An integrated framework for driving risk evaluation that combines lane-changing detection and an attention-based prediction model.

OBJECTIVE: In recent years, the increase in traffic accidents has emerged as a significant social issue that poses a serious threat to public safety. The objective of this study is to predict risky driving scenarios to improve road safety. METHODS: On the basis of data collected from naturalistic driving real-vehicle experiments, a comprehensive framework for identifying and analyzing risky driving scenarios, which combines an integrated lane-changing detection model and an attention-based long short-term memory (LSTM) prediction model, is proposed. The performance of the 4 machine learning methods on the CULane data set is compared in terms of model running time and running speed as evaluation metrics, and the ultrafast network with the best performance is selected as the method for lane line detection. We compared the performance of LSTM and attention-based LSTM on the basis of the prediction accuracy, recall, precision, and F1 value and selected the better model (attention-based LSTM) for risky scenario prediction. Furthermore, Shapley additive explanation analysis (SHAP) is used to understand and interpret the prediction results of the model. RESULTS: In terms of algorithm efficiency, the running time of the ultrafast lane detection network only requires 4.1 ms, and the average detection speed reaches 131 fps. For prediction performance, the accuracy rate of attention-based LSTM reaches 96%, the precision rate is 98%, the recall rate is 96%, and the F1 value is 97%. CONCLUSIONS: The improved attention-based LSTM model is significantly better than the LSTM model in terms of convergence speed and prediction accuracy and can accurately identify risky scenarios that occur during driving. The importance of factors varies by risky scenario. The characteristics of the yaw rate, speed stability, vehicle speed, acceleration, and lane change significantly influence the driving risk, among which lane change has the greatest impact. This study can provide real-time risky scenario prediction, warnings, and scientific decision guidance for drivers.

Chromone components of Saposhnikovia divaricate attenuate rheumatoid arthritis development by inhibiting the inflammatory response.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (Turcz.) Schisck., a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood. AIM OF THE STUDY: To explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model. MATERIAL AND METHODS: Surface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting. RESULTS: CHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), TNF-α, and IL-17A proteins in the joints of CHR-treated mice. CONCLUSION: CHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.

BAFF overexpression in triple-negative breast cancer promotes tumor growth by inducing IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses.

PURPOSE: Despite BAFF's (B cell activating factor, BAFF) known influence on B cell survival and proliferation, its specific effects within the tumor microenvironment remain unclear. We aimed to elucidate how BAFF overexpression in breast cancer cells impacts tumor growth and the functions of T and B cells in the tumor microenvironment. METHODS: BAFF was overexpressed in the 4T1 mouse triple-negative breast cancer cell line, and tumor growth, immune cell infiltration, and activity were assessed in vitro and in vivo using flow cytometry, co-culture assays, and mouse tumor models with B cell depletion. RESULTS: BAFF overexpression in 4T1 cells promoted tumor growth in vivo, suppressed CD8+ T cell activity, and increased IL-10-secreting CD5+ regulatory B cells in tumors. 4T1/BAFF cells directly enhanced IL-10 production in CD5+ B cells via BAFF/BAFF-receptor interactions, and IL-10 from CD5+ B cells inhibited IFN-γ secretion by T cells. B cell depletion partially reversed the tumor-promoting effects of BAFF overexpression. Our study reveals a novel mechanism by which BAFF can foster tumor progression, with the induction of IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses appearing to be a key component of BAFF's tumor-promoting activity. CONCLUSION: These findings underscore the complex immunomodulatory effects that BAFF exerts in the tumor microenvironment and point to BAFF-induced regulatory B cells as a potential new therapeutic target in breast cancer that warrants further investigation.

Clinical adverse events to letairis: a real-world drug safety study based on FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Letairis (ambrisentan), an endothelin receptor antagonist (ERA), is a critical medication for pulmonary arterial hypertension (PAH). Despite its efficacy, its safety profile is under scrutiny, warranting a detailed analysis. RESEARCH DESIGN AND METHODS: This study leveraged the FDA Adverse Event Reporting System (FAERS) from Q1 2007 to Q4 2023, focusing on Letairis as the primary suspect in adverse events. Employing advanced data mining techniques, such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), the study aimed to uncover safety signals. RESULTS: A total of 43,774 cases were identified, with Letairis implicated in 16,038,963 adverse event reports. There was a notable predominance of female patients (75.30%), with a median age around 64 years. Severe outcomes, including hospitalization (51.63%) and fatalities (20.44%), were prevalent. Signal strength analysis highlighted concerns in infections and infestations, as well as cardiac disorders. CONCLUSION: The analysis underscores the need for vigilant pharmacovigilance and highlights Letairis's potential to induce serious AEs, particularly in female and elderly populations. These findings are instrumental in guiding clinical practice and future drug safety assessments.

