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BackgroundSchizophrenia is a persistent incurable mental disorder and is characterized by the manifestation of negative emotions and behaviors with anxiety and depression, fear and insecurity, self-harm and social withdrawal. The intricate molecular mechanisms underlying this phenomenon remain largely elusive. Accumulating evidence points towards the gut microbiota exerting an influence on brain function via the gut-brain axis, potentially contributing to the development of schizophrenia. Therefore, the objective of this study is to delineate the gut microbial composition and metabolic profile of fecal samples from individuals with schizophrenia.MethodsLiquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal RNA (16S rRNA) gene sequencing were employed to analyze fecal metabolites and gut microbiota profiles in a cohort of 29 patients diagnosed with schizophrenia and 30 normal controls. The microbial composition of fecal samples was determined through the 16S rRNA gene sequencing, and microbial α-diversity and β-diversity indices were calculated. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to analyze the distribution of samples. The metabolites and gut microbiota exhibiting differential expression were identified through the application of biological variance criteria. Co-occurrence analysis of bacteria and metabolites was conducted using the spearman’s rank correlation coefficient and visualized in a circular layout with the Cytoscape software.ResultsThe findings of the study indicated a lack of substantial evidence supporting significant disparities in α-diversity and β-diversity between individuals with schizophrenia and normal controls. In terms of metabolomics, a discernible pattern in sample distribution between the two groups was observed. Our analysis has revealed 30 bacterial species and 45 fecal metabolites that exhibited notable differences in abundance between individuals diagnosed with schizophrenia and normal controls. These alterations in multilevel omics have led to the development of a co-expression network associated with schizophrenia. The perturbed microbial genes and fecal metabolites consistently demonstrated associations with amino acid and lipid metabolism, which play essential roles in regulating the central nervous system.ConclusionOur results offered profound insights into the impact of imbalanced gut microbiota and metabolism on brain function in individuals with schizophrenia.

Abstract Realization of stable and industrial-level H2O2 electroproduction still faces great challenge due large partly to the easy decomposition of H2O2. Herein, a two-dimensional dithiine-linked phthalocyaninato cobalt (CoPc)-based covalent organic framework (COF), CoPc-S-COF, was afforded from the reaction of hexadecafluorophthalocyaninato cobalt (II) with 1,2,4,5-benzenetetrathiol. Introduction of the sulfur atoms with large atomic radius and two lone-pairs of electrons in the C-S-C linking unit leads to an undulated layered structure and an increased electron density of the Co center for CoPc-S-COF according to a series of experiments in combination with theoretical calculations. The former structural effect allows the exposition of more Co sites to enhance the COF catalytic performance, while the latter electronic effect activates the 2e− oxygen reduction reaction (2e− ORR) but deactivates the H2O2 decomposition capability of the same Co center, as a total result enabling CoPc-S-COF to display good electrocatalytic H2O2 production performance with a remarkable H2O2 selectivity of >95% and a stable H2O2 production with a concentration of 0.48 wt% under a high current density of 125 mA cm−2 at an applied potential of ca. 0.67 V versus RHE for 20 h in a flow cell, representing the thus far reported best H2O2 synthesis COFs electrocatalysts.

Abstract Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P

Wheat sharp eyespot is a prevalent soil-borne disease that causes substantial economic losses in agriculture. Metconazole, a new triazole broad-spectrum fungicide, has demonstrated effective control of soil-borne diseases. Multi-walled carbon nanotubes (MWCNTs) are an innovative adsorbent material known for their large surface area and high absorptive capacity. This study identifies MWCNTs as the optimal adsorption material for metconazole, achieving an adsorption rate of 85.27% under optimal conditions (stirring time of 30 min and feeding ratio of 6:1). The optimized formula consists of 1.5% dispersant sodium wood, 1% emulsifier BY-112, 2% AEO-15, 3% glycol, 3% filmogen, and 4% red dyes. A 0.5% MWCNT–metconazole suspension concentrate for seed coating (FSC) significantly enhances the inhibitory effect of metconazole on wheat growth and promotes root development. At the tillering stage, a coating ratio of 1:100 shows a marked impact on wheat growth, and MWCNTs can improve the control effect of metconazole to Rhizoctonia cerealis. This work offers a novel approach for applying metconazole in a wheat suspension concentrate for seed coating.

Abstract Background Cancer stem cells are pivotal in cancer progression and therapy, including lung adenocarcinoma (LUAD). High NCAPG level is implicated in malignant tumorigenesis, but investigations on NCAPG and LUAD stem cells are warranted. Hence, projecting the impact of NCAPG on cell stemness and the targeted therapy for LUAD is of the essence. Methods Bioinformatics analyzed NCAPG expression in LUAD tissues. qRT‐PCR assayed NCAPG expression in LUAD cells. CCK‐8 assessed cell viability and cell sphere‐forming assay measured sphere‐forming ability. Western blot assessed expression of stem cell‐related markers (CD133, CD44, Oct‐4) and specific genes (HK2, PKM2, LDHA) related to glycolysis metabolism pathway. Cellular glycolytic capacity was assayed by glycolytic metabolites pyruvic acid, lactate, citrate, and malate assay kits, and extracellular acidification rate and oxygen consumption rate analyzers. Results NCAPG was upregulated in LUAD and enriched in the aerobic glycolysis pathway, and its expression was positively correlated with that of glycolytic marker genes. Cell function assays revealed that NCAPG stimulated proliferation, stemness, and glycolytic activity of LUAD cells. Rescue experiments unveiled that 2‐DG (glycolysis inhibitor) was able to reverse the stimulative impact of NCAPG overexpression on proliferation, stemness, and glycolytic activity of LUAD cells. Conclusion NCAPG stimulated LUAD cell stemness through activation of glycolysis pathway. NCAPG may be possible biomarker for diagnosis and target for treatment of LUAD.

According to the standard, after the anti-corrosion coating is immersed for a certain period of time, if there is no foaming, cracking, falling off, etc., the evaluation result is qualified. However, the adhesion and the corrosion resistance of some of the qualified coatings are greatly reduced. In this paper, eight kinds of anti-corrosion coatings qualified after soaking were selected, and the dry adhesion and wet adhesion after soaking in acidic environment were tested. The test results showed that the adhesion of some coatings after immersion was greatly reduced or lost, the metal matrix has obvious corrosion characteristics; the adhesion of some coatings was reduced; the adhesion of the two kinds of anti-corrosion coatings cured at room temperature was slightly increased. It can be seen that by comparing the dry/wet adhesion of the coating or tracking the change of adhesion during the coating service, the maintenance performance and development trend of the coating performance can be quantitatively grasped.

