Understanding Care Needs of Older Adults with Disabilities: A Scoping Review.

Purpose: To conducted a scoping review of care needs of older adults with disabilities at home and in the community and provide a comprehensive understanding of the essential needs of older adults with disabilities. Methods: Eight databases were searched for relevant Chinese and English studies (supplemented by retrospective references of the included studies) from the establishment of the database to February 13, 2023. An thematic synthesis approach was used to qualitatively integrate the retrieved studies and identify need-related themes. Results: A total of 6239 studies were retrieved, 2557 were de-weighted and excluded, and 56 were obtained after the double screening. Studies were from 11 countries. Thirty-three studies used a self-prepared survey instrument to investigate needs, and the other research tools commonly used were secondary databases and the Long-Term Care Needs of the Disabled Scale. A total of 78 specific need items were identified and summarized into three need themes based on the ICF framework: physical functioning needs, activity and participation needs, and environment needs. Conclusion: The complex physical and mental health conditions faced by older adults with disabilities result in multifaceted, integrated needs that are difficult to identify and meet. Current research on older adults with disabilities is limited to common care. Future research should focus on the specificities of the older disabled population and understand the diverse care needs of people with disabilities in order to better target care services for this group. Policymakers should formulate more operational and strategic measures based on the actual needs of older adults with disabilities to expand the coverage of services and to pinpoint care services.

Periplogenin inhibits pyroptosis of fibroblastic synoviocytes in rheumatoid arthritis through the NLRP3/Caspase-1/GSDMD signaling pathway.

Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.

Association of socioeconomic status and poststroke cognitive function: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors are at high risk of coping with cognitive problems after stroke. In recent decades, the relationship between socioeconomic status (SES) and health-related outcomes has been a topic of considerable interest. Learning more about the potential impact of SES on poststroke cognitive dysfunction is of great importance. OBJECTIVE: The purpose of this systematic review and meta-analysis was to summarize the association between SES and poststroke cognitive function by quantifying the effect sizes of the existing studies. METHOD: We searched studies from PubMed, Ovid, Embase, Cochrane, Scopus, and PsychINFO up to January 30th 2024 and the references of relevant reviews. Studies reporting the risk of poststroke cognitive dysfunction as assessed by categorized SES indicators were included. The Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality were used to evaluate the study quality. Meta-analyses using fixed-effect models or random-effect models based on study heterogeneity were performed to estimate the influence of SES on cognitive function after stroke, followed by subgroup analyses stratified by study characteristics. RESULTS: Thirty-four studies were eligible for this systematic review and meta-analysis. Of which, 19 studies reported poststroke cognitive impairment (PSCI) as the outcome, 13 reported poststroke dementia (PSD), one reported both PSCI and PSD, and one reported vascular cognitive impairment no dementia. The findings showed that individuals with lower SES levels had a higher risk of combined poststroke cognitive dysfunction (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.59-2.29), PSCI (OR = 2.09, 95% CI = 1.57-2.78), and PSD (OR = 1.95, 95% CI = 1.48-2.57). Subgroup analyses stratified by SES indicators demonstrated the protective effects of education and occupation against the diagnoses of combined poststroke cognitive dysfunction, PSCI, and PSD. CONCLUSIONS: Stroke survivors belonging to a low SES are at high risk of poststroke cognitive dysfunction. Our findings add evidence for public health strategies to reduce the risk of poststroke cognitive dysfunction by reducing SES inequalities.

Profiling of urinary steroids aided by lithium ion adduction-based ultrahigh-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: As 3-OH-containing steroids are prone to dehydration by conventional electrospray ionization, reducing detection sensitivity, Li ion adduction-based ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS), developed to prevent dehydration and effectively detect 3-OH steroids, was applied for profiling total and free steroids in urine. METHODS: Free urinary steroids were isolated directly from urine by solid-phase extraction (SPE) with 80% acetonitrile. The total steroids were prepared by enzymatic treatment of urine with a cocktail of sulfatase and glucronidase, protein precipitation, and separation with the above SPE. In order to detect as many steroid types as possible, UHPLC/MS/MS (Li method) with Li+ solution added after the column was used for analysis in addition to the conventional method of detecting protonated ions (H method). The 13 3-OH steroids and the remaining 16 steroids were quantified by standard curves prepared using product ion transitions derived from [M + Li]+ and MH+ , respectively. RESULTS: Two groups of human urine, male and female urine, were analyzed. 3-OH steroids could be detected with greater sensitivity using the Li method than the conventional method. The absolute amounts of each steroid were normalized based on creatinine levels. The difference between the male and female groups are clearly attributable to sex steroids. CONCLUSIONS: Twenty-nine total steroids and 19 free steroids were identified in a limited volume (240 mL) of urine. Of these, 13 3-OH steroids were better detected by Li+ adduction-based UHPLC/MS/MS.

