Macrophage-Derived GSDMD Plays an Essential Role in Atherosclerosis and Cross Talk Between Macrophages via the Mitochondria-STING-IRF3/NF-κB Axis.

BACKGROUND: Macrophages play a crucial role in atherosclerotic plaque formation, and the death of macrophages is a vital factor in determining the fate of atherosclerosis. GSDMD (gasdermin D)-mediated pyroptosis is a programmed cell death, characterized by membrane pore formation and inflammatory factor release. METHODS: ApoE-/- and Gsdmd-/- ApoE-/- mice, bone marrow transplantation, and AAV (adeno-associated virus serotype 9)-F4/80-shGSDMD (shRNA-GSDMD) were used to examine the effect of macrophage-derived GSDMD on atherosclerosis. Single-cell RNA sequencing was used to investigate the changing profile of different cellular components and the cellular localization of GSDMD during atherosclerosis. RESULTS: First, we found that GSDMD is activated in human and mouse atherosclerotic plaques and Gsdmd-/- attenuates the atherosclerotic lesion area in high-fat diet-fed ApoE-/- mice. We performed single-cell RNA sequencing of ApoE-/- and Gsdmd-/- ApoE-/- mouse aortas and showed that GSDMD is principally expressed in atherosclerotic macrophages. Using bone marrow transplantation and AAV-F4/80-shGSDMD, we identified the potential role of macrophage-derived GSDMD in aortic pyroptosis and atherosclerotic injuries in vivo. Mechanistically, GSDMD contributes to mitochondrial perforation and mitochondrial DNA leakage and subsequently activates the STING (stimulator of interferon gene)-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) axis. Meanwhile, GSDMD regulates the STING pathway activation and macrophage migration via cytokine secretion. Inhibition of GSDMD with GSDMD-specific inhibitor GI-Y1 (GSDMD inhibitor Y1) can effectively alleviate the progression of atherosclerosis. CONCLUSIONS: Our study has provided a novel macrophage-derived GSDMD mechanism in the promotion of atherosclerosis and demonstrated that GSDMD can be a potential therapeutic target for atherosclerosis.

How Society Anxiety Influences Attention Control in College Students: The Moderated Mediation Effect of Cognitive Flexibility and Resting-state Electroencephalography Activity.

Social anxiety is a prevalent issue among college students, adversely affecting their overall well-being. Drawing from the cognitive model of social anxiety and attention control theory, heightened levels of social anxiety may correspond to poorer attention control ability. However, little is known about the underlying cognitive mechanisms of the relationship between social anxiety and attention control. To address this research gap, the current study recruited a sample of 156 college students (56 women) who underwent self-report measures of social anxiety, cognitive flexibility, and attention control, followed by a resting-state EEG recording. The results revealed a significant negative predictive effect of social anxiety on attention control, with cognitive flexibility partially mediating this relationship. Furthermore, resting-state theta power emerged as a significant moderator, accentuating the negative impact of social anxiety on cognitive flexibility among individuals with lower theta power. In addition, frontal alpha asymmetry (FAA) demonstrated a moderating effect, with lower FAA intensifying the predictive influence of cognitive flexibility on attention control. Taken together, these results suggested that social anxiety can predict attention control either directly or indirectly via the mediating role of cognitive flexibility, and lower theta power and FAA has a risk amplification effect, which provide novel insights into the treatment and prevention of social anxiety and its negative impact on college students.

AKI-Pro score for predicting progression to severe acute kidney injury or death in patients with early acute kidney injury after cardiac surgery.

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.

Discovery of novel natural cardiomyocyte protectants from a toxigenic fungus Stachybotrys chartarum.

