Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

The efficacy of root canal therapy, as a core intervention for endodontic and periapical diseases, is highly dependent on the effectiveness of antimicrobial drugs. Although traditional drugs such as calcium hydroxide, chlorhexidine, and antibiotic pastes commonly used in the clinic play a role in preventing and controlling infections, they have obvious limitations. These drugs influence the mechanical properties of dentin, insufficiently solubilize necrotic tissues, and are susceptible to bacterial resistance, which makes achieving the desired effectiveness and safety difficult. Traditional macromolecular root canal drugs also face the challenge of the complexity of the root canal system. With the rapid development of material science in recent years, new antimicrobial agents have emerged. Metallic nanomaterials such as silver nanoparticles and zinc oxide nanoparticles are widely used in the medical field due to their unique physicochemical properties and superior antimicrobial properties. Chitosan nanoparticles have superior biosafety, calcium hydroxide nanoparticles compensate for the limitations of traditional calcium hydroxide formulations, and quaternary ammonium polyethyleneimine nanoparticles can confer antimicrobial properties to existing oral materials. Novel antimicrobial nanoparticles using nano-delivery systems, such as mesoporous calcium silicate and mesoporous silica, carry antimicrobial molecules with significant advantages in terms of anti-biofilm, biosafety, and promotion of tissue repair. Further, these agents reduce drug resistance, which improves prospects for application compared to traditional root canal disinfection drugs. The breakthrough of nanotechnology provides a novel direction for the innovation of root canal treatment drugs. Therefore, this paper reviews the research progress of nano-antimicrobial materials in root canal therapy.

ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids （SCFAs）. MethodsRats were randomly divided into a control group， a high-dose group of Dictamni Cortex （8.1 g·kg^-1）， a medium-dose group （2.7 g·kg^-1）， and a low-dose group （0.9 g·kg^-1）. Except for the control group， the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the level of cytokines， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）， in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction （Real-time PCR） technology was used to detect the expression level of tight junction proteins， including zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 mRNAs， in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group， all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum， increased TNF-α （P<0.01）， IL-6 （P<0.01）， and IL-1β （P<0.01） levels in the ileal tissue， and decreased the expression level of ZO-1 （P<0.05， P<0.01）， Occludin （P<0.01）， and Claudin-1 （P<0.05） in the ileal tissue， with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group， after Dictamni Cortex intervention， the level of 14 metabolites was significantly increased （P<0.05， P<0.01）， and the level of seven metabolites was significantly decreased （P<0.05， P<0.01） in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways， including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid， butyric acid， acetic acid， caproic acid， isobutyric acid， isovaleric acid， valeric acid， and isocaproic acid in the ileal contents of rats. Compared with those in the control group， the level of isobutyric acid， isovaleric acid， and valeric acid were significantly increased， while the level of propionic acid， butyric acid， and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention （P<0.05， P<0.01）. ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism， primary bile acid biosynthesis， and metabolic pathways for SCFAs.

Objective To analyze the trend of influenza epidemic intensity in Urumqi City, Xinjiang, in early 2023, and to provide a reference basis for influenza surveillance, prevention and control. Methods Based on the daily number of influenza cases in Urumqi from January 1, 2023 to March 26, 2023, a generalized linear model was established to correlate the cumulative number of cases with the number of days of illness, and the corresponding doubling time was calculated. Results A total of 9 243 influenza cases were included in this study, including 7733 confirmed cases and 1510 suspected cases. The peak incidence of influenza occurred in March, and 6039 positive cases were detected, with a positivity rate of 78.09%. The age group of 3-6 years old had the highest proportion of influenza positive cases, accounting for 32.20%. The longest doubling time among confirmed cases was 13.49 (95% CI:11.95-15.47) in stage 2 (January 22 to February 13), and the shortest was in stage 3 (February 14 to March 26), which was 9.41 (95% CI:8.24-10.91). Conclusion The shorter the doubling time, the faster the speed of influenza transmission, and it is necessary to strengthen the prevention and control of influenza in winter and spring.

BACKGROUND: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

This study explores the basic characteristics and potential functions of the terpene synthase(TPS) gene family members in Lonicera japonica. The L. japonica TPS(LjTPS) gene family was identified and functionally analyzed using bioinformatics methods. The results showed that a total of 70 members of the LjTPS gene family were identified in L. japonica, with protein lengths ranging from 130 to 1 437 amino acids. Most of these proteins were hydrophilic, and they were unevenly distributed across nine chromosomes. Phylogenetic analysis showed that the LjTPS gene family members were divided into six subfamilies, mainly consisting of members from the TPS-a, TPS-b, and TPS-e subfamilies. Promoter cis-acting element analysis showed that LjTPS members contained a large number of stress-responsive cis-acting elements. Aphid inoculation experiments showed that key enzyme genes in the MVA pathway for terpenoid backbone synthesis in L. japonica, such as HMGS, HMGR, MK, MPD, and the key enzyme gene in the DXP pathway, DXS, exhibited an initial increase followed by a decrease under aphid stress. The qRT-PCR analysis showed that the expression levels of the α-farnesene synthase genes LjTPS34 and LjTPS39 were down-regulated, while the expression levels of(E)-β-caryophyllene synthase genes LjTPS15 and LjTPS17 were up-regulated 12 h before aphid feeding, then began to decline. Farnesyl pyrophosphate synthase(FPS), which interacted with these genes, also displayed a pattern of increasing followed by decreasing expression. The expression of linalool synthase genes LjTPS12 and LjTPS33 was significantly up-regulated after 72 h of aphid feeding(P<0.000 1), reaching 24.39 and 22.64 times the initial expression, respectively. This pattern was in close alignment with the trend of linalool content in L. japonica. This study provides a theoretical foundation for future research on the interaction between L. japonica and pests, as well as on the functional roles of the LjTPS gene family.
Animals ; Aphids/physiology* ; Alkyl and Aryl Transferases/chemistry* ; Lonicera/parasitology* ; Phylogeny ; Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Multigene Family ; Terpenes/metabolism*