The feasibility and safety of biomaterials for posterior scleral reinforcement in rabbits.

To explore the feasibility and safety of biomaterials for posterior scleral reinforcement (PSR) in rabbits. Decellularization and genipin crosslink were applied to the fresh bovine pericardium and porcine endocranium, and then mechanical properties, suture retention strength, and stability were tested. PSR operation was performed on 24 rabbit eyes using treated biological materials. Ophthalmic examination was performed regularly before and after PSR operation (1 week, 1 month, 3 months, 6 months). To evaluate the effectiveness, A ultrasound, diopter, and optical coherence tomography were conducted. General condition, fundus photograph, and pathological examination were recorded to evaluate the safety. Compared with genipin crosslinked bovine pericardium (Gen-BP) (21.29 ± 13.29 Mpa), genipin crosslinked porcine endocranium (Gen-PE) (34.85 ± 3.67 Mpa,P< 0.01) showed a closer elastic modulus to that of genipin crosslinked human sclera. There were no complications or toxic reactions directly related to the materials. Capillary hyperplasia, inflammatory cell infiltration, and collagen fiber deposition were observed, and the content of type I collagen fibers increased after PSR. Overall, the choroidal thickness of treated eyes was significantly thickened at different time points after PSR, which were 96.84 ± 21.08 µm, 96.72 ± 22.00 µm, 90.90 ± 16.57 µm, 97.28 ± 14.74 µm, respectively. The Gen-PE group showed changes that were almost consistent with the overall data. Gen-BP and Gen-PE are safe biological materials for PSR. The Gen-PE group demonstrated more significant advantages over the Gen-BP group in terms of material properties.

[Comparison of the Prognostic Value of C-Reactive Protein to Albumin Ratio and Glasgow Prognostic Score in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes. RESULTS: ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 (P =0.002) and 0.695 (P =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years (P =0.025), ECOG score ≥2 (P =0.004), Lugano stage III-IV (P < 0.001), non-germinal center B-cell-like (non-GCB) subtype (P =0.035), elevated lactate dehydrogenase (LDH) ( P < 0.001), extranodal involved site >1 (P =0.004) and IPI score >2 (P < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% vs 80.0%, P =0.035; CRR: 63.6% vs 32.5%, P =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached vs 67 months, P =0.0026; median OS: not reached vs 67 months, P =0.002), while there was no statistical difference in PFS (P =0.11) and OS (P =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS. CONCLUSION: CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.

Zinc-Doped BiOBr Hollow Microspheres for Enhanced Visible Light Photocatalytic Degradation of Antibiotic Residues.

Photocatalysis represents an effective technology for environmental remediation. Herein, a series of Zn-doped BiOBr hollow microspheres are synthesized via one-pot solvothermal treatment of bismuth nitrate and dodecyl ammonium bromide in ethylene glycol along with a calculated amount of zinc acetate. Whereas the materials morphology and crystal structure remain virtually unchanged upon Zn-doping, the photocatalytic performance toward the degradation of ciprofloxacin is significantly improved under visible light irradiation. This is due to the formation of a unique band structure that facilitates the separation of photogenerated electron-hole pairs, reduced electron-transfer resistance, and enhanced electron mobility and carrier concentration. The best sample consists of a Zn doping amount of 1%, which leads to a 99.2% degradation rate of ciprofloxacin under visible photoirradiation for 30 min. The resulting photocatalysts also exhibit good stability and reusability, and the degradation intermediates exhibit reduced cytotoxicity compared to ciprofloxacin. These results highlight the unique potential of BiOBr-based photocatalysts for environmental remediation.

Biomarkers and Tourette syndrome: a systematic review and meta-analysis.

