Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases.

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Deep learning in pulmonary nodule detection and segmentation: a systematic review.

OBJECTIVES: The accurate detection and precise segmentation of lung nodules on computed tomography are key prerequisites for early diagnosis and appropriate treatment of lung cancer. This study was designed to compare detection and segmentation methods for pulmonary nodules using deep-learning techniques to fill methodological gaps and biases in the existing literature. METHODS: This study utilized a systematic review with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed, Embase, Web of Science Core Collection, and the Cochrane Library databases up to May 10, 2023. The Quality Assessment of Diagnostic Accuracy Studies 2 criteria was used to assess the risk of bias and was adjusted with the Checklist for Artificial Intelligence in Medical Imaging. The study analyzed and extracted model performance, data sources, and task-focus information. RESULTS: After screening, we included nine studies meeting our inclusion criteria. These studies were published between 2019 and 2023 and predominantly used public datasets, with the Lung Image Database Consortium Image Collection and Image Database Resource Initiative and Lung Nodule Analysis 2016 being the most common. The studies focused on detection, segmentation, and other tasks, primarily utilizing Convolutional Neural Networks for model development. Performance evaluation covered multiple metrics, including sensitivity and the Dice coefficient. CONCLUSIONS: This study highlights the potential power of deep learning in lung nodule detection and segmentation. It underscores the importance of standardized data processing, code and data sharing, the value of external test datasets, and the need to balance model complexity and efficiency in future research. CLINICAL RELEVANCE STATEMENT: Deep learning demonstrates significant promise in autonomously detecting and segmenting pulmonary nodules. Future research should address methodological shortcomings and variability to enhance its clinical utility. KEY POINTS: Deep learning shows potential in the detection and segmentation of pulmonary nodules. There are methodological gaps and biases present in the existing literature. Factors such as external validation and transparency affect the clinical application.

FABP3 Induces Mitochondrial Autophagy to Promote Neuronal Cell Apoptosis in Brain Ischemia-Reperfusion Injury.

This study elucidates the molecular mechanisms by which FABP3 regulates neuronal apoptosis via mitochondrial autophagy in the context of cerebral ischemia-reperfusion (I/R). Employing a transient mouse model of middle cerebral artery occlusion (MCAO) established using the filament method, brain tissue samples were procured from I/R mice. High-throughput transcriptome sequencing on the Illumina CN500 platform was performed to identify differentially expressed mRNAs. Critical genes were selected by intersecting I/R-related genes from the GeneCards database with the differentially expressed mRNAs. The in vivo mechanism was explored by infecting I/R mice with lentivirus. Brain tissue injury, infarct volume ratio in the ischemic penumbra, neurologic deficits, behavioral abilities, neuronal apoptosis, apoptotic factors, inflammatory factors, and lipid peroxidation markers were assessed using H&E staining, TTC staining, Longa scoring, rotation experiments, immunofluorescence staining, and Western blot. For in vitro validation, an OGD/R model was established using primary neuron cells. Cell viability, apoptosis rate, mitochondrial oxidative stress, morphology, autophagosome formation, membrane potential, LC3 protein levels, and colocalization of autophagosomes and mitochondria were evaluated using MTT assay, LDH release assay, flow cytometry, ROS/MDA/GSH-Px measurement, transmission electron microscopy, MitoTracker staining, JC-1 method, Western blot, and immunofluorescence staining. FABP3 was identified as a critical gene in I/R through integrated transcriptome sequencing and bioinformatics analysis. In vivo experiments revealed that FABP3 silencing mitigated brain tissue damage, reduced infarct volume ratio, improved neurologic deficits, restored behavioral abilities, and attenuated neuronal apoptosis, inflammation, and mitochondrial oxidative stress in I/R mice. In vitro experiments demonstrated that FABP3 silencing restored OGD/R cell viability, reduced neuronal apoptosis, and decreased mitochondrial oxidative stress. Moreover, FABP3 induced mitochondrial autophagy through ROS, which was inhibited by the free radical scavenger NAC. Blocking mitochondrial autophagy with sh-ATG5 lentivirus confirmed that FABP3 induces mitochondrial dysfunction and neuronal apoptosis by activating mitochondrial autophagy. In conclusion, FABP3 activates mitochondrial autophagy through ROS, leading to mitochondrial dysfunction and neuronal apoptosis, thereby promoting cerebral ischemia-reperfusion injury.

