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Abstract Four-membered carbocycles are among the most sought-after backbones which are commonly found in biologically active molecules. However, difficulties on their producing are existing due to its highly strained ring system. On the other hand, cyclobutanols can be straightforwardly prepared and can serves as precursors for synthesizing cyclobutane derivatives. Here we report an example of regioselective aminocarbonylation of cyclobutanols in which the cyclobutane core remained intact. The method exhibits good functional group compatibility, as well as high regio- and stereoselectivity, offering new pathways for synthesizing several pharmaceuticals. Furthermore, this strategy enables the rapid installation of cyclobutane as a conformational restricted skeleton, greatly facilitating direct access to valuable drug molecules that require conformational restriction.

Abstract Hydrogen-bonded assembly of multiple components into well-defined icosahedral capsules akin to virus capsids has been elusive. In parallel, constructing robust zeolitic-like cluster-based supramolecular frameworks (CSFs) without any coordination covalent bonding linkages remains challenging. Herein, we report a cluster-based pseudoicosahedral H-bonded capsule Cu60, which is buckled by the self-organization of judiciously designed constituent copper clusters and anions. The spontaneous formation of the icosahedron in the solid state takes advantage of 48 charge-assisted CH···F hydrogen bonds between cationic clusters and anions (PF6 -), and is highly sensitive to the surface protective ligands on the clusters with minor structural modification inhibiting its formation. Most excitingly, an extended three-periodic robust zeolitic-like CSF, is constructed by edge-sharing the resultant icosahedrons. The perpendicular channels of the CSF feature unusual 3D orthogonal double-helical patterns. The CSF material not only keeps its single-crystal character in the desolvated phase, but also exhibits excellent chemical and thermal stabilities as well as long-lived phosphorescence emission.

Abstract To examine the association and modifiable risk factors between grip strength (GS) and Parkinson’s disease (PD) incidence considering genetic factors, a total of 411,648 individuals without PD at baseline from the UK Biobank were included. GS was measured by a hydraulic dynamometer. The polygenic risk score assessed the genetic predisposition. Multivariable Cox regression models were performed. During a median follow-up of 12.3 years, 2409 individuals developed PD. Compared with those with high GS, low-GS individuals had a 58.5% increased risk of PD (42.7%–76.1%), and 16.3% of this excess risk could be explained by adjusted risk factors. Low GS and high genetic predisposition contribute to the highest PD risk in an additive interaction. We observed that low GS was associated with higher PD incidence, particularly among individuals with high genetic predisposition. In addition to enhancing GS, interventions targeting risk factors (e.g., unhealthy lifestyles) might also reduce the excess risk.

Abstract Removal of confined space carbon dioxide (CO2) that is in low concentration and with coexisting water is necessary but challenging by physical adsorption method. To make the removal process effective, rendering the nanopore surface hydrophobic to resist water is the popular way. Instead of preventing water from occupying the nanopores, in this work, we propose to utilize the guest water for the spatially selective formation of local surface bound water and further induce the preferential CO2 capture. We observe an anomalous enhancement of CO2 capture performance under humid conditions over carbon nanopores with spatially selective polar sites. It is evidenced that the surface bound water is formed at non-CO2-selective areas of polar carbon nanopores, thus creating additional CO2 trapping sites. This work may inspire the design of environment tolerable materials for molecular separation and purification under harsh conditions.

Abstract In this paper, we would like to point out that in the scenario that the right-handed neutrinos suddenly gain some masses much larger than the temperature of the Universe at that time so that the washout effects for the lepton asymmetry generated from their decays can be neglected safely, the purely flavored leptogenesis scenario (in which the total CP asymmetries for the decays of the right-handed neutrinos are vanishing and the successful leptogenesis is realized by virtue of the flavor non-universality of the washout effects) cannot work in the usual way any more. For this problem, we put forward that the flavor non-universality of the conversion efficiencies from the flavored lepton asymmetries to the baryon asymmetry via the sphaleron processes may play a crucial role. And we will study if the requisite baryon asymmetry can be successfully reproduced from such a mechanism in the scenarios that the right-handed neutrino masses are hierarchical and nearly degenerate, respectively. A detailed study shows that this mechanism can be viable in both these two scenarios.

Abstract Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand’s C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide–receptor system.