Stachybatranones A-F (1a/1b and 2-6) and three known analogues, namely methylatranones A and B (7 and 8) and atranone B (9), were isolated and identified from a toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated via the extensive spectroscopic data, comparison of the experimental electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analyses. Structurally, compounds 2-6 belonged to a rare class of C-alkylated dolabellanes, featuring a unique five-membered hemiketal ring and a γ-butyrolactone moiety both fused to an 11-membered carbocyclic system, while compound 1 (1a/1b) represented the first example of a 5-11-6-fused atranone possessing a 2,3-butanediol moiety. The cardiomyocyte protective activity assay revealed that compounds 1-9 ameliorated cold ischemic injury at 24 h post cold ischemia (CI), with compounds 1 and 4 acting in a dose-dependent manner. Moreover, compound 1 prevented cold ischemia induced dephosphorylation of PI3K and AKT acting in a dose-dependent manner. In this study, a new class of natural products were found to protect cardiomyocytes against cold ischemic injury, providing a potential option for the development of novel cardioprotectants in heart transplant medicine.

The development of Tibetan children's racial bias in empathy: The mediating role of ethnic identity and wrongfulness of ethnic intergroup bias.

OBJECTIVES: Individuals often automatically have more empathy for same-race members. However, there are no studies on racial bias in empathy (RBE) among Tibetan school-aged children. The present study aimed to examine the development of RBEs, including racial bias in cognitive empathy, affective empathy, and behavioral empathy, in Tibetan school-aged children. METHOD: In Experiment 1 (N = 108, aged 7-12), ethnic identity was primed using Tibetan and Han names. Then negative and neutral events were applied to measure the RBEs of Tibetan children. In Experiment 2 (N = 148, aged 7-12), negative events were replaced by pain events. In Experiment 3 (N = 60, aged 7-12), Tibetan children's ethnic identity and the awareness of the wrongfulness of ethnic intergroup bias were added to examine the underlying mechanism. RESULT: Results found that RBEs increased among Tibetan children aged 7-10 and decreased among those aged 11-12, Moreover, we analyzed age as a continuous variable and found that 10 years old was the inflection point in the development of RBEs in Tibetan children. Importantly, children aged 11-12 years old realized more wrongfulness of ethnic intergroup bias than children aged 7-10. The ethnic identity of Tibetan children aged 7-10 mediated the relation between age group and RBEs. And the wrongfulness of ethnic intergroup bias mediated the link between age group and RBEs in Tibetan children aged 9-12. CONCLUSION: Our study sheds light on the development of RBEs in Tibetan school-aged children and highlights the importance of identifying the appropriate timing for intervening in prejudice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Related factors to illness perception of individuals with diabetic foot ulcers: A structural equation modelling test.

BACKGROUND: Diabetic foot is a common and severe complication of diabetes with limited movement, emotional distress, and poor quality of life. Illness perception was introduced to improve patients' psychological status and quality of life with diabetic foot ulcers. The aim of the study is to explore the related factors of illness perception, and to structure an illness perception model of patients with diabetic foot ulcers. METHODS: We recruited 208 patients with diabetic foot ulcers from six hospitals from April 2021 to February 2022. A multicentered cross-sectional study was conducted to collect the data. Questionnaires included illness perception, coping behavior, emotional status, and quality of life. We performed multiple linear regression analysis with illness perception as the dependent variable, and evaluated the goodness of fit of the resulting structural equations models based on covariance structural analysis. RESULTS: Illness perception was negatively related to coping behavior and quality of life, and it was positively correlated with yield-coping behavior, anxiety, and depression. The pain, diabetes duration, quality of life, yield-coping strategy, and sex were the factors that affected illness perception in patients with DFUs (P＜0.05). The resulting model was found to exhibit goodness of fit. CONCLUSION: Illness perception had an especially strong and direct impact on quality of life, depression, and anxiety. Therefore, it is significant to improve illness perception in patients with DFUs, and provide positive support based on cognitive behavioral therapy to improve illness perception, quality of life, and emotional status.

Novel GSDMD inhibitor GI-Y1 protects heart against pyroptosis and ischemia/reperfusion injury by blocking pyroptotic pore formation.

