Prevalence and risk factors of low vitamin D levels in children and adolescents with familial hypokalemic periodic paralysis.

Patients with familial hypokalemic periodic paralysis (HOKPP) experience episodes of reversible immobility and are at an increased risk of limited sunlight exposure, potentially leading to vitamin D deficiency. However, there is a lack of data on vitamin D levels in this population. We investigated serum vitamin D levels and their associated factors in children with HOKPP. This study included 170 genetically-confirmed children with HOKPP, aged 3-18 years, and 170 age-, sex-, and body mass index (BMI)-matched healthy controls from the Korean Channelopathy Study, a prospective controlled investigation. Anthropometric and clinical characteristics were recorded, and serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and intact parathyroid hormone (PTH) were analyzed. Vitamin D deficiency (< 20 ng/mL) was observed in 87.0% of the patients compared to 45.5% of the controls (P < 0.05) during the summer-fall season. During the winter-spring season, 91.7% of the patients and 73.4% of the controls were deficient (P < 0.05). A strong positive correlation was found between onset age of the first paralytic attack and vitamin D levels (r = 0.78, P < 0.01). Conversely, the frequency and duration of paralytic attacks were negatively correlated with vitamin D levels (r = -0.82 and r = -0.65, P < 0.01, respectively). Age, BMI, age at onset, frequency and duration of attacks, and PTH levels were independently associated with vitamin D levels (ß = -0.10, -0.12, 0.19, -0.27, -0.21, and -0.13, P < 0.05, respectively). CONCLUSIONS: Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics. We recommend routine screening for vitamin D levels in these patients to address this prevalent deficiency. Considering the high prevalence of vitamin D deficiency observed, further research on other diseases characterized by reversible immobility is warranted. WHAT IS KNOWN: • A correlation between immobility and low serum vitamin D levels has been established. However, the vitamin D status of patients with familial hypokalemic periodic paralysis (HOKPP) who experience periods of reversible immobility remains unknown. WHAT IS NEW: • Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics.

Effects of Factors Influencing Scar Formation on the Scar Microbiome in Patients with Burns.

Skin microbiome dysbiosis has deleterious effects, and the factors influencing burn scar formation, which affects the scar microbiome composition, are unknown. Therefore, we investigated the effects of various factors influencing scar formation on the scar microbiome composition in patients with burns. We collected samples from the burn scar center and margin of 40 patients with burns, subgrouped by factors influencing scar formation. Scar microbiome composition-influencing factors were analyzed using univariate and multivariate analyses. Skin graft, hospitalization period, intensive care unit (ICU) admission, burn degree, sex, age, total body surface area burned (TBSA), time post-injury, transepidermal water loss, the erythrocyte sedimentation rate, and C-reactive protein levels were identified as factors influencing burn scar microbiome composition. Only TBSA and ICU admission were associated with significant differences in alpha diversity. Alpha diversity significantly decreased with an increase in TBSA and was significantly lower in patients admitted to the ICU than in those not admitted to the ICU. Furthermore, we identified microorganisms associated with various explanatory variables. Our cross-sectional systems biology study confirmed that various variables influence the scar microbiome composition in patients with burns, each of which is associated with various microorganisms. Therefore, these factors should be considered during the application of skin microbiota for burn scar management.

Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.

BACKGROUND: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. OBJECTIVE: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. METHODS: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. RESULTS: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. CONCLUSION: CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

A microfluidics-enabled automated workflow of sample preparation for MS-based immunopeptidomics.

Mass spectrometry (MS)-based immunopeptidomics is an attractive antigen discovery method with growing clinical implications. However, the current experimental approach to extract HLA-restricted peptides requires a bulky sample source, which remains a challenge for obtaining clinical specimens. We present an innovative workflow that requires a low sample volume, which streamlines the immunoaffinity purification (IP) and C18 peptide cleanup on a single microfluidics platform with automated liquid handling and minimal sample transfers, resulting in higher assay sensitivity. We also demonstrate how the state-of-the-art data-independent acquisition (DIA) method further enhances the depth of tandem MS spectra-based peptide sequencing. Consequently, over 4,000 and 5,000 HLA-I-restricted peptides were identified from as few as 0.2 million RA957 cells and a melanoma tissue of merely 5 mg, respectively. We also identified multiple immunogenic tumor-associated antigens and hundreds of peptides derived from non-canonical protein sources. This workflow represents a powerful tool for identifying the immunopeptidome of sparse samples.

