Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion.

We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.

SEC: A core hub during cell fate alteration.

Pol II pause release is a rate-limiting step in gene transcription, influencing various cell fate alterations. Numerous proteins orchestrate Pol II pause release, thereby playing pivotal roles in the intricate process of cellular fate modulation. Super elongation complex (SEC), a large assembly comprising diverse protein components, has garnered attention due to its emerging significance in orchestrating physiological and pathological cellular identity changes by regulating the transcription of crucial genes. Consequently, SEC emerges as a noteworthy functional complex capable of modulating cell fate alterations. Therefore, a comprehensive review is warranted to systematically summarize the core roles of SEC in different types of cell fate alterations. This review focuses on elucidating the current understanding of the structural and functional basis of SEC. Additionally, we discuss the intricate regulatory mechanisms governing SEC in various models of cell fate alteration, encompassing both physiological and pathological contexts. Furthermore, leveraging the existing knowledge of SEC, we propose some insightful directions for future research, aiming to enhance our mechanistic and functional comprehension of SEC within the diverse landscape of cell fate alterations.

Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry.

Monitoring mitochondrial esterase activity is crucial not only for investigating mitochondrial metabolism but also for assessing the effectiveness of mitochondrial-targeting prodrugs. However, accurately detecting esterase activity within mitochondria poses challenges due to its ubiquitous presence in cells and the uncontrolled localization of fluorogenic probes. To overcome this hurdle and reveal variations among different mitochondria, we isolated mitochondria and preserved their activity and functionality in a buffered environment. Subsequently, we utilized a laboratory-built nano-flow cytometer in conjunction with an esterase-responsive calcein-AM fluorescent probe to measure the esterase activity of individual mitochondria. This approach enabled us to investigate the influence of temperature, pH, metal ions, and various compounds on the mitochondrial esterase activity without any interference from other cellular constituents. Interestingly, we observed a decline in the mitochondrial esterase activity following the administration of mitochondrial respiratory chain inhibitors. Furthermore, we found that mitochondrial esterase activity was notably higher in the presence of a high concentration of ATP compared to that of ADP and AMP. Additionally, we noticed a correlation between elevated levels of complex IV and increased mitochondrial esterase activity. These findings suggest a functional connection between the mitochondrial respiratory chain and mitochondrial esterase activity. Moreover, we detected an upsurge in mitochondrial esterase activity during the early stages of apoptosis, while cellular esterase activity decreased. This highlights the significance of analyzing enzyme activity within specific organelle subregions. In summary, the integration of a nano-flow cytometer and fluorescent dyes introduces a novel method for quantifying mitochondrial enzyme activity with the potential to uncover the alterations and unique functions of other mitochondrial enzymes.

M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy.

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

Salivary microbiota and metabolic phenotype of patients with recurrent aphthous ulcers.

OBJECTIVES: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown. SUBJECTS AND METHODS: 16S rRNA sequencing (16S rRNA-seq) and non-targeted liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105). RESULTS: Findings from 16S rRNA -seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC-MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA-seq and LC-MS data revealed a significant association between salivary microbiota and metabolites in RAU patients. CONCLUSIONS: Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU.

Long-term effects of climate factors on dengue fever over a 40-year period.

