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Interactions between adipose tissue, liver and immune system are at the center of metabolic dysfunction-associated steatotic liver disease and type 2 diabetes. To address the need for an accurate in vitro model, we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells. Using this MPS, we find that increasing the adipocyte-to-hepatocyte ratio moderately affects hepatocyte function, whereas macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease. We also use our MPS to identify and characterize pharmacological intervention strategies for hepatic steatosis and systemic insulin resistance and find that the glucagon-like peptide-1 receptor agonist semaglutide improves hepatocyte function by acting specifically on adipocytes. These results establish our MPS modeling the adipose tissue-liver axis as an alternative to animal models for mechanistic studies or drug discovery in metabolic diseases.

Abstract Pulmonary fibrosis is a chronic interstitial lung disease with no curative therapeutic treatment, leading to significant mortality. The aims of this study were to investigate the regulatory mechanisms of mitophagy in the progression of pulmonary fibrosis. Through bioinformatics analysis, we identified the downregulation of long-chain fatty acyl-CoA synthetase 1 (ACSL1) as being associated with the severity of pulmonary fibrosis. A pulmonary fibrosis model was established through bleomycin (BLM) exposure both in vivo and in vitro. Mitoquinone (MitoQ) pretreatment significantly decreased redox damage, stabilized mitochondrial membrane potential (MMP), improved mitochondrial dynamics, and activated PINK1/Parkin-mediated mitophagy, thereby alleviating pulmonary fibrosis. In vitro, overexpression of ACSL1 mitigated mitochondrial damage and restored PINK1/Parkin-mediated mitophagy under BLM exposure. In contrast, ACSL1 inhibition exacerbated pulmonary fibrosis, and these adverse effects could not be reversed by MitoQ treatment. Taken together, our study reveals a novel mechanism underlying the pathogenesis of pulmonary fibrosis and suggests a potential therapeutic target for its treatment.

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

Abstract VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.

Objective Lupus nephritis （LN） is the most common and serious organ involvement in patients with systemic lupus erythematosus. Immunosuppressant therapy can significantly improve the renal function outcome of patients. The purpose of this study is to evaluate the effect of tacrolimus combined with glucocorticoid on LN patients and provide theoretical rationales for managing LN. Methods Such Chinese and English databases as PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure （CNKI）, Wanfang Medical Network and VIP Information Chinese Periodical Service Platform were searched until February 2023. Review Manager and Sata software were employed for system analysis. For continuous variables, standardized mean difference （SMD） and its 95%CI were used. And relative risk （RR） and its 95%CI were employed for binary variables. Cochrane's bias risk tool was utilized for evaluating the bias and risks of eligible studies. Results A total of 12 articles involving 1360 LN patients were finally included. As compared with control group, tacrolimus plus glucocorticoid could significantly improve the partial remission rate （RR value of 1.33, P = 0.02）, effective rate （RR value of 1.28, P＜0.001）, creatinine level （SMD value of −1.12, P = 0.0009） and 24-hour urine protein level （SMD of −1.88, P＜0.001）. And it did not elevate the occurrence of gastrointestinal discomfort, liver dysfunction or infection. Conclusion Tacrolimus plus glucocorticoid therapy helps to improve renal function outcomes of LN patients.

Solar radiation plays a pivotal role in urban microclimate, significantly, impacting building energy consumption and renewable energy utilization. Utilizing a comprehensive three- and-a- half-year dataset of high-precision urban microclimate, this study proposes a three-step approach to solar radiation prediction: 1) Data Preprocessing and Characterization: The microclimate data are meticulously preprocessed and categorized, with solar radiation values categorized into three resolutions: total daily solar radiation, hourly solar radiation, and 30-min solar radiation. 2) Feature Selection: Various climatic parameters are carefully selected for solar radiation prediction at different resolutions. 3) Machine Learning Models: Three machine learning models, namely Long Short-Term Memory (LSTM), Random Forest (RF) and Support Vector Regression (SVR), are employed for solar radiation prediction. The results show that all three models exhibit prediction accuracy with closely matched errors. Particularly noteworthy findings include SVR’s superior performance in predicting total daily solar radiation with a minimal error rate of about 6.0% and an impressive coefficient of determination of 0.9789. LSTM exhibits adaptability, achieving R2 values of 0.9906 and 0.9956 for hourly and 30-min radiation predictions, respectively. This study offers valuable insights into solar radiation and its implications for building energy research. It underscores that large datasets enable accurate solar radiation predictions, even when excluding certain parameters like daily maximum temperature and relative humidity.