A novel photocurable pullulan-based bioink for digital light processing 3D printing.

Digital light processing has significant advantages, such as high repeatability, low failure rate, and no extrusion shear force. To make it possible to print complex structures with high resolution, the consecutive development of photocurable ink materials is indispensable. In this work, photo-functionalized pullulan (Pul-NB) was prepared by introducing norbornene groups into pullulan chains, and an ink material suitable for photocurable printing was prepared by thiol-ene click reaction. The rheology, water absorption, and mechanical properties of the Pul-NB precursor solution and photocurable hydrogel were investigated. The optimal composition of Pul-NB ink for three-dimensional (3D) printing was obtained by adjusting the degree of substitution, Pul-NB concentration, and thiol crosslinking agent. This novel bioink for digital light processing 3D printing showed good printability and high shape fidelity. This ink material provides an excellent alternative for printing biomimetic soft tissue organs, high-throughput tissue models, soft robots, etc.

Sex differences in the skin microbiome of burn scars.

Sex differences are observed in various spectrums of skin diseases, and there are differences in wound healing rate. Herein, sex differences were identified for the newly healed skin microbiome of burn patients. Fifty-two skin samples (26 normal skin, 26 burn scars) were collected from 26 burn patients (12 male, 14 female) and microbiota analysis was performed. The correlation between skin microbiota and biomechanical properties of burn scars was also investigated. There were no significant differences in clinical characteristics between male and female patients. Considering the biomechanical properties of burn scars and normal skin around it performed before sample collection, the mean erythema level of men's normal skin was significantly higher than that of women, whereas the mean levels of melanin, transepidermal water loss and skin hydration showed no significant sex differences. The erythrocyte sedimentation rate was significantly higher in females than that in males. Alpha diversity showed no significant differences between normal skin and burn scars in the male group. However, the scar was significantly higher than that of normal skin in the female group. Microbial network analysis revealed that the male group had more complex microbial network than the female group. Additionally, in the male group, the edge density and clustering coefficient were higher in burn scars when compared to normal skin, than the female group. There were sex differences in the results of microbiome of normal skin and burn scars. Some of the altered microbiota have been correlated with the biomechanical properties of burn scars. In conclusion, sex difference in the burn scar microbiome was confirmed. These results suggest that burn treatment strategies should vary with sex.

Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin.

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell-cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 µg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.

Advances of SHP2 modulators in the cancer immunotherapy / 药学学报

Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.

Effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery.METHODS: A total of 60 patients(60 eyes)with primary pterygium who underwent pterygium surgery were randomly divided into control group and study group, with 30 cases(30 eyes)in each group. In the control group, patients were treated with pranoprofen eye drops, tobramycin dexamethasone eye drops, and deproteinized calf blood extract eye gel after the surgery. In the study group, patients were treated by oral modified Chufeng Yisun Decoction in addition to the treatments in the control group. The changes of ocular irritation symptoms, ocular inflammatory signs, tear interleukin 6(IL-6)levels, and tear ferning test(TFT)of patients in the two groups were assessed.RESULTS: The visual analogue scale(VAS)in patients of both groups was significantly lower at 2d and 1wk after the surgery than that at 1d after the surgery(all P&#x0026;#x003C;0.01), and the VAS of the study group was significantly better than that of the control group at 2d and 1wk after surgery(P&#x0026;#x003C;0.01). The ocular signs integrals(OSI)and TFT results of both groups at 1wk were significantly lower than those at 1d after the surgery(all P&#x0026;#x003C;0.01), and the OSI and TFT were also lower in the study group than in the control group at 1wk after the surgery(all P&#x0026;#x003C;0.01). In addition, the concentration of tear IL-6 in both groups was significantly lower at 1wk after the surgery than 1d after the surgery(all P&#x0026;#x003C;0.01), and it was also significantly lower in the study group than in the control group at 1wk after the surgery(P&#x0026;#x003C;0.05).CONCLUSION: The combination of Chufeng Yisun Decoction and conventional treatment of western has a better effect on controlling ocular surface inflammation after pterygium surgery.

