Effectiveness of inactivated COVID-19 vaccines in preventing COVID-19-related hospitalization during the Omicron BF.7-predominant epidemic wave in Beijing, China: a cohort study.

BACKGROUND: To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. METHODS: We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. RESULTS: 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: - 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. CONCLUSION: Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.

Efficacy of sexual stimulation in the treatment of distal ureteral stones: A meta-analysis.

Introduction: This study aimed to compare the clinical efficacy of sexual stimulation with that of placebo in the treatment of distal ureteral stones. Methods: We searched PubMed, Web of Science, Cochrane Library, and Google Scholar from January 1, 2000 to December 31, 2022 for studies comparing the efficacy of sexual stimulus with that of placebo for the treatment of distal ureteral stones. RevMan 5.3 software was used to pool the data. The study protocol was registered on PROSPERO (Registration Number: CRD42023432408). Results: A total of six randomized controlled trials comprising 535 cases of distal ureteral stones were included in this study. Among these, 273 cases were associated with sexual intercourse or masturbation 3-4 times a week, while 262 cases only received symptomatic treatment. The pooled results showed that the 2-week [risk ratios (RR) = 1.77, 95 % confidence interval (CI): 1.34, 2.33] and 4-week [RR = 1.48, 95 % CI: 1.29, 1.69] ureteral stone expulsion rates of the sexually stimulated group were significantly higher than those of the placebo group (ps < 0.01). Additionally, sexual stimulation was associated with a shorter ureteral stone expulsion time [weighted mean differences (WMD) = -3.74, 95 % CI: -6.27, -1.22, p < 0.01] and a decreased prevalence of renal colic attacks [WMD = -0.61, 95 % CI: -1.01, -0.22, p < 0.01] compared with those of the placebo group. Conclusion: Appropriate sexual stimulation can enhance the spontaneous expulsion of distal ureteral stones in patients presenting with tolerable pain.

Nogo-B inhibition facilitates cholesterol metabolism to reduce hypercholesterolemia.

The strategy of lowering cholesterol levels by promoting cholesterol excretion is still lacking, and few molecular targets act on multiple cholesterol metabolic processes. In this study, we find that Nogo-B deficiency/inhibition simultaneously promotes hepatic uptake of cholesterol and cholesterol excretion. Nogo-B deficiency decreases cholesterol levels by activating ATP-binding cassette transporters (ABCs), apolipoprotein E (ApoE), and low-density lipoprotein receptor (LDLR) expression. We discover that Nogo-B interacts with liver X receptor α (LXRα), and Nogo-B deficiency inhibits ubiquitination degradation of LXRα, thereby enhancing its function on cholesterol excretion. Decreased cellular cholesterol levels further activate SREBP2 and LDLR expression, thereby promoting hepatic uptake of cholesterol. Nogo-B inhibition decreases atherosclerotic plaques and cholesterol levels in mice, and Nogo-B levels are correlated to cholesterol levels in human plasma. In this study, Nogo-B deficiency/inhibition not only promotes hepatic uptake of blood cholesterol but also facilitates cholesterol excretion. This study reports a strategy to lower cholesterol levels by inhibiting Nogo-B expression to promote hepatic cholesterol uptake and cholesterol excretion.

iPLA2ß regulates the dual effects of arachidonic acid in thyroid cancer.

BACKGROUND: Abnormal arachidonic acid metabolism in the tumor microenvironment is closely related to cancer progression; however, thyroid cancer was rarely researched. METHODS: Through lipidomic analysis, we disclosed that dysregulated arachidonic acid metabolism plays dual effects on thyroid cancer. The promoting role of arachidonic acid in the progression of thyroid cancer cells was evaluated utilizing cell viability (CCK-8 assay) and transwell invasion assays, confirmed by corresponding inhibitors. Lipid peroxidation and the use of various cell death inhibitors confirmed that arachidonic acid confers vulnerability to ferroptosis in thyroid cancer. The roles of arachidonic acid and ferroptosis inducer in thyroid cancer were assessed in a xenograft mouse model. RESULTS: On one hand, arachidonic acid promotes the progression of thyroid cancer through the cyclooxygenase/prostaglandin pathway; on another hand, arachidonic acid confers vulnerability to ferroptosis through lipoxygenases. Moreover, iPLA2ß drives converse roles of arachidonic acid between cancer-progression and ferroptosis vulnerability through releasing free arachidonic acid from the cell membrane. Finally, we confirmed high arachidonic acid diet promotes the development of thyroid cancer in vivo, whereas ferroptosis inducer sulfasalazine dramatically reduced tumor growth of mice with feeding arachidonic acid. CONCLUSIONS: Our research demonstrated the roles of iPLA2ß in conversing dual effects of arachidonic acid in thyroid cancer and provides ferroptosis inducer as a potential therapeutic strategy.

