Integrative radiopathomics model for predicting progression-free survival in patients with nonmetastatic nasopharyngeal carcinoma.

PURPOSE: To construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients. METHODS: 357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test. RESULTS: The radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724-0.871) in the training set and 0.785 (95% CI: 0.716-0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553-0.706; pathomics: 0.732, 95% CI: 0.662-0.802; clinical model: 0.655, 95% CI: 0.581-0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001). CONCLUSION: The developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.

Comparative analysis of the liver transcriptome in the red-eared slider (Trachemys scripta elegans) post exposure to noise.

Exposure to noise can cause non-auditory health problems and has been widely studied in mammals such as rats and rabbits. However, the non-auditory effects of noise exposure on reptiles (such as red-eared sliders) remain unclear. In this study, we determined the noise exposure-induced transcriptomic changes in the liver of red-eared slider (Trachemys scripta elegans) using Illumina Novaseq6000 sequencing technology. The transcriptome analysis identified 176 differentially expressed genes (DEGs), which were mainly enriched in lipid metabolism. KEGG analysis showed that by affecting the peroxisome proliferator activated receptor (PPAR) signaling pathway these DEGs increased lipid synthesis and decreased lipid oxidation. The Oil Red O staining results validated our data that noise exposure increased hepatic lipid deposition. Thus, noise exposure may lead to lipid accumulation and toxicity, mitochondrial damage, and accelerated oxidative stress. Our findings provide insights into the molecular process underlying non-auditory damage caused by noise exposure in T. scripta elegans.

Predicting progression-free survival in patients with epithelial ovarian cancer using an interpretable random forest model.

Prognostic models play a crucial role in providing personalised risk assessment, guiding treatment decisions, and facilitating the counselling of patients with cancer. However, previous imaging-based artificial intelligence models of epithelial ovarian cancer lacked interpretability. In this study, we aimed to develop an interpretable machine-learning model to predict progression-free survival in patients with epithelial ovarian cancer using clinical variables and radiomics features. A total of 102 patients with epithelial ovarian cancer who underwent contrast-enhanced computed tomography scans were enrolled in this retrospective study. Pre-surgery clinical data, including age, performance status, body mass index, tumour stage, venous blood cancer antigen-125 (CA125) level, white blood cell count, neutrophil count, red blood cell count, haemoglobin level, and platelet count, were obtained from medical records. The volume of interest for each tumour was manually delineated slice-by-slice along the boundary. A total of 2074 radiomic features were extracted from the pre- and post-contrast computed tomography images. Optimal radiomic features were selected using the Least Absolute Shrinkage and Selection Operator logistic regression. Multivariate Cox analysis was performed to identify independent predictors of three-year progression-free survival. The random forest algorithm developed radiomic and combined models using four-fold cross-validation. Finally, the Shapley additive explanation algorithm was applied to interpret the predictions of the combined model. Multivariate Cox analysis identified CA-125 levels (P = 0.015), tumour stage (P = 0.019), and Radscore (P < 0.001) as independent predictors of progression-free survival. The combined model based on these factors achieved an area under the curve of 0.812 (95 % confidence interval: 0.802-0.822) in the training cohort and 0.772 (95 % confidence interval: 0.727-0.817) in the validation cohort. The most impactful features on the model output were Radscore, followed by tumour stage and CA-125. In conclusion, the Shapley additive explanation-based interpretation of the prognostic model enables clinicians to understand the reasoning behind predictions better.

Comparative study on the transcriptional activities of grass carp (Ctenopharyngodon idellus) peroxisome proliferator-activated receptors induced by different fatty acids.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are part of the nuclear hormone receptor family, playing a crucial role in gene expression regulation. They serve as a connection between lipid metabolism disorders and innate immunity by being activated by fatty acids and their derivatives, facilitating signal transduction between the cell surface and nucleus. However, the specific transcriptional effects of different fatty acids (FAs) in fish are not yet fully understood. In our research, we identified and characterized PPARs in grass carp (Ctenopharyngodon idellus). The complete coding sequences of pparαa, pparαb, pparγ, pparδa, and pparδb were 1443 bp, 1404 bp, 1569 bp, 1551 bp, and 1560 bp in length, respectively. Pparα showed the highest expression in the liver, pparγ was mainly expressed in abdominal adipose tissue, and pparδ exhibited increased expression in the heart compared to other tissues. Gene localization analysis revealed that only pparδa was present in both the nucleus and cytoplasm, while the other four genes were exclusively located in the nucleus. Furthermore, our study explored the influence of various fatty acids (docosahexaenoic acid, palmitic acid, lauric acid and oleic acid at concentrations of 0, 50, 100, and 200 µM) on the transcriptional activities of different PPARs, demonstrating the diverse effects of fatty acid ligands on PPAR transcriptional activity. These results have significant implications for understanding the regulation of PPARs transcriptional activity.