Modified basalt fiber filled in constructed wetland-microbial fuel cell: Comparison of performance and microbial impacts under PFASs exposure.

Basalt fiber (BF) with modification of iron (Fe-MBF) and calcium (Ca-MBF) were filled into constructed wetland-microbial fuel cell (CW-MFC) for innovative comparison of improved performance under perfluorooctanoic acid (PFOA) exposure. More enhancement on nitrogen and phosphorus removal was observed by Fe-MBF than Ca-MBF, with significant increase of ammonium (NH4+-N) removal by 3.36-5.66 % (p < 0.05) compared to control, even under PFOA stress. Markedly higher removal efficiency of PFOA by 4.76-8.75 % (p < 0.05) resulted from Fe-MBF, compared to Ca-MBF and control BF groups. Besides, superior electrochemical performance was found in Fe-MBF group, with maximum power density 28.65 % higher than control. Fe-MBF caused higher abundance of dominant microbes on electrodes ranged from phylum to family. Meanwhile, ammonia oxidizing bacteria like Nitrosomonas was more abundant in Fe-MBF group, which was positively correlated to NH4+-N and total nitrogen removal. Some other functional genera involved in denitrification and phosphorus-accumulation were enriched by Fe-MBF on electrodes and MBF carrier, including Dechloromonas, Candidatus_Competibacter, and Pseudomonas. Additionally, there were more biomarkers in Fe-MBF group, like Pseudarcobacter and Acidovorax, conducive to nitrogen and iron cycling. Most functional genes of nitrogen, carbon, and sulfur metabolisms were up-regulated with Fe-MBF filling, causing improvement on nitrogen removal.

Updated information concerning trends in suicide rates in elderly in China, 2002-2020.

The aim of this study was to investigate trends in suicide rates (SRs) among the elderly in China. Annual data on SRs among Chinese people ≥ the age of 65 were collected from China's Health Statistics Yearbook from 2002 to 2020. Then, data were stratified by age, region, and sex. Standardized SRs were calculated and analyzed using a conventional joinpoint regression model. Results revealed that overall, SRs among the elderly in China tended to decline from 2002-2020. Fluctuations in SRs, including in 2004-2005 due to the SARS epidemic, in 2009-2010 due to the economic crisis, and in 2019-2020 due to the COVID-19 pandemic, were also observed. Data suggested a relatively greater crude SR among the elderly (vs. young people), in males (vs. females), and in people living in a rural area (vs. those living in an urban area). SRs tended to rise with age. Joinpoint regression analysis identified joinpoints only for males ages 65-69 and over the age of 85 living in a rural area, suggesting that individuals in these groups are more sensitive to negative stimuli and more likely to commit suicide, necessitating closer attention. The findings from this study should help to make policy and devise measures against suicide in the future.

Endothelial Autophagy Promotes Atheroprotective Communication Between Endothelial and Smooth Muscle Cells via Exosome-Mediated Delivery of miR-204-5p.

BACKGROUND: Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the biological mechanism involved in cellular communication among these cells and whether this biological mechanism can be used to treat atherosclerosis remain unknown. We hypothesized that endothelial autophagy mediates the cellular communication in vascular tissue through exosome-mediated delivery of atherosclerosis-related genes. METHODS: Rapamycin and adeno-associated virus carrying Atg7 short hairpin RNA under the Tie (TEK receptor tyrosine kinase) promoter were used to activate and inhibit vascular endothelial autophagy in high-fat diet-fed ApoE-/- mice, respectively. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue were used to explore the effects of endothelial autophagy on endothelial function and atherosclerosis and its molecular mechanisms. Quantitative polymerase chain reaction and miRNA sequencing were performed to determine changes in miRNA expression in exosomes. Immunofluorescence and exosome coculture experiments were conducted to examine the role of endothelial autophagy in regulating the communication between endothelial cells and smooth muscle cells (SMCs) via exosomal miRNA. RESULTS: Endothelial autophagy was inhibited in thoracic aortas of high-fat diet-fed ApoE-/- mice. Furthermore, rapamycin alleviated high-fat diet-induced atherosclerotic burden and endothelial dysfunction, while endothelial-specific Atg7 depletion aggravated the atherosclerotic burden. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue analysis revealed that miR-204-5p was significantly increased in endothelial cells after high-fat diet exposure, which directly targeted Bcl2 to regulate endothelial cell apoptosis. Importantly, endothelial autophagy activation decreased excess miR-204-5p by loading miR-204-5p into multivesicular bodies and secreting it through exosomes. Moreover, exosomal miR-204-5p can effectively transport to SMCs, alleviating SMC calcification by regulating target proteins such as RUNX2 (runt-related transcription factor 2). CONCLUSIONS: Our study revealed the exosomal pathway by which endothelial autophagy protects atherosclerosis: endothelial autophagy activation transfers miR-204-5p from endothelial cells to SMCs via exosomes, both preventing endothelial apoptosis and alleviating SMC calcification. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2200064155.