Dynamics of epitranscriptomes uncover translational reprogramming directed by ac4C in rice during pathogen infection.

Messenger RNA modifications play pivotal roles in RNA biology, but comprehensive landscape changes of epitranscriptomes remain largely unknown in plant immune response. Here we report translational reprogramming directed by ac4C mRNA modification upon pathogen challenge. We first investigate the dynamics of translatomes and epitranscriptomes and uncover that the change in ac4C at single-base resolution promotes translational reprogramming upon Magnaporthe oryzae infection. Then by characterizing the specific distributions of m1A, 2'O-Nm, ac4C, m5C, m6A and m7G, we find that ac4Cs, unlike other modifications, are enriched at the 3rd position of codons, which stabilizes the Watson-Crick base pairing. Importantly, we demonstrate that upon pathogen infection, the increased expression of the ac4C writer OsNAT10/OsACYR (N-ACETYLTRANSFERASE FOR CYTIDINE IN RNA) promotes translation to facilitate rapid activation of immune responses, including the enhancement of jasmonic acid biosynthesis. Our study provides an atlas of mRNA modifications and insights into ac4C function in plant immunity.

Predictive value of white matter hyperintensity burden combined with collateral circulation in mechanical thrombectomy for acute anterior circulation large vessel occlusion.

OBJECTIVE: To investigate the correlation and predictive value of white matter hyperintensity (WMH) burden in conjunction with collateral circulation during mechanical thrombectomy (MT) for acute anterior circulation occlusion. METHODS: A database comprising consecutive registrations of patients who underwent mechanical thrombectomy for acute anterior circulation large vessel occlusive cerebral infarction at Nanjing Drum Tower Hospital from January 2018 to December 2021 was analyzed. Collateral circulation was assessed using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scoring criteria. The good collateral group included ASITN/SIR grades 3 and 4, while the poor collateral group included grades 1 and 2. Additionally, white matter hyperintensity burden was evaluated using white matter hyperintensity volume and the Fazekas scoring system. A favorable functional outcome was defined as a modified Rankin scale (mRS) of 0-2 at 90 days. Multivariable logistic regression analyses and Spearman correlation analysis were employed to assess the correlation between white matter hyperintensity burden and unfavorable outcomes in mechanical thrombectomy. RESULTS: A total of 123 patients who underwent mechanical thrombectomy for acute anterior circulation occlusion were included (56.9 % male). Favorable outcomes were observed in 45.5 % (56/123) of cases. Those with a low ASITN/SIR scale (r = -1.33, 95 % CI: 0.26 (0.09-0.78), P=0.01; cutoff value = 2.5), low low-density lipoprotein cholesterol (LDL-C) level (r = -1.00, 95 % CI: 0.37 (0.15-0.92), P=0.03; cutoff value = 2.26), and high white matter hyperintense volume (r = 0.28, 95 % CI: 1.33 (1.03-1.71), P=0.03; cutoff value = 10.03) were more likely to experience unfavorable outcomes. Moreover, when compared to ASITN/SIR scale (AUC=89.6, 95 % CI: 0.09-0.78) and LDL level (AUC=62.8, 95 % CI: 0.15-0.92), white matter hyperintense volume demonstrated greater accuracy in predicting poor outcomes (AUC=94.4, 95 % CI: 1.03-1.71). Importantly, white matter hyperintense volume showed a positive correlation with the modified Rankin Scale (mRS) Score (r = 0.8289, P<0.0001). In brief, the burden of white matter hyperintensity is negatively correlated with collateral circulation in mechanical thrombectomy for acute anterior circulation occlusion. CONCLUSIONS: The higher the burden of white matter hyperintensity, the worse the collateral circulation in mechanical thrombectomy for acute anterior circulation occlusion. The combination of high white matter hyperintensity volume and poor collateral circulation enhances might predict a worse clinical outcome of mechanical thrombectomy with acute anterior circulation occlusion.

Perylene-Diimide-Based Supramolecular Radical Anion as a Platform for Highly Effective Photoreduction of Inert Sulfoxide to Sulfide.

Due to the limitations of common photoredox catalysts, unlocking their applications in photoreduction reactions remains an ongoing challenge. We herein present a supramolecular radical anion, PDI(CB[7])2, that formed by the assembly of perylene diimide derivative (PDI) and cucurbit[7]uril (CB[7]) via a host-guest interaction for an effective photoreduction reaction. Studies revealed that it could effectively accomplish a consecutive excitation process by two-photon excitation, enabling a potent photoreductant PDI(CB[7])2• - * that can even reduce the inert feedstocks, such as sulfoxides to sulfides. Mechanistic investigations indicate that, besides exceptional photophysical properties, supramolecular PDI(CB[7])2 also significantly enhances the lifetime and robustness of the in situ generated higher energy photoreductant PDI(CB[7])2• - * upon second quantum photon excitation, leading to the observed highly active photoreducing behavior.

