Deciphering the Transcription Factor Landscape in Neuroendocrine Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation.

Background and Objective: Prostate cancer (PCa) is a leading cause of cancer mortality in men, with neuroendocrine prostate cancer (NEPC) representing a particularly resistant subtype. The role of transcription factors (TFs) in the progression from prostatic adenocarcinoma (PRAD) to NEPC is poorly understood. This study aims to identify and analyze lineage-specific TF profiles in PRAD and NEPC and illustrate their dynamic shifts during NE transdifferentiation. Methods: A novel algorithmic approach was developed to evaluate the weighted expression of TFs within patient samples, enabling a nuanced understanding of TF landscapes in PCa progression and TF dynamic shifts during NE transdifferentiation. Results: unveiled TF profiles for PRAD and NEPC, identifying 126 shared TFs, 46 adenocarcinoma-TFs, and 56 NEPC-TFs. Enrichment analysis across multiple clinical cohorts confirmed the lineage specificity and clinical relevance of these lineage-TFs signatures. Functional analysis revealed that lineage-TFs are implicated in pathways critical to cell development, differentiation, and lineage determination. Novel lineage-TF candidates were identified, offering potential targets for therapeutic intervention. Furthermore, our longitudinal study on NE transdifferentiation highlighted dynamic TF expression shifts and delineated a three-phase hypothesis for the process comprised of de-differentiation, dormancy, and re-differentiation. and proposing novel insights into the mechanisms of PCa progression. Conclusion: The lineage-specific TF profiles in PRAD and NEPC reveal a dynamic shift in the TF landscape during PCa progression, highlighting three distinct phases of NE transdifferentiation.

Berberine directly targets AKR1B10 protein to modulate lipid and glucose metabolism disorders in NAFLD.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR) is the main active component from Coptidis rhizome, a well-known Chinese herbal medicine used for metabolic diseases, especially diabetes for thousands of years. BBR has been reported to cure various metabolic disorders, such as nonalcoholic fatty liver disease (NAFLD). However, the direct proteomic targets and underlying molecular mechanism of BBR against NAFLD remain less understood. AIM OF THE STUDY: To investigate the direct target and corresponding molecular mechanism of BBR on NAFLD is the aim of the current study. MATERIALS AND METHODS: High-fat diet (HFD)-fed mice and oleic acid (OA) stimulated HepG2 cells were utilized to verify the beneficial impacts of BBR on glycolipid metabolism profiles. The click chemistry in proteomics, DARTS, CETSA, SPR and fluorescence co-localization analysis were conducted to identify the targets of BBR for NAFLD. RNA-seq and shRNA/siRNA were used to investigate the downstream pathways of the target. RESULTS: BBR improved hepatic steatosis, ameliorated insulin resistance, and reduced TG levels in the NAFLD models. Importantly, Aldo-keto reductase 1B10 (AKR1B10) was first proved as the target of BBR for NAFLD. The gene expression of AKR1B10 increased significantly in the NAFLD patients' liver tissue. We further demonstrated that HFD and OA increased AKR1B10 expression in the C57BL/6 mice's liver and HepG2 cells, respectively, whereas BBR decreased the expression and activities of AKR1B10. Moreover, the knockdown of AKR1B10 by applying shRNA/siRNA profoundly impacted the beneficial effects on the pathogenesis of NAFLD by BBR. Meanwhile, the changes in various proteins (ACC1, CPT-1, GLUT2, etc.) are responsible for hepatic lipogenesis, fatty acid oxidation, glucose uptake, etc. by BBR were reversed by the knockdown of AKR1B10. Additionally, RNA-seq was used to identify the downstream pathway of AKR1B10 by examining the gene expression of liver tissues from HFD-fed mice. Our findings revealed that BBR markedly increased the protein levels of PPARα while downregulating the expression of PPARγ. However, various proteins of PPAR signaling pathways remained unaffected post the knockdown of AKR1B10. CONCLUSIONS: BBR alleviated NAFLD via mediating PPAR signaling pathways through targeting AKR1B10. This study proved that AKR1B10 is a novel target of BBR for NAFLD treatment and helps to find new targets for the treatment of NAFLD by using active natural compounds isolated from traditional herbal medicines as the probe.

Associations of incident female breast cancer with long-term exposure to PM2.5 and its constituents: Findings from a prospective cohort study in Beijing, China.

