Improving the sulfite-detection performance of a fluorescent probe via post-synthetic modification with a metal-organic framework.

In this work, a post-synthetic modification strategy was attempted to improve the performance of the probe for sulfite detection. The assembled platform UiO-66-NH-DQA, which was acquired by anchoring the sulfite-response fluorescent probe DQA onto the surface of UiO-66-NH2via amide covalent bonds, exhibited enhanced fluorescence intensity and practical intracellular imaging capability. In spite of the structural similarity, as verified by characterization tests, the conversion rate of post-synthetic modification was calculated as 35%, equaling an approximate assembly ratio of 1 : 2 between UiO-66-NH2 and DQA. Most significantly, conversion into UiO-66-NH-DQA led to a 5.6-fold enhancement in the reporting signal with a red shift of 20 nm. For sulfite detection, the linear range was 0-150 µM, with a limit of detection value of 0.025 µM. UiO-66-NH-DQA retained advantages including high stability (within pH 5.0-9.0), rapid response (within 15 min) and high selectivity. Based on low cytotoxicity and relatively rapid cellular uptake, UiO-66-NH-DQA achieved the imaging of both the exogenous and endogenous sulfite levels in living cells. In particular, its rapid cell-permeating capability was guaranteed during the modification. The post-synthetic modification strategy reported herein has potential for improving the practical properties of fluorescent monitoring materials.

Changes and Influencing Factors of Corneal Endothelial Cells and Central Corneal Thickness after Pediatric Cataract Surgery.

INTRODUCTION: This study aimed to examine the impact of cataract surgery on the corneal endothelium and central corneal thickness (CCT) in pediatric patients, and to identify the factors associated with corneal alterations. METHODS: This retrospective study included consecutive children undergoing bilateral or unilateral cataract surgery and intraocular lens (IOL) implantation at the Eye Hospital of Wenzhou Medical University, with or without posterior capsulorhexis and anterior vitrectomy, and an age-matched normal control group. This study aimed to assess whether changes in corneal parameters, including CCT, corneal endothelial cell density (CD), average cell area (AVE), standard deviation of size (SD), coefficient of variation (CV), percentage of hexagonal cells (6A) before and after surgery, and endothelial cell loss (ECL) differed among the bilateral cataract, unilateral cataract, and control groups. Furthermore, the potential effects of anterior vitrectomy, axial length (AL), preoperative anterior chamber depth (ACD), surgical duration, horizontal corneal diameter (HCD), intraoperative pupil diameter (PD), and the number of corneal sutures on corneal endothelial parameters and CCT were investigated. RESULTS: A total of 107 eyes from 107 children were included in the study. In the bilateral cataract group, CD significantly decreased, AVE and CCT significantly increased, and ECL was significantly higher than in the control group. The unilateral cataract group also exhibited a significant increase in CCT. Additionally, the number of corneal sutures was negatively correlated with CD, and PD was negatively correlated with CV in the unilateral cataract group. CONCLUSION: Cataract surgery in pediatric patients results in increased CCT, reduced CD, and morphological changes in corneal cells. A greater number of corneal sutures and a smaller PD increased the risk of CD reduction and elevated CV in the unilateral cataract group, underscoring the need for ophthalmologists to minimize corneal damage in these children.

An overview of the production and use of Bacillus thuringiensis toxin.

The widespread utilization of traditional chemical pesticides has given rise to numerous negative impacts, leading to a surge in interest in exploring environmentally friendly alternatives. Bacillus thuringiensis (Bt), a bacterium renowned for its insecticidal properties, produces Cry proteins during its lifecycle. These proteins have distinct advantages over traditional chemical pesticides, including higher environmental safety, broader insecticidal spectra, and lower pesticide residues. Consequently, the discovery and application of Bt hold immense significance in plant disease and pest management, as well as in plant protection. Currently, Bt preparations occupy a prominent position as the world's largest and most widely used biopesticides. This article comprehensively reviews the fundamental aspects, insecticidal mechanisms, practical applications, and fermentation technologies related to Bt.

A novel longitudinal connectivity index to evaluate reticular river networks based on the combination of network maximum flow and resistance distance.

