Graphdiyne as a Highly Efficient and Neuron-Targeted Photothermal Transducer for in Vivo Neuromodulation.

Photothermal modulation of neural activity offers a promising approach for understanding brain circuits and developing therapies for neurological disorders. However, the low neuron selectivity and inefficient light-to-heat conversion of existing photothermal nanomaterials significantly limit their potential for neuromodulation. Here, we report that graphdiyne (GDY) can be developed into an efficient neuron-targeted photothermal transducer for in vivo modulation of neuronal activity through rational surface functionalization. We functionalize GDY with polyethylene glycol (PEG) through noncovalent hydrophobic interactions, followed by antibody conjugation to specifically target the temperature-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) on the surface of neural cells. The nanotransducer not only exhibits high photothermal conversion efficiency in the near-infrared region but also shows great TRPV1-targeting capability. This enables photothermal activation of TRPV1, leading to neurotransmitter release in cells and modulation of neural firing in living mice. With its precision and selectivity, the GDY-based transducer provides an innovative avenue for understanding brain function and developing therapeutic strategies for neurodegenerative diseases.

Development of Fluorenyl-Based Copolyimines with Adjustable Mechanical Properties, Recyclability and Friction Resistance.

Dynamic polyimines are a class of fascinating dynamic polymers with recyclability and reparability owing to their reversible Schiff-base reactions. However, balancing the dynamic properties and mechanical strength of dynamic polyimines presents a major challenge due to the dissociative and associative nature of the imine bonds. Herein, we introduced bulky fluorene groups and polyether amine into the skeleton of polyimine networks to achieve a tradeoff in comprehensive properties. The resulting dynamic polyimines with fluorene groups (Cardo-DPIs) were successfully synthesized by combining the rigid diamine 9,9-bis(4-aminophenyl)fluorene and the flexible polyether amine, demonstrating a high tensile strength of 64.7 MPa. Additionally, Cardo-DPIs films with more content of rigid fluorene groups exhibited higher water resistance, glass transition temperature and wear-resisting ability. Moreover, the Cardo-DPIs films not only efficiently underwent thermal reshaping, but also exhibited excellent self-healing capabilities and chemical degradation in acidic solutions. Furthermore, the resulting films can achieve fully closed-loop recovery by free amine solution for 2 h at room temperature. This study broadens the scope of dynamic polyimine materials and promotes the balanced development of their functional and mechanical properties.

Does air pollution fuel irrational behaviors in stock investments?

This paper investigates the influence of air pollution on irrational behaviors in stock trading through behavioral experiments in laboratory, simulating air pollution by burning straw and mosquito coils. The results of this study show that air pollution significantly improves disposition effect and repurchase effect in an asymmetric way, which are thought as irrational behaviors in stock investments, making subjects prefer selling winning stocks (part of disposition effect) and repurchasing stocks that have fallen in price since the sale (part of repurchase effect). Furthermore, regret, a negative emotion, is the psychological mechanism by which air pollution influences the irrational behaviors.

