Deciphering the Interplay between the Epithelial Barrier, Immune Cells, and Metabolic Mediators in Allergic Disease.

Chronic exposure to harmful pollutants, chemicals, and pathogens from the environment can lead to pathological changes in the epithelial barrier, which increase the risk of developing an allergy. During allergic inflammation, epithelial cells send proinflammatory signals to group 2 innate lymphoid cell (ILC2s) and eosinophils, which require energy and resources to mediate their activation, cytokine/chemokine secretion, and mobilization of other cells. This review aims to provide an overview of the metabolic regulation in allergic asthma, atopic dermatitis (AD), and allergic rhinitis (AR), highlighting its underlying mechanisms and phenotypes, and the potential metabolic regulatory roles of eosinophils and ILC2s. Eosinophils and ILC2s regulate allergic inflammation through lipid mediators, particularly cysteinyl leukotrienes (CysLTs) and prostaglandins (PGs). Arachidonic acid (AA)-derived metabolites and Sphinosine-1-phosphate (S1P) are significant metabolic markers that indicate immune dysfunction and epithelial barrier dysfunction in allergy. Notably, eosinophils are promoters of allergic symptoms and exhibit greater metabolic plasticity compared to ILC2s, directly involved in promoting allergic symptoms. Our findings suggest that metabolomic analysis provides insights into the complex interactions between immune cells, epithelial cells, and environmental factors. Potential therapeutic targets have been highlighted to further understand the metabolic regulation of eosinophils and ILC2s in allergy. Future research in metabolomics can facilitate the development of novel diagnostics and therapeutics for future application.

A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

Capsiate ameliorates secondary hyperparathyroidism by improving insulin sensitivity and inhibiting angiogenesis.

Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.

POU2F2-mediated upregulation of lncRNA PTPRG-AS1 inhibits ferroptosis in breast cancer via miR-376c-3p/SLC7A11 axis.

Background: Triple-negative breast cancer (TNBC) is a subtype of BC with high rates of mortality. The mechanism of PTPRG-AS1 in ferroptosis of TNBC was investigated. Methods: Chromatin immunoprecipitation and dual-luciferase reporter assays were used to measure intermolecular relationships. MTT and colony formation assays detected cell viability and proliferation. Kits detected Fe2+ and reactive oxygen species levels. The role of PTPRG-AS1 in tumor growth was analyzed in vivo. Results: PTPRG-AS1 was increased in TNBC tissues and cells. PTPRG-AS1 silencing increased the reduction of glutathione and GPX4, increased Fe2+ and reactive oxygen species in erastin-treated cells and inhibited proliferation. POU2F2 transcriptionally upregulated PTPRG-AS1. PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11. PTPRG-AS1 knockdown suppressed tumor growth in vivo. Conclusion: POU2F2 transcriptionally activates PTPRG-AS1 to modulate ferroptosis and proliferation by miR-376c-3p/SLC7A11, promoting TNBC.

Triple-negative breast cancer (TNBC) is a kind of breast cancer with high recurrence and low survival rates. Activation of the ferroptosis pathway can inhibit BC proliferation and distant metastasis. Therefore, identifying effective biomarkers and molecular mechanisms of ferroptosis in TNBC is important for its earlier detection and therapy. PTPRG-AS1 is a new type of lncRNA discovered in recent years that is increased in various diseases and is related to prognosis. In the present study, the authors found that POU2F2 promoted PTPRG-AS1 transcription. PTPRG-AS1 knockdown activated ferroptosis in TNBC and inhibited proliferation. Mechanistically, PTPRG-AS1 targeted miR-376c-3p to upregulate SLC7A11, thereby inhibiting ferroptosis and promoting TNBC development. These results indicate that PTPRG-AS1 is a possible therapeutic target in TNBC.

Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice.