Objective: This research aims to investigate whether peripheral biomarkers might differentiate individuals with Tourette syndrome (TS) from those without the condition. Methods: A broad range of databases was searched through November 2022. This study employed a systematic literature review and subsequent meta-analysis of case-control studies that assessed the aberration of biomarkers of patients with TS and controls. Results: A total of 81 studies were identified, out of which 60 met the eligibility criteria for inclusion in the meta-analysis. Following a meticulous screening procedure to determine the feasibility of incorporating case-control studies into the meta-analysis, 13 comparisons were statistically significant [CD3+ T cell, CD4+ T cell, CD4+ T cell to CD8+ T cell ratio, NK-cell, anti-streptolysin O antibodies, anti-DNase antibodies, glutamic acid (Glu), aspartic acid (Asp), ferritin (Fe), zinc (Zn), lead (Pb), vitamin D, and brain-derived neurotrophic factor (BDNF)]. Publication bias was found for anti-streptolysin O antibodies. Suggestive associations were evidenced for norsalsolinol (NSAL), neuron-specific enolase (NSE), and S100B. Conclusion: In this study, we present empirical evidence substantiating the link between several peripheral biomarkers and the early diagnosis of TS. Larger and more standardized studies are necessary to replicate the observed results, elucidate the specificity of the biomarkers for TS, and evaluate their precision for use in clinical settings.

Defect Engineering of Bi2WO6 for Enhanced Photocatalytic Degradation of Antibiotic Pollutants.

Infiltration of excessive antibiotics into aquatic ecosystems plays a significant role in antibiotic resistance, a major global health challenge. It is therefore critical to develop effective technologies for their removal. Herein, defect-rich Bi2WO6 nanoparticles are solvothermally prepared via epitaxial growth on pristine Bi2WO6 seed nanocrystals, and the efficiency of the photocatalytic degradation of ciprofloxacin, a common antibiotic, is found to increase markedly from 62.51% to 98.27% under visible photoirradiation for 60 min. This is due to the formation of a large number of structural defects, where the synergistic interactions between grain boundaries and adjacent dislocations and oxygen vacancies lead to an improved separation and migration efficiency of photogenerated carriers and facilitate the adsorption and degradation of ciprofloxacin, as confirmed in experimental and theoretical studies. Results from this work demonstrate the unique potential of defect engineering for enhanced photocatalytic performance, a critical step in removing antibiotic contaminants in aquatic ecosystems.

A new butenolide with antifungal activity from solid co-cultivation of Irpex lacteus and Nigrospora oryzae.

A new antifungal butenolide irperide (1) along with five known compounds were isolated from the co-culture of endophyte Irpex lacteus and pathogenic Nigrospora oryzae. The structure of 1, including the absolute configuration, was elucidated by analysis of NMR, HR-ESI-MS data and ECD spectra. Compounds 1, 4 and 6 exhibited significant antifungal activity against Aspergillus fumigatus, with MIC values of 1, 2 and 1 µg/mL, respectively.

[Cox model analysis of curative effect and prognostic factors of oral robot-assisted RPLN dissection for head and neck malignancies].

PURPOSE: To investigate the efficacy and prognostic factors of oral robot-assisted retropharyngeal lymph node (RPLN) dissection in the treatment of head and neck malignancies. METHODS: Sixty-eight patients with head and neck malignant tumors who were treated in our hospital from January 2017 to December 2019 and followed up until December 2022 were treated by oral robot-assisted RPLN dissection. The clinical remission rate, clinical control rate, operation time, intraoperative blood loss, length of hospital stay, and the survival rate and survival time at 1, 2 and 3 years of follow-up were compared. SPSS 22.0 software package was used for statistical analysis of the data. RESULTS: All 68 patients with head and neck tumors were successfully treated by oral robot-assisted RPLN resection, and no complications such as postpharyngeal incision massive bleeding, Horner syndrome, aspiration pneumonia were found in all patients. The follow-up was 3 years, the survival time was(31.15±4.93) months, the survival rate was 91.18%(62/68) at the first year, 85.29%(58/68) at the second year and 70.59% (48/68) at the third year. There was no significant difference in 3-year survival rate among different genders, ages, disease types, primary lesions, exocapsular lymph node invasion and peripheral nerve invasion (P＞0.05). There were significant differences in the 3-year survival rate of different T stages, N stages, TNM stages, maximum diameter of invaded lymph nodes and vascular cancer thrombus(P＜0.05). Cox proportional risk regression model analysis showed that stage T3 to 4, stage N2b to 3, stage Ⅳb TNM, maximum diameter of invaded lymph node ＞6 cm and vascular cancer thrombi were independent risk factors affecting the 3-year survival rate of head and neck cancer patients after surgery(P＜0.05). CONCLUSIONS: Oral robotic assisted RPLN dissection has certain efficacy in the treatment of head and neck malignant tumors, but the survival rate of patients is affected by T stage, N stage, TNM stage, maximum diameter of invaded lymph nodes, vascular cancer thrombolus and other factors, which should be paid more attention in clinic.

