SEA Anemone-inspired Conducting Polymer Sensing Platform for Integrated Detection of Tumor Protein Marker and Circulating Tumor Cell.

Combining the detection of tumor protein markers with the capture of circulating tumor cells (CTCs) represents an ultra-promising approach for early tumor detection. However, current methodologies have not yet achieved the necessary low detection limits and efficient capture. Here, we introduced a novel polypyrrole nanotentacles sensing platform featuring anemone-like structures capable of simultaneously detecting protein biomarkers and capturing CTCs. The incorporation of nanotentacles significantly enhanced the electrode surface area, providing abundant active sites for antibody binding. This enhancement allowed detecting nucleus matrix protein22 (NMP22) and bladder tumor antigen (BTA) with 2.39 and 3.12 pg/mL detection limit, respectively. Furthermore, our developed sensing platform effectively captured MCF-7 cells in blood samples with a detection limit of fewer than 10 cells/mL, attributed to the synergistic multivalent binding facilitated by the specific recognition antibodies and the positive charge on the nanotentacles surface. This sensing platform demonstrated excellent detection capabilities and outstanding capture efficiency, offering a simple, accurate, and efficient strategy for early tumor detection. This article is protected by copyright. All rights reserved.

Localized Surface Plasmon Resonance-Enhanced Photocatalytic Antibacterial of In-situ Sprayed 0D/2D Heterojunction Composite Hydrogel for Treating Diabetic Wound.

Chronic diabetic wounds pose significant challenges due to uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The rapid advancement of photo-responsive antibacterial therapy showed promise in addressing these complex issues, particularly utilizing 2D heterojunction materials, which offer unique properties. Herein, we designed an in situ sprayed Bi/BiOCl 0D/2D heterojunction composite fibrin gel with the characteristics of rapid formation and effective near-infrared activation for the treatment of non-healing diabetes-infected wounds. The sprayed composite gel can provide protective shielding for skin tissues and promote endothelial cell proliferation, vascularization, and angiogenesis. The Bi/BiOCl 0D/2D heterojunction, with its localized surface plasmon resonance (LSPR), can overcome the wide bandgap limitation of BiOCl, enhancing the generation of local heat and reactive oxygen species under near-infrared irradiation. This facilitated bacterial elimination and reduced inflammation, supporting the accelerated healing of diabetes-infected wounds. Our study underscores the potential of LSPR-enhanced heterojunctions as advanced wound therapies for chronic diabetic wounds. This article is protected by copyright. All rights reserved.

Low shear stress induces macrophage infiltration and aggravates aneurysm wall inflammation via CCL7/CCR1/TAK1/ NF-κB axis.

BACKGROUND: This study aimed to elucidate the mechanism by which wall shear stress (WSS) influences vascular walls, accounting for the susceptibility of intracranial aneurysms (IAs) to rupture. METHOD: We collected blood samples from the sacs of 24 ruptured and 28 unruptured IAs and analyzed the expression of chemokine CCL7 using enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression analyses were employed to assess clinical data, aneurysm morphology, and hemodynamics in both groups. Pearson correlation analysis investigated the relationship between CCL7 expression in aneurysm sac blood and WSS. Additionally, we established a bionic cell parallel plate co-culture shear stress model and a mouse low shear stress (LSS) model. The model was modulated using CCL7 recombinant protein, CCR1 inhibitor, and TAK1 inhibitor. We further evaluated CCL7 expression in endothelial cells and the levels of TAK1, NF-κB, IL-1ß, and TNF-α in macrophages. Subsequently, the intergroup differences in expression were calculated. RESULTS: CCL7 expression was significantly higher in the ruptured group compared to the unruptured group. Hemodynamic analysis indicated that WSS was an independent predictor of the risk of aneurysm rupture. A negative linear correlation was observed between CCL7 expression and WSS. Upon addition of CCL7 recombinant protein, upregulation of CCR1 expression and increased levels of p-TAK1 and p-p65 were observed. Treatment with CCR1 and TAK1 inhibitors reduced inflammatory cytokine expression in macrophages under LSS conditions. Overexpression of TAK1 significantly alleviated the inhibitory effects of CCR1 inhibitors on p-p65 and inflammatory cytokines. CONCLUSION: LSS prompts endothelial cells to secrete CCL7, which, upon binding to the macrophage surface receptor CCR1, stimulates the release of macrophage inflammatory factors via the TAK1/NF-κB signaling pathway. This process exacerbates aneurysm wall inflammation and increases the risk of aneurysm rupture.

