Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Objective:To explore the expressions of long noncoding RNA (lncRNA) homeobox A11 antisense RNA (HOXA11-AS) and lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) in hypopharyngeal carcinoma tissues and their relationships with prognosis.Methods:Prospectively, 80 patients with hypopharyngeal carcinoma who were treated in Handan Central Hospital from February 2019 to February 2021 were selected. The hypopharyngeal carcinoma tissues resected surgically and the adjacent normal tissues (more than 2 cm away from the edge of the cancer tissue) were obtained. The expressions of HOXA11-AS and LEF1-AS1 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues and adjacent normal tissues were compared. The relationships between their expressions and clinicopathological features were analyzed. The Kaplan-Meier method was used to analyze the relationships between high/low expressions of HOXA11-AS and LEF1-AS1 and the prognosis of patients with hypopharyngeal carcinoma.Results:The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were higher than those in adjacent normal tissues (all P<0.05). The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were related to tumor node metastasis (TNM) stage, degree of differentiation, and lymph node metastasis (all P<0.05). The 3-year overall survival rates of patients with high expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were lower than those of patients with low expressions (all P<0.05). Conclusions:The expressions of HOXA11-AS and LEF1-AS1 are increased in hypopharyngeal carcinoma tissues, which are related to poor prognosis of patients with hypopharyngeal carcinoma.

Objective:To explore the expressions of long noncoding RNA (lncRNA) homeobox A11 antisense RNA (HOXA11-AS) and lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) in hypopharyngeal carcinoma tissues and their relationships with prognosis.Methods:Prospectively, 80 patients with hypopharyngeal carcinoma who were treated in Handan Central Hospital from February 2019 to February 2021 were selected. The hypopharyngeal carcinoma tissues resected surgically and the adjacent normal tissues (more than 2 cm away from the edge of the cancer tissue) were obtained. The expressions of HOXA11-AS and LEF1-AS1 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues and adjacent normal tissues were compared. The relationships between their expressions and clinicopathological features were analyzed. The Kaplan-Meier method was used to analyze the relationships between high/low expressions of HOXA11-AS and LEF1-AS1 and the prognosis of patients with hypopharyngeal carcinoma.Results:The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were higher than those in adjacent normal tissues (all P<0.05). The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were related to tumor node metastasis (TNM) stage, degree of differentiation, and lymph node metastasis (all P<0.05). The 3-year overall survival rates of patients with high expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were lower than those of patients with low expressions (all P<0.05). Conclusions:The expressions of HOXA11-AS and LEF1-AS1 are increased in hypopharyngeal carcinoma tissues, which are related to poor prognosis of patients with hypopharyngeal carcinoma.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

AIM: To study the effect of intense pulsed light(IPL)combined with meibomian gland massage on postoperative dry eye in cataract patients with meibomian gland dysfunction(MGD).METHODS: A retrospective analysis was conducted on the general data of 100 patients(100 eyes)with cataract and postoperative dry eye syndrome accompanied by MGD treated in our hospital from June 2022 to June 2023. They were divided into a control group(n=50)and an observation group(n=50)according to different treatment methods, and received meibomian gland massage and meibomian gland massage combined with IPL treatment, respectively. The tear film break-up time(BUT), Schirmer I test(S I t), meibomian gland secretion score, ocular surface disease index(OSDI), ocular staining score(OSS), and treatment efficacy of the two groups of patients were compared before treatment and at 1 wk and 1 and 3 mo after treatment.RESULTS: The BUT and SIt in both groups after treatment were higher than those before treatment, while the secretion of meibomian gland, OSS score, and OSDI score were lower than those before treatment(all P<0.05); the observation group had higher levels of BUT and SIT at 1 wk, 1 and 3 mo compared to the control group(all P<0.05), and lower levels of meibomian gland secretion, OSS score, and OSDI score compared to the control group(all P<0.05); the effective rate of treatment in the observation group was 86.0%, which was higher than that in the control group(68.0%; P<0.05).CONCLUSION: IPL combined with meibomian gland massage for treating postoperative dry eye in cataract patients with MGD can promote the extension of BUT, increase tear secretion, and reduce OSS and OSDI scores.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

Objective:To investigate the association between solid fuel use for heating, smoking, and respiratory diseases.Methods:This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases.Results:Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios ( HR) (95% CI) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95% CI) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions:The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.