Abstract Background Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015–2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life’s Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. Results In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. Conclusion Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Abstract Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

Objective To investigate the effect of salidroside (SAL) on the proliferation and migration of human vascular endothelial cell line EA.hy926. Methods The cells were divided into control group and test groups of 1,10 and 100 nmol/L SAL, 10 nmol/L SAL+2 μg/mL avastin (vascular endothelial growth factor(VEGF) blocker) group, 10 nmol/L SAL+2 μg/mL IgG (blocker negative control) group, 10 nmol/L SAL+8 μg/mL avastin group, 10 nmol/L SAL+8 μg/mL IgG group, 10 μmol/L YC-1[hypoxia inducible factor-1α(HIF-1α) blocker] group and 10 μmol/L YC-1+10 nmol/L SAL group. The proliferation and migration of EA.hy926 cells were detected by MTS assay and Transwell cell migration experiments. RT-qPCR and Western blot were used to measure the gene and protein level of HIF-1α and VEGF. The luciferase report gene experiment was used to find the effect of SAL on HIF-1α transcription activity of EA.hy926 cells.The guanylate cyclase activator (YC-1) was used as a HIF-1α blocker to verify potential effect of SAL on the expression of VEGF through HIF-1α. Results SAL significantly promoted proliferation of EA.hy926 cells (P＜0.05)and the proliferation promoting effect of SAL(10 nmol/L) was significantly reduced by the VEGF blocker bevacizumab avastin(2 μg/mL) (P＜0.05). SAL significantly promoted migration of EA.hy926 cells (P＜0.05), and this effect was significantly inhibited by avastin(8 μg/mL)(P＜0.05). SAL increased the expression of HIF-1α and VEGF gene and protein, and promoted the transcription of HIF-1α (P＜0.05).The level of HIF-1α and VEGF protein decreased by YC-1, a HIF-1α blocker(P＜0.05). Conclusions HIF-1α/VEGF pathway is potentially involved in SAL promoted proliferation and migration of EA.hy926 cells.

Ultraviolet mutagenesis is a safe and efficient method to induce mutations in laver. It has the advantages of non-pollution, high efficiency, easy operation, and low cost. It has been primarily used for mutagenesis of the filament, protoplast, or blade of cultivated Pyropia species, but is rarely used to induce genetic mutants from germinating conchospore. The germination period of conchospores is the period of meiosis in Pyropia haitanensis. The four progeny cells of germinating conchospores are linearly arranged forming a meiotic tetrad. The tetrad cells that undergo genetic recombination can determine the developmental pattern and segregation of traits in the thallus. In this study, short-wave ultraviolet (UV-C) irradiation with different doses (50, 100, 200, 300, 400, 500, and 600 J/m2) was used to induce color mutants during the germination of conchospores in P. haitanensis. The results showed that low-dose irradiation (50 J/m2) promoted the germination of conchospores, while irradiation doses above 100 J/m2 inhibited the germination and growth of tetrad germlings. Therefore, low-doses of UV-C irradiation were used in the production to promote the germination of conchospores and improve the production efficiency of laver. In the dose range of 50–400 J/m2, the frequency of color chimeras increased with increasing irradiation intensity. When the dose was 300 J/m2 and 400 J/m2, and the pigmentation mutation rate was 15.22% and 17.18%, respectively, and the death rate of conchospores was 51.70% and 61.00%, respectively. In the dose range of 50–500 J/m2, with the increase in UV-C irradiation dose, the proportion of 2-color sectored chimera showed a trend of first decreasing and then increasing, and the proportion of 3- and 4-color sectored chimera showed a trend of first increasing and then decreasing. Among them, the regenerated color chimeras that appear were generally 2- and 3-color sectored chimera, yet the proportion of 4-color sectored chimera was the least. When the irradiation intensity reached 500 J/m2, the majority of the conchospores died, and the death rate was 83.98%, and the frequency of color mutants was significantly lower than that of 300 J/m2 and 400 J/m2 dose groups. These results indicate that the mutagenesis effect was the best when the dose was 300 or 400 J/m2, which was convenient to obtain abundant genetic recombination and genetic variation in progeny cells. In addition, UV-C irradiation also had a significant effect on the early development of conchospores and phenotypes of pigmentation mutant arranged in tetrad germlings, which was mainly manifested in the large number of color-sectored blades developed from the irradiated conchospores. Simultaneously, UV-C irradiation retarded the development of cells at the top of conchospore germlings, inhibited the development of cells at the middle base toward the poles, and increased the lateral development, resulting in the decrease in blade aspect ratios. Somatic cell germlings with single colored pigmentation were also isolated from color sectored chimeras by enzymatic hydrolysis. The color species of the five monochromatic mutants obtained were basically consistent with the pigment variant sectors observed on color-sectored thallus, indicating that the obtained color mutants were derived from a single mutant cell on the maternal color-sectored thallus. In conclusion, UV-C irradiations can effectively mutate the conchospores of P. haitanensis, and appropriate irradiation doses (300 or 400 J/m2) can obtain a certain number of color-sectored thallus. This study provides a novel pathway for the preparation of artificial color mutants and mutation breeding in P. haitanensis.