OBJECTIVE: To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula (4HF) and doxorubicin in triple-negative breast cancer (TNBC). METHODS: Murine-derived triple-negative mammary carcinoma cell line, 4T1 cells, was cultured and inoculated into mouse mammary glands. Sixty-six mice were randomly assigned into 6 groups (n=11 in ench): naïve, control, LD 4HF (low dose 4HF), HD 4HF (high dose 4HF), LD 4HF + D (low dose and doxorubicin), and D (doxorubicin). Apart from the naïve group, each mouse received subcutaneous inoculation with 5 × 105 4T1 cells resuspended in 100 µL of normal saline in the mammary fat pads. Starting from the day of tumor cell inoculation, tumors were grown for 6 days. The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF, respectively. The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin (5 mg/kg). The D group received weekly intraperitoneal injections of doxorubicin (5 mg/kg). The treatment naïve mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week. The control group received daily oral gavage of 0.2 mL double-distilled water. The treatment period was 30 days. At the end of treatment, mice organs were harvested to analyze immunological activities via immunophenotyping, gene and multiplex analysis, histological staining, and gut microbiota analysis. RESULTS: Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens (P<0.05), altered the hypoxia and overall immune lymphocyte landscape, and manipulated gut microbiota to favor the anti-tumor immunological activities. Moreover, immunosuppressive genes, cytokines, and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated (P<0.05). 4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response (P<0.05). CONCLUSION: The above results provide evidence for evaluating the immune regulating mechanisms of 4HF in breast cancer and support its clinical significance in its potential as an adjunctive therapeutic agent or immune supplement.

Adjuvant activities of immunostimulating natural products: Astragalus membranaceus (Fisch.) Bge. and Coriolus versicolor in BNT162b2 vaccination against COVID-19 infection.

The global pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been developing all over the world for more than 3 years. In late 2020, several variants of concern of SARS-CoV-2 virus emerged, with increased viral fitness and transmissibility by mutations of the spike proteins of the viral particle, denting hopes of the use of early-generation vaccines for a widespread protective immunity against viral infection. The use of adjuvants may enhance the immune responses of the conventional application of the COVID-19 vaccine. We have shown that the water extract of 2 ß-glucan-enriched immunostimulating natural products, Astragalus membranaceus (Fisch.) Bge. (AM) and Coriolus versicolor (CV), could induce innate immunity-related cytokines from human monocytes (CCL5, interleukin [IL]-6, IL-10, and tumor necrosis factor α) and monocyte-derived dendritic cells (IL-1ß, IL-10, IL-12, and tumor necrosis factor α). Using BALB/c mice, orally administrated AM and CV (1,384 and 742 mg/kg/d) for 4 d after vaccination, respectively, could enhance (1) the immunoglobulin G binding activities of BNT162b2 vaccination against ancestral and Delta SARS-CoV-2 spike proteins by 5.8- and 4.3-fold, respectively; (2) the immunoglobulin G3 subclass production of BNT162b2 vaccination against ancestral and variant SARS-CoV-2 spike proteins; and (3) the in vitro antibody-neutralizing activities of BNT162b2 vaccinated mice. In conclusion, combining AM and CV was effective in acting as an oral adjuvant with the messenger RNA vaccine BNT162b2 to improve the antigen binding activities against SARS-CoV-2 ancestral and variant SARS-CoV-2 spike proteins, probably via trained immunity of macrophages and dendritic cells.

Global research trends and prospects related to tumor microenvironment within Triple Negative Breast Cancer: a bibliometric analysis.

