Comparison and subsets analysis of peripheral CD4+T cells in patients with psoriasis and psoriatic arthritis.

Psoriatic arthritis (PsA) is a disease that transformed from psoriasis (PsO), and its underlying mechanisms are still not fully understood. Overactivation of the immune system is a key factor driving inflammatory diseases. Our goal is to define the unbalanced subsets of peripheral blood CD4 +T cells between PsO and PsA patients. Blood samples from 43 patients (23 PsA and 20 PsO) and 36 healthy donors (HD) were studied. Peripheral blood mononuclear cells (PBMC) were separated from blood and underwent fluorescent staining to assess CD4+T cell subsets by flow cytometry. We found that frequencies of various CD4+T cells including Th1, Th2, Th17, and Tfh were higher in the patients with PsO or PsA than those of healthy donors, indicating the general expansion of CD4+T cells in inflammatory conditions. More importantly, we observed the significant imbalance of Th1/Th2 between patients with PsO and PsA. Pearson correlation analysis showed that Th1/Th2 ratio was positively correlated with disease activity in psoriatic arthritis (DAPSA), Tfh/Tfr ratio was positively correlated with DAPSA score and visual analogue scale (VAS) score in PsA patients. Together, our results highlight the CD4+T cell changes in the transition from PsO to PsA, may contribute to early assessment and intervention.

Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists.

BACKGROUND: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. METHODS: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. RESULTS: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%). CONCLUSION: The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Sequential multi-parametric MRI in assessment of the histological subtype and features in the malignant pleural mesothelioma xenografts.

Objective: It is still a challenge to find a noninvasive technique to distinguish the histological subtypes of malignant pleural mesothelioma (MPM) and characterize the development of related histological features. We investigated the potential value of multiparametric MRI in the assessment of the histological subtype and development of histologic features in the MPM xenograft model. Methods: MPM xenograft models were developed by injecting tumour cells into the right axillary space of nude mice. The T1, T2, R2*, T2*, apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) at 14 d, 28 d, and 42 d were measured and compared between the epithelial and biphasic MPM. Correlations between multiparametric MRI parameters and histologic features, including necrotic fraction (NF) and microvessel density (MVD), were analysed. Results: This study found that T2, T2* and IVIM-DWI parameters can reflect the spatial and temporal heterogeneity of MPM. Compared to the epithelial MPM, T2 and T2* were higher and ADC, D, D*, and f were lower in the biphasic MPM (P < 0.05). MRI parameters were different in different stages of epithelial and biphasic MPM. Moderate correlations were found between ADC and tumor volume and NF in the epithelial MPM, and there was a correlation between f and tumor volume and NF and MVD in the two groups. Conclusion: MRI parameters changed with tumor progression in a xenograft model of MPM. MRI parameters may provide useful biomarkers for evaluating the histological subtype and histological features development of MPM.

Dual-layer spectral detector CT (SDCT) can improve the detection of mixed ground-glass lung nodules.

BACKGROUND: Mixed ground-glass lung nodules are a high-risk factor for lung adenocarcinoma. This study aimed to analyze the value of SDCT electron density imaging in the detection of mixed ground-glass lung nodules (GGNs). METHOD: 150 patients with GGNs confirmed by chest SDCT and surgical pathology were retrospectively analyzed. GGNs were screened by two senior radiologists by the double-blind method based on conventional CT and SDCT electron density images. Average CT values and electron density (ED) values of GGNs were measured for all, solid and ground-glass. RESULT: Thirty pGGN cases determined by conventional CT were found to be mGGN on electron density images, including 23 in the invasive adenocarcinoma group (detection rate of 35.38%), which was significantly higher than that of the PGL group (14.89%, P < 0.05). In electron density images, average CT values and ED values in the PGL and invasive adenocarcinoma groups with pGGNs were no difference. The average CT value and ED value were significantly higher in the mGGN invasive adenocarcinoma group compared with the PGL group (P < 0.05). Meanwhile, ROC curve analysis of average CT value and ED value revealed AUC values for mGGN infiltration of 0.759 and 0.752. CONCLUSION: SDCT can improve GGN visualization and increase the detection rate of mGGN compared with conventional CT. Attention should be paid to invasive adenocarcinoma for lung GGNs detected as mGGNs with high average CT value or ED value.