This study aimed to investigate the association between long-term exposure to fine particulate matter (PM2.5) and its constituents (black carbon (BC), ammonium (NH4+), nitrate (NO3-), organic matter (OM), inorganic sulfate (SO42-)) and incident female breast cancer in Beijing, China. Data from a prospective cohort comprising 85,504 women enrolled in the National Urban Cancer Screening Program in Beijing (2013-2019) and the Tracking Air Pollution in China dataset are used. Monthly exposures were aggregated to calculate 5-year average concentrations to indicate long-term exposure. Cox models and mixture exposure models (weighted quantile sum, quantile-based g-computation, and explanatory machine learning model) were employed to analyze the associations. Findings indicated increased levels of PM2.5 and its constituents were associated with higher breast cancer risk, with hazard ratios per 1-µg/m3 increase of 1.02 (95% confidence interval (CI): 1.01, 1.03), 1.39 (95% CI: 1.16, 1.65), 1.28 (95% CI: 1.12, 1.46), 1.15 (95% CI: 1.05, 1.24), 1.05 (95% CI: 1.02, 1.08), and 1.15 (95% CI: 1.07, 1.23) for PM2.5, BC, NH4+, NO3-, OM, and SO42-, respectively. Exposure-response curves demonstrated a monotonic risk increase without an evident threshold. Mixture exposure models highlighted BC and SO42- as key factors, underscoring the importance of reducing emissions of these pollutants.

Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism.

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.

Influence of motor capacity of the lower extremity and mobility performance on foot plantar pressures in community-dwelling older women.

Objectives: To investigate the associations of motor capacity of the lower extremity and mobility performance in daily physical activities with peak foot plantar pressures during walking among older women. Methods: Using the data collected among 58 community-dwelling older women (68.66 ± 3.85 years), Pearson correlation and multiple linear regression analyses were performed to analyze the associations of motor capacity of the lower extremity (the 30-s chair stand test, the timed one-leg stance with eyes closed, and the Fugl-Meyer assessment of lower extremity), mobility performance in daily physical activities (the average minutes of moderate to vigorous physical activity every day and the metabolic equivalents), and foot plantar pressures (peak force and peak pressure) with the age and body fat percentage as covariates. Results: (1) The motor capacity of the lower extremity has higher explanatory power for peak foot plantar pressures compared with the mobility performance in daily physical activities. (2) Higher body fat percentage was positively associated with peak force and pressure, while a lower score on the Fugl-Meyer assessment of lower extremity was negatively associated with both of them. (3) The metabolic equivalents were positively associated with the peak force, while the 30-s chair stand test was negatively associated with it. Conclusions: Mobility performance in daily physical activities can be significant predictors for peak foot plantar pressures among older women. The significant predictor variables include the Fugl-Meyer assessment of lower extremity, the 30-s chair stand test, and metabolic equivalents.

Metal telluride nanosheets by scalable solid lithiation and exfoliation.

Transition metal tellurides (TMTs) have been ideal materials for exploring exotic properties in condensed-matter physics, chemistry and materials science1-3. Although TMT nanosheets have been produced by top-down exfoliation, their scale is below the gram level and requires a long processing time, restricting their effective application from laboratory to market4-8. We report the fast and scalable synthesis of a wide variety of MTe2 (M = Nb, Mo, W, Ta, Ti) nanosheets by the solid lithiation of bulk MTe2 within 10 min and their subsequent hydrolysis within seconds. Using NbTe2 as a representative, we produced more than a hundred grams (108 g) of NbTe2 nanosheets with 3.2 nm mean thickness, 6.2 µm mean lateral size and a high yield (>80%). Several interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance, were observed that are generally restricted to highly crystalline MTe2 nanosheets. The TMT nanosheets also perform well as electrocatalysts for lithium-oxygen batteries and electrodes for microsupercapacitors (MSCs). Moreover, this synthesis method is efficient for preparing alloyed telluride, selenide and sulfide nanosheets. Our work opens new opportunities for the universal and scalable synthesis of TMT nanosheets for exploring new quantum phenomena, potential applications and commercialization.

Right superior frontal gyrus: A potential neuroimaging biomarker for predicting short-term efficacy in schizophrenia.

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ.

In situ one step growth of amorphous tin oxide electron transport layer for high-performance perovskite solar cells.