Background and aims: The tumor microenvironment (TME) has pivotal parts within multiple tumor models of onset/progression, such as triple-negative breast cancer (TNBC). This bibliometric analysis was developed to explore trends and research niches revolving around TME in TNBC. Methods: Web of Science Core Collection was queried for identifying studies linked with TME in TNBC, after which the VOSviewer, CiteSpace, and R software programs were used to conduct bibliometric analyses and to generate corresponding visualizations. Results: In total, this study included 1,604 studies published from 2005-2023. The USA and China exhibited the highest numbers of citations, and the research institutions with the greatest output in this field included Harvard University, the University of Texas System, and Fudan University. Ying Wang from Sun Yat-Sen University was the most published and most cited author in this space. The highest number of articles were published in Cancer, while the greatest co-citation number was evident in Breast Cancer Research. Important keywords related to this research topic included metastasis, tumor-infiltrating lymphocytes, immunotherapy, chemotherapy, and nanoparticles. In particular, pembrolizumab, immunotherapy, nanoparticles, combination treatment, and biomarkers were topics of marked interest in recent reports. Conclusion: The TME in TNBC is an area of rapidly growing and evolving research interest, with extensive global collaboration helping to drive this field forward. Antitumor therapies targeting the TME in TNBC patients represent an emerging topic of future research, providing opportunities for translational findings. The results of this analysis may provide additional guidance for work focused on the TME in TNBC.

Progress in copper-based materials for wound healing.

Chronic wounds have become the leading cause of death, particularly among diabetic patients. Chronic wounds affect ~6.5 million patients each year, according to statistics, and wound care and management incur significant financial costs. The rising prevalence of chronic wounds, combined with the limitations of current treatments, necessitates the development of new and innovative approaches to accelerate wound healing. Copper has been extensively studied for its antibacterial and anti-inflammatory activities. Copper in its nanoparticle form could have better biological properties and many applications in health care.

Creating a Vaccine-like Supplement against Respiratory Infection Using Recombinant Bacillus subtilis Spores Expressing SARS-CoV-2 Spike Protein with Natural Products.

Vaccination is the most effective method of combating COVID-19 infection, but people with a psychological fear of needles and side effects are hesitant to receive the current vaccination, and alternative delivery methods may help. Bacillus subtilis, a harmless intestinal commensal, has recently earned a strong reputation as a vaccine production host and delivery vector, with advantages such as low cost, safety for human consumption, and straightforward oral administration. In this study, we have succeeded generating "S spores" by engineering B. subtilis with spore coat proteins resembling the spike (S) protein of the ancestral SARS-CoV-2 coronavirus. With the addition of two immunostimulating natural products as adjuvants, namely Astragalus membranaceus (Fisch.) Bge (AM) and Coriolus versicolor (CV), oral administration of S spores could elicit mild immune responses against COVID-19 infection without toxicity. Mucosal IgA against the S protein was enhanced by co-feeding with AM and CV in an S spores-inoculated mouse model. Faster and stronger IgG responses against the S protein were observed when the mice were fed with S spores prior to vaccination with the commercial COVID-19 vaccine CoronaVac. In vitro studies demonstrated that AM, CV, and B. subtilis spores could dose-dependently activate both macrophages and dendritic cells by secreting innate immunity-related IL-1ß, IL-6, and TNF-α, and some other proinflammatory chemokines and cytokines. In conclusion, the combination of S spores with AM and CV may be helpful in developing a vaccine-like supplement against respiratory infection.

Angiogenesis and flap-related research: A bibliometric analysis.

