their disrupted function in sepsis remains unclear. Here, we found that macrophages exhibited the impaired endocytosis capabilities in sepsis by Single-cell RNA sequencing and bulk RNA sequencing. Caveolae protein Caveolin-1 (Cav-1) of macrophages was inactivated by SHP2 rapidly during Escherichia coli (E.coli) infection. Allosteric inhibitor of SHP2 effectively maintains Cav-1 phosphorylation to enhance macrophage to endocytose and eliminate bacteria. Additionally, TLR4 endocytosis of macrophage was also enhanced upon E.coli infection by SHP099, inducing an increased and rapidly resolved inflammatory response. In vivo, pretreatment or posttreatment with inhibitor of SHP2 significantly reduced the bacterial burden in organs and mortality of mice subjected E.coli infection or CLP-induced sepsis. The cotreatment of inhibitor of SHP2 with an antibiotic conferred complete protection against mortality in mice. Our findings suggest that Cav-1-mediated endocytosis and bacterial elimination may play a critical role in the pathogenesis of sepsis, highlighting inhibitor of SHP2 as a potential therapeutic agent for sepsis.

Abstract Lambert–Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX‐1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56‐year‐old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX‐1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow‐up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long‐term follow‐up and screening for occult SCLC in LEMS patients with positive SOX‐1 antibodies are very important.

Fecal scores are crucial for assessing the digestive and gastrointestinal status of animals. The Bristol fecal scoring system is a commonly used method for the subjective evaluation of host feces, there is limited research on fecal scoring standards for fattening Hu sheep. In this study, Hu sheep were collected for rumen, rectum, and colon contents for 16S rDNA sequencing. 514 Hu sheep feces were scored based on the Bristol fecal scoring system, and production performance at each stage was measured. Finally, we developed the scoring standard of the manure of Hu sheep in the fattening period (a total of five grades). The result shows that moisture content significantly increased with higher grades (p < 0.05). We analyzed the relationship between fecal scores and production traits, blood indices, muscle nutrients, and digestive tract microorganisms. The growth traits (body weight, body height, body length, average daily gain (ADG), and average daily feed intake (ADFI) during 80–180 days), body composition traits of the F3 group, and the carcass traits were found to be significantly higher (p < 0.05) than those of the F1 and F2 groups. There was no significant difference in gastrointestinal microflora diversity among all groups (p > 0.05). Significant differences were observed in Aspartate aminotransferase, Glucose, Total bilirubin, and Red Blood Cell Count between groups (p < 0.05). The mutton moisture content in group F4 was significantly higher than in the other groups, and the protein content was also the lowest (p < 0.05). The results of the correlation analysis demonstrated that Actinobacteria, Peptostreptococcaceae, Acidaminococcales, Gammaproteobacteria, and Proteobacteria were the significant bacteria affecting fecal scores. In addition, Muribaculaceae and Oscillospiraceae were identified as the noteworthy flora affecting growth performance and immunity. This study highlights the differences in production traits and blood indicators between fecal assessment groups and the complex relationship between intestinal microbiota and fecal characteristics in Hu sheep, suggesting potential impacts on animal performance and health, which suggest strategies for improved management.

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.

Ferulic acid (FA) and ferulic acid methyl ester (FAM) are important phenolic compounds in Baijiu. In this study, the interaction of FA and FAM with human serum albumin (HSA) and lysozyme (LZM) was investigated using multispectral methods and molecular dynamics simulation. FA and FAM could interact with HSA and LZM, changing the conformation and hydrophilicity of the protein. The quenching mechanisms of FA-HSA, FA-LZM, FAM-HSA, and FAM-LZM were all static-quenching. In the FA-HSA, FAM-HSA, and FA-LZM systems, the interaction forces were mainly hydrophobic interactions and hydrogen bonding. In the FAM-LZM system, the interaction forces were mainly hydrophobic interactions, hydrogen bonding, and van der Waals force. Common metal ions such as K+, Ca2+, Cu2+, Mg2+, and Mn2+ could affect the binding ability of FA and FAM to HSA and LZM. Moreover, FA and FAM could increase the stability of HSA and LZM, and the protein bound to FA/FAM was more stable than the free protein. FA and FAM had varying degrees of impact on the physiological activities of HSA and LZM. This study provides relevant information on the interactions and metabolic mechanisms of FA and its derivatives with endogenous proteins.