EASIX and m-EASIX Predict CRS and ICANS in Pediatric and AYA Patients post CD19-CAR T cell Therapy.

Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) are complications of CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy. The Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) scores have been retrospectively proven to be predictive of CRS and ICANS in adult CAR T cell recipients. However, these scores have not been evaluated in pediatric cohorts. We retrospectively report on 76 pediatric, adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with CD19-CAR T cells at St. Jude Children's Research Hospital or John's Hopkins Hospital. Data included patient-, disease-, and treatment characteristics. EASIX and m-EASIX scores were calculated at days -5 pre, 0 and +3 post CAR T cell infusion. CRS and ICANS occurred in 47 and 17 patients, respectively. At all evaluated time points, compared to those with no/mild CRS/ICANS, median EASIX scores were higher for patients who developed severe CRS and any-grade ICANS, and median m-EASIX scores were higher in patients who developed severe CRS and severe ICANS. Receiver Operating Characteristic (ROC) curve analysis showed that both scores were strong predictors of CRS, especially severe CRS, at all time points. Any grade and severe ICANS were best predicted by both scores at day +3. m-EASIX uniformly outperformed EASIX, except for predicting any grade ICANS. Our results validate the potential utility for EASIX and m-EASIX scores for predicting CAR T-cell related complications for pediatric and AYA patients.

A new red phosphor for high time-resolved thermal sensitivity and plant growth.

Luminous materials with a rapid lifetime response have garnered significant interest in sensing technology. In this work, the transition element Mn doped phosphor Sr2TiO4:Mn4+ was synthesized by a traditional high temperature solid phase method. The emission peak of Sr2TiO4:0.009Mn4+ aligns closely with the absorption peak of phytochrome Pfr. The temperature-dependent photoluminescence (PL) spectra and lifetime of Sr2TiO4:0.009Mn4+ were examined within the temperature range of 273-323 K. The temperature sensing characteristics based on the lifetime were analyzed, and the maximum relative sensitivity was 14.93% K-1 at 309 K. The high sensitivity of the Sr2TiO4:0.009Mn4+ phosphor makes it a promising material for temperature sensing applications.

Initial ribociclib plus endocrine therapy for HR+/HER2- advanced breast cancer in pre- and postmenopausal Chinese women: Primary results from a phase 2 randomized study.

BACKGROUND: The MONALEESA­7 and ­2 phase 3 randomized trials demonstrated a statistically significant progression­free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre­ and postmenopausal patients with hormone receptor­positive (HR+)/human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre­ and postmenopausal patients with HR+/HER2­ ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA­7 and ­2 studies. METHODS: Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator­assessed PFS. RESULTS: As of April 25, 2022, the median follow­up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. CONCLUSIONS: These data demonstrate a favorable benefit­risk profile for ribociclib + ET in Chinese patients.

A preliminary study on ultrasound techniques applied to evaluate the curative effect of botulinum toxin type a in hypertrophic scars.

Objective: To validate the feasibility of ultrasound in assessing the curative effect of botulinum toxin type A (BTXA) in treating hypertrophic scar (HS). Methods: Eight healthy New Zealand long-eared rabbits were utilized in the study. Four wounds, each measuring 1.0 cm in diameter, were created on both ears of each rabbit. Immediately after surgery, each of these wounds received an injection containing a distinct concentration of BTXA. On postoperative week 6, scar thickness, vascularity, and hardness were assessed based on high frequency ultrasound (HFUS), superb microvascular imaging (SMI), shear wave elastography (SWE), Masson staining, and immunohistochemical staining for CD31. Results: All wounds healed well, and HSs formed after 6 weeks post-surgery. Scar thickness based on HFUS presented a significant decrease with increasing BTXA concentration (p < 0.05), aligning with the gross morphology. Simultaneously, scar stiffness, evaluated using SWE, showed a significant decrease in accordance with the variation of the collagen volume fraction, which refers to the ratio of the collagen positive area to the total area (p < 0.05). Although the vascularity index obtained by SMI did not exhibit a statistically significant change across different BTXA concentrations, this technique effectively illustrated the microvascular perfusion in HS. Immunohistochemical staining for CD31 revealed that BTXA inhibited angiogenesis. Conclusion: HFUS and SWE displayed excellent performance in evaluating HS thickness and stiffness. SMI showed a good performance in reflecting microvascular signals in HS. These ultrasound techniques have great potential in assessing the therapeutic effect of BTXA in HS.