BACKGROUND: Dengue fever stands as one of the most extensively disseminated mosquito-borne infectious diseases worldwide. While numerous studies have investigated its influencing factors, a gap remains in long-term analysis, impeding the identification of temporal patterns, periodicity in transmission, and the development of effective prevention and control strategies. Thus, we aim to analyze the periodicity of dengue fever incidence and explore the association between various climate factors and the disease over an extended time series. METHODS: By utilizing monthly dengue fever cases and climate data spanning four decades (1978-2018) in Guangdong province, China, we employed wavelet analysis to detect dengue fever periodicity and analyze the time-lag relationship with climate factors. Additionally, Geodetector q statistic was employed to quantify the explanatory power of each climate factor and assess interaction effects. RESULTS: Our findings revealed a prolonged transmission period of dengue fever over the 40-year period, transitioning from August to November in the 1970s to nearly year-round in the 2010s. Moreover, we observed lags of 1.5, 3.5, and 3 months between dengue fever and temperature, relative humidity, and precipitation, respectively. The explanatory power of precipitation, temperature, relative humidity, and the Oceanic Niño Index (ONI) on dengue fever was determined to be 18.19%, 12.04%, 11.37%, and 5.17%, respectively. Dengue fever exhibited susceptibility to various climate factors, with notable nonlinear enhancement arising from the interaction of any two variables. Notably, the interaction between precipitation and humidity yielded the most significant effect, accounting for an explanatory power of 75.32%. CONCLUSIONS: Consequently, future prevention and control strategies for dengue fever should take into account these climate changes and formulate corresponding measures accordingly. In regions experiencing the onset of high temperatures, humidity, and precipitation, it is imperative to initiate mosquito prevention and control measures within a specific window period of 1.5 months.

Generation time-out grows up: young adults' reports about childhood time-out use and their mental health, attachment, and emotion regulation.

Time-out (TO) is a widely utilised parental discipline technique with a strong evidence-base that nonetheless has attracted controversy regarding potential adverse effects on mental health in developing children. Associations between TO implementation and mental health outcomes have rarely been investigated, especially through the eyes of children who grew up experiencing TO. This study recruited 407 university students (Study 1) and a community sample of 535 young adults (Study 2); both samples aged 18-30 years. Young adults were surveyed on their retrospective reports of childhood TO experience, childhood experiences of adversity, perceived parenting style and parental attachment, and their current mental health outcomes (attachment style, emotion regulation and mental health). In Study 1, 334 (82.1%) young adults reported experiencing TO in childhood, but with widely varied implementation that differed considerably from its evidence-based ideal. Reports of more TO appropriate implementation were associated with less avoidant attachment, better mental health, and emotion regulation, over and above the effects associated with authoritative parenting and secure attachment in childhood. While exposure to childhood adversity was associated with poorer adulthood outcomes, TO implementation did not moderate the association. Study 2 replicated most findings from Study 1, except that appropriate TO implementation displayed a positive association with mental health and no associations with anxious and avoidant attachment and emotion regulation. These findings suggest the safety of TO use with young children, including those who experienced childhood adversity, and highlight the importance of disseminating sufficient parenting information on TO in the community.

Apigenin alleviates doxorubicin-induced myocardial pyroptosis by inhibiting glycogen synthase kinase-3ß in vitro and in vivo.

Apigenin, a natural flavonoid compound found in chamomile (Matricaia chamomilla L.) from the Asteraceae family, has been shown in our previous study to possess antimyocardial hypertrophy and anti-cardiac fibrosis effects. However, its effects and mechanisms on the pyroptosis of cardiomyocytes induced by doxorubicin (DOX) are poorly understood. The objective of this study was to investigate the role of GSK-3ß and the effects of apigenin in DOX-induced cardiotoxicity. H9c2 cells stimulated with DOX were treated with SB216763 and apigenin. Additionally, a mouse model of DOX-induced cardiotoxicity was prepared and further treated with apigenin and SB216763 for 30 days. The findings revealed that treatment with SB216763 or apigenin resulted in a significant reduction in the levels of pyroptosis-related factors. Furthermore, the phosphorylation of GSK-3ß was enhanced while the phosphorylation of nuclear factor-kB (NF-κB) p65 was reduced following treatment with either SB216763 or apigenin. Conversely, the effects of apigenin treatment were nullified in siRNA-GSK-3ß-transfected cells. Results from computer simulation and molecular docking analysis supported that apigenin could directly target the regulation of GSK-3ß. Therefore, our study confirmed that the inhibition of GSK-3ß and treatment with apigenin effectively suppressed the pyroptosis of cardiomyocytes in both DOX-stimulated H9c2 cells and mice. These benefits may be attributed in part to the decrease in GSK-3ß expression and subsequent reduction in NF-κB p65 activation. Overall, our findings revealed that the pharmacological targeting of GSK-3ß may offer a promising therapeutic approach for alleviating DOX-induced cardiotoxicity.