Unveiling hope: how social support reciprocity shields against the shadows of intimate partner violence and suicidal ideation in rural Chinese older adults.

The paper titled "A systematic review of psychosocial protective factors against suicide and suicidality among older adults" by Ki and colleagues is a thought-provoking review that emphasizes the importance of improving protective factors for the development of suicide prevention and intervention in older adults, rather than just focusing on risk factors. Since the coronavirus disease 2019 (COVID-19) pandemic, media coverage of mental health and suicide has gained widespread attention. Suicide may become a more pressing issue due to the enormous economic and social toll of the spreading epidemic. Therefore, this systematic review is relevant in preventing suicide among older adults in the "post-pandemic" periods of COVID-19.In this study, the authors highlight the importance of examining the moderating or mediating role of protective factors in suicide, due to the fact that suicide prevention must take into account a variety of factors simultaneously. More importantly, most studies focused primarily on received support among interpersonal protective factors, neglecting the role of support given to others, which might be more beneficial for older adults' well-being. The thought that ensues is what role will social support reciprocity play in specific risk factors and suicidal behavior.

Joint Association of Combined Healthy Lifestyle Factors and Hearing Loss with Cognitive Impairment in China.

BACKGROUND: Hearing loss and lifestyle factors have been associated with cognitive impairment. We aimed to explore the joint association of combined healthy lifestyle factors and hearing loss with cognitive impairment, which has been scarcely studied. METHODS: This baseline study used data from the CHOICE-Cohort study (Chinese Hearing Solution for Improvement of Cognition in Elders). Hearing loss was assessed by the better-ear pure-tone average (BPTA). A composite healthy lifestyle score was built based on never smoking, never drinking, regular physical activity, and balanced diet. Cognitive impairment was diagnosed by the Mini-Mental State Examination (MMSE) score of less than 24. RESULTS: We included 17057 participants aged 60 years or older in China (mean age 69.8 [SD 6.2] years, 55.7% female). Among the participants, 48.3% (n=8234) had mild hearing loss, and 25.8% (n=4395) had moderate or greater hearing loss. The proportion of participants with healthy lifestyle scores of 0-1, 2, 3, and 4 was 14.9% (n=2539), 29.3% (n=5000), 37.4% (n=6386), and 18.4% (n=3132), respectively. 29.6% (n=5057) participants had cognitive impairment. When compared to those with normal hearing and healthy lifestyle (scores of 3-4), participants with hearing loss plus unhealthy lifestyle (scores of 0-2) exhibited approximately twofold increased risk of cognitive impairment (OR=1.92, 95% CI 1.70-2.18). Conversely, the risk was greatly attenuated by adherence to healthy lifestyle in individuals with hearing loss (OR=1.57, 95% CI 1.40-1.76). CONCLUSIONS: Our findings demonstrated adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of cognitive impairment among participants with hearing loss.

Effects of vitamin D supplementation on muscle strength in middle-aged and elderly individuals: a retrospective, propensity score-matched study.

Introduction: The aim of this study is to investigate the impact of vitamin D supplementation on the muscle strength of the elderly. Methods: This retrospective, propensity score-matched study included 160 middle-aged and elderly individuals from a community in Beijing, China. The control group (n=110) received health education and lifestyle guidance, while the intervention group (n=50) was given oral vitamin D supplementation in addition to health education and lifestyle guidance. All participants underwent laboratory tests, muscle function, and physical function at baseline and follow-up. Results: In the propensity score-matched cohort of 41 patients per group, the levels of serum calcium and 25-hydroxyvitamin D in both groups were improved significantly by the end of the study (p<0.05), with the intervention group showing a more significant improvement. The muscle strength of the left lower limb in the intervention group significantly increased after the intervention (p<0.05). The results also showed that the grip strength and pinch strength of the patients in both groups increased after the intervention, and the difference between the two groups was statistically significant (p<0.05). Discussion: The findings of this study suggest that vitamin D supplementation, in conjunction with lifestyle guidance and health education, is beneficial for enhancing the upper and lower limb strength of patients.