[Anti-diabetic active constituents of pomegranate peel-derived extracellular nanovesicles].

Pomegranate peel-derived extracellular nanovesicles(PPENs) were isolated and purified by ultra-high speed centrifugation and sucrose density gradient centrifugation. Their morphology and structure were characterized. In vitro α-glucosidase inhibition assay and model test of insulin resistance(IR) in HepG2 cells showed that PPENs had good anti-diabetic activity. The IC_(50) value of α-glucosidase inhibition was(35.3±1.1) µg·mL~(-1), significantly better than the positive drug acarbose. At a concentration of 100 µg·mL~(-1), PPENs could increase the glucose absorption of IR cells significantly. Lipidome, proteome, and metabolite analysis of PPENs were performed using chromatography-mass spectrometry. MicroRNA(miRNA) sequences were identified, and target genes of miRNA were predicted. The analysis results indicated that PPENs contained abundant lipids and transport proteins, providing a material basis for the transportation and distribution of PPENs in tissue. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis suggested that lipids and miRNAs may be the key components of PPENs to exert anti-diabetic activity.

Robotic-assisted low anterior resection for rectal cancer shows similar clinical efficacy to laparoscopic surgery: A propensity score matched study.

BACKGROUND: Rectal cancer ranks as the second leading cause of cancer-related mortality worldwide, necessitating surgical resection as the sole treatment option. Over the years, there has been a growing adoption of minimally invasive surgical techniques such as robotic and laparoscopic approaches. Robotic surgery represents an innovative modality that effectively addresses the limitations associated with traditional laparoscopic techniques. While previous studies have reported favorable perioperative outcomes for robot-assisted radical resection in rectal cancer patients, further evidence regarding its oncological safety is still warranted. AIM: To conduct a comparative analysis of perioperative and oncological outcomes between robot-assisted and laparoscopic-assisted low anterior resection (LALAR) procedures. METHODS: The clinical data of 125 patients who underwent robot-assisted low anterior resection (RALAR) and 279 patients who underwent LALAR resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to November 2022 were retrospectively analyzed. After performing a 1:1 propensity score matching, the patients were divided into two groups: The RALAR group and the LALAR group (111 cases in each group). Subsequently, a comparison was made between the short-term outcomes within 30 d after surgery and the 3-year survival outcomes of these two groups. RESULTS: Compared to the LALAR group, the RALAR group exhibited a significantly earlier time to first flatus [2 (2-2) d vs 3 (3-3) d, P = 0.000], as well as a shorter time to first fluid diet [4 (3-4) d vs 5 (4-6) d, P = 0.001]. Additionally, the RALAR group demonstrated reduced postoperative indwelling catheter time [2 (1-3) d vs 4 (3-5) d, P = 0.000] and decreased length of hospital stay after surgery [5 (5-7) d vs 7(6-8) d, P = 0.009]. Moreover, there was an observed increase in total cost of hospitalization for the RALAR group compared to the LALAR group [10777 (10780-11850) dollars vs 10550 (8766-11715) dollars, P = 0.012]. No significant differences were found in terms of conversion rate to laparotomy or incidence of postoperative complications between both groups. Furthermore, no significant disparities were noted regarding the 3-year overall survival rate and 3-year disease-free survival rate between both groups. CONCLUSION: Robotic surgery offers potential advantages in terms of accelerated recovery of gastrointestinal and urologic function compared to LALAR resection, while maintaining similar perioperative and 3-year oncological outcomes.

Double Balloon Combined with Oxytocin in Labor Induction: Analysis of Multivariate Factors Affecting the Efficacy of Cervical Ripening.

Objective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction. Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups. Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257-2.112), fetal distress (OR = 1.371, 95% CI: 1.331-2.633), and the placement of cervical ripening balloon catheter for >12h (OR = 1.563, 95% CI: 1.231-3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455-0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for >12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714-0.811). Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.

Mendelian randomization evidence for the causal effect of mental well-being on healthy aging.

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

New evidence: Metformin unsuitable as routine adjuvant for breast cancer: a drug-target mendelian randomization analysis.

PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.

Impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease.

ABSTRACT: Serial cardiovascular magnetic resonance evaluation of children and young adults with SCD who underwent hematopoietic cell transplantation showed mean ECV, representing diffuse myocardial fibrosis, decreased 3.4% from baseline to 12 months posttransplantation. This trial was registered at www.clinicaltrials.gov as #NCT04362293.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.

Identification of a novel hypoglycemic small molecule, trans-2, 4-dimethoxystilbene by rectifying gut microbiota and activating hepatic AMPKα-PPARγ pathway through gut-liver axis.

With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6 J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders.