Silicon Waveguide-Integrated Platinum Telluride Midinfrared Photodetector with High Responsivity and High Speed.

The detection of mid-infrared light, covering a variety of molecular vibrational spectra, is critical for both civil and military purposes. Recent studies have highlighted the potential of two-dimensional topological semimetals for mid-infrared detection due to their advantages, including van der Waals (vdW) stacking and gapless electronic structures. Among them, mid-infrared photodetectors based on type-II Dirac semimetals have been less studied. In this paper, we present a silicon waveguide integrated type-II Dirac semimetal platinum telluride (PtTe2) mid-infrared photodetector, and further improve detection performance by using PtTe2-graphene heterostructure. For the fabricated silicon waveguide-integrated PtTe2 photodetector, with an external bias voltage of -10 mV and an input optical power of 86 nW, the measured responsivity is 2.7 A/W at 2004 nm and a 3 dB bandwidth of 0.6 MHz is realized. For the fabricated silicon waveguide-integrated PtTe2-graphene photodetector, as the external bias voltage and input optical power are 0.5 V and 0.13 µW, a responsivity of 5.5 A/W at 2004 nm and a 3 dB bandwidth of 35 MHz are obtained. An external quantum efficiency of 119% can be achieved at an input optical power of 0.376 µW.

Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas.

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of ß-catenin and active-ß-catenin by increasing the proportion of ubiquitinated ß-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-ß-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.

Genotoxicity and cytotoxicity evaluation of a heat-not-burn product.

'Heat-not-burn' products (HnBP) contain lower levels of harmful substances than traditional cigarettes, but the use of these products warrants further toxicological evaluation. We have compared the cytotoxicity and genotoxicity of a heat-not burn product with conventional cigarettes, in vivo and in vitro. Male Sprague Dawley rats were exposed to mainstream smoke from conventional cigarettes or a HnBP, for 4 or 28 days, followed by isolation of bone marrow polychromatic erythrocytes (PCE) and histological examination of the testes. Chinese hamster lung fibroblast cells were exposed in vitro to total particulate matter from cigarette smoke obtained through Cambridge filters. The cytotoxicity and genotoxicity of total particulate matter were assessed by the neutral red uptake assay, chromosome aberration assay, in vitro micronucleus test, comet assay, and Ames assay. In the short-term exposure rat models, only the conventional-cigarettes group showed a significant increase in the ratio of micronuclei to total PCE. There was no significant difference in rat testis histology in the long-term exposure models. In vitro, in the neutral red uptake assay, the HnBP product showed lower cytotoxicity than conventional cigarettes. Conventional cigarettes showed greater genotoxicity in the chromosome aberration assay, high-dose Ames tests with exogenous metabolic activation, and micronucleus tests. In summary, our results suggest that HnBP have lower cytotoxicity and genotoxicity than conventional cigarettes.

Recent research of peptide-based hydrogel in nervous regeneration.

Neurological disorders exert significantly affect the quality of life for patients, necessitating effective strategies for nerve regeneration. Both traditional autologous nerve transplantation and emerging therapeutic approaches encounter scientific challenges due to the complex nature of the nervous system and the unsuitability of the surrounding environment for cell transplantation. Tissue engineering techniques offer a promising path for neurotherapy. Successful neural tissue engineering relies on modulating cell differentiation behavior and tissue repair by developing biomaterials that mimic the natural extracellular matrix (ECM) and establish a three-dimensional microenvironment. Peptide-based hydrogels have emerged as a potent option among these biomaterials due to their ability to replicate the structure and complexity of the ECM. This review aims to explore the diverse range of peptide-based hydrogels used in nerve regeneration with a specific focus on dipeptide hydrogels, tripeptide hydrogels, oligopeptide hydrogels, multidomain peptides (MDPs), and amphiphilic peptide hydrogels (PAs). Peptide-based hydrogels offer numerous advantages, including biocompatibility, structural diversity, adjustable mechanical properties, and degradation without adverse effects. Notably, hydrogels formed from self-assembled polypeptide nanofibers, derived from amino acids, show promising potential in engineering neural tissues, outperforming conventional materials like alginate, poly(ε-caprolactone), and polyaniline. Additionally, the simple design and cost-effectiveness of dipeptide-based hydrogels have enabled the creation of various functional supramolecular structures, with significant implications for nervous system regeneration. These hydrogels are expected to play a crucial role in future neural tissue engineering research. This review aims to highlight the benefits and potential applications of peptide-based hydrogels, contributing to the advancement of neural tissue engineering.