High-Throughput Screening of Stapled Helical Peptides in Drug Discovery.

Therapeutic peptides have revolutionized treatment for a number of human diseases. In particular, the past two decades have witnessed rapid progress of stapled helical peptides in drug discovery. Stapled helical peptides are chemically modified and constrained in their bioactive α-helical conformation. Compared to unstabilized linear peptides, stapled helical peptides exhibit superior binding affinity and selectivity, enhanced membrane permeability, and improved metabolic stability, presenting exciting promise for targeting otherwise challenging protein-protein interfaces. In this Perspective, we summarize recent applications of high-throughput screening technologies for identification of potent stapled helical peptides with optimized binding properties. We expect to provide a broad reference to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.

An ankylosing spondylitis risk variant alters osteoclast differentiation.

OBJECTIVE: To explore whether the variants in non MHC proteasome gene are associated with AS and explain the role of the variant in the disease. MATERIAL AND METHODS: Case-control analysis to identify AS predisposition genes; dual-luciferase reporter assay, immunoblot analysis and osteoclastogenesis assays to detect the function of the positive variant. Affected individuals were diagnosed according to the modified New York Criteria by at least two experienced rheumatologists, and rechecked by another rheumatologist. RESULTS: The study included 1037 AS patients and 1014 no rheumatic and arthritis disease controls. The main age of AS onset is between 16 and 35 years old. HLA-B27-positive subjects comprised 90.0% of patients. A nonsynonymous SNP rs12717 in proteasome gene PSMB1 significantly associated with AS. Individuals with CC genotype had a higher onset risk compared with those with GG/GC genotypes (OR = 1.89, P = 0.0047). We also discovered that PSMB1 regulates the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) signalling pathway and the disease-associated variant PSMB1-Pro11 significantly inhibits RANKL-induced NF-κB pathway in osteoclast differentiation via the degradation of IKK-ß compared with PSMB1-Ala11. RANKL induced osteoclast differentiation was significantly lower in primary monocyte osteoclast precursor from individuals with genotype PSMB131C/31C compared with individuals with genotype PSMB131G/31G. CONCLUSIONS: These results reveal a novel understanding of the bone formation and reabsorbing imbalance in AS. The new bone formation phenotype can be attributed to the inhibition of osteoclast differentiation by a more functional PSMB1 gene.

Identification of BIK as an unfavorable prognostic marker and novel therapeutic target in microsatellite stable colorectal cancer harboring KRAS mutations.

KRAS mutations lead to persistent activation of multiple downstream effectors that drive the cancer phenotype. Approximately 30%-50% of colorectal cancer (CRC) patients harbor KRAS mutations, which confer more aggressive tumor biology and shorter overall survival (OS), especially in microsatellite stable (MSS) metastatic CRC. Given that KRAS mutant protein has been proven difficult to target directly, identifying genes that function closely with KRAS and targeting these genes seems to be a promising therapeutic strategy for KRAS-mutated MSS CRC. Here, KRAS function-sensitive genes were identified by assessing the correlation between gene dependency scores from CRISPR knockout screens and KRAS mRNA expression in KRAS-mutated MSS CRC cell lines in the Cancer Cell Line Encyclopedia (CCLE) database. If the correlation coefficient was ≥ 0.6, the gene was considered a KRAS function-sensitive gene. Then KRAS function-sensitive genes related to prognosis were screened out in The Cancer Genome Atlas (TCGA) cohort, and the prognostic value was validated in the Gene Expression Omnibus (GEO) cohort. Single-sample gene set enrichment analysis (ssGSEA) was performed to investigate the potential mechanisms. PockDrug-Server was used to predict the druggability of candidate genes. The results showed that in 20 KRAS-mutated MSS CRC cell lines, 13 genes were identified as KRAS function-sensitive genes. Of these 13 genes, only BIK expression was significantly associated with progression-free survival (PFS) and OS, and the BIK-high patients had significantly poorer PFS (HR=3.18, P=0.020) and OS (HR=4.74, P=0.030) than the BIK-low patients. Multivariate Cox regression analysis revealed high BIK expression as an independent predictor for poorer prognosis in KRAS-mutated MSS CRC. The prognostic value of BIK was also successfully validated in a GEO cohort. The results of ssGSEA showed that the BIK-high group was more prone to strong metastasis activity than the BIK-low group. Pocket druggability prediction analysis presented that BIK had three druggable pockets, and their druggability scores were above 0.8. These findings suggested that BIK is a promising prognostic marker and therapeutic target in KRAS-mutated MSS CRC.