S100A9 aggravates early brain injury after subarachnoid hemorrhage via inducing neuroinflammation and inflammasome activation.

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality, and its severity is closely related to the short-term prognosis of SAH patients. S100 calcium-binding protein A9 (S100A9) has been shown to be associated with some neurological diseases. In this study, the concentration of S100A9 in clinical cerebrospinal fluid samples was detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between S100A9 and the prognosis of patients was explored. In addition, WT mice and S100A9 knockout mice were used to establish an in vivo SAH model. Neurological scores, brain water content, and histopathological staining were performed after a specified time. A co-culture model of BV2 and HT22 cells was treated with heme chloride to establish an in vitro SAH model. Our study confirmed that the expression of S100A9 protein in the CSF of SAH patients is increased, and it is related to the short-term prognosis of SAH patients. S100A9 protein is highly expressed in microglia in the central nervous system. S100A9 gene knockout significantly improved neurological function scores and reduced neuronal apoptosis. S100A9 protein can activate TLR4 receptor, promote nuclear transcription of NF-κB, increase the activation of inflammatory body, and ultimately aggravate nerve injury.

NIR-responsive micropatterned nanocomposite functionalized implant for sequential antibacterial and osteogenesis.

The long-term durability of the implant is influenced by two significant clinical challenges, namely bacterial infection and fixation loosening. Conventional implant materials have failed to meet the demands of the dynamic process of infectious bone repair, which necessitates early-stage bacterial sterilization and a conducive environment for late-stage osteogenesis. Consequently, there is an urgent requirement for an implant material that can sequentially regulate antibacterial properties and promote osteogenesis. The study aimed to develop a micropatterned graphene oxide nanocomposite on titanium implant (M-NTO/GO) for the sequential management of bacterial infection and osteogenic promotion. M-NTO/GO exhibited a micropattern nanostructure surface and demonstrated responsiveness to near-infrared (NIR) light. Upon NIR light irradiation, M-NTO/GO exhibited effective antibacterial properties, achieving antibacterial rates of 96.9% and 98.6% against E. coli and S. aureus, respectively. Under no-light condition, the micropatterned topography of M-NTO/GO exhibited the ability to induce directed cell growth, enhance cell adhesion and spreading, and facilitate osteogenic differentiation. These findings suggest the successful development of a functionalized micropatterned nanocomposite implant capable of sequentially regulating antibacterial and osteogenesis activity. Consequently, this highly effective strategy holds promise for expanding the potential applications of orthopedic implants.

Candidate circRNAs related to skeletal muscle development in Dazu black goats.

Circular RNA (CircRNA), as a classical noncoding RNA, has been proven to regulate skeletal muscle development (SMD). However, the molecular genetic basis of circRNA regulation in muscle cells remains unclear. In this study, the expression patterns of circRNAs in the longissimus dorsi muscle at embryonic day 75 and postnatal day 1 in DBGs were investigated to identify the key circRNAs that play an important role in SMD in goats. A total of 140 significantly and differentially expressed circRNAs (DEcircRNAs) were identified among the groups at different developmental stages. Among the 116 host genes (HGs) of DEcircRNAs, 76 were significantly and differentially expressed, which was confirmed by previous RNA_seq data. Furthermore, the expression pattern of 10 DEcircRNAs with RT-qPCR was verified, which showed 80% concordance rate with that of RNA_seq datasets. Moreover, the authenticity of seven randomly selected DEcircRNAs was verified by PCR Sanger sequencing. Based on the functional annotation results, among the 76 significantly and differentially expressed HGs, 74 were enriched in 845 GO terms, whereas 35 were annotated to 85 KEGG pathways. The results of this study could provide a comprehensive understanding of the genetic basis of circRNAs involved in SMD and muscle growth.

Ferroptosis: a potential therapeutic target for stroke.

Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation, differing from apoptosis, necroptosis, and autophagy in several aspects. Ferroptosis is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism imbalance. In this review, we discuss ferroptosis-related metabolisms, important molecules directly or indirectly targeting iron metabolism and lipid peroxidation, and transcriptional regulation of ferroptosis, revealing the role of ferroptosis in the progression of stroke. We present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on stroke. Our review facilitates further understanding of ferroptosis pathogenesis in stroke, proposes new targets for the treatment of stroke, and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.

Inhibition of S100A9 alleviates neurogenic pulmonary edema after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Neurogenic pulmonary edema (NPE) frequently arises as a complication subsequent to subarachnoid hemorrhage (SAH). Heterodimers of S100A8 and S100A9 are commonly formed, thereby initiating an inflammatory reaction through receptor binding on the cell surface. Paquinimod serves as a specific inhibitor of S100A9. The objective of this investigation is to assess the impact of Paquinimod administration and S100A9 knockout on NPE following SAH. METHODS: In this study, SAH models of C57BL/6J wild-type (WT) and S100A9 knockout mice were established through intravascular perforation. These models were then divided into several groups, including the WT-sham group, S100A9-KO-sham group, WT-SAH group, WT-SAH + Paquinimod group, and S100A9-KO-SAH group. After 24 h of SAH induction, pulmonary edema was assessed using the lung wet-dry weight method and Hematoxylin and eosin (HE) staining. Additionally, the expression levels of various proteins, such as interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), occludin, claudin-3, Bax, Bcl-2, TLR4, MYD88, and pNF-κB, in lung tissue were analyzed using western blot and immunofluorescence staining. Lung tissue apoptosis was detected by TUNEL staining. RESULTS: Firstly, our findings indicate that the knockout of S100A9 has a protective effect on early brain injury following subarachnoid hemorrhage (SAH). Additionally, the reduction of brain injury after SAH can also alleviate neurogenic pulmonary edema (NPE). Immunofluorescence staining and western blot analysis revealed that compared to SAH mice with wild-type S100A9 expression (WT-SAH), the lungs of S100A9 knockout SAH mice (S100A9-KO-SAH) and mice treated with Paquinimod exhibited decreased levels of inflammatory molecules (IL-1ß and TNF-α) and increased levels of tight junction proteins. Furthermore, the knockout of S100A9 resulted in upregulated expression of the apoptotic-associated protein Bax and down-regulated expression of Bcl-2. Furthermore, a decrease in TLR4, MYD88, and phosphorylated pNF-κB was noted in S100A9-KO-SAH and Paquinimod treated mice, indicating the potential involvement of the TLR4/MYD88/NF-κB signaling pathway in the inhibition of the protective effect of S100A9 on NPE following SAH. CONCLUSION: The knockout of S100A9 not only ameliorated initial cerebral injury following subarachnoid hemorrhage (SAH), but also mitigated SAH-associated neurogenic pulmonary edema (NPE). Additionally, Paquinimod was found to diminish NPE. These findings imply a correlation between the central nervous system and peripheral organs, highlighting the potential of safeguarding the brain to mitigate harm to peripheral organs.

CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway.

C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) is an essential kinase that regulates inflammation in immune cells through multiple signaling pathways. This study aims to explore the effect of CXCR4 and BTK on neuroinflammation in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Our results showed that the expression of CXCR4 and p-BTK increased significantly at 24 h after SAH in vivo and in vitro. Ibrutinib improved neurological impairment, BBB disruption, cerebral edema, lipid peroxidation, neuroinflammation and neuronal death at 24 h after SAH. Inhibition of BTK phosphorylation promoted the in vitro transition of hemin-treated proinflammatory microglia to the anti-inflammatory state, inhibited the p-P65 expression and microglial pyroptosis. NLRP3 deficiency can significantly reduce pyroptosis in SAH mice. Moreover, CXCR4 inhibition can suppress NLRP3-mediated pyroptosis, NF-κB activation and NOX2 expression in vitro, and ibrutinib can abolish CXCR4-aggravated BBB damage and pyroptosis in EBI after SAH. The levels of CXCR4 in CSF of SAH patients is significantly increased, and it is positively correlated with GSDMD and IL-1ß levels, and have a moderate diagnostic value for outcome at 6-month follow-up. Our findings revealed the effect of CXCR4 and P-BTK on NLRP3-mediated pyroptosis and lipid peroxidation after SAH in vivo and in vitro, and the potential diagnostic role of CXCR4 in CSF of SAH patients. Inhibition of CXCR4-BTK axis can significantly attenuate NLRP3-mediated pyroptosis and lipid peroxidation by regulating NF-κB activation in EBI after SAH.

