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Background: As the most common chronic liver disease worldwide, the natural history of metabolic dysfunction-associated steatotic liver disease (MASLD) in general population is barely reported., Methods: The Shanghai Suburban Adult Cohort and Biobank study recruited 36,404 adults between 2016 and 2017, and followed up 25,085 participants between 2019 and 2023 in Songjiang District. A questionnaire survey was conducted by face-to-face interview, and physical examination and laboratory tests were conducted. MASLD was diagnosed by liver ultrasound and the cardiometabolic risk factors (CMRF)., Results: A total of 36,122 and 21,831 participants met the criteria for baseline and follow-up analyses. The prevalence of MASLD at baseline was 36.8% overall, and 73.6% among those with a BMI over 28 kg/m 2 . After a median follow-up time of 4.26 years, the incidence density for MASLD was 8.4, and the recovery density was 11.4 per 100 person-years overall, and was 20.0 and 8.4 per 100 person-years for those with baseline BMI over 28 kg/m 2 . Per 1 kg/m 2 increase in baseline BMI was associated with an 15% increase in incidence (HR=1.15, 95%CI: 1.14-1.17) and an 8% decrease in recovery (HR=0.92, 95%CI: 0.90-0.93). From baseline to follow-up visit, participants who remained non-obese, or remained normal cardiometabolic status always showed the lowest incidence and the highest recovery rate, followed by those with improved status., Conclusions: The prevalence and incidence of MASLD were high among Shanghai residents, and active recovery was also observed. Obesity was the most important risk factor, and weight loss and lipid level reduction were beneficial for preventing or reversing MASLD.

Human papillomavirus (HPV) infection can cause condyloma acuminatum (CA), which is characterized by a high incidence and a propensity for recurrence after treatment. Angiogenesis plays an important role in the occurrence and development of CA. Seryl-tRNA synthetase (SerRS) is a newly identified, potent anti-angiogenic factor that directly binds to the vascular endothelial growth factor (VEGFA) promoter, thereby suppressing its transcription. Emodin is a natural anthraquinone derivative that can promote SerRS expression. This study aimed to investigate the effects of emodin on CA and explore combined treatment strategies. The HPV-infected cell line SiHa was treated with either DMSO, emodin, ALA-PDT or a combination of emodin and ALA-PDT. We observed the effects on cell proliferation, apoptosis and the SerRS-VEGFA pathway. Our findings demonstrated that emodin targets angiogenesis through the SerRS-VEGFA pathway, resulting in the inhibition of SiHa cell proliferation and promotion of apoptosis (p < 0.001). To verify the therapeutic effect of emodin combined with ALA-PDT on HPV-associated tumours in vivo, we established an animal xenograft model by subcutaneously inoculating mice with SiHa cells (n = 4). The results showed that the combination of emodin and ALA-PDT significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.001), thus showing an inhibitory effect on tumour (p < 0.001). Furthermore, we determined that the mechanism underlying the decrease in VEGFA expression after emodin combined with ALA-PDT in CA may be attributed to the promotion of SerRS expression (p < 0.001). The combination of emodin and ALA-PDT holds promise as a novel therapeutic target for CA by targeting neovascularization in condyloma tissues., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, with an escalating incidence rate and a notable potential (up to 5%) for metastasis. Ultraviolet radiation (UVA and UVB) exposure is the primary risk factor for cSCC carcinogenesis, with literature suggesting ultraviolet radiation (UVR) promotes vascular endothelial growth factor A (VEGFA) expression. This study aims to investigate UVR-induced upregulation of VEGFA and explore combination therapeutic strategies. The skin squamous cell carcinoma cell line A431 was exposed to specific durations of ultraviolet radiation. The effect of emodin on ATR/SerRS/VEGFA pathway was observed. The cell masses were also transplanted subcutaneously into mice (n = 8). ATR inhibitor combined with emodin was used to observe the growth and angiogenesis of the xenografts. The results showed that UV treatment significantly enhanced the phosphorylation of SerRS and the expression level of VEGFA in A431 cells (p < 0.05). Treatment with emodin significantly inhibited this expression (p < 0.05), and the combination of emodin and ATR inhibitor further enhanced the inhibitory effect (p < 0.05). This phenomenon was further confirmed in the xenograft model, which showed that the combination of ATR inhibitor and emodin significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.05), thus showing an inhibitory effect on cSCC. This study innovatively reveals the molecular mechanism of UV-induced angiogenesis in cSCC and confirms SerRS as a novel target to inhibit cSCC angiogenesis and progression in vitro and in vivo studies., (© 2024 Wiley Periodicals LLC.)

