Quercetin-loaded Human Umbilical cord Mesenchymal Stem Cell-derived sEVs for Spinal Cord Injury Recovery.

Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood-brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury.

Factors affecting functional disability in patients with non-specific chronic low back pain: a cross-sectional study.

Background: Knowledge about factors affecting functional disability in patients with non-specific chronic low back pain (NSCLBP) is helpful in guiding treatment, but there has been little systematic research on this topic. This study aimed to identify independent factors contributing to functional disability in NSCLBP patients especially the impact of sagittal parameters and body postures in work, learning, and daily life. Methods: Sociodemographic data, sagittal parameters, Oswestry Disability Index (ODI), Numeric Rating Scale (NRS), and 36-item Short Form Health Survey (SF-36) of NSCLBP patients were collected. Patients were divided into a low-functional disability group (ODI ≤ 20) and a high-functional disability group (ODI > 20), and the ODI was converted to ranked ODI (RODI) accordingly. Sociodemographic data, sagittal parameters, NRS, and SF-36 were compared by univariate analysis between both groups. A correlation analysis of the aforementioned factors with the RODI was conducted. The sociodemographic data and sagittal parameters related to the RODI were analyzed by logistic regression to select potential RODI-associated factors. The level of significance was set at P < 0.05. Results: Age, educational background, daily main posture while working or learning (DMPWL), daily standing time while working or learning (DSTTWL), daily sitting time while resting (DSITR), sacral slope-pelvic tilt (SS-PT), spinosacral angle (SSA), NRS, and SF-36 (except mental health, MH) were different between the two groups (P < 0.05). Correlation analysis showed that they were related to the RODI (P < 0.05). The logistic regression analysis indicated that the regression coefficients of a college degree, postgraduate diploma, DSITR, and SSA were (B = -0.197; P = 0.003), (B = -0.211; P = 0.006), (B = -0.139; P = 0.039), and (B = -0.207; P = 0.001), respectively, and the odds ratio (OR) and 95% confidence interval (CI) were 0.489 (0.308; 0.778), 0.299 (0.125; 0.711), 0.875 (0.772; 0.993), and 0.953 (0.925; 0.981), respectively. Conclusion: Educational background, DSITR, and SSA are independent factors affecting functional disability in NSCLBP patients. NSCLBP patients with a lower educational background, shorter DSITR, or smaller SSA should be taken into account in clinical practice and therapeutic choices. Extending sitting time for rest and the avoidance of a forward-leaning standing position are beneficial for reducing functional disability in NSCLBP.

Shaking table test on damage mechanism of bedrock and overburden layer slope based on the time-frequency analysis method.

To systematically analyze the damage caused by bedrock and overburden layer slope under seismic action, a set of large-scale shaking table test was designed and completed. Interpolation of the acceleration amplification coefficient, Hilbert-Huang transform and transfer function was adopted. The damage mechanisms of the bedrock and overburden layer slopes under seismic action are systematically summarized in terms of slope displacement, acceleration field, vibration amplitude, energy, vibration frequency, and damage level. The results show a significant acceleration amplification effect within the slope under seismic action and a localized amplification effect at the top and trailing edges of the slope. With an increase in the input seismic intensity, the difference in the vibration amplitude between the overburden layer and bedrock increased, low-frequency energy of the overburden layer was higher than that of the bedrock, and the vibration frequency of the overburden layer was smaller than that of the bedrock. These differences cause the interface to experience cyclic loading continuously, resulting in the damage degree of the overburden layer at the interface being larger than that of the bedrock, reduction of the shear strength, and eventual formation of landslides. The displacement in the middle of the overburden is always greater than that at the top. Therefore, under the action of an earthquake and gravity, the damage mode of the bedrock and overburden layer slope is such that the leading edge of the critical part pulls and slides at the trailing edge, and multiple tensile cracks are formed on the slope surface.

Renal B-lymphoblastic lymphoma with hematuria as the first symptom diagnosed in urine cytology: A case report and literature review.

