Diagnostic value of DNA or RNA-based metagenomic next-generation sequencing in lower respiratory tract infections.

Objectives: We aimed to evaluate and compare the diagnostic performance of RNA-mNGS and DNA-mNGS workflow in bacterial pneumonia, fungal pneumonia and tuberculosis. Methods: A total of 134 cases suspected pneumonia undergoing both DNA and RNA based mNGS of bronchoalveolar lavage fluid (BALF) and also traditional etiological examination were evaluated retrospectively.Sensitivity, specificity, PPV, NPV and accuracy rate of DNA and RNA based mNGS were estimated. Results: In the diagnosis performance of bacterial pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS(82.3 % vs. 61.9 %, P < 0.01). There was no significant difference of sensitivity between the two process(71.4 % vs. 85.7 %, P = 0.375).In the diagnosis performance of fungal pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS (72.3 % vs. 27.3 %,p < 0.001). There was no significant difference of sensitivity between the two process(96.5 % vs. 98.8 %,p = 0.125).In the diagnosis performance of tuberculosis in LRTIs,the sensitivity of DNA-mNGS was higher than that of RNA-mNGS (91.7 % vs. 33.3 %,p = 0.016),the specificity was similar in the two process (100 %). Conclusions: RNA-mNGS may reduced the misdiagnosis rate of bacterial and fungal pathogens in LRTIs.Compared to RNA-mNGS, DNA-mNGS may could improve the diagnostic rate of tuberculosis.

Prevalence and Burden of Multiple Sclerosis in China, 1990-2019: Findings From the Global Burden of Disease Study 2019.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is the leading cause of neurologic disability in young adults, but the burden caused by MS in China is lacking. We aimed to comprehensively describe the prevalence and health loss due to MS by demographic and geographical variables from 1990 to 2019 across China. METHODS: Data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). We used GBD methodology to systematically analyze the prevalence, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to MS by age, sex, and location from 1990 to 2019 in mainland China and its provinces. We also compared the MS burden in China with the world and other Group of 20 (G20) countries. RESULTS: In 2019, 42,571 (95% uncertainty interval [UI] 33,001-53,329) individuals in China had MS, which doubled from 1990. The age-standardized prevalence rate of MS was 2.32 per 100,000 (95% UI 1.78-2.91), which increased by 23.31% (95% UI 20.50-25.89) from 1990, with most of the growth occurring after 2010. There was a positive latitudinal gradient with the increasing prevalence from south to north across China. The total DALYs caused by MS were 71,439 (95% UI 58,360-92,254) in 2019, ranking China third among G20 countries. Most of the MS burden in China derived from premature mortality, with the higher fraction of YLLs than that at the global level and most other G20 countries. From 1990 to 2019, the age-standardized DALY and YLL rate had nonsignificant changes; however, the age-standardized YLD rate substantially increased by 23.33% (95% UI 20.50-25.89). The geographic distribution of MS burden varied at the provincial level in China, with a slight downward trend in the age-standardized DALY rates along with increasing Socio-Demographic Index over the study period. DISCUSSION: Although China has a low risk of MS, the substantial and increasing prevalent cases should not be underestimated. The high burden due to premature death and geographic disparity of MS burden reveals insufficient management of MS in China, highlighting the needs for increased awareness and effective intervention.

Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.

CONTEXT: The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown. OBJECTIVE: This study explores the mechanisms of GGD against cardiac hypertrophy. MATERIALS AND METHODS: Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10-5 g/mL) and GGD (10-5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis. RESULTS: Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10-6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD. DISCUSSION AND CONCLUSIONS: Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.

Targeting tumor cell-to-macrophage communication by blocking Vtn-C1qbp interaction inhibits tumor progression via enhancing macrophage phagocytosis.

Background: Cancer cells are capable of evading clearance by macrophages through overexpression of anti-phagocytic surface proteins known as "don't eat me" signals. Monoclonal antibodies that antagonize the "don't-eat-me" signaling in macrophages and tumor cells by targeting phagocytic checkpoints have shown therapeutic promises in several cancer types. However, studies on the responses to these drugs have revealed the existence of other unknown "don't eat me" signals. Moreover, identification of key molecules and interactions regulating macrophage phagocytosis is required for tumor therapy. Methods: CRISPR screen was used to identify genes that impede macrophage phagocytosis. To explore the function of Vtn and C1qbp in phagocytosis, knockdown and subsequent functional experiments were conducted. Flow cytometry were performed to explore the phagocytosis rate, polarization of macrophage, and immune microenvironment of mouse tumor. To explore the underlying molecular mechanisms, RNA sequencing, immunoprecipitation, mass spectrometry, and immunofluorescence were conducted. Then, in vivo experiments in mouse models were conducted to explore the probability of Vtn knockdown combined with anti-CD47 therapy in breast cancer. Single-cell sequencing data from the Gene Expression Omnibus from The Cancer Genome Atlas database were analyzed. Results: We performed a genome-wide CRISPR screen to identify genes that impede macrophage phagocytosis, followed by analysis of cell-to-cell interaction databases. We identified a ligand-receptor pair of Vitronectin (Vtn) and complement C1Q binding protein (C1qbp) in tumor cells or macrophages, respectively. We demonstrated tumor cell-secreted Vtn interacts with C1qbp localized on the cell surface of tumor-associated macrophages, inhibiting phagocytosis of tumor cells and shifting macrophages towards the M2-like subtype in the tumor microenvironment. Mechanistically, the Vtn-C1qbp axis facilitated FcγRIIIA/CD16-induced Shp1 recruitment, which reduced the phosphorylation of Syk. Furthermore, the combination of Vtn knockdown and anti-CD47 antibody effectively enhanced phagocytosis and infiltration of macrophages, resulting in a reduction of tumor growth in vivo. Conclusions: This work has revealed that the Vtn-C1qbp axis is a new anti-phagocytic signal in tumors, and targeting Vtn and its interaction with C1qbp may sensitize cancer to immunotherapy, providing a new molecular target for the treatment of triple-negative breast cancer.

Association of Morphology of Lenticulostriate Arteries and Proximal Plaque Characteristics With Single Subcortical Infarction: A Whole-Brain High-Resolution Vessel Wall Imaging Study.

BACKGROUND: We aimed to investigate the association of characteristics of lenticulostriate artery (LSA) morphology and parental atheromatous disease (PAD) with single subcortical infarction (SSI) and to explore whether the LSA morphology is correlated with proximal plaque features in asymptomatic PAD. METHODS AND RESULTS: Patients with acute SSI were prospectively enrolled and classified as large- and small-SSI groups. The clinical data and imaging features of LSA morphology (branches, length, dilation, and tortuosity) and middle cerebral artery plaques (normalized wall index, remodeling index, enhancement degree, and hyperintense plaques) were evaluated. Logistic regression was performed to determine the association of large SSIs with morphologic features of LSAs and plaques. The Spearman correlation between the morphologic characteristics of LSAs and plaque features in asymptomatic PAD was analyzed. Of the 121 patients recruited with symptomatic PAD, 102 had coexisting asymptomatic contralateral PAD. The mean length of LSAs (odds ratio, 0.84 [95% CI, 0.73-0.95]; P=0.007), mean tortuosity of LSAs (odds ratio, 1.13 [95% CI, 1.05-1.22]; P=0.002), dilated LSAs (odds ratio, 22.59 [95% CI, 2.46-207.74]; P=0.006), and normalized wall index (odds ratio, 1.08 [95% CI, 1.01-1.15]; P=0.022) were significantly associated with large SSIs. Moreover, the normalized wall index was negatively correlated with the mean length of LSAs (r=-0.348, P<0.001), and the remodeling index was negatively correlated with the mean tortuosity of LSAs (r=-0.348, P<0.001) in asymptomatic PAD. CONCLUSIONS: Our findings suggest that mean length of LSAs, mean tortuosity of LSAs, dilated LSAs, and normalized wall index are associated with large SSIs. Moreover, plaque features in asymptomatic PAD are correlated with morphologic features of LSAs.