A sodium alginate gel bead adsorbent doping with amidoxime-modified hydroxyapatite for the efficient adsorption of uranium.

In this work, the modified­sodium alginate gel beads were prepared by sol-gel method. Due to the presence of water channels in the sodium alginate gel bead, amidoxime groups and PO43- were exposed to the surface of the adsorbent to the maximum extent, resulting in the excellent adsorption capacity of modified­sodium alginate gel beads. The introduction of amidoxime-modified hydroxyapatite significantly improved the adsorption capacity and the adsorption rate of the gel beads. The adsorption capacity increased from 308.7 to 466.0 mg/g and the adsorption equilibrium time was shortened from 300 min to 120 min. The modified­sodium alginate gel bead possessed the advantages of short adsorption time, high adsorption efficiency and large adsorption capacity, which could be regarded as a potential adsorbent for uranium. Moreover, the uranium removal ability on the modified gel beads was mainly attributed to the Coulomb force between PO43- and uranium and the complexation between uranium and amidoxime groups. In summary, this work would provide a new idea for the modification and application of sodium alginate-based materials.

Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study.

BACKGROUND: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. METHODS: A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. RESULTS: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. CONCLUSION: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.

Mechanistic insight into biotransformation of novel triazine-based flame retardant 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione by human cytochrome P450s.

The escalating focus on the environmental occurrence and toxicology of emerging pollutants underscores the imperative need for a profound exploration of their metabolic transformations mediated by human CYP450 enzymes. Such investigations have the potential to unravel the intricate metabolite profiles, substantially altering the toxicological outcomes. In this study, we integrated the computational simulations with in vitro metabolism experiments to investigate the metabolic activity and mechanism of an emerging pollutant, 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione (TDBP-TAZTO), catalyzed by human CYP450s. The results highlight the important contributions of CYP2E1, 3A4 and 2C9 to the biotransformation of TDBP-TAZTO, leading to the identification of four distinct metabolites. The effective binding conformations governing biotransformation reactions of TDBP-TAZTO within active CYP450s are unveiled. Structural instability of primary hydroxyTDBP-TAZTO products suggests three potential outcomes: (1) generation of an alcohol metabolite through successive debromination and reduction reactions, (2) formation of a dihydroxylated metabolite through secondary hydroxylation by CYP450, and (3) production of an N-dealkylated metabolite via decomposition and isomerization reactions in the aqueous environment. The formation of a desaturated debrominated metabolite may arise from H-abstraction and barrier-free Br release during the primary oxidation, potentially competing with the generation of hydroxyTDBP-TAZTO. These findings provide detailed mechanistic insight into TDBP-TAZTO biotransformation by CYP450s, which can enrich our understanding of the metabolic fate and associated health risk of this chemical.

Nursing management of cognitive dysfunction in adults with brain injury: Summary of best evidence-practiced strategies.

