The impact of a curriculum-based research training program on medical students' research productivity and future research interests: a longitudinal study.

BACKGROUND: Incorporating scientific research into undergraduate medical education is necessary for the quality of future health care. However, providing rigorous research training to a large number of medical students at one institution remains one of the major challenges. The authors studied the impact of a curriculum-based Research Training Program (RTP) for all undergraduate students at Zhejiang University School of Medicine (ZUSM) on research productivity and future research interests. METHODS: Medical students (n = 2,213) from ZUSM who completed the course of RTP between 2013 and 2020 were studied. The authors measured the academic performance, research publications, and research projects of students across years, and evaluated potential factors that contribute to student research productivity and increased interest in future research. RESULTS: Across the years, there was an increase in the number of student publications, a greater proportion of students with publications, and a greater proportion of projects involving three or more students (P < .01 for all). The academic performance of the course was associated with increased publications (P = .014), whereas overall satisfaction of the course (OR 2.07, 95% CI [1.39, 3.10], P < .001), Skill Composite Score (SCS) (OR 1.70, 95% CI [1.16, 2.50], P = .007), and male gender (OR 1.50, 95% CI [1.06, 2.12], P = .022) were associated with increased future research interests. CONCLUSIONS: The findings suggest that the curriculum-based RTP improved students' research productivity, and that overall program satisfaction and self-assessed performance were associated with increased students' intent to participate in future research.

Efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor hydrogel in treating second- or third-degree burn wounds in children: a systematic review and meta-analysis.

Background: The efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) hydrogel in adults with deep partial-thickness burns have been confirmed. However, the clinical safety and efficacy analysis of rhGM-CSF in pediatrics is lacking, and the results are questionable. Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of rhGM-CSF hydrogel in children with second- or third-degree burn injury to provide evidence-based medicine for clinical application. Methods: Articles on rhGM-CSF hydrogel for the treatment of pediatric burn wounds were retrieved from PubMed, Embase, WOS, Cochrane Central Registry of Controlled Trials, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), China National Knowledge Infrastructure (CNKI) and Wanfang from the inception of the databases to March 2024. Two reviewers screened articles and extracted the following data: general characteristics, intervention and treatment course, outcome measure. The meta-analysis was conducted using Revman 5.4 software. Results: Eight reports (336 patients: experimental 175, control 161) were ultimately included in the meta-analysis, which showed that the experimental group (rhGM-CSF hydrogel ± other therapy) was superior to the control group (treatments without rhGM-CSF hydrogel) in terms of the wound healing rates at day 7 [mean difference (MD) =13.63, 95% confidence interval (CI): 7.25 to 20.00, P<0.001], day 14 (MD =15.59, 95% CI: 12.50 to 18.69, P<0.001), and day 21 (MD =7.47, 95% CI: 7.36 to 7.58, P<0.001), and the wound healing time (MD =-3.10, 95% CI: -3.50 to -2.71, P<0.001), and the differences were statistically significant. For the risks of bias, one study had a "high risk" in allocation sequence concealment, and the others were classified as "low risk" and "unclear risk". Conclusions: rhGM-CSF hydrogel is significantly effective in improving the wound healing rate and shortening the wound healing time in children with second- or third-degree burns.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 µm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Application and research progress of magnetic resonance proton density fat fraction in metabolic dysfunction-associated steatotic liver disease: a comprehensive review.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is a chronic liver disorder associated with disturbances in lipid metabolism. The disease is prevalent worldwide, particularly closely linked with metabolic syndromes such as obesity and diabetes. Magnetic Resonance Proton Density Fat Fraction (MRI-PDFF), serving as a non-invasive and highly quantitative imaging assessment tool, holds promising applications in the diagnosis and research of MASLD. This paper aims to comprehensively review and summarize the applications and research progress of MRI-PDFF technology in MASLD, analyze its strengths and challenges, and anticipate its future developments in clinical practice.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

CmPIF8-CmERF27-CmACS10-mediated ethylene biosynthesis modulates red light-induced powdery mildew resistance in oriental melon.