Effect of placental mesenchymal stem cells on promoting the healing of chronic burn wounds.

The treatment of chronic burn wounds is difficult in clinical practice. The ideal therapy is required to be continuously explored. Mesenchymal stem cells revolutionize the treatment of many diseases. The placental mesenchymal stem cells (PMSCs) have the characteristics of easy access, strong proliferation ability and multi-directional differentiation potential. The aim of this study was to investigate the potential of PMSCs in chronic burn wound healing. In this study, species of bacteria of 317 patients with chronic burn wounds have been analyzed. Samples of chronic burn wound fluid were collected from representative patients and then co-cultured with cells. In vitro studies showed that chronic burn wound fluid inhibited the proliferation of human keratinocytes and fibroblasts, while PMSCs can counteract the effects of burn wound fluid on inhibiting the proliferation and migration of human keratinocytes and fibroblasts. In addition, in vivo studies showed that a rat chronic burn wound model was successfully created. The expression of MMP-2, MMP-9, MDA, IL-6 and TNF-α in chronic burn wounds was significantly higher than that in acute burn wounds. Finally, the rat chronic burn wound model was used to verify that placental mesenchymal stem cell transplantation increased the wound healing rate, decreased the wound healing time, and promoted wound healing by increasing the thickness of epidermis and promoting the expression of P63 and CK10. The findings provide support for the hypothesis that PMSCs promote the repair of chronic burn wounds and key scientific data for the application of PMSCs as a new method for treating chronic burn wounds.

Impact of web-based positive psychological intervention on emotions, psychological capital, and quality of life in gastric cancer patients on chemotherapy.

BACKGROUND: Gastric cancer is a malignant digestive tract tumor that originates from the epithelium of the gastric mucosa and occurs in the gastric antrum, particularly in the lower curvature of the stomach. AIM: To evaluate the impact of a positive web-based psychological intervention on emotions, psychological capital, and quality of survival in gastric cancer patients on chemotherapy. METHODS: From January 2020 to October 2023, 121 cases of gastric cancer patients on chemotherapy admitted to our hospital were collected and divided into a control group (n = 60) and an observation group (n = 61) according to the admission order. They were given either conventional nursing care alone and conventional nursing care combined with web-based positive psychological interventions, respectively. The two groups were compared in terms of negative emotions, psychological capital, degree of cancer-caused fatigue, and quality of survival. RESULTS: After intervention, the number of patients in the observation group who had negative feelings toward chemotherapy treatment was significantly lower than that of the control group (P < 0.05); the Positive Psychological Capital Questionnaire score was considerably higher than that of the control group (P < 0.05); the degree of cancer-caused fatigue was significantly lower than that of the control group (P < 0.05); and the Quality of Life Scale for Cancer Patients (QLQ-30) score was significantly higher than that of the control group (P < 0.05). CONCLUSION: Implementing a web-based positive psychological intervention for gastric cancer chemotherapy patients can effectively improve negative emotions, enhance psychological capital, and improve the quality of survival.

TRIM59 is required for mouse GC-1 cell maintenance through modulating the ubiquitination of AXIN1.

Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate ß-catenin signaling. Furthermore, activation of ß-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

Mitochondrial STED Imaging and Membrane Potential Monitoring with a Cationic Molecular Probe.

Mitochondria are essential organelles that not only undergo dynamic morphological changes but also exhibit functional activities such as mitochondrial membrane potential (MMP). While super-resolution techniques such as stimulated emission depletion (STED) nanoscopy can visualize the ultrastructure of mitochondria and the MMP probe can monitor mitochondria function, few dyes meet both demands. Here, a small molecule (MitoPDI-90) based on perylene diimide with cationic groups is reported and used for mitochondrial STED imaging and MMP indication. Characterized by excellent photostability, biocompatibility, and high quantum yield, MitoPDI-90 exhibits STED imaging compatibility, facilitating visualization of mitochondrial cristae and time-lapse imaging of highly dynamic mitochondria in living cells. Besides, MitoPDI-90 targets the mitochondria through electrical potential, also enabling live-cell MMP monitoring. MitoPDI-90 allows for super-resolution visualization and time-lapse imaging of mitochondria, and more importantly, indication of changes in MMP, providing insight into the functional activity of live-cell mitochondria.