Copper-catalyzed reactions of α,ß-unsaturated N-tosylhydrazones with diaryliodonium salts to construct N-arylpyrazoles and diaryl sulfones.

Herein, an economical copper-catalyzed reaction of α,ß-unsaturated N-tosylhydrazones with diaryliodonium salts to construct both N-arylpyrazoles and diaryl sulfones has been developed. Both the p-toluenesulfonyl anion and the 3-arylpyrazole intermediates were formed in situ from N-tosylhydrazones. Subsequently, the former reacted rapidly with diaryliodonium salts to give diaryl sulfones and aryl iodide intermediates, and the latter reacted with aryl iodide to give N-arylpyrazoles under copper-catalyzed conditions. Using unsymmetrical mesityl phenyliodonium salts as substrates, mesityl p-toluenesulfide was obtained as the major product. This reaction took full advantage of the "waste" part of substrates to form an extra diaryl sulfone.

[GAO Shu-zhong's clinical experience in "seeking yin from yang needling method" based on "qi street" and "four seas" theories].

The paper introduces professor GAO Shu-zhong's understanding on "seeking yin from yang needling method" and its clinical application on the basis of "qi street" and "four seas" theories. Through professor GAO's clinical practice for years, he integrates and extendes the theories of "seeking yin from yang", "qi street" and "four seas" in Huangdi Neijing (The Yellow Emperor's Inner Classic). In this specific acupuncture method, in reference with the theories of "qi street" and "four seas", acupuncture is exerted on yang part of body, e.g. the back and lumber region to treat the diseases of yin parts, e.g. the chest and abdomen, which is differentiated as yin-yang imbalance in pathogenesis. In order to fully explain the clinical curative effect of "seeking yin from yang needling method", the common diseases in clinic, e.g. the disorders of heart, spleen and stomach systems, as well as the gynecology are taken as examples in the paper.

GAO Shu-zhong's clinical experience in "seeking yin from yang needling method" based on "qi street" and "four seas" theories / 中国针灸

The paper introduces professor GAO Shu-zhong's understanding on "seeking yin from yang needling method" and its clinical application on the basis of "qi street" and "four seas" theories. Through professor GAO's clinical practice for years, he integrates and extendes the theories of "seeking yin from yang", "qi street" and "four seas" in Huangdi Neijing (The Yellow Emperor's Inner Classic). In this specific acupuncture method, in reference with the theories of "qi street" and "four seas", acupuncture is exerted on yang part of body, e.g. the back and lumber region to treat the diseases of yin parts, e.g. the chest and abdomen, which is differentiated as yin-yang imbalance in pathogenesis. In order to fully explain the clinical curative effect of "seeking yin from yang needling method", the common diseases in clinic, e.g. the disorders of heart, spleen and stomach systems, as well as the gynecology are taken as examples in the paper.

Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway.

BACKGROUND: Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. METHODS: Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca2+]i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. RESULTS: Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca2+]i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-ß1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl3 could not further increase the [Ca2+]i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca2+]i and CaN signaling but had no effect on CaSR expression. CONCLUSION: The activation of CaN pathway and the increase of [Ca2+]i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

Animal and Organoid Models of Liver Fibrosis.