"One-Pot" Readout Cyano-Programmable SERS-Encoded Platform Enables Ultrasensitive and Interference-Free Detection of Multitarget Bioamines.

Surface-enhanced Raman spectroscopy (SERS) detection platforms with high signal-to-noise ratio in the "biological-silent" region (1800-2800 cm-1) are presently being developed for sensing and imaging applications, overcoming the limitations of traditional SERS studies in the "fingerprint" region. Herein, a series of cyano-programmable Raman reporters (RRs) operating in the "biological-silent" region were designed based on 4-mercaptobenzonitrile derivatives and then embedded in core-shell Au@Ag nanostars using a "bottom-up" strategy to provide SERS enhancement and encapsulation protection. The approach enabled the "one-pot" readout interference-free detection of multiple bioamines (histamine, tyramine, and ß-phenethylamine) based on aptamer-driven magnetic-induced technology. Three cyano-encoded SERS tags resulted in separate SERS signals for histamine, tyramine, and ß-phenethylamine at 2220, 2251, and 2150 cm-1, respectively. A target-specific aptamer-complementary DNA competitive binding strategy allowed the formation of microscale core-satellite assemblies between Fe3O4-based magnetic beads and the SERS tags, enabling multiple SERS signals to be observed simultaneously under a 785 nm laser excitation laser. The LODs for detection of the three bioamines were 0.61 × 10-5, 2.67 × 10-5, and 1.78 × 10-5 mg L-1, respectively. The SERS-encoded platform utilizing programmable reporters provides a fast and sensitive approach for the simultaneous detection of multiple biomarkers, paving the way for routine SERS analyses of multiple analytes in complex matrices.

Enhancing DNA-based nanodevices activation through cationic peptide acceleration of strand displacement.

Dynamic DNA-based nanodevices offer versatile molecular-level operations, but the majority of them suffer from sluggish kinetics, impeding the advancement of device complexity. In this work, we present the self-assembly of a cationic peptide with DNA to expedite toehold-mediated DNA strand displacement (TMSD) reactions, a fundamental mechanism enabling the dynamic control and actuation of DNA nanostructures. The target DNA is modified with a fluorophore and a quencher, so that the TMSD process can be monitored by recording the time-dependent fluorescence changes. The boosting effect of the peptides is found to be dependent on the peptide/DNA N/P ratio, the toehold/invader binding affinity, and the ionic strength with stronger effects observed at lower ionic strengths, suggesting that electrostatic interactions play a key role. Furthermore, we demonstrate that the cationic peptide enhances the responsiveness and robustness of DNA machinery tweezers or logic circuits (AND and OR) involving multiple strand displacement reactions in parallel and cascade, highlighting its broad utility across DNA-based systems of varying complexity. This work offers a versatile approach to enhance the efficiency of toehold-mediated DNA nanodevices, facilitating flexible design and broader applications.

An In Vitro Study of the Impact of IL-17A and IL-22 on Ciliogenesis in Nasal Polyps Epithelium via the Hippo-YAP Pathway.

