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The source and process of mandible development are significantly different from those of other bones in the body, and abnormal development can lead to various bone-related diseases, seriously affecting the quality of life of patients. In recent years, the role of the Hedgehog signaling pathway in bone development has received increasing attention. The Hedgehog gene includes three subtypes: Sonic Hedgehog (Shh), Indian Hedgehog (Ihh), and Desert Hedgehog (Dhh). Shh and Ihh can participate in bone metabolism regulation through various pathways, with Shh primarily involved in limb development and Ihh playing a key role in endochondral osteogenesis. The Hedgehog signaling pathway includes Hedgehog signaling protein ligands, Patched (Ptch) receptors, Smoothed (Smo) receptors, nuclear transcription factors, glioma-associated oncogene homologues (Gli), and downstream target genes. The activation of typical Hedgehog signaling pathways requires the involvement of Gli, whereas atypical Hedgehog signaling is mainly regulated by Ptch, Smo, and others. Shh regulates various biological behaviors during early vertebrate embryogenesis, such as organ differentiation, neural stem formation, stem cell differentiation and proliferation, limb bone development, and tooth germ development. During the process of bone cell differentiation, Shh, Ptch1, and Gli1 are expressed in osteoblasts, further promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and chondrocytes. IHh plays an indispensable functional role in bone growth, development, and homeostasis and participates in the formation of intramembrane bone collars, proliferation, and maturation of chondrocytes. IHh is expressed in mature skull osteoblasts and can act as a promoter of bone factor regulation of Ptch and bone morphogenetic protein (BMP) expression to induce intramembrane ossification. Brain and muscle ARNT-like protein 1 (BMAL1) can regulate the Hedgehog signaling pathway by binding to Ptch1 and Ihh, playing a crucial role in cartilage formation and endochondral osteogenesis in the temporomandibular joint. Hedgehog signal activators can improve the reduction in mandibular bone mass caused by BMAL1 deficiency. Hedgehog signaling imbalance can have a significant impact on bone development and lead to a series of bone diseases, such as abnormal bone development, fractures, osteoporosis, and osteoarthritis. The mechanism of the Hedgehog signaling pathway in relation to mandibular diseases has not been fully elucidated, and future research should seek to further explore Hedgehog signaling as a potential target for treating mandibular developmental-related diseases.

Abstract We consider a simplified model of double scaled SYK (DSSYK) in which the Hamiltonian is the position operator of the Harmonic oscillator. This model captures the high temperature limit of DSSYK but could also be defined as a quantum theory in its own right. We study properties of the emergent geometry including its dynamics in response to inserting matter particles. In particular, we find that the model displays de Sitter-like properties such as that infalling matter reduces the rate of growth of geodesic slices between the two boundaries. The simplicity of the model allows us to compute the full generating functional for correlation functions of the length mode or any number of matter operators. We provide evidence that the effective action of the geodesic length between boundary points is non-local. Furthermore, we use the on-shell solution for the geodesic lengths between any two boundary points to reconstruct an effective bulk metric and reverse engineer the dilaton gravity theory that generates this metric as a solution.

Abstract Alzheimer’s disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC50 of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile. Graphical Abstract

In 2022, the U.S. Preventive Services Task Force (USPSTF) updated its recommendations, reviewing the evidence of the benefits and harms of behavioral counseling interventions aimed at promoting healthy behaviors in adults without cardiovascular disease risk factors. The conclusions of this review align with the 2017 guidelines. Behavioral counseling interventions in adults without cardiovascular disease risk factors result in minimal net benefits. Therefore, it is recommended that clinicians make individualized decisions on whether to provide or recommend behavioral counseling interventions to adults without cardiovascular disease risk factors to promote a healthy diet and physical activity (Grade C). This article provides a comprehensive interpretation of the guidelines in the context of the current status of cardiovascular disease prevention in China, offering valuable insights into cardiovascular disease prevention practices among Chinese adults.