Expression profiling of Spodoptera exigua (Lepidoptera: Noctuidae) microRNAs and microRNA core genes by Bacillus thuringiensis GS57 infection.

MicroRNAs (miRNAs) are endogenous, non-coding RNAs, which are functional in a variety of biological processes through post-transcriptional regulation of gene expression. However, the role of miRNAs in the interaction between Bacillus thuringiensis and insects remains unclear. In this study, small RNA libraries were constructed for B. thuringiensis-infected (Bt) and uninfected (CK) Spodoptera exigua larvae (treated with double-distilled water) using Illumina sequencing. Utilising the miRDeep2 and Randfold, a total of 233 known and 726 novel miRNAs were identified, among which 16 up-regulated and 34 down-regulated differentially expressed (DE) miRNAs were identified compared to the CK. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that potential target genes of DE miRNAs were associated with ABC transporters, fatty acid metabolism and MAPK signalling pathway which are related to the development, reproduction and immunity. Moreover, two miRNA core genes, SeDicer1 and SeAgo1 were identified. The phylogenetic tree showed that lepidopteran Dicer1 clustered into one branch, with SeDicer1 in the position closest to Spodoptera litura Dicer1. A similar phylogenetic relationship was observed in the Ago1 protein. Expression of SeDicer1 increased at 72 h post infection (hpi) with B. thuringiensis; however, expression of SeDicer1 and SeAgo1 decreased at 96 hpi. The RNAi results showed that the knockdown of SeDicer1 directly caused the down-regulation of miRNAs and promoted the mortality of S. exigua infected by B. thuringiensis GS57. In conclusion, our study is crucial to understand the relationship between miRNAs and various biological processes caused by B. thuringiensis infection, and develop an integrated pest management strategy for S. exigua via miRNAs.

Neurological activation during verbal fluency task and resting-state functional connectivity abnormalities in obsessive-compulsive disorder: a functional near-infrared spectroscopy study.

Objective: This study aims to investigate the activation of frontotemporal functional brain areas in patients with Obsessive-Compulsive Disorder (OCD) during a Verbal Fluency Task (VFT), and to compare their brain functional connectivity in a resting state with that of healthy controls. The goal is to deepen our understanding of the neuropathological mechanisms underlying OCD. Methods: 32 patients with OCD and 32 controls matched for age, gender, handedness, and years of education participated in this study, they were divided into OCD group and healthy comtrol group. We conducted VFT task tests and 10-minute resting state tests on both groups by using functional Near-Infrared Spectroscopy (fNIRS). The VFT was utilized to assess the activation (beta values) and the integral and centroid values of the frontal and bilateral temporal lobes, including brain areas BA9 and 46 (dorsolateral prefrontal cortex), BA10 (frontal pole), BA45 (inferior frontal gyrus), BA21 (middle temporal gyrus), and BA22 (superior temporal gyrus). We evaluated the functional connectivity levels of these areas during the resting state. Differences in these measures between OCD patients and healthy controls were analyzed using two-sample independent t-tests and non-parametric Mann-Whitney U tests. Results: During VFT, OCD had smaller integral values(z=5.371, p<0.001; t=4.720, p<0.001), and larger centroid values(t=-2.281, p=0.026; z=-2.182, p=0.029) compared to healthy controls, along with a reduced number of activated channels detected by fNIRS. Additionally, activation values (ß) in various functional brain areas, including BA9, BA46, BA10, BA45, BA21, and BA22, were significantly lower in the OCD group (all p< 0.01). In the resting state, notable disparities in functional connectivity were observed between the inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC) in the OCD group, in comparison to the control group. Specifically, there was a significant increase in connectivity between the left IFG and right DLPFC, suggesting the presence of altered connectivity patterns in these areas. Conclusions: The study highlights significant disparities in neural activation and functional connectivity between OCD patients and healthy controls during VFT. Specifically, reduced activation was noted in the frontal and bilateral temporal lobes of OCD patients, alongside alterations in resting-state functional connectivity between the IFG and DLPFC. These findings contribute to our understanding of the neurobiological underpinnings of OCD and may guide future therapeutic strategies.