Resilience during lockdown: a longitudinal study investigating changes in behaviour and attitudes among older females during COVID-19 lockdown in the UK.

In order to slow the spread of COVID-19, on March 23, 2020, a strict lockdown was implemented in the UK. This was followed by alternating periods of less restrictive lockdowns until most public health restrictions were lifted in the summer of 2021. While these measures were necessary, they significantly affected people's daily activities, lifestyles, and mental well-being.This paper presents a longitudinal research study that focused on females aged 55 + in the UK, aiming to understand how COVID-19 and the subsequent 15-month period of lockdowns affected their lifestyles and emotions. The study collected data through online surveys, where respondents reported the frequency and mode of access to activities, and their positive and negative emotional experiences during distinct study phases that encompassed both lockdown and less strict periods.In contrast to previous studies highlighting vulnerabilities for females and the elderly during lockdowns, this research found that the studied group maintained an overall positive outlook throughout the study period and successfully adapted to the lockdowns by increasing their engagement in certain activities, in particular, activities like 'getting active'. In addition, our findings indicate rapid adaptive behaviour change towards many online activities, such as cultural activities. However, the study also revealed negative emotions and a decrease in some activities during the second lockdown in 2020 and the subsequent lockdowns in 2021, underscoring the challenges inherent in prolonged periods of confinement. In addition, the study found negative affect associated with some activities, including working and studying from home.The findings provide valuable insights into how females aged over 55 coped with stressful circumstances, which can inform the development of resilient and mental health-conscious public health policies and responses in preparation for future pandemics or other hazards.

Vigor King mitigates spermatogenic disorders caused by environmental estrogen zearalenone exposure.

Zearalenone (ZEN) has been shown to cause reproductive damage by inducing oxidative stress. Astaxanthin and L-carnitine are widely used to alleviate oxidative stress and promote sperm maturation. However, it remains uncertain whether they are effective in mitigating spermatogenesis disorders induced by ZEN. This study aimed to investigate the therapeutic efficacy and potential mechanisms of Vigor King (Vig), a compound preparation primarily consisting of astaxanthin and L-carnitine, in alleviating ZEN-induced spermatogenesis disorders. In the experiment, mice received continuous oral gavage of ZEN (80 µg/kg) for 35 days, accompanied by a rescue strategy with Vig (200 mg/kg). The results showed that Vig effectively reduced the negative impact on semen quality and improved the structural and functional abnormalities of the seminiferous epithelium caused by ZEN. Additionally, the accumulation of reactive oxygen species (ROS), DNA double-strand breaks, apoptosis, and autophagy abnormalities were all significantly ameliorated. Intriguingly, the GSK3ß-dependent BTRC-NRF2 signaling pathway was found to play an important role in this process. Furthermore, testing of offspring indicated that Vig could extend its protective effects to the next generation, effectively combating the transgenerational toxic effects of ZEN. In summary, our research suggests that Vig supplementation holds considerable promise in alleviating spermatogenesis disorders induced by zearalenone.

Study on the Effect of Precise Prevention of H-Type Hypertension, Cardiovascular, and Cerebrovascular Risks in Qingyuan District.

Objective: To explore the relationship between controlling the development of H-type hypertension and the effectiveness of precision prevention of cardiovascular risk. Methods: 518 patients with essential hypertension with hyperhomocysteinemia diagnosed in December 2019 to February 2020 in Qingyuan District Public Hospital were recruited as the experimental sample for prospective analysis and were equally divided into control and experimental groups according to their order of admission, i.e., 259 patients in each group. The control group was treated with antihypertensive drugs only, while the experimental group was given enalapril folic acid tablets (0.8 mg/d) and vitamin B once daily in addition to antihypertensive drugs, and then monitored for plasma Hcy levels, cardiovascular event rates, and survival at one year. Results: After treatment, the plasma Hcy levels of the experimental group were significantly lower than those of the control group (P < .001). During treatment, the total incidence of cardiovascular disease in the experimental group was less than that in the control group (P < .05). One year after the end of treatment, the mortality rate due to cardiovascular disease in the control group was higher than that in the experimental group (P < .05). Conclusion: It is worthwhile to promote the use of targeted management of patients with H-type hypertension to prevent the occurrence of cardiovascular diseases, improve Hcy levels, and stabilize blood pressure levels in patients.