Screening of active ingredients for estrogenic effect of total flavonoids from Cuscutae Semen / 中国药房

OBJECTIVE To screen the active ingredient with estrogenic effect from total flavonoids of Cuscutae Semen. METHODS The estrogenic effect of total flavonoids from 10 batches of Cuscutae Semen was evaluated with mouse uterus coefficient and endometrial thickness as evaluation indexes， establish its fingerprint and calibrate the common peak. Common peak and spectrum-effect relationship of the above two indicators were analyzed by bivariate relationship analysis and grey correlation analysis to screen active components with estrogenic effect. UPLC-Q-TOF-MS technology was used to characterize the active components. RESULTS The estrogenic effect of total flavonoids from 10 batches of Cuscutae Semen was good. Twenty-eight and thirty-three common peaks of total flavonoids in Cuscutae Semen were obtained in the positive and negative ion modes respectively. The constituents represented by peaks 7，10，12-16，26 in positive ion mode and peaks 2，5，8，9，12，16，19，22-26 in negative ion mode were highly correlated with the estrogenic effect of total flavonoids from Cuscutae Semen. Further identification showed that the active substances with estrogenic effect from the total flavonoids of Cuscutae Semen were 5，7，3′， 4′-tetramethoxyflavone， 6- O-（trans） p-coumarin-furanfructose-（2→1）-glucopyranoside， rutin， kaempferol-3，7-diglucoside， apigenin-7-O-glucoside， hyperoside， baicalin， quercitin， quercetin， apigenin， kaempferol， isorhamnetin， rhododendron， isoquercetin， kaempferol-3-furan arabinoside， 2，6-octadecanediacetylic acid. CONCLUSIONS A total of 16 chemical components with estrogenic effect are screened from total flavonoids of Cuscutae Semen in the study， which can provide reference for the development of phytoestrogens.

Plasmid DNA extraction by double magnetic beads method and its application / 生物工程学报

Plasmids are the most commonly used gene carriers in the field of gene synthesis and sequencing. However, the main problems faced by traditional plasmid DNA extraction technology are low extraction throughput and high production cost, so they cannot meet the growing demand. In this study, a double-magnetic-bead method (DMBM) for plasmid extraction was developed based on the principle of plasmid extraction. The effects of the input of magnetic beads, the size of plasmid DNA fragments, and the volume of bacterial on plasmid DNA extraction were explored. In addition, the quality, throughput, and cost of plasmid DNA extraction were also compared between this technique and the commercial plasmid DNA extraction kits. The results showed that the DMBM can meet the needs of extracting plasmid DNA with different cell densities and fragment lengths. Moreover, the sensitivity and quality of plasmid extraction by the DMBM method were both superior to those of the centrifugal adsorption column method. In addition, this technique could be applied on a 96-channel automated nucleic acid extractor, resulting in higher purity of the extracted plasmid DNA, 80% reduction in extraction time, and 57.1% reduction in cost. It also reduces manual operations, achieving high-throughput and low-cost plasmid DNA extraction, thus may facilitate gene synthesis and sequencing.

Effect and potential mechanism of sodium ferulate on corneal endothelial dysfunction and CEC injury / 中国药房