Inhibition of CCR1 attenuates neuroinflammation via the JAK2/STAT3 signaling pathway after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Neuroinflammation is an important mechanism underlying brain injury caused by subarachnoid hemorrhage (SAH). C-C chemokine receptor type 1 (CCR1)-mediated inflammation is involved in the pathology of many central nervous system diseases. Herein, we investigated whether inhibition of CCR1 alleviated neuroinflammation after experimental SAH and aimed to elucidate the mechanisms of its potential protective effects. METHODS: To analyze SAH transcriptome data R studio was used, and a mouse model of SAH was established using endovascular perforations. In this model, the selective CCR1 antagonist Met-RANTES (Met-R) and the CCR1 agonist recombinant CCL5 (rCCL5) were administered 1 h after SAH induction. To investigate the possible downstream mechanisms of CCR1, the JAK2 inhibitor AG490 and the JAK2 activator coumermycin A1 (C-A1) were administered 1 h after SAH induction. Furthermore, post-SAH evaluation, including SAH grading, neurological function tests, Western blot, the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Fluoro-Jade B and fluorescent immunohistochemical staining were performed. Cerebrospinal fluid (CSF) samples were detected by ELISA. RESULTS: CCL5 and CCR1 expression levels increased significantly following SAH. Met-R significantly improved neurological deficits in mice, decreased apoptosis and degeneration of ipsilateral cerebral cortex neurons, reduced infiltrating neutrophils, and promoted microglial activation after SAH induction. Furthermore, Met-R inhibited the expression of p-JAK2, p-STAT3, interleukin-1ß, and tumor necrosis factor-α. However, the protective effects of Met-R were abolished by C-A1 treatment. Furthermore, rCCL5 injection aggravated neurological dysfunction and increased the expression of p-JAK2, p-STAT3, interleukin-1ß, and tumor necrosis factor-α in SAH mice, all of which were reversed by the administration of AG490. Finally, the levels of CCL5 and CCR1 were elevate in the CSF of SAH patient and high level of CCL5 and CCR1 levels were associated with poor outcome. CONCLUSION: The present results suggested that inhibition of CCR1 attenuates neuroinflammation after SAH via the JAK2/STAT3 signaling pathway, which may provide a new target for the treatment of SAH.

Comparative Transcriptomic Profiling in Ovarian Tissues of Lohmann Hens and Chengkou Mountain Chicken.

BACKGROUND: As a crucial economic characteristic and a major indicator of reproductive performance in layers, egg production is controlled by a series of complex regulatory heredity basis. In particular, the interacting regulatory function between noncoding RNAs (ncRNAs) and coding RNA plays important roles in regulating laying performance. METHODS: In this study, the RNA sequencing (RNA-seq) of ovarian tissues from Lohmann hens (n = 3) and Chengkou Mountain chicken (n = 3) under the laying peak period was performed to identify RNA transcriptional differences among different laying-performance populations. RESULTS: Results showed that the expression level of 303 mRNAs, 68 long ncRNAs (lncRNAs), 533 circular RNAs (circRNAs), and 79 microRNAs (miRNAs) was significantly different among the groups. Functional enrichment analysis of these differentially expressed (DE) mRNAs revealed that the laying process was implicated in numerous significantly enriched pathways (p < 0.05), such as the neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and calcium-signaling pathway. Furthermore, the lncRNA/circRNA-miRNA-mRNA regulatory networks related to the regulation of laying performance were constructed. Some randomly selective DE RNAs were verified by Real Time Quantitative (RT-qRCR), indicating that the bioinformatics analysis results of RNA-seq data were credible. CONCLUSIONS: This study could increase our understanding of the heredity basis of transcriptome in the laying performance of chicken.