Abstract Objective This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. Methods We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. Results Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). Conclusion Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

Abstract Chiral amides are important structure in many natural products and pharmaceuticals, yet their efficient synthesis from simple amide feedstock remains challenge due to its weak Lewis basicity. Herein, we describe our study of the enantioselective synthesis of chiral amides by N-alkylation of primary amides taking advantage of an achiral rhodium and chiral squaramide co-catalyzed carbene N–H insertion reaction. This method features mild condition, rapid reaction rate (in all cases 1 min) and a wide substrate scope with high yield and excellent enantioselectivity. Further product transformations show the synthetic potential of this reaction. Mechanistic studies reveal that the non-covalent interactions between the catalyst and reaction intermediate play a critical role in enantiocontrol.

BackgroundCDGSH iron-sulfur domain 2 (CISD2), an iron-sulfur protein with a [2Fe-2S] cluster, plays a pivotal role in the progression of various cancers, including Diffuse Large B-cell Lymphoma (DLBCL). However, the mechanisms by which CISD2 regulates the occurrence and development of DLBCL remain to be fully elucidated.MethodsThe potential role of CISD2 as a predictive marker in DLBCL patients treated with the R-CHOP regimen was investigated through bioinformatics analysis and clinical cohort studies. DLBCL cell lines (SUDHL-4 and HBL-1) were employed in this research. Adenoviral (AV) plasmids were used to either silence or overexpress CISD2 in these DLBCL cell lines. Additionally, the induction of ferroptosis in DLBCL cell lines was assessed. Various parameters, including cell proliferation, intracellular free iron levels, lipid peroxides, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), were measured. Furthermore, the expression of proteins associated with ferroptosis and ferritinophagy was analyzed. Drug-resistant DLBCL cell lines were developed by gradually increasing doxorubicin (DOX) concentration over 6 months. The biological role of CISD2 in these drug-resistant DLBCL cell lines was subsequently assessed.ResultsElevated CISD2 levels were found to be associated with decreased sensitivity of DLBCL patients to the R-CHOP regimen, as indicated by bioinformatics and clinical cohort analysis. Silencing CISD2 significantly reduced cell proliferation, increased iron accumulation, depleted glutathione (GSH), and elevated malondialdehyde (MDA) levels, alongside the accumulation of ROS and increased MMP. Additionally, BECN1 and NCOA4 expressions were upregulated, while p62, FTH1, and GPX4 expressions were downregulated. Conversely, overexpression of CISD2 reversed these effects. Treatment of DLBCL cell lines with Erastin led to decreased CISD2 levels. Notably, in drug-resistant DLBCL cell lines, CISD2 knockdown promoted ferroptosis and ferritinophagy, restoring sensitivity to DOX and enhancing the efficacy of Erastin treatment.ConclusionOur findings suggest that CISD2 may play a role in the drug resistance observed in DLBCL patients. Inhibition of CISD2 could enhance ferroptosis and ferritinophagy, potentially improving the sensitivity of DLBCL cells to DOX treatment.

Purpose: To investigate the effects of hydroxybutyl chitosan (HBCS) with and without 5-fluorouracil (5-FU) during endoscopic endonasal dacryocystorhinostomy (Endo-DCR). In addition, the present study observed the impact of HBCS and 5-FU on the functions of the nasal mucosal cell population in vivo. Methods: Patients were randomized into HBCS (group A), HBCS combined with 5-FU (group B), and gelatin sponge control group (group C). 16S rRNA high-throughput sequencing technology examined the conjunctival sac and nasal flora changes. In addition, CCK8, cell scratching, and flow cytometry were used to investigate the effects of HBCS and 5-FU on the nasal mucosal cell populations. Results: Subjects in groups A, B, and C had anastomotic areas of 21.83 ± 12.69 mm2, 21.57 ± 14.53 mm2, and 12.45 ± 8.16 mm2, respectively (P = 0.0359). Group A had less severe epiphora than the other two groups at 1-, 2-, and 12-week postoperative follow-up (P < 0.05). Complications around the anastomosis in group A were the least severe of the three groups (P = 0.0259). After surgery, the proportion of pathogenic bacteria in the conjunctival sac and nasal cavity was higher in groups A and B than in healthy adults. At the 2-week follow-up, the structure of nasal flora in group A was more similar to that of the healthy adults compared to group B. Conclusion: Intraoperative use of HBCS at the anastomose improves the postoperative outcome of En-DCR. 5-FU cannot give better postoperative results in En-DCR and is detrimental to the normalization of the postoperative flora in patients with chronic dacryocystitis. At the cellular level, both HBCS and 5-FU inhibit the migration of nasal mucosal cell populations, and 5-FU inhibits proliferation but does not promote apoptosis.