Reticular river networks, essential for ecosystems and hydrology, pose challenges in assessing longitudinal connectivity due to complex multi-path structures and variable flows, exacerbated by human-made infrastructures like sluices. Existing tools inadequately track water flow's spatiotemporal changes, highlighting the need for targeted methods to gauge connectivity within complex river network systems. The Hydraulic Capacity Connectivity Index (HCCI) was developed adopting complex network theory. This involves river networks mapping, nodes and edges construstion, weight factor definition, maximum flow and resistance distance calculation. The connectivity between nodes is represented by the product of the maximum flow and the inverse of the resistance distance. The mean connectivity of each node with all other nodes, denoted as the node connectivity capacity Ci, and the HCCI of the whole river network is defined as the mean of the Ci for all nodes. The HCCI was firstly applied to a symmetrical virtual river network to investigate the factors influencing the HCCI. The results revealed that Ci showed a radial decreasing pattern from the obstructed river reach outwards, and the boundary rivers play the most significant role in regulating the flow dynamics. Subsequently, the HCCI was applied to a real river network in the Yandu district, followed by spatiotemporal statistical analysis comparing with 1D hydraulic model's simulated river discharge. Results showed a high correlation (Pearson coefficient of 0.89) between the HCCI and monthly average river discharge at the global scale. At the local scale, the geographically weighted regression model demonstrated the strong explanatory power of Ci in predicting the distribution of river reach discharge. This suggests that the HCCI addresses multi-path connectivity assessment challenge in reticular river networks, precisely characterizing spatiotemporal flow dynamics. Furthermore, since HCCI is based on a complex network model that can calculate the connectivity between all river node pairs, it is theoretically applicable to other types of river networks, such as dendritic river networks. By identifying low-connectivity areas, HCCI can guide managers in developing scientifically sound and effective strategies for restoring river network hydrodynamics. This can help prevent water stagnation and degradation of water quality, which is beneficial for environmental protection and water resource management.

Developing a fluorescent probe containing benzofuranone moiety for imaging sulphite in living hypoxia pulmonary cells.

In this work, a benzofuranone-derived fluorescent probe BFSF was developed for imaging the sulphite level in living hypoxia pulmonary cells. Under the excitation of 510 nm, BFSF showed a strong fluorescence response at 570 nm when reacted with sulphite. In the solution system, the constructed hypercapnia and serious hypercapnia conditions did not affect the fluorescence response. In comparison with the recently reported probes, BFSF suggested the advantages including rapid response, steady signal reporting, high specificity and low cytotoxicity upon living lung cells. Under a normal incubation atmosphere, BFSF realized the imaging of both exogenous and endogenous sulphite in living pulmonary cells. In particular, BFSF achieved imaging the decrease of the sulphite level under severe hypoxia as well as the recovery of the sulphite level with urgent oxygen supplement. With the imaging capability for the sulphite level in living pulmonary cells under hypoxia conditions, BFSF together with the information herein was meaningful for investigating the anaesthesia-related biological indexes.

Cancer Stemness Online: A Resource for Investigating Cancer Stemness and Associations with Immune Response.

Cancer progression involves the gradual loss of a differentiated phenotype and the acquisition of progenitor and stem-cell-like features, which are potential culprits of immunotherapy resistance. Although the state-of-art predictive computational methods have facilitated the prediction of cancer stemness, currently there is no efficient resource that can meet various usage requirements. Here, we present the Cancer Stemness Online, an integrated resource for efficiently scoring cancer stemness potential at the bulk and single-cell levels. The resource integrates 8 robust predictive algorithms as well as 27 signature gene sets associated with cancer stemness for predicting stemness scores. Downstream analyses were performed from five different aspects, including identifying the signature genes of cancer stemness, exploring the associations with cancer hallmarks, cellular states, the immune response, and communication with immune cells; investigating the contributions to patient survival; and performing a robustness analysis of cancer stemness among different methods. Moreover, the pre-calculated cancer stemness atlas for more than 40 cancer types can be accessed by users. Both the tables and diverse visualizations of the analytical results are available for download. Together, Cancer Stemness Online is a powerful resource for scoring cancer stemness and expanding the downstream functional interpretation, including immune response as well as cancer hallmarks. Cancer Stemness Online is freely accessible at http://bio-bigdata.hrbmu.edu.cn/CancerStemnessOnline.

The fully activated open state of KCNQ1 controls the cardiac "fight-or-flight" response.

