Neferine mitigates angiotensin II-induced atrial fibrillation and fibrosis via upregulation of Nrf2/HO-1 and inhibition of TGF-ß/p-Smad2/3 pathways.

BACKGROUND: Atrial fibrillation (AF) is often associated with atrial fibrosis and oxidative stress. Neferine, a bisbenzylisoquinoline alkaloid, has been reported to exert an antiarrhythmic effect. However, its impact on Angiotensin II (Ang II) infusion-induced AF and the underlying mechanism remains unclear. This study aimed to investigate whether neferine alleviates Ang II-induced AF and explore the underlying mechanisms. METHODS: Mice subjected to Ang II infusion to induce AF were concurrently treated with neferine or saline. AF incidence, myocardial cell size, fibrosis, and oxidative stress were then examined. RESULTS: Neferine treatment inhibited Ang II-induced AF, atrial size augmentation, and atrial fibrosis. Additionally, we observed that Ang II increased reactive oxygen species (ROS) generation, induced mitochondrial membrane potential depolarization, and reduced glutathione (GSH) and superoxide dismutase (SOD) levels, which were reversed to some extent by neferine. Mechanistically, neferine activated the Nrf2/HO-1 signaling pathway and inhibited TGF-ß/p-Smad2/3 in Ang II-infused atria. Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, reduced the anti-oxidative effect of neferine to some extent and subsequently abolished the beneficial effect of neferine on Ang II-induced AF. CONCLUSIONS: These findings provide hitherto undocumented evidence that the protective role of neferine in Ang II-induced AF is dependent on HO-1.

The Discovery of a Multidomain Mannanase Containing Dual-Catalytic Domain of the Same Activity: Biochemical Properties and Synergistic Effect.

In recent years, the wide application of mannan has driven the demand for the exploration of mannanase. As one of the main components of hemicellulose, mannan is an important polysaccharide that ruminants need to degrade and utilize, making rumen a rich source of mannanases. In this study, gene mining of mannanases was performed using bioinformatics, and potential dual-catalytic domain mannanases were heterologously expressed to analyze their properties. The hydrolysis pattern and enzymatic products were identified by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). A dual-catalytic domain mannanase Man26/5 with the same function as the substrate was successfully mined from the genome of cattle rumen microbiota. Compared to the single-catalytic domain, its higher thermal stability (≤50 °C) and catalytic efficiency confirm the synergistic effect between the two catalytic domains. It exhibited a unique "crab-like" structure where the CBM located in the middle is responsible for binding, and the catalytic domains at both ends are responsible for cutting. The exploration of its multidomain structure and synergistic patterns could provide a reference for the artificial construction and molecular modification of enzymes.

Effect of Neutrophil-to-Lymphocyte Ratio on Post-TAVR Mortality and Periprocedural Pulmonary Hypertension.

Aims: To evaluate the impact of neutrophil-to-lymphocyte ratio (NLR) on periprocedural pulmonary hypertension (PH) and 3-month all-cause mortality in patients with aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) and to develop a nomogram for predicting the mortality for these patients. Methods and Results: 124 patients undergoing TAVR were categorized into three groups according to systolic pulmonary artery pressure (sPAP): Group I (no PH, n = 61) consisted of patients with no pre- and post-TAVR PH; Group II (improved PH, n = 35) consisted of patients with post-TAVR systolic pulmonary artery pressure (sPAP) decreased by more than 10 mmHg compared to pre-TAVR levels; and Group III (persistent PH, n = 28) consisted of patients with post-TAVR sPAP no decrease or less than 10 mmHg, or new-onset PH after the TAVR procedure. The risk of all-cause mortality within 3 months tended to be higher in Group II (11.4%) and Group III (14.3%) compared to Group I (3.3%) (P=0.057). The multinomial logistic regression analysis demonstrated a positive correlation between NLR and both improved PH (OR: 1.182, 95% CI: 1.036-1.350, P=0.013) and persistent PH (OR: 1.181, 95% CI: 1.032-1.352, P=0.016). Kaplan-Meier analysis revealed a significant association between higher NLR and increased 3-month all-cause mortality (16.1% vs. 3.1% in lower NLR group, P=0.021). The multivariable Cox regression analysis confirmed that NLR was an independent predictor for all-cause mortality within 3 months, even after adjusting for clinical confounders. A nomogram incorporating five factors (BNP, heart rate, serum total bilirubin, NLR, and comorbidity with coronary heart disease) was developed. ROC analysis was performed to discriminate the ability of the nomogram, and the AUC was 0.926 (95% CI: 0.850-1.000, P < 0.001). Conclusions: Patients with higher baseline NLR were found to be at an increased risk of periprocedural PH and all-cause mortality within 3 months after TAVR.

