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The reconstruction of neural function and recovery of chronic damage following traumatic brain injury (TBI) remain significant clinical challenges. Exosomes derived from neural stem cells (NSCs) offer various benefits in TBI treatment. Numerous studies confirmed that appropriate preconditioning methods enhanced the targeted efficacy of exosome therapy. Interferon-gamma (IFN-γ) possesses immunomodulatory capabilities and is widely involved in neurological disorders. In this study, IFN-γ was employed for preconditioning NSCs to enhance the efficacy of exosome (IFN-Exo, IE) for TBI. miRNA sequencing revealed the potential of IFN-Exo in promoting neural differentiation and modulating inflammatory responses. Through low-temperature 3D printing, IFN-Exo was combined with collagen/chitosan (3D-CC-IE) to preserve the biological activity of the exosome. The delivery of exosomes via biomaterial scaffolds benefited the retention and therapeutic potential of exosomes, ensuring that they could exert long-term effects at the injury site. The 3D-CC-IE scaffold exhibited excellent biocompatibility and mechanical properties. Subsequently, 3D-CC-IE scaffold significantly improved impaired motor and cognitive functions after TBI in rat. Histological results showed that 3D-CC-IE scaffold markedly facilitated the reconstruction of damaged neural tissue and promoted endogenous neurogenesis. Further mechanistic validation suggested that IFN-Exo alleviated neuroinflammation by modulating the MAPK/mTOR signaling pathway. In summary, the results of this study indicated that 3D-CC-IE scaffold engaged in long-term pathophysiological processes, fostering neural function recovery after TBI, offering a promising regenerative therapy avenue.

C32H32CdN10OCl2, monoclinic, C2/c (no. 15), a = 28.820(3) Å, b = 13.1075(2) Å, c = 16.7266(19) Å, β = 149.29(3)°, Z = 4, V = 3226.9(15) Å3, Rgt(F) = 0.0341, wRref(F2) = 0.0893, T = 293(2) K.

C11H12CdN6Cl2, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 6.8644(8) Å, b = 10.4577(8) Å, c = 10.6304(12) Å, α = 112.218(9)°, β = 94.638(9)°, γ = 93.289(8)°, Z = 2, V = 700.93(13) Å3, R gt(F) = 0.0427, wR ref(F 2) = 0.1137, T = 293(2) K.

To reduce energy consumption, a new pulping process called A-D-E-RC (acidification/desalination/electrolysis/recycle-cooking) was developed by a research group in Guangxi University of China. The present work focuses on the step of recycle cooking (RC) to further investigate the technical feasibility of A-D-E-RC methods. Golden bamboo grass was considered as fiber source material for pulp, and it was cooked with the acidic treating of wastewater from black liquor. Then, the pulp obtained from each cooking was made into paper to test the changes in its physical properties. As a result, the pulp yield increased from 43.9% to 50.2%, after re-using acidified black liquor, and the paper's tear index and tensile index were improved. Therefore, this study demonstrated the feasibility of recycle cooking (RC) fiber materials for pulp applied the acidic treating wastewater from black liquor, and thereby, it further identifies the technical feasibility of A-D-E-RC pulping methods.

To reduce energy consumption, a new pulping process called A-D-E-RC (acidification/desalination/electrolysis/recycle-cooking) was developed by a research group in Guangxi University of China. The present work focuses on the step of recycle cooking (RC) to further investigate the technical feasibility of A-D-E-RC methods. Golden bamboo grass was considered as fiber source material for pulp, and it was cooked with the acidic treating of wastewater from black liquor. Then, the pulp obtained from each cooking was made into paper to test the changes in its physical properties. As a result, the pulp yield increased from 43.9% to 50.2%, after re-using acidified black liquor, and the paper's tear index and tensile index were improved. Therefore, this study demonstrated the feasibility of recycle cooking (RC) fiber materials for pulp applied the acidic treating wastewater from black liquor, and thereby, it further identifies the technical feasibility of A-D-E-RC pulping methods.

Abstract Background Fatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows. Results A total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows. Conclusions Our data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.