The cardiac KCNQ1+KCNE1 (I Ks ) channel regulates heart rhythm in both normal and stress conditions. Under stress, the ß-adrenergic stimulation elevates the intracellular cAMP level, leading to KCNQ1 phosphorylation by protein kinase A and increased I Ks , which shortens action potentials to adapt to accelerated heart rate. An impaired response to the ß-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1). However, the underlying mechanism of ß-adrenergic stimulation of I Ks remains unclear, impeding the development of new therapeutics. Here we find that the unique properties of KCNQ1 channel gating with two distinct open states are key to this mechanism. KCNQ1's fully activated open (AO) state is more sensitive to cAMP than its' intermediate open (IO) state. By enhancing the AO state occupancy, the small molecules ML277 and C28 are found to effectively enhance the cAMP sensitivity of the KCNQ1 channel, independent of KCNE1 association. This finding of enhancing AO state occupancy leads to a potential novel strategy to rescue the response of I Ks to ß-adrenergic stimulation in LQT1 mutants. The success of this approach is demonstrated in cardiac myocytes and also in a high-risk LQT1 mutation. In conclusion the present study not only uncovers the key role of the AO state in I Ks channel phosphorylation, but also provides a new target for anti-arrhythmic strategy. Significance statement: The increase of I Ks potassium currents with adrenalin stimulation is important for "fight-or-flight" responses. Mutations of the IKs channel reducing adrenalin responses are associated with more lethal form of the type-1 long-QT syndrome (LQT). The alpha subunit of the IKs channel, KCNQ1 opens in two distinct open states, the intermediate-open (IO) and activated-open (AO) states, following a two-step voltage sensing domain (VSD) activation process. We found that the AO state, but not the IO state, is responsible for the adrenalin response. Modulators that specifically enhance the AO state occupancy can enhance adrenalin responses of the WT and LQT-associated mutant channels. These results reveal a mechanism of state dependent modulation of ion channels and provide an anti-arrhythmic strategy.

Partially coherent Pearcey-Gauss source with hyperbolic sine correlation of the spatial spectrum.

By designing the intricate coherence structure, we are able to create a desired beam profile and trajectory. Our research focus lies on the Fourier plane, specifically emphasizing the coherence of spatial frequencies, and we find it can be seen as a constant system response. A theoretical framework is developed, and experimental studies are conducted to generate a light field of the spatial spectrum with a complex correlation using the pseudo-mode superposition method. We successfully produce partially coherent Pearcey-Gauss beams whose spatial spectrum is hyperbolic sine correlational. Interestingly, these beams maintain the distinctive propagation properties of the Pearcey pattern while exhibiting the remarkable ability to split the mainlobe into two separate lobes.

CanCellVar: A database for single-cell variants map in human cancer.

Numerous variants, including both single-nucleotide variants (SNVs) in DNA and A>G RNA edits in mRNA as essential drivers of cellular proliferation and tumorigenesis, are commonly associated with cancer progression and growth. Thus, mining and summarizing single-cell variants will provide a refined and higher-resolution view of cancer and further contribute to precision medicine. Here, we established a database, CanCellVar, which aims to provide and visualize the comprehensive atlas of single-cell variants in tumor microenvironment. The current CanCellVar identified ∼3 million variants (∼1.4 million SNVs and ∼1.4 million A>G RNA edits) involved in 2,754,531 cells of 5 major cell types across 37 cancer types. CanCellVar provides the basic annotation information as well as cellular and molecular function properties of variants. In addition, the clinical relevance of variants can be obtained including tumor grade, treatment, metastasis, and others. Several flexible tools were also developed to aid retrieval and to analyze cell-cell interactions, gene expression, cell-development trajectories, regulation, and molecular structure affected by variants. Collectively, CanCellVar will serve as a valuable resource for investigating the functions and characteristics of single-cell variations and their roles in human tumor evolution and treatment.

A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains.

Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cell-to-cell variability, but also precisely regulate transcription and differentiation. Although over 20 TAD callers are able to detect TAD, their usability in biomedicine is confined by a disagreement of outputs and a limit in understanding TAD hierarchy. We compare 13 computational tools across various conditions and develop a metric to evaluate the similarity of TAD hierarchy. Although outputs of TAD hierarchy at each level vary among callers, data resolutions, sequencing depths, and matrices normalization, they are more consistent when they have a higher similarity of larger TADs. We present comprehensive benchmarking of TAD hierarchy callers and operational guidance to researchers of life science researchers. Moreover, by simulating the mixing of different types of cells, we confirm that TAD hierarchy is generated not simply from stacking Hi-C heatmaps of heterogeneous cells. Finally, we propose an air conditioner model to decipher the role of TAD hierarchy in transcription.

Isoflurane Preconditioning Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting miR-195-3p Expression.

