Curcumin for gastric cancer: Mechanism prediction via network pharmacology, docking, and in vitro experiments.

BACKGROUND: Curcumin originates from the natural herb turmeric, and its antitumor effects have been known about for a long time. However, the mechanism by which curcumin affects gastric cancer (GC) has not been elucidated. AIM: To elucidate the potential mechanisms of curcumin in the treatment of GC. METHODS: Network pharmacological approaches were used to perform network analysis of Curcumin. We first analyzed Lipinski's Rule of Five for the use of Curcumin. Curcumin latent targets were predicted using the PharmMapper, SwissTargetPrediction and DrugBank network databases. GC disease targets were mined through the GeneCard, OMIM, DrugBank and TTD network databases. Then, GO enrichment, KEGG enrichment, protein-protein interaction (PPI), and overall survival analyses were performed. The results were further verified through molecular docking, differential expression analysis and cell experiments. RESULTS: We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets. The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways. Following PPI analysis, 6 hub targets were identified, namely, estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6 (CYP2B6). These factors are correlated with decreased survival rates among patients diagnosed with GC. Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes. The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation. mRNA levels of hub targets CYP3A4, MAPK14, CYP1A2, and CYP2B6 in BGC-823 cells were significantly increased in each dose group. CONCLUSION: Curcumin can play an anti-GC role through a variety of targets, pathways and biological processes.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

Adaptability to the environment of protease by secondary structure changes and application to enzyme-selective hydrolysis.

The reactions involving enzymes are significantly influenced by various environmental factors. Clarity of how the activity and structure of proteases impact their function is crucial for more efficient application of enzymes as a tool. The impact of temperature, pH, and ionic strength on changes in protease activity, secondary structure, and protein conformation during enzymatic hydrolysis were investigated in this study. The enzymatic activity and secondary structure of acid-base protease were found to undergo significant modifications under different physical conditions, as demonstrated by UV spectrophotometry and FTIR spectroscopy analysis. Specifically, variations in α-helix and ß-fold content were observed to correlate with changes in enzyme activity. Molecular simulation analysis revealed that physical conditions have varying effects on the protease, particularly influencing enzyme activity and secondary structure. Evaluation of the proteases indicated alterations in both enzyme activity and structure. This treatment selectively hydrolyzed ß-lactoglobulin and reduced sensitization. These findings offer novel perspectives on the functionalities and regulatory mechanisms of proteases, as well as potential industrial applications.

MiR-184-3p in the paraventricular nucleus participates in the neurobiology of depression via regulation of the hypothalamus-pituitary-adrenal axis.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Scalp acupuncture targets for neurological disorders：evidence from neuroimaging studies (part 2). / åŸºäºŽç¥žç»å½±åƒå­¦çš„å¸¸è§ç¥žç»ç³»ç»Ÿç–¾ç— å¤´é’ˆåˆºæ¿€é¶ç‚¹ç ”ç©¶ï¼ˆä¸‹ï¼‰.