Cytological examination of urine sediment is a helpful diagnostic tool for identifying renal involvement by hematological malignancies. We present the case of a 47-year-old man who was diagnosed with extranodal B-lymphoblastic lymphomas after presenting with gross hematuria as his first symptom. The presence of lymphoma cells in the urine led to a diagnosis confirmed through an immunophenotypic study using cell block sections of urine centrifuge sediment and core needle biopsy histology of the right renal pelvis mass. This case highlights the usefulness of a urine cytological study in diagnosing lymphoma involvement in the genitourinary tract. Furthermore, this paper reviews relevant literature on diagnosing lymphoma involvement from urine sediment.

Correlation between sagittal parameters and disability of patients with nonspecific chronic low back pain: a cross-sectional study of 435 subjects.

BACKGROUND CONTEXT: Sagittal parameters are significantly correlated with health-related quality of life (HRQoL) in adult spinal deformity patients. Their association with HRQoL in patients with nonspecific chronic low back pain (NSCLBP) is unclear. PURPOSE: To analyze the correlation between sagittal parameters and disability in NSCLBP patients. DESIGN: A cross-sectional study. PATIENT SAMPLE: Subjects included 435 patients with NSCLBP divided into low disability and high disability groups. OUTCOME MEASURES: Function was measured using the Oswestry Disability Index (ODI). Pain intensity was measured using the Numeric Rating Scale (NRS) and HRQoL was measured using 36-item Short Form Health Survey (SF-36). METHODS: Sagittal parameters, demographic data, ODI, SF-36 eight-dimensional scores and NRS scores of patients with NSCLBP were collected. Taking ODI=20 as the cut-off value, patients were divided into low disability group (ODI≤20) and high disability group (ODI>20), and ODI were converted to Ranked ODI (RODI) accordingly. Univariate analysis of the correlation among age, gender, body mass index (BMI), sagittal parameters, RODI, SF-36 eight-dimensional scores, NRS scores were then conducted. The variables related to RODI were analyzed by logistic regression to discover their independent influence on RODI. p<.05 was considered to indicate statistical significance. RESULTS: A total of 435 patients with NSCLBP were included. Univariate correlation analysis showed that the correlation coefficients between age, sacral slope-pelvic tilt (SS-PT), spinosacral angle (SSA) and RODI were (r=0.126, p<.01), (r=-0.115, p<.05), (r=-0.116, p<.05), respectively. The logistic regression analysis indicated that the regression coefficients of age and SSA were 0.030 (p=.001), -0.044 (p=.002), respectively, and the odds ratio and 95% confidence interval (CI) were 1.031 (1.012, 1.050), 0.957 (0.930, 0.985). CONCLUSIONS: Age and SSA are independent factors for disability of NSCLBP. SSA can comprehensively reflect the sagittal balance of the spine of patients with NSCLBP. Decreased SSA represents poor sagittal balance, which will increase the disability of NSCLBP.

The Impact of the Foliar Application of Amino Acid Aqueous Fertilizer on the Flavor of Potato Tubers.

The quality of the flavor of potatoes is a crucial determinant in the commercial success of a potato variety. Plant nutrition promotes the synthesis of amino acids, and the application of exogenous amino acids has the potential to enhance the flavor quality of potatoes. In this experiment, Dian Shu 1418 and Dian Shu 23 were used as the materials, and different amino acid foliar spray trials were designed. The free amino acid content in potato tubers is determined based on high-performance liquid chromatography, and volatile tuber flavor compounds are detected using gas chromatography-mass spectrometry. The results showed that the amino acid foliar spray effectively increased the content of glycine, methionine, and phenylalanine in the tubers, subsequently increasing the levels of 2,3-dimethyl-pyrazine and 2-ethyl-3-methyl-pyrazine, enhancing the roasted fragrance characteristics of the potatoes. The experimental results provide a reference for cultivating flavor enhancement in potato tubers.

Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes.