Identification and structural characterization of a novel chondroitin sulfate-specific carbohydrate-binding module: The first member of a new family, CBM100.

Chondroitin sulfate is a biologically and commercially important polysaccharide with a variety of applications. Carbohydrate-binding module (CBM) is an important class of carbohydrate-binding protein, which could be utilized as a promising tool for the applications of polysaccharides. In the present study, an unknown function domain was explored from a putative chondroitin sulfate lyase in PL29 family. Recombinant PhCBM100 demonstrated binding capacity to chondroitin sulfates with Ka values of 2.1 ± 0.2 × 106 M-1 and 6.0 ± 0.1 × 106 M-1 to chondroitin sulfate A and chondroitin sulfate C, respectively. The 1.55 Å resolution X-ray crystal structure of PhCBM100 exhibited a ß-sandwich fold formed by two antiparallel ß-sheets. A binding groove in PhCBM100 interacting with chondroitin sulfate was subsequently identified, and the potential of PhCBM100 for visualization of chondroitin sulfate was evaluated. PhCBM100 is the first characterized chondroitin sulfate-specific CBM. The novelty of PhCBM100 proposed a new CBM family of CBM100.

Discovery and characterization of a novel carbohydrate-binding module: a favorable tool for investigating agarose.

BACKGROUND: Agarose, mainly composed of 3,6-anhydro-α-l-galactopyranose (LA) and ß-d-galactopyranose (G) units, is an important polysaccharide with wide applications in food, biomedical and bioengineering industries. Carbohydrate-binding modules (CBMs) are favorable tools for the investigations of polysaccharides. Few agarose-binding CBMs have been hitherto reported, and their binding specificity is unclear. RESULTS: An unknown domain with a predicted ß-sandwich fold was discovered from a ß-agarase of the marine bacterium Wenyingzhuangia fucanilytica CZ1127T . The expressed protein WfCBM101 could bind to agarose and exhibited relatively weak affinity for porphyran, with no affinity for the other seven examined polysaccharides. The protein binds to the tetrasaccharide (LA-G)2 , but not to the major tetrasaccharide contained in porphyran. The sequence novelty and well-defined binding function of WfCBM101 shed light on a novel CBM family (CBM101). Furthermore, the feasibility of WfCBM101 for visualizing agarose in situ was confirmed. CONCLUSION: A novel CBM, WfCBM101, with a desired specificity for agarose was discovered and characterized, which represents a new CBM family. The CBM could be utilized as a promising tool for studies of agarose. © 2023 Society of Chemical Industry.

Abnormal caudate nucleus activity in patients with depressive disorder: Meta-analysis of task-based functional magnetic resonance imaging studies with behavioral domain.

During task-based functional magnetic resonance imaging (t-fMRI) patients with depressive disorder (DD) have shown abnormal caudate nucleus activation. There have been no meta-analyses that are conducted on the caudate nucleus using Activation Likelihood Estimation (ALE) in patients with DD, and the relationships between abnormal caudate activity and different behavior domains in patients with DD remain unclear. There were 24 previously published t-fMRI studies included in the study with the caudate nucleus as the region of interest. Meta-analyses were performed using the method of ALE. Included five ALE meta-analyses: (1) the hypoactivated caudate nucleus relative to healthy controls (HCs); (2) the hyper-activated caudate nucleus; (3) the abnormal activation in the caudate nucleus in the emotion domain; (4) the abnormal activation in cognition domain; (5) the abnormal activation in the affective cognition domain. Results revealed that the hypo-/hyper-activity in the caudate subregions is mainly located in the caudate body and head, while the relationships between abnormal caudate subregions and different behavior domains are complex. The hypoactivation of the caudate body and head plays a key role in the emotions which indicates there is a positive relationship between the decreased caudate activity and depressed emotional behaviors in patients with DD.