Activation of gasdermin D (GSDMD) and its concomitant cardiomyocyte pyroptosis are critically involved in multiple cardiac pathological conditions. Pharmacological inhibition or gene knockout of GSDMD could protect cardiomyocyte from pyroptosis and dysfunction. Thus, seeking and developing highly potent GSDMD inhibitors probably provide an attractive strategy for treating diseases targeting GSDMD. Through structure-based virtual screening, pharmacological screening and subsequent pharmacological validations, we preliminarily identified GSDMD inhibitor Y1 (GI-Y1) as a selective GSDMD inhibitor with cardioprotective effects. Mechanistically, GI-Y1 binds to GSDMD and inhibits lipid- binding and pyroptotic pore formation of GSDMD-N by targeting the Arg7 residue. Importantly, we confirmed the cardioprotective effect of GI-Y1 on myocardial I/R injury and cardiac remodeling by targeting GSDMD. More extensively, GI-Y1 also inhibited the mitochondrial binding of GSDMD-N and its concomitant mitochondrial dysfunction. The findings of this study identified a new drug (GI-Y1) for the treatment of cardiac disorders by targeting GSDMD, and provide a new tool compound for pyroptosis research.

Nomogram to Predict Recurrence and Guide a Pragmatic Surveillance Strategy After Resection of Hepatoid Adenocarcinoma of the Stomach: A Retrospective Multicenter Study.

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.

The health-promoting anthocyanin petanin in Lycium ruthenicum fruit: a promising natural colorant.

Acylated anthocyanins derived from dietary sources have gained significant attention due to their health-promoting properties and potential as natural colorants with high stability. However, exploration of the functional food products using acylated anthocyanins enriched in fruits and vegetables remains largely delayed in food industries. The black goji (Lycium ruthencium) fruit (LRF) is a functional food that is extensively used due to its exceptionally high levels of acylated anthocyanins, including petanin. This review provides a comprehensive summary of the functional properties and anthocyanin components of LRF. The stability, bioaccessibility, bioavailability, and bioactivities of petanin, the major anthocyanin component, are compared with those of LRF anthocyanin extracts and other food sources. Furthermore, the biosynthetic pathway and regulatory network of petanin in LRF are proposed and constructed, respectively. The key genes that could be potentially used for metabolic engineering to produce petanin are predicted. Finally, the potential application of petanin derivatives in the food industry is also discussed. This review presents comprehensive and systematic information about the dual-function of petanin as a bioactive component and a promising natural colorant for future food industrial applications.

Cybervictimization and nonsuicidal self-injury: The mediating role of depressive symptoms and the moderating role of emotional reactivity.

BACKGROUND: Nonsuicidal self-injury (NSSI) has garnered growing attention in recent years, and cybervictimization (CV) has been identified as a risk factor for NSSI among adolescents. However, little is known about this association's longitudinal mediating and moderating mechanisms. Guided by the experiential avoidance model, the present study used a short longitudinal design to examine the mediating role of depressive symptoms and the moderating role of emotional reactivity between CV and NSSI. METHODS: A total of 577 Chinese middle school students (Mage = 14.38, SD = 0.67) completed the measures of CV, NSSI, depressive symptoms, and emotional reactivity. They provided data in two waves (T1 and T2, 6 months apart). RESULTS: The results found a longitudinal association between CV and NSSI as well as the mediating role of depressive symptoms. Moreover, emotional reactivity amplified the relationship between CV and NSSI via depressive symptoms; specifically, the relationship between depressive symptoms and NSSI was only significant for adolescents with high emotional reactivity. CONCLUSION: The current study has found that emotional reactivity moderated the indirect effect of depressive symptoms on the relationship between CV and NSSI. These findings have implications for the identification and intervention of NSSI in early adolescents.

Harnessing the Genetic Basis of Sorghum Biomass-Related Traits to Facilitate Bioenergy Applications.