Up-regulation of BTN3A1 on CD14+ cells promotes Vγ9Vδ2 T cell activation in psoriasis.

Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14+ cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.

Distinct non-clock-like signatures of the basal cell carcinomas from three sisters with a lethal Gorlin-Goltz syndrome.

BACKGROUND: Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. METHODS: In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. RESULTS: The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. CONCLUSIONS: The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions.

MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis.

Aims: To assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population. Methods: This prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed. Results: The rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04). Conclusions: This study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.

Plantamajoside promotes metformin-induced apoptosis, autophagy and proliferation arrest of liver cancer cells via suppressing Akt/GSK3ß signaling.

Metformin, a well-known antidiabetic drug, exhibits anticancer effect in a variety of cancers, including liver cancer. Plantamajoside (PMS), a phenylethanoid glycoside compound isolated from Plantago asiatica, is proved to possess anticancer effects, too. In our study, we hypothesized that PMS might promote metformin mediated anticancer effects on liver cancer. The half maximal inhibitory concentration (IC50) of metformin was evaluated by cell viability assay. The influence of PMS on proliferation, migration, invasion and apoptosis of metformin-treated cells was evaluated by BrdU incorporation assay, flow cytometry, western blot, wound scratch healing assay, transwell cell migration assay and immunofluorescence. A fasting/feeding mouse model was built to evaluate the influence of PMS on metformin sensitivity in vivo. PMS (2.5, 10 or 40 µg/mL) treatment reduced the IC50 of metformin under different glucose concentrations. PMS (10 µg/mL) promoted metformin (5 mm) induced apoptosis and autophagy, and inhibition on proliferation, migration and invasion of HepG2 and HuH-7 cells. In the fasting/feeding mouse model, PMS (50 mg/kg) promoted metformin (200 mg/kg) induced proliferation arrest and apoptosis in vivo. Meanwhile, PMS reduced the level of pAkt(ser473) and GSK3ß(ser9) in HepG2 and HuH-7 cells. Restoration of Akt/GSK3ß signaling by a constitutively activated myr-Akt1 abrogated the effects of PMS on metformin-treated liver cancer cells. Our results demonstrated that PMS promoted the anticancer effects of metformin on liver cancer in vitro and in vivo.

The difference of lipid profiles between psoriasis with arthritis and psoriasis without arthritis and sex-specific downregulation of methotrexate on the apolipoprotein B/apolipoprotein A-1 ratio.

BACKGROUND: Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. OBJECTIVE: To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). METHODS: In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. RESULTS: Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. CONCLUSION: PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. TRIAL REGISTRATION: ChiCTR2000036192.

Identification of proteins associated with development of psoriatic arthritis in peripheral blood mononuclear cells: a quantitative iTRAQ-based proteomics study.

BACKGROUND: Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. METHODS: We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. RESULTS: We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p < 0.05) in the comparison of all psoriatic patients versus healthy controls, PsO group versus healthy controls, PsA group versus healthy controls, and PsA group versus PsO group, respectively. Among these proteins, 14 proteins may represent promising biomarkers for PsA: SIRT2, NAA50, ARF6, ADPRHL2, SF3B6, SH3KBP1, UBA3, SCP2, RPS5, NUDT5, NCBP1, SYNE1, NDUFB7, HTATSF1. Furthermore, western blotting confirmed that SIRT2 expression was significantly higher in PBMCs from PsA patients than PsO and healthy controls, and was negatively correlated with the phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK; p = 0.006, r = - 0.582). CONCLUSIONS: This pilot study provided a broad characterization of the proteome of PBMCs in PsA as compared to PsO and healthy controls, which may help to provide prospective strategies for PsA diagnosis.