Diarrheas are common risks faced by piglets during the weaning period. This study investigated the alleviating effects of artificial parasin I protein (API) on growth performance and intestinal health of weaned pigs upon enterotoxigenic Escherichia coli (ETEC) challenge. Sixty piglets were randomly divided into five groups and fed a basal diet (CON) or basal diet supplemented with API at 0, 750, and 1500 mg/kg or antibiotics for 5 weeks. On d 15 and 25, piglets were challenged with ETEC K88 except for the CON group. Before the ETEC challenge (d 1–14), dietary API supplementation improved growth performance, and 750 mg API increased (P

Abstract Background Due to the high prevalence of multimorbidity and realistic health service demands for fall prevention, there is growing interest in the association between multimorbidity and falls. Our study aimed to identify multimorbidity patterns among Chinese older adults and explore the association between multimorbidity patterns and falls. Methods Data from 4,579 Chinese community-dwelling older adults was included in this analysis. Information regarding falls and 10 chronic conditions was collected. An exploratory factor analysis was performed to determine multimorbidity patterns. Regression models were fitted to explore the associations of individual chronic disease or multimorbidity patterns with falls. Results Among 4,579 participants, 368 (8.0%) were defined as fallers, including 92 (2.0%) frequent fallers, and multimorbidity affected 2,503 (54.7%) participants. Older adults with multimorbidity were more likely to be fallers [odds ratio (OR) = 1.3, P = 0.02] and frequent fallers (OR = 1.7, P = 0.04). Three multimorbidity patterns were identified (i.e., cardiovascular-metabolic diseases, psycho-cognitive diseases and organic diseases), and the associations between psycho-cognitive diseases/organic diseases and prevalent falls or frequent falls were found to be significant. Conclusions The psycho-cognitive disease pattern and organic disease pattern are significantly associated with falls. Therefore, more attention should be paid to patients with psycho-cognitive diseases and timely, targeted diagnostic and treatment services should be provided in fall prevention.

Abstract Background Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection. Methods The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented. Results A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P

Abstract Objective To investigate the relationship between central venous pressure (CVP) and acute right ventricular (RV) dysfunction in critically ill patients on mechanical ventilation. Methods This retrospective study enrolled mechanically ventilated critically ill who underwent transthoracic echocardiographic examination and CVP monitoring. Echocardiographic indices including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tricuspid lateral annular systolic velocity wave (S’) were collected to assess RV function. Patients were then classified into three groups based on their RV function and presence of systemic venous congestion as assessed by inferior vena cava diameter (IVCD) and hepatic vein (HV) Doppler: normal RV function (TAPSE ≥ 17 mm, FAC ≥ 35% and S’ ≥9.5 cm/sec), isolated RV dysfunction (TAPSE 20 mm and HV S

Lakes are important carbon sinks in terrestrial ecosystems. Currently, most of lake carbon burial research in China only considers organic carbon burial and has neglected inorganic carbon burial, which will lead to an underestimation of the total carbon burial capacity of lakes. This situation is particularly significant in the humid eastern plain region. In order to comprehensively understand the carbon burial characteristics of lakes in the eastern plain and evaluate the contributions of organic and inorganic carbon burial to total carbon burial more reasonably. This research chooses Hongze Lake as study site, which is a representative lake in the eastern plain region. Based on the 210Pb-137Cs chronological sequence, combined with the C/N and δ13C characteristics in sediments, the carbon burial characteristics of Hongze Lake sediments in the past 60 years were explored by analyzing the spatiotemporal changes of organic and inorganic carbon content in typical rock cores (numbered HZH-12) and 11 other surface sediments. C/N and δ13C shows that endogenous organic carbon is the main source of organic carbon inHongze Lake . The significant synergistic changes in the accumulation rates of organic and inorganic carbon over the past 60 years (R2=0.76, p

Abstract Background Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. Methods In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. Results We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. Conclusions This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis. Graphical Abstract