To investigate the role of microRNA-195-3p (miR-195-3p) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. AC16 human cardiomyocyte cells were cultured and pretreated with different concentrations of isoflurane (ISO) (1%, 2%, and 3%), followed by 6 h each of hypoxia and reoxygenation to construct H/R cell models. The optimum ISO concentration was assessed based on the cell viability. miR-195-3p expression was regulated by in vitro cell transfection. Cell viability was determined by MTT assay, and apoptosis was evaluated by flow cytometry. The levels of myocardial injury and inflammation were determined by enzyme-linked immunosorbent assay. Compared with the control group, the cell viability of the H/R group had significantly decreased and that of ISO pretreatment had increased in a dose-dependent manner. Therefore, we selected a 2% ISO concentration for pretreatment. MiR-195-3p expression had significantly increased in the H/R group and decreased after 2% ISO pretreatment. Additionally, the number of apoptotic cells and the levels of lactate dehydrogenase, creatine kinase-myoglobin binding, cardiac troponin I, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α had increased significantly. ISO preconditioning inhibited H/R-induced AC16 cell damage, whereas miR-195-3p overexpression reversed the protective effects of ISO on cardiomyocytes. The expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was reduced in the H/R-induced AC16 cells, and PTEN is a downstream target gene of miR-195-3p. Preconditioning with 2% ISO plays a protective role in H/R-induced AC16 cell damage by inhibiting miR-195-3p expression.

Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2-DRP Pathway to Exert Protective Effect on Lipopolysaccharide-Induced Myocardial Injury.

Farnesoid X receptor (FXR) plays critical regulatory roles in cardiovascular physiology/pathology. However, the role of FXR agonist obeticholic acid (OCA) in sepsis-associated myocardial injury and underlying mechanisms remain unclear. C57BL/6J mice are treated with OCA before lipopolysaccharide (LPS) administration. The histopathology of the heart and assessment of FXR expression and mitochondria function are performed. To explore the underlying mechanisms, H9c2 cells, and primary cardiomyocytes are pre-treated with OCA before LPS treatment, and extracellular signal-regulated protein kinase (ERK) inhibitor PD98059 is used. LPS-induced myocardial injury in mice is significantly improved by OCA pretreatment. Mechanistically, OCA pretreatment decreased reactive oxygen species (ROS) levels and blocked the loss of mitochondrial membrane potential (ΔΨm) in cardiomyocytes. The expression of glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and nuclear factor erythroid 2-related factor 2 (NRF-2) increased in the case of OCA pretreatment. In addition, OCA improved mitochondria respiratory chain with increasing Complex I expression and decreasing cytochrome C (Cyt-C) diffusion. Moreover, OCA pretreatment inhibited LPS-induced mitochondria dysfunction via suppressing ERK1/2-DRP signaling pathway. FXR agonist OCA inhibits LPS-induced mitochondria dysfunction via suppressing ERK1/2-DRP signaling pathway to protect mice against LPS-induced myocardial injury.

The death risk of pediatric patients with cancer-related sepsis requiring continuous renal replacement therapy: a retrospective cohort study.

OBJECTIVE: To assess the outcome of patients with cancer-related sepsis requiring continuous renal replacement therapy (CRRT) in a single-center pediatric intensive care unit (PICU). METHOD: Children with sepsis who necessitate CRRT from January 2017 to December 2021 were enrolled. The patients with leukemia/lymphoma or solid tumors were defined as underlying cancer. Multivariate logistic regression analysis was performed to identify the death risk factors in patients with cancer-related sepsis. RESULTS: A total of 146 patients were qualified for inclusion. Forty-six (31.5%) patients with cancer-related sepsis and 100 (68.5%) non-cancer-related sepsis. The overall PICU mortality was 28.1% (41/146), and mortality was significantly higher in cancer-related sepsis patients compared with non-cancer patients (41.3% vs. 22.0%, p = 0.016). Need mechanical ventilation, p-SOFA, acute liver failure, higher fluid overload at CRRT initiation, hypoalbuminemia, and high inotropic support were associated with PICU mortality in cancer-related sepsis patients. Moreover, levels of IL-6, total bilirubin, creatinine, blood urea nitrogen, and international normalized ratio were significantly higher in non-survivors than survivors. In multivariate logistic regression analysis, pediatric sequential organ failure assessment (p-SOFA) score (OR:1.805 [95%CI: 1.047-3.113]) and serum albumin level (OR: 0.758 [95%CI: 0.581 -0.988]) were death risk factors in cancer-related sepsis receiving CRRT, and the AUC of combined index of p-SOFA and albumin was 0.852 (95% CI: 0.730-0.974). CONCLUSION: The overall PICU mortality is high in cancer-related sepsis necessitating CRRT. Higher p-SOFA and lower albumin were independent risk factors for PICU mortality.

