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Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100β, albumin, MMP-9, MMP-2, MMP-12, IL-1β, TNF-α, IL-6, IFN-γ, TGF-β, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed.

Abstract Background Spinal cord injury (SCI) causes nearly all patients to suffer from protracted disabilities. An emerging therapeutic strategy involving the recruitment of endogenous neural stem cells (NSCs) has been developed. However, endogenous NSCs in the adult spinal cord differentiate into mostly astrocytes after traumatic injury, forming glial scars, which is a major cause of regeneration failure in SCI. Thus, understanding which factors drive the activation and differentiation of endogenous NSCs after SCI is critical for developing therapeutic drugs. Methods The infiltration, state, and location of CD8+ T cells in spinal cord after traumatic injury were analyzed by flow cytometry and immunofluorescence (IF) staining. The Basso Mouse Scale (BMS) scores and rotarod testing were used for motor behavioral analysis. NSCs were co-cultured with CD8+ T cells. EdU assay was used to detect proliferative cells. Western blotting was used to analyze the expression levels of STAT1, p-STAT1, and p27. ChIP-seq and ChIP-qRT-PCR analyses were used to detect the downstream of STAT1. Nestin-CreERT2::Ai9 transgenic mice were used to genetic lineage tracing of Nestin+ NSCs after SCI in vivo. Results A prolonged increase of activated CD8+ T cells occurs in the injured spinal cords. The behavioral analysis demonstrated that the administration of an anti-CD8 antibody promotes the recovery of locomotor function. Then, we discovered that CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1 pathway in vitro. ChIP-seq and ChIP-qRT-PCR analysis revealed that STAT1 could directly bind to the promoters of astrocyte marker genes GFAP and Aldh1l1. Genetic lineage tracing of Nestin+ NSCs demonstrated that most NSCs differentiated into astrocytes following SCI. Depleting CD8+ T cells reduced the differentiation of NSCs into astrocytes and instead promoted the differentiation of NSCs into oligodendrocytes. Conclusion In conclusion, CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1-GFAP/Aldhl1l axis. Our study identifies INF-γ as a critical mediator of CD8+ T-cell-NSC cross talk and a potential node for therapeutic intervention in SCI.

Introduction: Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Broad knowledge about the genetics, epidemiology and clinical management of T1D has been achieved, but understandings about the cell varieties in the bone marrow during T1D remain limited. Objectives: We aimed to present a profile of the bone marrow cells and reveal the relationship of bone marrow and osteopenia in streptozotocin (STZ)-induced T1D mice. Methods: The whole bone marrow cells from the femurs and tibias of healthy (group C) and STZ-induced T1D mice (group D) were collected for single-cell RNA sequencing analysis. Single-cell flow cytometry and immunohistochemistry were performed to confirm the proportional changes among bone marrow neutrophils (BM-neutrophils) (Cxcr2+, Ly6g+) and B lymphocytes (Cd19+). X-ray and micro-CT were performed to detect bone mineral density. The correlation between the ratio of BM-neutrophils/B lymphocytes and osteopenia in STZ-induced T1D mice was analyzed by nonparametric Spearman correlation analysis. Results: The bone marrow cells in groups C and D were divided into 12 clusters, and 249 differentially expressed genes were found. The diversity of CD45+ immune cells between groups C and D were greatly affected: the proportion of BM-neutrophils showed a significant increase while the proportion of B lymphocytes in group D showed a significant decrease. X-ray and micro-CT analyses confirmed that osteopenia occurred in group D mice. In addition, the results of single-cell flow cytometry and correlation analysis showed that the ratio of BM-neutrophils/B lymphocytes negatively correlated with osteopenia in STZ-induced T1D mice. Conclusion: A single-cell RNA sequencing analysis revealed the profile and heterogeneity of bone marrow immune cells in STZ-induced T1D mice for the first time. The ratio of BM-neutrophils/B lymphocytes negatively correlated with osteopenia in STZ-induced T1D mice, which may enhance understanding for treating T1D and preventing T1D-induced osteopenia.

Abstract Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of microglia repopulation after SCI remain unknown. Here, we used single-cell RNA sequencing to portray the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. B cells and migDCs, located in the meninges under physiological conditions, are involved in immune surveillance. Microglia quickly reduced, and peripheral myeloid cells infiltrated three days-post-injury (dpi). At 14 dpi, microglia repopulated, myeloid cells were reduced, and lymphocytes infiltrated. Importantly, genetic lineage tracing of nestin+ and Cx3cr1+ cells in vivo showed that the repopulation of microglia was derived from residual microglia after SCI. We found that residual microglia regress to a developmental growth state in the early stages after SCI. Hif1α promotes microglial proliferation. Conditional ablation of Hif1α in microglia causes larger lesion sizes, fewer axon fibers, and impaired functional recovery in the late stages after SCI. Our results mapped the immune heterogeneity in SCI and raised the possibility that targeting Hif1α may help in axon regeneration and functional recovery after SCI.