Interactive attack-defense for generalized person re-identification.

Generalized Person Re-Identification (GReID) aims to develop a model capable of robust generalization across unseen target domains, even with training on a limited set of observed domains. Recently, methods based on the Attack-Defense mechanism are emerging as a prevailing technology to this issue, which treats domain transformation as a type of attack and enhances the model's generalization performance on the target domain by equipping it with a defense module. However, a significant limitation of most existing approaches is their inability to effectively model complex domain transformations, largely due to the separation of attack and defense components. To overcome this limitation, we introduce an innovative Interactive Attack-Defense (IAD) mechanism for GReID. The core of IAD is the interactive learning of two models: an attack model and a defense model. The attack model dynamically generates directional attack information responsive to the current state of the defense model, while the defense model is designed to derive generalizable representations by utilizing a variety of attack samples. The training approach involves a dual process: for the attack model, the aim is to increase the challenge for the defense model in countering the attack; conversely, for the defense model, the focus is on minimizing the effects instigated by the attack model. This interactive framework allows for mutual learning between attack and defense, creating a synergistic learning environment. Our diverse experiments across datasets confirm IAD's effectiveness, consistently surpassing current state-of-the-art methods, and using MSMT17 as the target domain in different protocols resulted in a notable 13.4% improvement in GReID task average Rank-1 accuracy. Code is available at: https://github.com/lhf12278/IAD.

MiR-26b-5p/TET3 regulates the osteogenic differentiation of human bone mesenchymal stem cells and bone reconstruction in female rats with calvarial defects.

BACKGROUND: MicroRNAs (miRNAs) play critical roles in the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs), but the mechanism by which miRNAs indirectly modulate osteogenesis remains unclear. Here, we explored the mechanism by which miRNAs indirectly modulate gene expression through histone demethylases to promote bone regeneration. METHODS AND RESULTS: Bioinformatics analysis was performed on hBMSCs after 7 days of osteogenic induction. The differentially expressed miRNAs were screened, and potential target mRNAs were identified. To determine the bioactivity and stemness of hBMSCs and their potential for bone repair, we performed wound healing, Cell Counting Kit-8 (CCK-8), real-time reverse transcription quantitative polymerase chain reaction (RT‒qPCR), alkaline phosphatase activity, alizarin red S (ARS) staining and radiological and histological analyses on SD rats with calvarial bone defects. Additionally, a dual-luciferase reporter assay was utilized to investigate the interaction between miR-26b-5p and ten-eleven translocation 3 (TET3) in human embryonic kidney 293T cells. The in vitro and in vivo results suggested that miR-26b-5p effectively promoted the migration, proliferation and osteogenic differentiation of hBMSCs, as well as the bone reconstruction of calvarial defects in SD rats. Mechanistically, miR-26b-5p bound to the 3' untranslated region of TET3 mRNA to mediate gene silencing. CONCLUSIONS: MiR-26b-5p downregulated the expression of TET3 to increase the osteogenic differentiation of hBMSCs and bone repair in rat calvarial defects. MiR-26b-5p/TET3 crosstalk might be useful in large-scale critical bone defects.

Research on the Solid-Liquid Composite Casting Process of Incoloy825/P110 Steel Composite Pipe.

Bimetallic composites have a wide range of application prospects in various industries. Different bonding temperatures, as one of the influencing factors, directly affect the bonding effectiveness as well as the performance and application of the materials. Using metallurgical bonding techniques ensures a strong bond at the interface of bimetallic materials, resulting in high-quality composite pipe billets. This paper describes an Incoloy825/P110 steel bimetal composite material made by the solid-liquid composite method. By utilizing ProCAST 14.5 software for simulation and deriving theoretical formulas, an initial range of temperatures for bimetallic preparation has been tentatively determined. And this temperature range will be utilized for on-site experiments to prepare bimetallic samples. After the preparation process is completed, samples will be selected. The influence of the external mold temperature on the interface bonding of Incoloy825/P110 steel solid-liquid composite material is studied using an ultra-depth three-dimensional morphology microscope and a scanning electron microscope. Through research, the optimal preheating temperature range for the solid-liquid composite outer mold of Incoloy825/P110 bimetallic composite material has been determined. The casting temperature of the inner mold has a significant impact on the interface bonding of this bimetal composite material. As the casting temperature of the inner mold increases, the interface thickness gradually increases. At lower temperatures, the interface thickness is lower and the bonding is poorer. At higher temperatures, melting may occur, leading to coarse grains at the interface. When the temperatures of the inner and outer molds are within a certain range, a new phase appears at the interface. Indeed, it increases the strength of the interface bonding. Due to co-melting of the bimetal near the interface, element migration occurs, resulting in increased Ni and Cr content at the interface and enhanced corrosion resistance.