A Causal Regulation Modeling Algorithm for Temporal Events with Application to Escherichia coli's Aerobic to Anaerobic Transition.

Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on Escherichia coli's (E. coli) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism's metabolic shifts. By applying our algorithm to a comprehensive E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli's AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.

Comparison of Facial Aesthetic Evaluation Given by Patients with Cleft Lip and/or Palate and Professionals: A Systematic Review.

OBJECTIVE: To compare the differences of facial aesthetic evaluation between patients with Cleft Lip and/or Palate (CL/P) and professionals for the treatment outcome of CL/P. DESIGN: This systematic review was conducted on MedLine, Web of Science, Embase and Cochrane Library databases. The Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool was used to evaluate the included researches. SETTING: Not applicable. PATIENTS, PARTICIPANTS: Patients with CL/P and professionals. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The facial aesthetic evaluation of patients with CL/P and professionals. RESULTS: Among the 1695 literatures retrieved, 22 articles were included, including 974 patients with CL/P and 251 professionals. The bias risk assessment on 21 articles was rated "Moderate" and only one article was rated "Serious". Due to the high heterogeneity of the included studies, meta-analysis was not possible, so descriptive analysis was conducted. Among the included studies, two articles indicated similar views from both groups, 19 noted differences between the two groups, of which three articles indicated more positive evaluation by professionals and nine articles indicated more positive evaluation by patients. CONCLUSIONS: The available data indicate that there is a difference between patients with CL/P and professionals in the aesthetic evaluation, but it is not clear which group is more positive. During the treatment of patients with CL/P, apart from the objective aesthetic evaluation, professionals should fully consider subjective ideas and self-assessment of patients, in order to improve the quality of life for patients.

[Inhibitory Effect of Ginsenoside Rg3 Combined With 5-Fluorouracil on Tumor Angiogenesis and Tumor Growth of Colon Cancer in Mice: An Experimental Study]. / 人参皂苷Rg3与5-æ°Ÿå°¿å˜§å•¶è”ç”¨å¯¹ç»“è‚ ç™Œå°é¼ è‚¿ç˜¤çš„è¡€ç®¡ç”Ÿæˆä¸Žè‚¿ç˜¤ç”Ÿé•¿æŠ‘åˆ¶æ•ˆæžœçš„å®žéªŒç ”ç©¶.