Introduction: We aimed to evaluated the effect of premixed insulin (Ins), premixed insulin combined with metformin (Ins+Met) or mulberry twig alkaloids(Ins+SZ-A) on blood glucose fluctuations in patients with type 2 diabetes (T2DM) using continuous glucose monitors (CGM). Methods: Thirty patients with T2DM and poor blood glucose control using drugs were evaluated for eligibility during the screening period. Subsequently, their original hypoglycemic drugs were discontinued during the lead-in period, and after receiving Ins intensive treatment for 2 weeks, they were randomly assigned to receive either Ins, Ins+Met, or Ins+SZ-A treatment for the following 12 weeks. The main efficacy endpoint comprised changes in their CGM indicators changes (mean blood glucose level [MBG], standard deviation of blood glucose [SDBG], mean amplitude of glycemic excursions [MAGE], postprandial glucose excursions [PPGE], the largest amplitude of glycemic excursions [LAGE], mean of daily difference [MODD], time in range between 3.9-10.0 mmol/L [TIR] and area under the curve for each meal [AUCpp]) during the screening, lead-in, and after 12-week treatment period. Changes in glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 1-h postprandial blood glucose (1h-PBG), 2-h postprandial blood glucose (2h-PBG), fasting blood lipids and postprandial blood lipids were also measured at baseline and after 12 weeks of treatment. Results: The CGM indicators of the three groups during the lead-in period all showed significant improvements compared to the screening period (P<0.05). Compared with those in the lead-in period, all of the CGM indicators improved in the the Ins+Met and Ins+SZ-A groups after 12 weeks of treatment (P<0.05), except for MODD. After 12-week treatment, compared with the Ins group, Ins+Met and Ins+SZ-A groups showed improved MBG, SDBG, TIR, breakfast AUCpp,lunch AUCpp, HbA1c, FBG, 1h-PBG, fasting blood lipid and postprandial blood lipid indicators (P<0.05). Further, the LAGE, PPGE, MAGE, dinner AUCpp and 2h-PBG levels of the Ins+SZ-A group were significantly lower than those of the Ins+Met and Ins groups (P<0.05). Conclusion: Our findings highlight the efficacy of combination therapy (Ins+SZ-A or Ins+Met) in improving blood glucose fluctuations, as well as blood glucose and lipid levels. Ins+SZ-A reduces postprandial blood glucose fluctuations more than Ins+Met and Ins groups. Trial registration number: ISRCTN20835488.

A case report of the treatment and care of decubitus ulcers in macaques with spinal cord injury.

Decubitus ulcers are a common spinal cord injury (SCI) complication that puts patients' lives in danger and has emerged as a more prevalent issue in modern clinical rehabilitation and care. Decubitus ulcers in humans can currently be treated in a number of different ways, but there are fewer studies on how to treat and care for decubitus ulcers in macaques. To treat a 20-year-old adult male macaque monkey with SCI and decubitus ulcers after a quarter transection of the thoracic spinal cord, a number of scientific care procedures and pharmaceutical treatments, such as dietary changes and topical or intravenous administration of medication, were carried out and continuously monitored in real-time. In comparison to the untreated group, we observed a significant improvement in decubitus wound healing in the macaques. In this article, we provide a good protocol for decubitus ulcer care after SCI and suggest that future experimental animal modeling needs to focus on issues such as care for postoperative complications.

Development of an innovative minimally invasive primate spinal cord injury model: A case report.

Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.

Ultrarapid-Acting Microneedles for Immediate Delivery of Biotherapeutics.

Subcutaneous (SC) injection is a common administration route for rapid and efficient delivery of biotherapeutics. However, syringe-based injections usually require professional assistance and are associated with pain and potential risks of infections, thus leading to undesired patient compliance and poor life quality. Herein, this work presents an ultrarapid-acting microneedle (URA-MN) patch for immediate transdermal delivery of therapeutics in a minimally invasive manner. Effervescent agents are incorporated into the tip of URA-MN for rapid generation of CO2 bubbles upon insertion into the skin, immediately powering the biotherapeutics release within a few minutes. The release kinetics of diverse agents including liraglutide (LRT), insulin, and heparin from the URA-MN patches are evaluated in three different mouse models, and the rapid release of biotherapeutics and potent therapeutic effects are achieved with only 5 min administration. Noteworthily, attributed to the short application duration and negligible residuals of MN matrix remaining in the skin, the URA-MN patch shows desirable biocompatibility after six-week administration.