Preparation, characterization, and application of gallic acid-mediated photodynamic chitosan-nanocellulose-based films.

In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e-12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products.

SENP1-Mediated HSP90ab1 DeSUMOylation in Cardiomyocytes Prevents Myocardial Fibrosis by Paracrine Signaling.

Myocardial infarction (MI) triggers a poor ventricular remodeling response, but the underlying mechanisms remain unclear. Here, the authors show that sentrin-specific protease 1 (SENP1) is downregulated in post-MI mice and in patients with severe heart failure. By generating cardiomyocyte-specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Increased cardiac fibrosis in the cardiomyocyte-specific SENP1 deletion mice, associated with increased fibronectin (Fn) expression and secretion in cardiomyocytes, promotes fibroblast activation in response to myocardial injury. Mechanistically, SENP1 deletion in mouse cardiomyocytes increases heat shock protein 90 alpha family class B member 1 (HSP90ab1) SUMOylation with (STAT3) activation and Fn secretion after ventricular remodeling initiated. Overexpression of SENP1 or mutation of the HSP90ab1 Lys72 ameliorates adverse ventricular remodeling and dysfunction after MI. Taken together, this study identifies SENP1 as a positive regulator of cardiac repair and a potential drug target for the treatment of MI. Inhibition of HSP90ab1 SUMOylation stabilizes STAT3 to inhibit the adverse ventricular remodeling response.

Research on narrative design of handicraft intangible cultural heritage creative products based on AHP-TOPSIS method.

To address the issues of subjectivity and bias that designers face in selecting and constructing narrative cultural themes when introducing narrative design methods into the design of handicraft intangible cultural heritage cultural and creative products, a model incorporating quantitative analysis methods into the narrative theme selection process is proposed. First, based on the theory of cultural levels and semiotic structure, a new narrative text structure is developed to enrich the narrative cultural themes of handicraft intangible cultural heritage. Second, a process model for constructing narrative texts of handicraft intangible cultural heritage is established using kansei engineering, factor analysis, and the TOPSIS method, to minimize the impact of subjective factors in the narrative theme selection process. Finally, using the design of Huangmei Cross Flower cultural and creative products as an example, the feasibility of the model is validated. This method model effectively reduces the transmission bias of cultural features in the narrative design process of handicraft intangible cultural heritage, providing a theoretical foundation for further design practice of handicraft intangible cultural heritage products.

CNT Composite ß-MnO2 with Fiber Cable Shape as Cathode Materials for Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries (AZIBs) have developed into one of the most attractive materials for large-scale energy storage owing to their advantages such as high energy density, low cost, and environmental friendliness. Nevertheless, the sluggish diffusion kinetics and inherent impoverished conductivity affect their practical application. Herein, the ß-MnO2 composited with carbon nanotubes (CNT@M) is prepared through a simple hydrothermal approach as a high-performance cathode for AZIBs. The CNT@M electrode exhibits excellent cycling stability, in which the maximum specific discharge capacity is 259 mA h g-1 at 3 A g-1, and there is still 220 mA h g-1 after 2000 cycles. The specific capacity is obviously better than that of ß-MnO2 (32 mA h g-1 after 2000 cycles). The outstanding electrochemical performance of the battery is inseparable from the structural framework of CNT and inherent high conductivity. Furthermore, CNT@M can form a complex conductive network based on CNTs to provide excellent ion diffusion and charge transfer. Therefore, the active material can maintain a long-term cycle and achieve stable capacity retention. This research provides a reasonable solution for the reliable conception of Mn-based electrodes and indicates its potential application in high-performance AZIB cathode materials.

Trace Iron-Doped Nickel-Cobalt selenide with rich heterointerfaces for efficient overall water splitting at high current densities.

