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.

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.

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.

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.

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.

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.

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.

E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma.

Ribonucleotide reductase (RR) is a rate-limiting enzyme that facilitates DNA replication and repair by reducing nucleotide diphosphates (NDPs) to deoxyribonucleotide diphosphates (dNDPs) and is thereby crucial for cell proliferation and cancer development. The E2F family of transcription factors includes key regulators of gene expression involved in cell cycle control. In this study, E2F8 expression was significantly increased in most cancer tissues of lung adenocarcinoma (LUAD) patients and was correlated with the expression of RRM2 through database and clinical samples analysis. The protein expression of E2F8 and RRM2 were positively correlated with tumor-node-metastasis (TNM) pathological stage, and high expression of E2F8 and RRM2 predicted a low 5-year overall survival rate in LUAD patients. Overexpression and knockdown experiments showed that E2F8 was essential for LUAD cell proliferation, DNA synthesis, and cell cycle progression, which were RRM2-dependent. Reporter gene, ChIP-qPCR, and DNA pulldown-Western blot assays indicated that E2F8 activated the transcription of the RRM2 gene by directly binding with the RRM2 promoter in LUAD cells. Previous studies indicated that inhibition of WEE1 kinase can suppress the phosphorylation of CDK1/2 and promote the degradation of RRM2. We further showed here that the combination of E2F8 knockdown with MK-1775, an inhibitor of WEE1 being evaluated in clinical trials, synergistically suppressed proliferation and promoted apoptosis of LUAD cells in vitro and in vivo. Thus, this study reveals a novel role of E2F8 as a proto-oncogenic transcription activator by activating RRM2 expression in LUAD, and targeting both the transcription and degradation mechanisms of RRM2 could produce a synergistic inhibitory effect for LUAD treatment in addition to conventional inhibition of RR enzyme activity.

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.

Diagnostic value of serum CA125 combined with PET/CT in ovarian cancer and tuberculous peritonitis in female patients.

PURPOSE: To evaluate the diagnostic value of serum CA125 combined with 18F-FDG PET/CT in ovarian cancer (OC) and tuberculous peritonitis (TBP) in female patients and to establish a diagnostic scoring system. METHOD: A total of 86 female patients (64 OC and 22 TBP) were included in this study. Serum CA125, PET/CT maximal intensity projection (MIP), maximal standardized uptake value, ovarian mass, ascites volume, and other indicators were analyzed and a diagnostic scoring system was established according to the weights of statistically significant indicators. RESULTS: Univariate analysis showed that serum CA125 in OC and TBP patients were 2079.9 ± 1651.3 U/mL and 448.3 ± 349.5 U/mL (P < 0.001). In MIP images, abdominal lesions were focal distribution in 92.2% (59/64) of OC patients and diffuse distribution in 95.5% (21/22) of TBP patients (P < 0.001). Ovarian masses could be observed in 82.8% (53/64) OC patients and 31.8% (7/22) TBP patients (P <0.001). The other indicators were not statistically significant. Logistic regression analysis showed that serum CA125 and MIP were independent risk factors for diagnosis. A diagnostic scoring system could be established based on serum CA125, MIP and ovarian mass, and the diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 98.4% (63/64), 95.5% (21/22), 97.7% (84/86), 98.4% (63/64), and 95.5% (21/22), respectively. CONCLUSION: Serum CA125 combined with PET/CT is of great value in the diagnosis of OC and TBP. A simple and efficient diagnostic scoring system can be established using serum CA125, MIP image feature, and ovarian mass.

Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study.

BACKGROUND: Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. METHODS: Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. RESULTS: Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45-0.59), and decreased HOMA-IR (ß = - 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06-1.15), and decreased HOMA-B (ß = - 0.04, SE = 0.01, P = 4.52 × 10-5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. CONCLUSIONS: This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

JMJD5 inhibits lung cancer progression by regulating glucose metabolism through the p53/TIGAR pathway.

Metabolic reprogramming is considered one of the main driving forces for tumor progression, providing energy and substrates of biosynthesis to support rapid neoplastic proliferation. Particularly, the tumor suppressor protein p53 was shown to revert the Warburg effect and play complex roles in regulating glucose metabolism. Jumonji C domain-containing protein 5 (JMJD5) has previously been reported as a negative regulator of p53. However, the role of JMJD5 in p53-mediated metabolic reprogramming remains elusive. Here, we discovered that knockdown of JMJD5 significantly enhances TIGAR expression in p53 wild-type non-small cell lung cancer (NSCLC) cells, which could further suppress glycolysis and promote the pentose phosphate pathway. Besides, JMJD5 knockdown promotes the NSCLC cell proliferation in vitro and xenograft tumor growth in vivo, while silencing TIGAR can abolish this effect. Low JMJD5 expression levels are associated with elevated TIGAR levels and correlates with poor prognosis in lung cancer patients. Taken together, our findings suggest that JMJD5 is a key regulator of tumor glucose metabolism by targeting the p53/TIGAR metabolic pathway.