The increasing consumption of paper products has led to a shortage of paper fiber raw materials. It is necessary to develop new plant materials to alleviate the shortage of fiber suitable for papermaking. In this study, the fast-growing plant golden bamboo grass (Arundo donax), which is cultivated and planted in Guangxi province of China, was used as a new material for pulping. The average pulp yield by cyclic-cooking method averaged 48.6%, being 4.1% greater than the pulp yield by the ordinary caustic soda method. Much of the increased yield was attributable to the reprecipitation of lignin onto the fibers. The paper properties of the pulp prepared by cycle-cooked method did not decrease significantly, compared with the pulp prepared by the usual single-cooked method. Therefore, the pulp met the requirements of national standards of many kinds of papers. However, the pulp was not suitable for bleaching, due to its high consumption of oxidizing agents to reach the required brightness. Therefore, this research demonstrates that the fast-growing plant, Arundo donax is a good raw material for pulp, and the innovative method of cycle-cooking method can significantly improve the pulp yield.

The increasing consumption of paper products has led to a shortage of paper fiber raw materials. It is necessary to develop new plant materials to alleviate the shortage of fiber suitable for papermaking. In this study, the fast-growing plant golden bamboo grass (Arundo donax), which is cultivated and planted in Guangxi province of China, was used as a new material for pulping. The average pulp yield by cyclic-cooking method averaged 48.6%, being 4.1% greater than the pulp yield by the ordinary caustic soda method. Much of the increased yield was attributable to the reprecipitation of lignin onto the fibers. The paper properties of the pulp prepared by cycle-cooked method did not decrease significantly, compared with the pulp prepared by the usual single-cooked method. Therefore, the pulp met the requirements of national standards of many kinds of papers. However, the pulp was not suitable for bleaching, due to its high consumption of oxidizing agents to reach the required brightness. Therefore, this research demonstrates that the fast-growing plant, Arundo donax is a good raw material for pulp, and the innovative method of cycle-cooking method can significantly improve the pulp yield.

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients.Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients.Design: Clinical study protocol, SPIRIT compliant.Setting: Prospective, single-center, randomized, and sham-controlled trial.Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients.Exposures: Intraoral or sham acupuncture.Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the “Drooling Severity and Frequency Scale” and “Functional Oral Intake Scale.” Results : : The results from this study will be published in peer-reviewed journals.Conclusion : : Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.

Given the challenge of definitively discriminating between chemical and nuclear explosions using seismic methods alone, surface detection of signature noble gas radioisotopes is considered a positive identification of underground nuclear explosions (UNEs). However, the migration of signature radionuclide gases between the nuclear cavity and surface is not well understood because complex processes are involved, including the generation of complex fracture networks, reactivation of natural fractures and faults, and thermo-hydro-mechanical-chemical (THMC) coupling of radionuclide gas transport in the subsurface. In this study, we provide an experimental investigation of hydro-mechanical (HM) coupling among gas flow, stress states, rock deformation, and rock damage using a unique multi-physics triaxial direct shear rock testing system. The testing system also features redundant gas pressure and flow rate measurements, well suited for parameter uncertainty quantification. Using porous tuff and tight granite samples that are relevant to historic UNE tests, we measured the Biot effective stress coefficient, rock matrix gas permeability, and fracture gas permeability at a range of pore pressure and stress conditions. The Biot effective stress coefficient varies from 0.69 to 1 for the tuff, whose porosity averages 35.3% ± 0.7%, while this coefficient varies from 0.51 to 0.78 for the tight granite (porosity

Debonding at the cement-casing interface is recognized as a principal failure mechanism leading to CO2 leakage in wells. This detachment gives rise to a microannulus, which notably possesses greater permeability than undamaged cement, undermining its sealing efficacy. Conventionally, the permeability of the microannulus is regarded as a uniform value throughout the well. However, fundamentally, a microannulus is one type of fracture, and its gap or aperture size is affected by the effective stress. In this work, we developed a unique experimental apparatus. This equipment facilitates the curing of cement inside a steel casing, the formation of a microannulus between the casing and the cement, and the investigation of the fluid flow dynamics along the microannulus under laboratory-replicated in situ conditions. The microannulus was formed by injecting fluid from one end of the setup, and receiving similar amount of fluid on the other end signified the development of the leakage channel. Additionally, strain gauges affixed to the casing’s external surface yielded key information on the microannulus’s opening and closure. We observed a noticeable decline in microannulus hydraulic aperture (or permeability) in relation to effective stress and an exponential equation fits their relationship. Our findings also indicate a distinct behavior when comparing liquid CO2 with water. Specifically, it is easier for liquid CO2 to create the microannulus. However, the hydraulic aperture range for this microannulus (0.7–6 μm) is considerably smaller than that created by water flow (2–17 μm). Finally, we integrated the stress-dependent microannulus aperture size into the combined analysis of well mechanical integrity and well leakage. The outcomes consistently demonstrated that when factoring in the stress-dependent aperture sizes, the leakage rates are 3–5 times compared to a fixed aperture model. The traditional assumption of a constant aperture significantly underestimates fluid leakage risks.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Abstract Scar tissue is the inevitable result of repairing human skin after it has been subjected to external destructive stimuli. It leads to localized damage to the appearance of the skin, accompanied by symptoms such as itching and pain, which reduces the quality of life of the patient and causes serious medical burdens. With the continuous development of economy and society, there is an increasing demand for beauty. People are looking forward to a safer and more effective method to eliminate pathological scarring. In recent years, adipose-derived stem cells (ADSCs) have received increasing attention from researchers. It can effectively improve pathological scarring by mediating inflammation, regulating fibroblast proliferation and activation, and vascular reconstruction. This review focuses on the pathophysiological mechanisms of hypertrophic scarring, summarizing the therapeutic effects of in vitro, in vivo, and clinical studies on the therapeutic effects of ADSCs in the field of hypertrophic scarring prevention and treatment, the latest application techniques, such as cell-free therapies utilizing ADSCs, and discussing the advantages and limitations of ADSCs. Through this review, we hope to further understand the characterization of ADSC and clarify the effectiveness of its application in hypertrophic scarring treatment, so as to provide clinical guidance.