The extensive use of fossil fuels and global climate change have raised ever-increasing attention to sustainable development, global food security and the replacement of fossil fuels by renewable energy. Several C4 monocot grasses have excellent photosynthetic ability, stress tolerance and may rapidly produce biomass in marginal lands with low agronomic inputs, thus representing an important source of bioenergy. Among these grasses, Sorghum bicolor has been recognized as not only a promising bioenergy crop but also a research model due to its diploidy, simple genome, genetic diversity and clear orthologous relationship with other grass genomes, allowing sorghum research to be easily translated to other grasses. Although sorghum molecular genetic studies have lagged far behind those of major crops (e.g., rice and maize), recent advances have been made in a number of biomass-related traits to dissect the genetic loci and candidate genes, and to discover the functions of key genes. However, molecular and/or targeted breeding toward biomass-related traits in sorghum have not fully benefited from these pieces of genetic knowledge. Thus, to facilitate the breeding and bioenergy applications of sorghum, this perspective summarizes the bioenergy applications of different types of sorghum and outlines the genetic control of the biomass-related traits, ranging from flowering/maturity, plant height, internode morphological traits and metabolic compositions. In particular, we describe the dynamic changes of carbohydrate metabolism in sorghum internodes and highlight the molecular regulators involved in the different stages of internode carbohydrate metabolism, which affects the bioenergy utilization of sorghum biomass. We argue the way forward is to further enhance our understanding of the genetic mechanisms of these biomass-related traits with new technologies, which will lead to future directions toward tailored designing sorghum biomass traits suitable for different bioenergy applications.

[Physical growth and dietary characteristics of children with attention deficit hyperactivity disorder: a cross-sectional study]. / æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥çš„ä½“æ ¼ç”Ÿé•¿å’Œè†³é£Ÿç‰¹å¾ï¼šä¸€é¡¹æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the physical growth and dietary characteristics of children with attention deficit hyperactivity disorder (ADHD), and to analyze their relationship with core symptoms of ADHD. METHODS: A total of 268 children who were newly diagnosed with ADHD in Children's Hospital of Nanjing Medical University from June to December 2020 were included in the ADHD group, and 102 healthy children who underwent physical examination during the same period were selected as the control group. Physical evaluations and dietary surveys were conducted for both groups. ADHD diagnosis and scoring were performed according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition). Factor analysis, Spearman correlation analysis, and mediation analysis were used to study the relationship between core symptoms of ADHD, dietary patterns, and physical growth. RESULTS: The rate of overweight/obesity in the ADHD group was significantly higher than that in the control group (35.8% vs 21.6%, P<0.05). Three dietary patterns were extracted from the food frequency questionnaire: vegetarian dietary pattern, traditional dietary pattern, and snack/fast food pattern. The factor score for the snack/fast food pattern in the ADHD group was higher than that in the control group (P<0.05). There was a significant positive correlation between ADHD symptom scores, snack/fast food pattern factor scores, and body fat percentage (P<0.05). The mediation analysis showed that the snack/fast food pattern played a partial mediating role in the relationship between ADHD symptom scores and body fat percentage, with a mediation proportion of 26.66%. CONCLUSIONS: The rate of overweight/obesity in children with ADHD is higher than that in non-ADHD children. Core symptoms of ADHD are related to dietary patterns and physical growth, with the snack/fast food pattern playing a partial mediating role in the relationship between core symptoms of ADHD and physical growth.

Propagation distance-resolved characteristics of copper plasma emission induced by axicon-focused femtosecond laser filamentation in air.

It is well known that Bessel beams have non-diffractive characteristics, which can be generated by Gaussian beams focused by an ideal axicon. In general, the length of filament generated by Bessel beams is longer than that by Gaussian beams and the electron density in the filament generated by Bessel beams is more uniform. This paper experimentally studied the propagation distance-resolved characteristics of copper plasma emission induced by axicon-focused femtosecond laser filamentation in the air. The evolution of the spectral intensity, plasma temperature, and electron density with the filament propagation path was obtained. The experiment results showed that when the base angle of the axicon was 5.0°, the spectral intensity along with the filament propagation path was more stable than that the base angle of the axicon was 0.5°. The changes in the plasma temperature and electron density along the filament propagation path were consistent with the change in the spectral intensity. This work provides a demonstration for the applications of filament-induced breakdown spectroscopy (FIBS), such as long-distance detection.