Prostate Health Index density aids the diagnosis of prostate cancer detected using magnetic resonance imaging targeted prostate biopsy in Taiwanese multicenter study.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted prostate biopsy is the current standard for diagnosing prostate cancer (PCa). However, studies evaluating the value of biomarkers, including prostate health index (PHI) and its derivatives using this method are limited. We aimed to investigate the efficacy of PHI density (PHID) in guiding MRI-targeted prostate biopsies to identify clinically significant prostate cancers (csPCa). METHODS: The multicenter prospectively registered prostate biopsy database from three medical centers in Taiwan included patients with PHI and MRI targeted and/or systematic prostate biopsies. We assessed the required values of prostate-specific antigen (PSA), prostate volume, PHI, PHID, and Prostate Imaging Reporting & Data System (PI-RADS) score using multivariable analyses, receiver operating characteristic curve analysis, and decision curve analyses (DCA). csPCa was defined as the International Society of Urological Pathology Gleason group ≥2 PCa, with an emphasis on reducing unwarranted biopsies. RESULTS: The study cohort comprised 420 individuals. Diagnoses of PCa and csPCa were confirmed in 62.4% and 47.9% of the participants, respectively. The csPCa diagnosis rates were increased with increasing PI-RADS scores (20.5%, 44.2%, and 73.1% for scores 3, 4, and 5, respectively). Independent predictors for csPCa detection included PHI, prostate volume, and PI-RADS scores of 4 and 5 in multivariable analyses. The area under the curve (AUC) for csPCa of PHID (0.815) or PHI (0.788) was superior to that of PSA density (0.746) and PSA (0.635) in the entire cohort, and the superiority of PHID (0.758) was observed in PI-RADS 3 lesions. DCA revealed that PHID achieved the best net clinical benefit in PI-RADS 3-5 and 4/5 cases. Among PI-RADS 3 lesions, cutoff values of PHID 0.70 and 0.43 could eliminate 51.8% and 30.4% of omitted biopsies, respectively. CONCLUSION: PHI-derived biomarkers, including PHID, performed better than other PSA-derived biomarkers in diagnosing PCa in MRI detected lesions.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

Broadband frequency comb generation through cascaded quadratic nonlinearity in thin-film lithium niobate microresonators.

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds.

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

The role of OsBZR4 as a brassinosteroid-signaling component in mediating atrazine and isoproturon degradation in rice.

Development of a biotechnological system for rapid degradation of pesticides is important to mitigate the environmental, food security, and health risks that they pose. Degradation of atrazine (ATZ) and isoproturon (IPU) in rice crops promoted by the brassinosteroid (BR) signaling component BRASSINAZOLE RESISTANT4 (OsBZR4) is explored. OsBZR4 is localized in the plasma membrane and nucleus, and is strongly induced by ATZ and IPU exposure. Transgenic rice OsBZR4-overexpression (OE) significantly enhances resistance to ATZ and IPU toxicity, improving growth, and reducing ATZ and IPU accumulation (particularly in grains) in rice crops. Genetic destruction of OsBZR4 (CRISPR/Cas9) increases rice sensitivity and leads to increased accumulation of ATZ and IPU. OE plants promote phase I, II, and III metabolic reactions, and expression of corresponding pesticide degradation genes under ATZ and IPU stress. UPLC-Q-TOF-MS/MS analysis reveals increased relative contents of ATZ and IPU metabolites and conjugates in OE plants, suggesting an increased OsBZR4 expression and consequent detoxification of ATZ and IPU in rice and the environment. The role of OsBZR4 in pesticide degradation is revealed, and its potential application in enhancing plant resistance to pesticides, and facilitating the breakdown of pesticides in rice and the environment, is discussed.

Extracellular volume fraction derived from dual-energy CT: a potential predictor for acute pancreatitis after pancreatoduodenectomy.

OBJECTIVES: To investigate the value of extracellular volume (ECV) fraction and fat fraction (FF) derived from dual- energy CT (DECT) for predicting postpancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD). METHODS: This retrospective study included patients who underwent DECT and PD between April 2022 and September 2022. PPAP was determined according to the International Study Group for Pancreatic Surgery (ISGPS) definition. Iodine concentration (IC) and FF of the pancreatic parenchyma were measured on preoperative DECT. The ECV fraction was calculated from iodine map images of the equilibrium phase. The independent predictors for PPAP were assessed by univariate and multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Sixty-nine patients were retrospectively enrolled (median age, 60 years; interquartile range, 55-70 years; 47 men). Of these, nine patients (13.0%) developed PPAP. These patients had lower portal venous phase IC, equilibrium phase IC, FF, and ECV fraction, and higher pancreatic parenchymal-to-portal venous phase IC ratio and pancreatic parenchymal-to-equilibrium phase IC ratio, compared with patients without PPAP. After multivariable analysis, ECV fraction was independently associated with PPAP (odd ratio [OR], 0.87; 95% confidence interval [CI]: 0.79, 0.96; p < 0.001), with an area under the curve (AUC) of 0.839 (sensitivity 100.0%, specificity 58.3%). CONCLUSIONS: A lower ECV fraction is independently associated with the occurrence of PPAP after PD. ECV fraction may serve as a potential predictor for PPAP after PD. CLINICAL RELEVANCE STATEMENT: DECT-derived ECV fraction of pancreatic parenchyma is a promising biomarker for surgeons to preoperatively identify patients with higher risk for postpancreatectomy acute pancreatitis after PD and offer selective perioperative management. KEY POINTS: PPAP is a complication of pancreatic surgery, early identification of higher-risk patients allows for risk mitigation. Lower DECT-derived ECV fraction was independently associated with the occurrence of PPAP after PD. DECT aids in preoperative PAPP risk stratification, allowing for appropriate treatment to minimize complications.