A comparative study of dietary amino acid patterns: unveiling growth, composition, and molecular signatures in juvenile Onychostoma macrolepis.

The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary amino acid pattern is crucial for optimal feed formulation. This study aimed to investigate the effects of the four different dietary amino acid patterns, i.e., anchovy fishmeal protein (FMP, control group) and muscle protein (MP), whole-body protein (WBP), fish egg protein (FEP) of juvenile Onychostoma macrolepis, on the growth performance, body composition, intestinal morphology, enzyme activities, and the expression levels of gh, igf, mtor genes in juveniles. In a 12-week feeding trial with 240 juveniles (3.46±0.04g), the MP group demonstrated superior outcomes in growth performance (FBW, WGR, SGR), feed utilization efficiency (PER, PRE, FCR). Notably, it exhibited higher crude protein content in whole-body fish, enhanced amino acid composition in the liver, and favorable fatty acid health indices (AI, TI, h/H) in muscle compared to other groups (P < 0.05). Morphologically, the MP and FMP groups exhibited healthy features. Additionally, the MP group displayed significantly higher activities of TPS, ALP, and SOD, along with elevated expression levels of gh, igf, mtor genes, distinguishing it from the other groups (P < 0.05). This study illustrated that the amino acid pattern of MP emerged as a suitable dietary amino acid pattern for juvenile Onychostoma macrolepis. Furthermore, the findings provide valuable insights for formulating effective feeds in conserving and sustainably farming protected species, enhancing the research's broader ecological and aquacultural significance.

MRI-based radiomics models predict cystic brain radionecrosis of nasopharyngeal carcinoma after intensity modulated radiotherapy.

Objective: To construct radiomics models based on MRI at different time points for the early prediction of cystic brain radionecrosis (CBRN) for nasopharyngeal carcinoma (NPC). Methods: A total of 202 injured temporal lobes from 155 NPC patients with radiotherapy-induced temporal lobe injury (RTLI) after intensity modulated radiotherapy (IMRT) were included in the study. All the injured lobes were randomly divided into the training (n = 143) and validation (n = 59) sets. Radiomics models were constructed by using features extracted from T2WI at two different time points: at the end of IMRT (post-IMRT) and the first-detected RTLI (first-RTLI). A delta-radiomics feature was defined as the percentage change in a radiomics feature from post-IMRT to first-RTLI. The radiomics nomogram was constructed by combining clinical risk factors and radiomics signatures using multivariate logistic regression analysis. Predictive performance was evaluated using area under the curve (AUC) from receiver operating characteristic analysis and decision curve analysis (DCA). Results: The post-IMRT, first-RTLI, and delta-radiomics models yielded AUC values of 0.84 (95% CI: 0.76-0.92), 0.86 (95% CI: 0.78-0.94), and 0.77 (95% CI: 0.67-0.87), respectively. The nomogram exhibited the highest AUC of 0.91 (95% CI: 0.85-0.97) and sensitivity of 0.82 compared to any single radiomics model. From the DCA, the nomogram model provided more clinical benefit than the radiomics models or clinical model. Conclusion: The radiomics nomogram model combining clinical factors and radiomics signatures based on MRI at different time points after radiotherapy showed excellent prediction potential for CBRN in patients with NPC.

Fish oil replacement with different vegetable oils in Onychostoma macrolepis: Effects on fatty acid metabolism based on whole-body fatty acid balance method and genes expression.