OBJECTIVES: Scalp acupuncture is a method of treating diseases by dividing and stimulating the corresponding function-oriented cortical scalp areas. It is a commonly used therapy for neurological disorders. However, the specific target selection for scalp acupuncture remains to be explored. This manuscript aims to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings and noninvasive brain stimulation. METHODS: Neurosynth-based meta-analysis of neuroimaging studies was conducted to identify brain stimulation targets of neurological disorders. The identified target regions were further projected to the scalp. The traditional acupoints and 10-20 EEG system were referenced for the localization of these targets. In this study, the "mild cognitive impairment" (MCI), "Alzheimer's disease" (AD) and "dementia" were used as the retrieval terms respectively, and a unity detection method was used to generate brain maps, with the default FDR (false discovery rate, P<0.01) threshold of Neurosynth set for subsequent exploration of various disease-related brain regions. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets for MCI, AD, and dementia were introduced in the present paper (part 2). Here are 3 target examples for each of these 3 diseases due to word limitation. 1) MCI：Based on the 81 papers retrieved, we identified 6 potential scalp acupuncture points for MCI, their corresponding brain regions, brain functions and the possible resultant effects of the scalp target acupoint stimulation respectively are as below. MCI1：the orbital part of the left inferior frontal gyrus (left Brodmann area ［BA］47), related to semantic coding, working memory and episodic memory, improving semantic coding and memory function；MCI2：the anterior motor area/left anterior central gyrus (left BA6), the motor center area, improving MCI motor function；MCI3：the left medial temporal gyrus (left BA21), related to the processing of speech, visual space, language and word understanding, improving language and memory. 2) AD：Based on the 196 papers retrieved, we found 6 potential scalp acupuncture targets for AD, their corresponding brain regions and brain functions of the 3 example targets respectively are as below. AD1：the left medial temporal gyrus (left BA21), participating in language and semantic processing, sentence and word generation, intent expression, deductive reasoning；AD2：the left angular gyrus (left BA39), related to semantic processing, word reading and comprehension, memory retrieval, attention and spatial cognition, reasoning, etc.；AD3：the left fusiform/suboccipital gyrus (left BA37), related to semantic classification, text generation, sign language, phonology processing, etc. 3) Dementia：Based on the 142 papers retrieved, we found 4 potential scalp acupuncture targets for dementia, their corresponding brain regions, brain functions and the possible targets of the proposed scalp stimulation respectively are as below. D1 and D2：the left inferior frontal gyrus (i.e., left BA46, and left BA47, respectively), being closely related to working memory, emotional response regulation, melody and other processing processes, may be suitable for treating memory decline and advanced executive dysfunction in patients with dementia；D3：the left medial temporal gyrus (left BA21), an important brain region for various sensory integration, cognitive processing and memory functions, and emotional processing, may be suitable for temporal dementia. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging findings and noninvasive brain stimulation. The proposed targets may also be used for treating these disorders using nerve/brain stimulation methods.

Dual-recognition "turn-off-on" fluorescent Biosensor triphenylamine-based continuous detection of copper ion and glyphosate applicated in environment and living system.

Heavy metal Cu2+ emitted in industry and residues of glyphosate pesticides are pervasive in ecosystems, accumulated in water bodies and organisms' overtime, constituting hazard to human and ecological balance. The development of rapid, highly selective, reversibility and sensitive biosensor in vivo detection for Cu2+ and glyphosate was imminent. A novel dual-recognition fluorescence biosensor MPH was successfully synthesized based on triphenylamine, which demonstrated remarkable ratiometric fluorescence quenching toward Cu2+, while MPH-Cu2+ (1:1) ensemble exhibited ratiometric fluorescence restoration for glyphosate, both with observable color changes in daylight and UV lamp. The biosensor exhibited rapid, outstanding selectivity, anti-interference, and multiple cycles reversibility through "turn-off-on" fluorescence towards Cu2+ and glyphosate, respectively. Surprisingly, the clearly binding mechanisms of MPH to Cu2+ and MPH-Cu2+ ensemble to glyphosate were determined, respectively, based on the Job's plot, FT-IR, ESI-HRMS, 1H NMR titration and theoretical calculations of dynamics and thermodynamics. In addition, biosensor MPH demonstrated successful detection of Cu2+ and glyphosate across diverse environmental samples including tap water, extraction solutions of traditional Chinese medicine honeysuckle and soil samples. In the meantime, fluorescence imaging of Cu2+ and glyphosate at both micro and macro scales in various living organisms, such as rice roots, MCF-7 cells, zebrafish, and mice, were successfully achieved. Overall, this work was expected to become a promising and versatile fluorescence biosensor for rapid and reversible detection of Cu2+ and glyphosate both in vitro and vivo.

Design, synthesis and biological evaluation of piperine derivatives as potent antitumor agents.

A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC50 values were determined to be 147.45 ± 6.05 µM, 11.86 ± 0.32 µM, and 10.50 ± 3.74 µM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 µM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer.

The clinical and pathological evaluation of patients with immunoglobulin A nephropathy by diffusion tensor imaging and intravoxel incoherent motion diffusion-weighted imaging.