Objective To investigate the current status of military training injuries among aviation cadets in a university,analyze the influencing factors and propose prevention and control measures.Methods Enrolled in the study in December 2021 were 605 male aviation cadets,of whom 192 were freshmen,202 were sophomores and 211 were juniors.A self-made questionnaire form was developed and used to investigate and analyze the occurrence of training injuries among aviation cadets.Results The rate of training injuries among the aviation cadets was 57.19%,of whom 43.75%were freshmen,60.40%were sophomores,and 66.35%were juniors.Injuries sites were mainly in the lower extremities,with freshmen,sophomores and juniors ranking the first,but with a decreasing trend.In injury-causing subjects,3 000 m race ranked the first in the freshmen,single parallel bars ranked the first in the sophomores,other factors ranked the first in the juniors.In terms of medical care,self-diagnosis and care accounted for 34.97%and outpatient medical care accounted for 46.82%,with the sum of them accounting for 81.79%.Conclusion There is a relatively high rate of training injuries among aviation cadets.The number of training injuries,affected injury sites,injury-causing subjects,onset of seasons and adverse factors vary with the advance of grades and display various features.Further emphasis on health education among aviation cadets and the improvement of outpatient medical service are of great importance to the prevention and treatment of training injuries among aviation cadets.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease globally,with only one Food and Drug Administration(FDA)-approved drug for its treatment.Given MASLD's complex pathophysiology,ther-apies that simultaneously target multiple pathways are highly desirable.One promising approach is dual-modulation of the famesoid X receptor(FXR),which regulates lipid and bile acid metabolism.However,FXR agonists alone are insufficient due to their limited anti-inflammatory effects.This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD.Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger(2018)for molecular docking.Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance(SPR)binding assay,reporter gene ana-lysis,and reverse transcription-polymerase chain reaction(RT-PCR).The anti-inflammatory properties of these compounds were eval-uated in AML12 cells treated with tumor necrosis factor-alpha(TNF-α).Dual-function compounds with FXR agonism and inflamma-tion inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α.The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid.Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists,with 15 exhibiting a strong affinity for FXR recombinant protein.Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb.Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones.Three compounds(2,6,and 8)were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors,while one compound(12)acted as an FXR agonist to inhibit inflammation.These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and in-flammation.In conclusion,compounds 2,6,and 8(genistein,biochanin A,and 7-methoxyisoflavone,respectively)were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation,serving as potential candidates or lead compounds for MASLD therapy.

Objective:To explore the relationship between the expression of long chain non coding ribonucleic acid (LncRNA) small nucleolar RNA host gene 1 (LncRNA SNHG1) and microRNA (miR)-143-3p in nasopharyngeal squamous cell carcinoma (HSCC) tissue and clinical pathological features and prognosis.Methods:A prospective selection was made from 97 HSCC patients admitted to the Handan Central Hospital from March 2016 to March 2018. Surgical resection of HSCC tissue and normal mucosa tissue adjacent to cancer were taken, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LncRNA SNHG1 and miR-143-3p. The patient′s survival status was followed up after leaving the hospital. We compared the differences in the expression of LncRNA SNlHG1 and miR-143-3p in HSCC tissues with different clinical pathological parameters, analyzed the correlation between LncRNA SNHG1 and miR-143-3p expression, and the relationship between LncRNA SNHG1 and miR-143-3p expression and the prognosis of HSCC patients.Results:The expression of LncRNA SNHG1 in HSCC tissue was higher than that in normal mucosa tissue adjacent to cancer ( P<0.05), and the expression of miR-143-3p was lower than that in normal mucosa tissue adjacent to cancer ( P<0.05). The expression of LncRNA SNHG1 in cancer tissues of HSCC patients with tumor node metastasis (TNM) stage Ⅲ, low to medium differentiation, and lymph node metastasis was higher than that of HSCC patients with TNM stage Ⅰ-Ⅱ, high differentiation, and no lymph node metastasis (all P<0.05), and the expression of miR-143-3p was lower than that of HSCC patients with TNM stage Ⅰ-Ⅱ, high differentiation, and no lymph node metastasis (all P<0.05). The expression of LncRNA SNHG1 in HSCC tissues is negatively correlated with the expression of miR-143-3p ( r=-0.522, P<0.05). The 5-year cumulative survival rate of HSCC patients with high expression of LncRNA SNHG1 was lower than that of HSCC patients with low expression of LncRNA SNHG1 ( P<0.05), and the 5-year cumulative survival rate of HSCC patients with low expression of miR-143-3p was lower than that of HSCC patients with high expression of miR-143-3p ( P<0.05). Multivariate Cox regression analysis showed that TNM stage Ⅲ and high expression of LncRNA SNHG1 were risk factors for poor prognosis in HSCC patients (all P<0.05), while high expression of miR-143-3p was a protective factor ( P<0.05). Conclusions:The expression of LncRNA SNHG1 is upregulated and miR-143-3p is downregulated in HSCC tissues, with a negative correlation between the two, which is related to the malignant pathological characteristics and poor prognosis of HSCC.