This study explored the effect of sesamol on the stability of walnut oil based on the changes of endogenous characteristics in the oxidation process, which provided a theoretical reference for the application of natural antioxidants in walnut oil. A total of 300 mg/kg sesamol (SP), compound antioxidant AC (sesamol 353.62 mg/kg, citric acid 149.60 mg/kg, and BHA 76.33 mg/kg) and 35% sesame oil (35%-SO) were added to walnut oil respectively; in addition, 200 mg/kg t-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and citric acid were used as controls and blank walnut oil to study their effects on peroxide value, acid value, carbonyl compounds, conjugated olefins, phenols, flavonoids, sterols, vitamin E, β-carotene, and 51 fatty acids of walnut oil and their correlation between endogenous antioxidant components. The results showed that the addition of SP, 35%-SO, and AC could inhibit the increase of peroxide value, acid value, and carbonyl compounds in walnut oil, and could inhibit the decrease of β-carotene, total phenols, total sterols, and vitamin E. SP and 35%-SO could inhibit the decrease of total flavonoids, and several antioxidants could inhibit the decrease of endogenous antioxidant components in walnut oil. At the same time, it can better inhibit the change of unsaturated fatty acids in walnut oil. By the end of oxidation, the unsaturated fatty acids of blank walnut oil decreased by 10.31%, but AC, SP, and 35%-SO treatment groups increased by 10.90, 5.09 and 4.13%, respectively. Indicating that it had a certain protective effect on unsaturated fatty acids in walnut oil. There was a certain correlation between the endogenous substances of walnut oil. so the addition of several antioxidants can enhance the endogenous antioxidants of walnut oil, inhibit the oxidation of unsaturated fatty acids, and inhibit the increase of carbonyl compounds, codienes, acid value, and peroxide value. SP and AC have better antioxidant effects on walnut oil and improve the stability of walnut oil.

IntroductionThe impacts of plastic pollution on soil ecosystems have emerged as a significant global environmental concern. The progress in understanding how plastic pollution affects soil microbial communities and ecological functions is essential for addressing this issue effectively.MethodsA bibliometric analysis was conducted on the literature from the Web of Science Core Collection database to offer valuable insights into the dynamics and trends in this field.ResultsTo date, the effects of plastic residues on soil enzymatic activities, microbial biomass, respiration rate, community diversity and functions have been examined, whereas the effects of plastic pollution on soil microbes are still controversial.DiscussionTo include a comprehensive examination of the combined effects of plastic residue properties (Type, element composition, size and age), soil properties (soil texture, pH) at environmentally relevant concentrations with various exposure durations under field conditions in future studies is crucial for a holistic understanding of the impact of plastic pollution on soil ecosystems. Risk assessment of plastic pollution, particularly for nanoplasctics, from the perspective of soil food web and ecosystem multifunctioning is also needed. By addressing critical knowledge gaps, scholars can play a pivotal role in developing strategies to mitigate the ecological risks posed by plastic pollution on soil microorganisms.

Spinal cord injury (SCI) is a central nervous system injury that leads to neurological dysfunction or paralysis, which seriously affects patients' quality of life and causes a heavy social and economic burden. The pathological mechanism of SCI has not been fully revealed, resulting in unsatisfactory clinical treatment. Therefore, more research is urgently needed to reveal its precise pathological mechanism. Numerous studies have shown that inflammation is closely related to various pathological processes in SCI. Inflammatory response is an important pathological process leading to secondary injury, and sustained inflammatory response can exacerbate the injury and hinder the recovery of neurological function after injury. Epigenetic modification is considered to be an important regulatory mechanism in the pathological process of many diseases. Epigenetic modification mainly affects the function and characteristics of genes through the reversibility of mechanisms such as DNA methylation, histone modification, and regulation of non-coding RNA, thus having a significant impact on the pathological process of diseases and the survival state of the body. Recently, the role of epigenetic modification in the inflammatory response of SCI has gradually entered the field of view of researchers, and epigenetic modification may be a potential means to treat SCI. In this paper, we review the effects and mechanisms of different types of epigenetic modifications (including histone modifications, DNA methylation, and non-coding RNAs) on post-SCI inflammation and their potential therapeutic effects on inflammation to improve our understanding of the secondary SCI stage. This review aims to help identify new markers, signaling pathways and targeted drugs, and provide theoretical basis and new strategies for the diagnosis and treatment of SCI.