Flow cytometric sorting is a vital tool in biological research and clinical diagnostics. Theoretically, a high‐speed jet‐in‐air sorter is a fluorescent‐activated cell sorting sorter that ideally processes cells with high purity, yield, and viability. However, high‐speed jet‐in‐air sorting is a complex process due to its inherent requirements for high fluidic stability and electronic and timing precision. Here, we report that an additional manual correction of drop delay leads to improved cell yield. Adding 2% FBS to the loading buffer had no significant effect on the fate of sorted cells in 4 h. However, the addition of a suitable concentration of FBS/BSA in the collecting buffer resulted in a notable increase in cell count and proliferation and a significant decrease in cell apoptosis for cell lines and primary cells. Moreover, the level of gene expression remained steady in the 5% FBS collecting buffer. In summary, here we demonstrate techniques that can be easily followed to refine sorted yields of healthy cells.

Spinal cord injury (SCI) can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research has shown that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. We thus investigate the alteration in gut microbiota and the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&E, Nissl, and immunofluorescence stainings. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and analyzed with 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolites indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and butyrate suppressed the expression of pro-inflammatory genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate.

Microglia are the resident immune cells in the central nervous system (CNS). After traumatic spinal cord injury (SCI), microglia undergo activation, proliferation, and changes in gene and protein expression and morphology, with detrimental and beneficial effects. Activated microglia cause secondary neuronal injury via the production of proinflammatory cytokines, reactive oxygen species, and proteases. However, activated microglia also promote neuronal repair through the secretion of anti-inflammatory growth factors and cytokines. Proinflammatory cytokines increase endothelial permeability, promote A1 astrocyte activation and axonal demyelination, and reduce neural stem/progenitor cells (NSPCs), leading to the exacerbation of neuronal injury. In contrast, anti-inflammatory factors facilitate angiogenesis, reduce reactive astrocytes, and promote axonal remyelination and the propagation of NSPCs, contributing to tissue repair and locomotor recovery. Due to its limited regenerative capacity, the CNS requires beneficial microglia for continuous protection against injury. Understanding and regulating microglial activation status are beneficial to reducing detrimental effects and promoting repair behaviors and to obtain more information on efficient therapies for traumatic SCI. This review discusses microglial activation and the differences between microglia and similar immune cells, microglial interactions with other cells in the spinal cord, and the progress in the development of therapies targeting microglia in SCI.

Cuckoo search algorithm (CS) is a powerful biological-inspired search algorithm, which is widely used in continuous space optimization problems. However, a single search strategy in CS makes all cuckoos have similar search behavior, and it is liable to plunges into local optimal. In addition, whether CS can successfully solve a problem largely depends on the value of control parameters. Using the trial and error method to determine the value of parameters will cost a lot of computational expense frequently. In order to solve these problems, a multi-strategy adaptive cuckoo algorithm (MSACS) is proposed in this paper. Firstly, five search strategies are adapted to cooperate with each other, and the use of various previous strategies and control parameters are studied. The probability of each strategy being used and the value of control parameters are changed adaptively. Then, the performance of MSACS is tested and evaluated on 24 common benchmark functions. Finally, several advanced CS algorithms, particle swarm algorithm (PSO) and differential evolution algorithm (DE) variants will be compared with MSACS. The results show that the MSACS is better than the algorithms above.

Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100β, albumin, MMP-9, MMP-2, MMP-12, IL-1β, TNF-α, IL-6, IFN-γ, TGF-β, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Second ejaculation can influence sperm quality which may define the first-line treatment. The purpose of this study was to evaluate the effectiveness of a second ejaculation in decreasing the unexpected intracytoplasmic sperm injection (ICSI) rate by a propensity score-matched (PSM) analysis. Methods Patients who were projected to undergo IVF were included between January 2016 and November 2021 in this monocentric, retrospective analysis. 2782 patients included in the study, 143 and 2639 patients were non-randomized in the unexpected ICSI and IVF groups, respectively. One hundred fourteen patients with unexpected ICSI produced two semen samples on the day of ovum pick-up. After 1:4 PSM, we matched 61 patients in the second ejaculation IVF group to 238 patients in the conventional IVF group. Outcomes of sperm quality, fertilization rate, embryo quality, and pregnancy were compared. Results Second ejaculation significantly improved sperm concentration, progressive motility before and after sperm swim-up, total progressive motility sperm count after swim-up, and decreased sperm DNA fragmentation (SDF). Sixty-one of 114 (53.5%) unexpected ICSI couples had enough total progressive motility sperm for IVF with the second ejaculation. There were no differences in basic clinical characteristics between couples in second ejaculation IVF and matched-conventional IVF group. For the two groups, no differences were observed in IVF outcomes. However, a significant increase in good-quality blastocyst rate was observed for second-ejaculation IVF couples. Univariate and multivariate linear regression analysis also confirmed that the second ejaculation was an independent risk factor for the good quality blastocyst rate. Conclusion Second ejaculation could be an economical and secure alternative to get good quality sperm, and blastocyst and decrease the rate of unexpected ICSI. Multicenter studies should be conducted to confirm the potential advantages of using second ejaculation IVF in effectively reducing the rate of ICSI.