Abstract Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Abstract The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

ObjectiveType 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD).MethodsThe study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis.ResultsT2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance.ConclusionsT2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

BackgroundClinical observations indicate that blood lipids may be risk factors for lateral epicondylitis (LE) of the humerus, and lipid-lowering drugs are also used for the prevention and treatment of tendon diseases, but these lack high-quality clinical trial evidence and remain inconclusive. Mendelian randomization (MR) analyses can overcome biases in traditional observational studies and offer more accurate inference of causal relationships. Therefore, we employed this approach to investigate whether blood lipids are risk factors for LE and if lipid-lowering drugs can prevent it.MethodsGenetic variations associated with lipid traits, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), were obtained from the UK Biobank and the Global Lipids Genetics Consortium (GLGC). Data on genetic variation in LE were sourced from FinnGen, including 24,061 patients and 275,212 controls. Subsequently, MR analyses were conducted to assess the potential correlation between lipid traits and LE. Additionally, drug-target Mendelian randomization analyses were performed on 10 drug targets relevant to LE. For those drug targets that yielded significant results, further analysis was conducted using colocalization techniques.ResultsNo correlation was found between three blood lipid traits and LE. Lipoprotein lipase (LPL) enhancement is significantly associated with a decreased risk of LE (OR = 0.76, [95% CI, 0.65–0.90], p = 0.001). The expression of LPL in the blood is associated with LE and shares a single causal variant (12.07%), greatly exceeding the probability of different causal variations (1.93%), with a colocalization probability of 86.2%.ConclusionThe three lipid traits are not risk factors for lateral epicondylitis. LPL is a potential drug target for the prevention and treatment of LE.

Summary: Background: Genome-wide association studies (GWAS) have revealed many brain disorder-associated SNPs residing in the noncoding genome, rendering it a challenge to decipher the underlying pathogenic mechanisms. Methods: Here, we present an unsupervised Bayesian framework to identify disease-associated genes by integrating risk SNPs with long-range chromatin interactions (iGOAT), including SNP-SNP interactions extracted from ∼500,000 patients and controls from the UK Biobank, and enhancer–promoter interactions derived from multiple brain cell types at different developmental stages. Findings: The application of iGOAT to three psychiatric disorders and three neurodegenerative/neurological diseases predicted sets of high-risk (HRGs) and low-risk (LRGs) genes for each disorder. The HRGs were enriched in drug targets, and exhibited higher expression during prenatal brain developmental stages than postnatal stages, indicating their potential to affect brain development at an early stage. The HRGs associated with Alzheimer's disease were found to share genetic architecture with schizophrenia, bipolar disorder and major depressive disorder according to gene co-expression module analysis and rare variants analysis. Comparisons of this method to the eQTL-based method, the TWAS-based method, and the gene-level GWAS method indicated that the genes identified by our method are more enriched in known brain disorder-related genes, and exhibited higher precision. Finally, the method predicted 205 risk genes not previously reported to be associated with any brain disorder, of which one top-risk gene, MLH1, was experimentally validated as being schizophrenia-associated. Interpretation: iGOAT can successfully leverage epigenomic data, phenotype–genotype associations, and protein–protein interactions to advance our understanding of brain disorders, thereby facilitating the development of new therapeutic approaches. Funding: The work was funded by the National Key Research and Development Program of China (2024YFF1204902), the Natural Science Foundation of China (82371482), Guangzhou Science and Technology Research Plan (2023A03J0659) and Natural Science Foundation of Guangdong (2024A1515011363).

Advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and polycyclic aromatic hydrocarbons (PAHs) are toxic substances that are produced in certain foods during thermal processing by using common high-temperature unit operations such as frying, baking, roasting, grill cooking, extrusion, among others. Understanding the formation pathways of these potential risk factors, which can cause cancer or contribute to the development of many chronic diseases in humans, is crucial for reducing their occurrence in thermally processed foods. During thermal processing, food rich in carbohydrates, proteins, and lipids undergoes a crucial Maillard reaction, leading to the production of highly active carbonyl compounds. These compounds then react with other substances to form harmful substances, which ultimately affect negatively the health of the human body. Although these toxic compounds differ in various forms of formation, they all partake in the common Maillard pathway. This review primarily summarizes the occurrence, formation pathways, and reduction measures of common toxic compounds during the thermal processing of food, based on independent studies for each specific contaminant in its corresponding food matrix. Finally, it provides several approaches for the simultaneous reduction of multiple toxic compounds.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified infectious ailment triggered by a new strain of bunyavirus. It is distinguished by elevated fatality rates, ranging from 12 % to 30 %. The mechanism underlying the development of severe illness caused by SFTS bunyavirus (SFTSV) is not yet fully understood. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, sequential serum samples from 29 patients with SFTS (15 mild, 14 severe cases) were examined. Flow cytometry was employed to scrutinize the phenotypic and functional characteristics of TLR2 expression on circulating CD4 T cells, CD8 T cells, and Tregs. In all admitted patients, the evaluation of correlations between the frequencies of the aforementioned cells and SFTS index (SFTSI) was conducted. For SFTS, the levels of TLR2 on CD4 T cells and Tregs were significantly heightened when compared to those in healthy subjects. Additionally, the expression of TLR2 on Tregs exhibited a positive correlation with Ki-67 expression in Tregs and the severity of disease. Additionally, compared with those in uninfected controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, Tregs may be activated and proliferate through the stimulation of the TLR2/NF-кB pathway in reaction to SFTSV infection.

ABSTRACT Vibrio vulnificus (Vv) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during Vv infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or Vv, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of Vv, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in Vv-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with Vv. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following Vv infection. In summary, our findings suggest that MNK promotes the Vv-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.IMPORTANCEMitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during Vibrio vulnificus (Vv) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

Abstract Background Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. Methods COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. Results The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1β attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1β/STAT1 signaling via MTs. Conclusions These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1β/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD. Graphical Abstract Schematic mechanisms underlying the regulatory effects of melatonin on macrophage polarization and apoptosis in IAV infection plus cigarette stimulation-induced AECOPD model.

Grain drying equipment is an important equipment in Chinese agricultural production process, which can significantly improve the quality of grain processing after harvest and reduce the loss rate of mildew and germination during grain storage. At present, the mechanical drying rate of grain in China was only about 30%, and its overall penetration rate still had a great opportunity to improve. The market for grain dryers has great potential for development, and under the encouragement of national policies, the research on the technology, technology and applicability of dryers has been also constantly improved. In recent years, most research on grain drying has focused on process optimization, while there has been less research on grain drying equipment, which has made it difficult to apply excellent process technology and restricted the progress of grain drying equipment. This paper summarized the latest large and medium-sized grain drying equipment and the existing main problems, and put forward some suggestions, which could provide a reference for the research and development of grain drying technology and equipment.

Porosity is a key parameter that affects the heat and moisture transfer within a grain pile. In order to investigate the distribution law of porosity in bulk grain piles in grain silos, grain compression experiment was carried out to obtain the porosity of different grain types under different moisture content and vertical pressure conditions. A porosity prediction model for grain cell based on GWO-BP neural network was proposed, and the model was compared with the porosity prediction results of BP neural network model and random forest model. Finally, the generalization ability of the model was verified using the grain cell box test. The results showed that the porosity prediction performance of the GWO-BP neural network model was the best, and the evaluation indexes of the model, including R2 of 0.960 5, RMSE of 0.013 7 and MAE of 0.013 1, were all within the permissible range. This study has provided a neural network prediction method for the determination of grain porosity, which could provide an important foundation for in-depth multi-field coupling analysis of grain piles and theoretical support for safe grain storage.