OBJECTIVE: To summarize the best evidence-based strategies for the management of cognitive dysfunction in patients with brain injury and to provide a reference for clinical nursing practice. DESIGN: Review. METHODS: The review was presented using PRISMA guidelines. A systematic search of evidence on the management of cognitive dysfunction in patients with brain injury was conducted in computerized decision systems, guideline websites, professional association websites and comprehensive databases from the date of creation to 21 June 2023. The types of evidence included were clinical decision making, guidelines, evidence summaries, best practices, recommended practices, expert consensus, systematic reviews and meta-analyses. Two researchers trained in evidence-based methodological systems independently evaluated the quality of the literature and extracted, integrated and graded the evidence for inclusion. RESULTS: A total of 20 articles were selected, including nine guidelines, three expert consensus articles, one clinical practice article and seven systematic reviews, and the overall quality of the literature was high. Thirty pieces of evidence were summarized in seven areas: assessment, multidisciplinary team, rehabilitation program, cognitive intervention, exercise intervention, music intervention and medication management. CONCLUSIONS: This study summarizes the latest evidence on the management of cognitive dysfunction in the care of adults with brain injury and provides a reference for clinical nursing practice. The best evidence should be selected for localized and individualized application in clinical work, and the best evidence should be continuously updated to standardize nursing practice. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Patients with cognitive impairment after brain injury often suffer from memory loss, attention deficit and disorientation and are unable to have a normal life and experience much enjoyment, which seriously affects their physical and mental health and creates a great burden of care for their families and society. Best evidence-based strategies for the nursing management of cognitive impairment in brain injury are essential for standardizing clinical nursing practice and providing timely, professional, systematic and comprehensive nursing interventions for patients. REPORTING METHOD: This review is reported following the PRISMA 2020 statement guidelines, as applicable, to enhance transparency in reporting the evidence synthesis. TRIAL AND PROTOCOL REGISTRATION: This study has been registered with the Fudan University Centre for Evidence-based Nursing, a JBI Centre of Excellence under registration number ES20232566, http://ebn.nursing.fudan.edu.cn/myRegisterList. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Structural characterization, chain conformation and immunomodulatory activity of a heteropolysaccharide from Inonotus hispidus.

A new polysaccharide (IHP-1aa) was isolated from the fruiting body of Inonotus hispidus by hot water extraction, ethanol precipitation and column chromatography. The molecular weight of IHP-1aa was 26.9 kDa. Structural analysis showed that IHP-1aa consisted of glucose (Glc), galactose (Gal), fucose (Fuc), mannose (Man) and contained a certain amount of 3-O-methylgalactose (3-O-Me-Gal). The structure was mainly composed of →6)-α/ß-D-Glcp-(1→, →6)-α-D-Galp-(1→, →6)-(3-O-Me)-α-D-Galp-(1→, →6)-α-D-Manp-(1 â†’ and →2, 6)-α-D-Galp-(1 â†’ as the main chain. Branched at O-2 with single ß-L-Fucp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-α-D-Glcp-(1 â†’ as major the side chain. The results of SEM, XRD and AFM combined with Congo red indicated that IHP-1aa may be amorphous granular chain conformation. In addition, IHP-1aa stimulated macrophage function and improved phagocytic ability of RAW264.7, as well as promoted the secretion of NO, TNF-α and IL-6. IHP-1aa, a 3-O-methylgalactose-containing heteropolysaccharide, was isolated for the first time from the I. hispidus, which may be used as a potential immunomodulator in functional foods.

Stigmasterol Depresses the Proliferation and Facilitates the Apoptosis of Fibroblast-Like Synoviocytes via the PI3K/AKT Signaling Pathway in Collagen-Induced Arthritis Rats.

Rheumatoid arthritis (RA) is a chronic disease characterized by persistent synovitis and angiogenesis. Its clinical manifestations are synovial hyperplasia and progressive destruction of bone and cartilage, eventually leading to joint deformation and even disability. The healing effect of monomer stigmasterol, the main active ingredient of the Jinwujiangu recipe the Chinese Herbal Compound, on RA has been confirmed in several studies. Fibroblast-like synoviocytes (FLS) are related to the occurrence and development of RA. This study aims to investigate the effects of stigmasterol on FLS cell proliferation and apoptosis, as well as its impact on FLS cell cycle proteins and key genes in the Phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway, providing insights into the development of stigmasterol as an alternative therapeutic drug for RA. We administered 20 g/kg stigmasterol to rats continuously for 5 d to obtain stigmasterol-containing serum, and established rat models of osteoarthritis induced by ossein to obtain FLS. To explore the effects of stigmasterol on the viability, migration, proliferation and apoptosis of collagen-induced arthritis (CIA)-FLS cells, we selected 0% (control), 5% (low concentration), 10% (medium concentration) and 20% (high concentration) drug-containing serum to intervene cells and conducted Cell Counting Kit-8 (CCK-8), Transwell, 5-ethynyl-2' -deoxyuridine (EdU) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) experiments, respectively. The results showed that compared with the control group, low, medium, and high serum significantly inhibited the activity, migration, and proliferation of FLS cells, and promoted their apoptosis, and high serum had the best effect. In addition, we investigated the mechanism of stigmasterol inhibiting FLS proliferation and promoting its apoptosis by qPCR, Western blot, and immunofluorescence assays. The results showed that stigmasterol significantly inhibited the expression of Cyclin D1, cyclin-dependent kinase 4 (CDK4), and Retinoblastoma (Rb), and decreased the expression of key genes kinase insert domain-containing receptor (KDR), PI3K, AKT, phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in the KDR-mediated PI3K/AKT signaling pathway, thus inhibiting the proliferation of FLS and promoting the apoptosis of FLS. It was suggested that stigmasterol may be a potential alternative drug for RA treatment.