BACKGROUND: Cilia loss and impaired motile ciliary functions are one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin-17A (IL-17A) and interleukin-22 (IL-22) are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL-17A and IL-22 on ciliated cells and investigate the potential involvement of Hippo-Yes-associated protein (YAP) signaling in their influence on ciliogenesis. METHODS: We assessed both the mRNA and protein expression levels of IL-17A and IL-22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL-17A and IL-22, we established a primary human nasal epithelial cell (hNEC) model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface (ALI) culture. Additionally, we employed the inhibitor verteporfin (VP) to investigate whether IL-17A andIL-22 exert their effects on ciliated cells via Hippo-YAP pathway. RESULTS: The mRNA and protein levels of IL-17A and IL-22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL-17A and IL-22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL-17A and IL-22 were found to reduce the number of ciliated cells. IL-17A, but not IL-22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL-17A only. YAP inhibitors, such as Verteporfin, markedly reversed the effects of IL-17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency. CONCLUSIONS: Both IL-17A and IL-22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL-17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.

Characterization of linoleate dioxygenases in basidiomycetes and the functional role of CcLdo1 in regulating fruiting body development in Coprinopsis cinerea.

Coprinopsis cinerea, a model fungus, is utilized for investigating the developmental mechanisms of basidiomycetes. The development of basidiomycetes is a highly organized process that requires coordination among genetic, environmental, and physiological factors. Oxylipins, a class of widely distributed signaling molecules, play crucial roles in fungal biology. Among oxylipins, the sexual pheromone-inducing factors (psi factors) have been identified as key regulators of the balance between asexual and sexual spore development in Ascomycetes. Linoleate dioxygenases are enzymes involved in the biosynthesis of psi factors, yet their specific physiological functions in basidiomycete development remain unclear. In this study, linoleate dioxygenases in basidiomycetes were identified and characterized. Phylogenetic analysis revealed that linoleate dioxygenases from Basidiomycota formed a distinct clade, with linoleate dioxygenases from Agaricomycetes segregating into three groups and those from Ustilaginomycetes forming a separate group. Both basidiomycete and ascomycete linoleate dioxygenases shared two characteristic domains: the N-terminal of linoleate dioxygenase domain and the C-terminal of cytochrome P450 domain. While the linoleate dioxygenase domains exhibited similarity between basidiomycetes and ascomycetes, the cytochrome P450 domains displayed high diversity in key sites. Furthermore, the gene encoding the linoleate dioxygenase Ccldo1 in C. cinerea was knocked out, resulting in a significant increase in fruiting body formation without affecting asexual conidia production. This observation suggests that secondary metabolites synthesized by CcLdo1 negatively regulate the sexual reproduction process in C. cinerea while not influencing the asexual reproductive process. This study represents the first identification of a gene involved in secondary metabolite synthesis that regulates basidiocarp development in a basidiomycete.

U.S.-U.K. PETs Prize Challenge: Anomaly Detection via Privacy-Enhanced Federated Learning.

Privacy Enhancing Technologies (PETs) have the potential to enable collaborative analytics without compromising privacy. This is extremely important for collaborative analytics can allow us to really extract value from the large amounts of data that are collected in domains such as healthcare, finance, and national security, among others. In order to foster innovation and move PETs from the research labs to actual deployment, the U.S. and U.K. governments partnered together in 2021 to propose the PETs prize challenge asking for privacy-enhancing solutions for two of the biggest problems facing us today: financial crime prevention and pandemic response. This article presents the Rutgers ScarletPets privacy-preserving federated learning approach to identify anomalous financial transactions in a payment network system (PNS). This approach utilizes a two-step anomaly detection methodology to solve the problem. In the first step, features are mined based on account-level data and labels, and then a privacy-preserving encoding scheme is used to augment these features to the data held by the PNS. In the second step, the PNS learns a highly accurate classifier from the augmented data. Our proposed approach has two major advantages: 1) there is no noteworthy drop in accuracy between the federated and the centralized setting, and 2) our approach is flexible since the PNS can keep improving its model and features to build a better classifier without imposing any additional computational or privacy burden on the banks. Notably, our solution won the first prize in the US for its privacy, utility, efficiency, and flexibility.

PIM1/NF-κB/CCL2 blockade enhances anti-PD-1 therapy response by modulating macrophage infiltration and polarization in tumor microenvironment of NSCLC.