Abstract Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Abstract Background Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. Methods The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (

Abstract Background The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. Results The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. Conclusion We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD. Graphical Abstract

Abstract Background The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival. Methods The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil‐to‐lymphocyte ratio (NLR) > 3. Model‐based causal mediation analysis was used to identify the mediators. Results A total of 52 270 (weighted population: 528506229) participants of the NHANES [mean follow‐up times: 10.2 years; mean age (SD): 47 (19.16) years] were included in the original cohort; and a total of 17 418 patients with cancer of INSCOC [mean follow‐up times: 2.9 years; mean age (SD): 57.37 (11.66) years] were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease [HR (95% CI): age ≥ 65 years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85)]. As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants [for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96]). The aged‐related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts [for obese, HR (95%CI): 0.65 (0.52, 0.81)]. The NLR is an important mediator of the effect of BMI on survival (proportion of mediation = 15.4%). Conclusions The obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all‐cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.

ObjectiveIn competitive sports, understanding how the perfectionistic climate within teams influences the performance of elite female athletes can provide valuable insights for enhancing coaching practice and athletic achievement. Based on the cognitive appraisal theory of stress, this study constructs a dual-path model using stressors and coping strategies as mediators, referred to as the Perfectionistic Climate on Athletic Performance model (PCPM). The study explores the predictive role of the perfectionistic climate within sports teams on the athletic performance of elite female basketball players.MethodsThe empirical study the relationships among the variables in the model using a sample of 125 core players from the top-level women’s basketball teams in the 24th CUBAL24 tournament in 2022. A Structural Equation Modeling (SEM) analysis was conducted using AMOS 20.0, primarily employing the bias-corrected Bootstrap method to test the dual-path model.ResultsThe findings reveal double-edged paths towards a perfectionistic climate on athletic performance. In the positive pathway, a perfectionistic climate can positively predict athletic performance through challenge-related sources of stress and positive coping strategies. In the negative pathway, a perfectionistic climate can negatively predict athletic performance through threat-related sources of stress and negative coping strategies.ConclusionCoaches need to pay attention to athletes’ cognitive evaluations of the perfectionistic climate as a source of pressure. By setting challenging goals, coaches can guide athletes to view the perfectionistic climate of the sports team as a source of challenging pressure, thus unleashing their potential. Coaches should actively guide athletes in coping with the pressure brought about by the perfectionistic climate, enhancing their ability to handle stress. This will enable athletes to better adapt to the team’s perfectionistic climate and further improve individual and team athletic performance.

As a complementary and alternative therapy, acupuncture is widely used in the prevention and treatment of various diseases. However, the understanding of the mechanism of acupuncture effects is still limited due to the lack of systematic biological validation. Notably, proteomics technologies in the field of acupuncture are rapidly evolving, and these advances are greatly contributing to the research of acupuncture. In this study, we review the progress of proteomics research in analyzing the molecular mechanisms of acupuncture for neurological disorders, pain, circulatory disorders, digestive disorders, and other diseases, with an in-depth discussion around acupoint prescription and acupuncture manipulation modalities. The study found that proteomics has great potential in understanding the mechanisms of acupuncture. This study will help explore the mechanisms of acupuncture from a proteomic perspective and provide information to support future clinical decisions.

Background: Previous research has suggested that dyslipidemia may be a risk factor for rotator cuff syndrome (RCS), and lipid-lowering drugs may aid in its treatment, though conclusions have not been definitive. Mendelian randomization is a statistical method that explores the causal relationships between exposure factors and diseases. It overcomes the confounding issues inherent in traditional observational studies, thereby providing more reliable causal inferences. We employed this method to investigate whether hyperlipidemia is a risk factor for rotator cuff syndrome and whether lipid-lowering drugs can effectively treat this condition.Methods: Genetic variations linked to lipid traits low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) were acquired from the UK Biobank and the Global Lipids Genetics Consortium (GLGC). Data on genetic variation in rotator cuff syndrome were obtained from FinnGen, including 24,061 patients and 275,212 controls. In the next step, we carried out two-sample Mendelian randomization analyses to determine whether lipid traits correlate with rotator cuff syndrome risk. Additionally, we performed drug-target Mendelian randomization (MR) analyses on 10 drug targets related to rotator cuff syndrome. For the drug targets that showed significant results, further analysis was done using Summary-data-based Mendelian Randomization (SMR) and colocalization techniques. We performed a mediation analysis to identify potential mediators between HMG-CoA reductase (HMGCR) and RCS.Results: No causative link was established between these lipid traits and rotator cuff syndrome. However, a significant association has been identified where HMGCR inhibition corresponds to a reduced risk of rotator cuff disease (OR = 0.68, [95% CI, 0.56–0.83], p = 1.510 × 10−4). Additionally, enhanced expression of HMGCR in muscle tissues is also linked to a decreased risk of rotator cuff syndrome (OR = 0.88, [95% CI, 0.76–0.99], p = 0.03). Body mass index (BMI) mediated 22.97% of the total effect of HMGCR on RCS.Conclusion: This study does not support low-density LDL-C, TG, and TC as risk factors for rotator cuff syndrome. HMGCR represents a potential pharmaceutical target for preventing and treating rotator cuff syndrome. The protective action of statins on the rotator cuff syndrome might not be associated with their lipid-lowering properties.