Berberine-loaded MSC-derived sEVs encapsulated in injectable GelMA hydrogel for spinal cord injury repair.

After spinal cord injury (SCI), local inflammatory response and fibrous scar formation severely hinder nerve regeneration. Berberine (Ber) has a powerful regulatory effect on the local microenvironment, but its limited solubility and permeability through the blood-brain barrier severely limit its systemic efficacy. Human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived small extracellular vesicles (sEVs) are natural nanocarriers with high cargo loading capacity, and can cross the blood-brain barrier. Most importantly, sEVs can improve drug solubility and drug utilization. Therefore, they can overcome many defects of Ber application. This experiment aimed to design a Ber-carrying hUC-MSCs-derived sEVs and GelMA hydrogel. Ber was loaded into sEVs (sEVs-Ber) by ultrasonic co-incubation with a drug loading capacity (LC) of 15.07%. The unhindered release of up to 80% of sEVs-Ber from GelMA hydrogel was accomplished for up to 14 days. And they could be directly absorbed by local cells of injury, allowing for direct local delivery of the drug and enhancing its efficacy. The experimental results confirmed injecting GelMA-sEVs-Ber into spinal cord defects could exert anti-inflammatory effects by regulating the expression of inflammatory factors. It also demonstrated the anti-fibrotic effect of Ber in SCI for the first time. The modulatory effects of sEVs and Ber on the local microenvironment significantly promoted nerve regeneration and recovery of motor function in post-SCI rats. These results demonstrated that the GelMA-sEVs-Ber dual carrier system is a promising therapeutic strategy for SCI repair.

Fibroblast growth factor 21 ameliorates behavior deficits in Parkinson's disease mouse model via modulating gut microbiota and metabolic homeostasis.

AIMS: The effects of FGF21 on Parkinson's disease (PD) and its relationship with gut microbiota have not been elucidated. This study aimed to investigate whether FGF21 would attenuate behavioral impairment through microbiota-gut-brain metabolic axis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mice model. METHODS: Male C57BL/6 mice were rendomized into 3 groups: vehicle (CON); MPTP 30 mg/kg/day i.p. injection (MPTP); FGF21 1.5 mg/kg/d i.p. injection plus MPTP 30 mg/kg/day i.p. injection (FGF21 + MPTP). The behavioral features, metabolimics profiling, and 16 s rRNA sequencing were performed after FGF21 treatment for 7 days. RESULTS: MPTP-induced PD mice showed motor and cognitive deficits accompanied by gut microbiota dysbiosis and brain-region-specific metabolic abnormalities. FGF21 treatment dramatically attenuated motor and cognitive dysfunction in PD mice. FGF21 produced a region-specific alteration in the metabolic profile in the brain in ways indicative of greater ability in neurotransmitter metabolism and choline production. In addition, FGF21 also re-structured the gut microbiota profile and increased the relative abundance of Clostridiales, Ruminococcaceae, and Lachnospiraceae, thereby rescuing the PD-induced metabolic disorders in the colon. CONCLUSION: These findings indicate that FGF21 could affect behavior and brain metabolic homeostasis in ways that promote a favorable colonic microbiota composition and through effects on the microbiota-gut-brain metabolic axis.

Wave Propagation Characteristics and Compaction Status of Subgrade during Vibratory Compaction.

Vibratory compaction status has a significant influence on the construction quality of subgrade engineering. This study carried out field experiments to study the propagation characteristics of the vertical vibration wave in the soil field along the traveling direction of the vibratory roller. The propagation coefficients of the peak acceleration at different positions and compacting rounds are compared in both the time and frequency domains. The compaction status is estimated in the form of dynamic modulus of deformation (Evd) obtained by plate load tests. The experiment results show that the propagation coefficient of peak acceleration is affected by the traveling speed, excitation amplitude, and frequency of the vibratory roller, as well as the compacting rounds. An exponential relationship between the wave amplitudes of the fundamental mode and higher-order modes is revealed. The amplitude of the fundamental wave is maximum at the speed of 3 km/h, whereas the amplitudes of higher-order waves have a maximum of 1.5 km/h. The influences of compaction rounds on the average value of Evd are also investigated to provide a practical reference for engineering construction.