Abstract Grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) are the most damaging pests to alpine meadows in the Qinghai–Tibetan Plateau (QTP). Here, we conducted extensive sampling from 39 geographic populations covering almost the entire distribution of the eight QTP Gynaephora (Hübner) species to investigate phylogeographic patterns and speciation based on two mitochondrial genes (COI and ND5). A total of 40 haplotypes were detected in the 39 populations, with >70% of all haplotypes not shared between populations. The monophyletic QTP Gynaephora migrated from non‐QTP regions during the Pliocene, corresponding to the uplift of the QTP, suggesting a mode of transport into the QTP. Among the eight QTP Gynaephora species described by morphological characteristics, two species (G. alpherakii and G. menyuanensis) were recovered as monophyletic groups (Clades B and C), while the remaining six formed two monophyletic clades: Clade A (G. qinghaiensis, G. jiuzhiensis, and G. qumalaiensis) and Clade D (G. aureata, G. ruoergensis, and G. minora). These results suggested that the number of the QTP Gynaephora species may be overestimated and further studies based on both morphological and nuclear gene data are needed. Genetic differentiation and speciation of the QTP Gynaephora were likely driven by the QTP uplifts and associated climate fluctuations during the Pleistocene, indicated by divergence time estimation, suggesting that isolation and subsequent divergence was the dominant mode of speciation. The Sanjiangyuan region (i.e., Clade A, characterized by high genetic diversity) may have been a glacial refugium of the QTP Gynaephora, as supported by analyses of gene flow and biogeography. High levels of genetic diversity were found in QTP Gynaephora, without population expansion, which may explain the high‐altitude adaptation and outbreaks of grassland caterpillars in alpine meadows of the QTP. This study provides the largest phylogeographic analysis of QTP Gynaephora and improves our understanding of the diversity and speciation of QTP insects.

IntroductionCasuarina equisetifolia is a common protective forest in coastal areas. However, artificial C. equisetifolia forests cannot self-renew, mainly due to the accumulation of allelochemicals. Endophytic bacteria may alleviate the root growth inhibition caused by allelochemicals in C. equisetifolia seedlings. B. amyloliquefaciens and B. aryabhattai were endophytic bacteria with strong allelopathy in C. equisetifolia root. The allelopathy mechanism of these two endophytes and their interaction with C. equisetifolia remains to be studied.MethodsWhole-genome sequencing of B. amyloliquefaciens and B. aryabhattai isolated from the roots of allelochemical-accumulating C. equisetifolia was performed using Illumina Hiseq and PacBio single-molecule sequencing platforms. Sterile seedlings of C. equisetifolia were treated with either individual or mixed bacterial cultures through root drenching. Transcriptional and metabolomics analyses were conducted after 3 days of infection.Results and discussionWhole-genome sequencing of Bacillus aryabhattai and Bacillus amyloliquefaciens showed that the two strains contained various horizontal gene transfer elements such as insertion sequence, prophage and transposon. In addition, these two strains also contain numerous genes related to the synthesis and catabolism of allelochemicals. After these two strains of bacteria were individually or mixed infected with C. equisetifolia, metabolomics and transcriptomic analysis of C. equisetifolia showed the 11 important secondary metabolite biosynthesis among them alkaloids biosynthesis, phenylpropanoid and terpenes biosynthesis and related genes were putatively regulated. Correlation analysis revealed that 48 differentially expressed genes had strong positive correlations with 42 differential metabolites, and 48 differentially expressed genes had strong negative correlations with 36 differential metabolites. For example, CMBL gene showed positive correlations with the allelochemical (-)-Catechin gallate, while Bp10 gene showed negative correlations with (-)-Catechin gallate.ConclusionThe intergenerational accumulation of allelochemicals may induce horizontal gene transfer in endogenic bacteria of Casuarina equisetifolia root. Endophytic Bacillus plays an allelopathic role by assisting the host in regulating gene expression and the production and/or variety of allelochemicals. This comprehensive study sheds light on the intricate genetic and metabolic interactions between Bacillus endophytes and C. equisetifolia. These findings provide insights into endophyte-mediated allelopathy and its potential uses in plant biology and forest sustainability.