Objective: To evaluate the inhibitory effect of ginsenoside Rg3 combined with 5-fluorouracil (5-FU) on tumor angiogenesis and tumor growth in colon cancer in mice. Methods: CT26 mouse model of colon cancer was established and the mice were randomly assigned to the control group, the ginsenoside Rg3 group, the 5-FU group, and the Rg3 combined with 5-FU group. The 5-FU group was injected intraperitoneally at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 10 days. Treatment for the Rg3 group was given at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 21 days via gastric gavage. The dose and the mode of treatment for the Rg3+5-FU combination group were the same as those for the 5-FU and the Rg3 group. The control group was intraperitoneally injected with 0.2 mL/d of normal saline for 10 days. The expression of vascular endothelial growth factor (VEGF) and CD31 and the microvascular density (MVD) of the tumor tissues were examined by immunohistochemistry. The blood flow signals and tumor necrosis were examined by color Doppler flow imaging (CDFI). The quality of life, survival rate, tumor volume, tumor mass, and tumor inhibition rate of the mice were monitored. Results: After 21 days of treatment, the tumor volume and the tumor mass of all treatment groups were significantly decreased compared with those the control group, with the combination treatment group exhibiting the most significant decrease. The tumor inhibition rates of the Rg3 group, the 5-FU group, and the combination group were 29.96%, 68.78%, and 73.42%, respectively. Rg3 treatment alone had inhibitory effect on tumor growth to a certain degree, while 5-FU treatment alone or 5-FU combined with Rg3 had a stronger inhibitory effect on tumor growth. The tumor inhibition rate of the combination group was higher than that of the 5-FU group, but the difference was not statistically significant (P>0.05). Color Doppler ultrasound showed that there were multiple localized and large tumor necrotic areas that were obvious and observable in the Rg3 group and the combination group, and that there were only small tumor necrotic areas in the 5-FU group and the control group. The tumor necrosis rate of the combination group was (55.63±3.12)%, which was significantly higher than those of the other groups (P<0.05). CDFI examination of the blood flow inside of the tumor of the mice showed that the blood flow signals in the combination group were mostly grade 0-Ⅰ, and that the blood flow signals in the control group were the most abundant, being mostly grade Ⅱ-Ⅲ. The abundance of the blood flow signals in the Rg3 and 5-FU groups were between those of the control group and the combination group. Compared with those of the control group, the expression levels of MVD and VEGF in the tumor tissues of the Rg3 group, the 5-FU group, and the combination group were significantly decreased, with the combination group showing the most significant decrease (P<0.05). HE staining results indicated that there was significant tumor necrosis in mice in the control group and that there were more blood vessels. In contrast, in the tumor of the Rg3 group and the 5-FU group, there were fewer blood vessels and necrotic gaps appeared within the tumors. In the combination group, the tumor tissues had the fewest blood vessels and rope-like necrosis was observed. The mice started dying on the 18th day after treatment started, and all the mice in the control group died on the 42nd day. By this time, there were 3, 5, and 7 mice still alive in the Rg3 group, the 5-FU group, and the combination group, respectively, presenting a survival rate of 30%, 50%, and 70%, respectively. All mice in all the groups died on day 60 after treatment started. Conclusion: Ginsenoside Rg3 combined with 5-FU can significantly inhibit tumor angiogenesis and tumor growth of colon cancer in mice and improve the survival and quality of life of tumor-bearing mice.

Enhancing Built-in Electric Fields via Molecular Symmetry Modulation in Supramolecular Photocatalysts for Highly Efficient Photocatalytic Hydrogen Evolution.

Nature-inspired supramolecular self-assemblies are attractive photocatalysts, but their quantum yields are limited by poor charge separation and transportation. A promising strategy for efficient charge transfer is to enhance the built-in electric field by symmetry breaking. Herein, an unsymmetric protonation, N-heterocyclic π-conjugated anthrazoline-based supramolecular photocatalyst SA-DADK-H+ was developed. The unsymmetric protonation breaks the initial structural symmetry of DADK, resulting in ca. 50-fold increase in the molecular dipole, and facilitates efficient charge separation and transfer within SA-DADK-H+. The protonation process also creates numerous active sites for H2O adsorption, and serves as crucial proton relays, significantly improving the photocatalytic efficiency. Remarkably, SA-DADK-H+ exhibits an outstanding hydrogen evolution rate of 278.2 mmol g-1 h-1 and a remarkable apparent quantum efficiency of 25.1 % at 450 nm, placing it among the state-of-the-art performances in organic semiconductor photocatalysts. Furthermore, the versatility of the unsymmetric protonation approach has been successfully applied to four other photocatalysts, enhancing their photocatalytic performance by 39 to 533 times. These findings highlight the considerable potential of unsymmetric protonation induced symmetry breaking strategy in tailoring supramolecular photocatalysts for efficient solar-to-fuel production.

Disturbance of neuron-microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron-microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron-microglia crosstalk and is involved in the pathogenic process of NPSLE. METHODS: Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. RESULTS: The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. CONCLUSION: GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron-microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.

Integrating transformer and imbalanced multi-label learning to identify antimicrobial peptides and their functional activities.

MOTIVATION: Antimicrobial peptides (AMPs) have the potential to inhibit multiple types of pathogens and to heal infections. Computational strategies can assist in characterizing novel AMPs from proteome or collections of synthetic sequences and discovering their functional abilities toward different microbial targets without intensive labor. RESULTS: Here, we present a deep learning-based method for computer-aided novel AMP discovery that utilizes the transformer neural network architecture with knowledge from natural language processing to extract peptide sequence information. We implemented the method for two AMP-related tasks: the first is to discriminate AMPs from other peptides, and the second task is identifying AMPs functional activities related to seven different targets (gram-negative bacteria, gram-positive bacteria, fungi, viruses, cancer cells, parasites and mammalian cell inhibition), which is a multi-label problem. In addition, asymmetric loss was adopted to resolve the intrinsic imbalance of dataset, particularly for the multi-label scenarios. The evaluation showed that our proposed scheme achieves the best performance for the first task (96.85% balanced accuracy) and has a more unbiased prediction for the second task (79.83% balanced accuracy averaged across all functional activities) when compared with that of strategies without imbalanced learning or deep learning. AVAILABILITY AND IMPLEMENTATION: The source code and data of this study are available at https://github.com/BiOmicsLab/TransImbAMP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

BACKGROUND: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. RESULTS: Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. CONCLUSION: Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

Pristane induced lupus mice as a model for neuropsychiatric lupus (NPSLE).

BACKGROUND: The pristane-induced lupus (PIL) model is a useful tool for studying environmental-related systemic lupus erythematosus (SLE). However, neuropsychiatric manifestations in this model have not been investigated in detail. Because neuropsychiatric lupus (NPSLE) is an important complication of SLE, we investigated the neuropsychiatric symptoms in the PIL mouse model to evaluate its suitability for NPSLE studies. RESULTS: PIL mice showed olfactory dysfunction accompanied by an anxiety- and depression-like phenotype at month 2 or 4 after pristane injection. The levels of cytokines (IL-1ß, IFN-α, IFN-ß, IL-10, IFN-γ, IL-6, TNF-α and IL-17A) and chemokines (CCL2 and CXCL10) in the brain and blood-brain barrier (BBB) permeability increased significantly from week 2 or month 1, and persisted throughout the observed course of the disease. Notably, IgG deposition in the choroid plexus and lateral ventricle wall were observed at month 1 and both astrocytes and microglia were activated. Persistent activation of astrocytes was detected throughout the observed course of the disease, while microglial activation diminished dramatically at month 4. Lipofuscin deposition, a sign of neuronal damage, was detected in cortical and hippocampal neurons from month 4 to 8. CONCLUSION: PIL mice exhibit a series of characteristic behavioral deficits and pathological changes in the brain, and therefore might be suitable for investigating disease pathogenesis and for evaluating potential therapeutic targets for environmental-related NPSLE.

The epidemiological characteristics and infection risk factors for extrapulmonary tuberculosis in patients hospitalized with pulmonary tuberculosis infection in China from 2017 to 2021.

BACKGROUND: Pulmonary tuberculosis (PTB) complicated with extrapulmonary tuberculosis (EPTB) infection can aggravate the disease, but there have been few reports. METHODS: Retrospective analysis was used to collect the clinical data of PTB patients with pathogen positive in a teaching hospital from 2017 to 2021. We describe the incidence, the invasive site of EPTB patients, and analyze the infection risk factors for PTB with EPTB by univariate and multivariate logistic regression models. We also compared the complications, disease burden with chi-square test and rank-sum test. RESULTS: A total of 1806 PTB were included, of which 263 (14.6%) were complicated with EPTB. The common invasive sites for EPTB were neck lymph nodes (16.49%), intestines (16.13%), and meninges (10.75%). Age ≤ 40 (OR = 1.735; 95%CI [1.267-2.376]; P = 0.001), malnutrition (OR = 2.029; 95%CI [1.097-3.753]; P = 0.022), anemia (OR = 1.739; 95%CI[1.127-2.683]; P = 0.012), and osteoporosis (OR = 4.147; 95%CI [1.577-10.905]; P = 0.004) were all independent risk factors for PTB infection with EPTB. The incidence of extrathoracic hydrothorax, intestinal bacterial infection, urinary tract bacterial infection, and abdominal bacterial infection were higher in patients with PTB with EPTB. PTB with EPTB patients also had longer median hospitalization durations (19 vs. 14 days), during which time they incurred higher total costs, laboratory test costs, imaging examination costs, and drug use costs. CONCLUSION: This study found important risk factors for PTB complicated with EPTB, such as age ≤ 40, malnutrition, anemia, and osteoporosis. PTB with EPTB patients have more extrapulmonary complications and higher hospitalization disease burden.