Adequate blood supply, a prerequisite for flap survival after grafting, makes angiogenesis of the flap the biggest problem to be solved. Researches have been conducted around vascularisation in correlation with flap grafting. However, bibliometric analyses systematically examining this research field are lacking. As such, we herein sought to conduct comprehensive comparative analyses of the contributions of different researchers, institutions, and countries to this research space in an effort to identify trends and hotspots in angiogenesis and vascularisation in the context of flap grafting. Publications pertaining to angiogenesis and vascularisation in the context of flap grafting were retrieved from the Web of Science Core Collection. References were then analysed and plotted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. In total, 2234 papers that were cited 40 048 times (17.63 citations/paper) were included in this analysis. The greatest number of studies were from the United States, with these studies exhibiting both the highest number of citations (13 577) and the greatest overall H-index (60). For The institutions that published the greatest number of studies were WENZHOU MEDICAL UNIVERSITY (681), while UNIVERSITY OF ERLANGEN NUREMBERG has the highest number of citations (1458), and SHANGHAI JIAO TONG UNIVERSITY holds the greatest overall H-index (20). The greatest number of studies in this research space were published by Gao WY, while Horch RE was the most commonly cited researcher in the field. The VOS viewer software clustered relevant keywords into three clusters, with clusters 1, 2, 3, and 4 corresponding to studies in which the keywords 'anatomy', 'survival', 'transplantation', 'therapy' most frequently appeared. The most promising research hotspot-related terms in this field included 'autophagy', 'oxidative stress', 'ischemia/reperfusion injury', which exhibited a most recent average appearing year (AAY) of 2017 and after. Generally speaking, the results of this analysis indicate that the number of articles exploring angiogenesis and flap-related research has risen steadily, with the United States and China being the two countries publishing the greatest proportion of studies in this field. The overall focus of these studies has shifted away from 'infratest and tissue engineering' towards 'mechanisms'. In the future, particular attention should be paid to emerging research hotspots, which include 'ischemia/reperfusion injury' and treatments for promoting vascularization, such as 'platelet-rich plasma'. In light of these findings, funding agencies should continue increasing their investment in the exploration of the concrete mechanisms and interventional therapeutic relevance of angiogenesis during flap transplantation.

Hemochromatosis as a secondary condition to systemic lupus erythematosus: A case report.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs and systems, including joints, the cardiovascular system, lungs, skin, kidneys, the nervous system, and blood. The clinical presentations of SLE are diverse and vary widely. In this report, we present a case of a patient whose SLE was complicated by hemochromatosis to enhance clinicians' comprehension of this infrequent or rare complication of SLE. We aim to provide insights into the diagnosis and treatment processes of this condition.

Platycodin D relieves rheumatoid arthritis by promoting apoptosis of mitochondria to inhibit activation of hedgehog pathway.

Rheumatoid arthritis (RA) displays very similar characteristics to those of tumor cells, platycodin D (PD) is a triterpenoid saponin abundant in Platycodon grandiflorum (PG), plays an important role in the inhibition of tumor growth. Our previous experiments confirmed that PD inhibited MH7A cell proliferation and migration, but it's possible mechanism remain unclear. This study aimed to reveal the mechanism of PD on RA, based on network pharmacology analysis. Rat of CIA was treated with the different doses PD. The arthritis score and paw volume were evaluated, ankle imaging changes were observed via myosseous ultrasound, all rats were anaesthetized by intraperitoneal injection of 25% urethane (1 mL/100 g), and ankle histopathology was observed using hematoxylin and eosin (HE) staining. Cell (MH7A) Counting Kit 8 (CCK8) was used to measure cell activity, and JC-1 assay kit and flow cytometry were employed to examine the cell mitochondrial membrane potential and apoptosis. The expression levels of Sonic hedgehog (Shh) signaling pathway-related proteins were observed by Western blotting. Cell inflammation levels of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 being determined via enzyme-linked immunoassay ELISA and q-PCR. In total, the saponin PD significantly improves joint synovium inflammation and apoptosis in CIA rats. The activity of administered MH7A was significantly inhibited, the mitochondrial membrane potential decreased, the expression level of the Shh signaling pathway-related protein SuFu increased, the expression levels of SHh and Gli decreased, and cell serum levels of TNF-a and IL-6 decreased significantly. Therefore, PD exhibits therapeutic potential for synovial hyperplasia in RA.

Inflammatory response: The target for treating hyperpigmentation during the repair of a burn wound.

Hyperpigmentation is a common complication in patients with burn injuries during wound healing; however, the mechanisms underlying its occurrence and development remain unclear. Recently, postinflammatory hyperpigmentation (PIH) was found to result from overproduction of melanin. Local or systemic inflammatory responses are often observed in patients who develop hyperpigmentation. However, we lack studies on the relationship between PIH and burn injury. Therefore, we comprehensively reviewed the existing literature on the melanogenesis of the skin, inflammatory mechanisms in pigmentation, and local or systemic alteration in inflammatory cytokines in patients suffering from burn trauma to elucidate the relationship between PIH and burn injury. We believe that this review will guide further research on regulating melanin production in the burn management process.

Biofilms in wound healing: A bibliometric and visualised study.

Bibliometric analyses are often used as a means of visualising the knowledge base and associated trends and patterns in a target scientific field based on a quantitative review of the corresponding literature. In this study, we explore the current status of research pertaining to biofilms in wound healing and elucidate trends in this research space. Through this process, we gain insight into findings from papers indexed in the Web of Science Core Collection. These references were then analysed and plotted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. The results provide a fresh perspective regarding global trends and hotspots in biofilm-related wound healing research. These findings also offer a foundation that researchers can use to identify active hotspots of scientific interest to guide further research endeavours.

Predictors of response of rituximab in rheumatoid arthritis by weighted gene co-expression network analysis.

PURPOSE: The purpose of this study was to identify a biomarker that can predict the efficacy of rituximab (RTX) in the treatment of rheumatoid arthritis (RA) patients. METHODS: Utilized weighted gene co-expression network analysis (WGCNA) and LASSO regression analysis of whole blood transcriptome data (GSE15316 and GSE37107) related to RTX treatment for RA from the GEO database, the critical modules, and key genes related to the efficacy of RTX treatment for RA were found. The biological functions were further explored through enrichment analysis. The area under the ROC curve (AUC) was validated using the GSE54629 dataset. RESULTS: WGCNA screened 71 genes for a dark turquoise module that were correlated with the efficacy of RTX treatment for RA (r = 0.42, P < 0.05). Through the calculation of gene significance (GS) and module membership (MM), 12 important genes were identified; in addition, 21 important genes were screened by the LASSO regression model; two key genes were obtained from the intersection between the important genes. Then, BANK1 (AUC = 0.704, P < 0.05) was identified as a potential biomarker to predict the efficacy of RTX treatment for RA by ROC curve evaluation of the treatment and validation groups. BANK1 gene expression was significantly decreased after RTX treatment, and a statistically significant difference was found (log FC = - 2.08, P < 0.05). Immune cell infiltration analysis revealed that the infiltration of CD4 + T cell memory subset was increased in the group with high BANK1 expression, and a statistically significant difference was found (P < 0.05). CONCLUSIONS: BANK1 can be used as a potential biomarker to predict the response of RTX treatment in RA patients. Key Points • Identifying the hub genes BANK1 as a potential biomarker to predict the response of RTX treatment in RA patients and confirming it in validation data. • Using the WGCNA approach and LASSO analyses to identify the BANK1 in a data set consisting of two GEO data merged and assessing the correlations between BANK1 and immune infiltration by CIBERSORT algorithm.

Postoperative antibiotics and infection rates after implant-based breast reconstruction: A systematic review and meta-analysis.

Purpose: Infection is the most common complication following breast implant surgery. Nevertheless, the systematic administration of antibiotics after breast implant surgery has been subjected to controversial debate. In this study, we sought to elucidate the association between infection and the use of antibiotics as an aftermath of breast implantation surgical procedures. Methods: Relevant studies were identified from PubMed, Web of Science, and EMBASE search mining. The extracted data included study type, basic characteristics, administrated antibiotic information, and clinical outcomes. Random-effects models were utilized to estimate outcomes, while study quality, statistical bias, and heterogeneity were also analyzed. Results: A total of 7 studies involving a total of 9,147 subjects were included. The results demonstrated that the use of antibiotics after breast implantation reduced the incidence of infection (risk ratio [RR]: 0.65, 95% CI, 0.46-0.90). Nevertheless, smoking, obesity and diabetes type II are risk factors for postoperative infections. Sensitivity analysis verified the robustness of the results. Conclusions: Our study identified the administration of antibiotics after breast implantation as an intervention that decreased the incidence of infection. Smoking, obesity, and diabetes type II are risk factors for postoperative infections. These findings strongly suggest that timely and effective antibiotic interventions will be crucial in future clinical practice, which may reduce the risk of postoperative infection following breast implantation.

Gasless endoscopic transaxillary thyroid surgery: CUSUM analysis of a single surgeon's experience from 105 preliminary procedures.

BACKGROUND: We aimed to evaluate the feasibility and oncologic safety of gasless endoscopic transaxillary thyroidectomy (TAT) in patients with thyroid diseases. Improvements in surgical techniques were also reported, and the learning curves of gasless endoscopic TAT were further studied. METHODS: An exact 1:1 matching analysis was performed to compare the technical safety and oncologic outcomes between TAT and conventional open surgery. A questionnaire was designed to evaluate the quality of life of enrolled patients. A cumulative summation analysis was designed for the quantitative estimation of the learning curves. RESULTS: A total of 105 consecutive patients who successfully received endoscopic TAT were retrospectively enrolled in the current study. A standard three-step working space making procedure, an approach that does not free the superficial part of the sternal head of the sternocleidomastoid muscle (SCM, NFSSH) and a "point to line to surface" en bloc procedure utilized in lobectomy with ipsilateral central neck dissection (CND), were introduced in our surgical procedures. The mean operation time in the TAT group was significantly longer than that in the conventional open group (86.9 ± 31.3 vs 44.2 ± 8.3, p < 0.001). Significant differences in the complication rate were not found between the two groups. Discomfort in the anterior neck area and SCM was relieved over time in most cases (verbal response scores (VRSs) were gradually decreased over time). The learning curves for working space making, ipsilateral thyroidectomy and the total endoscopic TAT approach were 45 cases, 25 cases and 42 cases, respectively. The operation time in the proficient group was significantly shorter than that in the learning group (67.0 ± 8.4 vs 112.3 ± 35.7, p < 0.001). VRSs in the SCM were significantly lower in the proficient group (for 1 week: 1.25 ± 0.65 vs 2.40 ± 0.63, p < 0.001; for 1 month: 0.81 ± 0.69 vs 1.81 ± 0.40, p < 0.001). CONCLUSIONS: Gasless endoscopic TAT was safe in a cohort of patients with thyroid diseases, with satisfactory surgical outcomes and cosmetic appearance. The learning curve for endoscopic TAT was approximately 42 cases. The proficiency of the endoscopic TAT approach depended primarily on the proficiency of working space making.

SLAMF8 promotes the proliferation and migration of synovial fibroblasts by regulating the ERK/MMPs signalling pathway.

Rheumatoid arthritis is troublesome to treat effectively and often requires concomitant long-term treatment. Meanwhile, synovial fibroblasts could induce inflammation response and lead to joint erosion, finally causing progressive joint destruction, disability, and increased mortality. This study focussed on the role of SLAM family member 8 (SLAMF8) in mediating cell function from rheumatoid arthritis synovial fibroblasts stimulated with TNF-α. Cell Counting Kit-8 (CCK-8) and colony-forming unit assay were used to evaluate cell proliferation. SLAMF8 expression was analysed by reverse transcription-quantitative PCR (RT-qPCR) and western blot. Annexin V-FITC/PI double staining was used to measure the apoptosis rate. The cell migration and invasion in TNF-α-stimulated MH7A (human rheumatoid arthritis synovial cell line) and HFLS-RA cells (human fibroblast-like synoviocytes: rheumatoid arthritis) were tested via wound healing assay and transwell migration assay. In the present study, after TNF-α treatments, the SLAMF8 mRNA and protein expression in both MH7A and HFLS-RA cell lines have a time-dependent increase. The attenuation of SLAMF8 ameliorated TNF-α-induced proliferation, invasion and migration in MH7A and HFLS-RA cells. Simultaneously, when SLAMF8 was silenced, the expression of p-ERK, MMP-1, and MMP-13 was suppressed significantly. In summary, these results indicated that the knockdown of the SLAMF8 significantly attenuated TNF-α-induced proinflammatory responses in MH7A and HFLS-RA cells. Therefore, SLAMF8 exhibits therapeutic potential for the management of inflammation in rheumatoid arthritis.

Gene Co-Expression Analysis Reveals Transcriptome Divergence between Wild and Cultivated Sugarcane under Drought Stress.

Drought is the main abiotic stress that constrains sugarcane growth and production. To understand the molecular mechanisms that govern drought stress, we performed a comprehensive comparative analysis of physiological changes and transcriptome dynamics related to drought stress of highly drought-resistant (ROC22, cultivated genotype) and weakly drought-resistant (Badila, wild genotype) sugarcane, in a time-course experiment (0 h, 4 h, 8 h, 16 h and 32 h). Physiological examination reviewed that ROC22, which shows superior drought tolerance relative to Badila, has high performance photosynthesis and better anti-oxidation defenses under drought conditions. The time series dataset enabled the identification of important hubs and connections of gene expression networks. We identified 36,956 differentially expressed genes (DEGs) in response to drought stress. Of these, 15,871 DEGs were shared by the two genotypes, and 16,662 and 4423 DEGs were unique to ROC22 and Badila, respectively. Abscisic acid (ABA)-activated signaling pathway, response to water deprivation, response to salt stress and photosynthesis-related processes showed significant enrichment in the two genotypes under drought stress. At 4 h of drought stress, ROC22 had earlier stress signal transduction and specific up-regulation of the processes response to ABA, L-proline biosynthesis and MAPK signaling pathway-plant than Badila. WGCNA analysis used to compile a gene regulatory network for ROC22 and Badila leaves exposed to drought stress revealed important candidate genes, including several classical transcription factors: NAC87, JAMYB, bHLH84, NAC21/22, HOX24 and MYB102, which are related to some antioxidants and trehalose, and other genes. These results provide new insights and resources for future research and cultivation of drought-tolerant sugarcane varieties.

IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis.

Atopic dermatitis (AD) represents a severe global burden on physical, physiological and mental health. Innate immune cell basophils are essential for provoking allergic inflammation in AD. However, the roles of novel immunoregulatory cytokine IL-37 in basophils remain elusive. We employed in vitro co-culture of human basophils and human keratinocyte HaCaT cells and an in vivo MC903-induced AD murine model to investigate the anti-inflammatory mechanism of IL-37. In the in vitro model, IL-37b significantly decreased Der p1-induced thymic stromal lymphopoietin (TSLP) overexpression in HaCaT cells and decreased the expression of TSLP receptor as well as basophil activation marker CD203c on basophils. IL-37 could also reduce Th2 cytokine IL-4 release from TSLP-primed basophils ex vivo. In the in vivo model, alternative depletion of basophils ameliorated AD symptoms and significantly lowered the Th2 cell and eosinophil populations in the ear and spleen of the mice. Blocking TSLP alleviated the AD-like symptoms and reduced the infiltration of basophils in the spleen. In CRISPR/Cas9 human IL-37b knock-in mice or mice with direct treatment by human IL-37b antibody, AD symptoms including ear swelling and itching were significantly alleviated upon MC903 challenge. Notably, IL-37b presence significantly reduced the basophil infiltration in ear lesions. In summary, IL-37b could regulate the TSLP-mediated activation of basophils and reduce the release of IL-4. The results, therefore, suggest that IL-37 may target TSLP-primed basophils to alleviate AD.