Occurrence and fate of N-nitrosamines in three full-scale drinking water treatment systems with different treatment trains.

The occurrence of mutagenic and carcinogenic N-nitrosamines in drinking water is of great concern. In this study, dynamics and removal of nine N-nitrosamines in three drinking water treatment systems of a southern city of China are monitored during one year of sampling. The impacts of physicochemical treatment units on the removal and generation of N-nitrosamines were evaluated. The O3 and KMnO4 based pre-oxidation units have caused an increase in N-nitrosamines concentration, with O3 showing the substantial generation of N-nitrosamines. The carbon filter and ultrafiltration membrane units were found effective in removing N-nitrosamine precursors. These drinking water treatment systems have been useful in removing N-nitrosamine precursors; meanwhile, a slight decrease was found in already formed N-nitrosamines concentration. However, N-nitrosomorpholine (NMOR) and N-nitrosodiphenylamine (NDPhA) were found resistant toward all kinds of physicochemical treatments, and negligible changes in concentration were noted in all drinking water treatment systems. The distribution networks in the city provided an effective contact period to residual chlorine and precursors, which caused an increase in N-nitrosamines concentration. Overall, N-nitrosodimethylamine (NDMA) and N-nitroso-diethylamine (NDEA) have been found near the cancer risk threshold (10-6) in all of the drinking water treatment systems, while the remaining seven N-nitrosamines were found below the risk level.

Upregulated hsa_circ_0000129 expression promotes proliferation and migration of breast cancer cells.

Circular RNAs (circRNAs) are considered potential biomarkers in the pathogenesis and detection of several types of cancer. The present study aimed to investigate the role of hsa_circ_0000129 in the pathogenesis and molecular mechanism underlying breast cancer. A total of 68 pairs of breast cancer and corresponding paracancerous tissue samples, three different breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and a normal human breast cell line (MCF-10A) were used to investigate the expression of hsa_circ_0000129. The effect of hsa_circ_0000129 on cell proliferation, migration and colony formation was assessed in MCF-7 and MDA-MB-468 cells, along with the expression of enhancer of zeste homolog 2 (EZH2). The results demonstrated that hsa_circ_0000129 expression was significantly higher in breast cancer tissues compared with normal tissues. In addition, high hsa_circ_0000129 expression was significantly associated with lymph node metastasis and a higher tumor-node-metastasis stage. Comparisons between the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) and MCF-10A cells indicated similar results. MCF-7 cells overexpressed with hsa_circ_0000129 significantly increased cell proliferation, migration and colony formation compared with the negative control group, the effects of which were reversed following hsa_circ_0000129 knockdown in MDA-MB-468 cells. Furthermore, EZH2 expression was positively associated with hsa_circ_0000129 expression. Taken together, the results of the present study suggest that hsa_circ_0000129 may represent a promising prognostic biomarker for breast cancer. In addition, the role of hsa_circ_0000129 in breast cancer cell lines indicates a mechanism for tumorigenesis, as well as a potent target for the treatment of malignant progression.

Determining the leading sources of N-nitrosamines and dissolved organic matter in four reservoirs in Southern China.