A new pair of 2,2ʹ-diamino-1,1ʹ-binaphthyl linked porphyrin dimers, (R)-/(S)-H, were synthesized to study their supramolecular interactions with a pair of chiral diamines ((R)-/(S)-PPDA) by using UV-Vis absorption, fluorescence and NMR titrations. The spectroscopic titrations indicated that sandwich-type 1:1 complexes were formed at low guest concentration and then transformed to 1:2 open complexes at high guest concentration. The supramolecular interactions afforded sensitive circular dichroism responses, and the CD signs of the 1:1 complexes are decided by the stereostructure of chiral diamine guests. Moreover, due to the shortened linking units, (R)-/(S)-H show more sensitive and predicable CD response than the previously reported hosts (R)-/(S)-H1 and this can be reasonably explained by DFT molecular modeling. The present results suggest (R)-/(S)-H are promising for chiral optical sensing.

Bovine laminitis leads to huge economic losses and animal welfare problems in the dairy industry worldwide. Numerous studies suggested that several metalloproteinases (MPs) may play vital roles in the failure of epidermal attachment. To the best of our knowledge, the present study is the first to investigate and characterize the gene-level changes in distinct MPs and endogenous inhibitors using oligofructose (OF)-induced bovine laminitis model. The objective of this study was to determine aberrant MPs and related inhibitors of bovine laminitis in gene level, and to provide reasonable directions for the further protein-level research. Twelve normal Chinese Holstein dairy heifers were randomly divided into treatment group (n = 6) and control group (n = 6). The heifers in the treatment group were administered with OF solutions at a dose of 17 g/kg of body weight via a stomach tube. The heifers were then humanely euthanized when they met the criteria of bovine laminitis. The heifers in the control group were administered with deionized water at a dose of 2 L/100 kg of body weight. They humanely euthanized at 72 h. The gene expressions of MPs and endogenous inhibitors, namely, matrix metalloproteinases (MMPs), A disintegrin and metalloproteinases (ADAMs), and A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), and tissue inhibitors of metalloproteinases (TIMPs) in the lamellae from two groups were determined via real-time quantitative PCR. The gene expressions of MMP-2, MMP-9, ADAMTS-4, and ADAMTS-5 significantly increased (P < 0.05), whereas that of TIMP-2 significantly decreased (P < 0.05) in the treatment group relative to the control group. No significant difference was found in the gene expressions of ADAM-10, ADAM-17, TIMP-1, and TIMP-3. These results indicated that the gene-level imbalanced condition of MPs and their TIMPs may be the basic cause for the failure of epidermal attachment. At the same time, more detailed protein-level studies would be needed to further clarify the roles of MPs and TIMPs in the pathogenesis of bovine laminitis, especially to MMP-2, MMP-9, ADAMTS-4, ADAMTS-5, TIMP-2 as well as related substrates (e.g., aggrecan and versican).

In order to study the movement mechanism of the scraper conveyor in the fully-mechanized mining face, the influence of cutting process, working face dip angle and thrust force of hydraulic support on the movement of scraper conveyor are analyzed comprehensively, the movement mechanism of scraper conveyor is clarified, the critical position and permissible movement value of the scraper conveyor are defined, the moving alert areas are set up, the movement states of scraper conveyor are clarified, ulteriorly the effective monitoring method and initiative control of scraper conveyor movement are put forward. The research shows that the propulsion difference of both ends, the change of working face dip angle, the relationship between support thrust and the scraper conveyor movement trend are the main reasons for the movement.The critical position and moving value at both ends are determined by the minimum width (0.8 m) of the safe exit of the coal mining face and the coal mining machine only just complete end oblique cutting. When the coal mining machine can just complete the oblique cutting at the head, the head position of the scraper conveyor is the critical position of rearward movement ; when the distance between the coal retaining plate of the bridge stage loader and the coal pillar is 0.8 m, the head position of the scraper conveyor is the critical position of forward movement. When the the coal mining machine can just complete the oblique cutting at the tail, the tail position of the scraper conveyor is the critical position of forward movement. When the distance between the tail of the scraper conveyor and the coal pillar is 0.8 m, the tail position of the scraper conveyor is the critical position of rearward movement. The permissible movement value of the scraper conveyor is the interval length between the critical position of rearward movement and the critical position of forward movement of scraper conveyor movement. For conducting timely warning and initiative measures to control scraper conveyor movement, permissible movement value is divided equally into five areas:serious area of foward movement, warning area of foward movement, normal area, warning area of rearward movement and serious area of rearward movement. The laser positioning method is used to record the horizontal offsets between the laser positioning point and the fiducial mark point, and the moving area of both ends is determined accurately. According to the moving areas of both ends of scraper conveyor, the moving states can be divided into normal state, single moving state and double moving state. Aiming at the specific movement state, according to local conditions, effective measures for initiative control of movement are put forward, such as adjusting cutting process, obliquity of working face, thrust direction of support and other measures. The relevant results have been applied in No.2 Coal Mine of Huayang New Material Co., Ltd., the permissible movement value of the head and tail of the 80807 working face are 0.8 m and 1.0 m respectively, and the moving alert area is divided, the moving state of scraper conveyor is accurately determined by laser monitoring, and initiative control measures are taken in time, and good control results have been achieved.

The hydraulic behavior of the connection between the floor failure area and the aquifer water-conductive zone is considered to be the root cause of mine water inrush disasters. Therefore, unraveling the floor failure mechanism is particularly important for safe coal mining above the high-confined aquifer. This paper estimates the depth of the baseplate failure to be 18.4–27.3 m by combining network parallel electrical methods with drilling visualization technology. The FLAC3D-based numerical model considering the strain hardening of caved rock was established with rigorous calibration and verification. The results showed that the depth of damage to the floor is 23.1 m, and the dominating floor failure mechanism is shear failure caused by the vertical stress exceeding the rock bearing capacity. Moreover, the stress recovery process of the baseplate does not alter the failure morphology of the baseplate. Based on the above research findings, the in-situ floor control technique of the working face No. 4305 is proposed and practiced in the field. Field measurements show that floor control performance is satisfactory with water inflow in the goaf being roughly stable at 50 m3/h. Our results can provide useful reference for safe mining above confined aquifer and prevention and mitigation of water-related hazards.

Abstract Background Children and adolescents diagnosed with major depressive disorder (MDD) often grapple with significant non-suicidal self-injury (NSSI), linked to interpersonal challenges, insecure attachment, and internet addiction. This study explores these relationships in children and adolescents using network analysis, drawing data from seven hospitals in China. Results The study included 162 youths with depressive disorder and 102 healthy controls from seven hospitals. The MDD + NSSI group exhibited severe internet addiction, heightened depressive symptoms, and insecure attachment. Network analysis identified central symptoms (compulsive use) and key bridge symptoms (tolerance symptoms) in the networks related to depressive symptoms, internet addiction, and attachments. These findings suggest potential targets for intervention among children and adolescents at risk for or suffering from depression. Conclusions This study sheds light on the intricate relationship between NSSI, attachment issues, and internet addiction in Chinese adolescents with MDD. The network analysis pinpointed central and key bridge symptoms, offering valuable insights for targeted interventions in children and adolescents at risk for or experiencing depression and associated challenges.