OBJECTIVES: To explore the efficacy of diffuse magnetic resonance imaging (MRI) for identifying clinicopathological changes in immunoglobulin A nephropathy (IgAN) patients. METHODS: The study enrolled IgAN patients and healthy volunteers. IgAN patients were divided into Group 1 [estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2], Group 2 (60 ≤ eGFR < 90 mL/min/1.73 m2), and Group 3 (eGFR < 60 mL/min/1.73 m2). Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion tensor imaging (DTI) were performed via 3.0 T magnetic resonance. Diffuse MRI, clinical, and pathological indicators were collected and analysed. P < .05 was considered statistically significant. RESULTS: Forty-six IgAN patients and twenty-seven volunteers were enrolled. The apparent diffusion coefficient, diffusion coefficient (D), perfusion fraction (f), and fractional anisotropy (FA) were significantly different among IgAN subgroups and controls. These parameters were positively correlated with eGFR and negatively with creatinine, and inversely correlated with glomerular sclerosis, interstitial fibrosis, and tubular atrophy (all P < .05). They had significantly high area under the curve (AUC) for distinguishing IgAN patients from controls, while FA had the highest AUC in identifying Group 1 IgAN patients from volunteers. CONCLUSIONS: DTI and IVIM-DWI had the advantage of evaluating clinical and pathological changes in IgAN patients. DTI was superior at distinguishing early IgAN patients and might be a noninvasive marker for screening early IgAN patients from healthy individuals. ADVANCES IN KNOWLEDGE: DTI and IVIM-DWI could evaluate clinical and pathological changes and correlated with Oxford classification in IgAN patients. They could also identify IgAN patients from healthy populations, while DTI had superiority in differentiating early IgAN patients.

Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic: A Cross-sectional Study.

OBJECTIVE: The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement. The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019 (COVID-19) pandemic and analyzed the influence of psychological state on medication safety. METHODS: Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits. Depression was evaluated by the Self-Rating Depression Scale (SDS). Anxiety was evaluated by the Self-Rating Anxiety Scale (SAS). Medication adherence was evaluated by the Morisky scale. RESULTS: A total of 309 patients (aged 52.2±11.4 years) were included in the present study. The SDS score of all included patients was 36.9±9.4 points, of which 11 (3.6%) patients were diagnosed as having depression. The SAS score of all included patients was 43.1±9.3 points, of which 71 (23%) patients were diagnosed as having anxiety. Seven patients (2.3%) had both anxiety and depression. Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression. Regarding anxiety, patients who underwent repeated operations had a 2.264-fold greater risk, and patients who received combination medication had a 2.140-fold greater risk. More bleeding events and coagulation disorders could be observed in patients with anxiety, depression or both. When anxiety occurred, patients showed worse medication adherence. However, depression had no significant effect on medication adherence. CONCLUSION: During the COVID-19 pandemic, the detection rate of mental illnesses such as anxiety and depression was high, which seriously affected the medication safety of warfarin. Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

In vitro evaluation of the impact of a bioceramic root canal sealer on the mechanical properties of tooth roots.

Bacground/purpose: Endodontically treated teeth are more prone to vertical root fracture with the mechanical property changes to some extent during root canal treatment. This study aimed to investigate the effects of a bioceramic sealer on the mechanical properties of tooth roots. Materials and methods: Dentin discs were dried by two different methods (ethanol drying and paper points drying) and then filled with a BC sealer named iRoot SP. SEM and EDS were used to analyze the newly formed minerals in dentin tubules. Elastic modulus and hardness of the secondary dentin in areas proximal to the primary dentin (PD-SD) and areas proximal to canal or iRoot SP (SD-C/SD-iRoot SP) were measured using nanoindentation technique. The compressive strength of roots filled with iRoot SP were tested by compressive loading test. Results: (1) Penetration and mineralization: Paper points drying was more conducive to iRoot SP adhesion, spreading and penetration into the dentin tubules than 95% ethanol drying. (2) Micromechanical properties: After filling root canal with iRoot SP, the elastic modulus and hardness of SD-iRoot SP were higher than those of PD-SD (P = 0.001 and P = 0.000). (3) Fracture resistance: The compressive strength of the roots filled with iRoot SP was not significantly different from that of the roots unprepared and unfilled (P = 0.957), but was higher than that of the roots prepared and unfilled (P = 0.009). Conclusion: Excessive drying (95% ethanol drying method) is not conducive to the penetration and mineralization of the BC sealer iRoot SP into dentin tubules. The good bioactivity of iRoot SP was responsible for increasing the elastic modulus and hardness of dentin, which strengthened the prepared roots.