Powdery mildew is a serious fungal disease in protected melon cultivation that affects the growth, development and production of melon plants. Previous studies have shown that red light can improve oriental melon seedlings resistance to powdery mildew. Here, after inoculation with Podosphaera xanthii, an obligate fungal pathogen eliciting powdery mildew, we found that red light pretreatment increased ethylene production and this improved the resistance of melon seedlings to powdery mildew, and the ethylene biosynthesis gene CmACS10 played an important role in this process. By analysing the CmACS10 promoter, screening yeast one-hybrid library, it was found that CmERF27 positively regulated the expression of CmACS10, increased powdery mildew resistance and interacted with PHYTOCHROME INTERACTING FACTOR8 (CmPIF8) at the protein level to participate in the regulation of ethylene biosynthesis to respond to the red light-induced resistance to P. xanthii, Furthermore, CmPIF8 also directly targeted the promoter of CmACS10, negatively participated in this process. In summary, this study revealed the specific mechanism by which the CmPIF8-CmERF27-CmACS10 module regulates red light-induced ethylene biosynthesis to resist P. xanthii infection, elucidate the interaction between light and plant hormones under biological stress, provide a reference and genetic resources for breeding of disease-resistant melon plants.

Biomimetic Design of Soil-Engaging Components: A Review.

Soil-engaging components play a critical role in agricultural production and engineering construction. However, the soil-engaging components directly interacting with the soil often suffer from the problems of high resistance, adhesion, and wear, which significantly reduce the efficiency and quality of soil operations. A large number of featured studies on the design of soil-engaging components have been carried out while applying the principles of bionics extensively, and significant research results have been achieved. This review conducts a comprehensive literature survey on the application of biomimetics in the design of soil-engaging components. The focus is on performance optimization in regard to the following three aspects: draught reduction, anti-adhesion, and wear resistance. The mechanisms of various biomimetic soil-engaging components are systematically explained. Based on the literature analysis and biomimetic research, future trends in the development of biomimetic soil-engaging components are discussed from both the mechanism and application perspectives. This research is expected to provide new insights and inspiration for addressing related scientific and engineering challenges.

Simulation and Structural Analysis of a Flexible Coupling Bionic Desorption Mechanism Based on the Engineering Discrete Element Method.

Soil adhesion is one of the important factors affecting the working stability and quality of agricultural machinery. The application of bionic non-smooth surfaces provides a novel idea for soil anti-adhesion. The parameters of sandy loam with 21% moisture content were calibrated by the Engineering Discrete Element Method (EDEM). The final simulated soil repose angle was highly consistent with the measured soil repose angle, and the obtained regression equation of the soil repose angle provides a numerical reference for the parameter calibration of different soils. By simulating the sinusoidal swing of a sandfish, it was found that the contact interface shows the phenomenon of stress concentration and periodic change, which reflects the effectiveness of flexible desorption and soil anti-adhesion. The moving resistance of the wedge with different wedge angles and different serrated structures was simulated. Finally, it was found that a 40° wedge with a high-tail sparse staggered serrated structure on the surface has the best drag reduction effect, and the drag reduction is about 10.73%.

Electrical injuries in children-a 6-year retrospective study.