Tin oxide used in electron transport layer (ETL) exhibits key role in transmitting electrons and blocking holes in perovskite solar cells (PSCs) device. However, crystal tin oxide nanoparticles (NPs) become necessary to form SnO2 film by method of spin-coating, resulting in possible surface defect and cracks among SnO2 NPs, corresponding to unsatisfied performance PSCs. Herein, an amorphous tin oxide thin film is creatively in situ grew onto Fluorine-doped Tin Oxide (FTO) substrate as ETL. The designed solar cell device with structure of FTO/SnO2/MAPbI3/Sprio-OMeTAD/Ag owns a champion photoelectric conversion efficiency (PCE) up to 17.64%, 76.20% of filling coefficient (FF), and 1.09 V of open-circuit voltage (Voc), in comparing with 16.43%, 64.35% and 1.05 V for control group (crystal tin oxide as ETL), respectively. Besides, the champion device keeps 83.33% of initial PCE under nitrogen (N2) condition for one month, in comparison with 76.09% for control group. This work provides a viable strategy for facile preparing amorphous tin oxide film based ETL in perovskite solar cells.

Construction and efficacy testing of DNA vaccines containing HLA-A*02:01-restricted SARS-CoV-2 T-cell epitopes predicted by immunoinformatics.

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.

[Liver impairment status toward workers exposed to vinyl chloride under different techniques].

OBJECTIVE: To analyse potential differences towards liver impairment status on vinyl chloride monomer(VCM) exposed population from technique under acetylene hydrochlorination to the one of ethylene oxychlorination respectively and to explore the possible reasons, which will pave the way for occupational health promotion in terms of hazard reduction. METHODS: a cross-sectional study was initiated between June and September in 2022 towards 2 groups of VCM exposed population from the facility of acetylene hydrochlorination(n=78) and the one of ethylene oxychlorination(n=69) in a PVC petrochemical complex enterprise(abbreviation of H) in Tianjin City. The demographic information concerning age, gender, messages on occupational history, field investigation were inquired through questionnaire interview. Then, venous blood(4 mL/person) and urine(10-50 mL/person) were collected during the physical exam phase and indices of 8-hydroxy-2 deoxyguanosine(8-OHdG) in blood and thiodiglycolic acid(TDGA) in urine were detected through ELISA and solid phase extraction-ion chromatography respectively. RESULTS: The 2 groups of population were matched well in terms of average age distribution and gender composition ratio, with significant differences on population composition ratio were found on variables of working years, alcohol consumption and daily sleeping duration(P<0.01 or P<0.05). It was found that the average content of TDGA in acetylene hydrochlorination group was(0.81±0.05)mg/L while the content in ethylene oxychlorination group reached to(0.83±0.06)mg/L, noteworthy differences were only found among 6 posts in the acetylene hydrochlorination group and 5 others in the ethylene oxychlorination group after classification for specific posts, however, the average concentration of 8-OHdG in acetylene hydrochlorination group(122(78.3, 168.8) µg/m~3) was different from the one in ethylene oxychlorination group(101.7(79.6, 149.7) µg/m~3)(Z=6.82, P<0.05). Moreover, a series of positive correlations in moderate intensity between 8-OHdG concentration and TDGA content were observed among posts of polymerization cleaners(r=0.53), aggregation operators(r=0.47), maintenance repairers(r=0.45), sampling operators(r=0.41) in acetylene hydrochlorination group(P<0.05) and posts of cracking reactants(r=0.64), DCS operators(r=0.51), oxychlorination operators(r=0.50) and chemical loaders(r=0.44) in ethylene oxychlorination group(P<0.05). Liver function indices such as content on ALT(χ~2=15.41, P<0.01), AST(χ~2=9.95, P<0.01) and ALP(χ~2=3.79, P<0.01) were different in the 2 groups population with statistical significance, then proportions on population composition ratio that exceeded normal ranges of indices on ALT, AST, AST/ALT ratio, ALP and Alb/Glb ratio were higher in acetylene hydrochlorination group than ones in ethylene oxychlorination group with great significance(P<0.05), so as to the abnormalities in liver B altrosonography test between groups(χ~2=17.33, P<0.01). Binary logistic regression model indicated that 8-OHdG concentration in blood that exceed 90 µg/m~3, TDGA content in urine that exceed 0.60 mg/L, working years that were over 10a, alcohol consumption, sleeping duration less than 6 h per day and male workers were potential risky factors for liver impairment(P<0.05). CONCLUSION: The degree on liver impairment status was higher in acetylene hydrochlorination group than ones in in ethylene oxychlorination group under the same PVC factory, which might be associated with the oxidative stress injury induced from the combination of higher VCM concentration at workplaces, longer cumulative exposure time, longer working years, alcohol consumption habits and sleep shortage caused by shift work patterns.