Abstract Thick-coal-seam with complex structures and thick-hard roof in the initial mining phase pose various challenges, including a long weighting interval, strong rock pressure, poor top coal caving performance (TCCP), and significant coal loss. These problems directly affect the safety and efficiency of the mining operations. This study employs the principles of elastic thin plates and ellipsoidal bodies to unravel the formation mechanism of strong rock pressure in thick-hard roof and the influence of parting on the TCCP. In addition, a hydraulic fracturing technique is proposed for safe-efficient recovery during the initial mining phase. The reliability of this technique is verified through numerical simulations and field experiments. The research findings reveal the following. (1) The primary causes of strong rock pressure in the mining face are attributed to a long weighting interval and wide collapse range of the main roof, and the weighting interval is primarily influenced by the thickness and tensile strength of the main roof. (2)The key factor affecting the TCCP is the cantilever beam structure formed by the fracture of the thick-hard parting, as it intersects the ellipsoidal body during coal caving. The simultaneous fracturing of both the top coal and roof can reduce the weighting interval on the working face. This process effectively decreased the strength of the thick-hard parting within the top coal, while simultaneously enhancing its load strength and eliminating the cantilever structure resulting from the parting fracture. It not only reduces the first weighting intensity but also promotes the early and proper coal release, thereby enhancing the TCCP and ensuring safe-efficient mining during the initial mining phase. (3) Aiming at the difference in the strengths of the top coal and roof, a graded hydraulic fracturing technique and system were proposed. Fracturing boreholes with a diameter of 60 mm, spacing of 10 m, and height of 20.85 m, which can economically and effectively ensure the fracturing results. Field applications have demonstrated that fractured coal and rocks in fracturing areas exhibit well-developed fractures. During the initial mining phase, the weighting interval in the working face was reduced by 20 m, resulting in a decrease in the overburden pressure and 26.9% reduction in the lumpiness of the top coal. Additionally, the recovery rate increased by 31.19%.

Abstract To investigate the vibration isolation effect of composite vibration isolation walls on surface vibrations in suburban railway deep tunnels under various influencing factors, an integrated numerical model of the train was initially developed. This model solved the wheel-rail interaction force and was applied to a three-dimensional volume coupling model of the track soil. Subsequently, the model's reliability was validated through comparison with measured data. Afterward, the vibration isolation effects of various types of EPS material vibration isolation walls were examined, with a focus on exploring the impact of thickness, material proportion, and relative positioning of the materials within the vibration isolation wall composed of EPS material and concrete. Research indicates that with an increase in the burial depth of a single material vibration isolation wall, its effective vibration isolation frequency range gradually widens. When the burial depth of the vibration isolation wall exceeds the tunnel burial depth, the vibration isolation effect is optimal. Composite vibration isolation walls, with thicknesses smaller than single-material vibration isolation walls, exhibit superior vibration isolation effects compared to their single-material counterparts. The effective vibration isolation frequency band of composite vibration isolation walls differs from that of single-material vibration isolation walls. Using the optimal-size vibration isolation wall of a single material as a composite vibration isolation wall enhances the vibration isolation effect of peak acceleration in the frequency domain by 16.58% and peak velocity by 16.95%. Moreover, frequency domain peak displacement experiences a 30.73% improvement in the vibration isolation effect.

Background: The need for primary percutaneous coronary intervention (PCI) and staged PCI strategy for ST-segment elevation myocardial infarction (STEMI) with multivessel coronary disease is well documented. This study aimed to evaluate the efficiency, safety, and cost benefit of quantitative flow ratio (QFR)-guided staged PCI in patients with STEMI. Methods: We conducted a retrospective study involving 2256 patients meeting STEMI criteria having at least one lesion (≥50 %) in non-infarct-related (NIR) arteries. These patients had undergone primary PCI for infarct-related (IR) arteries and staged PCI for NIR arteries. Patients were categorized into two groups based on the strategy guided either by QFR or quantitative coronary angiography (QCA) as determined by the clinicians during primary PCI in real-world. For patients guided by QFR, a threshold of ≤0.80 serves as the cut-off value for determining the need for PCI. We recorded the demographics, clinical data, and QFR values of none-infarct-related arteries. The efficiency, safety, and cost benefit of the QFR-guided staged PCI were evaluated. Results: The QCA-guided group had a higher rate of Killip II. In the QFR-guided group, there was a higher proportion of left anterior descending coronary artery lesions in infarct-related arteries. The mean QFR value of non-infarct-related (NIR) arteries remained consistent at 0.83 across both groups, irrespective of whether the measurement was taken during the primary PCI or the staged PCI phase. Among patients with QFR ≤0.8, the QFR values during staged PCI were significantly higher than that during primary PCI, with a significantly greater increase compared to patients with QFR >0.8. The proportion of staged PCI, number of stents per patient, and cost of staged PCI per patient were significantly lower in the QFR-guided group compared to the QCA-guided group. In the long-term follow-up period, there were no statistically significant differences between the two groups in terms of major adverse cardiac events and clinic visits, except for target vessel revascularization. Conclusions: QFR resulted in a reduction in the proportion of STEMI patients with multivessel coronary disease undergoing invasive coronary angiography and staged PCI. Furthermore, it decreased the incidence of target vessel revascularization (TVR) and medical costs, without increasing major adverse cardiovascular events. Our future work will focus on large multi-center perspective studies for the feasibility of QFR guided staged PCI in patients with STEMI.

An extensive network of cutaneous nerves, neuropeptides, and specific receptors richly innervates the skin and influences a variety of physiological and pathological processes. The sensory and autonomic nerve fibers secrete a variety of neuropeptides that are essential to the different phases of wound healing. In addition to initiating a neurogenic inflammatory response in the early stages of healing, neuropeptides also control wound healing by influencing immune cells, repair cells, and the growth factor network. However, the precise mechanism by which they accomplish these roles in the context of cutaneous wound healing is still unknown. Investigating the mechanisms of action of neuropeptides in wound healing and potential therapeutic applications is therefore urgently necessary. The present review discusses the process of wound healing, types of neuropeptides, potential mechanisms underlying the role of neuropeptides in cutaneous wound healing, as well as some neuropeptide-derived treatment strategies, such as hydrogels, new dressings, electro stimulation, and skin-derived precursors. Future in-depth mechanistic studies of neuropeptides in cutaneous wound healing may provide opportunities to develop therapeutic technologies that harness the roles of neuropeptides in the wound healing process.

Sjögren's syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands and can lead to various systemic symptoms impacting multiple organs. Despite its common occurrence, treatment options for SS have been largely limited, primarily focusing on alleviating symptoms rather than addressing the underlying autoimmune causes. A shift towards personalized medicine leads to the development of new therapeutic strategies aimed at targeting specific molecular pathways implicated in SS. Innovations in biologics are paving the way for inhibiting particular cytokines or cell surface molecules directly involved in the autoimmune mechanism. Furthermore, advancements in regenerative medicine, including the promising field of stem cell therapy, offer the potential for restoring or replacing the impaired salivary and lacrimal glands, providing hope for a more permanent resolution to this condition. This review encompasses cutting-edge treatment strategies for SS, spanning clinical and preclinical drugs to the latest treatment technology. Such advancements promise to drive targeted therapy development and inspire innovative ideas for treatment paradigms in SS.