Elevated infiltration of tumor-associated macrophages (TAMs) drives tumor progression and correlates with poor prognosis for various tumor types. Our research identifies that the ablation of the Pim-1 proto-oncogene (PIM1) in non-small cell lung cancer (NSCLC) suppresses TAM infiltration and prevents them from polarizing toward the M2 phenotype, thereby reshaping the tumor immune microenvironment (TME). The predominant mechanism through which PIM1 exerts its impact on macrophage chemotaxis and polarization involves CC motif chemokine ligand 2 (CCL2). The expression level of PIM1 is positively correlated with high CCL2 expression in NSCLC, conferring a worse overall patient survival. Mechanistically, PIM1 deficiency facilitates the reprogramming of TAMs by targeting nuclear factor kappa beta (NF-κB) signaling and inhibits CCL2 transactivation by NSCLC cells. The decreased secretion of CCL2 impedes TAM accumulation and their polarization toward a pro-tumoral phenotype. Furthermore, Dual blockade of Pim1 and PD-1 collaboratively suppressed tumor growth, repolarized macrophages, and boosted the efficacy of anti-PD-1 antibody. Collectively, our findings elucidate the pivotal role of PIM1 in orchestrating TAMs within the TME of NSCLC and highlight the potential of PIM1 inhibition as a strategy for enhancing the efficacy of cancer immunotherapy.

Pharmacological activity and clinical application analysis of traditional Chinese medicine ginger from the perspective of one source and multiple substances.

All types of ginger have common fundamental components, although they possess distinct strengths and inclinations when it comes to effectiveness and medicinal applications. Fresh ginger possesses the ability to effectively stimulate movement within the body, alleviate the act of vomiting, induce sweating, and provide relief for external syndromes. Dried ginger possesses both defensive and stimulant characteristics, which effectively raise the internal temperature and enhance the Yang energy. Fresh ginger is more hydrating than dried ginger, highly skilled at heating the Middle-jiao, alleviating pain, halting bleeding, and managing diarrhea. Dried ginger possesses the ability to alleviate coldness when consumed in a heated form, as well as to alleviate diarrhea when consumed in a heated form. It thrives in warm conditions and has a tendency to revert back to its warm nature. The moisture content of baked ginger is inferior to that of dried ginger, but it is highly effective in alleviating pain, bleeding, and diarrhea by warming the Middle-jiao. Ginger charcoal and stir-fried charcoal, produced through carbonization, have excellent heat retention properties and are effective in warming meridians and stopping bleeding. The potency and ability to spread of roasted ginger is less intense compared to fresh ginger, and its moisture content is not as low as that of dried ginger. The medicinal characteristics of this substance are gentle, making it beneficial for alleviating vomiting in patients who are physically frail. Its primary mode of action is on the Middle-jiao. Nevertheless, the main chemical compositions of various traditional Chinese medicines are nearly identical due to their shared base element. Ginger, in particular, possesses a range of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-bacterial, and anticoagulant properties. However, modern pharmacological research has not fully acknowledged the clinical medicinal value of ginger and consequently, fails to provide accurate guidance for clinical medication. This situation has a negative impact on the contemporary advancement of traditional Chinese medicine (TCM). The research on modernizing ginger is conducted by analyzing and considering the prospects. It is based on Traditional Chinese Medicine (TCM) theory and incorporates the comprehensive perspective of TCM philosophy. In order to modernize ginger, it is essential to have a proper knowledge of the concepts of "recognizing nature by efficacy, homology, and mutual expression of nature and efficacy" and "rationally utilizing modern drug research technology". By applying these principles, we can construct a bridge towards the advancement of ginger.

Effects of stimulating single acupoint and combination acupoints on diabetic gastroparesis: A randomised controlled trial study.

Background and aim: The most effective among the acupoints remains to be determined for treating diabetic gastroparesis (DGP). This study aimed to compare single and combination acupoints for their effectiveness in DGP. Experimental procedure: A prospective, patient-assessor-blinded randomised controlled trial was designed to compare the efficacy of 8-week acupuncture at a single acupoint (Zhongwan, CV-12), combination acupoints (Zhongwan, CV-12 and Zusanli, ST-36), and a sham-acupoint, in 99 adults with DGP. The primary clinical outcome was measured using the Gastroparesis Cardinal Symptom Index (GCSI), while barium meal examination, fasting plasma glucose, the 2-h plasma glucose, short-form health survey (SF-36), and GCSI subscales were performed for evaluating secondary clinical outcomes. These results were analysed by two factorial analysis of variance (ANOVA) test, Chi-Square, Fisher Exact, Kruskal-Wallis tests and Tukey's Honest Significant Difference (HSD) test. Results: After randomization, 97 patients completed the study. GCSI scores of all groups decreased during both post-treatment and the follow-up period, they were statistically significant compared to the baseline period (p < 0.01), but there was no significant difference among the groups (p > 0.05) during the post-treatment period. GCSI scores improved more in the combination acupoints group than in the single acupoint group which was better than the sham group after treatment. During the follow-up period, the same trend was observed. Conclusions: Among patients with DGP, the combination acupoints were more beneficial compared with single and sham acupoints. Trial registration number: NCT02452489.

Nicotinamide riboside alleviates ionizing radiation-induced intestinal senescence by alleviating oxidative damage and regulating intestinal metabolism.

INTRODUCTION: The intestine, frequently subjected to pelvic or abdominal radiotherapy, is particularly vulnerable to delayed effects of acute radiation exposure (DEARE) owing to its high radiation sensitivity. Radiation-induced intestinal senescence, a result of DEARE, profoundly affects the well-being and quality of life of radiotherapy patients. However, targeted pharmaceutical interventions for radiation-induced senescence are currently scarce. Our findings showcase that nicotinamide riboside(NR) effectively alleviates radiation-induced intestinal senescence, offering crucial implications for utilizing NR as a pharmacological agent to combat intestinal DEARE. OBJECTIVES: The aim of this study was to investigate the ability of NR to reduce radiation induced intestinal senescence and explore its related mechanisms. METHODS: Male C57BL/6J mice were randomly divided into CON, IR, and IR + NR groups. The mice in the IR and IR + NR groups were subjected to a 6.0 Gy γ-ray total body exposure. After 8 weeks, the mice in the IR + NR group received NR via gavage at a dose of 400 mg/kg/d for 21 days. Then the mice were used for sample collection. RESULTS: Our results demonstrate that NR can significantly mitigate radiation-induced intestinal senescence. Furthermore, our findings indicate that NR can mitigate oxidative damage, restore the normal function of intestinal stem cells, regulate the disruption of the intestinal symbiotic ecosystem and address metabolic abnormalities. In addition, the underlying mechanisms involve the activation of SIRT6, SIRT7 and the inhibition of the mTORC1 pathway by NR. CONCLUSION: In conclusion, our results reveal the substantial inhibitory effects of NR on radiation-induced intestinal senescence. These findings offer valuable insights into the potential therapeutic use of NR as a pharmacological agent for alleviating intestinal DEARE.

The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa. Methods: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis. Results: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (ß=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (ß=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (ß=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (ß=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%). Conclusions: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Micro-flow cell washing technique combined with single-cell Raman spectroscopy for rapid and automatic antimicrobial susceptibility test of pathogen in urine.

Facing the rapid spread of antimicrobial resistance, methods based on single-cell Raman spectroscopy have proven their advances in reducing the turn-around time (TAT) of antimicrobial susceptibility tests (AST). However, the Raman-based methods are still hindered by the prolonged centrifugal cell washing procedure, which may require complex labor operation and induce high mechanical stress, resulting in a pretreatment time of over 1 h as well as a high cell-loss probability. In this study, we developed a micro-flow cell washing device and corresponding Raman-compatible washing chips, which were able to automatically remove the impurities in the samples, retain the bacterial cell and perform Raman spectra acquisition in situ. Results of washing the 5- and 10-µm polymethyl methacrylate (PMMA) microspheres showed that the novel technique achieved a successful removal of 99 % impurity and an 80 % particle retention rate after 6 to 10 cycles of washing. The micro-flow cell washing technique could complete the pretreatment for urine samples in a 96-well plate within 10 min, only taking 15 % of the handling time required by centrifugation. The AST profiles of urine sample spiked with E. coli 25922, E. faecalis 29212, and S. aureus 29213 obtained by the proposed Raman-based approach were found to be 100 % consistent with the results from broth micro-dilution while reducing the TAT to 3 h from several days which is required by the latter. Our study has demonstrated the micro-flow cell washing technique is a reliable, fast and compatible approach to replace centrifuge washing for sample pretreatment of Raman-AST and could be readily applied in clinical scenarios.