Caged xanthones represent a class of natural secondary metabolites exhibiting significant potential as antitumor agents. These compounds are characterized by their distinct cage-like structures, which offer novel and compelling frameworks for drug design. Nonetheless, there exists a dearth of research focused on the structural modification of these compounds, particularly in relation to their cage-like architectures. This study aims to address this gap by introducing an innovative synthetic method for constructing a novel caged structure that incorporates a widely employed maleimide group. Drawing upon the well-established synthetic approach for dihydroxanthones previously developed within our research group, we successfully synthesized 13 new caged xanthones using the Diels-Alder reaction. Subsequently, we evaluated their anti-proliferative activity against HepG2, A549, and MDA-MB-231 cell lines. The results revealed that compound 10i exhibited IC 50 values of 15.86 µM ± 1.29, 19.27 µM ± 1.58, and 12.96 µM ± 0.09 against these cell lines, respectively. Further investigations into the mechanism of action of 10i demonstrated its ability to induce G2/M cell cycle arrest and initiate mitochondria-mediated apoptosis in breast cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing public health concern. Modifiable factors such as diet and lifestyle are of research interest in preventing or reversing the disease. The relationship between dairy products and NAFLD remains unclear., Methods: In this cohort study, 36,122 participants aged 20-74 were enrolled by multi-stage, stratified, randomized cluster sampling from 2016 to 2017. A total of 25,085 participants finished at least one follow-up visit from 2019 to 2023. Dairy intake was collected by food frequency questionnaire at baseline. NAFLD was defined as fatty liver diagnosed by ultrasonography with excessive alcohol drink excluded. Logistic regression and Cox proportional hazard models were used to analyze the association between dairy intake and NAFLD., Results: A total of 34,040 participants were included in the baseline analysis. The prevalence of NAFLD was inversely associated with dairy intake (OR >7vs 0 servings/week  = 0.91, 95% CI 0.84-0.98; OR per serving/day increase  = 0.95, 95% CI 0.92-0.99). 20,460 participants entered the follow-up analysis. Among 12,204 without NAFLD at baseline, 4,470 developed NAFLD after a median time of 4.3 years. The incidence of NAFLD was inversely associated with dairy intake (HR >7 vs 0 servings/week  = 0.89, 95% CI 0.81-0.98; HR per serving/day increase  = 0.94, 95% CI 0.89-0.99). Among 8256 with NAFLD at baseline, 3,885 recovered after 4.2-year follow-up. Total dairy intake did not show significant associations with recovery of NAFLD, and the HRs (95% CI) were 0.96 (0.87-1.06) for > 7 servings/week and 0.98 (0.93-1.03) for per serving/day increase., Conclusion: Dairy product intake of more than one serving per day was associated with a lower prevalence and incidence of NAFLD in Chinese population. However, total dairy intake did not show significant association in NAFLD reversal., (© 2024. Asian Pacific Association for the Study of the Liver.)

Objectives: To understand the sleep quality and its influencing factors in patients with type 2 diabetes mellitus (T2DM) who suffered diabetic peripheral neuropathy (DPN), and provide evidence for clinicians to carry out comprehensive intervention measures to improve the sleep quality of patients., Methods: Patients who were admitted to the Endocrinology Department of Affiliated Hospital of Zunyi Medical University were recruited from May to December 2022, and the investigation were conducted by face-to-face interview. The questionnaires included PSQI questionnaire and influencing factors, such as lifestyle and health status., Results: Among the 193 patients, 40.4% of the patients never took physical examination, 56.5% of the patients had duration of illness greater than 5 years, 61.7% of the patients had had an operation, 10.4% of the patients had bad dietary status, and 55.4% of the patients had physical pain. In addition, the PSQI general score was 8.34 ± 3.98, the occurrence rate of poor sleep quality (PSQI ≥ 8) was 54.4%, and the results showed that sleep quality of the physical pain group was worse than the no pain group. Moreover, the results of multivariate analysis revealed that the factors affecting sleep quality were lower frequency of exercise, bad dietary status, lower frequency of physical examination, longer duration of illness, and smoking, and the OR and 95% CI were [1.40, 1.04∼1.89], [3.42, 1.86∼6.29], [1.49, 1.01∼2.20], [1.78, 1.09∼2.92], [2.38, 1.17∼4.88], respectively., Conclusion: Patients with DPN have higher risk of poor sleep quality. Moreover, there were many risk factors associated with poor sleep quality, clinicians and health policymakers should timely detect and effectively intervene in these factors to improve the sleep quality, which is important to enhance the quality of life of T2DM patients complicated with DPN., Competing Interests: The authors declare there are no competing interests., (©2024 Fu et al.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent eczematous lesions and severe pruritus. The economic burden and time penalty caused by the relapse of AD reduce patients' life quality., Summary: AD has complex pathogenesis, including genetic disorders, epidermal barrier dysfunction, abnormal immune responses, microbial dysbiosis of the skin, and environmental factors. Recently, the role of innate immune cells in AD has attracted considerable attention. This review highlighted recent findings on innate immune cells in the onset and progression of AD., Key Messages: Innate immune cells play essential roles in the pathogenesis of AD and enough attention should be given for treating AD from the perspective of innate immunity in clinics., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