IntroductionAttempts to artificially activate unfertilized oocytes at 24 h post intracytoplasmic sperm injection (ICSI) have generally resulted in poor outcomes. This study aims to explore a new strategy for early judgement and rescue activation of unfertilized oocytes at 5 h post ICSI to avoid unexpected fertilization failure (UFF) or unexpected low fertilization (ULF) in ICSI cycles.MethodsFirstly, time-lapse data from 278 ICSI cycles were retrospectively analyzed to establish an indicator for fertilization failure prediction. Secondly, 14 UFF and 20 ULF cycles were enrolled for an observational study, early rescue oocyte activation (EROA) was performed on oocytes without post-ICSI Pb2 extrusion to investigate fertilization efficiency, embryo development and clinical outcomes.ResultsThe average time to Pb2 extrusion post-ICSI was 3.03±1.21 h, 95.54% of oocytes had extruded Pb2 before 5 h, and the sensitivity and specificity for monitoring Pb2 extrusion at 5 h by time-lapse imaging to predict fertilization were 99.59% and 99.78%, respectively. Early rescue activation of oocytes with no Pb2 extrusion resulted in acceptable fertilization and embryo developmental outcomes, in terms of the fertilization rate (75.00, 72.99%), 2PN fertilization rate (61.36, 56.93%), good-quality embryo rate (42.59, 50.00%), blastocyst formation rate (48.28, 46.03%), good-quality blastocyst rate (34.48, 33.33%), and oocyte utilization rate (36.36, 27.74%), for both UFF and ULF cycles. The clinical pregnancy, embryo implantation, and early miscarriage rates in the rescue oocyte activation group did not significantly differ from those in the Pb2 extrusion group. Fourteen unexpected fertilization failures and 20 low fertilization ICSI cycles were rescued and resulted in clinical pregnancy rates of 40.00% (4/10) and 57.14% (8/14), respectively. ConclusionsThis study demonstrates that monitoring Pb2 extrusion by time-lapse imaging can accurately predict fertilization outcomes, suggesting that early rescue oocyte activation at 5 h post ICSI is an effective strategy for avoiding unexpected fertilization failure and low fertilization in ICSI cycles.

BackgroundDoes short-interval second ejaculation improve sperm quality, embryo development and clinical outcomes for oligoasthenozoospermia males received intracytoplasmic sperm injection (ICSI) treatment?MethodsAll enrolled male patients underwent short-interval secondary ejaculation on the day of oocyte retrieval, and 786 sibling MII oocytes from 67 cycles were equally divided into two groups based on whether the injected spermatozoons originated from the first or second ejaculation. Semen parameters, embryo development efficiency, morphokinetic parameters and clinical outcomes were compared between the two groups to assess the efficiency and clinical value of short-interval second ejaculation in ICSI cycles.ResultsShort-interval second ejaculation significantly improved sperm motility, normal morphological rate, and sperm DNA integrity both before and after sperm swim-up. The high-quality blastocyst rate (24.79% versus 14.67%), available blastocyst rate (57.56% versus 48.44%), and oocyte utilization rate (52.93% versus 45.29%) were significantly higher in the second ejaculation group (P0.05). Time-lapse analysis showed that morphokinetic time points after the 7-cell stage were earlier in the second ejaculation group but without a significant difference (P>0.05), and abnormal embryo cleavage patterns between the two groups were not significantly different (P>0.05).ConclusionsShort-interval second ejaculation significantly improves sperm quality in oligoasthenozoospermic males, and is beneficial for blastocyst formation efficiency in ICSI cycles. This study suggested a non-invasive and simple but effective strategy for improving ICSI treatment outcomes.

Abstract Background Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol. Methods This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate. Results Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups. Conclusion This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019730 . Registered 26 November 2018.

Background: Low grade blastocyst (LGB) transfer results in varied live birth rates (5-39%). Only limited studies with small sample sizes (n=10-440) exist, due to LGB transfer being less desirable. Definitions of LGB and study designs are heterogenous, further confounding outcome interpretation. Aim: This study aimed to obtain sufficient LGB transfers to determine live birth rates, as well as allow subgroup analysis by blastocyst quality and maternal age. Method: This study was a multicentre, multinational retrospective cohort study across nine IVF clinics in China and New Zealand between 2012 to 2019. 6966 single blastocyst transfer cycles on days 5-7 (fresh and frozen) were collected; of these, 875 transfers were from LGBs (

Due to the structure of the rolling bearing itself and the complexity of its operating environment, the collected vibration signals tend to show strong non-stationary and time-varying characteristics. It has been a challenge to extract useful fault signature information from actual bearing vibration signals and identify bearing faults in the field of machinery in recent years. Therefore, this paper proposes a novel optimized self-adaptive deep belief network (DBN). The DBN is pre-trained by a minimum batch stochastic gradient descent, and then a back-propagation neural network and conjugate gradient descent are used to supervise and fine-tune the entire DBN model, which effectively improves the classification accuracy of the DBN. A salp swarm algorithm is used to optimize the DBN, and then the experience of the DBN structure is summarized. The vibration signal of the rolling bearing is analyzed by this method and it is confirmed that it has higher diagnostic accuracy and better convergence. [ABSTRACT FROM AUTHOR]