Due to the rapid loss of biodiversity and financial and human resource limitations, there is an urgent need to prioritize biodiversity conservation. Setting conservation priorities is also an important part of conservation biology. Species abundance, richness and International Union for Conservation of Nature (IUCN) ranks are the most commonly used methods for setting conservation priorities, but with the development of bioinformatics, many studies have also demonstrated the utility of incorporating phylogenetic diversity into species prioritization, with evolutionary distinctiveness (ED) and evolutionarily distinct and globally endangered (EDGE) being widely used to determine the prioritization of species for conservation, where ED measures the contribution of species to the overall evolutionary history, and EDGE considers both evolutionary distinctiveness and IUCN ranks. In this study, based on the vascular plant distribution data collected on the Qinghai-Tibet Plateau (QTP), we determined the conservation priorities of plants on the QTP according to ED and EDGE2 considering four extinction risk transformations, investigated the relationship between IUCN ranks and ED, evaluated the effects of unassessed (NA) data deficiency (DD) species on EDGE rankings, and determined the conservation efficiency of the QTP conservation network in areas with evolutionary history and explored the possibility of incorporating evolutionary history into species conservation priorities. The results showed that there was no significant relationship between the ED of vascular plants and the IUCN ranks on the QTP; the results of EDGE2 showed that the top 25 species, with 14 species common to all four transformations, possessed both high ED and IUCN ranks; when EDGE2 containing DD and NA species showed that DD and NA species accounted for a large percentage of the top 25 species for all four transformations, suggesting that they may have significant potential for evolutionary history conservation; that the conservation priority areas for endemic seed plants of the QTP are located in the Hengduan Mountains, the eastern Yarlung Zangbo River, the southern Qionglai Mountains, the western Gangdise Mountains and the southern Kunlun Mountains; and that the QTP conservation networks protect the only 38.2 % of the areas rich in evolutionary history. These results emphasize the need to incorporate evolutionary information into conservation biology, but it should also be considered in conjunction with existing taxonomic diversity methods as a complementary conservation tool to provide a new perspective on the conservation of QTP plant diversity.

Sjögren's syndrome (SS) is a chronic autoimmune disease that affects the exocrine glands and may lead to a range of systemic symptoms that impact various organs. Both innate and adaptive immune pathways might trigger the disease. Studying the signaling pathways underlying SS is crucial for enhancing diagnostic and therapeutic effectiveness. SS poses an ongoing challenge for medical professionals owing to the limited therapeutic options available. This review offers a comprehensive understanding of the intricate nature of SS, encompassing disease classification criteria, risk factors, and signaling pathways in immunity and inflammation. The advancements summarized herein have the potential to spark new avenues of research into SS.

Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic–pituitary–adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.

Gouty arthritis (GA), a metabolic and immunologic disease, primarily affects joints. Dysbiosis of intestinal flora is an important cause of GA. The metabolic disorders of intestinal flora leading to GA and immune disorders might play an important role in patients with hyperuricemia and established GA. However, the exact mechanisms, through which the dysbiosis of intestinal flora causes the development of GA, are not fully understood yet. Moreover, several therapies commonly used to treat GA might alter the intestinal flora, suggesting that modulation of the intestinal flora might help prevent or treat GA. Therefore, a better understanding of the changes in the intestinal flora of GA patients might facilitate the discovery of new diagnostic and therapeutic approaches. The current review article discusses the effects of intestinal flora dysbiosis on the pathogenesis of GA and the cross-regulatory effects between gut flora and drugs for treating GA. This article also highlights the modulatory effects of gut flora by traditional Chinese medicine (TCM) to lower uric acid levels and relieve joint pain as well as provides a summary and outlook, which might help guide future research efforts.

Chronic mountain sickness (CMS) poses a significant health risk to individuals who rapidly ascend to high altitudes, potentially endangering their lives. Nanoparticles (NPs) offer an effective means of transporting and delivering drugs, protecting nucleic acids from nuclease degradation, and mediating the expression of target genes in specific cells. These NPs are almost non-toxic and easy to prepare and store, possess a large surface area, exhibit good biocompatibility and degradability, and maintain good stability. They can be utilized in the treatment of CMS to enhance the therapeutic efficacy of drugs. This paper provides an overview of the impact of NPs on CMS, discussing their roles as nanocarriers and their potential in CMS treatment. It aims to present novel therapeutic strategies for the clinical management of CMS and summarizes the relevant pathways through which NPs contribute to plateau disease treatment, providing a theoretical foundation for future clinical research.

BackgroundThis study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.MethodsWe conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed.ResultsA positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors.ConclusionO_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague–Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

Due to the large mining area, the fully-mechanized top-caving mining with thick-hard roof is easy to form cantilever structure on the lateral roof of the working face, which on the one hand causes high stress level of adjacent roadway and serious deformation of roadway, on the other hand causes gas accumulation in corners, which brings severe challenges to safe and efficient mining of the mine. In this study, a mine facing such problems in Jincheng, China was taken as the research object. Based on the mechanical characteristics of coal and rock, the characteristics of overlying strata activity in the mining process of working face are mastered, and the dual effects of controlled transformation of lateral overlying strata structure on stress field and gas field were revealed. On this basis, roadway reinforcement and gas drainage schemes were put forward and applied. The results showed that the strength of the hard rock stratum was high in the triaxial stress environment, and it was not easily destroyed. However, once the strata exceed their strength threshold, they break down. In addition, the strength of coal is relatively low, and it is continuously deformed when the force exceeds its strength. The overlying strata structure after thick-hard roof fully-mechanized top-caving mining evolves in the following manner: “long cantilever length formed by the main roof being broken in the initial stage, voussoir beam formed by the upper hard roof being broken in the middle stage, and double cantilever beam formed by overlying strata compaction.” The stress carried by upper hard rock stratum is transferred to coal pillars, which is the main reason for the high stress environment of multi-purpose roadway with large coal pillars. The controlled transformation of lateral overlying strata structure by pre-splitting and roof cutting can realize the ''transfer-unloading'' of coal pillar stress and the ''plugging and driving'' of corner gas. Based on the hydraulic fracturing reconstruction of lateral overburden structure, the grouting reinforcement scheme of roadway and dynamic gas drainage scheme were put forward. The results demonstrated that after roof cutting, the maximum deformation of the surrounding rock in the multi-purpose roadway was reduced by approximately 90 %, and the maximum concentration of corner gas was decreased by 15.28 %. This approach successfully achieved a collaborative control effect on roadway surrounding rock stability and gas emission well within the safety limits.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Alpine wetlands play important ecological roles by maintaining biodiversity and enhancing ecosystem reliability, stability, and functionality. However, geological disasters, such as earthquakes, cause biodiversity loss and degradation of the alpine wetlands. The robust M7.4 Maduo earthquake in May 2021 resulted in a decrease in the abundance or regional die-off of aquatic organisms and alpine wetlands degradation on the Qinghai–Tibet Plateau that year. In the present follow-up study, we determined whether the biodiversity loss and degradation of alpine wetlands caused by this earthquake could self-restore after more than one year. In August 2022, we conducted field investigations at three representative sites in Maduo; determined several biodiversity indices, including species number, density, biomass, Shannon diversity, Margalef richness, and Pielou's evenness, of all the aquatic plants and macrobenthos in the earthquake-affected and unaffected alpine wetlands; and obtained soil samples for the determination of different parameters. All six biodiversity indices and the soil organic carbon and moisture contents in the unaffected wetlands were significantly higher than those indices in the degraded alpine wetlands, and the salinity in the unaffected wetlands was significantly lower than that in the degraded wetlands, implying that the lost biodiversity of aquatic organisms and deteriorated edaphic environment were still not restored. Furthermore, all six biodiversity indices of aquatic plants and macrobenthos were positively related to soil moisture and organic carbon contents and negatively correlated with salinity. This study provides scientific insights and suggestions for preventing geological disasters, protecting biodiversity and restoring alpine wetlands.