To evaluate the fatty acid (FA) metabolism status and possibility as a DHA source of farmed Onychostoma macrolepis, a total of 168 fish (2.03 ± 0.23 g) were fed four diets supplemented with fish oil (FO), linseed oil (LO), soybean oil (SO), and a mixture of LO and SO oil (MO), respectively, for 70 days. Body FA compositions were modified reflecting dietary FAs. Comparing liver and intestine fatty acids with fish fed four diets, the content of ARA in fish fed SO was significantly higher than others (P < 0.05), but showed no difference in muscle. The tissue FA profile showed that the FO-fed group successfully deposited DHA, while the LO-fed group converted ALA to DHA effectively, as well as the liver and intestine EPA was notably highest in the FO group, whereas no difference between the FO and LO group in the muscle. The FA results showed that the DHA contents in the muscle of Onychostoma macrolepis are at a medium-high level compared with several other fish species with the highest aquaculture yield. Correspondingly, in the fish fed diet with LO, SO, and MO, the genes of most FA biosynthesis, transportation, and transcriptional regulation factors were increased in the liver and muscle, but no significant difference was observed in the gene expression of Elovl4b, FATP1, and FABP10 in the muscle. In addition, the enzyme activity involved in PUFA metabolism was higher in fish fed vegetable oil-based diets, corroborating the results of the gene expression. Increased in vivo elongase and desaturase (Δ5, Δ6, and Δ9) activities were recorded in fish fed fish oil-devoid diets, which resulted in the appearance of products associated with elongase and desaturase activities in fish. Besides, as the specific n-3 PUFA synthesis substrate, the dietary supplementation of ALA not only retains most of the nutrition value but also ensures the muscular texture, such as fiber diameter and density. It is concluded that farmed O. macrolepis owns strong n-3 LC-PUFA biosynthetic capacity and high DHA contents so it can be a good DHA source for the population.

Research on social and economic factors influencing regional mortality patterns in China.

Regional population mortality correlates with regional socioeconomic development. This study aimed to identify the key socioeconomic factors influencing mortality patterns in Chinese provinces. Using data from the Seventh Population Census, we analyzed mortality patterns by gender and urban‒rural division in 31 provinces. Using a functional regression model, we assessed the influence of fourteen indicators on mortality patterns. Main findings: (1) China shows notable gender and urban‒rural mortality variations across age groups. Males generally have higher mortality than females, and rural areas experience elevated mortality rates compared to urban areas. Mortality in individuals younger than 40 years is influenced mainly by urban‒rural factors, with gender becoming more noticeable in the 40-84 age group. (2) The substantial marginal impact of socioeconomic factors on mortality patterns generally becomes evident after the age of 45, with less pronounced differences in their impact on early-life mortality patterns. (3) Various factors have age-specific impacts on mortality. Education has a negative effect on mortality in individuals aged 0-29, extending to those aged 30-59 and diminishing in older age groups. Urbanization positively influences the probability of death in individuals aged 45-54 years, while the impact of traffic accidents increases with age. Among elderly people, the effect of socioeconomic variables is smaller, highlighting the intricate and heterogeneous nature of these influences and acknowledging certain limitations.

Comorbidity risk and distribution characteristics of chronic diseases in the elderly population in China.

BACKGROUND: The risk of comorbid chronic diseases in elderly people is an important problem affecting their health and quality of life. We analyzed the incidence of chronic diseases for combinations of chronic diseases analyzed. METHODS: We used the original data to construct hypothetical cohorts of elderly individuals that evolved with age. The complex network was used to reduce the dimensionality of disease. The multistate transition model is used to calculate the incidence of each chronic disease, exploring comorbidity characteristics and rules. RESULTS: (1) By using complex network, seven chronic diseases were screened out in men, including hypertension, diabetes, heart disease, stroke, chronic lung disease, arthritis and dyslipidemia; six chronic diseases in women showed significant comorbidity except chronic lung disease. (2) Incidence show differences in age and sex; incidence of chronic diseases generally increased with age. (3) The marginal risk increases with the number of basic chronic diseases associated with comorbidities. (4) When hypertension is present as a basic disease, its impact on the risk of other chronic diseases is much less than that of other chronic diseases. (5) When diseases occur as basic chronic diseases, hypertension-heart disease and diabetes-dyslipidemia are combinations that have the greatest impact on each other in men; hypertension-heart disease in women. CONCLUSIONS: The incidence of chronic diseases in patients who have chronic diseases and will form comorbidities differs from that in healthy states, and the related effects of different chronic diseases also differ. Among these conditions, hypertension is caused by a special mechanism.

Evolution of radiation-induced temporal lobe injury after intensity-modulated radiation therapy in nasopharyngeal carcinoma: a large cohort retrospective study.