Abstract Background At present, heat stress (HS) has become a key factor that impairs broiler breeding industry, which causes growth restriction and poor meat quality of broilers. Selenium (Se) is an excellent antioxidant and plays a unique role in meat quality improvement. Recent years, nano-selenium (NanoSe) has received tremendous attention in livestock production, due to its characteristic and good antibacterial performance in vitro. Here, we developed the heat stressed-broiler model to investigate the protective effects of NanoSe on growth performance and meat quality of broilers and compare whether there are differences with that of other Se sources (Sodium selenite, SS; Selenoyeast, SeY; Selenomethionine, SeMet). Results HS jeopardized the growth performance and caused poor meat quality of breast muscle in broilers, which were accompanied by lowered antioxidant capacity, increased glycolysis, increased anaerobic metabolism of pyruvate, mitochondrial stress and abnormal mitochondrial tricarboxylic acid (TCA) cycle. All Se sources supplementation exhibited protective effects, which increased the Se concentration and promoted the expression of selenoproteins, improved the mitochondrial homeostasis and the antioxidant capacity, and promoted the TCA cycle and the aerobic metabolism of pyruvate, thus improved the breast muscle meat quality of broilers exposed to HS. However, unlike the other three Se sources, the protective effect of NanoSe on meat quality of heat stressed-broilers was not ideal, which exhibited limited impact on the pH value, drip loss and cooking loss of the breast muscle. Compared with the other Se sources, broilers received NanoSe showed the lowest levels of slow MyHC, the highest levels of fast MyHC and glycogen, the highest mRNA levels of glycolysis-related genes (PFKM and PKM), the highest protein expression of HSP60 and CLPP, and the lowest enzyme activities of GSH-Px, citroyl synthetase (CS) and isocitrate dehydrogenase (ICD) in breast muscle. Consistent with the SS, the Se deposition in breast muscle of broilers received NanoSe was lower than that of broilers received SeY or SeMet. Besides, the regulatory efficiency of NanoSe on the expression of key selenoproteins (such as SELENOS) in breast muscle of heat stressed-broilers was also worse than that of other Se sources. Conclusion Through comparing the meat quality, Se deposition, muscle fiber type conversion, glycolysis, mitochondrial homeostasis, and mitochondrial TCA cycle-related indicators of breast muscle in heat stressed broilers, we found that the protective effects of organic Se (SeY and SeMet) are better than that of inorganic Se (SS) and NanoSe. As a new Se source, though NanoSe showed some protective effect on breast muscle meat quality of heat stressed broilers, the protective effect of NanoSe is not ideal, compared with other Se sources.

Abstract Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC.

Abstract Theanine (Thea) is a unique metabolite in tea plants, but its physiological functions remain elusive. A low soil pH increases cadmium (Cd) availability, affecting the quality of tea plant products. In this study, we found that Thea reversed the Cd-induced reduction in free amino acid (FAA) and caffeine (CAF) in the young tea leaves, as well as the down-regulation in the expression of nitrate transporters CsNRT1.2 and CsNRT2.5, and genes responsible for the nitrogen (N) assimilation. We demonstrated that Thea could alleviate Cd-induced oxidative stresses and enhance photosynthesis. Moreover, an ATP-binding cassette (ABC) transporter, CsABCG11.2, could uptake distinct Cd substrates and the five major amino acids in tea plants. Heterologous expression of CsABCG11.2 in yeast indicated a competitive absorption between Cd and Thea in a concentration-dependent pattern. CsABCG11.2-overexpressing Arabidopsis plants exhibited increased sensitivity to Cd due to enhanced Cd concentration, accumulation in the shoots, and reduction in the primary root length. Exogenous application of Thea at environmentally regular levels attenuated the adverse effects of Cd-induced growth inhibition and chlorosis in CsABCG11.2-overexpressing Arabidopsis plants. Knockdown of CsABCG11.2 tea plants significantly lowered Cd levels in young shoots. Our results suggest that Thea plays beneficial roles in alleviating Cd stress directly or indirectly by modulating CsABCG11.2-mediated Cd uptake and translocation within plants.

Macrophage-myofibroblast transformation (MMT) has emerged as a discovery in the field of fibrotic disease research. MMT is the process by which macrophages differentiate into myofibroblasts, leading to organ fibrosis following organ damage and playing an important role in fibrosis formation and progression. Recently, many new advances have been made in studying the mechanisms of MMT occurrence in fibrotic diseases. This article reviews some critical recent findings on MMT, including the origin of MMT in myofibroblasts, the specific mechanisms by which MMT develops, and the mechanisms and effects of MMT in the kidneys, lungs, heart, retina, and other fibrosis. By summarizing the latest research related to MMT, this paper provides a theoretical basis for elucidating the mechanisms of fibrosis in various organs and developing effective therapeutic targets for fibrotic diseases.