IntroductionThe impact of nitrogen (N) deposition on the soil N-transforming process in grasslands necessitates further investigation into how N input influences the structural composition and diversity of soil N-cycling microbial communities across different grassland types.MethodsIn this study, we selected two types of grassland soils in northwest Liaoning, temperate steppe and warm-temperate shrub, and conducted short-term N addition experiments using organic N, ammonium N, and nitrate N as sources with three concentration gradients to simulate N deposition. Illumina MiSeq sequencing technology was employed to sequence genes associated with N-cycling microbes including N-fixing, ammonia-oxidizing and denitrifying bacteria, and ammonia-oxidizing archaea.Results and discussionThe results revealed significant alterations in the structural composition and diversity of the N-cycling microbial community due to N addition, but the response of soil microorganisms varied inconsistent among different grassland types. Ammonium transformation rates had a greater impact on soils from temperate steppes while nitrification rates were more influential for soils from warm-temperate shrubs. Furthermore, the influence of the type of N source on soil N-cycling microorganisms outweighed that of its quantity applied. The ammonium type of nitrogen source is considered the most influential driving factor affecting changes in the structure of the microbial community involved in nitrogen transformation, while the amount of low nitrogen applied primarily determines the composition of soil bacterial communities engaged in nitrogen fixation and nitrification. Different groups of N-cycling microorganisms exhibited distinct responses to varying levels of nitrogen addition with a positive correlation observed between their composition, diversity, and environmental factors examined. Overall findings suggest that short-term nitrogen deposition may sustain dominant processes such as soil-N fixation within grasslands over an extended period without causing significant negative effects on northwestern Liaoning’s grassland ecosystems within the next decade.

Abstract Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross‐linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over‐accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS‐responsive and Vitamin A (VA) decorated micelles (named LR‐SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR‐SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS‐responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross‐linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR‐SSVA is a safe and efficient ROS‐response and PSC‐targeted drug‐delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

Gliding is a crucial phase in swimming, yet the understanding of fluid force and flow fields during gliding remains incomplete. This study analyzes gliding through Computational Fluid Dynamics simulations. Specifically, a numerical model based on the Smoothed Particle Hydrodynamics (SPH) method for flow-object interactions is established. Fluid motion is governed by continuity, Navier-Stokes, state, and displacement equations. Modified dynamic boundary particles are used to implement solid boundaries, and steady and uniform flows are generated with inflow and outflow conditions. The reliability of the SPH model is validated by replicating a documented laboratory experiment on a circular cylinder advancing steadily beneath a free surface. Reasonable agreement is observed between the numerical and experimental drag force and lift force. After the validation, the SPH model is employed to analyze the passive drag, vertical force, and pitching moment acting on a streamlined gliding 2D swimmer model as well as the surrounding velocity and vorticity fields, spanning gliding velocities from 1 m/s to 2.5 m/s, submergence depths from 0.2 m to 1 m, and attack angles from −10° to 10°. The results indicate that with the increasing gliding velocity, passive drag and pitching moment increase whereas vertical force decreases. The wake flow and free surface demonstrate signs of instability. Conversely, as the submergence depth increases, there is a decrease in passive drag and pitching moment, accompanied by an increase in vertical force. The undulation of the free surface and its interference in flow fields diminish. With the increase in the attack angle, passive drag and vertical force decrease whereas pitching moment increases, along with the alteration in wake direction and the increasing complexity of the free surface. These outcomes offer valuable insights into gliding dynamics, furnishing swimmers with a scientific basis for selecting appropriate submergence depth and attack angle.