Exploring factors influencing visual disability in the elderly population of China: A nested case-control investigation.

Background: Factors influencing visual disability among the elderly in China remain largely unclear. We sought to determine the prevalence and identify risk factors for visual disability among older adults in China. Methods: We employed a nested case-control study design, utilising data from the China Health and Retirement Longitudinal Study (CHARLS) collected between 2011 and 2018. Cases and controls were matched by a ratio of 1:3 by age and sex. Conditional logistic regression identified factors associated with visual disability. Results: Prior to data matching, the cohort comprised 4729 complete samples, with 785 (16.6%) newly diagnosed cases of visual disability during the follow-up period. Following matching, 3132 subjects remained, with 783 in the case group and 2349 in the control group. Factors associated with the occurrence of visual disability in the elderly included per capita family income (odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.97-0.99), adequate sleep (OR = 0.75; 95% CI = 0.63-0.90), cognitive function (OR = 0.98; 95% CI = 0.96-0.99), heart disease (OR = 1.51; 95% CI = 1.20-1.89), kidney disease (OR = 1.45; 95% CI = 1.05-1.98), depression (OR = 1.04; 95% CI = 1.03-1.06), history of falls (OR = 1.34; 95% CI = 1.09-1.65), and cataracts (OR = 2.71; 95% CI = 1.81-4.07). Conclusions: Visual disability among the elderly in China remains a major concern. Per capita family income, adequate sleep, and cognitive function are protective factors, while heart disease, kidney disease, depression, history of falls, and cataracts are risk factors. Future efforts in preventing and treating visual disability in the elderly should target these high-risk factors and provide early interventions to this population.

[Establishment of risk prediction nomograph model for sepsis related acute respiratory distress syndrome].

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO2/FiO2), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO2/FiO2, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS: Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.

Rapid identification of α-glucosidase inhibitors from Poria using spectrum-effect, component knock-out, and molecular docking technique.

Instruction: Poria (Poria cocos) is known for its health-promoting effects and is consumed as a food due to its potential hypoglycemic activity. However, the composition of Poria is complex, and the bioactive compounds that inhibit α-glucosidase are not clear. Methods: In this study, the fingerprint of the Poria methanol extract characterized by high-performance liquid chromatography (HPLC) and the model of the corresponding spectrum-effect relationship for α-glucosidase was first established to screen the active compounds from Poria. Then, the predicted bioactive compounds were knocked out and identified using mass spectrometry. Finally, the potential binding sites and main bonds of each compound with α-glucosidase were studied using molecular docking. Results: The results have shown that at least 11 compounds from Poria could inhibit α-glucosidase effectively. Moreover, eight individual compounds, i.e., poricoic acid B (P8), dehydrotumulosic acid (P9), poricoic acid A (P10), polyporenic acid C (P12), 3- epidehydrotumulosic acid (P13), dehydropachymic acid (P14), 3-O-acetyl-16α-hydroxytrametenolic acid (P21), and pachymic acid (P22), were identified, and they exhibited effective inhibitory activity against α-glucosidase. Discussion: The possible inhibitory mechanism of them based on molecular docking showed that the binding sites are mainly found in the rings A, B, and C of these compounds, and C-3 C-16 and side chains of C-17, with the phenylalanine, arginine, tyrosine, histidine, and valine of α-glucosidase. The main interactions among them might be alkyl and hydrogen bonds, which theoretically verified the inhibitory activity of these compounds on α-glucosidase. The achievements of this study provided useful references for discovering bioactive compounds with hypoglycemic effects from Poria.