Liver fibrosis refers to the process underlying the development of chronic liver diseases, wherein liver cells are repeatedly destroyed and regenerated, which leads to an excessive deposition and abnormal distribution of the extracellular matrix such as collagen, glycoprotein and proteoglycan in the liver. Liver fibrosis thus constitutes the pathological repair response of the liver to chronic injury. Hepatic fibrosis is a key step in the progression of chronic liver disease to cirrhosis and an important factor affecting the prognosis of chronic liver disease. Further development of liver fibrosis may lead to structural disorders of the liver, nodular regeneration of hepatocytes and the formation of cirrhosis. Hepatic fibrosis is histologically reversible if treated aggressively during this period, but when fibrosis progresses to the stage of cirrhosis, reversal is very difficult, resulting in a poor prognosis. There are many causes of liver fibrosis, including liver injury caused by drugs, viral hepatitis, alcoholic liver, fatty liver and autoimmune disease. The mechanism underlying hepatic fibrosis differs among etiologies. The establishment of an appropriate animal model of liver fibrosis is not only an important basis for the in-depth study of the pathogenesis of liver fibrosis but also an important means for clinical experts to select drugs for the prevention and treatment of liver fibrosis. The present study focused on the modeling methods and fibrosis characteristics of different animal models of liver fibrosis, such as a chemical-induced liver fibrosis model, autoimmune liver fibrosis model, cholestatic liver fibrosis model, alcoholic liver fibrosis model and non-alcoholic liver fibrosis model. In addition, we also summarize the research and application prospects concerning new organoids in liver fibrosis models proposed in recent years. A suitable animal model of liver fibrosis and organoid fibrosis model that closely resemble the physiological state of the human body will provide bases for the in-depth study of the pathogenesis of liver fibrosis and the development of therapeutic drugs.

Synthesis, Characterization of Spirocyclic λ3 -Iodanes and Their Application to Prepare 4,1-Benzoxazepine-2,5-diones and 1,3-Diynes.

Herein, a [3+2] cycloaddition of aza-oxyallylic cations with ethynylbenziodoxolones for synthesis of new λ3 -iodanes containing spirocyclic 4-oxazolidinone has been developed. This cyclic λ3 -iodanes display stability in air and excellent solubility in organic solvent. Using them as substrate, both the 4,1-benzoxazepine-2,5-diones and symmetrical 1,3-diynes derivatives were afforded in high yield under copper(I)-catalyzed conditions.

[Regulatory effect of the pannexin1 channel on invasion and migration of testicular cancer Tcam-2 cells and its possible mechanism].

OBJECTIVE: To investigate the role of the pannexin-1 (Panx1) protein in the invasion and migration of testicular cancer Tcam-2 cells and its possible action mechanism. METHODS: Tcam-2 cells were treated with carbenoxolone (CBX) at 100 µmol/L and probenecid (PBN) 200 µmol/L. Then the intercellular fluorescence transmission was assessed by real-time fluorescence assay, the extracellular ATP concentration measured by chemi-luminescence immunoassay, the invasive and migratory abilities of the Tcam-2 cells detected by Transwell assay, and the expressions of the proteins Panx1, p-ERK1/2, ERK1/2, vimentin, MMP-9 and E-cadherin in the TM3 Leydig cells and testicular cancer Tcam-2 cells determined by Western blot. RESULTS: Western blot showed that the expression of the Panx1 protein was significantly higher in the testicular cancer Tcam-2 cells than in the TM3 Leydig cells (2.79 ± 0.17 vs 1.00 ± 0.06, P<0.05). The rates of intercellular fluorescence transmission in the Tcam-2 cells treated with CBX and PBN were markedly decreased as compared with the blank control group (ï¼»61.54 ± 3.30ï¼½% and ï¼»68.06 ± 4.03ï¼½% vs ï¼»99.50 ± 3.12ï¼½%, P<0.01), and so were the extracellular ATP concentrations (ï¼»57.06 ± 5.80ï¼½% and ï¼»56.42 ± 7.70ï¼½% vs ï¼»110 ± 8.16ï¼½%, P<0.01). The numbers of migrated Tcam-2 cells in the CBX and PBN groups were significantly reduced in comparison with that in the control (11.5 ± 1.11 and 8.25 ± 1.23 vs 331.00 ± 30.80, P<0.05), and so were those of the invaded ones (11.75 ± 3.77 and 11.5 ± 3.5 vs 89.00 ± 13.09, P<0.01). CBX and PBN significantly down-regulated the expression of p-ERK1/2 as compared with that in the blank control group (0.538 ± 0.05 and 0.476 ± 0.02 vs 0.98 ± 0.03, P<0.05), as well as those of vimentin (0.541 ± 0.09 and 0.705 ± 0.07, P<0.01) and MMP-9 (0.439 ± 0.08 and 0.557 ± 0.065, P<0.01) but up-regulated that of E-cadherin (3.896 ± 0.06 and 3.551 ± 0.04, P<0.01). CONCLUSIONS: The Panx1 protein is highly expressed in testicular cancer Tcam-2 cells. CBX and PBN can inhibit the function of the panneixn1 channel and reduce the invasive and migratory abilities of the Tcam-2 cells, which is associated with the decreased expression of the p-ERK1/2 protein.