Comparison of diagnostic performance among Abbott RealTime HCV Genotyping II, Abbott HCV Genotype plus RUO, and Roche Cobas HCV Genotyping assays for hepatitis C virus genotyping.

Comparison of diagnostic accuracy for commercial hepatitis C virus (HCV) genotyping (Abbott RealTime HCV Genotyping II, Roche Cobas Genotyping) and investigational Abbott HCV Genotype plus RUO assays designed to discriminate genotype (GT)-1a, 1b or 6 in cases of ambiguous GT from the Abbott commercial assay remains limited. 743 HCV-viremic samples were subjected to analysis using Abbott and Roche commercial as well as Abbott HCV Genotype plus RUO assays. Next-generation sequencing (NGS) targeting core region was employed as the reference standard. Diagnostic accuracy was reported as the number of participants (percentages) along with 95% confidence intervals (CIs). Using NGS, 741 samples (99.7%) yielded valid genotyping results. The diagnostic accuracies were 97.6% (95% CI: 96.1%-98.5%) and 95.3% (95% CI: 93.4%-96.6%) using Abbott and Roche commercial assays (p = 0.0174). Abbott commercial assay accurately diagnosed HCV GT-6a and 6w, whereas Roche commercial assay accurately diagnosed HCV GT-6a. Both assays demonstrated low accuracies for HCV GT-6b, 6e, 6g, and 6n. Abbott HCV Genotype plus RUO assay discriminated 13 of the 14 samples (92.9%; 95% CI: 64.2%-99.6%) that yielded ambiguous GT. Both assays were capable of diagnosing mixed HCV infections when the minor genotype comprised >8.4% of the viral load. The diagnostic performance of commercial HCV genotyping assays is commendable. Abbott assay demonstrated superior performance compared to Roche assay in diagnosing HCV GT-6. Abbott HCV Genotype plus RUO assay aids in discriminating ambiguous GT. Both commercial assays are proficient in diagnosing mixed HCV infections at a cut-off viral load of 8.4% in minor genotype.

Impact of peripheral anterior synechiae on the outcome of combined phacoemulsification, goniosynechialysis and goniotomy for primary angle-closure glaucoma and cataract: a multicenter observational study.

PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle-closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataract who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into three groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mmHg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred and four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery (P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the three groups (P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared to 180°≤PAS<270° (P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataract over one year period. However, the outcome was not correlated with preoperative extent of PAS. PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle-closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae.

An ultra-sensitive CRISPR-Cas12a and aptamer-based biosensor utilizing Entropy-driven catalytic DNA networks for precise detection of DNA Methyltransferase 1.