BACKGROUND: Previous studies have demonstrated conflicting findings regarding the initial MRI patterns of radiotherapy-induced temporal lobe injury (RTLI) and the evolution of different RTLI patterns. The aim of this study was to evaluate the initial MRI pattern and evolution of RTLI in patients with nasopharyngeal carcinoma (NPC) by means of a large cohort study. METHODS: Data of patients with RTLI were retrospectively collected from two hospitals between January 2011 and December 2021. The injured lobes were categorized into three patterns based on initial MRI patterns: isolated white matter lesions (WMLs), isolated contrast-enhanced lesions (CELs), and combined WMLs and CELs. The latency period, MRI appearances, and temporal changes in WMLs and CELs were evaluated. RESULTS: A total of 913 RTLI patients with 1092 injured lobes were included in this study. The numbers of isolated WMLs, isolated CELs, and combined WMLs and CELs identified at the first MRI detection were 7 (0.6%), 172 (15.8%), and 913 (83.6%), respectively. The evolution of bilateral RTLI was different in the same patient, and that of unilateral RTLI combined with WMLs and CELs also may occur asynchronously. The time intervals from the initial MRI detection of isolated WMLs, isolated CELs, combined WMLs and CELs to the last negative MRI scan were 8.6, 8.9 and 11.0 months, respectively. A significant difference was observed in the time intervals between the three patterns (H = 14.287, P = 0.001). And the time interval was identified as an independent factor influencing the initial MRI pattern of RTLI after Poisson regression (P = 0.002). CONCLUSION: Both WMLs and CELs could be the initial and only MRI abnormalities in patients with RTLI. This study is of great significance in accurately diagnosing RTLI early and providing timely treatment options. Additionally, it provides clinical evidence for guidelines on NPC, emphasizing the importance of regular follow-up of NPC patients.

Eicosapentaenoic acid (EPA) improves grass carp (Ctenopharyngodon idellus) muscle development and nutritive value by activating the mTOR signaling pathway.

Skeletal muscle is the mainly edible part of fish. Eicosapentaenoic acid (EPA) is a crucial nutrient for fish. This study investigated the effect of EPA on the muscle development of grass carp along with the potential molecular mechanisms in vivo and in vitro. Muscle cells treated with 50 µM EPA in vitro showed the elevated proliferation, and the expression of mammalian target of rapamycin (mTOR) signaling pathway-related genes was upregulated (P < 0.05). In vivo experiments, 270 grass carp (27.92 g) were fed with one of the three experimental diets for 56 days: control diet (CN), 0.3% EPA-supplement diet (EPA), and the diet supplemented with 0.3% EPA and 30 mg/kg rapamycin (EPA + Rap). Fish weight gain rate (WGR) was improved in EPA group (P < 0.05). There was no difference in the viscerosomatic index (VSI) and body height (BH) among all groups (P > 0.05), whereas the carcass ratio (CR) and body length in the EPA group were obviously higher than those of other groups (P < 0.05), indicating that the increase of WGR was due to muscle growth. In addition, both muscle fiber density and muscle crude protein also increased in EPA group (P < 0.05). The principal component analysis showed that total weight of muscle amino acid in EPA group ranked first. Dietary EPA also increased protein levels of the total mTOR, S6k1, Myhc, Myog, and Myod in muscle (P < 0.05). In conclusion, EPA promoted the muscle development and nutritive value via activating the mTOR signaling pathway.

MXene Enhanced 3D Needled Waste Denim Felt for High-Performance Flexible Supercapacitors.

MXene, a transition metal carbide/nitride, has been prominent as an ideal electrochemical active material for supercapacitors. However, the low MXene load limits its practical applications. As environmental concerns and sustainable development become more widely recognized, it is necessary to explore a greener and cleaner technology to recycle textile by-products such as cotton. The present study proposes an effective 3D fabrication method that uses MXene to fabricate waste denim felt into ultralight and flexible supercapacitors through needling and carbonization. The 3D structure provided more sites for loading MXene onto Z-directional fiber bundles, resulting in more efficient ion exchange between the electrolyte and electrodes. Furthermore, the carbonization process removed the specific adverse groups in MXenes, further improving the specific capacitance, energy density, power density and electrical conductivity of supercapacitors. The electrodes achieve a maximum specific capacitance of 1748.5 mF cm-2 and demonstrate remarkable cycling stability maintaining more than 94% after 15,000 galvanostatic charge/discharge cycles. Besides, the obtained supercapacitors present a maximum specific capacitance of 577.5 mF cm-2, energy density of 80.2 µWh cm-2 and power density of 3 mW cm-2, respectively. The resulting supercapacitors can be used to develop smart wearable power devices such as smartwatches, laying the foundation for a novel strategy of utilizing waste cotton in a high-quality manner.

lpla (lipoprotein lipase a) is a marker of early adipogenesis rather than late adipogenesis in grass carp (Ctenopharyngodon idellus).