Abstract Idiopathic fertility disorders are associated with mutations in various genes. Here, we report that coiled-coil glutamate-rich protein 1 (CCER1), a germline-specific and intrinsically disordered protein (IDP), mediates postmeiotic spermatid differentiation. In contrast, CCER1 deficiency results in defective sperm chromatin compaction and infertility in mice. CCER1 increases transition protein (Tnp1/2) and protamine (Prm1/2) transcription and mediates multiple histone epigenetic modifications during the histone-to-protamine (HTP) transition. Immiscible with heterochromatin in the nucleus, CCER1 self-assembles into a polymer droplet and forms a liquid-liquid phase-separated condensate in the nucleus. Notably, we identified loss-of-function (LoF) variants of human CCER1 (hCCER1) in five patients with nonobstructive azoospermia (NOA) that were absent in 2713 fertile controls. The mutants led to premature termination or frameshift in CCER1 translation, and disrupted condensates in vitro. In conclusion, we propose that nuclear CCER1 is a phase-separated condensate that links histone epigenetic modifications, HTP transitions, chromatin condensation, and male fertility.

Abstract Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in 36 NAFLD patients (NCT04140123). There were three cohorts. Each cohort included twelve patients, nine of whom received ZSP1601 50 mg once daily, 50 mg twice daily, or 100 mg twice daily, and three of whom received matching placebos for 28 days. The primary outcomes were the safety and tolerability of ZSP1601. A total of 27 (27/36, 75%) patients experienced at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild to moderate. There was no Serious Adverse Event. Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD.

Objective: Stroke is frequently associated with muscle mass loss. Treadmill training is considered the most effective treatment for sarcopenia. Circadian rhythms are closely related to exercise and have been extensively studied. The skeletal muscle has its molecular clock genes. Exercise may regulate skeletal muscle clock genes. This study evaluated the effects of early treadmill training on the skeletal muscle molecular clock machinery in rats with stroke and determined the relationship of these changes with exercise-induced improvements in skeletal muscle health. Materials and methods: Overall, 168 Sprague-Dawley rats were included in this study. We established an ischemic stroke rat model of sarcopenia. Finally, 144 rats were randomly allocated to four groups (36 per group): normal, sham, middle cerebral artery occlusion, and training. Neurological scores, rotating rod test, body weight, muscle circumference, wet weight, and hematoxylin-eosin staining were assessed. Twenty-four rats were used for transcriptome sequencing. Gene and protein expressions of skeletal muscles, such as brain muscle arnt-like 1, period 1, and period 2, were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays. Results: Neurological function scores and rotating rod test results improved after treadmill training. Nine differentially expressed genes were identified by comparing the sham group with the hemiplegic side of the model group. Seventeen differentially expressed genes were identified between the hemiplegic and non-hemiplegic sides. BMAL1, PER1, and PER2 mRNA levels increased on both sides after treadmill training. BMAL1 expression increased, and PER1 expression decreased on both sides, whereas PER2 expression decreased on the hemiplegic side but increased on the non-hemiplegic side. Conclusion: Treadmill training can mitigate muscle loss and regulate skeletal muscle clock gene expression following ischemic stroke. Exercise affects the hemiplegic side and has a positive regulatory effect on the non-hemiplegic side.

Gouty nephropathy (GN) is a metabolic disease with persistently elevated blood uric acid levels. The main manifestations of GN are crystalline kidney stones, chronic interstitial nephritis, and renal fibrosis. Understanding the mechanism of the occurrence and development of GN is crucial to the development of new drugs for prevention and treatment of GN. Currently, most studies exploring the pathogenesis of GN are primarily based on animal and cell models. Numerous studies have shown that inflammation, oxidative stress, and programmed cell death mediated by uric acid and sodium urate are involved in the pathogenesis of GN. In this article, we first review the mechanisms underlying the abnormal intrinsic immune activation and programmed cell death in GN and then describe the characteristics and methods used to develop animal and cell models of GN caused by elevated uric acid and deposited sodium urate crystals. Finally, we propose potential animal models for GN caused by abnormally high uric acid levels, thereby provide a reference for further investigating the methods and mechanisms of GN and developing better prevention and treatment strategies.

Study region: The Xiying River Basin is a typical inland mountainous watershed located in the Qilian Mountains. Study focus: This article reveals the change of runoff stable isotopes and their control mechanisms based on isotope data of different water bodies (precipitation, runoff, groundwater, and glacial snowmelt) in the Xiying River Basin from 2016 to 2021, combined with relevant meteorological observation data and the Normalized Vegetation Index (NDVI). New hydrological insights for the region: The results show that (1) meteorological factors control runoff isotope variations through controlling the evaporation process of runoff and the isotopic characteristics of recharge sources. (2) In areas with low vegetation cover, surface landscape features influence runoff isotopic composition by altering the isotopic characteristics of recharge sources. (3) In areas with high vegetation cover, surface vegetation cover affects runoff stable isotopes by controlling evapotranspiration processes. This study connects vegetation cover and runoff isotopes to explain the surface landscape control of runoff stable isotopes. It offers a more powerful reference for elucidating the factors influencing runoff isotopes in inland mountain watersheds.