Enantioselective metabolism of novel chiral insecticide Paichongding by human cytochrome P450 3A4: A computational insight.

As a novel chiral neonicotinoid insecticide, Paichongding (IPP) has been widely applied in agriculture due to its excellent insecticidal activity. However, the enantioselective metabolism of IPP stereoisomers (5R7R-IPP, 5S7S-IPP, 5R7S-IPP, and 5S7R-IPP) mediated by enzymes in non-target organisms, especially the cytochrome P450s (CYPs), remains unknown. To address this knowledge gap, we developed an integrated computational framework to elucidate the binding interactions and enantioselective metabolism of IPP stereoisomers in human CYP3A4. The results reveal that 5R7R-IPP shows much stronger binding affinity to CYP3A4 than 5S7S-IPP, while enantiomers 5R7S-IPP and 5S7R-IPP have no essential difference in their binding potential, owing to their specific interactions with key CYP3A4 residues. Although enantiomers 5R7R-IPP and 5S7S-IPP feature distinct binding modes resulting from the chiral differences, their transformation activities are slightly different, with C5 and C13 being the primary metabolic sites, respectively. In contrast, CYP3A4 preferably metabolizes 5R7S-IPP over 5S7R-IPP. The metabolism of epimers 5R7R-IPP and 5R7S-IPP share C5-hydroxylation routes due to the conserved 5R-conformaitons, but differ with the transformation routes at C11/C13 and C3 sites. The 7R-chirality of 5S7R-IPP significantly reduces the metabolic potency compared to 5S7S-IPP. CYP3A4-catalyzed hydroxylation and desaturation of IPP stereoisomers generate various chiral metabolites, with C5- and C13-hydroxyIPPs further transforming into depropylated products. Furthermore, the toxicity assessment reveals that IPP, along with the majority of its hydroxylated, desaturated, and depropylated metabolites, can potentially induce adverse effects on human health, specifically hepatotoxicity, respiratory toxicity, and carcinogenicity. This study provides valuable insights into the enantioselective fate of chiral IPP metabolism by CYP3A4, and the identified metabolites can serve as potential biomarkers for monitoring IPP exposure and associated health risk in human body.

Characteristic fragmentation of polyunsaturated fatty acids with allylic vicinal diols in positive-ion LC/ESI-MS/MS.

A characteristic fragmentation was observed for PUFAs that contain allylic vicinal diol groups (resolvin D1, D2, D4, E3, lipoxin A4, B4, and maresin 2), which were derivatized with N,N-dimethylethylenediamine (DMED), in positive-ion ESI-MS/MS. The findings indicate that when these compounds contain an allylic hydroxyl group that is located distal to the terminal DMED moiety in the case of resolvin D1, D4, and lipoxin A4, an aldehyde (-CH=O) is predominately formed, which arises from the breakdown in between vicinal diols, whereas, in the case of an allylic hydroxyl group that is located proximal to the DMED moiety, as in resolvin D2, E3, lipoxin B4, and maresin 2, an allylic carbene (-CH=CH-CH:) is formed. These specific fragmentations could be used as diagnostic ions for characterizing the above seven PUFAs. As a result, it was possible to detect resolvin D1, D2, E3, lipoxin A4, and B4 in sera (20 µl) obtained from healthy volunteers by multiple-reaction monitoring using LC/ESI-MS/MS.

IFNγ Transcribed by IRF1 in CD4+ Effector Memory T Cells Promotes Senescence-Associated Pulmonary Fibrosis.