Cross-patch feature interactive net with edge refinement for retinal vessel segmentation.

Retinal vessel segmentation based on deep learning is an important auxiliary method for assisting clinical doctors in diagnosing retinal diseases. However, existing methods often produce mis-segmentation when dealing with low contrast images and thin blood vessels, which affects the continuity and integrity of the vessel skeleton. In addition, existing deep learning methods tend to lose a lot of detailed information during training, which affects the accuracy of segmentation. To address these issues, we propose a novel dual-decoder based Cross-patch Feature Interactive Net with Edge Refinement (CFI-Net) for end-to-end retinal vessel segmentation. In the encoder part, a joint refinement down-sampling method (JRDM) is proposed to compress feature information in the process of reducing image size, so as to reduce the loss of thin vessels and vessel edge information during the encoding process. In the decoder part, we adopt a dual-path model based on edge detection, and propose a Cross-patch Interactive Attention Mechanism (CIAM) in the main path to enhancing multi-scale spatial channel features and transferring cross-spatial information. Consequently, it improve the network's ability to segment complete and continuous vessel skeletons, reducing vessel segmentation fractures. Finally, the Adaptive Spatial Context Guide Method (ASCGM) is proposed to fuse the prediction results of the two decoder paths, which enhances segmentation details while removing part of the background noise. We evaluated our model on two retinal image datasets and one coronary angiography dataset, achieving outstanding performance in segmentation comprehensive assessment metrics such as AUC and CAL. The experimental results showed that the proposed CFI-Net has superior segmentation performance compared with other existing methods, especially for thin vessels and vessel edges. The code is available at https://github.com/kita0420/CFI-Net.

Enhancing cancer therapy: The role of drug delivery systems in STAT3 inhibitor efficacy and safety.

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment.

Human umbilical cord blood mesenchymal stem cells mediate microglia activation and improve anxiety-like behavior in MIA-induced offspring of schizophrenic rats.

Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model. Open field, PPI, Western blotting, Q-PCR, and immunofluorescence were used to assess the biological effects of repeated tail vein injections of hUC-MSC in offspring rats following the MIA model of SCZ. The results indicated that offspring of MIA rats exhibited schizophrenia-like (SCZ-like) anxiety behavior, with observed microglial activation triggering neuroinflammation. Furthermore, levels of IBA1, HMGB1, and PSD95 were significantly up-regulated, while SYP was significantly down-regulated. It is suggested that hUCB-MSCs may act through HMGB1, Iba1, PSD95, and related pathway molecules to alleviate neuroinflammation and repair synaptic damage by regulating the activity state of microglia. Consequently, this could improve the abnormal behavior observed in MIA offspring rats.

Multiple exposure pathways and health risk assessment of PAHs in Lanzhou city, a semi-arid region in northwest China.

In the sparse studies for multiple pathway exposure, attention has predominantly been directed towards developed regions, thereby overlooking the exposure level and health outcome for the inhabitants of the semi-arid regions in northwest China. However, cities within these regions grapple with myriad challenges, encompassing insufficient sanitation infrastructure and outdated heating. In this study, we analyzed the characteristics and sources of polycyclic aromatic hydrocarbons (PAHs) pollution in PM2.5, water, diet, and dust during different periods in Lanzhou, and estimated corresponding carcinogenic health risk through inhalation, ingestion, and dermal absorption. Our observations revealed the concentrations of PAHs in PM2.5, food, soil, and water are 200.11 ng m-3, 8.67 mg kg-1, 3.91 mg kg-1, and 14.5 ng L-1, respectively, indicating that the Lanzhou area was seriously polluted. Lifetime incremental cancer risk (ILCR) showed a heightened cancer risk to men compared to women, to the younger than the elderly, and during heating period as opposed to non-heating period. Notably, the inhalation was the primary route of PAHs exposure and the risk of exposure by inhalation cannot be ignored. The total environmental exposure assessment of PAHs can achieve accurate prevention and control of PAHs environmental exposure according to local conditions and targets.

A new genus and three newly recorded species of Encyrtidae (Hymenoptera, Chalcidoidea) from China.

A new genus and species of Encyrtidae (Hymenoptera: Chalcidoidea), Apteronotus Kang, Hu & Luo, gen. nov. (type species A.indigus Kang, Hu & Luo, sp. nov.), associated with insects inhabiting Oxytropis spp., and three newly recorded species for China, Copidosomaclavatum, Ericydnusaeneus and Tetracnemuskozlovi, are described from the Altun Mountain Nature Reserve, Xinjiang. Detailed illustrations of all species were included to support the identification and further study.