Highly Effective Pyroelectric Catalysis for Simultaneous Tumor-Targeted Dynamic Therapy and Gentle Photothermal Therapy by Oxygen-Vacancy-Rich CeO2-BaTiO3 Nanorods.

Pyroelectric nanostructures can effectively generate temperature-mediated reactive oxygen species (ROS) through the pyroelectric effect, providing promise for treating hypoxic tumors; and therefore, the synergistic application of photothermal therapy (PTT) and pyroelectric dynamic therapy (PEDT) presents an intriguing approach for cancer therapy. However, this method still faces challenges in improving pyroelectric catalysis and achieving precise tumor localization. In this study, a nano-heterojunction based on CeO2-BaTiO3 nanorods (IR1061@PCBNR) is reported, which exhibits highly effective pyroelectric catalysis for simultaneous tumor-targeted dynamic therapy and gentle photothermal therapy through the utilization of the rich oxygen vacancies. The oxygen vacancies create active sites that facilitate the migration of pyroelectrically-induced charge carriers, improving charge separation and ROS generation. IR1061@PCBNR also demonstrates high tumor penetration; while, minimizing damage to normal cells. This precise nanomedicine strategy holds great potential for advancing dynamic cancer therapies by overcoming the limitations of conventional approaches.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

Background and objectives: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. Methods: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Results: Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Conclusion: Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

The Role of mRNA Alternative Splicing in Macrophages Infected with Mycobacterium tuberculosis: A Field Needing to Be Discovered.

Mycobacterium tuberculosis (Mtb) is one of the major causes of human death. In its battle with humans, Mtb has fully adapted to its host and developed ways to evade the immune system. At the same time, the human immune system has developed ways to respond to Mtb. The immune system responds to viral and bacterial infections through a variety of mechanisms, one of which is alternative splicing. In this study, we summarized the overall changes in alternative splicing of the transcriptome after macrophages were infected with Mtb. We found that after infection with Mtb, cells undergo changes, including (1) directly reducing the expression of splicing factors, which affects the regulation of gene expression, (2) altering the original function of proteins through splicing, which can involve gene truncation or changes in protein domains, and (3) expressing unique isoforms that may contribute to the identification and development of tuberculosis biomarkers. Moreover, alternative splicing regulation of immune-related genes, such as IL-4, IL-7, IL-7R, and IL-12R, may be an important factor affecting the activation or dormancy state of Mtb. These will help to fully understand the immune response to Mtb infection, which is crucial for the development of tuberculosis biomarkers and new drug targets.

Accuracy of Ten Intraocular Lens Formulas in Spherical Equivalent of Toric Intraocular Lens Power Calculation.

INTRODUCTION: The aim of this work is to evaluate the accuracy of the Barrett Universal II (BU II), Emmetropia verifying optical (EVO) 2.0, Haigis, Hoffer Q, Hoffer QST (Savini/Taroni) (HQST), Holladay 1, Kane, Ladas Super, Sanders-Retzlaff-Kraff/theoretical (SRK/T), and T2 intraocular lens (IOL) power formulas for calculating spherical equivalent (SE) of toric IOL. METHODS: This study enrolled consecutive patients who underwent phacoemulsification and toric IOL implantation at the Eye Hospital of Wenzhou Medical University in Hangzhou from 2015 to 2022. We compared the new-generation formulas with Gaussian optics-based standard formulas, and calculated the mean absolute error (MAE), median absolute error (MedAE), and percentage of eyes within ± 0.25 diopter (D), ± 0.50 D, ± 0.75 D and ± 1.00 D of the target refraction. Subgroup analyses were conducted based on the anterior chamber depth (ACD), keratometry (K), and toricity (T). RESULTS: A total of 207 eyes of 207 patients were included in this study. Overall, the Kane and EVO2.0 formulas demonstrated the lowest MedAEs. The EVO2.0 formula exhibited the highest percentage of eyes within ± 0.50 D, ± 0.75 D, ± 1.00 D. Moreover, the EVO2.0 formula showed the lowest MedAE for flat K subgroup, the highest percentage of eyes within ± 0.50 D, ± 1.00 D for shallow ACD subgroup, the highest percentage of eyes within ± 0.75 D for regular ACD, flat K, T2-T3, T4-T5 subgroups. The Kane and formula performed the lowest MedAE in the T4-T5 subgroup. CONCLUSIONS: Application of the Kane and EVO2.0 formulas significantly improved the prediction of postoperative SE outcome for toric IOL compared to the other formulas.