Diagnostic performance of deep learning-based vessel extraction and stenosis detection on coronary computed tomography angiography for coronary artery disease: a multi-reader multi-case study.

BACKGROUND: Post-processing and interpretation of coronary CT angiography (CCTA) imaging are time-consuming and dependent on the reader's experience. An automated deep learning (DL)-based imaging reconstruction and diagnosis system was developed to improve diagnostic accuracy and efficiency. METHODS: Our study including 374 cases from five sites, inviting 12 radiologists, assessed the DL-based system in diagnosing obstructive coronary disease with regard to diagnostic performance, imaging post-processing and reporting time of radiologists, with invasive coronary angiography as a standard reference. The diagnostic performance of DL system and DL-assisted human readers was compared with the traditional method of human readers without DL system. RESULTS: Comparing the diagnostic performance of human readers without DL system versus with DL system, the AUC was improved from 0.81 to 0.82 (p < 0.05) at patient level and from 0.79 to 0.81 (p < 0.05) at vessel level. An increase in AUC was observed in inexperienced radiologists (p < 0.05), but was absent in experienced radiologists. Regarding diagnostic efficiency, comparing the DL system versus human reader, the average post-processing and reporting time was decreased from 798.60 s to 189.12 s (p < 0.05). The sensitivity and specificity of using DL system alone were 93.55% and 59.57% at patient level and 83.23% and 79.97% at vessel level, respectively. CONCLUSIONS: With the DL system serving as a concurrent reader, the overall post-processing and reading time was substantially reduced. The diagnostic accuracy of human readers, especially for inexperienced readers, was improved. DL-assisted human reader had the potential of being the reading mode of choice in clinical routine.

Unmanned Aerial Vehicle Mediated Drug Delivery for First Aid.

Timely administration of key medications toward patients with sudden diseases is critical to saving lives. However, slow transport of first-aid therapeutics and the potential absence of trained people for drug usage can lead to severe injuries or even death. Herein, an unmanned aerial vehicle (UAV)-mediated first-aid system for targeted delivery (uFAST) is developed. It allows unattended administration of emergency therapeutics-loaded transdermal microneedle (MN) patches toward patients to relieve symptoms by a contact-triggered microneedle applicator (CTMA). The implementability and safety of the uFAST for first aid is demonstrated in a severe hypoglycemic pig model by automatically delivering a glucagon patch with immediate and bioresponsive dual release modes. This platform technique may facilitate the development of UAV-mediated first-aid treatments for other sudden diseases.

Polysaccharides from Enteromorpha prolifera alleviate hypercholesterolemia via modulating the gut microbiota and bile acid metabolism.

Polysaccharides from Enteromorpha prolifera (EP) possess multiple biological activities, while the role of EP in hypercholesterolemia and its relationship with the gut microbiota have not been elucidated. To address this issue, fifty male C57BL/6J mice were randomly subjected to a basal diet and a high-fat and high-cholesterol diet, and 3 treatment groups were fed an HFHC diet supplemented with different dosages of EP (100, 200 and 300 mg kg-1 day-1) for 12 weeks. Here we show that EP intervention lowered serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and inhibited hepatic cholesterol deposition. EP intervention also upregulated the gene expression related to the hepatic cholesterol uptake and bile acid synthetic pathway. Apart from that, EP altered the gut microbiota, pre-dominantly increasing microbes associated with bile acid metabolism, such as norank_f_ Muribaculaceae. Moreover, bile acid profile analysis revealed that EP could alter the fecal bile acid profile and reduce fecal conjugated bile acids. Further correlation analysis indicated the negative correlation of Bacteroides, norank_f_ Muribaculaceae and Ileibacterium abundance with the levels of fecal conjugated bile acids and serum TC and LDL-C, while the abundance of Proteobacteria and Lachnoclosteridium showed a positive association with conjugated bile acids and serum TC. To sum up, the above findings revealed that EP may alleviate hypercholesterolemia and regulate cholesterol metabolism in ways that promote a favorable fecal microbiota composition and modulate bile acid metabolism.