A base-promoted cascade reaction of α,ß-unsaturated N-tosylhydrazones with o-hydroxybenzyl alcohols: highly regioselective synthesis of N-sec-alkylpyrazoles.

An efficient method for the synthesis of N-sec-alkylpyrazoles through a base-promoted cascade cyclization/Michael addition reaction of α,ß-unsaturated N-tosylhydrazones with ortho-hydroxybenzyl alcohols has been developed. The desired products containing di- or triaryl groups at the same carbon atom were afforded in good to excellent yields with excellent regioselectivities (>20 : 1). Moreover, a three-component reaction of ortho-hydroxybenzyl alcohols, α,ß-unsaturated N-tosylhydrazones and saturated N-tosylhydrazones also took place to afford pyrazoles in good yields. This reaction offers a new route to triarylmethanes with a simple operation and is applicable for large-scale synthesis.

A TaqMan probe-based real-time PCR to differentiate porcine epidemic diarrhea virus virulent strains from attenuated vaccine strains.

Porcine epidemic diarrhea virus (PEDV) is an important pathogen causing severe watery diarrhea, vomiting, dehydration, and death in sucking piglets. Attenuated vaccines have been used widely in sows in order to protect piglets through passive lactogenic immunity. Rapid and sensitive detection methods for differentiating attenuated vaccine strains from virulent ones are essential and practical in PEDV prevention and control. Based on the deletion mutation in ORF3 gene sequence, a TaqMan probe-based real-time quantitative PCR (TaqMan qPCR) was developed to distinguish PEDV virulent strains from attenuated vaccine ones in this study. The TaqMan qPCR could specifically detect PEDV virulent strain but not attenuated vaccine strain and other viruses. At least 37 DNA copies and PEDV of 0.995 TCID50 could be detected by TaqMan qPCR. The reproducibility was evaluated using various dilution of plasmids carrying PEDV ORF3 gene and virulent PEDV, and the inter-assay coefficient of variation (CV) was less than 0.44%. The TaqMan qPCR was further applied to detect 38 samples including intestines and their contents, fecal swabs, and mesenteric lymph nodes. Meanwhile, indirect immunofluorescence assay (IFA) was employed to detect PEDV-specific antigen. PEDV positive rates were 31.58% (12/38) and 26.32% (10/38) by TaqMan PCR and IFA, respectively, which suggested that the former was more sensitive than the latter. The TaqMan qPCR based on PEDV ORF3 gene could be a valuable tool in diagnose of porcine epidemic diarrhea and in molecular epidemiological study of the virulent PEDV.

Uptake and Translocation of Styrene Maleic Anhydride Nanoparticles in Murraya exotica Plants As Revealed by Noninvasive, Real-Time Optical Bioimaging.

This work reports the in vivo uptake and translocation of PNPs in the one-year grown terrestrial plant, Murraya exotica ( M. exotica), as investigated by two-photon excitation and time-resolved (TPE-TR) optical imaging with a large field of view (FOV, 32 × 32 mm2) in a noninvasive and real-time manner. The PNPs (⟨ Rh⟩ = 12 ± 4.5 nm) synthesized from poly(styrene- co-maleic anhydride) (SMA) were Eu-luminescence labeled (λL ≈ 617 nm). On exposing the roots of living M. exotica plants to the colloidal suspension of SMA PNPs at different concentrations, the spatiotemporal evolution of SMA PNPs along plant stems (60 mm in length) were monitored by TPE-TR imaging, which rendered rich information on the uptake and translocation of PNPs without any interference from the autofluorescence of the plant tissues. The TPE-TR imaging combined with the high-resolution anatomy revealed an intercell-wall route in the lignified epidermis of M. exotica plants for SMA PNP uptake and translocation, as well as the similar accumulation kinetics at different positions along the plant stems. We modeled the accumulation kinetics with Gaussian distribution to account for the trapping probability of a SMA PNP by the lignified cell walls, allowing the statistical parameters, the average trapping time ( tm) and its variance (σ), to be derived for the quantification of the PNP accumulation in individual plants. The TPE-TR imaging and the analysis protocols established herein will be helpful in exploring the mechanism of plant-PNP interaction under physiological condition.

Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro-transforming growth factor α membrane trafficking to promote breast cancer progression.

BACKGROUND: Epidermal growth factor receptor (EGFR) signalling is critical in epithelial cancer development. Human rhomboid family-1 (RHBDF1) facilitates the secretion of TGFα, an EGFR ligand, in breast cancer; however, the underlying mechanism remains unclear. We evaluated the role for RHBDF1 in clathrin-coated vesicle (CCV)-dependent pro-TGFα membrane trafficking in breast cancer cells upon stimulation by G-protein coupled receptor (GPCR) agonists. METHODS: RHBDF1 was silenced in various breast cancer cells using shRNA. TGFα levels, subcellular localization, and secretion were evaluated using ELISA, immunofluorescent staining, and coimmunoprecipitation. Phosphorylation and expression of relevant proteins were measured by western blotting. RHBDF1-dependent cell viability and invasion were measured. FINDINGS: RHBDF1 mediates GPCR agonist-induced EGFR phosphorylation by promoting TGFα secretion in various types of breast cancer cells. RHBDF1 not only mediates ADAM17-dependent shedding of TGFα, but is essential in membrane trafficking of pro-TGFα. RHBDF1 silencing results in blocking of clathrin uncoating from CCV, a crucial step for the plasma membrane release of pro-TGFα. Interaction of RHBDF1 with auxilin-2, a CCV protein, determines the recruitment of HSC70 to CCV to facilitate clathrin uncoating. RHBDF1 function is required for the proliferation and mobility of breast cancer cells upon stimulation by Sphingosine 1 Phosphate (S1P), a GPCR agonist. We demonstrate a significant correlation between RHBDF1 overexpression and EGFR activation in breast cancer tissues. INTERPRETATION: RHBDF1 is an indispensable component of the protein trafficking machinery involved in GPCR-mediated EGFR transactivation, and is an attractive therapeutic target for cancer. FUND: National Natural Science Foundation of China (81,672,740 to ZSZ, 81,272,356 and 81,330,029 to LYL).

Mucosal fluid evaporation is not the method of heat dissipation from fourth-degree laryngopharyngeal burns.

This study was designed to explore whether mucosal fluid evaporation represents a method of heat dissipation from thermal air inhalation injury and to assess laryngopharyngeal tissue damage according to heat quantity changes of dry air and vapour. Fifteen adult male beagles were divided into five groups to inhale heated air or vapour for 10 min as follows: control group (ordinary air), group I (91-110 °C heated air), group II (148-175 °C heated air), group III (209-227 °C heated air), and group IV (96 °C saturated vapour). The heat quantity changes of the dry air and vapour were calculated via thermodynamic formulas. The macroscopic and histological features of the laryngopharynxes were examined and assessed by various tissue damage grading systems. Group IV exhibited the most serious laryngopharyngeal damage, including cilia exfoliation, submucosal thrombosis, glandular atrophy, and chondrocyte degeneration, which is indicative of fourth-degree injury. The quality, heat quantity, and proportional reduction of heat quantity of vapour in group IV were all higher than those in the other groups. Furthermore, we found that mucosal fluid evaporation is not the method of heat dissipation from thermal air inhalation injury used by the airways. Laryngopharyngeal tissue damage depends chiefly on the heat quantity of vapour in the air.

Metal-Free Ring-Expansion Reaction of Six-membered Sulfonylimines with Diazomethanes: An Approach toward Seven-Membered Enesulfonamides.

A new metal-free, ring-expansion reaction of six-membered N-sulfonylimines with unstable diazomethanes, generated in situ from the N-tosylhydrazones, has been developed. This reaction delivers valuable seven-membered enesulfonamides by a Tiffeneau-Demjanov rearrangement and intramolecular proton transfer tautomerization process. Moreover, this ring-expansion reaction can be carried out in a one-pot fashion and scaled up to the gram scale by using aryl aldehydes, without the need to isolate the N-tosylhydrazone.