Physiologically aged lungs are prone to senescence-associated pulmonary diseases (SAPD). This study aimed to determine the mechanism and subtype of aged T cells affecting alveolar type II epithelial (AT2) cells, which promote the pathogenesis of senescence-associated pulmonary fibrosis (SAPF). Cell proportions, the relationship between SAPD and T cells, and the aging- and senescence-associated secretory phenotype (SASP) of T cells between young and aged mice were analyzed using lung single-cell transcriptomics. SAPD was monitored by markers of AT2 cells and found to be induced by T cells. Furthermore, IFNγ signaling pathways were activated and cell senescence, SASP, and T cell activation were shown in aged lungs. Physiological aging led to pulmonary dysfunction and TGF-ß1/IL-11/MEK/ERK (TIME) signaling-mediated SAPF, which was induced by senescence and SASP of aged T cells. Especially, IFNγ was produced by the accumulated CD4+ effector memory T (TEM) cells in the aged lung. This study also found that physiological aging increased pulmonary CD4+ TEM cells, IFNγ was produced mainly by CD4+ TEM cells, and pulmonary cells had increased responsiveness to IFNγ signaling. Specific regulon activity was increased in T cell subclusters. IFNγ transcriptionally regulated by IRF1 in CD4+ TEM cells promoted the epithelial-to-mesenchymal transition by activating TIME signaling and cell senescence of AT2 cells with aging. Accumulated IRF1+CD4+ TEM produced IFNγ in lung with aging and anti-IRF1 primary antibody treatment inhibited the expression of IFNγ. Aging might drive T cell differentiation toward helper T cells with developmental trajectories and enhance cell interactions of pulmonary T cells with other surrounding cells. Thus, IFNγ transcribed by IRF1 in CD4+ effector memory T cells promotes SAPF. IFNγ produced by CD4+ TEM cells in physiologically aged lungs could be a therapeutic target for preventing SAPF.

Bioinspired Carbon Superstructures for Efficient Electromagnetic Shielding.

Biologically inspired superstructural materials exhibit wide application prospects in many fields, in terms of mitigating increasingly serious electromagnetic (EM) pollution in the civil field. Here, we successfully obtain bamboo slices with uniform pore size distribution through the advanced bamboo transverse splitting technology developed by our group previously and prepare large-scale honeycomb-like carbon-based tubular array (CTA) structures with a controllable pore size, graphitization degree, and selectable conductivity property. Based on the simulation and experimental results, the EM shielding performance of CTAs is proven to be sensitive to the microchannel aperture size and the EM energy incident angle, which is attributed to the difference in the propagation rate of induced electrons in different directions. Among the candidates, CTA-middle-1500 exhibits the best shielding performance against incident EM energy with average SE/ρ values of 123.7 and 144.5 dB cm3 g-1 for perpendicular and parallel directions, respectively, showing its application potential as a lightweight and efficient EM shielding material. The predicted optimal incident angle for CTA-middle-1500 against EM energy radiation is 15°, with the largest RCS reduction value of 26.1 dB m2. The excellent EM shielding performance is attributed to the good reflection capacity involved with the high conductivities of the CTAs.

Bmi-1 Overexpression Improves Sarcopenia Induced by 1,25(OH)2 D3 Deficiency and Downregulates GATA4-Dependent Rela Transcription.

Sarcopenia increases with age, and an underlying mechanism needs to be determined to help with designing more effective treatments. This study aimed to determine whether 1,25(OH)2 D3 deficiency could cause cellular senescence and a senescence-associated secretory phenotype (SASP) in skeletal muscle cells to induce sarcopenia, whether GATA4 could be upregulated by 1,25(OH)2 D3 deficiency to promote SASP, and whether Bmi-1 reduces the expression of GATA4 and GATA4-dependent SASP induced by 1,25(OH)2 D3 deficiency in skeletal muscle cells. Bioinformatics analyses with RNA sequencing data in skeletal muscle from physiologically aged and young mice were conducted. Skeletal muscles from 2-month-old young and 2-year-old physiologically aged wild-type (WT) mice and 8-week-old WT, Bmi-1 mesenchymal transgene (Bmi-1Tg ), Cyp27b1 homozygous (Cyp27b1-/- ), and Bmi-1Tg Cyp27b1-/- mice were observed for grip strength, cell senescence, DNA damage, and NF-κB-mediated SASP signaling of skeletal muscle. We found that muscle-derived Bmi-1 and vitamin D receptor (VDR) decreased with physiological aging, and DNA damage and GATA4-dependent SASP activation led to sarcopenia. Furthermore, 1,25(OH)2 D3 deficiency promoted DNA damage-induced GATA4 accumulation in muscles. GATA4 upregulated Rela at the region from -1448 to -1412 bp at the transcriptional level to cause NF-κB-dependent SASP for aggravating cell senescence and muscular dysfunction and sarcopenia. Bmi-1 overexpression promoted the ubiquitination and degradation of GATA4 by binding RING1B, which prevented cell senescence, SASP, and dysfunctional muscle, and improved sarcopenia induced by 1,25(OH)2 D3 deficiency. Thus, Bmi-1 overexpression improves sarcopenia induced by 1,25(OH)2 D3 deficiency, downregulates GATA4-dependent Rela transcription, and sequentially inhibits GATA4-dependent SASP in muscle cells. Therefore, Bmi-1 overexpression could be used for translational gene therapy for the ubiquitination of GATA4 and prevention of sarcopenia. © 2023 American Society for Bone and Mineral Research (ASBMR).

