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The neuromuscular junction (NMJ) consists of three components, namely presynaptic motor neurons, postsynaptic muscle fibers and perisynaptic Schwann cells (PSCs). The role of Schwann cells (SCs) in regulating NMJ structural and functional development remains unclear. In this study, mice with conditional inactivation of neurofibromin 1 (Nf1) and phosphatase and tensin homolog (Pten), specifically in SCs, resulted in delayed NMJ maturation that led to delayed muscle growth, recapitulating the muscular dystrophy condition observed in human neurofibromatosis type I syndrome (NF1) patients. Expression levels of NMJ development related molecules such as cholinergic receptor, nicotinic, alpha polypeptide 1 (Chrna1), agrin (Agrn), dystrophin, muscular dystrophy (Dmd), laminin, beta 2 (Lamb2) and dystroglycan 1 (Dag1) were also downregulated. To further explore the molecular alterations in these SCs, NF1- and PTEN-related pathways were analyzed in mutant sciatic nerves. As expected, hyperactive RAS/PI3K/AKT/mTOR signaling pathways were identified, suggesting the importance of these pathways for NMJ development, and subsequent muscle maturation.

Interleukin 4 （IL-4） has a variety of immune functions, including helper T-cell （Th-cell） differentiation and innate immune-response processes. However, the impact of IL-4 on gamma delta （γδ） T cells remains unclear. In this study, we investigate the effects of IL-4 on the activation and proliferation of γδ T cells and the balance between variable delta 1 （Vδ1） and Vδ2 T cells in humans. The results show that I L-4 inhibits the activation of y8 T cells in the presence of γδ T-cell receptor （TCR） stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated γδ T cells and increased the levels of Vδ1 T cells, which in turn inhibited V82 T-cell growth via significant IL-10 secretion. VδI T cells secreted significantly less interferon gamma （IFNy） and more IL-10 relative to Vδ2. Furthermore, Vδ1 T cells showed relatively low levels of Natural Killer Group 2D （NKG2D） expression in the presence of IL-4, suggesting that Vδ1 T cells weaken the γδ T cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in γδ T cell-mediated anti-tumor immunity.

Iron-mediated sp-sp3 C-C bond formation through the cross dehydrogenative coupling（CDC） of terminal alkynes with benzylic ethers or alkanes has been developed.The inexpensive iron salt is used as the catalyst to make this transformation environmentally benign.Iron-mediated sp-sp3 C-C bond formation through the cross dehydrogenative coupling（CDC） of terminal alkynes with benzylic ethers or alkanes has been developed.The inexpensive iron salt is used as the catalyst to make this transformation environmentally benign.

Spectral confocal sensors are effective for measuring displacements. The core of the spectral confocal measurement system is a dispersive objective lens that uses optical dispersion to establish a one-to-one correspondence between the focusing position and wavelength, achieving high-resolution measurements in the longitudinal direction. Despite significant progress in dispersive objective lenses for spectral confocal sensor systems, challenges such as a limited dispersion range, high cost, and insufficient measurement accuracy persist. To expand the measurement range and improve the accuracy of the spectral confocal sensor, we designed a compact, long-axial dispersion objective lens. This lens has a simple structure that requires only six lens elements, two of which form cemented doublets. The system length is 58 mm, with a working distance of 46 ± 6 mm and a dispersion range of 12 mm within the wavelength range of 450–656 nm. The lens has an object-side numerical aperture (NA) of 0.22 and an image-side NA between 0.198 and 0.24, ensuring high light energy utilization. Finally, a spectral confocal measurement system was constructed based on the designed dispersive objective lens, and performance evaluation tests were conducted. The test results showed that the system achieved a resolution of 0.15 μm and a maximum linear error of ±0.7 μm, demonstrating high-precision measurement capabilities. The proposed lens design enables the development of more portable and cost-effective spectral confocal sensors.

Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. : A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. : GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. : Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.