One of the primary threats to coal mine safety production is the sudden extensive fracturing and collapse of thick and hard roof strata. A range of uniaxial compression experiments with acoustic emission (AE) monitoring was performed for studying the mechanical properties and crack evolution of thick and hard roof sandstone specimens. AE temporal response analysis revealed that the damage process of thick and hard roof sandstone specimens exhibited distinct stages. Additionally, AE event localization indicated that microcracks within the thick and hard roof sandstone specimens propagated from the ends to the middle of the specimens during the loading process, eventually leading to severe failure. The b-value analysis demonstrated that during the early loading stage, the scale of internal microcracks within the thick and hard roof sandstone specimens gradually decreased with the optimization of the load-bearing structure. In the later loading stage, the scale of microcracks increased with the deterioration of the load-bearing structure. Furthermore, RA–AF analysis revealed that the specimens experienced combined tensile–shear failure, primarily dominated by tensile failure throughout. The AE characteristics observed during the deformation of thick and hard sandstone can provide references for the monitoring of roof stability and early warning of potential disasters in thick and hard sandstone conditions.

For understanding the mechanical performance and strain energy evolution mechanism of thick hard roof sandstone samples, a sequence of uniaxial compression trials with acoustic emission (AE) monitoring were carried out. The results indicate: (1) The stress-strain curve of the thick hard roof sandstone specimens exhibits distinct stage characteristics. Based on the evolvement of instantaneous axial stiffness, it is separated into Fracture Closure Phase, Elastic Deformation Phase, Steady Fracture Expansion Phase, Unsteady Fracture Expansion Phase, and Post-Peak Phase. (2) The AE energy and cumulative count curves of the thick hard roof sandstone specimens also exhibit significant stage characteristics and can be mutually corroborated with the stage division of the stress-strain curve. (3) Based on the energy conservation principle, the evolution of strain energy density in the thick hard roof sandstone specimens under uniaxial compression loading was analyzed, and plastic strain energy increment was employed to study the stage characteristics of strain energy dissipation. (4) A damage constitutive model for the thick hard roof sandstone specimens was constructed, considering the characteristics of strain energy dissipation. This model effectively describes the stress-strain relationship among the samples, which undergo strain hardening, strain softening, and sudden destruction.

Polyphenols are the most prevalent naturally occurring phytochemicals in the human diet and range in complexity from simple molecules to high-molecular-weight polymers. They have a broad range of chemical structures and are generally categorized as “neuroprotective”, “anti-inflammatory”, and “antioxidant” given their main function of halting disease onset and promoting health. Research has shown that some polyphenols and their metabolites can penetrate the blood–brain barrier and hence increase neuroprotective signaling and neurohormonal effects to provide anti-inflammatory and antioxidant effects. Therefore, multi-targeted modulation of polyphenols may prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for difficult-to-treat neuropsychiatric disorders. Therefore, multi-target modulation of polyphenols has the potential to prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for such nervous system diseases. Herein, we review the therapeutic benefits of polyphenols on autism-spectrum disorders, anxiety disorders, depression, and sleep disorders, along with in vitro and ex vivo experimental and clinical trials. Although their methods of action are still under investigation, polyphenols are still seldom employed directly as therapeutic agents for nervous system disorders. Comprehensive mechanistic investigations and large-scale multicenter randomized controlled trials are required to properly evaluate the safety, effectiveness, and side effects of polyphenols.

IntroductionAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ–mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer’s disease.

IntroductionThis study sought to explore the immunogenicity of a booster dose of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in people living with human immunodeficiency virus (HIV) and identify the factors affecting the magnitude of anti-SARS-CoV-2 antibody levels.Materials and methodsA total of 34 people living with HIV (PLWH) and 34 healthy donors (HD) were administered a booster dose of the same SARS-CoV-2 vaccine. Anti-SARS-CoV-2 antibody and immunoglobulin G (IgG) levels were measured using the SARS-CoV-2 S protein neutralizing antibody Enzyme-Linked Immunosorbent Assay (ELISA) and 2019-nCov IgG Chemiluminescent Immunoassay Microparticles, respectively. Spearman correlation analysis was used to measure the correlation between laboratory markers and neutralizing antibody and IgG levels. Peripheral blood mononuclear cells (PBMCs) were extracted from each subject using density gradient centrifugation and the numbers of memory T and T follicular helper (Tfh) cells were determined using flow cytometry.ResultsPLWH had a marked reduction in CD4 and B cell levels that was accompanied by a lower CD4/CD8 T cell ratio. However, those who received a supplementary dose of inactivated SARS-CoV-2 vaccines exhibited antibody positivity rates that were analogous to levels previously observed. The booster vaccine led to a reduction in IgG and neutralizing antibody levels and the amplitude of this decline was substantially higher in the PLWH than HD group. Correlation analyses revealed a strong correlation between neutralizing antibody levels and the count and proportion of CD4 cells. Anti-SARS-CoV-2 IgG antibody levels followed a similar trend. The expression of memory T and Tfh cells was considerably lower in the PLWH than in the HD group.DiscussionPLWH had an attenuated immune response to a third (booster) administration of an inactivated SARS-CoV-2 vaccine, as shown by lower neutralizing antibody and IgG levels. This could be attributed to the reduced responsiveness of CD4 cells, particularly memory T and cTfh subsets. CD4 and cTfh cells may serve as pivotal markers of enduring and protective antibody levels. Vaccination dose recalibration may be critical for HIV-positive individuals, particularly those with a lower proportion of CD4 and Tfh cells.

In arid oasis regions, water resources are severely scarce, with agricultural water usage far exceeding that of more humid areas. As a result, assessing non-productive water losses in farmland becomes crucial for estimating the water requirements reliant on irrigation for oasis cultivation. From April 2018 to October 2021, we established an observation system in the Minqin Oasis farmland. By utilizing hydrogen and oxygen isotopes in precipitation, soil water, and maize stem xylem water, we quantified the non-productive water loss (FE) and soil water infiltration rate (fe) in maize fields. Our findings indicate: (1) The average non-productive losses from rainfall and irrigation in arid maize fields were 39 %, with peak losses reaching 58 %; (2) Non-productive losses due to evapotranspiration were mainly observed in June and July, while losses from infiltration predominantly occurred in April-May and August-September; (3) Crop evapotranspiration capacity emerged as a significant factor influencing evaporation losses, while individual irrigation amounts and rainfall determined soil infiltration losses. We believe that judiciously managing irrigation volume and adjusting irrigation strategies in arid farmlands could unlock substantial potential for conserving water resources.

