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The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. The most common form of NCD is metabolic diseases, which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum. Protein posttranslational modification (PTM) is an important term that refers to biochemical modification of specific amino acid residues in target proteins, which immensely increases the functional diversity of the proteome. The range of PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, and several novel PTMs. Here, we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences, including diabetes, obesity, fatty liver diseases, hyperlipidemia, and atherosclerosis. Building upon this framework, we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications, showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials, and offer future perspectives. Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.

Background Inner myometrial laceration (IML) is a rare but potentially life-threatening obstetric emergency that can cause severe antepartum or postpartum haemorrhage. The pathogenesis of this condition is not fully understood, and this condition is often associated with abnormal uterine contractions, fetal position factors, or obstetric interventions. Its clinical manifestations are nonspecific, making early diagnosis difficult and leading to potential misdiagnosis or missed diagnosis. Case presentation This report describes a 26-year-old primigravida at 38⁺¹ weeks gestation who underwent oxytocin induction for preeclampsia. During induction, she suddenly developed 1200 ml of vaginal bleeding. An emergency caesarean section revealed a 4 cm inner myometrial laceration on the posterior wall of the lower uterine segment, with the serosal layer intact. Haemostasis was successfully achieved using a “figure-of-8” suture combined with a continuous suture, supplemented with bilateral ligation of the ascending branches of the uterine arteries. The patient recovered well postoperatively, with no complications during follow-up, and her uterus was preserved. Conclusion IML is an important and occult cause of refractory antepartum or postpartum haemorrhage. Diagnosis relies on careful intraoperative exploration. Individualized suturing techniques and necessary vascular ligation are key to preserving fertility, whereas hysterectomy should be reserved as a last resort when conservative measures fail. Enhancing clinical vigilance for IML, early surgical exploration, and targeted repair is crucial for improving maternal and fetal outcomes.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

In a recent article published in Nature, Chen et al. reported that pregestational hyperglycemia rendered offspring vulnerable to glucose intolerance due to insufficient TET3‐mediated 5‐methylcytosine oxidation and DNA demethylation, resulting in hypermethylation and reduction of insulin‐secreting genes.

•LAG and iCVR corrections increased similarity of resting-state intrinsic patterns in stroke patients.•Corrected rs-fMRI metrics showed greater sensitivity to detect between-group differences.•Guidance on best corrections for each rs-fMRI metric was provided for stroke. Resting-state functional magnetic resonance imaging (rs-fMRI) is a prominent tool for investigating functional deficits in stroke patients. However, the extent to which the hemodynamic lags (LAG) and the intrinsic cerebrovascular reactivity (iCVR) may affect the rs-fMRI metrics in different scales needs to be clarified for ischemic stroke. In this study, 73 ischemic stroke patients and 74 healthy controls (HC) were recruited to investigate how the correction of the LAG and/or iCVR would influence resting-state functional magnetic resonance imaging (rs-fMRI) metrics of three different spatial scales (local-scale, meso-scale and global-scale) in ischemic stroke. The analysis revealed that the Stroke pattern of all functional metrics using different correction strategies resembled the HC pattern. The highest overlap was observed in the Stroke pattern with correction for both LAG and iCVR, while the pattern without correction showed the lowest overlap. Most functional metrics after correction showed higher sensitivity in detecting between-group differences than those without correction. Moreover, our results were generally reproducible in an independent dataset. Collectively, these findings emphasize the necessity of considering LAG and iCVR effects to investigate stroke-related functional alterations, and highlight the significance of correction strategies for accurately interpreting the findings in rs-fMRI study of ischemic stroke.

Background Emergency caesarean section (ECS) is an effective method for rapid termination of pregnancy and for saving maternal and foetal life in emergencies. Experts recommend that the interval from decision of operation to the decision to delivery interval (DDI) should be shortened as much as possible. Studies have shown that improving communication skills among staff by performing simulation drills shortens DDI, thus reducing the occurrence of adverse obstetric events and protecting maternal and child safety. In situ simulation (ISS) training is a simulation-based training approach for clinical team members conducted in a real-world clinical setting. In August 2020, Anhui Maternal and Child Health Hospital began ISS training on the rapid obstetric response team (RRT) in our hospital area for emergency caesarean section. This study aimed to investigate the effect of implementing in situ simulation training for emergency caesarean section on maternal and child outcomes by comparing maternal and child-related data on emergency caesarean section in two hospital areas. Methods Data on cases of emergency caesarean delivery implemented in two hospital districts from August 2020 to August 2022 were collected: 19 in the untrained group and 26 in the training group. The two groups were compared concerning the interval from the decision of operation to the decision to delivery interval (DDI), the interval from the decision of operation to the initiation of skin incision, the interval from skin incision to the decision to delivery interval, and the neonatal situation. Results Primary outcome comparison: The training group had a significantly shorter interval between the DDI compared to the untrained group (8.14 ± 3.13 vs. 11.03 ± 3.52, P  = 0.006). Secondary outcomes comparison: The training group had a significantly shorter interval between the decision to cut skin compared to the untrained group (6.45 ± 2.21 vs. 9.95 ± 4.02, P  = 0.001). However, there was no significant difference in the interval between cutting skin and infant delivery between the two groups (2.24 ± 0.08 vs. 2.18 ± 0.13, P  > 0.05). Additionally, the Apgar score at 1 min after birth was higher in the training group compared to the untrained group (7.29 ± 2.38 vs. 6.04 ± 1.46, P  < 0.05). Conclusions The DDI for emergency caesarean section procedures can be significantly shortened, and neonatal Apgar scores at 1 min improved by implementing in situ simulation training for emergency caesarean section in obstetric rapid response teams. In situ simulation training is an effective tool for training in emergency caesarean section procedures and is worth promoting.