Glucose-responsive microneedle patch for closed-loop dual-hormone delivery in mice and pigs.

Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).

Kimura disease, a rare cause of inguinal lymphadenopathy: A case report.

Kimura's disease (KD) is a rare chronic granulomatous disease of unknown etiology that mainly involves damage to lymph nodes, soft tissues, and salivary glands. The clinical symptoms are mainly painless subcutaneous soft tissue masses, often involving head and neck lymph nodes and salivary glands, and are mainly characterized by diffuse eosinophilic infiltration, lymphocyte, and vascular proliferation. There are few reports in the literature that KD affects only inguinal lymph nodes. We report in this study a 41-year-old male patient who presented to the hospital for medical help with soft tissue masses in the groin. Magnetic resonance imaging (MRI) showed multiple abnormal soft tissue nodules around the iliac vessels in the left groin, and a contrast-enhanced scan showed obvious homogeneous enhancement. Diffusion-weighted imaging showed limited movement of water molecules and showed an obvious high signal. Fluoro18-labeled deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was recommended for further evaluation of the patient's general condition, and the results showed that except for the radioactive uptake in the lesions in the left groin region, no obvious abnormality was found in the rest of the body. Based on these imaging findings, the patient was first suspected to have malignant lesions, and then the patient underwent histopathological examination, which was confirmed to be KD. Our case study suggests that KD affects only the inguinal lymph nodes is rare and should be considered as one of the imaging differential diagnoses for lymphadenopathy such as lymphoma, metastases, and Castleman's disease.

Astrocyte-derived sEVs alleviate fibrosis and promote functional recovery after spinal cord injury in rats.

After spinal cord injury (SCI), there are complex pathological states in which the formation of scar tissues is a great obstacle to nerve repair. There are currently many potential treatments that can help to reduce the formation of glial scars. However, little attention has been paid to fibrous scarring. Astrocytes have neuroprotective effects on the central nervous system. Similar to other cells, they release small extracellular vesicles (sEVs). Astrocytes, pericytes, endothelial cells, and the basement membrane constitute the blood-spinal cord barrier. It can be seen that astrocytes are structurally closely related to pericytes that form fibrous scars. In this study, astrocyte-derived sEVs were injected into rats with SCI to observe the formation of fibrosis at the site of spinal cord injury. We found that astrocyte-derived sEVs can be ingested by pericytes in vitro and inhibit the proliferation and migration of pericytes. In vivo, astrocyte-derived sEVs could converge around the injury, promote tissue repair, and reduce fibrosis formation, thus promoting the recovery of limb function and improving walking ability. In conclusion, sEVs derived from astrocytes can reduce fibrosis and improve functional recovery after SCI, which provides a new possibility for the study of SCI.

Calorie restriction on normal body weight mice prevents body weight regain on a follow-up high-fat diet by shaping an obesity-resistant-like gut microbiota profile.

Calorie restriction (CR) is one of the most common approaches for obesity treatment, but whether resuming ad libitum feeding after CR in normal-weight mice can affect excessive weight regain remains poorly studied. To address this issue, male C57BL/6 mice were placed in three groups: a control group (n = 10), a group fed normal diet with 30% CR (n = 20); and a group fed a HF diet (n = 30). After four weeks, the CR group was fed either a normal diet (NDCR, n = 10) or a high-fat diet (HFCR, n = 10) for an additional eight weeks. At the end of the experiment, mice in the HF group ranked in the upper and lower thirds for weight gain were designated as obesity-prone (HFOP, n = 10) and obesity-resistant (HFOR, n = 10), respectively. CR delayed weight regain and visceral fat accumulation. Gut microbiota in the HFCR group were more similar to the HFOR group than the HFOP group, mainly due to reversion of the decreased level of Clostridiales induced by CR. Mediation analysis showed that Clostridiales may delay body weight regain by affecting the interconversion of succinate and fumarate. Random forest and structural equation analyses showed Christensenellaceae were the most important biomarker for alleviation of obesity. In conclusion, CR shapes an obesity-resistant-like gut microbiota profile that may attenuate body weight regain.