Lipoprotein lipase (LPL) functions as a marker of adipocyte differentiation in mammals, but little is known about its role in fish adipogenesis. The aim of this research is to investigate the function of Lpl in adipocyte differentiation in fish. In this paper, we isolated and characterized lipoprotein lipase a (lpla) and lipoprotein lipase b (lplb) from grass carp (Ctenopharyngodon idellus). The complete coding sequence of lpla and lplb was 1524 bp and 1503 bp in length, coding for 507 amino acids and 500 amino acids, respectively. Both lpla and lplb mRNA were expressed in a great number of tissues. During adipogenesis, the level of lpla mRNA reached its maximum at day 2 and then dropped gradually, while the level of lplb mRNA had no significant changes, indicating that lpla and lplb may have different function in the differentiation of grass carp adipocyte. Furthermore, inhibition of lpla by inhibitor of LPL(GSK264220A) at early time points most clearly reduced adipogenesis, whereas these effects were less pronounced at later stages, suggesting that lpla predominantly affects early adipogenesis rather than late adipogenesis. Based on these findings, it can be inferred that lpla and lplb in grass carp may have distinct roles in the differentiation of grass carp adipocyte, and lpla may play an important role in the early adipogenesis rather than late adipogenesis in grass carp.

Assessment of black soldier fly (Hermetia illucens) larvae meal as a potential substitute for soybean meal on growth performance and flesh quality of grass carp Ctenopharyngodon idellus.

A 90-day feeding trial was conducted to assess the effects of black soldier fly larvae meal (BSFLM) as a replacement for soybean meal (SM) on growth performance and flesh quality of grass carp. A total of 420 grass carp (299.93 ± 0.85 g) were randomly divided into 7 groups (triplicate) and fed 7 diets with SM substitution of 0% (SM, control), 15% (BSFLM15), 30% (BSFLM30), 45% (BSFLM45), 60% (BSFLM60), 75% (BSFLM75) and 100% (BSFLM100) by BSFLM. The growth performance of grass carp in the BSFLM75 and BSFLM100 groups were significantly lower compared to other groups (P < 0.05). The mid-gut villus height was the lowest in the BSFLM100 group (P < 0.05). Muscle nutritional value was improved due to increased DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), total HUFA (highly unsaturated fatty acids) and glycine levels, and reached the optimum in the BSFLM100 group (P < 0.05). According to the results of principal component analysis and weight analysis of muscle texture and body color, all the BSFLM diets except BSFLM15 could improve muscle texture and body color and reached the optimum level in the BSFLM100 group. Muscle drip loss and hypoxanthine content were the lowest and muscle antioxidant capacity was the highest in the BSFLM75 group, and water- and salt-soluble protein contents reached the optimum level in the BSFLM60 group (P < 0.05). Dietary BSFLM significantly reduced muscle fiber area and diameter, and increased muscle fiber density and the proportion of small fiber (diameter <20 µm) (P < 0.05). Additionally, sarcomere lengths in the BSFLM75 and BSFLM100 groups were significantly higher than that in the SM group (P < 0.05). The mRNA relative expression levels of MyoD, Myf5, MyHC and FGF6b were remarkably up-regulated at an appropriate dietary BSFLM level (P < 0.05). In conclusion, BSFLM could replace up to 60% SM without an adverse effect on growth performance and improve the flesh quality of grass carp. The optimum levels of dietary BSFLM were 71.0 and 69.1 g/kg diet based on the final body weight and feed conversion ratio. The flesh quality was optimal when dietary SM was completely replaced with BSFLM (227 g/kg diet).

Improving flesh quality of grass carp (Ctenopharyngodon idellus) by completely replacing dietary soybean meal with yellow mealworm (Tenebrio molitor).