Aims/Introduction The coronavirus disease 2019 (COVID‐19) pandemic urged authorities to impose rigorous quarantines and brought considerable changes to people’s lifestyles. The impact of these changes on glycemic control has remained unclear, especially the long‐term effect. We aimed to investigate the impact of COVID‐19 lockdown on glycemic control in children and adolescents with type 1 diabetes. Materials and Methods This observational study enrolled children with type 1 diabetes using continuous glucose monitoring. Continuous glucose monitoring data were extracted from the cloud‐based platform before, during and after lockdown. Demographics and lifestyle change‐related information were collected from the database or questionnaires. We compared these data before, during and after lockdown. Results A total of 43 children with type 1 diabetes were recruited (20 girls; mean age 7.45 years; median diabetes duration 1.05 years). We collected 41,784 h of continuous glucose monitoring data. Although time in range (3.9–10.0 mmol/L) was similar before, during and after lockdown, the median time below range <3.9 mmol/L decreased from 3.70% (interquartile range [IQR] 2.25–9.53%) before lockdown to 2.91% (IQR 1.43–5.95%) during lockdown, but reversed to 4.95% (IQR 2.11–9.42%) after lockdown (P = 0.004). Time below range <3.0 mmol/L was 0.59% (IQR 0.14–2.21%), 0.38% (IQR 0.05–1.35%) and 0.82% (IQR 0.22–1.69%), respectively (P = 0.008). The amelioration of hypoglycemia during lockdown was more prominent among those who had less time spent <3.9 mmol/L at baseline. During lockdown, individuals reduced their physical activity, received longer sleep duration and spent more time on diabetes management. In addition, they attended outpatient clinics less and turned to telemedicine more frequently. Conclusion Glycemic control did not deteriorate in children and teenagers with type 1 diabetes around the COVID‐19 pandemic. Hypoglycemia declined during lockdown, but reversed after lockdown, and the changes related to lifestyle might not provide a long‐term effect. Glycemic control did not deteriorate in type 1 diabetes patients around the COVID‐19 pandemics. There was a small, but significant, improvement in hypoglycemia in people with type 1 diabetes during lockdown for COVID‐19, but such improvement disappeared after lockdown. A stable and relaxed lifestyle might lead to better glycemic control, but lifestyle changes might not provide a long‐term effect.

Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Background Major depressive disorder (MDD) is currently recognized as the most common and debilitating psychiatric disorder worldwide, while the pathophysiological mechanisms underlying MDD remain unclear. This study aims to investigate neurovascular coupling (NVC) alteration in MDD patients and its correlation with disease severity and sex. Methods Arterial spin labeling and blood-oxygen-level-dependent data were collected from 51 MDD patients and 51 healthy controls (HCs). Spatial and temporal correlations between the amplitude of low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) were analyzed as NVC metrics. Differences between groups and subgroups, as well as correlations between ALFF-CBF coupling and clinical measurements, were explored. Results First, spatial correlations found that, compared to HCs, MDD patients showed reduced whole-brain ALFF-CBF coupling, with subgroup analysis revealing significant reductions in severe and female MDD patients. Second, temporal correlation analysis showed that, compared to HCs, moderate MDD patients demonstrated increased ALFF-CBF coupling in the left insula, whereas severe MDD patients showed reduced coupling in the left anterior cingulate cortex and increased coupling in the right superior occipital gyrus. In subgroup analysis, male MDD patients presented lower ALFF-CBF coupling in the left superior frontal orbital gyrus. Third, the spatial correlation of ALFF-CBF coupling in female MDD patients was negatively correlated with anxiety symptom scores. Conclusions NVC decoupling reflects a potential neuropathological mechanism in MDD, with heterogeneous spatial-temporal patterns based on disease severity and sex.

Acute ischaemic stroke (AIS) is a major cause of disability and death, which is a serious threat to human health and life. Wasp venom extracted from Vespa magnifica Smith (Vespidae) could treat major neurological disorders. This study investigated the effects of wasp venom on AIS in rats. We used a transient middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats (260-280 g, n = 8-15) with a sham operation group being treated as negative control. MCAO rats were treated with wasp venom (0.05, 0.2 and 0.6 mg/kg, i.p.) using intraperitoneal injection. After treatment 48 h, behavioural tests, cortical blood flow (CBF), TTC staining, H&E staining, Nissl staining, TUNEL assay, immunohistochemistry (IHC) and ELISA were employed to investigate neuroprotective effects of wasp venom. Compared with the MCAO group, wasp venom (0.6 mg/kg) improved neurological impairment, accelerated CBF recovery (205.6 ± 52.92 versus 216.7 ± 34.56), reduced infarct volume (337.1 ± 113.2 versus 140.7 ± 98.03) as well as BBB permeability as evidenced by changes in claudin-5 and AQP4. In addition, function recovery of stroke by wasp venom treatment was associated with a decrease in TNF-α, IL-1β, IL-6 and inhibition activated microglia as well as apoptosis. Simultaneously, the wasp venom regulated the angiogenesis factors VEGF and b-FGF in the brain. Wasp venom exhibited a potential neuroprotective effect for AIS. In the future, we will focus on determining whether the observed actions were due to a single compound or the interaction of multiple components of the venom.