In vivo visualization of tumor-associated macrophages re-education by photoacoustic/fluorescence dual-modal imaging with a metal-organic frames-based caspase-1 nanoreporter.

Tumor-associated macrophages (TAMs) are vital in the tumor microenvironment, contributing to immunosuppression and therapy tolerance. Despite their importance, the precise re-education of TAMs in vivo continues to present a formidable challenge. Moreover, the lack of real-time and efficient methods to comprehend the spatiotemporal kinetics of TAMs repolarization remains a significant hurdle, severely hampering the accurate assessment of treatment efficacy and prognosis. Herein, we designed a metal-organic frameworks (MOFs) based Caspase-1 nanoreporter (MCNR) that can deliver a TLR7/8 agonist to the TAMs and track time-sensitive Caspase-1 activity as a direct method to monitor the initiation of immune reprogramming. This nanosystem exhibits excellent TAMs targeting ability, enhanced tumor accumulation, and stimuli-responsive behavior. By inducing the reprogramming of TAMs, they were able to enhance T-cell infiltration in tumor tissue, resulting in inhibited tumor growth and improved survival in mice model. Moreover, MCNR also serves as an activatable photoacoustic and fluorescent dual-mode imaging agent through Caspase-1-mediated specific enzyme digestion. This feature enables non-invasive and real-time antitumor immune activation monitoring. Overall, our findings indicate that MCNR has the potential to be a valuable tool for tumor immune microenvironment remodeling and noninvasive quantitative detection and real-time monitoring of TAMs repolarization to immunotherapy in the early stage.

Exploring the effects and mechanisms of Guizhigancao Decoction on heart failure using an integrated approach based on experimental support and network pharmacology strategy.

Background and aim: HF (Heart Failure) is the leading cause of mortality and is a significant clinical problem affecting millions of patients worldwide. To date, the mechanisms of HF remain largely elusive. The effective treatments contributing to HF remain incompletely understood. Therefore, the development of an effective strategy for HF is urgently needed. Experimental procedure: In the present study, we devoted to investigating the effective treatments and sought to systematically decipher the related molecular mechanisms of Guizhigancao Decoction (GZGCD, Cinnamomum cassia Presl and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle) for treating HF. We examined the therapeutic effect of GZGCD on HF in vivo. An integrative approach combining biomarker examination, echocardiography, myocardial fibrosis and cardiac apoptosis condition using Masson and TUNEL staining was performed to assess the efficacy of GZGCD against HF. Subsequently, comprehensive network pharmacology analyses were performed to explore the mechanisms involved in GZGCD therapeutic effects on HF. Results and conclusions: The results showed that GZGCD could reverse cardiac function in rats with HF by reducing NT-proBNP, increasing EF, decreasing LVESV, LVEDV, LVIDs, LVIDd, increasing running time, and ameliorate myocardial collagen fiber hyperplasia and cardiomyocyte apoptosis. We showed that GZGCD might contribute to HF treatment via oxidative related pathways through bioinformatics. Eventually, promising compound quercetin in GZGCD for HF therapeutics was proposed in database-based analysis. Collectively, our findings indicate that GZGCD has a treatment effect on HF. We proposed that GZGCD might contribute HF treatment via oxidative response-related pathways.

An efficient convolutional neural network-based diagnosis system for citrus fruit diseases.