Developing bifunctional electrocatalysts based on non-precious metals for overall water splitting, while maintaining high catalytic activity and stability under high current densities, remains challenging. Herein, we successfully constructred trace iron-doped nickel-cobalt selenide with abundant CoSe2 (210)-Ni3Se4 (202) heterointerfaces via a simple one-step selenization reaction. The synthesized Fe-NiCoSex/NCFF (NCFF stands for nickel-cobalt-iron foam) exhibits outstanding hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activity with low overpotentials of 328 mV for HER and 345 mV for OER at a high current density of 1000 mA cm-2, while maintaining stability for over 20 h. Additionally, the Fe-NiCoSex/NCFF exhibits the lowest Tafel slope values for both HER (33.7 mV dec-1) and OER (55.92 mV dec-1), indicating the fastest kinetics on its surface. The Fe-NiCoSex/NCFF features uniformly distributed micrometer-sized selenide particles with dense nanowires on their surface, providing a large reactive surface area and abundant active sites. Moreover, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) analyses reveal that the catalyst is composed of nickel, cobalt, and iron, forming micrometer-sized particles with both crystalline and amorphous phases, thereby enhancing HER and OER performance under high current density. Density functional theory (DFT) calculations demonstrate that the heterostructure CoSe2 (210)-Ni3Se4 (202), with high electron density and suitable adsorption capacity for reaction intermediates, and low energy barriers for HER (-0.384 eV) and OER (ΔG1st: 0.243 eV, ΔG2nd: 0.376 eV), serves as an active center for both HER and OER.

Circulating immune cells and risk of osteosarcoma: a Mendelian randomization analysis.

Objectives: Osteosarcoma (OS) is the primary bone tumor originating from transformed mesenchymal cells. It is unclear whether associations between specific circulating immune cells and OS are causal or due to bias. To clarify whether predicted genetically altered circulating immune cells are associated with OS development, we performed a two-sample Mendelian randomization (MR) analysis. Methods: The genetic variants strongly associated with immune cell traits as instrumental variables (IVs) were used to perform MR analyses. The effect of specific immune cells on OS risk was measured using the summary statistics from the genome-wide association studies (GWAS). Results: Our findings indicate that CD80 on CD62L+ myeloid dendritic cell and CD28-CD4-CD8- T-cell absolute count are positively associated with OS (CD80 on CD62L+ myeloid dendritic cell, OR: 3.41 [95% CI: 1.40 to 8.31], p = 0.007; CD28-CD4-CD8- T-cell absolute count, OR: 4.49 [95% CI: 1.29 to 15.62], p = 0.018). It is also found that CD20 has a negative effect on CD24+CD27+ B cell on OS (OR: 0.32 [95% CI: 0.14 to 0.72], p = 0.006) and a similar impact on IgD+ CD38- B cell on OS (OR: 0.19 [95% CI: 0.05 to 0.68], p = 0.011). Conclusions: These findings illustrate that the genetic predisposition to specific immune cells can exert a causal effect on OS risk, which confirms the crucial role played by immunity in OS development. Particularly, the causal association between immune cells and OS underscores the evidence for exploring the new treatment strategy for OS in the future.

Electrostatic Force-Assisted Transfer of Flexible Silicon Photodetector Focal Plane Arrays for Image Sensors.

Flexible photodetectors are pivotal in contemporary optoelectronic technology applications, such as data reception and image sensing, yet their performance and yield are often hindered by the challenge of heterogeneous integration between photoactive materials and flexible substrates. Here, we showcase the potential of an electrostatic force-assisted transfer printing technique for integrating Si PIN photodiodes onto flexible substrates. This clean and dry process eliminates the need for chemical etchants, making it a highly desirable method for manufacturing high-performance flexible photodetector arrays, expanding their widespread applications in electronic eyes, robotics, and human-machine interaction. As a demonstration, a 5 × 5 flexible Si photodetector focal plane array is constructed for imaging sensors and shaped into a convex semicylindrical form to achieve a π field of view with long-term mechanical and thermal stability. Such an approach provides a high yield rate and consistent performance, with the single photodetector demonstrating exceptional characteristics, including a responsivity of 0.61 A/W, a response speed of 39.77 MHz, a linear dynamic range of 108.53 dB, and a specific detectivity of 2.75 × 1012 Jones at an applied voltage of -3 V at 940 nm.

Microchip Liquid-Phase Ion Trap for Online Mass Spectrometry Analysis.

Liquid-phase ion trapping (LPIT) was proposed recently for ion manipulations in liquid channels. When coupled with mass spectrometry, LPIT exhibits considerable potential in applications such as target enrichment and bottom-up proteomics. However, further evolution of LPIT techniques requires flexible field designs including electric and fluid fields. In this study, LPIT was constructed and implemented on microfluidic chips. Utilizing conductive polymers, nonlinear potential distribution was achieved in the liquid channel, enabling the focusing of ions at distinct locations based on their effective charges and hydrodynamic radii. The integration of an electrospray ionization source facilitated coupling of the LPIT chip with a mass spectrometer. The working mechanism and parameter optimizations were explored through a combination of theoretical analysis and numerical simulations. Experiments showcased the LIPT chip's proficiency in enrichment and separation capabilities. The detection sensitivity of the following mass spectrometer could be improved by ∼10-fold. A good linearity (R2 > 0.99) was obtained for reserpine in the range of 1-100 ng/mL. The separation capability was demonstrated using a mixture of 11 amino acids.

The impact of chronic pain and depression on medication for opioid use disorder treatment: A mixed-methods analysis.

Background: Opioid use disorder (OUD) is associated with significant morbidity and mortality. Medication for opioid use disorder (MOUD) is a cost-effective treatment, but retention rates vary widely. Aim: Mixed methods studies are needed to better understand how depression and pain impact the experience of OUD and MOUD treatment experiences. Methods: Participants were recruited from an urban addiction treatment center in the United States. Along with demographic characteristics, current pain severity, pain interference, pain catastrophizing, and depression were assessed via self-report. Correlational analyses, multivariable logistic regression models, Fisher exact tests, and Wilcoxon signed rank tests were used to examine the impact of demographic characteristics, physical pain, and depression on multiple treatment outcomes: 90-day treatment engagement (total number of dispensed MOUD doses), retention (yes/no still in treatment at 90 days), and opioid use (positive/negative urinalysis for opioids at 90 days). Ten participants were interviewed about their history with physical pain, depression, opioid use, and OUD treatment experiences. Themes were identified using a rapid analysis, top-down approach. Results: Fifty participants enrolled in the study and received buprenorphine (12%) or methadone (88%). Older age was associated with 90-day treatment engagement. Higher depression scores were associated with a positive opioid urinalysis at 90-day follow-up. In interviews, participants reported experiencing chronic physical pain and depression before and during their OUD and an interest in addressing mental and physical health in addiction treatment. Conclusions: Addressing co-occurring physical and mental health concerns during MOUD treatment has the potential to improve the treatment experience and abstinence from opioids.

Increasing the frequency of plant-based food intake in daily diets reduces the risk of cardiovascular disease among elderly Chinese: a cohort study.

Objective: There is limited research on the relationship between the frequency of plant-based food intake and the risk of cardiovascular disease (CVD) among elderly Chinese. This study aims to evaluate the association between plant-based dietary index (PDI) and CVD risks, providing evidence for elderly Chinese to reduce CVD risks by increasing the frequency of plant-based food consumption. Methods: This study analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2011-2018, employing a multivariate modified Poisson regression model, trend tests, and restricted cubic spline (RCS) analysis to assess the linear and non-linear relationship between the PDI and CVD risks. Subgroup analyses and interaction tests were conducted to evaluate the robustness and population-specificity of the results. Results: This study included a total of 1,414 elderly Chinese, and at the end of follow-up, 487 participants had developed CVD. The multivariate modified Poisson regression model revealed a negative association between PDI and CVD risks [RR = 0.983, 95%CI = (0.970, 0.997)]. Similarly, the multivariate trend test (p = 0.031) and RCS analysis (P for nonlinear = 0.600) indicated a linear relationship between PDI and CVD risks. Subgroup analyses showed that the relationship between PDI and CVD risk was not influenced by gender, BMI, smoking, alcohol use, or exercise. Conclusion: The PDI was negatively correlated with CVD risks, indicating that increasing the frequency of plant-based food intake in the diet may reduce CVD risks among elderly Chinese.