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

Deqi is an important prerequisite for acupuncture to achieve optimal efficacy. Chinese medicine has long been concerned with the relationship between Deqi and the clinical efficacy of acupuncture. However, the underlying mechanisms of Deqi are complex and there is a lack of systematic summaries of objective quantitative studies of Deqi. Acupuncture Deqi can achieve the purpose of treating diseases by regulating the interaction of local and neighboring acupoints, brain centers, and target organs. At local and neighboring acupoints, Deqi can change their tissue structure, temperature, blood perfusion, energy metabolism, and electrophysiological indicators. At the central brain level, Deqi can activate the brain regions of the thalamus, parahippocampal gyrus, postcentral gyrus, insular, middle temporal gyrus, cingulate gyrus, etc. It also has extensive effects on the limbic-paralimbic-neocortical-network and default mode network. The brain mechanisms of Deqi vary depending on the acupuncture techniques and points chosen. In addition, Deqi 's mechanism of action involves correcting abnormalities in target organs. The mechanisms of acupuncture Deqi are multi-targeted and multi-layered. The biological mechanisms of Deqi are closely related to brain centers. This study will help to explore the mechanism of Deqi from a local-central-target-organ perspective and provide information for future clinical decision-making.

Abstract Regulation of myeloid cell activity is critical for successful myelin regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis (MS). Here, we show aromatic alpha-keto acids (AKAs) generated from the amino acid oxidase, interleukin-4 induced 1 (IL4I1), promote efficient remyelination in mouse models of MS. During remyelination, myeloid cells upregulated the expression of IL4I1. Conditionally knocking out IL4I1 in myeloid cells impaired remyelination efficiency. Mice lacking IL4I1 expression exhibited a reduction in the AKAs, phenylpyruvate, indole-3-pyruvate, and 4-hydroxyphenylpyruvate, in remyelinating lesions. Decreased AKA levels were also observed in people with MS, particularly in the progressive phase when remyelination is impaired. Oral administration of AKAs modulated myeloid cell-associated inflammation, promoted oligodendrocyte maturation, and enhanced remyelination in mice with focal demyelinated lesions. Transcriptomic analysis revealed AKA treatment induced a shift in metabolic pathways in myeloid cells and upregulated aryl hydrocarbon receptor activity in lesions. Our results suggest myeloid cell-associated aromatic amino acid metabolism via IL4I1 produces AKAs in demyelinated lesions to enable efficient remyelination. Increasing AKA levels or targeting related pathways may serve as a strategy to facilitate the regeneration of myelin in inflammatory demyelinating conditions.

Abstract According to the expression of miRNA in pathological processes, miRNAs can be divided into oncogenes or tumor suppressors. Prediction of the regulation relations between miRNAs and small molecules (SMs) becomes a vital goal for miRNA-target therapy. But traditional biological approaches are laborious and expensive. Thus, there is an urgent need to develop a computational model. In this study, we proposed a computational model to predict whether the regulatory relationship between miRNAs and SMs is up-regulated or down-regulated. Specifically, we first use the Large-scale Information Network Embedding (LINE) algorithm to construct the node features from the self-similarity networks, then use the General Attributed Multiplex Heterogeneous Network Embedding (GATNE) algorithm to extract the topological information from the attribute network, and finally utilize the Light Gradient Boosting Machine (LightGBM) algorithm to predict the regulatory relationship between miRNAs and SMs. In the fivefold cross-validation experiment, the average accuracies of the proposed model on the SM2miR dataset reached 79.59% and 80.37% for up-regulation pairs and down-regulation pairs, respectively. In addition, we compared our model with another published model. Moreover, in the case study for 5-FU, 7 of 10 candidate miRNAs are confirmed by related literature. Therefore, we believe that our model can promote the research of miRNA-targeted therapy.

Abstract Background The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. Methods In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. Results The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13–1.33), 34% (internal test cohort, 95%CI = 1.11–1.62), and 35% (external validation cohort, 95%CI = 1.14–1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22–1.71; internal test cohort, HR = 1.62, 95%CI = 1.12–2.36; external validation cohort, HR = 1.61, 95%CI = 1.15–2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05–4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42–3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52–4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24–2.55] in patients with cancer cachexia. Conclusion The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Abstract Solid granular proppant particles are widely used in oil and gas development to sustain permeability through fractures after hydraulic stimulation. Similar proppants are of interest for geothermal applications where the goal of sustaining permeability is the same, but the harsh geothermal environment risks rapid proppant degradation that will reduce fracture permeability. Here, we present proppant conductivity experiments using saw cut granite, tensile fractured granite, and aluminum control specimens packed with sintered bauxite ceramic proppants at concentrations of 0.0, 0.1, and 1.0 kg/m2. Simulated geothermal conditions included temperatures up to 130 °C and normal closure stresses up to 60 MPa. Compared to unpropped specimens, peak fracture conductivity enhancement was up to 6 orders of magnitude. At simulated geothermal conditions, proppants were able to sustain fracture conductivity over 60 h, but chemical dissolution and decreasing permeability over time were evident. Irreversible conductivity reductions with crushing and embedment of proppants during loading stages were also observed. Overall, sintered bauxite proppant remains a promising option for low-temperature binary-cycle enhanced geothermal systems.