BACKGROUND: This study aimed to assess the clinical epidemiological characteristics of children with electrical injuries and discuss the countermeasures for the prevention of electrical injuries in children. METHODS: The children with electrical injuries were grouped according to whether or not they were admitted to the hospital for treatment into inpatient and outpatient groups. Clinical data such as gender, causes of injury and injury-causing voltage distribution in different age groups were analyzed. The factors affecting hospitalization were subjected to χ2 test, Kruskal-Wallis H test, and logistic regression analysis. RESULTS: A total of 321 children were included with 37 divided into inpatient group and 284 divided into outpatient group. The incidence of electrical injuries was highest in children ≤6 years old and in the summer. There were significantly different in gender, place of occurrence, cause of injury and injury-causing voltage between the two groups (p < 0.05). Injury-causing voltage is an independent risk factor affecting hospitalization of children with electrical injuries (OR = 0.116, 95 %CI = 0.040-0.334, p = 0.000). In children ≤6 years old, boys suffered electrical injuries more frequently than girls; battery powered vehicle (47.53 %) was primarily the cause of injury; most of the patients (64.64 %) were exposed to low voltage below 100 Vs, mainly in the case of adolescent children. CONCLUSION: Male preschoolers accounted for the majority of electrical injury cases, and these accidents mostly happened in household electrical appliances and household battery cars. Overall, it is necessary to improve family electrical safety education and reinforce protective measures against electric injury to children.

Resolvins protect against diabetes-induced colonic oxidative stress, barrier dysfunction, and associated diarrhea via the HO-1 pathway.

Diabetes is associated with increased oxidative stress, leading to altered tight junction formation and increased apoptosis in colonic epithelial cells. These changes may lead to intestinal barrier dysfunction and corresponding gastrointestinal symptoms in patients with diabetes, including diarrhea. The aim of this study was to characterize the effect and mechanism of Resolvin D1 (RvD1) on diabetes-induced oxidative stress and barrier disruption in the colon. Mice with streptozotocin-induced diabetes were treated with RvD1 for 2 weeks, then evaluated for stool frequency, stool water content, gut permeability, and colonic transepithelial electrical resistance as well as production of reactive oxygen species (ROS), apoptosis, and expression of tight junction proteins Zonula Occludens 1 (ZO-1) and occludin. The same parameters were assessed in human colonoid cultures subjected to elevated glucose. We found that RvD1 treatment did not affect blood glucose, but normalized stool water content and prevented intestinal barrier dysfunction, epithelial oxidative stress, and apoptosis. RvD1 also restored ZO-1 and occludin expression in diabetic mice. RvD1 treatment increased phosphorylation of Akt and was accompanied by a 3.5-fold increase in heme oxygenase-1 (HO-1) expression in the epithelial cells. The protective effects of RvD1 were blocked by ZnPP, a competitive inhibitor of HO-1. Similar findings were observed in RvD1-treated human colonoid cultures subjected to elevated glucose. In conclusion, Oxidative stress in diabetes results in mucosal barrier dysfunction, contributing to the development of diabetic diarrhea. Resolvins prevent ROS-mediated mucosal injury and protect gut barrier function by intracellular PI3K/Akt activation and subsequent HO-1 upregulation in intestinal epithelial cells. These actions result in normalizing stool frequency and stool water content in diabetic mice, suggesting that resolvins may be useful in the treatment of diabetic diarrhea.

The clinical characteristics and risk factors for necrotizing soft tissue infection in children.

Importance: Necrotizing soft tissue infection (NSTI) is a serious infectious disease. However, the early clinical manifestations and indicators of NSTI in children are still unclear. Objective: The purpose of this study was to analyze the clinical characteristics and risk factors of NSTI in pediatric patients. Methods: A total of 127 children with skin and soft tissue infection (SSTI) were treated at our hospital and divided into two groups: the NSTI group and the non-NSTI group, based on their discharge diagnosis from January 2011 to December 2022. Then, we collected and analyzed the clinical characteristics and risk factors of all patients, including sex and age, disease inducement, admission temperature, local skin manifestations, infection site, the presence of sepsis, bacterial culture, and laboratory indicators. Results: In our study, there was a statistical difference in the age distribution and disease inducement between NSTI and non-NSTI groups. The occurrence of local skin manifestations (blisters/bullae and ecchymosis) and the presence of sepsis significantly increased in the NSTI group compared to the non-NSTI group. Additionally, only the platelet count on laboratory tests was statistically different between the NSTI and non-NSTI groups. Finally, the logistic regression analysis suggested that local skin manifestations such as blisters/bullae, and ecchymosis, as well as the presence of sepsis, were identified as risk factors for NSTI. Interpretation: Children with SSTI and skin manifestations such as blisters/bullae, ecchymosis, and the presence of sepsis are at a higher risk of developing NSTI. These symptoms serve as useful indicators for early detection of NSTI.