This study aimed to investigate the effect of L-theanine in regulating the intestinal antioxidant of weaned piglets and its underlying mechanism. We found that L-theanine increased the activities of antioxidant enzymes and the level of GSH, while decreased the MDA content of weaned piglet jejunum mucosa and H2O2-induced IPEC-J2 cells. In addition, the mRNA expression of SOD1, SOD2, GPx1, CAT, HO-1 and NQO1 was also significantly increased in jejunum mucosa and H2O2-induced IPEC-J2 cells by L-theanine treatment. Furthermore, L-theanine promoted the nuclear Nrf2 expression and decreased the keap1 expression. However, blocking of Nrf2 signaling by ML385 (the Nrf2 inhibitor) repressed the promoting effects of L-theanine on the activities of antioxidative enzymes and the expression of antioxidant related genes, while increased the MDA content and keap1 expression in IPEC-J2 cells. These data provided the first evidence that L-theanine improved intestinal antioxidant ability of weaned piglets by activating Nrf2 signaling pathway.

The massive yield of brewers’ spent grain (BSG) waste inevitably threaten environmental health. Here, solid-state fermentation (SSF) technology featuring multi-strain (MS) inoculation and high-throughput sequencing technology were employed to facilitate the sustainable and clean recycling of BSG waste while revealing the associated underlying microbiological and metabolic mechanisms. MS inoculation displayed a lower pH value (3.91 vs. 4.12) and neutral detergent fiber content (446.24 vs. 476.23 g/kg DM), a higher levels of lactic acid (86.64 vs. 33.07 g/kg DM), acetic acid (6.13 vs. 4.87 g/kg DM), propionic acid (2.78 vs. 2.18 g/kg DM) and crude protein (307.5 vs. 289.15 g/kg DM) than those in the control group. Moreover, MS inoculation inhibited the formation of non-protein-N and ammonia-N, and spoilage microorganism resuscitation, while enhanced substrate preservation. Microbiologically, during the SSF, the group treated with MS inoculation exhibited an increase in the relative abundance of Leuconostoc (0.58%∼6.60%), Weissella (6.22%∼15.42%), Enterococcus (3.15%∼9.08%), Bacillus (17.63%∼31.29%), Lactobacillus (12.89%∼8.29%), Pseudoalteromonas (12.87%∼16.29%), and a decrease in the relative abundance of Acinetobacter (0.79%∼0.02%) and Enterobacteriaceae (0.78%∼0.24%). Metabolically, starch and sucrose metabolism, arginine and proline metabolism, and phenylalanine metabolism significantly influenced the quality of extruded BSG fermented by MS during SSF. The examination of the correlation between the microbiota, metabolites, and fermentation parameters revealed that complex interactions between microbes and the environment factors impact metabolite production. Collectively, inoculating with MS improved fermentation quality and stability, facilitated the clean recycling of BSG, which is linked to complex interactions among microbes, the environment factors and metabolite production.

BackgroundWheat germ is known for its antioxidant, anti-inflammatory, and disease resistance properties in animals. However, its effect on the gut of Sichuan white geese remains unclear.MethodIn this study, thirty 250-day-old geese were divided into three equal groups, the control group, LWG group (21.8% wheat germ) and HWG group (43.6% wheat germ), the experiment lasted 12 weeks. We assessed various aspects of geese intestinal health, including barrier function, digestibility, antioxidant capacity, immunity, microbiota, and metabolism.ResultsThe study revealed a significant increase in villus height (VH), villus height-to-crypt depth (VH/CD) ratio, amylase, and lipase activities in the duodenum and ileum, increased putrescine levels in the duodenum and jejunum, as well as spermidine levels in the jejunum (P < 0.05). LWG increased the total antioxidant capacity (T-AOC) in the duodenum, while decreasing levels of intestinal malondialdehyde (MDA), serum lipopolysaccharide (LPS), interleukin-6 (IL-6), and diamine oxidase (DAO) activity (P < 0.05). Furthermore, LWG increased the relative abundance of Oscillospiraceae_unclassified, Ligilactobacillus, and Roseburia, as well as increased levels of acetic acid, butyric acid, and valeric acid, while decreasing the relative abundance of Subdoligranulum, Flavonifractor, and Klebsiella. Additionally, we observed 17 up-regulated genes and 25 down-regulated genes in the jejunum, which are associated with the cell cycle and immunity. These genes play roles in pathways such as the p53 signaling pathway, cell cycle regulation, and pathways associated with immune modulation. On the other hand, HWG increased intestinal VH and spermidine levels, as well as amylase and lipase activities in the duodenum (P < 0.05). It also elevated ileal T-AOC and sIgA levels (P < 0.05), while reducing intestinal MDA content, serum LPS levels, DAO activity, and propionic acid in cecum contents (P < 0.05). Moreover, HWG increased the relative abundance of Ligilactobacillus, Oscillospiraceae_unclassified, and Roseburia (P < 0.05).ConclusionOverall, wheat germ diets, particularly the LWG diet demonstrated the ability to enhance antioxidant capacity, digestibility, immunity, and barrier properties of the intestinal tract, while modulating the gut microbiota and metabolism. Therefore, wheat germ diets hold promise in improving intestinal health by preserving barrier function and regulating flora structure.

Tea tree is a fluorine (F)-enriched plant, leading to much concern about the safety of drinking tea from tea tree (Camellia sinensis (L.) Kuntze). Tea tree is a perennial leaf-harvested crop, and tea production in China is generally categorized as spring tea, summer tea and autumn tea in its annual growth rounds. However, the seasonally dynamic changes of F content and accumulation in the leaves and its drinking safety are poorly understood. In this study, 85 tea varieties cultivated under the same conditions were investigated to analyze the seasonal variation of F content and it’s relationships with F accumulation, aluminum (Al), calcium (Ca) and manganese (Mn) and hazard quotient (HQ) in young leaves (one bud and two leaves, YL) and mature leaves (canopy leaves, ML). The average F contents and accumulations were 350 mg kg−1 and 203 g ha−1 in YL, and they were 2451 mg kg−1 and 2578 g ha−1 in ML, respectively, with F mainly accumulated in ML. As the growing season progresses, the F content showed a gradual increase in YL, while a decrease in ML, inferring that F may be redistributed from mature leaves to young leaves. Additionally, the F content was quite different among tea varieties which are suitable for processing oolong tea, green tea, and black tea, with higher F accumulation in oolong tea varieties than in green and black tea varieties. Moreover, F content and accumulation could be obviously affected by the geographical origin of the tea tree varieties, with significantly higher F content in the varieties from F rich fluorite belts than other regions. Furthermore, F content and accumulation showed a significant positive correlation with the content of Al and Mn (p < 0.05). Based on a daily tea consumption of 8.7 g, the HQ was investigated to show that the proportion of tea leaves with HQ

Abstract Background Verticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality worldwide. The strain KRS010 was isolated from the seed of Verticillium wilt-resistant Gossypium hirsutum cultivar “Zhongzhimian No. 2.” Results The strain KRS010 has a broad-spectrum antifungal activity to various pathogenic fungi as Verticillium dahliae, Botrytis cinerea, Fusarium spp., Colletotrichum spp., and Magnaporthe oryzae, of which the inhibition rate of V. dahliae mycelial growth was 73.97% and 84.39% respectively through confrontation test and volatile organic compounds (VOCs) treatments. The strain was identified as Bacillus altitudinis by phylogenetic analysis based on complete genome sequences, and the strain physio-biochemical characteristics were detected, including growth-promoting ability and active enzymes. Moreover, the control efficiency of KRS010 against Verticillium wilt of cotton was 93.59%. After treatment with KRS010 culture, the biomass of V. dahliae was reduced. The biomass of V. dahliae in the control group (Vd991 alone) was 30.76-folds higher than that in the treatment group (KRS010+Vd991). From a molecular biological aspect, KRS010 could trigger plant immunity by inducing systemic resistance (ISR) activated by salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Its extracellular metabolites and VOCs inhibited the melanin biosynthesis of V. dahliae. In addition, KRS010 had been characterized as the ability to promote plant growth. Conclusions This study indicated that B. altitudinis KRS010 is a beneficial microbe with a potential for controlling Verticillium wilt of cotton, as well as promoting plant growth.

Abstract Background Oral frailty has become a worldwide problem among older adults. Although researchers have conducted various studies on oral frailty, its definition remains controversial. Purpose To clarify the concept of oral frailty. Methods Online databases PubMed, Web of Science, CINAHL, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang database were searched from inception to September 20, 2023. The reference lists of relevant studies were searched manually. Eligible articles, theses, and books were analyzed using Walker & Avant’s concept analysis model. Results The attributes of oral frailty were abnormal oral structure and/or decline in multi-faceted oral function and coexisting decline in physical, cognitive and social functions. Its antecedents were aging, social frailty, and severe periodontitis, whereas its consequences were decline in physical health and mental health, social withdrawal, lower quality of life and systemic frailty. Conclusion Oral frailty could result in worse conditions among older adults physically, psychologically and socially. Tools based on the concept analysis need to be developed to comprehensively assess oral frailty.

Abstract Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

Given the substantial environmental pollution from industrial expansion, environmental protection has become particularly important. Nowadays, anion exchange membranes (AEMs) are widely used in wastewater treatment. With the use of polyvinyl alcohol (PVA), ethylene-vinyl alcohol (EVOH) copolymer, and methyl iminodiacetic acid (MIDA), a series of cross-linked AEMs were successfully prepared using the solvent casting technique, and the network structure was formed in the membranes due to the cross-linking reaction between PVA/EVOH and MIDA. Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy were used to analyze the prepared membranes. At the same time, its comprehensive properties which include water uptake, linear expansion rate, ion exchange capacity, thermal stability, chemical stability, and mechanical stability were thoroughly researched. In addition, diffusion dialysis performance in practical applications was also studied in detail. The acid dialysis coefficient (UH+) ranged from 10.2 to 35.6 × 10−3 m/h. Separation factor (S) value ranged from 25 to 38, which were all larger than that of the commercial membrane DF-120 (UH+: 8.5 × 10−3 m/h, S: 18.5). The prepared membranes had potential application value in acid recovery. HIGHLIGHTS The preparation method of the membranes is simple.; The membrane is based on PVA/EVOH/MIDA.; The raw materials are cheap and easy to obtain.; The acid recovery performance is excellent by diffusion dialysis.; The prepared membranes had potential application value in acid recovery.;

The evaluation of equipment comprehensive support effectiveness is affected by research and development support, personnel support, equipment support, maintenance support, and other aspects. How to evaluate the equipment’s comprehensive support effectiveness scientifically, objectively, and reasonably plays an important role in improving the equipment’s comprehensive support effectiveness of the army and promoting the generation of combat effectiveness of the army. Based on the research and analysis of related issues, the evaluation index system of equipment comprehensive support effectiveness is constructed. The analytic hierarchy process (AHP) and fuzzy comprehensive evaluation are combined to determine the weight of each evaluation index factor and the reasonable evaluation of support effectiveness. Finally, the equipment’s comprehensive support effectiveness is evaluated through the example analysis system. The results show that this method has certain reference significance and guidance for scientific and reasonable evaluation of equipment comprehensive support effectiveness.

Abstract Background Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. Methods The National Health and Nutrition Examination Survey (2013–2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR)

Abstract Powered by data-driven technologies, precision agriculture offers immense productivity and sustainability benefits. However, fragmentation across farmlands necessitates distributed transparent automation. We developed an edge computing framework complemented by auction mechanisms and fuzzy optimizers that connect various supply chain stages. Specifically, edge computing offers powerful capabilities that enable real-time monitoring and data-driven decision-making in smart agriculture. We propose an edge computing framework tailored to agricultural needs to ensure sustainability through a renewable solar energy supply. Although the edge computing framework manages real-time crop monitoring and data collection, market-based mechanisms, such as auctions and fuzzy optimization models, support decision-making for smooth agricultural supply chain operations. We formulated invisible auction mechanisms that hide actual bid values and regulate information flows, combined with machine learning techniques for robust predictive analytics. While rule-based fuzzy systems encode domain expertise in agricultural decision-making, adaptable training algorithms help optimize model parameters from the data. A two-phase hybrid learning approach is formulated. Fuzzy optimization models were formulated using domain expertise for three key supply chain decision problems. Auction markets discover optimal crop demand–supply balancing and pricing signals. Fuzzy systems incorporate domain knowledge into interpretable crop-advisory models. An integrated evaluation of 50 farms over five crop cycles demonstrated the high performance of the proposed edge computing-oriented auction-based fuzzy neural network model compared with benchmarks.