Trimetazidine affects pyroptosis by targeting GSDMD in myocardial ischemia/reperfusion injury.

OBJECTIVE: Trimetazidine (TMZ) exerts a strong inhibitory effect on ischemia/reperfusion (I/R) injury. Inflammation plays a key role in I/R injury. We hypothesized that TMZ may protect cardiomyocytes from I/R injury by inhibiting inflammation. METHODS: The left anterior descending coronary artery was ligated for 30 min followed by 6 h of reperfusion to establish a model of I/R injury. H9c2 cardiomyocytes were subjected to 2 h of hypoxia and 3 h of normoxic conditions to establish a model of hypoxia/reoxygenation (H/R) injury. We monitored the change in pyroptosis by performing Western blot analysis, microscopy and ELISA. RESULTS: I/R and H/R treatment stimulated gasdermin D-N domain (GSDMD-N) expression in cardiomyocytes (sham onefold vs. I/R 2.5-fold; control onefold vs. H/R 2.0-fold). Moreover, TMZ increased the viability of H9c2 cardiomyocytes subjected to H/R treatment (H/R 65.0% vs. H/R + TMZ 85.3%) and reduced the infarct size in vivo (I/R 47.0% vs. I/R + TMZ 28.3%). H/R and I/R treatment increased the levels of TLR4, MyD88, phospho-NF-κB p65 and the NLRP3 inflammasome; however, TMZ reduced the expression of these proteins. Additionally, TMZ inhibited noncanonical inflammasome signaling induced by I/R injury. CONCLUSIONS: In summary, TMZ alleviated pyroptosis induced by myocardial I/R injury through the TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway. Therefore, TMZ represents an alternative treatment for myocardial I/R injury.

Gut microbiome alterations in colitis rats after moxibustion at bilateral Tianshu acupoints.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is closely related to the gut microbiota. Moxibustion has been used to improve the inflammation and gastrointestinal dysfunctions in gastrointestinal disorders such as UC. In this study, we investigated whether moxibustion could improve the gut microbial dysbiosis induced by dextran sulphate sodium. METHODS: Twenty-five male rats were randomly assigned into five groups. The UC rat model was established by administering DSS solution. The rats in the moxibustion and normal rats with moxibustion groups were treated with moxibustion at Tianshu (bilateral, ST25) points, and the mesalazine group rats were treated with mesalazine once daily for 7 consecutive days. Disease activity index (DAI) and haematoxylin and eosin staining were used to evaluate the effect of moxibustion. Gut microbiota profiling was conducted by metagenomic high throughput sequencing technology. The gut microbiota composition, diversity and function were analyzed and compared using metagenomics methodologies. RESULTS: The DAI scores and histopathology scores in the moxibustion and mesalazine groups were significantly decreased compared with the UC group (P < 0.01). Moxibustion treatment increased abundance levels of Bacteroidetes, Actinobacteria, Ascomycota, Synergistetes and decreased abundance of Firmicutes, Proteobacteria. At the genus level, the abundance of Bacteroides, Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2, were increased and Bacteroides_bacterium_H3, Parabacteroides, Porphyromonas, Alistipes, Parasutterella were decreased in the UC group in comparsion with those in the NG group. Moxibustion increased the abundance of Bacteroides and Bacteroides_bacterium_H3 and decreased Bacteroides_bacterium_M7, Prevotella, Bacteroidales_bacterium_H2. In UC group, the specie Bacteroides_massiliensis was negatively (P < 0.05) correlated with IL-23, Bacteroides_eggerthii_CAG109 and Bacteroides_eggerthii were negatively (P < 0.05) correlated with TGF-ß. And the species Prevotella_sp_CAG1031 and Bacteroides_bacterium_H2 were significant positively (P < 0.05) correlated with IL-23. In addition, compare with the normal group, genes involved in certain metabolic pathways, such as energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, were under-represented in the UC group, and these changes in the metabolic pathways could be reversed by moxibustion treatment and mesalazine treatment. CONCLUSIONS: Our findings suggest that moxibustion treatment may protect the host from mucosal inflammation by modulating the intestinal microbiota community.