A comparative study on the effectiveness of online and in-class team-based learning on student performance and perceptions in virtual simulation experiments.

BACKGROUND: The swift transition to online teaching in medical education has presented the challenge of replicating in-class engagement and interaction essential for active learning. Despite online team-based learning (TBL) offering potential solutions through structured cooperative activities, its efficacy in virtual simulation experiment courses remains scantily researched. This study investigates the effectiveness of online TBL for teaching virtual patient experiments in a basic medical laboratory course and contrasts it with traditional offline teaching in terms of student performance and perceptions. METHODS: A comparative analysis involved 179 Year 3 medical students using online TBL, face-to-face TBL (FTF-TBL), and the flipped classroom (FC) approach. The learning outcomes were assessed based on experiment reports, IRAT scores, TRAT scores, and final exam performance. Students' perceptions of both online and in-class TBL methodologies were also surveyed. RESULTS: Both online and in-class TBL groups demonstrated comparable academic outcomes and surpassed the FC group in academic performance. Students displayed a marked preference for the TBL format (whether online or in-class), valuing its enhancement of learning interest and practical knowledge application. Nevertheless, refinements in discussion efficiency, platform convenience, and student-instructor interaction were indicated as potential areas of improvement in the online setting. CONCLUSIONS: Online TBL, along with its in-class counterpart, showed superior academic performance and a more positive learning experience compared to the FC group. These findings underscore the potential of online TBL in adapting to modern pedagogical challenges and enriching medical education through virtual simulation experiments.

Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function.

Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Mendelian randomization (MR) to estimate the gene-specific causal effect of omega-3 fatty acids (N = 114,999) on cognitive function (N = 300,486). Tissue- and cell type-specific effects of FADS1/FADS2 expression on cognitive function were estimated using brain tissue cis-expression quantitative trait loci (cis-eQTL) datasets (GTEx, N ≤ 209; MetaBrain, N ≤ 8,613) and single cell cis-eQTL data (N = 373), respectively. These causal effects were further evaluated in whole blood cis-eQTL data (N ≤ 31,684). A series of sensitivity analyses were conducted to validate MR assumptions. Leave-one-out MR showed a FADS gene-specific effect of omega-3 fatty acids on cognitive function [ß = -1.3 × 10-2, 95% confidence interval (CI) (-2.2 × 10-2, -5 × 10-3), P = 2 × 10-3]. Tissue-specific MR showed an effect of increased FADS1 expression in cerebellar hemisphere and FADS2 expression in nucleus accumbens basal ganglia on maintaining cognitive function, while decreased FADS1 expression in nine brain tissues on maintaining cognitive function [colocalization probability (PP.H4) ranged from 71.7% to 100.0%]. Cell type-specific MR showed decreased FADS1/FADS2 expression in oligodendrocyte was associated with maintaining cognitive function (PP.H4 = 82.3%, respectively). Increased FADS1/FADS2 expression in whole blood showed an effect on cognitive function maintenance (PP.H4 = 86.6% and 88.4%, respectively). This study revealed putative causal effect of FADS1/FADS2 expression in brain tissues and blood on cognitive function. These findings provided evidence to prioritize FADS gene as potential target gene for maintenance of cognitive function.

Early-life famine exposure, adulthood obesity patterns, and risk of low-energy fracture.