White children's prosocial behavior toward White versus Black peers: The role of children's effortful control and parents' implicit racial attitudes.

White children's effortful control (EC), parents' implicit racial attitudes, and their interaction were examined as predictors of children's prosocial behavior toward White versus Black recipients. Data were collected from 171 White children (55% male, Mage = 7.13 years, SD = 0.92) and their parent in 2017. Prosocial behavior toward White peers was predicted by children's higher EC. When predicting prosocial behavior toward Black peers and prosocial disparity (the difference between White and Black recipients), parents' implicit racial attitudes moderated the relation between children's EC and children's prosocial behavior. Specifically, children's EC was positively associated with prosocial behavior toward Black peers (and negatively related to inequity in prosocial behavior) only when parents exhibited less implicit racial bias.

White children's empathy-related responding and prosocial behavior toward White and Black children.

Relations among White (non-Latinx) children's empathy-related responding, prosocial behaviors, and racial attitudes toward White and Black peers were examined. In 2017, 190 (54% boys) White 5- to 9-year-old children (M = 7.09 years, SD = 0.94) watched a series of videos that depicted social rejection of either a White or Black child. Empathy-related responses, prosocial behaviors, and racial attitudes were measured using multiple methods. Results showed that younger children showed less facial concern toward Black than White peers and greater increases with age in concern and prosocial behaviors (sharing a desirable prize) for Black, compared to White, targets. Children's facial anger increased with age for White but not Black targets. The findings can extend our understanding children's anti-racism development.

Dominoes with interlocking consequences triggered by zinc: involvement of microelement-stimulated MSC-derived exosomes in senile osteogenesis and osteoclast dialogue.

As societal aging intensifies, senile osteoporosis has become a global public health concern. Bone microdamage is mainly caused by processes such as enhancing osteoclast activity or reducing bone formation by osteoblast-lineage cells. Compared with young individuals, extracellular vesicles derived from senescent bone marrow mesenchymal stem cells(BMSCs) increase the transient differentiation of bone marrow monocytes (BMMs) to osteoclasts, ultimately leading to osteoporosis and metal implant failure. To address this daunting problem, an exosome-targeted orthopedic implant composed of a nutrient coating was developed. A high-zinc atmosphere used as a local microenvironmental cue not only could inhibit the bone resorption by inhibiting osteoclasts but also could induce the reprogramming of senile osteogenesis and osteoclast dialogue by exosome modification. Bidirectional regulation of intercellular communication via cargoes, including microRNAs carried by exosomes, was detected. Loss- and gain-of-function experiments demonstrated that the key regulator miR-146b-5p regulates the protein kinase B/mammalian target of rapamycin pathway by targeting the catalytic subunit gene of PI3K-PIK3CB. In vivo evaluation using a naturally-aged osteoporotic rat femoral defect model further confirmed that a nutrient coating substantially augments cancellous bone remodeling and osseointegration by regulating local BMMs differentiation. Altogether, this study not only reveals the close link between senescent stem cell communication and age-related osteoporosis but also provides a novel orthopedic implant for elderly patients with exosome modulation capability.