The presence of carcinogenic N-nitrosamines and dissolved organic matter (DOM) in freshwater is a significant concern from the perspective of public health and drinking water treatment plant operation. This study investigated the N-nitrosamines concentration and their precursors' distributions, and DOM composition in four reservoirs located in a southern city of China. A total of 22 renowned precursors were identified. Precursors from industrial and pharmaceutical origins were found to be dominant in all reservoirs; however, traces of pesticide-based precursors, i.e. pirimicarb and cycluron were also found. The distribution of nine N-nitrosamines was substantially different among the reservoirs. N-Nitrosodibutylamine (NDBA), N-Nitrosopiperidine (NPIP), N-Nitrosodimethylamine (NDMA), and N-Nitrosopyrrolidine (NPYR) were abundantly present in all reservoirs. Most of N-nitrosamines except NDMA and N-nitrosodiethylamine (NDEA) were far below the generally accepted cancer risk of 10-6, and NDMA/NDEA were found close to the risk level (10-6). Anthropogenic DOM was dominant in three reservoirs as depicted by a higher biological index (BIX) than the humification index (HIX). By the principle component analysis, BIX appeared as an indicator of N-nitrosamines (except NDEA and NPIP). A strong and direct relationship was observed between the NDMA-formation potential (FP) and concentration of total N-nitrosamines (∑NA), and BIX. These results confirmed that the anthropogenic activities were the leading source of DOM and N-nitrosamines in this city based on land-use.

Photocatalytic degradation of ranitidine and reduction of nitrosamine dimethylamine formation potential over MXene-Ti3C2/MoS2 under visible light irradiation.

Photocatalysis is an effective method to degrade ranitidine (RAN), which is a typical precursor of nitrosamine dimethylamine (NDMA), an extremely potent human carcinogen. Herein, MXene-Ti3C2/MoS2 composites were prepared by a hydrothermal treatment aiming to use them for the photocatalytic degradation of RAN and the reduction of NDMA formation potential (NDMA-FP) under visible light irradiation for the first time. The analysis of the morphology, chemical composition and structure of these composites as well as the results of electrochemical experiments showed that a heterojunction was formed between MoS2 and Ti3C2, which facilitated the separation of electron-hole pairs and charge transfer, and thereby the photocatalytic performance. The MXene-Ti3C2/MoS2 composite (MT-4) exhibited the best photocatalytic performance in 60 min, with the highest RAN degradation and mineralization efficiencies of 88.4% and 73.58%, and the lowest NDMA-FP of 2.01%. Active species, including •O2- radicals, h+ and •OH radicals, all contributed to the degradation of RAN, among which •OH radicals were the main active species involved in the photocatalytic activity. The mechanism of the photocatalytic degradation of RAN over MXene-Ti3C2/MoS2 photocatalyst under visible light irradiation was proposed. This work opens up a new perspective on the applications of MXene-based materials for photocatalytic degradation of challenging pollutants.

Application of esophageal wire traction in lymph node dissection during three-hole thoracoscopic McKeown esophagectomy.

INTRODUCTION: The quality of left recurrent laryngeal nerve lymph node dissection is critical in esophageal cancer. We investigated whether esophageal wire traction in three-hole thoracoscopic esophagectomy can improve the same. MATERIAL AND METHODS: We retrospectively analyzed the data of 98 patients who underwent thoracoscopic esophagectomy in our center from January 2018 to July 2018: 36 patients with esophageal wire traction and 62 patients without traction (control group). The clearance time for left recurrent laryngeal nerve lymph nodes, thoracic bleeding volume, number of left recurrent laryngeal nerve lymph nodes, and complications were recorded. RESULTS: The observation group had a shorter clearance time for the left recurrent laryngeal nerve lymph nodes (15.8 ± 6.9 min vs. 20.00 ± 6.2 min), less thoracic bleeding (55.8 ± 30.2 mL vs. 70.7 ± 30.3 mL), and higher number of dissected left recurrent laryngeal lymph nodes (3.3 ± 1.4 vs. 2.5 ± 1.1) than the control group. There was no significant difference in the incidence of anastomotic leakage, pulmonary infection, arrhythmia, chylothorax, and nerve injury. CONCLUSIONS: Esophageal wire traction shortens the clearance time for the left recurrent laryngeal nerve lymph nodes, reduces thoracic bleeding, and improves the quality of left recurrent laryngeal nerve lymph node dissection in three-hole thoracoscopic esophagectomy.

Mvda is required for zebrafish early development

BACKGROUND: The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoin- flammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish. METHODS: Morpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP)yl transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo. RESULTS: As expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants. CONCLUSIONS: These findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.