Malnutrition in early life increases the risk of osteoporosis, but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown. This study included 5323 community-dwelling subjects aged ⩾40 years from China. Early-life famine exposure was identified based on the participants' birth dates. General obesity was assessed using the body mass index (BMI), and abdominal obesity was evaluated with the waist-to-hip ratio (WHR). Low-energy fracture was defined as fracture occurring after the age of ⩾40 typically caused by falls from standing height or lower. Compared to the nonexposed group, the group with fetal, childhood, and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios (ORs) and 95% confidence intervals (CIs) of 3.55 (1.57-8.05), 3.90 (1.57-9.71), and 3.53 (1.05-11.88), respectively, but not in men. Significant interactions were observed between fetal famine exposure and general obesity with fracture among women (P for interaction = 0.0008). Furthermore, compared with the groups with normal BMI and WHR, the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture (OR, 95% CI: 3.32, 1.17-9.40). These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

The Design and Experimental Validation of a Biomimetic Stubble-Cutting Device Inspired by a Leaf-Cutting Ant's Mandibles.

Under the conditions of conservation tillage, the existence of the root-soil complex greatly increases the resistance and energy consumption of stubble-cutting blades, especially in Northeast China. In this research, the corn root-soil complex in Northeast China was selected as the research object. Based on the multi-toothed structure of the leaf-cutting ant's mandibles and the unique bite mode of its mandibles on leaves, a gear-tooth, double-disk, bionic stubble-cutting device (BSCD) was developed by using a combination of power cutting and passive cutting. The effects of rotary speed, tillage depth, and forward speed on the torque and power of the BSCD were analyzed using orthogonal tests, and the results showed that all of the factors had a large influence on the torque and power, in the order of tillage depth > rotary speed > forward speed. The performance of the BSCD and the traditional power straight blade (TPSB) was explored using comparative tests. It was found that the optimal stubble-cutting rate of the BSCD was 97.4%. Compared with the TPSB, the torque of the BSCD was reduced by 15.2-16.4%, and the power was reduced by 9.2-11.3%. The excellent performance of the BSCD was due to the multi-toothed structure of the cutting edge and the cutting mode.

Ferroelectric Resistance Switching in Epitaxial BiFeO3/La0.7Sr0.3MnO3 Heterostructures.

BiFeO3/La0.7Sr0.3MnO3 (BFO/LSMO) epitaxial heterostructures were successfully synthesized by pulsed laser deposition on (001)-oriented SrTiO3 single-crystal substrates with Au top electrodes. Stable bipolar resistive switching characteristics regulated by ferroelectric polarization reversal was observed in the Au/BFO/LSMO heterostructures. The conduction mechanism was revealed to follow the Schottky emission model, and the Schottky barriers in high-resistance and low-resistance states were estimated based on temperature-dependent current-voltage curves. Further, the observed memristive behavior was interpreted via the modulation effect on the depletion region width and the Schottky barrier height caused by ferroelectric polarization reversal, combining with the oxygen vacancies migration near the BFO/LSMO interface.

Circ_0099630 knockdown alleviates lipopolysaccharide-induced injuries of human periodontal ligament cells through the inhibition of TLR4 by releasing miR-409-3p.

BACKGROUND: Periodontitis triggers tooth loss and affects the health of population worldwide. Emerging evidence hints that circular RNAs (circRNAs) are involved in various diseases, including periodontitis. This study aimed to investigate the role of circ_0099630 in the progression of periodontitis. METHODS: Periodontitis cell model was constructed by treating human periodontal ligament cells (HPDLCs) with lipopolysaccharide (LPS). Quantitative real-time PCR was used to analyze the expression of circ_0099630, microRNA-409-3p (miR-409-3p) and toll-like receptor 4 (TLR4) mRNA. Western blot was used for detecting protein levels of TLR4, cleaved-caspase 3, Bcl-2, CyclinD1 and NF-κB signaling markers. For function analyses, cell proliferation was assessed by CCK-8 assay and EdU assay. The releases of pro-inflammation factors were monitored by ELISA kits. The potential relationship between miR-409-3p and circ_0099630 or TLR4 was verified by dual-luciferase reporter assay, RIP assay and pull-down assay. RESULTS: The expression of circ_0099630 and TLR4 was elevated in periodontitis patients and LPS-treated HPDLCs. LPS induced HPDLC proliferation inhibition, apoptosis and inflammatory responses, while circ_0099630 knockdown or TLR4 knockdown alleviated these injuries. Besides, TLR4 overexpression reversed the inhibitory effect of circ_0099630 knockdown on LPS-induced HPDLC injuries. Mechanism analysis showed that circ_0099630 positively regulated TLR4 expression by acting as miR-409-3p sponge. MiR-409-3p restoration largely ameliorated LPS-induced HPDLC injuries by depleting TLR4. Moreover, LPS activated the NF-κB signaling pathway, while circ_0099630 knockdown inhibited the activity of NF-κB signaling via the miR-409-3p/TLR4 axis. CONCLUSION: Circ_0099630 knockdown relieved LPS-induced HPDLC injury by miR-409-3p/TLR4 axis, suggesting that circ_0099630 might be a potential target for periodontitis treatment.

Evaluating the Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Bowel Disease via Circulating Metabolites: A Mediation Mendelian Randomization Study.

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

Implications of Advances in Studies of O6-Methylguanine-DNA- Methyltransferase for Tumor Prognosis and Treatment.

O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair enzyme, which reverses the alkylation of guanine O6 through directtransfer of the methyl group, maintains the gene stability and avoids tumor occurrence. Studies have shown that MGMT gene methylation, polymorphism and protein expression are involved in the process of various tumor development, such as colon cancer, gastric carcinoma, etc. MGMT gene promotes methylation, protein expression and enzyme activity from various tissues, which resultsin different effects on the prognosis of patients. MGMT promoter methylation is a positive factor for the prognosis of Glioblastoma (GBM), which can prolong overall survival and progression-free survival, reduce the resistance of tumor cells to temozolomide treatment, and improve the prognosis. The treatment of tumors based on MGMT focuses on three aspects: targeting MGMT to increase the sensitivity of alkylated drug therapy in tumors, immunotherapy combined with alkylated agents on tumor treatment, and treatment for patients with MGMT promoter non-methylation. Similarly, a number of studies have targeted MGMT to reduce alkylated agent resistance in other systems. Although numerous studies on MGMT in tumors have been reported, there are problems that need to be solved, such as selection and consensus of MGMT promoter methylation detection methods (CpG detection sites, cut-off value) and the treatment of MGMT non-methylated GBM patients, especially elderly patients. In this review, we describe the regulation of MGMT expression and its role inchemotherapy, especially in gliomas. Further studies exploring new methods targeting MGMT with better curative effect and less toxicity are advocated. We anticipate that these developments will be progressive and sufficiently used for clinical application.

JMJD5 inhibits lung cancer progression by facilitating EGFR proteasomal degradation.

Aberrant activation of epidermal growth factor receptor (EGFR) signaling is closely related to the development of non-small cell lung cancer (NSCLC). However, targeted EGFR therapeutics such as tyrosine kinase inhibitors (TKIs) face the challenge of EGFR mutation-mediated resistance. Here, we showed that the reduced JmjC domain-containing 5 (JMJD5) expression is negatively associated with EGFR stability and NSCLC progression. Mechanically, JMJD5 cooperated with E3 ligase HUWE1 to destabilize EGFR and EGFR TKI-resistant mutants for proteasomal degradation, thereby inhibiting NSCLC growth and promoting TKI sensitivity. Furthermore, we identified that JMJD5 can be transported into recipient cells via extracellular vesicles, thereby inhibiting the growth of NSCLC. Together, our findings demonstrate the tumor-suppressive role of JMJD5 in NSCLC and suggest a putative therapeutic strategy for EGFR-related NSCLC by targeting JMJD5 to destabilize EGFR.