Thyroid hormone activities of neutral and anionic hydroxylated polybrominated diphenyl ethers to thyroid receptor ß: A molecular dynamics study.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been identified as the strong endocrine disrupting chemicals to humans, which show structural similarity with endogenous thyroid hormones (THs) and thus disrupt the functioning of THs through competitive binding with TH receptors (TRs). Although previous studies have reported the hormone activities of some OH-PBDEs on TH receptor ß (TRß), the interaction mechanism remains unclear. Furthermore, hydroxyl dissociation of OH-PBDEs may alter their TR disrupting activities, which has not yet been investigated in depth. In this work, we selected 18 OH-PBDEs with neutral and anionic forms and performed molecular dynamics (MD) simulations to estimate their binding interactions with the ligand binding domain (LBD) of TRß. The results demonstrate that most of OH-PBDEs have stronger binding affinities to TRß-LBD than their anionic counterparts, and the hydroxyl dissociation of ligands differentiate the major driving force for their binding. More Br atoms in OH-PBDEs can result in stronger binding potential with TRß-LBD. Moreover, 5 hydrophobic residues, including Met313, Leu330, Ile276, Leu346, and Phe272, are identified to have important contributions to bind OH-PBDEs. These results clarify the binding mechanism of OH(O-)-PBDEs to TRß-LBD at the molecular level, which can provide a solid theoretical basis for accurate assessment of TH disrupting effects of these chemicals.

Usability evaluation of mHealth apps for elderly individuals: a scoping review.

BACKGROUND: Usability is a key factor affecting the acceptance of mobile health applications (mHealth apps) for elderly individuals, but traditional usability evaluation methods may not be suitable for use in this population because of aging barriers. The objectives of this study were to identify, explore, and summarize the current state of the literature on the usability evaluation of mHealth apps for older adults and to incorporate these methods into the appropriate evaluation stage. METHODS: Electronic searches were conducted in 10 databases. Inclusion criteria were articles focused on the usability evaluation of mHealth apps designed for older adults. The included studies were classified according to the mHealth app usability evaluation framework, and the suitability of evaluation methods for use among the elderly was analyzed. RESULTS: Ninety-six articles met the inclusion criteria. Research activity increased steeply after 2013 (n = 92). Satisfaction (n = 74) and learnability (n = 60) were the most frequently evaluated critical measures, while memorability (n = 13) was the least evaluated. The ratios of satisfaction, learnability, operability, and understandability measures were significantly related to the different stages of evaluation (P < 0.05). The methods used for usability evaluation were questionnaire (n = 68), interview (n = 36), concurrent thinking aloud (n = 25), performance metrics (n = 25), behavioral observation log (n = 14), screen recording (n = 3), eye tracking (n = 1), retrospective thinking aloud (n = 1), and feedback log (n = 1). Thirty-two studies developed their own evaluation tool to assess unique design features for elderly individuals. CONCLUSION: In the past five years, the number of studies in the field of usability evaluation of mHealth apps for the elderly has increased rapidly. The mHealth apps are often used as an auxiliary means of self-management to help the elderly manage their wellness and disease. According to the three stages of the mHealth app usability evaluation framework, the critical measures and evaluation methods are inconsistent. Future research should focus on selecting specific critical measures relevant to aging characteristics and adapting usability evaluation methods to elderly individuals by improving traditional tools, introducing automated evaluation tools and optimizing evaluation processes.