Harnessing virus flexibility to selectively capture and profile rare circulating target cells for precise cancer subtyping.

The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young's modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL-1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity.

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.

Three new compounds from the fruits of Solanum virginianum L. and their anti-inflammatory activities.

Three new compounds 1-glyceryl 9(ß), 10(α), 11(ß)-trihydroxy-12(Z)-octadecenoate, 2'S-20-O-p-hydroxyphenylpropionyloxy-20-hyd-roxyarachidic acid glycerol ester (2), 3-O-α-l-arabinopyranosyl-(1→6)-ß-d-glucopyranoside of ethyl (3S)-hydroxybutanoate (3), as well as a new natural product (4) were isolated from the fruits of Solanum virginianum L. The structures of 26 compounds were determined by comprehensive spectroscopic analyses, NMR calculation, chemical methods, and comparisons of spectroscopic data. Compounds 2 and 16 exhibited good anti-inflammatory activity in the LPS-induced RAW 264.7 inflammatory model with IC50 values of 16.75 ± 1.54 and 22.43 ± 2.01 µM, respectively.

Performance analysis of non-invasive prenatal testing for trisomy 13, 18, and 21: A large-scale retrospective study (2018-2021).

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

[Non-targeted renal metabolomics reveals multi-target effects of Dahuang Zhechong Pills on renal aging in rats].

This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.

Unraveling colorectal cancer prevention: The vitamin D - gut flora - immune system nexus.

Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.

Development of a Prediction Model and Corresponding Scoring Table for Postherpetic Neuralgia Using Six Machine Learning Algorithms: A Retrospective Study.

INTRODUCTION: Postherpetic neuralgia (PHN), a complication of herpes zoster, significantly impacts the quality of life of affected patients. Research indicates that early intervention for pain can reduce the occurrence or severity of PHN. This study aims to develop a predictive model and scoring table to identify patients at risk of developing PHN following acute herpetic neuralgia, facilitating informed clinical decision-making. METHODS: We conducted a retrospective review of 524 hospitalized patients with herpes zoster at The First Affiliated Hospital of Zhejiang Chinese Medical University from December 2020 to December 2023 and classified them according to whether they had PHN, collecting a comprehensive set of 30 patient characteristics and disease-related indicators, 5 comorbidity indicators, 2 disease score values, and 10 serological indicators. Relevant features associated with PHN were identified using the least absolute shrinkage and selection operator (LASSO). Then, the patients were divided into a training set and a test set in a 4:1 ratio, with comparability tested using univariate analysis. Six models were established in the training set using machine learning methods: support vector machines, logistic regression, random forest, k-nearest neighbor, gradient boosting, and neural network. The performance of these models was evaluated in the test set, and a nomogram based on logistic regression was used to create a PHN prediction score table. RESULTS: Eight non-zero characteristic variables selected from the LASSO regression results were included in the model, including age [area under the curve (AUC) = 0.812, p < 0.001], Numerical Rating Scale (NRS) (AUC = 0.792, p < 0.001), receiving treatment time (AUC = 0.612, p < 0.001), rash recovery time (AUC = 0.680, p < 0.001), history of malignant tumor (AUC = 0.539, p < 0.001), history of diabetes (AUC = 0.638, p < 0.001), varicella-zoster virus immunoglobulin M (AUC = 0.620, p < 0.001), and serum nerve-specific enolase (AUC = 0.659, p < 0,001). The gradient boosting model outperformed other classifier models on the test set with an AUC of 0.931, 95% confidence interval (CI) (0.882-0.980), accuracy of 0.886 (95% CI 0.809-0.940). In the test set, our predictive scoring table achieved an AUC of 0.820 (95% CI 0.869-0.970) with accuracy of 0.790 (95% CI 0.700-0.864). CONCLUSION: This study presents a methodology for predicting the development of postherpetic neuralgia in shingles patients by analyzing historical case data, employing various machine learning techniques, and selecting the optimal model through comparative analysis. In addition, a logistic regression model has been used to create a scoring table for predicting the postherpetic neuralgia.