Ionic liquid-assisted synthesis of In2O3 nanoparticles for ppb-level NO2 sensing at low temperature.

Highly sensitive detection of nitric dioxide (NO2) has recently attracted much attention due to its harmful to the human health even at a low concentration of 0.1 parts per million (ppm). Herein, In2O3 nanoparticles (NPs) were prepared via a facile ionic liquid (IL) assisted solvothermal method with subsequent calcination and then were analyzed through the characterization of X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption techniques. Morphological characterization demonstrated that the resultant compounds were In2O3 NPs with a diameter ranging from 20 to 30 nm. The gas sensor based on the In2O3 NPs prepared with IL exhibited excellent NO2-sensing properties in terms of fast response/recovery speed (26.6/10.0 s), high response (310.0), good repeatability and long-term stability to 10 ppm NO2 gas at low working temperature of 92 °C. The gas-sensing mechanism of In2O3 NPs to NO2 was represented to the surface adsorption control model and the possibilities relating to the improved NO2 sensing performance of the In2O3 NPs synthesized with IL-assisted were also discussed in detail.

Temperature seasonality and soil phosphorus availability shape ginseng quality via regulating ginsenoside contents.

The accumulation of secondary metabolites in Panax ginseng Meyer (P. ginseng) exhibits significant geographical variation, normally due to environmental factors. The current study aimed at elucidating the key environmental factors modulating the accumulation of secondary metabolites in P. ginseng. Plant and the associated soil samples were collected from ten geographical locations within the latitudinalrange of 27.09°N - 42.39°N and longitudinal range of 99.28°E - 128.19°E. 12 secondary metabolites in P. ginseng toots were measured. And the correlation between secondary metabolites with a series of soil properties and 7 climatic factors were investigated through Pearson's correlation, mantel test, random forest and pathway analysis. The results revealed that climatic factors were stronger drivers of ginseng secondary metabolite profile than soil nutrients. Specifically, temperature seasonality (TS) and soil available phosphorus (AP) were the most effective environments to have significantly and positively influence on the secondary metabolites of ginseng. This findings contribute to identifying optimal cultivation areas for P. ginseng, and hopefully establishing methods for interfering/shaping microclimate for cultivating high-quality P. ginseng.

Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women.

BACKGROUND: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Purification, structural characterization, and bioactive properties of exopolysaccharides from Saccharomyces cerevisiae HD-01.

Exopolysaccharides (EPSs), which show excellent biological activities, like anti-tumor, immune regulation, and anti-oxidation activities, have gained widespread attention. In this study, an EPS-producing Saccharomyces cerevisiae HD-01 was identified based on 18S rDNA sequence analysis and an API 20C test. The purified HD-01 EPS was obtained by gel filtration chromatography. High-performance liquid chromatography (HPLC), gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR) revealed that it was a heteropolysaccharide composed of α-1 (38.3%), α-1, 2 (17.5%), α-1, 6 (14.8%)-linked mannose and α-1, 2, 3, 6 (24.3%), α-1 (3.3%), ß-1, 4 (1.8%)-linked glucose. Chemical composition and elemental analysis indicated the existence of sulfation modifications. A scanning electron microscope (SEM) and an atomic force microscope (AFM) revealed that it exhibited a flaky structure with thorn-like protrusions on the three-dimensional surface. X-ray diffraction (XRD) revealed that it was an amorphous non-crystalline substance. HD-01 EPS had great thermostability; probiotic properties; strong antioxidant properties to DPPH, ABTS, and hydroxyl; and good reducing power. The MTT, NO, and neutral red assays demonstrated that it had a great immunomodulatory effect on macrophages RAW264.7. All results suggested that the HD-01 EPS had the potential to be applied in the food and pharmaceutical fields.

The mediating effect of sleep quality on solid cooking fuel use and psychological distress among rural older adults: evidence from Shandong, China.