SHAP based predictive modeling for 1 year all-cause readmission risk in elderly heart failure patients: feature selection and model interpretation.

Heart failure (HF) is a significant global public health concern with a high readmission rate, posing a serious threat to the health of the elderly population. While several studies have used machine learning (ML) to develop all-cause readmission risk prediction models for elderly patients with HF, few have integrated ML-selected features with those chosen by human experts to assess HF patients readmission. A retrospective analysis of 8396 elderly HF patients hospitalized at the Affiliated Hospital of North Sichuan Medical College from January 1, 2018 to December 31, 2021 was conducted. Variables selected by XGBoost, LASSO regression, and random forest constituted the machine group, while the human expert group comprised variables chosen by two experienced cardiovascular professors. The variables selected by both groups were combined to form a human-machine collaboration group. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) method was used to elucidate the importance of each predictive feature, explain the impact of individual features on the model, and provide visual representation. A total of 73 features were included for model development. The human-machine collaboration model, utilizing CatBoost, achieved an AUC of 0.83617, an F1-score of 0.73521, and a Brier score of 0.16536 on the validation set. This model demonstrated superior predictive performance compared to those created solely by human experts or machine. The SHAP plot was then used to visually display the feature analysis of the human-machine collaboration model, revealing HGB, NT-proBNP, smoking history, NYHA classification, and LVEF as the 5 most important features. This study indicate that the human-machine collaboration model outperforms those relying solely on human expert selection or machine algorithm at predicting all-cause readmission in elderly HF patients. The application of the SHAP method enhanced the interpretability of the model outcomes, aiding clinicians in accurately pinpointing risk factors associated with HF readmission. This advancement enables the formulation of tailored treatment strategies, offering a more personalized approach to patient care.

Celiac disease and attention-deficit/hyperactivity disorder: a bidirectional Mendelian randomization analysis.

Background: Recent observational research suggests a potential link between celiac disease (CeD) and an increased incidence of attention-deficit/hyperactivity disorder (ADHD). However, the genetic relationship between CeD and ADHD remains unclear. In order to assess the potential genetic causality between these two conditions, we conducted a Mendelian randomization (MR) analysis. Methods: We performed a bidirectional MR analysis to investigate the relationship between CeD and ADHD. We carefully selected single nucleotide polymorphisms (SNPs) from publicly available large-scale genome-wide association studies (GWAS) databases, employing rigorous quality screening criteria. MR estimates were obtained using four different methods: fixed-effect inverse variance weighted (fe-IVW), random-effect inverse variance weighting (re-IVW), weighted median (WM), and MR-Egger. The robustness and reliability of our findings were confirmed through sensitivity analyses, assessment of instrumental variable (IV) strength (F-statistic), and statistical power calculations. Results: Our MR analyses did not reveal any significant genetic associations between CeD and ADHD (fe-IVW: OR = 1.003, 95% CI = 0.932-1.079, P = 0.934). Similarly, in the reverse direction analysis, we found no evidence supporting a genetic relationship between ADHD and CeD (fe-IVW: OR = 0.850, 95% CI = 0.591-1.221, P = 0.378). Various MR approaches consistently yielded similar results. Sensitivity analysis indicated the absence of significant horizontal pleiotropy or heterogeneity. However, it's important to note that the limited statistical power of our study may have constrained the causal analysis of the exposure's influence on the outcome. Conclusions: Our findings do not provide compelling evidence for a genetic association between CeD and ADHD within the European population. While the statistical power of our study was limited, future MR research could benefit from larger-scale datasets or datasets involving similar traits. To validate our results in real-world scenarios, further mechanistic studies, large-sample investigations, multicenter collaborations, and longitudinal studies are warranted.

Cinnamaldehyde inhibits the NLRP3 inflammasome by preserving mitochondrial integrity and augmenting autophagy in Shigella sonnei-infected macrophages.

BACKGROUND: Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1ß and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. METHODS: Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. RESULTS: CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1ß and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. CONCLUSION: CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.