Abstract Background The aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%. Results Dietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P

In the present study, the chronic heat stress (CHS) broiler model was developed to investigate the potential protection mechanism of organic selenium (selenomethionine, SeMet) on CHS-induced skeletal muscle growth retardation and poor meat quality. Four hundred Arbor Acres male broilers (680 ± 70 g, 21 d old) were grouped into 5 treatments with 8 replicates of 10 broilers per replicate. Broilers in the control group were raised in a thermoneutral environment (22 ± 2 °C) and fed with a basal diet. The other four treatments were exposed to hyperthermic conditions (33 ± 2 °C, 24 h in each day) and fed on the basal diet supplied with SeMet at 0.0, 0.2, 0.4, and 0.6 mg Se/kg, respectively, for 21 d. Results showed that CHS reduced (P

Natural macromolecules like alginate and gelatin are employed to create medication delivery systems that are both safe and effective. Zirconium nanoparticles (ZrO2 NPs) have been proposed as a means of enhancing the alginate-gelatin hydrogel's physical and biological properties. This study combines the synthesis of the biopolymers gelatin and alginate nanofibers with nanoparticles of zirconium oxide (GA/NF– ZrO2 NPs). UV, XRD, FTIR, and SEM were used to characterize the synthesized nanofibers. The expression of osteogenic genes was analyzed by western blotting and qualitative real-time polymerase chain reaction (qRT-PCR). Based on our findings, MC3T3-E1 cells are performed for cell viability, apoptosis and reactive oxygen species production by GA/NF– ZrO2 NPs through the Wnt/β-catenin signaling pathway. Cell migration was accelerated at 75 μg/mL concentration after 24 h of damage in a scratch wound healing assay. Proliferation of the MC3T3-E1 cell line was also detected. GA/NF–ZrO2 NPs influenced the osteogenic variation of MC3T3-E1 cells by inducing autophagy. Furthermore, the impact of obstruction on the temporomandibular joint (TMJ) is a subject of ongoing discussion and analysis within the context of animal models. Coordinated GA/NF–ZrO2 NPs on biomaterial nanofibers could be used to introduce physical signals for modifying MC3T3-E1 responds for orthodontic engineering constructs.

Purpose To investigate the preventive effect of aerobic exercise on renal damage caused by obesity.Methods The mice in the Control (Con) and Control + Exercise (Con + Ex) groups received a standard chow diet for the 21-week duration of the study, while the High-fat diet (HFD) group and High-fat diet + Exercise (HFD + Ex) group were fed an HFD. Mice were acclimated to the laboratory for 1 week, given 12 weeks of being on their respective diets, and then the Con + Ex and HFD + Ex groups were subjected to moderate intensity aerobic treadmill running 45 min/day, 5 days/week for 8 weeks.Results We found that HFD-induced obesity mainly impacts kidney glycerin phospholipids, glycerides, and fatty acyls, and aerobic exercise mainly impacts kidney glycerides, amino acids and organic acids as well as their derivatives. We identified 18 metabolites with significantly altered levels that appear to be involved in aerobic exercise mediated prevention of HFD-induced obesity and renal damage, half of which were amino acids and organic acids and their derivatives.Conclusion Aerobic exercise rewires kidney metabolites to reduce high-fat diet-induced obesity and renal injury.