An Interview Study of College Students' Health Emergency Literacy in the Context of COVID-19 Normalized Prevention and Control.

Objective: To explore the changes in college students' awareness of health protection under the normalization of COVID-19, and to seek its connection with the epidemic management in colleges and universities, so as to provide reference information for continuous health education activities and the cultivation of college students' health emergency literacy in colleges and universities. Methods: Qualitative interviews were used to understand the extent of health emergency literacy among college students enrolled in the context of a normalized epidemic and the factors associated with it that cause changes around a question outline. Results: The interviewees generally had a lax mentality in the late stage of the interview, the importance they attached to epidemic prevention and control decreased significantly, and the way to know about epidemic protection measures and other knowledge was mainly through the mass news media. All respondents affirm the importance of social software for outbreak prevention and control. All 17 interviewees were able to mention basic outbreak protection methods, but 15 of them showed inconsistent behavior in words and actions later. Conclusion: The vast majority of respondents' health emergency literacy appears to weaken in the late stages of epidemic normalization, and the effect of traditional approaches used by universities to improve college students' health emergency literacy is weak.

The transcription factor CmERFI-2 represses CmMYB44 expression to increase sucrose levels in oriental melon fruit.

Soluble sugar accumulation in fruit ripening determines fleshy fruit quality. However, the molecular mechanism for this process is not yet understood. Here, we showed a transcriptional repressor, CmMYB44 regulates sucrose accumulation and ethylene synthesis in oriental melon (Cucumis. melo var. makuwa Makino) fruit. Overexpressing CmMYB44 suppressed sucrose accumulation and ethylene production. Furthermore, CmMYB44 repressed the transcriptional activation of CmSPS1 (sucrose phosphate synthase 1) and CmACO1 (ACC oxidase 1), two key genes in sucrose and ethylene accumulation, respectively. During the later stages of fruit ripening, the repressive effect of CmMYB44 on CmSPS1 and CmACO1 could be released by overexpressing CmERFI-2 (ethylene response factor I-2) and exogenous ethylene in "HS" fruit (high sucrose accumulation fruit). CmERFI-2 acted upstream of CmMYB44 as a repressor by directly binding the CmMYB44 promoter region, indirectly stimulating the expression level of CmSPS1 and CmACO1. Taken together, we provided a molecular regulatory pathway mediated by CmMYB44, which determines the degree of sucrose and ethylene accumulation in oriental melon fruit and sheds light on transcriptional responses triggered by ethylene sensing that enable the process of fruit ripening.

CmMYB44 might interact with CmAPS2-2 to regulate starch metabolism in oriental melon fruit.

Sugar content is one of the determining factors for melon fruit maturity. Studies have shown that starch gradually degrades during fruit ripening, resulting in sugar accumulation. But the specific relationship between starch metabolism and sucrose accumulation was still unknown. Here, the starch and sugar contents, the activities of key enzymes and the expression patterns of genes related to starch-sucrose metabolism were determined in the fruit of high sugar and starch variety 'HS' and low sugar and starch variety 'LW'. It was found that starch accumulated during fruit development process, and then degraded at 30 days after anthesis (DAA), which was synchronized with sucrose accumulation in 'HS' fruit, while starch and sucrose contents were always at a lower level during 'LW' fruit maturation. Furthermore, starch metabolism-related enzymes (Adenine dinucleotide phosphate -glucose pyrophosphorylase (AGPase), α-amylase (AMY), ß-amylase (BMY)) and the key enzymes for sucrose accumulation (sucrose phosphate synthase (SPS) and sucrose synthase (SS)) were significantly increased at ripening stage of 'HS' fruit, and their activities were consistent with the expressions of CmAPS2-2, CmAMY2, CmBAM1, CmBAM9 and CmSPS1. However, the contents of starch and sucrose and the activities of AGPase and SPS in 'LW' fruit didn't change significantly. We discovered an R2R3-type MYB transcription factor, CmMYB44, screened from yeast one hybrid library, could directly bind to the promoter of CmAPS2-2 to inhibit its transcription. These results revealed that the targeted down-regulation of CmAPS2-2 by CmMYB44 might be involved in the starch accumulation process, which affect the flavor quality of oriental melon fruit.