For humans, ARTs (assisted reproductive technologies) have become the most effective method to treat subfertility/infertility in clinic. To obtain enough oocytes during ART, ovarian stimulation is performed by exogenous hormones, and some patients undergo several ovarian stimulation cycles. Although some adverse effects of ARTs on women and offspring are reported, few studies are focused on the effects of multiple superovulation on ovarian reserve. In the present study, we found that repeated superovulation significantly reduced primordial follicle number and the serum AMH. Compared to the decreased antral follicle number, the expression of genes related to primordial follicle activation, such as Foxo3, Akt, and Rptor, and the atretic follicle number in ovaries were increased by superovulation times. We further found that repeated superovulation reduced the plasma level of FSH, LH, and estradiol, and increased the expression of genes related to apoptosis (Bax, Casp3 (caspase-3), Casp8, and Casp9) in granulosa cells, providing evidence that repeated superovulation disrupted the balance between survival and death in granulosa cells. In summary, our results suggest that repeated superovulation has adverse effects on folliculogenesis.

Purposes: This study aimed to investigate the efficacy of ultrasound (US)-, computed tomography (CT)-, and magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study included 141 patients with HCC who were treated with US-guided (n = 29), CT-guided (n = 50), or MRI-guided RFA (n = 62). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), technique success (TS), and technique efficacy (TE). Cox model and logistic regression were used to determine the risk factors for tumor recurrence and TE. Results: The US, CT, and MRI groups did not show a significant difference in terms of baseline variables. The three groups did not differ significantly in PFS rate (P = 0.072) and OS rate (P = 0.231). The PFS rates at 3 years for the US, CT, and MRI groups were 40.90%, not reached, and 14.80%, respectively. The OS rates at 3 years were 94.70%, 97.50%, and 85.50% for US, CT, and MRI groups, respectively. No significant differences were observed between the three groups in terms of TS rate (P = 0.113) and TE rate (P = 0.682). In multivariate analysis, liver cirrhosis (P = 0.001), level of alpha-fetoprotein (AFP, P = 0.004), and number of tumors (P = 0.012) were independent risk factors for PFS. For TE, the level of AFP (P = 0.018) was an independent factor. Conclusion: US-, CT-, and MRI-guided RFA was effective for treating HCC patients. Liver cirrhosis, AFP level, and tumor number were associated with tumor recurrence, and the level of AFP was an independent risk factor affecting TE.

Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs). As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

Hydrogel electrolytes, which feature intriguing characteristics of being soft and wet, accompanied with high solubility of zinc salts, are especially advantageous for fabricating flexible Zn-based batteries. Furthermore, the abundant and tunable chemistries of hydrogels offer opportunities to bestow novel affiliated functionalities, such as super toughness, extreme temperature tolerance, stimuli-responsive properties, and self-healing capability, by engineering polymer chains and chemical structures to fabricate flexible batteries with unprecedentedly scintillating functions. Herein, the design principles of functional hydrogel electrolytes including polymer chemistry, synthesis methods, characterisation and versatility demonstration for flexible Zn-based batteries are comprehensively reviewed. Relevant challenges and perspectives are also analysed and discussed. This review provides a comprehensive understanding for recent advances of flexible Zn-based batteries with hydrogel electrolytes, with a focus on smart batteries with multifunctionalities. Challenges and perspectives for future wearable applications are also discussed.

The knife-like structure generally develops on the weathered surfaces of dolostone, characterized by irregular distribution of karst ditches, whereas the mechanism driving its development remains unclear. This study aims to elucidate these mechanisms by investigating the roles of dedolomitization and subsequent dissolution, which are hypothesized to be crucial in the formation of this distinctive structure. We employ petrographic and geochemical analyses of oolitic dolostone from the Cambrian Zhangxia Formation, North China Craton, to explore these processes. The oolitic dolostone contains primary limestone, dolomitized crust, calcium-rich metasomatic zones, and calcite veins. The calcium-rich metasomatic zones exhibit a high degree of dissolution-related reformation. Micro-XRF analysis demonstrates that the metasomatic zones of dolostone are more calcium-rich than the undedolomitized dolostone. The high Ca/Mg ratio (19.38) and strong dedolomitization within the calcium-rich metasomatic zones indicate a low degree of resistance to dissolution. The process of dedolomitization was induced by a hydrothermal fluid at a paleotemperature of ca. 65.55℃ as indicated by the carbon and oxygen (C-O) isotopes of the calcium-rich metasomatic zones. Our results demonstrate that dedolomitization, facilitated by the interaction of primary limestone with calcium-rich hydrothermal fluids, led to the formation of calcium-rich metasomatic zones within the fractures. The calcite veins are generated from calcium-saturated hydrothermal fluids. We propose that the knife-like structure results from two processes: dedolomitization, which decreases the resistance to dissolution, followed by an increased degree of dissolution in the calcium-rich metasomatic zones.