Effects of different precursors on the structure of lignin-based biochar and its ability to adsorb benzopyrene from sesame oil.

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.

Clinical distinctions in symptomatology and psychiatric comorbidities between misdiagnosed bipolar I and bipolar II disorder versus major depressive disorder.

BACKGROUND: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . METHODS: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. RESULTS: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . CONCLUSION: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Precise Structural Analysis of Neutral Glycans Using Aerolysin Mutant T240R Nanopore.

Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance of glycans. However, glycan research has lagged behind that of DNA and protein due to the challenges posed by structural heterogeneity and isomerism (i.e., structures with equal molecular weights) the lack of high-efficiency structural analysis techniques. Nanopore technology has emerged as a sensitive single-molecule biosensor, shining a light on glycan analysis. However, a significant number of glycans are small and uncharged, making it challenging to elicit identifiable nanopore signals. Here we introduce a R-binaphthyl tag into glycans, which enhances the cation-π interaction between the derivatized glycan molecules and the nanopore interface, enabling the detection of neutral glycans with an aerolysin nanopore. This approach allows for the distinction of di-, tri-, and tetrasaccharides with monosaccharide resolution and has the potential for group discrimination, the monitoring of enzymatic transglycosylation reactions. Notably, the aerolysin mutant T240R achieves unambiguous identification of six disaccharide isomers, trisaccharide and tetrasaccharide linkage isomers. Molecular docking simulations reveal that multiple noncovalent interactions occur between residues R282, K238, and R240 and the glycans and R-binaphthyl tag, significantly slowing down their translocation across the nanopore. Importantly, we provide a demonstration of the kinetic translocation process of neutral glycan isomers, establishing a solid theoretical foundation for glycan nanopore analysis. The development of our technology could promote the analysis of glycan structural isomers and has the potential for nanopore-based glycan structural determination and sequencing.

Safety and clinical efficacy of double posterolateral coaxial portals for endoscopic management of posterior ankle impingement syndrome.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

Motoric cognitive risk syndrome as a predictor of adverse health outcomes: A systematic review and meta-analysis.

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCC) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD) and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aim to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from seven electronic databases. The Newcastle Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR=2.02; 95%CI=1.94-2.11), cognitive impairment (adjusted RR=1.72; 95%CI=1.49-1.99), falls (adjusted RR=1.32; 95%CI=1.17-1.50), mortality (adjusted RR=1.66; 95%CI=1.32-2.10); MCR had more prominent predictive efficacy for AD (adjusted RR=2.23; 95%CI=1.81-2.76) compared to VaD (adjusted RR=3.78; 95%CI=0.49-28.95), while excluding analyses from the study that utilized the Timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (HR=1.69; 95%CI=1.08-2.02) and frailty (OR=5.53; 95%CI=1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR=1.22; 95%CI=1.11-1.34 vs. adjusted RR=1.19; 95%CI= 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis, and provide evidence to support future targeted interventions.