Introduction: Fruit diseases have a serious impact on fruit production, causing a significant drop in economic returns from agricultural products. Due to its excellent performance, deep learning is widely used for disease identification and severity diagnosis of crops. This paper focuses on leveraging the high-latitude feature extraction capability of deep convolutional neural networks to improve classification performance. Methods: The proposed neural network is formed by combining the Inception module with the current state-of-the-art EfficientNetV2 for better multi-scale feature extraction and disease identification of citrus fruits. The VGG is used to replace the U-Net backbone to enhance the segmentation performance of the network. Results: Compared to existing networks, the proposed method achieved recognition accuracy of over 95%. In addition, the accuracies of the segmentation models were compared. VGG-U-Net, a network generated by replacing the backbone of U-Net with VGG, is found to have the best segmentation performance with an accuracy of 87.66%. This method is most suitable for diagnosing the severity level of citrus fruit diseases. In the meantime, transfer learning is applied to improve the training cycle of the network model, both in the detection and severity diagnosis phases of the disease. Discussion: The results of the comparison experiments reveal that the proposed method is effective in identifying and diagnosing the severity of citrus fruit diseases identification.

Understanding acid hydrolysis of corn stover during densification pretreatment for quantitative predictions of enzymatic hydrolysis efficiency using modified pretreatment severity factor.

DLCA(sa) pretreatment (densifying lignocellulosic biomass with sulfuric acid followed by autoclave treatment), featured with low treatment temperature and densification, demonstrate high efficiency in biomass pretreatment. In this study, the effects of temperature, acid loading, time on the hydrolysis of xylan, cellulose and lignin during DLCA(sa) pretreatment were systematically investigated. It was shown that DLCA(sa) pretreatment can effectively solubilize xylan, achieving an 84% xylose recovery under mild conditions (130 °C, 30 min, and 0.125 g/g acid loading). The conventional pretreatment severity factor correlated and further modified to improve the accuracy in evaluating the xylan hydrolysis. Additionally, a mathematical model based on the xylan hydrolytic kinetics was proposed to predict the enzymatic hydrolysis. Kinetic model suggested that mechanical densification facilitates the penetration of acid into the biomass matrix, leading to increased accessibility of xylan to acid catalysis.

In situ fluorescence-photoacoustic measurement of the changes of brown adipose tissue in mice under hindlimb unloading.

Space travel causes rapid weight loss of astronauts, but the underlying reasons are still obscure. Brown adipose tissue (BAT) is a well-known thermogenesis tissue that is innervated by sympathetic nerves, and norepinephrine stimulation can promote the thermogenesis and angiogenesis of BAT. Herein, the structural and physiological changes of BAT as well as serological indicators were investigated in mice under hindlimb unloading (HU) to simulate a weightless environment in space. The results showed that long-term HU could induced the thermogenic activation of BAT by upregulating the mitochondrial uncoupling protein. Further, peptide-conjugated indocyanine green was developed to target the vascular endothelial cells of BAT. Noninvasive fluorescence-photoacoustic imaging presented the neovascularization of BAT on the micron scale in the HU group, accompanying by the increase of vessel density. Downward trend of serum triglyceride and glucose level of mice treated with HU proved the more heat production and energy consumption in BAT compared with the control group. This study suggested that HU may be an effective strategy to curb the occurrence of obesity, whereas fluorescence-photoacoustic dual-modal imaging showed capability of assessing BAT activity.NEW & NOTEWORTHY We found that the mechanism of weight loss of astronauts in space flight may be that hindlimb unloading (HU) promotes the activation of brown adipose tissue (BAT) and the increase of uncoupling protein (UCP1) expression, which accelerates the body's heat production. Meanwhile, the activation of BAT is accompanied by the proliferation of blood vessels. With the help of peptide CPATAERPC conjugated indocyanine green targeting to vascular endothelial cells, fluorescence-photoacoustic imaging has selectively tracked the vascular structure of BAT on the micron scale, which provided noninvasive imaging tools to in situ measure the changes of BAT.

Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor ß type II receptor.