BACKGROUND: Exposure to indoor air pollution from solid cooking fuel use may increase mental disorders risk through pathways such as oroxidative stress, neuroinflammation, or cerebrovascular damage. However, few studies have explored the underlying mechanism between solid cooking fuel use and psychological distress. The present study aims to investigate the mediating role of sleep quality on the relationship between solid cooking fuel use and psychological distress among older adults in rural Shandong, China. METHODS: This study used the cross-sectional data from the second follow-up survey of the Shandong Rural Elderly Health Cohort (SREHC). A total of 3,240 rural older adults were included in the analysis. Logistic regression and the Karlson, Holm, and Breen (KHB) mediation analyses were performed to investigate the relationship between solid cooking fuel use and psychological distress, as well as the mediating role of sleep quality in this association. RESULTS: This study found that solid cooking fuel use was significantly and positively associated with psychological distress among older adults in rural Shandong, China (OR = 1.38, 95% CI: 1.12,1.70). Mediation analysis revealed that sleep quality mediated the association between solid cooking fuel use and psychological distress among older adults (ß = 0.06, P = 0.011). The mediation effect accounted for 16.18% of the total effect. CONCLUSIONS: Our study showed that solid cooking fuel use was associated with psychological distress among rural older adults, and sleep quality mediated this association. Interventions should focus on addressing cooking fuel types and poor sleep quality to reduce psychological distress. In the future, more aggressive environmental protection policies would be needed to lessen the adverse effects of indoor air pollution on the health of older adults in rural China.

Does contracting family doctor promote primary healthcare utilization among older adults? - evidence from a difference-in-differences analysis.

INTRODUCTION: In 2016, the Chinese government officially scaled up family doctor contracted services (FDCS) scheme to guide patients' health seeking behavior from tertiary hospitals to primary health facilities. METHODS: This study evaluated the overall gate-keeping effects of this scheme on healthcare utilization of rural residents by using a difference-in-differences (DiD) design. The analysis was based on Shandong Rural Elderly Health Cohort 2019 and 2020. Participants who contracted FDCS in second round and were not contracted with a family doctor in the first round were regarded as treatment group. In total, 310 respondents who have used medical care were incorporated for final study. RESULTS: Participants who contracted FDCS (treatment group) experienced a significant decline in the mean level of first-contact health-care facilities, decreasing from 2.204 to 1.981. In contrast, participants who did not contract FDCS (control group), showed an increasing trend in the mean level of first-contact health-care facilities, rising from 2.128 to 2.445. Our results showed that contracting FDCS is associated with approximately 0.54 extra lower mean level of first-contact health-care facilities (P = 0.03, 95% CI: -1.03 to 0.05), which suggests an approximately 24.5% reduction in the mean first-contact health-care facility level for participants compared with contracted FDCS than those who did not. CONCLUSIONS: The study suggested primary healthcare quality should be strengthened and restrictive first point of contact policy should be enacted to establish ordered healthcare seeking behavior among rural residents.

Cathepsin B modulates microglial migration and phagocytosis of amyloid ß in Alzheimer's disease through PI3K-Akt signaling.

The approval of anti-amyloid ß (Aß) monoclonal antibodies (lecanemab) for the treatment of patients with early preclinical stage of Alzheimer's disease (AD) by the Food and Drug Administration, suggests the reliability and importance of brain Aß clearance for AD therapy. Microglia are the main phagocytes that clear Aß in the brain, but the underlying regulatory mechanism is unclear. Here, we investigate the critical role of cathepsin B (CatB) in modulating microglial Aß clearance from mouse brain. Wild-type or CatB-/- mice were injected with Aß into the hippocampus from 1 to 3 weeks. Mice were evaluated for cognitive change, Aß metabolism, neuroinflammation. Microglia and neuron cultures were prepared to verify the in vivo results. The statistical analyses were performed by student's t test, one-way ANOVA with a post hoc Tukey's test using the GraphPad Prism software package. CatB deficiency significantly reduces Aß clearance efficiency and aggravates mouse cognitive decline. Exogenous Aß markedly increases CatB expression in activated microglia. Transcriptome analysis and in vitro cell culture experiments demonstrate that CatB is associated with gene clusters involved in migration, phagocytosis, and inflammation. In addition, transcriptome analysis and immunoblotting suggest that CatB modulates microglial Aß clearance via PI3K-AKT activation. Our study unveils a previously unknown role of CatB in promoting microglial functionality during Aß clearance.