Serine/arginine-rich splicing factors (SRSFs), part of the serine/arginine-rich (SR) protein family, play a crucial role in precursor RNA splicing. Abnormal expression of SRSFs in tumors can disrupt normal RNA splicing, contributing to tumor progression. Notably, SRSF7 has been found to be upregulated in hepatocellular carcinoma (HCC), yet its specific role and molecular mechanisms in HCC pathogenesis are not fully understood. We investigated the expression and prognostic significance of SRSF7 in HCC using bioinformatics database analysis. In HepG2 cells, the expressions of SRSF7 and glycolytic enzymes were analyzed using qRT-PCR, and Western blot. Glucose uptake and lactate production were quantified using relevant reagent kits. Additionally, cell proliferation, clonogenicity, invasion, and apoptosis were evaluated using MTS assay, clonal formation assay, Transwell assay, and mitochondrial membrane potential assay, respectively. This study demonstrated significant overexpression of SRSF7 in HCC tissue, correlating with poor prognosis. Knockdown of SRSF7 in HepG2 cells resulted in inhibited proliferation, clonogenicity, and invasion, while apoptosis was enhanced. This knockdown also decreased glucose uptake and lactate production, along with a reduction in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). Furthermore, SRSF7 downregulation increased the pyruvate kinase muscle 1 (PKM1)/PKM2 ratio. The glycolytic boost due to PKM2 overexpression partially counteracted the effects of SRSF7 silencing on HepG2 cell growth. The knockdown of SRSF7 impairs aerobic glycolysis and growth in HepG2 cells by downregulating PKM2 expression.

The regulation of immune functions and the maintenance of homeostasis in the internal environment are both integral to human gut microbiota (GM). If GM is disturbed, it can result in a range of autoimmune diseases, including chronic inflammatory skin conditions. Chronic inflammatory skin diseases driven by T or B-cell-mediated immune reactions are complex, including the most prevalent diseases and some rare diseases. Expanding knowledge of GM dysbiosis in chronic inflammatory skin diseases has emerged. The GM has some causal roles in the pathogenesis of these skin conditions. Targeting microbiota treatment, particularly fecal microbiota transplantation (FMT), is considered to be a promising strategy. FMT was commonly used in intestinal diseases by reshaping and balancing GM, serving as a reasonable administration in these skin inflammatory diseases. This paper summarizes the existing knowledge of GM dysbiosis in chronic inflammatory skin diseases and the research data on FMT treatment for such conditions.

ABSTRACT: Rising temperatures and intensified agricultural practices have heightened heat stress (HS)-related challenges in poultry farming, notably heat-induced sudden death in chickens. Wenchang chickens, recognized for their heat resistance, have emerged as the potential candidates for improving the economic efficiency of poultry farming. The adrenal gland plays a crucial role in preventing HS-induced heart failure sudden death by secreting hormones. However, little is known about the damage to and resilience of Wenchang chicken adrenal glands during HS. In this study, 34 healthy Wenchang chickens with similar weights were selected for formal experimentation, with 10 as the control group (Con). Following a single exposure to acute HS of 42 ± 1°C and 65% relative humidity for 5 h, 15 deceased individuals formed the HS death (HSD) group, and 9 survived comprised the HS survival (HSS) group. ELISA revealed significant higher (P < 0.05) levels of COR and NE in the HSS and the lowest levels of CORT and EPI in the HSD. Histopathological analysis indicated major degeneration in HSS cortical and chromaffin cells and extensive cell necrosis (nuclear pyknosis) in HSD. Proteomic analysis identified 572 DEPs in HSD vs. Con and 191 DEPs in HSS vs. Con. Bioinformatics highlighted ER protein processing, especially ERAD as a key pathway for heat stress resistance (HSR) in the adrenal gland, with HSPH1, DNAJA1, HSP90AA1, HSPA8 and HERPUD1 identified as regulating key molecules. Western blotting validated significantly higher (P < 0.01) protein levels in both HSS and HSD compared to the Con. Immunohistochemical staining showed increased cytoplasmic HSPH1-positive signal intensity under HS and enhanced HSP90AA1 nuclear signals, strongest in HSS. In summary, HS induces pathological damage in Wenchang chicken adrenal glands, affecting hormone secretion, and various heat shock proteins play crucial roles in cellular resistance. These results elucidate the biological basis of HSR in Wenchang chickens from the perspective of the adrenal gland and provide necessary research foundations for enhancing economic performance of various broilers in high-heat environments and screening drugs for HS treatment.