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Microglia have been recently shown to manifest a very interesting phenotypical heterogeneity across different regions in the mammalian central nervous system (CNS). However, the underlying mechanism and functional meaning of this phenomenon are currently unclear. Baseline diversities of adult microglia in their cell number, cellular and subcellular structures, molecular signature as well as relevant functions have been discovered. But recent transcriptomic studies using bulk RNAseq and single-cell RNAseq have produced conflicting results on region-specific signatures of microglia. It is highly speculative whether such spatial heterogeneity contributes to varying sensitivities of individual microglia to the same physiological and pathological signals in different CNS regions, and hence underlie their functional relevance for CNS disease development. This review aims to thoroughly summarize up-to-date knowledge on this specific topic and provide some insights on the potential underlying mechanisms, starting from microgliogenesis. Understanding regional heterogeneity of microglia in the context of their diverse neighboring neurons and other glia may provide an important clue for future development of innovative therapies for neuropsychiatric disorders.

Background The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls. Methods Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I 2 statistic, and publication bias was assessed using funnel plots, Begg’s test, and Egger’s tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI). Results A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity ( I 2  = 11%) among the included studies. Vitamin D supplementation at 800–1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74–0.95). In addition, 800–1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800–1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800–1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64–0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800–1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52–0.86) but not in individuals with > 50 nmol/L 25(OH)D. Conclusion Vitamin D supplementation at 800–1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = −0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways.

Human activity recognition (HAR) based on wearable sensors has emerged as a low-cost key-enabling technology for applications such as human–computer interaction and healthcare. In wearable sensor-based HAR, deep learning is desired for extracting human active features. Due to the spatiotemporal dynamic of human activity, a special deep learning network for recognizing the temporal continuous activities of humans is required to improve the recognition accuracy for supporting advanced HAR applications. To this end, a residual multifeature fusion shrinkage network (RMFSN) is proposed. The RMFSN is an improved residual network which consists of a multi-branch framework, a channel attention shrinkage block (CASB), and a classifier network. The special multi-branch framework utilizes a 1D-CNN, a lightweight temporal attention mechanism, and a multi-scale feature extraction method to capture diverse activity features via multiple branches. The CASB is proposed to automatically select key features from the diverse features for each activity, and the classifier network outputs the final recognition results. Experimental results have shown that the accuracy of the proposed RMFSN for the public datasets UCI-HAR, WISDM, and OPPORTUNITY are 98.13%, 98.35%, and 93.89%, respectively. In comparison with existing advanced methods, the proposed RMFSN could achieve higher accuracy while requiring fewer model parameters.

Heart failure (HF) is a complex disorder that has an association with increased morbidity and mortality rates globally. The association of statin use with mortality rate in individuals with HF remains unclear. To examine the association of statin use with the short-term and long-term all-cause mortality rate in critically ill individuals with HF. We performed a retrospective cohort analysis based on the Medical Information Mart for Intensive Care (MIMIC)-IV database. The critically ill people with HF were assigned to a statin group and a non-statin group according to whether they had been treated with statin or not during hospitalization. The Kaplan-Meier (KM) method and Cox proportional hazard models were adopted to explore the link between statin administration and the 30-day, 90-day, as well as 1-year mortality rates. To ensure the robustness of the findings, a 1:1 nearest propensity-score matching (PSM) was also performed. The current research included 11,381 patients for the final analysis, with 7,561 in the statin group and 3,820 in the non-statin group. After multiple confounders were adjusted, we found that the Cox regression models revealed great beneficial effects of statin therapy on the 30-day, 90-day, as well as 1-year mortality rates among critically ill individuals with HF in the fully adjusted model. PSM also achieved consistent results. After PSM, the risk of mortality reduced by 23% for the 30-day mortality (HR = 0.77, 95%CI: 0.68-0.88, < 0.001), 16% for the 90-day mortality rate (HR = 0.84, 95%CI: 0.75-0.93, < 0.001), and 12% for the 1-year mortality rate (HR = 0.88, 95%CI: 0.81-0.97, = 0.007). Patients treated with rosuvastatin had the greatest reduction in mortality rate. The 30-day, 90-day, and 1-year all-cause mortality rates were remarkably lower in patients who were treated with low-dose statins. Our study unveiled that statin use was related to decreased short-term and long-term all-cause mortality rates in critically ill individuals with HF. Rosuvastatin was associated with the greatest reduction of all-cause mortality rates. Low-dose statins can significantly reduce short-term and long-term mortality, while high-dose statins are not significantly correlated with mortality. However, the results are not conclusive and should be interpreted with caution.

Water and nutrient are two critical factors that limit plant growth to spatial-temporal extents. Tree root foraging behavior has not received adequate attention in heterogeneous soil environments in temperate forest under drought pressure. In this study, birch ( Betula platyphylla ) and larch ( Larix olgensis ) seedlings were raised in pots in a split-root system with artificially heterogeneous soil environments to study the root foraging response to drought. Potted space was split into two halves where substrates were mixed with fertilizers in 67.5 mg nitrogen (N) plant -1 (N-P 2 O 5 -K 2 O, 14-13-13) to both halves as to create a homogeneous condition. Otherwise, a rate of 135 mg N plant -1 of fertilizers was delivered to a random half to create a heterogeneous condition. Half of seedlings were fully sub-irrigated every three days with the other half received the drought treatment by being watered every six days. Both birch and larch seedlings showed greater net shoot growth and biomass increment in well-watered condition, while root morphology was promoted by drought. Both species placed more fine roots with higher root N concentration in nutrient-enriched patches. In the heterogeneous pattern, birch showed a higher foraging precision assessed by biomass and greater foraging plasticity assessed in morphology and physiology. In contrast, larch seedlings had higher root N concentration in the well-watered condition. Neither species showed a significant response of N utilization to the heterogeneous pattern, but both used more N when water supply was improved. Overall, birch is better at acclimating to heterogeneous soil conditions, but its ability to seize N was lower than larch when drought was alleviated.