To avoid false negative results due to the low cross-reactivity rate (CR) in rapid immunoassay, a group-specific antibody with homogeneous CR toward target compounds is needed for accuracy. In this study, tylosin (TYL) and tilmicosin (TM) were selected as model molecules. Firstly, two-dimensional similarity, electrostatic potential energy, spatial conformation and charge distribution of the haptens TYL-CMO, TYL-6-ACA, TYL-4-APA, TYL-CHO and DES-CMO and target compounds of TYL and TM were obtained using Gaussian 09W and Discovery Studio. The optimal hapten was DES-CMO because it is the most similar to TYL and TM. Subsequently, the mAb 14D5 cell line was obtained with IC 50 values of 1.59 and 1.72 ng/mL for TYL and TM, respectively, and a CR of 92.44%. Finally, amorphous carbon nanoparticles (ACNPs) were conjugated with mAb 14D5 to develop an accurate lateral flow immunoassay (LFA) for detection of TYL and TM by the reflectance value under natural light. The recoveries of TYL and TM ranged from 77.18 to 112.04% with coefficient of variation < 13.43%. The cut-off value in milk samples was 8 ng/mL, and the limits of detection were 11.44, 15.96, 22.29 and 25.53 μg/kg for chicken muscle, bovine muscle, porcine muscle and porcine liver samples, respectively, and the results being consistent with HPLC-UV. The results suggest that the developed LFA is accurate and potentially useful for on-site screening of TYL and TM in milk and animal tissue samples., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Clusiaceae plants contain a wide range of biologically active metabolites that have gotten a lot of interest in recent decades. The chemical compositions of these plants have been demonstrated to have positive effects on a variety of ailments. The species has been studied for over 70 years, and many bioactive compounds with antioxidant, anti-proliferative, and anti-inflammatory properties have been identified, including xanthones, polycyclic polyprenylated acylphloroglucinols (PPAPs), benzophenones, and biphenyls. Prenylated side chains have been discovered in many of these bioactive substances. To date, there have been numerous studies on PPAPs and xanthones, while no comprehensive review article on biphenyls from Clusiaceae has been published. The unique chemical architectures and growing biological importance of biphenyl compounds have triggered a flurry of research and interest in their isolation, biological evaluation, and mechanistic studies. In particular, the FDA-approved drugs such as sonidegib, tazemetostat, daclatasvir, sacubitril and trifarotene are closely related to their biphenyl-containing moiety. In this review, we summarize the progress and development in the chemistry and biological activity of biphenyls in Clusiaceae, providing an in-depth discussion of their structural diversity and medicinal potential. We also present a preliminary discussion of the biological effects with or without prenyl groups on the biphenyls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DZ declared a past co-authorship with the author HX to the handling editor., (Copyright © 2022 Wang, Huang, Zhang, Zheng and Xu.)