In order to find viable alternative protein sources for aquaculture, we evaluated the effect of partial or complete replacement of dietary soybean meal with yellow mealworm (TM) on the flesh quality of grass carp. In this study, 180 grass carp (511.85 ± 0.25 g) were fed 3 experimental diets in which 0% (CN), 30% (YM30) and 100% (YM100) dietary soybean meal was replaced by TM for 90 d. The results showed that growth performance, biological parameters and serum antioxidant capacity of grass carp were not affected by dietary TM (P > 0.05). Both muscle and whole body crude protein were obviously promoted with the increase of dietary TM (P < 0.05), and the concentration of heavy metal in muscle was not influenced (P > 0.05), indicating that food safety was not influenced by TM. Dietary TM improved muscle textural characteristics by elevating adhesiveness, springiness and chewiness in YM100 (P < 0.05). In addition, the muscle tenderness was significantly increased by declining the shear force (P < 0.05). The muscle fiber density in YM30 &YM100 and length of dark bands and sarcomeres in YM100 were obviously increased (P < 0.05). The expression of myf5, myog and myhc exhibited a significant upward trend with the increase of dietary TM (P < 0.05), which promoted fiber density, length of sarcomere and texture of grass carp muscle. According to the results of metabolomics, the arachidonate (ARA) and eicosapentaenoic acid (EPA) were notably elevated in YM30 and YM100, which indicated that the improvement of flesh quality of grass carp may contribute to the dietary TM influence on muscle lipid metabolism, especially the polyunsaturated fatty acids. In conclusion, TM can completely replace dietary soybean meal and improve the nutritional value of grass carp.

Sphingosine-1-phosphate receptor modulation improves neurogenesis and functional recovery after stroke.

Cerebral ischemia activates neural progenitors that participate in brain remodeling following acute injury. Sphingosine-1-phosphate receptor (S1PR) signaling governs cell proliferation and mobilization, yet its potential impact on neural progenitors and stroke recovery remains poorly understood. The goal of this study was to investigate the impact of S1PR modulation on post-stroke neurogenesis and functional recovery, using a S1PR modulator BAF312. Mice were subjected to 60 min middle cerebral artery occlusion (MCAO) and received BAF312 starting from day 3 after MCAO until the end of experiment. BAF312 facilitated motor function recovery in MCAO mice until day 14 after surgery. Flow cytometry analysis revealed that BAF312 treatment led to an increase of type A cells in subventricular zone (SVZ), but not other progenitor cell subsets in MCAO mice. We found an increase of BrdU incorporation in SVZ DCX+ cells from MCAO mice receiving BAF312 and augmented proliferation of DCX+ cells in cultured neurospheres isolated from SVZ tissues. Notably, a S1PR1 antagonist W146 abolished BAF312-induced increase of SVZ type A cells from MCAO mice and proliferation of DCX+ cells in cultured neurospheres. Additionally, the benefit of BAF312 to improve neurogenesis and stroke recovery remains in Rag2-/- mice lacking of T and B cells. Our results demonstrate that S1PR modulation improves neurogenesis and functional recovery following brain ischemia.

Alzheimer's disease alters the transcriptomic profile of natural killer cells at single-cell resolution.

Alzheimer's disease (AD) is the most common dementia without an effective cure at least partially due to incomplete understanding of the disease. Inflammation has emerged as a central player in the onset and progression of AD. As innate lymphoid cells, natural killer (NK) cells orchestrate the initiation and evolution of inflammatory responses. Yet, the transcriptomic features of NK cells in AD remain poorly understood. We assessed the diversity of NK cells using web-based single-cell RNA sequencing data of blood NK cells from patients with AD and control subjects and flow cytometry. We identified a contraction of NK cell compartment in AD, accompanied by a reduction of cytotoxicity. Unbiased clustering revealed four subsets of NK cells in AD, i.e., CD56bright NK cells, CD56dim effector NK cells, adaptive NK cells, and a unique NK cell subset that is expanded and characterized by upregulation of CX3CR1, TBX21, MYOM2, DUSP1, and ZFP36L2, and negatively correlated with cognitive function in AD patients. Pseudo-temporal analysis revealed that this unique NK cell subset was at a late stage of NK cell development and enriched with transcription factors TBX21, NFATC2, and SMAD3. Together, our study identified a distinct NK cell subset and its potential involvement in AD.

Bone marrow hematopoiesis drives multiple sclerosis progression.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6Chigh monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders.