The SHH-GLI1 pathway is required in skin expansion and angiogenesis.

To investigate the role of GLI1 on skin proliferation and neovascularization during skin expansion in mice. We constructed GLI1-cre/R26-Tdtomato and GLI1-cre/R26-mtmg gene-tagged skin expansion mouse models. Using a two-photon in vivo imaging instrument to observe the changes in the number and distribution of GLI1(+) cells during the expansion process and to clarify the spatial relationship between GLI1(+) cells and blood vessels during the expansion process. In vitro proliferation assays were performed to further validate the effects of SHH (sonic hedgehog) and its downstream component GLI1 on cell proliferation viability. Finally, qRT-PCR was used to verify the changes in proliferation, angiogenesis-related factors, SHH signalling pathway-related factors, and the role of GLI1 cells in the process of skin expansion in mice. The number of GLI1(+) cells increased during dilation and were attached to the outer membrane of the vessel. The epidermis was thickened and the dermis thinned after the dilated skin was taken, while the epidermal thickening was suppressed and the dermis became thinner after the GLI1 cells were inhibited. The non-inhibited group showed a significant increase in PCNA positivity with prolonged dilation compared to the GANT61(GLI specificity inhibitor) inhibited group; CD31 immunofluorescence showed a significant increase in the number of dilated skin vessels and a significant decrease in the number of vessels after treatment with GANT61 inhibitor. In vitro proliferation results showed that SHH signalling activator significantly increased the proliferation viability of GLI1(+) hair follicle mesenchymal stem cells, while GNAT61 significantly inhibited the proliferation viability of GLI1(+) hair follicle mesenchymal stem cells. GLI1 is necessary for proliferation and neovascularization in expansion skin of mice through activation of the SHH signalling pathway.

The Effect of Trans-Sutural Distraction Osteogenesis on Nasal Bone, Nasal Septum, and Nasal Airway in the Treatment for Midfacial Hypoplasia in Growing Patients.

The purposes of this study were to analyze the effect of trans-sutural distraction osteogenesis (TSDO) on nasal bone, nasal septum, and nasal airway in the treatment of midfacial hypoplasia. A total of 29 growing patients with midfacial hypoplasia who underwent TSDO by a single surgeon were enrolled. The 3-dimensional measurement of nasal bone and nasal septum changes was performed using computed tomography (CT) images obtained preoperatively (T0) and postoperatively (T1). One patient was selected to establish 3-dimensional finite element models to simulate the characteristics of nasal airflow field before and after traction. After traction, the nasal bone moved forward significantly ( P <0.01). The septal deviation angle was lower than that before traction (14.43±4.70 versus 16.86 ±4.59 degrees) ( P <0.01). The length of the anterior and posterior margin of the vomer increased by 21.4% ( P <0.01) and 27.6% ( P <0.01), respectively, after TSDO. The length of the posterior margin of the perpendicular plate of ethmoid increased ( P <0.05). The length of the posterior inferior and the posterior superior margin of the nasal septum cartilage increased ( P <0.01) after traction. The cross-sectional area of nasal airway on the deviated side of nasal septum increased by 23.0% after traction ( P <0.05). The analysis of nasal airflow field showed that the pressure and velocity of nasal airflow and the nasal resistance decreased. In conclusion, TSDO can promote the growth of the midface, especially nasal septum, and increase the nasal space. Furthermore, TSDO is conductive to improve nasal septum deviation and decrease nasal airway resistance.

Two previously undescribed phthalides from Talaromyces amestolkiae, a symbiotic fungus of Syngnathus acus.

Amestolkins A (1) and B (2), two previously undescribed phthalides sharing the same planar structure of (1, 5-dihydroxyhexyl)-7-hydroxyisobenzofuran-1(3H)-one were isolated from Talaromyces amestolkiae. Their absolute configurations were elucidated by comprehensive analyses of spectroscopic evidences in high-resolution electrospray mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) combined with electronic circular dichroism (ECD) and NMR calculations. 1 and 2 showed anti-neuroinflammatory activity by inhibiting the gene expressions of proinflammatory factors including C-C motif chemokine ligand 2 (CCL-2), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as attenuating the excretion of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells at the concentration of 30 µM.

Terpene Glycosides from Sanguisorba officinalis and Their Anti-Inflammatory Effects.

Two new terpene glycosides (1-2) along with two known analogs (3-4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Novel Polyketides Produced by the Endophytic Fungus Aspergillus Fumigatus from Cordyceps Sinensis.

Five new polyketides, including two pairs of enantiomers and a racemate, were isolated from the fermentation broth of Aspergillus fumigatus, an endophytic fungus isolated from Cordyceps sinensis. Their structures were identified using one-dimensional (1D) and two-dimensional (2D) NMR experiments, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. Compounds 1a and 2a exhibited inhibitory activity against the MV4-11 cell line in vitro, with IC50 values of 23.95 µM and 32.70 µM, respectively.

Objective and subjective evaluation of the efficacy of trans-sutural distraction osteogenesis: A correlation analysis between computed tomography measurements and FACE-Q scores.

Previous studies on the efficacy of trans-sutural distraction osteogenesis (TSDO) to treat midface hypoplasia caused by cleft lip and palate (CLP) have mainly focused on objective measurements while ignoring the subjective feelings of patients. This study aimed to analyse the changes in and correlation between computed tomography (CT) measurements and FACE-Q scores in patients who underwent TSDO by performing a comprehensive evaluation from both objective and subjective perspectives. This retrospective study included 25 patients with an average age of 10.7 years who had midface hypoplasia caused by CLP and underwent TSDO between August 2018 and December 2022. The average follow-up time was 18.8 ± 7.7 months. Facial morphology and CT measurements, including A-CR, N-A⊥HR, the SNA angle and the L-ZA, indicated significant improvements in midface concavity (all p < 0.0001). All FACE-Q scores (except for facial function) exhibited a significant increase. The ΔA-CR, ΔN-A⊥HR, and ΔSNA angle were strongly correlated with specific aspects of the FACE-Q-Appearance items, including the ΔFACE-Q-Appearance of the cheeks (all p < 0.0001), the ΔFACE-Q-Appearance of the face (all p < 0.0001), the ΔFACE-Q-Appearance of the jaws (all p < 0.01), the ΔSatisfaction with decision (all p < 0.0001) and the ΔSatisfaction with outcome (all p < 0.001). However, the ΔA-CR, ΔN-A⊥HR, and ΔSNA were weakly correlated with other FACE-Q-Health-related quality of life and function items. These findings suggest that both CT findings and FACE-Q scores have their own emphases and advantages. It is necessary to establish an integrated curative effect evaluation model that combines FACE-Q scores with CT measurements to evaluate both the physical health and psychological status of patients.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. METHODS: Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. RESULTS: Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. CONCLUSION: According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Advances in hyaluronic acid production: Biosynthesis and genetic engineering strategies based on Streptococcus - A review.

Hyaluronic acid (HA), which is a highly versatile glycosaminoglycan, is widely applied across the fields of food, cosmetics, and pharmaceuticals. It is primary produced through Streptococcus fermentation, but the product presents inherent challenges concerning consistency and potential pathogenicity. However, recent strides in molecular biology have paved the way for genetic engineering, which facilitates the creation of high-yield, nonpathogenic strains adept at synthesizing HA with specific molecular weights. This comprehensive review extensively explores the molecular biology underpinning pivotal HA synthase genes, which elucidates the intricate mechanisms governing HA synthesis. Moreover, it delineates various strategies employed in engineering HA-producing strains.

Early warm compress treatment can promote recanalization of vascular embolisms and reduce tissue necrosis after polymethyl methacrylate injection.

Injection of fillers for soft tissue augmentation can lead to a variety of complications, among which vascular occlusion caused by intravascular injection of filler will induce severe or permanent damage. The treatment strategies for intravascular embolization caused by injection include warm compress application, but the exact beneficial effects of this therapy have not been confirmed. The purpose of this study is to construct an intravascular injection embolism model and observe the effectiveness of warm and cold compress through a randomized, controlled trial. Thirty rabbit's sixty ears were randomly divided into warm compress group, cold compress group, and control group. Polymethyl methacrylate (PMMA) was slowly injected into the central ear artery (CEA) to cause vascular embolism. Warm compress and cold compress treatment were performed respectively. The vascular recanalization and other related indexes were observed at 30 min, 1 day, and 7 days after injection, and the tissue necrosis was analyzed at 7 days. In the early stage of vascular embolization, warm compress can immediately promote vascular dilatation, blood circulation and partial blood flow recovery. One day after intravascular injection, warm compress can reduce intravascular embolization and reduce the incidence of tissue necrosis. At 7 days after intravascular injection, the vessels in the cold compress and control groups were still embolized while the percentage of recanalization in the warm compress group was 47.4% (P < 0.000). Early-stage warm compress after intravascular PMMA injection is conducive to recanalization of vascular embolization and reducing tissue necrosis.

Combining Diced Cartilage with Chondrocyte Spheroids in GelMA Hydrogel: An Animal Study in Diced Cartilage Grafting Technique.

BACKGROUND: The phenotype maintenance of diced cartilage is a very important factor to reduce cartilage absorption rate in augmentation rhinoplasty. A novel method which combined diced cartilage with chondrocyte spheroids in gelatin methacrylate (GelMA) hydrogel may have potentially good performance in phenotype maintenance, and is worth exploring. METHODS: The complex grafts formed by loading diced cartilage with chondrocyte spheroids into GelMA hydrogel were used as the experimental group, and the grafts formed of diced cartilage in GelMA were used as the control group. The two groups of grafts were implanted subcutaneously in nude mice. After 1 month and 3 months, the grafts were taken for general observation and histological analysis. The diameter changes of cartilage, the nuclei loss of chondrocyte, and glycosaminoglycan secretion were analyzed. RESULTS: Chondrocyte spheroids with obvious proliferation can be seen in the experimental group. Some diced cartilages had become a whole through the interconnection of chondrocyte spheroids. In addition, the diameter of the chondrocyte spheroids-diced cartilage complex in the experimental group increased significantly, and its nuclei loss rate was less than 1/2 of that in the control group. The maintenance of proteoglycans in diced cartilages in the experimental group was significantly better than that in the control group. CONCLUSION: The combination of diced cartilage with chondrocyte spheroids in GelMA hydrogel can significantly reduce the absorption of cartilage extracellular matrix, enhance phenotype maintenance during subcutaneous ectopic implantation, and can produce inter-chondral connections.

Poly(I:C)-induced maternal immune activation causes elevated self-grooming in male rat offspring: Involvement of abnormal postpartum static nursing in dam.

Introduction: Maternal immune activation (MIA) is closely related to the onset of autism-like behaviors in offspring, but the mechanism remains unclear. Maternal behaviors can influence offspring's development and behaviors, as indicated in both human and animal studies. We hypothesized that abnormal maternal behaviors in MIA dams might be other factors leading to delayed development and abnormal behaviors in offspring. Methods: To verify our hypothesis, we analyzed poly(I:C)-induced MIA dam's postpartum maternal behavior and serum levels of several hormones related to maternal behavior. Pup's developmental milestones and early social communication were recorded and evaluated in infancy. Other behavioral tests, including three-chamber test, self-grooming test, open field test, novel object recognition test, rotarod test and maximum grip test, were performed in adolescence of pups. Results: Our results showed that MIA dams exhibit abnormal static nursing behavior but normal basic care and dynamic nursing behavior. The serum levels of testosterone and arginine vasopressin in MIA dams were significantly reduced compared with control dams. The developmental milestones, including pinna detachment, incisor eruption and eye opening, were significantly delayed in MIA offspring compared with control offspring, while the weight and early social communication showed no significant differences between the two groups. Behavioral tests performed in adolescence showed that only male MIA offspring display elevated self-grooming behaviors and reduced maximum grip. Discussion: In conclusion, MIA dams display abnormal postpartum static nursing behavior concomitantly with reduced serum levels of testosterone and arginine vasopressin, possibly involving in the pathogenesis of delayed development and elevated self-grooming in male offspring. These findings hint that improving dam's postpartum maternal behavior might be a potential regime to counteract delayed development and elevated self-grooming in male MIA offspring.

Identification of HMOX1 as a Critical Ferroptosis-Related Gene in Atherosclerosis.

Ferroptosis is a novel form of programmed iron-dependent cell death. The ferroptosis-related genes (FRGs) have been recognized as biomarkers for cancers. Increasing evidence has indicated that ferroptosis is involved in the process of atherosclerosis. However, the potential FRGs used for the diagnosis, prognosis and therapy for atherosclerosis are still unclear. We aimed to identify the ferroptosis-related differentially expressed genes (DEGs) of atherosclerosis. We downloaded the mRNA-sequencing data of patients with atherosclerosis from the Gene Expression Omnibus (GEO) database. HMOX1 was identified as an essential ferroptosis-related DEG by bioinformatic analysis of the GSE28829 and GSE43292 datasets. The pro-ferroptotic effect of HMOX1 was validated through cell experiments. Then we conducted a single-gene analysis of HMOX1 and found that high-expression of HMOX1 in atherosclerotic plaques was accompanied by matrix metalloproteinases (MMPs) producing and M0 macrophages infiltration. Taken together, our present study suggested HMOX1 as a potential diagnostic biomarker for atherosclerosis and provided more evidence about the vital role of ferroptosis in atherosclerosis progression.

Research advances in the structures and biological activities of secondary metabolites from Talaromyces.

The genus Talaromyces belongs to the phylum Ascomycota of the kingdom Fungi. Studies have shown that Talaromyces species yield many kinds of secondary metabolites, including esters, terpenes, steroids, alkaloids, polyketides, and anthraquinones, some of which have biological activities such as anti-inflammatory, bacteriostatic, and antitumor activities. The chemical constituents of fungi belonging to the genus Talaromyces that have been studied by researchers over the past several years, as well as their biological activities, are reviewed here to provide a reference for the development of high-value natural products and innovative uses of these resources.

Two new nor-sesquiterpenoids from Fusarium tricinctum, an endophytic fungus isolated from Ligusticum chuanxiong.

As part of our search for compounds with cytotoxicity from endophytes of traditional Chinese medicines, two novel nor-sesquiterpenoids (1-2) with a new skeleton containing a tetrahydrofuran moiety were isolated form a rice medium of Fusarium tricinctum, an endophytic fungus isolated from the root of Ligusticum chuanxiong. The structures of these two previously undescribed compounds were elucidated by interpretation of the spectroscopic evidences including NMR correlations as well as MS data. The absolute configurations of these two compounds were confirmed by TD-DFT-ECD calculations. An MTT assay indicated that compound 1 exhibited moderate cytotoxic activity against MV4-11 with an IC50 value of 22.29 µM.

Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion.

Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11-21 of Shank3, leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3-deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3-depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3-deficient rats. It is worth to note that Shank3-deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3-related neurodevelopmental disorders.