In peptide amphiphile, The positively charged amino acid arginine can inspire the ordered self-assembly of gold nanocomposites (AuNPs), transfer positive charge to AuNPs, and weaken the aggregation of AuNPs by electrostatic repulsion, whereas hydrophobic fatty acid chains regulate the self-assembly of AuNPs through hydrophobic interaction, which may be a novel strategy to overcome disordered arrangement and aggregation of AuNPs to obtain an ultra-sensitive electrochemical immunosensor for determining the total aflatoxin amount. In this study, a peptide amphiphile (C14R5), composed of five arginine residues as the hydrophilic chain and myristic acid as the hydrophobic chain, inspired AuNPs to form monodispersed hollow raspberry-like AuNPs (rasAuNPs). rasAuNPs could captured and immobilized large amounts of aflatoxin antigens via the Au-S bonds, resulting in binding to more anti-aflatoxin antibodies. In the absence of aflatoxins, the enriched antigens bound to abundant antibodies, resulting in a low blank signal current. By contrast, in the presence of aflatoxins, enough antibodies could bind to the targets and less antibodies could recognize the antigens, increasing the detection signal intensity. Under the optimal conditions, the developed sensor demonstrated a wide linear range (0.13-29.06 pg mL -1 ) and a low limit of detection for total aflatoxins (0.05 pg mL -1 ) using a mixed standard (AFB1: AFB2: AFG1: AFG2 with a weight ratio of 1:1:1:1) in peanut, peanut milk, and maize powder samples. Hence, this novel strategy improves the sensitivity of electrochemical sensors and can be easily applied to detect other small molecule compound for the purpose of food safety., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in IL-10-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction., (© 2022. The Author(s).)

Objectives: This study aims to investigate the association between CD4 + T cell count and combined antiretroviral therapy (cART) with the prevalence of anal human papillomavirus (HPV) infection among HIV-positive male cohort in China., Methods: A survey was conducted in men from a HIV cohort in Taizhou, China between 2016 and 2019. A face-to-face questionnaire interview was administered, and an anal-canal swab was collected for HPV genotyping., Results: A total of 766 HIV-positive men were recruited. The HPV prevalence was lower among those with increased CD4 + T cell count than those with decreased or unchanged (46.5 vs. 56.6%, p = 0.033) from baseline. In multivariable models, having the current CD4 + T cell count of 350-499 cells/µL (aOR 0.28, 95% CI 0.13-0.64), and of ≥ 500 cells/µL (aOR 0.26, 95% CI 0.11-0.60) were associated with lower prevalence of any type HPV infection compared with those with < 200 cells/µL. Having taken NVP + 3TC + AZT was inversely associated with any high-risk (HR)-HPV (aOR 0.47, 95% CI 0.25-0.90) and any low-risk (LR)-HPV infection (aOR 0.40, 95% CI 0.18-0.88), compared with those taking EFV + 3TC + TDF., Conclusions: Increased CD4 + T cell count at follow-up was significantly associated with lower prevalence of anal HPV infection. Inverse associations between NVP + 3TC + AZT and HR-HPV or LR-HPV infecton were observed., (© 2022. The Author(s).)

Liver function abnormalities are common in patients with inflammatory arthritis. However, the precise mechanism is still unclear. In this study, inflammatory arthritis was established in mice by subcutaneous injection of complete Freund's adjuvant, and the intravenous injection of concanavalin A (Con A) was employed to induce acute immune-mediated hepatitis in mice. The result showed that the arthritis mice were more susceptible to ConA-induced hepatitis than the control mice, as evidenced by increased hepatic necrosis, elevated serum alanine aminotransferase activity, and raised inflammatory cytokines. Besides, the in vitro assay demonstrated that the T cells from arthritis mice were more sensitive to the Con A stimulation than those from control mice. Moreover, we determined that the level of leptin, a kind of adipokine, was significantly increased in the serum and hepatic T cells of arthritis mice. Interestingly, the data indicated that the enhanced expression of leptin in hepatic T cells is responsible for the hypersensitivity of arthritis mice-derived T cells to Con A challenge. Collectively, our findings demonstrate an unexpected role of leptin in the connection between inflammatory arthritis and acute immune-mediated hepatitis, thus providing new insight into the clinical therapy of arthritis-related liver dysfunction., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

1,2-Dihydroxanthones (DHXs) are core structures of natural products and useful building blocks in organic synthesis. So far, they have been less studied. In this report, a mild, efficient and green method for the synthesis of 1,2-dihydroxanthones has been developed in one pot through Claisen condensation and O-cyclization under waste-induced relay catalysis with minimum organic solvents. The by-product (HMDS or NH3·H2O) of the first step turned out to be the promoter for the second step, which could efficiently proceed in aqueous media without the addition of other catalysts. The reactions using trifluoroethyl salicylates could be performed under mild conditions to ensure the generation of vulnerable DHXs in high yields. The substrate scope is very broad regardless of the substituent type and its position on the structure. Specifically, the versatility of DHXs was demonstrated by their conversion to xanthones and other complex structures.