Iodine deficiency threatens women of reproductive-age (15-49 years) worldwide, increasing risks of thyroid dysfunction and developmental abnormalities. Accurate trend prediction is essential for targeted prevention strategies. To investigates the global, regional, and national disease burden of iodine deficiency among reproductive-age women from 1990 to 2019, as well as projected trends through 2035. Using Global Burden of Disease 2019 data, we assessed prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) across 204 countries/territories (1990-2019). Age-period-cohort Bayesian model was used to predict trends from 2020 to 2035. In 2019, 81.4 million women of reproductive age globally had iodine deficiency (age-standardized prevalence: 2871.7/100,000), reflecting a 13.3% reduction since 1990. The condition caused 1.1 million YLDs (age-standardized rate: 38.4/100,000), marking a 27.4% decrease from 1990. Projections suggest sustained declines through 2035. Notably, a strong inverse correlation emerged between Socio-demographic Index (SDI) and disease burden, with a correlation coefficient of -0.58 (95% CI: -0.63 to -0.53, <0.001). Geographically, the highest burden clustered in Central Sub-Saharan Africa, South Asia, and Eastern Sub-Saharan Africa, with Somalia, the Democratic Republic of the Congo, and Congo having the highest national prevalence. The global burden of iodine deficiency among women of reproductive age has decreased substantially since 1990. Nonetheless, considerable challenges persist in lower SDI regions, especially affecting women within the reproductive age. Addressing these inequities in global iodine nutrition and alleviate the iodine deficiency-related burden, targeted implementation strategies and continuous monitoring measures are urgently needed.

The determining of landslide-prone areas in mountainous terrain is essential for land planning and hazard mitigation. In this paper, a comparative study using three statistical models including weight of evidence model (WoE), logistic regression model (LR) and support vector machine method (SVM) was undertaken in the Zhouqu to Wudu segment in the Bailong River Basin, Southern Gansu, China. Six conditionally independent environmental factors, elevation, slope, aspect, distance from fault, lithology and settlement density, were selected as the explanatory variables that may contribute to landslide occurrence based on principal component analysis (PCA) and Chi-square test. The relation between landslide distributions and these variables was analyzed using the three models and the results then used to calculate the landslide susceptibility (LS). The performance of the models was then evaluated using both the highly accurate deformation signals produced by using the Small Baseline Subset Interferometric Synthetic Aperture Radar technique and Receiver Operating Characteristic (ROC) curve. Results show more deformation points in areas with high and very high LS levels, and also more stable points in areas with low and very low LS levels for the SVM model. In addition, the SVM has larger area under the ROC curve. It indicates that the SVM has better prediction accuracy and classified ability. For the interpretability, the WoE derives the class of factors that most contributed to landsliding in the study area, and the LR reveals that factors including elevation, settlement density and distance from fault played major roles in landslide occurrence and distribution, whereas the SVM cannot provide relative weights for the variables. The outperformed SVM could be employed to determine potential landslide zones in the study area. Outcome of this research would provide preliminary basis for general land planning such as choosing new urban areas and infrastructure construction in the future, as well as for landslide hazard mitigation in Bailong River Basin.

Background The blood urea nitrogen to creatinine ratio (BCR) and estimated plasma volume status (ePVS) may be prognostic markers in heart failure (HF), but their combined efficacy is unclear. This research aims to determine the prognostic utility of BCR and ePVS in critically ill HF patients in the intensive care unit. Methods Data from the MIMIC-IV database were analyzed. ePVS was calculated using hemoglobin and hematocrit levels with Strauss-derived Duarte method. The primary outcome was 1-year all-cause mortality (ACM). Receiver operating characteristic (ROC) curves identified cutoff values for BCR and ePVS. To assess the connection between BCR, ePVS, and 1-year ACM, the Kaplan-Meier (KM) method, Cox proportional hazards models, subgroup analysis, and limited cubic spline were employed. Harrell’s C statistic evaluated predictive power. Results Among 11,066 participants, optimal thresholds for mortality were BCR > 22.81 and ePVS > 7.16 ml/g. BCR demonstrated a non-linear J-shaped correlation with ACM, while ePVS displayed a linear relationship. Multivariate Cox analysis indicated higher level of BCR was linked to higher 1-year ACM (HR = 1.39, 95% CI: 1.30–1.49, P  < 0.001), as was increased level of ePVS (HR = 1.09, 95% CI: 1.02–1.16, P  = 0.012). Notably, HF patients with both high BCR and ePVS faced a significantly greater mortality risk than those with lower levels of both markers (HR = 1.54, 95% CI: 1.40–1.69, P  < 0.001). Combining BCR and ePVS improved prognostic accuracy. Conclusions BCR and ePVS independently predict 1-year ACM in HF patients, with their combined use offering improved prognostic accuracy.