Factors Associated With Psychological Wellbeing in Home Care Older Adults With Alzheimer's Disease: A Longitudinal Analysis.

The long-term symptoms associated with Alzheimer's disease pose significant challenges to the psychological wellbeing of patients. This longitudinal study aims to analyze the effects of socioeconomic factors and physical health factors on the psychological wellbeing of older patients diagnosed with Alzheimer's disease (AD) receiving home care, as well as the moderating role of aging and care support in influencing their psychological wellbeing. Data from the Health and Retirement Study (N = 628 older Alzheimer's patients) were analyzed using pooled ordinary least squares fixed-effects models. Findings suggest that Alzheimer's patients' psychological wellbeing was significantly affected by factors including cohabitation, gender, assistance frequency, age, education, and daily activity challenges, with assistance and increasing age mitigating some daily difficulties. The findings underline the multifactorial nature of psychological wellbeing among older Alzheimer's patients in home care and the critical role of social and physical health determinants in shaping these outcomes.

Association between brominated flame retardants and risk of endocrine-related cancer: A systematic review and meta-analysis.

BACKGROUND: The incidence of endocrine-related cancer, which includes tumors in major endocrine glands such as the breast, thyroid, pituitary, and prostate, has been increasing year by year. Various studies have indicated that brominated flame retardants (BFRs) are neurotoxic, endocrine-toxic, reproductive-toxic, and even carcinogenic. However, the epidemiological relationship between BFR exposure and endocrine-related cancer risk remains unclear. METHODS: We searched the PubMed, Google Scholar, and Web of Science databases for articles evaluating the association between BFR exposure and endocrine-related cancer risk. The odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were used to assess the association. Statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Begg's test was performed to evaluate the publication bias. RESULTS: We collected 15 studies, including 6 nested case-control and 9 case-control studies, with 3468 cases and 4187 controls. These studies assessed the risk of breast cancer, thyroid cancer, and endocrine-related cancers in relation to BFR levels. Our findings indicate a significant association between BFR exposure in adipose tissue and an increased risk of breast cancer. However, this association was not observed for thyroid cancer. Generally, BFR exposure appears to elevate the risk of endocrine-related cancers, with a notable increase in risk linked to higher levels of BDE-28, a specific polybrominated diphenyl ether congener. CONCLUSIONS: In conclusion, although this meta-analysis has several limitations, our results suggest that BFR exposure is a significant risk factor for breast cancer, and low-brominated BDE-28 exposure could significantly increase the risk of endocrine-related cancers. Further research is essential to clarify the potential causal relationships between BFRs and endocrine-related cancers, and their carcinogenic mechanisms.

Redox-dependent Cd2+ inhibition of BK-type Ca2+-activated K+ channels.

Large-conductance Ca2+-activated K+ channels (BK channels) are formed by Slo1 subunits as a homotetramer. Besides Ca2+, other divalent cations, such as Cd2+, also activate BK channels when applied intracellularly by shifting the conductance-voltage relation to more negative voltages. However, we found that if the inside-out patch containing BK channels was treated with solution containing reducing agents such as dithiothreitol (DTT), then subsequent Cd2+ application completely inhibited BK currents. The DTT-dependent Cd2+ inhibition could be reversed by treating the patch with solutions containing H2O2, suggesting that a redox reaction regulates the Cd2+ inhibition of BK channels. Similar DTT-dependent Cd2+ inhibition was also observed in a mutant BK channel, Core-MT, in which the cytosolic domain of the channel is deleted, and in the proton-activated Slo3 channels but not observed in the voltage-gated Shaker K+ channels. A possible mechanism for the DTT-dependent Cd2+ inhibition is that DTT treatment breaks one or more disulfide bonds between cysteine pairs in the BK channel protein and the freed thiol groups coordinate with Cd2+ to form an ion bridge that blocks the channel or locks the channel at the closed state. However, surprisingly, none of the mutations of all cysteine residues in Slo1 affect the DTT-dependent Cd2+ inhibition. These results are puzzling, with an apparent contradiction: on one hand, a redox reaction seems to regulate Cd2+ inhibition of the channel, but on the other hand, no cysteine residue in the Slo1 subunit seems to be involved in such inhibition.