The gut microbiota consists of a dynamic multispecies community living within a particular niche in a mutual synergy with the host organism. Recent findings have revealed roles for the gut microbiota in the modulation of host immunity and the development and progression of immune-mediated diseases. Besides, growing evidence supports the concept that some metabolites mainly originated from gut microbiota are linked to the immune regulation implicated in systemic inflammatory and autoimmune disorders. In this chapter, we describe the recent advances in our understanding of how host-microbiota interactions shape the immune system, how they affect the pathogenesis of immune-associated diseases and the impact of these mechanisms in the efficacy of disease therapy.

Objective: To find a suitable dividing value to classify cystatin C and evaluate the association between cognition and levels of cystatin C., Methods: Using data from the China Health and Retirement Longitudinal Study, We conducted a longitudinal analysis of a prospective cohort of 6,869 middle-aged and older Chinese without cognitive impairment at baseline. Levels of cystatin C were categorized into 2 groups by method of decision tree. Logistic regression models evaluated whether cystatin C was related to cognitive impairment., Results: Respondents were categorized as lower levels of cystatin C and higher levels of cystatin C, cut-point was 1.11 mg/L. Higher levels of cystatin C was associated with the odds of cognitive impairment (OR, 1.56; 95% CI, 1.10-2.22) after multivariable adjustment. Respondents with higher levels of cystatin C had worse cognition scores., Conclusions: We found a suitable dividing value of cystatin C in middle-aged and older Chinese.

Mannan-binding lectin (MBL) is a vital element in the host innate immune system, which is primarily produced by the liver and secreted into the circulation. Low serum level of MBL is reported to be associated with an increased risk of arthritis. However, the underlying mechanism by which MBL contributes to the pathogenesis of arthritis is poorly understood. In this study, we investigated the precise role of MBL on the course of experimental murine adjuvant-induced arthritis (AIA). MBL-deficient (MBL -/- ) AIA mice showed significantly increased inflammatory responses compared with wild-type C57BL/6 AIA mice, including exacerbated cartilage damage, enhanced histopathological features and high level of tartrate-resistant acid phosphatase (TRAP)-positive cells. MBL protein markedly inhibited the osteoclast formation from human blood monocytes induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in vitro . Mechanistic studies established that MBL inhibited osteoclast differentiation via down-regulation of p38 signaling pathway and subsequent nuclear translocation of c-fos as well as activation of nuclear factor of activated T-cells c1 (NFATc1) pathway. Importantly, we have provided the evidence that concentrations of MBL correlated negatively with the serum levels of amino-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (β-CTX), serum markers of bone turnover, in patients with arthritis. Our study revealed an unexpected function of MBL in osteoclastogenesis, thus providing new insight into inflammatory arthritis and other bone-related diseases in patients with MBL deficiency.

Many human action sequences, such as speaking and performing music, are inherently rhythmic: Sequence events are produced at quasi-regular temporal intervals. A wide range of interindividual variation has been noted in spontaneous production rates of these rhythmic action sequences. Dynamical theories of motor coordination suggest that individuals spontaneously produce rhythmic sequences at a natural frequency characterized by minimal energy expenditure and maximal temporal stability, relative to other frequencies. We tested this hypothesis by comparing the temporal variability with which musicians performed rhythmic melodies at their natural spontaneous rate with variability in their performances at faster and slower rates. Musicians' temporal variability was lowest during performances at their spontaneous rate; in addition, performers' tempo drift during trials at other rates showed bias toward their spontaneous rate. This study provides the first direct evidence that spontaneous rates of motor coordination represent optimally stable natural frequencies of endogenous rhythms.

This paper is concerned with the problem of designing fuzzy controllers for a class of nonlinear dynamic systems. The considered nonlinear systems are described by T-S fuzzy models with nonlinear local models, and the fuzzy models have fewer fuzzy rules than conventional T-S fuzzy models with local linear models. A new fuzzy control scheme with local nonlinear feedbacks is proposed, and the corresponding control synthesis conditions are given in terms of solutions to a set of linear matrix inequalities (LMIs). In contrast to the existing methods for fuzzy control synthesis, the new proposed control design method is based on fewer fuzzy rules and less computational burden. Moreover, the local nonlinear feedback laws in the new fuzzy controllers are also helpful in achieving good control effects. Numerical examples are given to illustrate the effectiveness of the proposed method.