Elevated circulating levels of gasdermin D are related to acute myocardial infarction and pyrogptosis.

BACKGROUND: Acute myocardial infarction (AMI) is one of the leading contributors to morbidity and mortality worldwide, with a prevalence of nearly three million people, and more than one million deaths reported in the United States every year. Gasdermin D (GSDMD) is involved in the development of atherosclerosis as a key protein of proptosis. This study was designed to determine the potential relationship of GSDMD with AMI in Chinese patients. METHODS: One hundred patients with AMI and 50 controls were consecutively enrolled in this prospective observational study. GSDMD expression levels and other clinical variables in peripheral blood mononuclear cells (PBMCs) were measured upon admission to the hospital. All patients were followed up for 360 days, and the endpoint was considered the occurrence of major adverse cardiovascular events (MACE). RESULTS: GSDMD expression levels in the PBMCs of patients with AMI were significantly higher than those in the controls. Moreover, our analysis showed that GSDMD was an independent biomarker of AMI and had a promising diagnostic ability for it. Finally, the results suggested that high expression of GSDMD and diabetes increased the risk of MACE after AMI. CONCLUSIONS: This study indicated that the GSDMD expression level in PBMCs was elevated in AMI patients and was closely associated with the pyroptosis of AMI.

Clinical efficacy of melatonin as adjunctive therapy to non-surgical treatment of periodontitis: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the effect of adjunctive melatonin supplementation on clinical outcomes after non-surgical periodontal treatment. METHODS: PubMed, Embase, and Web of Science databases were systematically searched for randomised controlled trials (RCTs) of melatonin adjuvant therapy for periodontitis from inception until May 2021. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered on The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021250630). The risk of bias of included studies was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. The pooled effect estimates were calculated by a random-effects model, and results were expressed as weighted mean differences (WMD). RESULTS: Seven RCTs comprising 412 participants were included in the meta-analysis. The pooled results showed that adjuvant use of melatonin for non-surgical periodontal treatment significantly improved the probing depth (PD) [WMD = - 1.18, 95% CI (- 1.75, - 0.62) I2 = 85.7%], clinical attachment loss (CAL) [WMD = - 1.16, 95% CI (- 1.60, - 0.72) I2 = 76.7%] and gingival index (WMD = - 0.29, 95%CI [- 0.48, - 0.11], I2 = 63.6%) compared with non-surgical treatment alone. In addition, subgroup analysis showed that higher doses of melatonin (3-10 mg) significantly improved PD [WMD = - 1.32, 95%CI (- 2.31, - 0.15) I2 = 93%] and CAL [WMD = - 1.30, 95%CI (- 1.80, - 0.81) I2 = 73.7%] compared with lower doses of melatonin (< 3 mg). CONCLUSIONS: We found that adjunctive melatonin supplementation can significantly improve the periodontal status after non-surgical treatment, suggesting that melatonin may be a new adjuvant therapy for periodontitis when non-surgical periodontal treatment alone cannot achieve the desired improvement.

Risk factors for midcourse correction during treatment of first series of aligners with Invisalign.