ObjectiveThe study aimed to investigate the comprehensive characteristics of brain functional activity and integration in patients with subcortical stroke using dynamic and static analysis methods and to examine whether alterations in brain functional activity and integration were associated with clinical symptoms of patients.MethodsDynamic amplitude of low-frequency fluctuation (dALFF), static amplitude of low-frequency fluctuation (sALFF), dynamic degree centrality (dDC), and static degree centrality (sDC) were calculated for 19 patients with right subcortical stroke, 16 patients with left subcortical stroke, and 25 healthy controls (HC). Furthermore, correlation analysis was performed to investigate the relationships between changes in brain functional measurements of patients and clinical variables.ResultsGroup comparison results showed that significantly decreased dALFF in the left angular (ANG_L) and right inferior parietal gyrus (IPG_R), decreased sALFF in the left precuneus (PCUN_L), and decreased sDC in the left crus II of cerebellar hemisphere (CERCRU2_L) and IPG_R, while significantly increased sDC in the right lobule X of cerebellar hemisphere (CER10_R) were detected in patients with right subcortical stroke relative to HC. Patients with left subcortical stroke showed significantly decreased sALFF in the left precuneus (PCUN_L) but increased sDC in the right hippocampus (HIP_R) compared with HC. Additionally, the altered sDC values in the CER10_R of patients with right subcortical stroke and in the HIP_R of patients with left subcortical stroke were associated with the severity of stroke and lower extremities motor function. A correlation was also found between the altered sALFF values in the PCUN_L of patients with left subcortical stroke and lower extremities motor function.ConclusionThese findings suggest that time-varying brain activity analysis may supply complementary information for static brain activity analysis. Dynamic and static brain functional activity and integration analysis may contribute to a more comprehensive understanding of the underlying neuropathology of dysfunction in stroke patients.

Abstract Background Previous studies have shown that depression was associated with HTR3B gene. The aim of this study was to investigate the relationship between polymorphisms of the HTR3B gene and depression and its executive dysfunction in Chinese Han population. Methods A total of 229 patients with depressive disorder and 202 healthy controls were enrolled. Six Single nucleotide polymorphism sites (SNPs) including rs10789970, rs4938056, rs12421126, rs1176744, rs2276305 and rs12795805 were genotyped by Snapshot. Clinical features were collected using a general demographic questionnaire. The 24-item Hamilton Depression Scale (HAMD) was used to assess the symptoms’ severity of the patients. The patients' executive function was assessed using a series of cognitive tests including Maze Test, Symbolic Coding Test, Spatial Span Inverse Order Test, Linking Test, and Emotional Management Test. Results The genotypic and allelic distributions of rs1176744 in HTR3B gene were significantly different (χ2 = 11.129, P = 0.004, χ2 = 9.288, P = 0.002, respectively) between patients and controls. The A allele was positively correlated with depression. The proportion of A carriers was significantly higher and that of C carriers was lower in patients than those in controls. Patients had significantly lower scores of Spatial Span Inverse Order Test in carriers of A allele at locus rs1176744 and higher scores in carriers of C alleles at locus rs1176744 and rs12795805. Conclusions The polymorphisms of HTR3B gene may be associated with depression in Chinese Han population. The A allele of rs1176744 may increase the risk of developing depression and executive dysfunction while C alleles of rs1176744 and rs12795805 may be the protective factors for executive dysfunction in patients with depression.

Abstract Cinnamon aqueous extract’s active substance base remains unclear and its mechanisms, mainly the therapeutic target of anti-Alzheimer’s disease (AD)-related GABAergic synaptic dysfunction, remain unclear. Here, 30 chemical components were identified in the aqueous extract of cinnamon using LC/MS; secondly, we explored the brain-targeting components of the aqueous extract of cinnamon, and 17 components had a good absorption due to the blood–brain barrier (BBB) limitation; thirdly, further clustering analysis of active ingredient targets by network pharmacology showed that the GABA pathway with GABRG2 as the core target was significantly enriched; then, we used prominent protein–protein interactions (PPI), relying on a protein-metabolite network, and identified the GABRA1, GABRB2 and GABRA5 as the closest targets to GABRG2; finally, the affinity between the target and its cognate active compound was predicted by molecular docking. In general, we screened five components, methyl cinnamate, propyl cinnamate, ( +)-procyanidin B2, procyanidin B1, and myristicin as the brain synapse-targeting active substances of cinnamon using a systematic strategy, and identified GABRA1, GABRB2, GABRA5 and GABRG2 as core therapeutic targets of cinnamon against Alzheimer's disease-related GABAergic synaptic dysfunction. Exploring the mechanism of cinnamon’ activities through multi-components and multiple targets strategies promise to reduce the threat of single- target and symptom-based drug discovery failure.

Abstract Background Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that involves damage to the peripheral nervous system. The course of the disease can progress for more than 8 weeks, with frequent incidences of relapse-remission courses. This article reported a rare combination of CIDP with fluctuating symptoms, recurrence-remission, and comorbidity with psoriasis. Case presentation A 29-year-old male patient with repeated limb weakness and numbness was admitted to the hospital several times in the past six months. He had a history of psoriasis for 6 years, and the medications (clobetasol propionate ointment and calcipotriol ointment) treated for psoriasis were discontinued 1 year ago. During the hospitalization, repeated intravenous injections of human immunoglobulin G (IVIg), immunoadsorption, and secukinumab were performed. Nerve electrophysiology tests, ganglioside autoantibody spectrum tests, and clinical MRC muscle strength scores were performed on a regular basis to confirm the diagnosis of CIDP. The patient was regularly followed up. Results After repeated rounds of human IVIg and immunoadsorption, the patient’s MRC score was increased by ≥ 6 points. The first ganglioside autoantibody spectrum test showed anti-GQ1b IgG ( +) and anti-GM1 IgM ( +) antibodies, and all were negative after re-examination. Finally, the patient was treated with the IL-17A inhibitor secukinumab for psoriasis. During 7 months of follow-up, the CIDP and psoriasis symptoms are relatively stable. Conclusion Combination of IVIg and immunoadsorption was highly effective in treating CIDP complicated with psoriasis. The clinical manifestations of CIDP are diverse. When relapse-remission occurs in the course of the disease, it is necessary to clarify whether it is combined with other autoimmune diseases and should control the autoimmune diseases as soon as possible.

ObjectiveCognitive impairment is a detrimental complication of stroke that compromises the quality of life of the patients and poses a huge burden on society. Due to the lack of effective early prediction tools in clinical practice, many researchers have introduced machine learning (ML) into the prediction of post-stroke cognitive impairment (PSCI). However, the mathematical models for ML are diverse, and their accuracy remains highly contentious. Therefore, this study aimed to examine the efficiency of ML in the prediction of PSCI.MethodsRelevant articles were retrieved from Cochrane, Embase, PubMed, and Web of Science from the inception of each database to 5 December 2022. Study quality was evaluated by PROBAST, and c-index, sensitivity, specificity, and overall accuracy of the prediction models were meta-analyzed.ResultsA total of 21 articles involving 7,822 stroke patients (2,876 with PSCI) were included. The main modeling variables comprised age, gender, education level, stroke history, stroke severity, lesion volume, lesion site, stroke subtype, white matter hyperintensity (WMH), and vascular risk factors. The prediction models used were prediction nomograms constructed based on logistic regression. The pooled c-index, sensitivity, and specificity were 0.82 (95% CI 0.77–0.87), 0.77 (95% CI 0.72–0.80), and 0.80 (95% CI 0.71–0.86) in the training set, and 0.82 (95% CI 0.77–0.87), 0.82 (95% CI 0.70–0.90), and 0.80 (95% CI 0.68–0.82) in the validation set, respectively.ConclusionML is a potential tool for predicting PSCI and may be used to develop simple clinical scoring scales for subsequent clinical use.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=383476.