Machine Learning Reveals Serum Glycopatterns as Potential Biomarkers for the Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant chronic liver condition globally, and underdiagnosis is common, particularly in mild cases, attributed to the asymptomatic nature and traditional ultrasonography's limited sensitivity to detect early-stage steatosis. Consequently, patients may experience progressive liver pathology. The objective of this research is to ascertain the efficacy of serum glycan glycopatterns as a potential diagnostic biomarker, with a particular focus on the disease's early stages. We collected a total of 170 serum samples from volunteers with mild-NAFLD (Mild), severe-NAFLD (Severe), and non-NAFLD (None). Examination via lectin microarrays has uncovered pronounced disparities in serum glycopatterns identified by 19 distinct lectins. Following this, we employed four distinct machine learning algorithms to categorize the None, Mild, and Severe groups, drawing on the alterations observed in serum glycopatterns. The gradient boosting decision tree (GBDT) algorithm outperformed other models in diagnostic accuracy within the validation set, achieving an accuracy rate of 95% in differentiating the None group from the Mild group. Our research indicates that employing lectin microarrays to identify alterations in serum glycopatterns, when integrated with advanced machine learning algorithms, could constitute a promising approach for the diagnosis of NAFLD, with a special emphasis on its early detection.

Effect of free and bound proanthocyanidins from Chinese quince on heterocyclic aromatic amine formation and quality in fried chicken.

The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose-dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p < 0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein-rich foods that are subsequently fried.

Association of anhedonia with brain-derived neurotrophic factor and interleukin-10 in major depressive disorder.

BACKGROUND: Anhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. METHODS: This study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. RESULTS: Demographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. CONCLUSION: These findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia. Clinicl Trial Registration Number: NCT03790085.

Novel pyxinol amide derivatives bearing an aliphatic heterocycle as P-glycoprotein modulators for overcoming multidrug resistance.

P-glycoprotein (Pgp) modulators are promising agents for overcoming multidrug resistance (MDR) in cancer chemotherapy. In this study, via structural optimization of our lead compound S54 (nonsubstrate allosteric inhibitor of Pgp), 29 novel pyxinol amide derivatives bearing an aliphatic heterocycle were designed, synthesized, and screened for MDR reversal activity in KBV cells. Unlike S54, these active derivatives were shown to transport substrates of Pgp. The most potent derivative 4c exhibited promising MDR reversal activity (IC50 of paclitaxel = 8.80 ± 0.56 nM, reversal fold = 211.8), which was slightly better than that of third-generation Pgp modulator tariquidar (IC50 of paclitaxel = 9.02 ± 0.35 nM, reversal fold = 206.6). Moreover, the cytotoxicity of this derivative was 8-fold lower than that of tariquidar in human normal HK-2 cells. Furthermore, 4c blocked the efflux function of Pgp and displayed high selectivity for Pgp but had no effect on its expression and distribution. Molecular docking revealed that 4c bound preferentially to the drug-binding domain of Pgp. Overall, 4c is a promising lead compound for developing Pgp modulators.

Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Design, Synthesis, and Biological Activity of Novel Triketone-Containing Phenoxy Nicotinyl Inhibitors of HPPD.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.

CADM2 participates in endometriosis development by influencing the epithelial-mesenchymal transition.

Endometriosis (EM) is a common gynecologic condition that often leads to infertility in women of reproductive age. Cell adhesion molecule 2 (CADM2) is involved in maintaining cell adhesion and polarity, as well as suppressing tumors. However, the role and mechanism of CADM2 in endometriosis is unclear. Therefore, this study evaluated the expression levels of CADM2 and epithelial-mesenchymal transition (EMT)-related marker proteins (E-cadherin, α-SMA, and N-cadherin). Compared to normal endometrial tissue, CADM2 was expressed at low levels in ectopic endometrial tissue from patients with EM. We performed clone formation assays, wound healing assays, and Transwell cell invasion assays to investigate the effects of CADM2 on the biological behavior of endometriosis epithelial cells (11Z) and ectopic endometrial stromal cells (EESCs). The growth, migration, and invasion abilities of these cells were significantly inhibited by overexpression of CADM2. The results were reversed after the knockdown of CADM2. Finally, western blotting (WB) was utilized to detect the effect of CADM2 on EMT in endometriosis cells. CADM2 inhibited EMT in endometriosis cells. In conclusion, our study suggests that CADM2 is a negative regulator of endometriosis development and may inhibit endometriosis development by suppressing EMT.