Abstract Background Antiretroviral therapy (ART) can reduce viral load in individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals still cannot achieve optimal immune recovery even after ART. Hence, we described the profile of peripheral immune cells and explored the association with disease progression in patients infected with HIV-1. Methods Mass cytometry analysis was used to characterize the circulating immune cells of 20 treatment-naïve (TNs), 20 immunological non-responders (INRs), 20 immunological responders (IRs), and 10 healthy controls (HCs). Correlation analysis was conducted between cell subpopulation percentages and indicators including HIV-1 cell-associated (CA)-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio. Results Global activation, immunosenescence, and exhaustion phenotypes were observed in myeloid cells and T cells from individuals with HIV-1 infection. We also found that specific subsets or clusters of myeloid, CD4+ T, and CD8+ T cells were significantly lost or increased in TN individuals, which could be partially restored after receiving ART. The percentages of several subpopulations correlated with HIV-1 CA-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio, suggesting that changes in immune cell composition were associated with therapeutic efficacy. Conclusion These data provide a complete profile of immune cell subpopulations or clusters that are associated with disease progression during chronic HIV-1 infection, which will improve understanding regarding the mechanism of incomplete immune recovery in INRs.

Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. Methods High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. Results Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. Conclusions These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

Abstract Background The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. Methods This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG‐PS). Survival data were analysed using univariate and multivariate Cox regression analyses. Results The area under the curve, concordance index and survival analysis showed that C‐reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non‐cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08–5.32); high CAR, HR (95% CI) = 2.92 (1.88–4.55); high CRP, HR (95% CI) = 3.12 (2.08–4.67)] indicated a worse prognosis, compared with non‐cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65–3.16); high CAR, HR (95% CI) = 2.36 (1.71–3.25); high CRP, HR (95% CI) = 2.58 (1.85–3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG‐PS 2, HR (95% CI) = 1.61 (1.04–2.50); ECOG‐PS 3/4, HR (95% CI) = 2.91 (1.69–5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG‐PS 2, HR (95% CI) = 1.28 (0.90–1.81); ECOG‐PS 3/4, HR (95% CI) = 2.41 (1.32–4.39]). Patients with CRC cachexia with an ECOG‐PS score of 2 or 3–4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG‐PS score of 0/1 and a low inflammation. Conclusions The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG‐PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG‐PS in patients with CRC cachexia could provide a simple survival prediction.

Salinity severely affects plant growth and development. Thus, it is crucial to identify the genes functioning in salt stress response and unravel the mechanism by which plants against salt stress. This study used the phosphoproteomic assay and found that 123 of the 4 000 quantitative analyzed phosphopeptides were induced by salt stress. The functional annotation of the non-redundant protein database (NR) showed 23 differentially expressed transcription factors, including a phosphopeptide covering the Serine 31 in the RAV (related to ABI3/VP1) transcription factor (named SiRAV1). SiRAV1 was located in the nucleus. Phenotypic and physiological analysis showed that overexpressing SiRAV1 in foxtail millet enhanced salt tolerance and alleviated the salt-induced increases of H2O2 accumulation, malondialdehyde (MDA) content, and percent of electrolyte leakage. Further analysis showed that SiRAV1 positively regulated SiCAT expression to modulate the catalase (CAT) activity by directly binding to the SiCAT promoter in vivo and in vitro. Moreover, we found that phosphorylation of SiRAV1 at the Ser31 site positively regulated salt tolerance in foxtail millet via enhancing its binding ability to SiCAT promoter but did not affect its subcellular localization. Overall, our results define a mechanism for SiRAV1 function in salt response where salt-triggered phosphorylation of SiRAV1 at Ser31 enhances its binding ability to SiCAT promoter, and the increased SiCAT expression contributes to salt tolerance in foxtail millet.

Abstract Objective The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer. Methods From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention. Results After the intervention, the anxiety score (t = 6.656, p