Traumatic or non-traumatic spinal cord injury (SCI) can lead to severe disability and complications. The incidence of SCI is high, and the rehabilitation cycle is long, which increases the economic burden on patients and the health care system. However, there is no practical method of SCI treatment. Recently, transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, has been shown to induce changes in plasticity in specific areas of the brain by regulating the activity of neurons in the stimulation site and its functionally connected networks. TMS is a new potential method for the rehabilitation of SCI and its complications. In addition, TMS can detect the activity of neural circuits in the central nervous system and supplement the physiological evaluation of SCI severity. This review describes the pathophysiology of SCI as well as the basic principles and classification of TMS. We mainly focused on the latest research progress of TMS in the physiological evaluation of SCI as well as the treatment of motor dysfunction, neuropathic pain, spasticity, neurogenic bladder, respiratory dysfunction, and other complications. This review provides new ideas and future directions for SCI assessment and treatment.

Objective: To observe the clinical efficacy and safety of Yiqi Yangxue formula (YQYXF) on knee osteoarthritis (KOA), and to explore the underlying therapeutic mechanism of YQYXF through endogenous differential metabolites and their related metabolic pathways.Methods: A total of 61 KOA patients were recruited and divided into the treatment group (YQYXF, 30 cases) and the control group (celecoxib, Cxb, 31 cases). Effects of these two drugs on joint pain, swelling, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) were observed, and their safety and adverse reactions were investigated. In animal experiments, 63 SD rats were randomly divided into normal control (NC) group, sham operation (sham) group, model (KOA) group, Cxb group, as well as low-dose (YL), medium-dose (YM), and high-dose groups of YQYXF (YH). The KOA rat model was established using a modified Hulth method. Ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS)-based metabolomics technology was used to analyze the changes of metabolites in plasma samples of rats. Comprehensive (VIP) >1 and t-test p < 0.05 conditions were used to screen the disease biomarkers of KOA, and the underlying mechanisms of YQYXF were explored through metabolic pathway enrichment analysis. The related markers of YQYXF were further verified by ELISA (enzyme-linked immunosorbent assay).Results: YQYXF can improve joint pain, swelling, range of motion, joint function, Michel Lequesen index of severity for osteoarthritis (ISOA) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, ESR, and CRP. No apparent adverse reactions were reported. In addition, YQYXF can improve cartilage damage in KOA rats, reverse the abnormal changes of 16 different metabolites, and exert an anti-KOA effect mainly through five metabolic pathways. The levels of reactive oxygen species (ROS) and glutathione (GSH) were significantly decreased after the treatment of YQYXF.Conclusion: YQYXF can significantly improve the clinical symptoms of KOA patients without obvious adverse reactions. It mainly improved KOA through modulating lipid metabolism-related biomarkers, reducing lipid peroxidation and oxidative stress.

Abstract Background Trans-cinnamaldehyde (TCA) is one of the main pharmaceutical ingredients of Cinnamomum cassia Presl, which has been shown to have therapeutic effects on a variety of cardiovascular diseases. This study was carried out to characterize and reveal the underlying mechanisms of the protective effects of TCA against cardiac hypertrophy. Methods We used phenylephrine (PE) to induce cardiac hypertrophy and treated with TCA in vivo and in vitro. In neonatal rat cardiomyocytes (NRCMs), RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to identify potential pathways of TCA. Then, the phosphorylation and nuclear localization of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-related kinase (ERK) were detected. In adult mouse cardiomyocytes (AMCMs), calcium transients, calcium sparks, sarcomere shortening and the phosphorylation of several key proteins for calcium handling were evaluated. For mouse in vivo experiments, cardiac hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, and the expression of hypertrophic genes and proteins. Results TCA suppressed PE-induced cardiac hypertrophy and the phosphorylation and nuclear localization of CaMKII and ERK in NRCMs. Our data also demonstrate that TCA blocked the hyperphosphorylation of ryanodine receptor type 2 (RyR2) and phospholamban (PLN) and restored Ca2+ handling and sarcomere shortening in AMCMs. Moreover, our data revealed that TCA alleviated PE-induced cardiac hypertrophy in adult mice and downregulated the phosphorylation of CaMKII and ERK. Conclusion TCA has a protective effect against PE-induced cardiac hypertrophy that may be associated with the inhibition of the CaMKII/ERK pathway.

Ischemic stroke is a leading cause of death and disability in the world. At present, reperfusion therapy and neuroprotective therapy, as guidelines for identifying effective and adjuvant treatment methods, are limited by treatment time windows, drug bioavailability, and side effects. Nanomaterial-based drug delivery systems have the characteristics of extending half-life, increasing bioavailability, targeting drug delivery, controllable drug release, and low toxicity, thus being used in the treatment of ischemic stroke to increase the therapeutic effects of drugs. Therefore, this review provides a comprehensive overview of nanomaterial-based drug delivery systems from nanocarriers, targeting ligands and stimulus factors of drug release, aiming to find the best combination of nanomaterial-based drug delivery systems for ischemic stroke. Finally, future research areas on nanomaterial-based drug delivery systems in ischemic stroke and the implications of the current knowledge for the development of novel treatment for ischemic stroke were identified.

Abstract Background Recent studies have shown that the excitatory amino acid transporters (EAATs) are associated with schizophrenia. The aim of this study was to investigate the relationship between the polymorphism of EAAT1 and EAAT2 genes and schizophrenia in Chinese Han population. Methods A total of 233 patients with schizophrenia and 342 healthy controls were enrolled. Two SNPs in EAAT1 gene (rs2269272, rs2731880) and four SNPs in EAAT2 gene (rs12360706, rs3088168, rs12294045, rs10836387) were genotyped by SNaPshot. Clinical features were collected using a self-made questionnaire. Psychotic symptoms of patients were measured by the Positive and Negative Syndrome Scale (PANSS), and patients’ cognitive function was assessed by Matrics Consensus Cognitive Battery (MCCB). Results Significant difference in allelic distributions between cases and controls was confirmed at locus rs12294045 (Ρ = 0.004) of EAAT2 gene. Different genotypes of rs12294045 were associated with family history (P = 0.046), in which patients with CT genotype had higher proportion of family history of psychosis. The polymorphism of rs12294045 was related to working operational memory (LNS: P = 0.016) and verbal learning function (HVLT-R: P = 0.042) in patients in which CT genotype had lower scores. However, these differences were no longer significant after Bonferroni correction. Conclusions Our study showed that the polymorphism of rs12294045 in EAAT2 gene may be associated with schizophrenia in Chinese Han population. CT genotype may be one of the risk factors for family history and cognitive deficits of patients.