Novel Heredity Basis of the Four-Horn Phenotype in Sheep Using Genome-Wide Sequence Data.

Horns are an important breeding trait for sheep. However, no widely recognized viewpoint on the regulatory genes and mechanisms of horns is available, and the genetic basis of the four-horn phenotype (FHP) is unclear. This work conducted a genome-wide association study with 100 sheep genomes from multiple breeds to investigate the genetic basis of the FHP. The results revealed three significant associations (corrected as p < 1.64 × 10-8) of the InDels (CHR2: g.133,742,709delA, g.133,743,215insC, and g.133,743,940delT) for FHP in the intergenic sequence (IGS) between the MTX2 and the LOC105609047 of CHR2. Moreover, 14 significant associations (corrected as p < 1.42 × 10-9) of SNPs with the FHP phenotype were identified in CHR2 and CHR16, including five (e.g., CHR16: g.40,351,378G > A and g.40,352,577G > A) located in the intron of the ADAMTS12 gene, eight (e.g., CHR2: g.133,727,513C > T and g.133,732,145T > G) in the IGS between MTX2 and LOC105609047, and only one (CHR2: g.133,930,761A > G) in the IGS between HOXD1 and MTX2. Obvious divergence was also observed in genotype patterns between the FHP and others (two horns and hornless) in the HOXD1 and ADAMTS12 gene regions. An extremely significant linkage also occurred between Loci I and Loci II within 100 individuals (LD = -156.02186, p < 0.00001). In summary, our study indicated that the genomic sequences from CHR2 and CHR16 contributed to the FHP in sheep, specifically the key candidate genes HOXD1 and ADAMTS12. These results improved our understanding of the Mendelian genetic basis of the FHP in sheep.

A Pilot Fuzzy System with Virtual Reality for Mild Cognitive Impairment (MCI) Assessment.

Mild cognitive impairment (MCI) is when brain function declines. MCI is the gray area transitioning from normal aging to the AD stage. Currently, the majority of early MCI diagnoses are processed through comprehensive neuropsychological tests. These tests may take the form of interviews, paper-and-pencil tests, or computer-based tests. There may be resistance from the subject if he/she has to undergo many screening tests simultaneously for multiple evaluation information, resulting in execution difficulty. The objectives of this study are to use 3D virtual reality to create an entertaining test scenario integrating the Mini-Cog, SPMSQ, MMSE, SLUMS, CDR, and CASI for middle-aged to older adults, furthermore, to employ fuzzy logic control (FLC) technology to develop a "MCI assessment system" for obtaining some pilot information for MCI assessment. There were 24 middle-aged to older adults aged from 50 to 65 years who participated in the evaluation experiment. The results showed that the MCI assessment system developed in this study is highly correlated with the traditional screening tests, including the Mini-Cog, SPMSQ, MMSE, SLUMS, and CASI. The assessment system can provide an integrated reference score for clinic workers in making judgments. In addition, the distribution of the System Usability Scale (SUS) evaluation scores for the MCI assessment system revealed that 87.5% were grade C (good to use) or above and 29.2% were grade B (extremely good to use) or above. The assessment system received positive feedback from the subjects.

Complex multi-fault rupture and triggering during the 2023 earthquake doublet in southeastern Türkiye.

Two major earthquakes (MW 7.8 and MW 7.7) ruptured left-lateral strike-slip faults of the East Anatolian Fault Zone (EAFZ) on February 6, 2023, causing >59,000 fatalities and ~$119B in damage in southeastern Türkiye and northwestern Syria. Here we derived kinematic rupture models for the two events by inverting extensive seismic and geodetic observations using complex 5-6 segment fault models constrained by satellite observations and relocated aftershocks. The larger event nucleated on a splay fault, and then propagated bilaterally ~350 km along the main EAFZ strand. The rupture speed varied from 2.5-4.5 km/s, and peak slip was ~8.1 m. 9-h later, the second event ruptured ~160 km along the curved northern EAFZ strand, with early bilateral supershear rupture velocity (>4 km/s) followed by a slower rupture speed (~3 km/s). Coulomb Failure stress increase imparted by the first event indicates plausible triggering of the doublet aftershock, along with loading of neighboring faults.