ObjectiveMeige syndrome (MS) is an adult-onset segmental dystonia for which no satisfactory remedy currently exists. Our team developed a novel surgical approach called bilateral trigeminal/facial nerve combing (BTFC). This study aimed to evaluate the outcomes of patients who underwent BFTC (Clinical Trial Registry Number: ChiCTR2000033481).MethodWe assigned 22 patients with MS to undergo BTFC. The primary outcome was assessed using the movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) at 12 months postoperatively. The second outcome was evaluated using the Medical Outcome Study (MOS) 36-item Short Form Health Survey (SF-36), the dysfunction subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-D), and the sub-item scores of the BFMDRS-M. Safety outcomes included the House-Brackmann (HB) functional grading score and the visual analog scale (VAS) for facial numbness.ResultsAt the final follow-up at 12 months, the BFMDRS-M showed a mean improvement of 70.7% from baseline. Mean scores of the BFMDRS-M sub-motor (including the eyes, mouth, and speech/swallowing) improved by 65.6, 81.00, and 60%, respectively. The median score of the total BFMDRS-D score was 0.70 ± 1.17 compared with 1.86 ± 2.21 at baseline. There were no serious operative complications in this population. The quality of life of the patients significantly improved (P < 0.05).ConclusionBFTC has proven to be effective in relieving the symptoms of Meige syndrome. This novel surgical approach offers a new alternative treatment for patients who have failed to respond to medications, botulinum toxin injections, and deep brain stimulation (DBS).Clinical Trial Registrationhttps://www.chictr.org.cn/bin/project/edit?pid=54567, ChiCTR2000033481.

Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a life-threatening risk. Near-infrared (NIR)-assisted photothermal antibacterial combined with antioxidant hydrogel has shown significant potential in the healing of infected wounds. However, existing photothermal agents are typically metal-based, complicated to synthesize, or pose biosafety hazards. In this study, we utilized plant-derived blackcurrant extract (B) as a natural source for both photothermal and antioxidant properties. By incorporating B into a G-O hydrogel crosslinked through Schiff base reaction between gelatin (G) and oxidized pullulan (O), the resulting G-O-B hydrogel exhibited good injectability and biocompatibility along with robust photothermal and antioxidant activities. Upon NIR irradiation, the controlled temperature (around 45–50 °C) generated by the G-O-B hydrogel resulted in rapid (10 min) and efficient killing of Staphylococcus aureus (99 %), Escherichia coli (98 %), and Pseudomonas aeruginosa (82 %). Furthermore, the G-O-B0.5 hydrogel containing 0.5 % blackcurrant extract promoted collagen deposition, angiogenesis, and accelerated burn wound closure conclusively, demonstrating that this well-designed and extract-contained hydrogel dressing holds immense potential for enhancing the healing process of bacterial-infected burn wounds.

BackgroundAssessing volume status in septic shock patients is crucial for tailored fluid resuscitation. Estimated plasma volume status (ePVS) has emerged as a simple and effective tool for evaluating patient volume status. However, the prognostic value of ePVS in septic shock patients remains underexplored.MethodsThe study cohort consisted of septic shock patients admitted to the ICU, sourced from the MIMIC-IV database. Patients were categorized into two groups based on 28-day survival outcomes, and their baseline characteristics were compared. According to the ePVS (6.52 dL/g) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low ePVS groups. A multivariable Cox regression model was utilized to evaluate the association between ePVS and 28-day mortality rate. The Kaplan–Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test.ResultsA total of 7,607 septic shock patients were included in the study, among whom 2,144 (28.2%) died within 28 days. A J-shaped relationship was observed between ePVS at ICU admission and 28-day mortality, with an increase in mortality risk noted when ePVS exceeded 6.52 dL/g. The high ePVS group exhibited notably higher mortality rates compared to the low ePVS group (28-day mortality: 26.2% vs. 30.2%; 90-day mortality: 35% vs. 42.3%). After adjustment for confounding factors, ePVS greater than 6.52 dL/g independently correlated with an increased risk of 28-day mortality (HR: 1.20, 95% CI: 1.10–1.31, p

Abstract Background Intrauterine growth retardation (IUGR) affects intestinal growth, morphology, and function, which leads to poor growth performance and high mortality. The present study explored whether maternal dietary methyl donor (MET) supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth, function, and DNA methylation of the ileum in a porcine IUGR model. Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery. After farrowing, 8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum. Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets. Moreover, maternal MET supplementation significantly reduced the plasma concentrations of isoleucine, cysteine, urea, and total amino acids in sows and newborn piglets. It also increased lactase and sucrase activity in the jejunum of newborn piglets. MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets. DNA methylation analysis of the ileum showed that MET supplementation increased the methylation level of DNA CpG sites in the ileum of newborn piglets. Down-regulated differentially methylated genes were enriched in folic acid binding, insulin receptor signaling pathway, and endothelial cell proliferation. In contrast, up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosynthetic process. Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets, which may be associated with better intestinal function and methylation status.

Abstract Background Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. Methods In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. Results Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. Conclusion Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.