BACKGROUND: The transforming growth factor ß (TGFß) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFß type II receptor (TGFßR2), followed by the recruitment of TGFßR1 finally triggering downstream signaling pathway. AIM: To find drugs targeting TGFßR2 that inhibit TGFßR1/TGFßR2 complex formation, theoretically inhibit TGFß signaling pathway, and thereby ameliorate liver fibrosis. METHODS: Food and Drug Administration-approved drugs were screened for binding affinity with TGFßR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8 (CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect. RESULTS: We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine (DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFß induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFßR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFßR2 disrupted the binding of TGFßR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson's trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver. CONCLUSION: DHE alleviates liver fibrosis by binding to TGFßR2 thereby suppressing TGFß signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice.

Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

A Preliminary Study of Ultrasound-Guided Microwave Ablation for Nonpuerperal Mastitis Treatment.

Introduction: This study investigated the feasibility of ultrasound (US)-guided microwave ablation (MWA) as a treatment for nonpuerperal mastitis (NPM). Methods: Fifty-three patients with NPM diagnosed by biopsy and treated with US-guided MWA at the Affiliated Hospital of Nantong University between September 2020 and February 2022 were classified according to whether they underwent MWA alone (n = 29) or MWA with incision and drainage (n = 24). Patients were followed up by interviews, physical and US examinations, and evaluation of breast skin at 1 week and 1, 2, and 3 months after treatment. Data from these patients were prospectively collected and retrospectively analyzed. Results: The overall mean patient age was 34.42 ± 9.20 years. The groups differed significantly by age, involved quadrants, and the initial maximum diameter of lesions. In the MWA group, the cure rate was 34.48%, and the apparent efficiency rate was 65.52%. In the MWA with incision and drainage, the apparent efficiency rate was 91.66%, and the effective rate was 4.17%. The excellent rate for breast aesthetics in the MWA group was 79.31%, and the good rate was 20.69%. The excellent rate in the MWA with incision and drainage group was 45.83%, the good rate was 41.67%, and the qualified rate was 12.5%. The mean maximum diameter of lesions in the two groups decreased significantly. Conclusion: For NPM with small lesions in a single quadrant, MWA therapy is a direct and effective method. For larger lesions involving two or more quadrants, the combined treatment of MWA with incision and drainage showed significant improvement in a short period. MWA treatment of NPM has importance for further research and clinical applications.

Cardiac arrest caused by coronary occlusion during transcatheter aortic valve implantation: a unique cause.

Coronary artery occlusion (CAO) is a rare but life-threatening complication of transcatheter aortic valve implantation (TAVI). The mechanism of CAO is the displacement of the native calcified valve leaflet over the coronary ostium. Here, we report on a woman who experienced sudden cardiac arrest and abrupt CAO during TAVI, which was caused by two different original obstructions, a rupture of aortic plaque or a partial tear of the aortic intima blocking the upper 2/3 of the left main trunk (LMT) ostium, and the transcatheter heart valve (THV) blocking the lower 1/3 of the LMT ostium. She was eventually successfully treated with the chimney stenting technique. Aortography other than coronary angiography was used to ascertain CAO. In patients presenting with abrupt cardiac arrest or cardiogenic shock with LMT occlusion, there must be prompt identification, and the causes of CAO may be various and rare. The identification of CAO relies not only on CAG but also on aortography, especially if the locations and origins of obstructions are special. Supportive therapy with an attempt at percutaneous revascularization is necessary. Pre-procedural assessment is crucial prior to TAVI interventions. In cases with high risk of CAO, upfront coronary artery protection can be provided.

Light calcium carbonate improves pullulan biosynthesis by Aureobasidium pullulans under high concentration of sugar.