Synergy of S-vacancy and heterostructure in BiOCl/Bi2S3-x boosting room-temperature NO2 sensing.

The special physicochemical properties of Bi2S3 nanomaterial endow it to be exceptional NO2 sensing properties. However, sensors based on pure Bi2S3 cannot detect trace NO2 at room temperature effectively due to the scanty active sites and poor charge transfer efficiency. Herein, vacancy defect and heterostructure engineering are rationally integrated to explore BiOCl/Bi2S3-x heterostructure with rich S vacancies to enhance NO2 sensing performance. The optimized sensor based on S-vacancy-rich BiOCl/Bi2S3-x heterostructure exhibited a high response value (Rg/Ra = 29.1) to 1 ppm NO2 at room temperature, which was about 17 times compared to the pristine Bi2S3. Meanwhile, the BiOCl/Bi2S3-x sensor also exhibited a short response time (36 s) towards 1 ppm NO2 and a low theoretical detection limit (2 ppb). The superior response value of S-vacancy-rich BiOCl/Bi2S3-x heterostructures was ascribed to the improved electron migration at the heterointerface and the additional exposed active sites caused by the S vacancies in Bi2S3-x. Additionally, the sensors based on S-vacancy-rich BiOCl/Bi2S3-x heterostructures showed good long-term stability, outstanding selectivity, and good flexibility. This study offers an effective method for synergistically engineering defect and heterostructure to enhance gas sensing properties at room temperature.

Fast and slow intraplate ruptures during the 19 October 2020 magnitude 7.6 Shumagin earthquake.

Strong tsunami excitation from slow rupture of shallow subduction zone faults is recognized as a key concern for tsunami hazard assessment. Three months after the 22 July 2020 magnitude 7.8 thrust earthquake struck the plate boundary below the Shumagin Islands, Alaska, a magnitude 7.6 aftershock ruptured with complex intraplate faulting. Despite the smaller size and predominantly strike-slip faulting mechanism inferred from seismic waves for the aftershock, it generated much larger tsunami waves than the mainshock. Here we show through detailed analysis of seismic, geodetic, and tsunami observations of the aftershock that the event implicated unprecedented source complexity, involving weakly tsunamigenic fast rupture of two intraplate faults located below and most likely above the plate boundary, along with induced strongly tsunamigenic slow thrust slip on a third fault near the shelf break likely striking nearly perpendicular to the trench. The thrust slip took over 5 min, giving no clear expression in seismic or geodetic observations while producing the sizeable far-field tsunami.

Genetic modification of miR-34a enhances efficacy of transplanted human dental pulp stem cells after ischemic stroke.

Human dental pulp stem cells (hDPSCs) promote recovery after ischemic stroke; however, the therapeutic efficacy is limited by the poor survival of transplanted cells. For in vitro experiments in the present study, we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion. We found that miRNA-34a-5p (miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs. Inhibition of miR-34a facilitated the proliferation and antioxidant capacity and reduced the apoptosis of hDPSCs. Moreover, dual-luciferase reporter gene assay showed WNT1 and SIRT1 as the targets of miR-34a. In miR-34a knockdown cell lines, WNT1 suppression reduced cell proliferation, and SIRT1 suppression decreased the antioxidant capacity. Together, these results indicated that miR-34a regulates cell proliferation and antioxidant stress via targeting WNT1 and SIRT1, respectively. For in vivo experiments, we injected genetically modified hDPSCs (anti34a-hDPSCs) into the brains of mice. We found that anti34a-hDPSCs significantly inhibited apoptosis, reduced cerebral edema and cerebral infarct volume, and improved motor function in mice. This study provides new insights into the molecular mechanism of the cell proliferation and antioxidant capacity of hDPSCs, and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.

A 1.1 Mb duplication CNV on chromosome 17 contributes to skeletal muscle development in Boer goats.

The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940-60151302 bp) with overlapping genes (e.g., ARHGAP10, NR3C2, EDNRA, PRMT9, and TMEM184C). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes ( ARHGAP10, NR3C2, and EDNRA) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of SAA3. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.