Exercise intervention in middle-aged and elderly individuals with insomnia improves sleep and restores connectivity in the motor network.

Exercise is a potential treatment to improve sleep quality in middle-aged and elderly individuals. Understanding exercise-induced changes in functional plasticity of brain circuits that underlie improvements in sleep among middle-aged and older adults can inform treatment of sleep problems. The aim of the study is to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. The trial was registered with Chinese Clinical Trial Register (ChiCTR2000033652). We recruited 84 healthy sleepers and 85 individuals with insomnia. Participants with insomnia were assigned to receive either a 12-week exercise intervention or were placed in a 12-week waitlist control condition. Thirty-seven middle-aged and older adults in the exercise group and 30 in the waitlist group completed both baseline and week 12 assessments. We found that middle-aged and older adults with insomnia showed significantly worse sleep quality than healthy sleepers. At the brain circuit level, insomnia patients showed decreased connectivity in the widespread motor network. After exercise intervention, self-reported sleep was increased in the exercise group (P < 0.001) compared to that in the waitlist group. We also found increased functional connectivity of the motor network with the cerebellum in the exercise group (P < 0.001). Moreover, we observed significant correlations between improvement in subjective sleep indices and connectivity changes within the motor network. We highlight exercise-induced improvement in sleep quality and functional plasticity of the aging brain.

Zebrafish live imaging: a strong weapon in anticancer drug discovery and development.

Developing anticancer drugs is a complex and time-consuming process. The inability of current laboratory models to reflect important aspects of the tumor in vivo limits anticancer medication research. Zebrafish is a rapid, semi-automated in vivo screening platform that enables the use of non-invasive imaging methods to monitor morphology, survival, developmental status, response to drugs, locomotion, or other behaviors. Zebrafish models are widely used in drug discovery and development for anticancer drugs, especially in conjunction with live imaging techniques. Herein, we concentrated on the use of zebrafish live imaging in anticancer therapeutic research, including drug screening, efficacy assessment, toxicity assessment, and mechanism studies. Zebrafish live imaging techniques have been used in numerous studies, but this is the first time that these techniques have been comprehensively summarized and compared side by side. Finally, we discuss the hypothesis of Zebrafish Composite Model, which may provide future directions for zebrafish imaging in the field of cancer research.

Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.

Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington's disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington's disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer's disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration.

Angelica keiskei water extract Mitigates Age-Associated Physiological Decline in Mice.

OBJECTIVE: Angelica keiskei is a medicinal and edible plant that has been reported to possess potent antioxidant properties in several in vitro models, but its effectiveness on naturally aging organisms is still lacking. This study explores the antioxidant and health-promoting effects of Angelica keiskei in naturally aging mice. METHODS: We treated 48-week-old mice with Angelica keiskei water extract (AKWE) 30 days, and measured indicators related to aging and antioxidants. In addition, we conducted network pharmacology analysis, component-target molecular docking, real-time PCR, and MTS assays to investigate relevant factors. RESULTS: The results indicated that administration of AKWE to mice led to decrease blood glucose levels, improve muscle fiber structure, muscle strength, gait stability, and increase levels of glutathione and superoxide dismutase in serum. Additionally, it decreased pigmentation of the heart tissues. Angelica keiskei combats oxidative stress by regulating multiple redox signaling pathways, and its ingredients Coumarin and Flavonoids have the potential to bind to SIRT3 and SIRT5. CONCLUSIONS: Our findings indicated the potential of Angelica keiskei as a safe and effective dietary supplement to combat aging and revealed the broad prospects of medicinal and edible plants for addressing aging and age-related chronic diseases.

Reduction of Backward Scatterings at the Low-Coherence Kunwu Laser Facility.

We report the first experimental observation on the reduction of backward scatterings by an instantaneous broadband laser with 0.6% bandwidth in conditions of interest for inertial confinement fusion at the low-coherence Kunwu laser facility. The backscatter of stimulated Brillouin scattering (SBS) was robustly reduced by half at intensities of 1-5×10^{14} W/cm^{2} with the 0.53-µm broadband laser in comparison with the monochromatic laser. As SBS dominates energy loss of laser-plasma interactions, the reduction of that demonstrates the enhancement of laser-target coupling by the use of broadband laser. The mitigation of filamentation leads to the reduction of stimulated Raman backscattering at low intensities. In addition, the three-halves harmonic emission was reduced with the broadband laser as well.