The effects of light calcium carbonate (CaCO3) on pullulan biosynthesis by Aureobasidium pullulans NCPS2016 were investigated. Light CaCO3 enhanced pullulan production by 12.4 % when added to the low concentration of fructose broth compared with K2HPO4. Pullulan production was further improved when increasing both the concentrations of light CaCO3 and fructose. Compared to K2HPO4, light CaCO3 improved the activities of UDP-glucose pyrophosphorylase, α-phosphoglucose mutase, UDP-glucosyltransferase, and glucosyltransferase relevant to pullulan biosynthesis, and the gene transcriptional levels of UDP-glucose pyrophosphorylase, α-phosphoglucose mutase, UDP-glucosyltransferase, and glucose kinase were enhanced. During 30-liter fermentation, 144.3 g/L of purified pullulan was produced from 200 g/L of fructose and 15 g/L of light CaCO3 within 168 h, with the yield and productivity of 0.72 g/g and 0.86 g/L/h respectively. This is the first report that light CaCO3 improves pullulan production significantly.

Loss of SQSTM1/p62 Induces Obesity and Exacerbates Alcohol-Induced Liver Injury in Aged Mice.

BACKGROUND: Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice. METHODS: Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis. RESULTS: Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury. CONCLUSIONS: Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.

Characterization of the effects of binary probiotics and wolfberry dietary fiber on the quality of yogurt.

The effects of binary probiotics (Lacticaseibacillus casei CGMCC1.5956 and Lactiplantibacillus plantarum subsp. plantarum CGMCC 1.5953) in conjunction with wolfberry dietary fiber (WDF) on yogurt quality were investigated in this study. d-fructose, ß-d-glucose, 6-acetyl-d-glucose, and 1-ketose in WDF significantly improved syneresis, apparent viscosity, and elastic behavior of yogurt. Binary probiotics were more suitable for fermenting WDF yogurt than single probiotics, resulting in a higher viable count (9.39 lg (CFU/mL)) and unique flavor. Binary probiotics can promote the production of tyrosol by L. casei 56 through the tyrosine metabolic pathway, thereby enhancing the resistance of L. casei 56 and L. plantarum 53 to their environment and promoting growth. Pyridine, 2,3,4,5-tetrahydro- and prenol might be responsible for the high odor scores in the sensory evaluation of WDF yogurt prepared using binary probiotics. In summary, combining binary probiotics and WDF can significantly improve yogurt quality and add value to the final product.

VMP1 regulates hepatic lipoprotein secretion and NASH independent of autophagy.

VMP1 is an ER membrane protein with phospholipid scramblase activity that has a critical role in regulating phagophore expansion and autophagosome closure. VMP1 also regulates lipid droplet formation and lipoprotein secretion in cultured cells and zebrafish. In a recent study, we showed that mice with hepatic deletion of Vmp1 have impaired very-low-density lipoprotein (VLDL) secretion and develop nonalcoholic steatohepatitis (NASH) even when fed with regular chow diet. Mechanistically, deletion of Vmp1 leads to decreased hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels as well as altered PC and PE acyl chain compositions resulting in the accumulation of neutral lipid structures in the ER phospholipid bilayer and decreased pre-VLDL assembly. These studies provide novel mechanistic insights into the non-autophagic functions of VMP1 in regulating lipoprotein secretion.

Investigation of oral health knowledge and attitudes towards oral health education among elementary school teachers in Zunyi.

OBJECTIVES: This study aimed to investigate the oral health knowledge of elementary school teachers and assess their attitude towards oral health education in Zunyi. METHODS: A total of 636 teachers from 10 primary schools in Zunyi were selected by stratified sampling, and their general information, oral health care habits, results of oral health knowledge questionnaire, and attitude towards oral health and oral health education were investigated. Data were statistically analyzed using SPSS 21.0. RESULTS: A total of 614 teachers answered the questionnaires. Only 8.8% brush their teeth for more than three minutes, 23.8% brush their teeth horizontally, 64.7% do not performteeth cleaning, and 78.2% do not use floss. Teachers have a weak understanding that six-year teeth are permanent, that pit and fissure sealing could prevent dental caries, and that dental floss could remove dental plaque. However, their attitude towards oral health and oral health education was found to be good. CONCLUSIONS: Schools could improve teachers' oral health know-ledge by organizing training and other activities. Teachers could also play an active role in leading and cultivating school-age children to establish good oral habits.