DNA Methyltransferase 1 (DNMT1) serves as a crucial biomarker associated with various diseases and is essential for evaluating DNA methylation levels, diagnosing diseases, and evaluating prognosis. As a result, a convenient, quantitative, and sensitive assay for detecting DNMT1 is in high demand. However, current techniques for DNMT1 detection struggle to balance accuracy, low cost, and high sensitivity, limiting their clinical usefulness. To address this challenge, we have developed a DNMT1 detection method (CAED), which combines aptamer-specific recognition with a highly programmable Entropy-driven catalysis DNA network and is further integrated with the CRISPR-Cas12a system. This innovative approach achieves a detection limit as low as 90.9 fmol/L. To demonstrate the clinical applicability and significance of our CAED method, we successfully measured DNMT1 levels in 10 plasma samples 10 cervical tissue samples. These results underscore the potential of our method as an accurate, affordable, and ultra-sensitive tool for evaluating DNMT1 levels. This innovative method offers a potent means for assessing DNMT1 levels and significantly advances disease diagnosis and health risk prediction. Plus, it establishes an innovative design framework for CRISPR-Cas12a-based biosensors, tailored explicitly for enzyme content quantification.

MRI morphometry of the anterior and posterior cerebellar vermis and its relationship to sensorimotor and cognitive functions in children.

INTRODUCTION: The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions. METHODS: Typically developing children (TDC; n=38; age 9-15) and healthy adults (HAC; n=31; 18-40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV. RESULTS: TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ. CONCLUSIONS: In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The "inverted U" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.

M2 macrophage-derived exosomal circTMCO3 acts through miR-515-5p and ITGA8 to enhance malignancy in ovarian cancer.

Tumor-associated macrophages of the M2 phenotype promote cancer initiation and progression. Importantly, M2 macrophage-derived exosomes play key roles in the malignancy of cancer cells. Here, we report that circTMCO3 is upregulated in ovarian cancer patients, and its high expression indicates poor survival. M2-derived exosomes promote proliferation, migration, and invasion in ovarian cancer, but these effects are abolished by knockdown of circTMCO3. Furthermore, circTMCO3 functions as a competing endogenous RNA for miR-515-5p to reduce its abundance, thus upregulating ITGA8 in ovarian cancer. miR-515-5p inhibits ovarian cancer malignancy via directly downregulating ITGA8. The decreased oncogenic activity of circTMCO3-silencing exosomes is reversed by miR-515-5p knockdown or ITGA8 overexpression. Exosomal circTMCO3 promotes ovarian cancer progression in nude mice. Thus, M2 macrophage-derived exosomes promote malignancy by delivering circTMCO3 and targeting the miR-515-5p/ITGA8 axis in ovarian cancer. Our findings not only provide mechanistic insights into ovarian cancer progression, but also suggest potential therapeutic targets.

A polyetheretherketone framework removable partial denture for a 6-year-old child with nonsyndromic oligodontia made using glass-ceramic hemispheres to enhance retention: A clinical report.

A 6-year-old child with nonsyndromic oligodontia in the mixed dentition received a removable dental prosthesis with a polyetheretherketone framework and artificial gingiva, restoring esthetics and function. Computer-aided design and computer-aided manufacturing hemispherical glass-ceramic attachments were added to the teeth under the guidance of acid-etching and bonding guides to obtain an undercut area. The bonding and cementation of the attachments and the prosthesis delivery were completed in a single visit. This method offers a suitable prosthodontic treatment option for treating children with oligodontia in the mixed dentition.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients.

Aims: The population pharmacokinetic (PPK) model-based machine learning (ML) approach offers a novel perspective on individual concentration prediction. This study aimed to establish a PPK-based ML model for predicting tacrolimus (TAC) concentrations in Chinese renal transplant recipients. Methods: Conventional TAC monitoring data from 127 Chinese renal transplant patients were divided into training (80%) and testing (20%) datasets. A PPK model was developed using the training group data. ML models were then established based on individual pharmacokinetic data derived from the PPK basic model. The prediction performances of the PPK-based ML model and Bayesian forecasting approach were compared using data from the test group. Results: The final PPK model, incorporating hematocrit and CYP3A5 genotypes as covariates, was successfully established. Individual predictions of TAC using the PPK basic model, postoperative date, CYP3A5 genotype, and hematocrit showed improved rankings in ML model construction. XGBoost, based on the TAC PPK, exhibited the best prediction performance. Conclusion: The PPK-based machine learning approach emerges as a superior option for predicting TAC concentrations in Chinese renal transplant recipients.

Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.