Adjustments in energy metabolism of brown adipose tissue in heat-acclimated Kunming mice.

The thermogenic capacity of brown adipose tissue (BAT) in rodents decreases with prolonged heat exposure. However, the underlying mechanisms are not well understood. In this study, Kunming mice were acclimated at 23 ± 1 °C and 33 ± 1 °C for four weeks each to examine the body heat balance and BAT alterations. Results showed that heat-acclimated Kunming mice exhibited reduced body mass and elevated body temperature. Additionally, they displayed lower resting metabolic rates, diminished non-shivering thermogenesis, and reduced BAT thermogenic function. Metabolically, there was a significant reduction in several key metabolites involved in energy metabolism in BAT, including thiamine pyrophosphate, citric acid, cis-Aconitate, isocitric acid, oxoglutaric acid, succinate, fumarate, L-Malic acid, oxaloacetate, flavin mononucleotide, nicotinamide adenine dinucleotide, and adenosine 5'-triphosphate. These findings suggest that BAT adapts to heat acclimation by regulating pathways related to pyruvate oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, which may help maintain thermal homeostasis in Kunming mice.

Near-infrared visualisation of single microparticle electrochemistry for batteries.

While optical microscopy of single particle electrochemistry has proven insightful for future nanoparticle-based batteries, little is explored for micron-sized particles of more practical interest. This is largely hindered by the currently limited methodology. Accordingly, we report transmission optical microscopy using near-infrared light for accessing intra-particle electrochemistry in virtue of strong light penetration as compared to visible light. Using near-infrared (λ > 730 nm) bright-field microscopy, the redox electrochemistry of single LiCoO2 microparticles can be readily measured based on the measurements of optical contrast changes during electrochemical cycling. Further using the established methodology, we discover that the solid-state diffusion inside most single microparticles is distinctly directional, instead of in an isotropic manner from outer to inner as observed for the other particles. This phenomenon is also observed using dark field scattering microscopy with near-infrared light, suggesting non-uniform crystal inner structures responsible for the geometrically asymmetric heterogeneity of charge transfer kinetics within each single particle. These results indicate potential opportunities offered by the near-infrared optical methodology for operando studying practical battery materials.

Trends in maternal and child health in China and its urban and rural areas from 1991 to 2020: a joinpoint regression model.

The long-term trends in maternal and child health (MCH) in China and the national-level factors that may be associated with these changes have been poorly explored. This study aimed to assess trends in MCH indicators nationally and separately in urban and rural areas and the impact of public policies over a 30‒year period. An ecological study was conducted using data on neonatal mortality rate (NMR), infant mortality rate (IMR), under-five mortality rate (U5MR), and maternal mortality ratio (MMR) nationally and separately in urban and rural areas in China from 1991 to 2020. Joinpoint regression models were used to estimate the annual percentage changes (APC), average annual percentage changes (AAPC) with 95% confidence intervals (CIs), and mortality differences between urban and rural areas. From 1991 to 2020, maternal and child mortalities in China gradually declined (national AAPC [95% CI]: NMRs - 7.7% [- 8.6%, - 6.8%], IMRs - 7.5% [- 8.4%, - 6.6%], U5MRs - 7.5% [- 8.5%, - 6.5%], MMRs - 5.0% [- 5.7%, - 4.4%]). However, the rate of decline nationally in child mortality slowed after 2005, and in maternal mortality after 2013. For all indicators, the decline in mortality was greater in rural areas than in urban areas. The AAPCs in rate differences between rural and urban areas were - 8.5% for NMRs, - 8.6% for IMRs, - 7.7% for U5MRs, and - 9.6% for MMRs. The AAPCs in rate ratios (rural vs. urban) were - 1.2 for NMRs, - 2.1 for IMRs, - 1.7 for U5MRs, and - 1.9 for MMRs. After 2010, urban‒rural disparity in MMR did not diminish and in NMR, IMR, and U5MR, it gradually narrowed but persisted. MCH indicators have declined at the national level as well as separately in urban and rural areas but may have reached a plateau. Urban‒rural disparities in MCH indicators have narrowed but still exist. Regular analyses of temporal trends in MCH are necessary to assess the effectiveness of measures for timely adjustments.