INTRODUCTION: This study aimed to analyze risk factors for midcourse correction (MC) during the first series of aligners in treatments with Invisalign (Align Technology, Santa Clara, Calif). METHODS: Three hundred and fourteen patients treated with Invisalign were divided into MC and non-midcourse correction groups according to whether they completed the first series of aligners. Differences between these groups were compared with independent sample t tests, chi-square tests, and Wilcoxon rank sum tests. A multivariate logistic regression analysis was performed to identify independent risk factors, including gender, age, extraction treatment, interproximal reduction, correction steps (steps in first series treatment), overbite, overjet, the curve of Spee, Angle classification, and crowding. RESULTS: The percentage of females (86.3%), Angle Class I malocclusion (62.4%), and nonextraction (56.1%) was relatively higher in all 314 patients. More than half of the patients (73.6%) completed the first series of aligners. Differences between the groups in the number of patients with extraction, correction steps, and the curve of Spee were significant (P <0.05). The proportions of MC were 41.3% and 14.8% in extraction and nonextraction patients, respectively. More initially planned correction steps were seen in the MC group (53.4 ± 15.6 steps). Extraction (adjusted odds ratio, 0.375; P = 0.001) and correction steps (adjusted odds ratio, 1.06; P <0.001) were independent risk factors for MC. CONCLUSIONS: Extraction and the number of initially planned correction steps are independent risk factors for MC. In patients with complex dentofacial abnormalities, such as extraction, MC may be needed to achieve predicted changes.

STAT3 Promotes Schistosome-Induced Liver Injury by Inflammation, Oxidative Stress, Proliferation, and Apoptosis Signal Pathway.

Schistosomiasis is a parasitic helminth disease that can cause organ lesions leading to health damage. During a schistosome infection, schistosome eggs can flow into the liver along the portal vein. Numerous inflammatory cells gather around the eggs, causing granulomas and fibrosis in the liver. In this process, many molecules are involved in the initiation and regulation of the fibrous scar formation. However, the precise molecular mechanisms responsible for the progression of granuloma formation and fibrosis initiation caused by schistosome infection have not been extensively studied. In this study, C57BL/6 wild-type mice and Stat3flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum Liver injury, effector molecule levels, and RNA transcriptome resequencing of liver tissue were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 (signal transducer and activator of transcription 3) in Schistosoma-induced liver injury in mice. After 6 weeks postinfection, there was obvious liver fibrosis. A sustained pathological process (inflammation, oxidative stress, proliferation, and apoptosis) occurred in S. japonicum-induced liver fibrosis initiation. Meanwhile, we observed activation of the STAT3 pathway in hepatic injury during S. japonicum infection by RNA transcriptome resequencing. Liver deficiency of phospho-STAT3 alleviated infection-induced liver dysfunction, hepatic granuloma formation, and fibrosis initiation. It also promoted STAT3-dependent apoptosis and reduced liver inflammation, oxidative stress, and proliferation. Our results suggest that STAT3 signal pathway and its mediating inflammation, oxidative stress, proliferation, and apoptosis are involved in S. japonicum-induced liver injury and may be a new potential guideline for the treatment of schistosomiasis.

Bioactive Polyketide-Terpenoid Hybrids from a Soil-Derived Fungus Bipolaris zeicola.

Nine novel polyketide-terpenoid hybrids (1-9), characterized by a 1-alkylated-3,5-dihydroxyphenyl derivative coupled with a modified farnesyl pyrophosphate (FPP) unit, were isolated from a soil-derived fungus Bipolaris zeicola. Their structures were determined by comprehensive spectroscopic data, single-crystal X-ray diffraction analyses, and electronic circular dichroism calculations. Structurally, compounds 1, 2, 5, and 6 possess a rare thiazole moiety; compounds 3 and 4 are the first examples of meroterpenoids featuring an undescribed 6/6/6/6/5 pentacyclic system and bearing a tetrahydrofuran ring fused to a polyketide and a sesquiterpenoid subunit; compounds 7 and 8 possess a rare 2H-1,4-thiazin-3(4H)-one moiety; and compound 9 represents the first example of meroterpenoid having an unusual thiazol-2(3H)-one moiety. The bioactivity assays revealed that compounds 1, 2, 5, 6, and 9 exhibited a significant immunosuppressive effect against concanavalin A (ConA)-induced T lymphocyte proliferation with IC50 values ranging from 5.6 to 8.8 µM, and compounds 1, 2, and 4 exhibited moderate cytotoxic activities with IC50 values ranging from 18.4 to 29.4 µM.