Abstract Background Plant immunity relies on the perception of immunogenic signals by cell-surface and intracellular receptors and subsequent activation of defense responses like programmed cell death. Under certain circumstances, the fine-tuned innate immune system of plants results in the activation of autoimmune responses that cause constitutive defense responses and spontaneous cell death in the absence of pathogens. Results Here, we characterized the onset of leaf death 12 (old12) mutant that was identified in the Arabidopsis accession Landsberg erecta. The old12 mutant is characterized by a growth defect, spontaneous cell death, plant-defense gene activation, and early senescence. In addition, the old12 phenotype is temperature reversible, thereby exhibiting all characteristics of an autoimmune mutant. Mapping the mutated locus revealed that the old12 phenotype is caused by a mutation in the Lectin Receptor Kinase P2-TYPE PURINERGIC RECEPTOR 2 (P2K2) gene. Interestingly, the P2K2 allele from Landsberg erecta is conserved among Brassicaceae. P2K2 has been implicated in pathogen tolerance and sensing extracellular ATP. The constitutive activation of defense responses in old12 results in improved resistance against Pseudomonas syringae pv. tomato DC3000. Conclusion We demonstrate that old12 is an auto-immune mutant and that allelic variation of P2K2 contributes to diversity in Arabidopsis immune responses.

Abstract The most abundant human milk oligosaccharide 2′‐fucosyllactose (2′‐FL) is a valuable component that has gained significant attention from the food industry. To biosynthesize 2′‐FL, various Escherichia coli K12 derivatives have been genetically modified. To further enhance the application performance of E. coli K12, a novel E. coli K12 derivative BL27 was used as a chassis cell in this study, and modular pathway enhancement was performed to achieve de novo synthesis of 2′‐FL. The futC gene encoding α‐1,2‐fucosyltransferase was introduced, and the wcaJ gene was knocked out to prevent the conversion of GDP‐ l‐fucose to colanic acid. Next, the effects of overexpressing transcriptional regulators rcsA and rcsB and knocking out transcriptional regulators mcbR and waaF were evaluated to optimize the colanic acid pathway. The expression level, solubility, and activity of FutC were improved through genomic integration, TrxA‐tag fusion, and double mutation in F40S/Q237S. Fermentation conditions were optimized to achieve maximum 2′‐FL titers of 3.86 and 23.56 g/L in shake‐flask and fed‐batch cultivation, respectively. Over 85% of the products were successfully excreted into extracellular and almost no byproduct 2′,3‐difucosyllactose was generated. This study has explored a new microbial platform and modification strategies for the synthesis of 2′‐FL and provides opportunities for its commercial production.

Abstract The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.

Abstract Cancer cells exhibit elevated lipid synthesis. In breast and other cancer types, genes involved in lipid production are highly upregulated, but the mechanisms that control their expression remain poorly understood. Using integrated transcriptomic, lipidomic, and molecular studies, here we report that DAXX is a regulator of oncogenic lipogenesis. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipogenesis, and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and DAXX mutants unable to bind SREBP1/2 have weakened activity in promoting lipogenesis and tumor growth. Remarkably, a DAXX mutant deficient of SUMO-binding fails to activate SREBP1/2 and lipogenesis due to impaired SREBP binding and chromatin recruitment and is defective of stimulating tumorigenesis. Hence, DAXX’s SUMO-binding activity is critical to oncogenic lipogenesis. Notably, a peptide corresponding to DAXX’s C-terminal SUMO-interacting motif (SIM2) is cell-membrane permeable, disrupts the DAXX-SREBP1/2 interactions, and inhibits lipogenesis and tumor growth. These results establish DAXX as a regulator of lipogenesis and a potential therapeutic target for cancer therapy.

In order to compare the effects of fermentation by different strains on the quality of noni fruit Jiaosu, noni juice was fermented with Lactobacillus rhamnosus 12 (LGG), Lactobacillus plantarum 08 (LP-08), Lactobacillus plantarum K11 (LP-K11), Pediococcus pentosaceus 03 (PP) and Bifidobacterium lactis 36 (BLA), respectively. The effects of different strains on the physicochemical properties, antioxidant activities and flavor substances of noni juice were investigated. The results showed that among the five strains, LP-08 had the strongest organic acid-producing ability at the end of fermentation, followed by BLA. LP-08 also had the strongest ability to utilize reducing sugar. After 5 days of fermentation, the polyphenol contents were significantly increased by 29.74% and 28.54% from the original level (P