OBJECTIVE To investigate the effect and potential mechanism of sodium ferulate （SF） on corneal endothelial dysfunction and corneal endothelial cell （CEC） injury. METHODS The male New Zealand rabbits were divided into control group， benzalkonium chloride （BAK） group and BAK+SF group， with 6 rabbits in each group. Except for control group， the other groups were given BAK into the anterior chamber to induce bullous keratopathy model， and BAK+SF group then given SF solution 200 mg/kg intraperitoneally the next day after surgery， twice a day， for consecutive 14 d. The transparency of corneal and edema of corneal stroma in each group of rabbits （before and on the 1st， 7th， and 14th day after surgery） were observed， and the corneal thickness （14th day after surgery） and intraocular pressure （1st to 14th day after surgery） were measured. On the 14th day after operation， the corneal endothelial structure was evaluated and the expressions of functionally related proteins [phalloidin， zonula occludens-1 （ZO-1）， Na+/K+-ATPase， Ki67] were detected. On the 14th day after surgery， the corneal tissue was collected in BAK group， the primary rabbit CECs were isolated and cultured， and they were divided into blank group and SF groups with different mass concentrations. The cell viabilities after being cultured for different time， and the protein expressions of Ras homologous gene family A （RhoA）， bone morphogenetic protein receptor 1A （BMPR1A） and BMRP2 were determined in each group. RESULTS Compared with BAK group， the transparency of corneal and edema of corneal stroma were gradually improved， and the corneal thickness was significantly decreased in BAK+SF group （P＜0.05）. The rabbit CECs in BAK+SF group were only damaged to zone B and showed a normal hexagonal endothelial cells structure. The protein expressions of phalloidin， ZO-1， Na+/K+-ATPase and Ki67 in BAK+SF group were significantly increased （P＜0.05）. When SF concentration was lower than and equal to 200 mg/L， it could promote the proliferation of rabbit CEC， in concentration manner （P＜0.05） and time-dependent trend. SF at concentrations of 50， 100， and 200 mg/L could up-regulate the protein expressions of RhoA， BMPR1A and BMPR2 in concentration-dependent manner （P＜0.05）. CONCLUSIONS SF can improve the transparency of corneal and edema of corneal stroma in bullous keratopathy model rabbits， reduce corneal thickness， maintain the integrity of corneal endothelium structure， and promote the recovery of corneal endothelial function； this compound can promote the proliferation of CEC， the mechanism of which may be related to the activation of RhoA-ROCK-BMP pathway.

Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis / 中华劳动卫生职业病杂志

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS / 法医学杂志

OBJECTIVES@#To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples.@*METHODS@#The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode.@*RESULTS@#The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%.@*CONCLUSIONS@#The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

The therapeutic effects of human embryonic stem cells-derived immunity-and-matrix regulatory cells on membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (MN) is a kidney-specific autoimmune disease. Human embryonic stem cells-derived immunity-and-matrix regulatory cells (hESC-IMRCs) have immunoregulatory functions. We hypothesized that hESC-IMRCs might have therapeutic effects on MN and be a potential treatment in clinical practice. METHODS: Rats of Heymann nephritis were injected with sheep anti-rat Fx1A serum. hESC-IMRCs were intravenously administrated upon the detection of proteinuria, with 6 × 106 cells (high-dose) or 3 × 106 cells (low-dose) in 1 ml every other day. Splenocytes and IMRCs were co-cultured at different times and ratios. Cell types and cytokines were detected by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The urinary protein of rats with Heymann nephritis was reduced remarkably to a level comparable to negative controls, in both low-dose (45.6 vs. 282.3 mg/d, P < 0.001) and high-dose (35.2 vs. 282.3 mg/d, P < 0.001) hESC-IMRC treatment groups. IgG and C3 deposit, glomerular basement membrane thickness and foot process effacement were alleviated and the reduced podocin was recovered in the kidneys. The proportions of CD4 + CD25 + T cells in circulation and spleen were increased, and the circulating level of IL-10 was increased, after IMRC interventions. IL-17 and TNF-α were reduced after IMRCs treatments. IL-10 increased remarkably in the co-culture supernatant of lymphocytes and IMRCs at 48 h with ratio 10:1. CONCLUSIONS: The intravenously delivered hESC-IMRCs alleviated proteinuria and kidney injuries of Heymann nephritis, by their immunosuppressive functions through regulatory T cells and IL-10. These pre-clinical results indicate that IMRCs worth careful consideration for human trials in the treatment of MN.

Exosomes derived from human hypertrophic scar fibroblasts induces smad and TAK1 signaling in normal dermal fibroblasts.

Post-burn hypertrophic scars are characterized by excessive accumulation of extracellular matrix secreted by fibroblasts. Exosomes are membrane lipid extracellular vesicles that play a pivotal role in cellular communication. Previous studies revealed the role of stem cell-derived exosomes in repairing damaged tissues, and also showed that cancer cell-derived exosomes could affect the disease pathogenesis. However, the functional properties of exosomes derived from hypertrophic scar fibroblasts (HTSFs) have not yet been studied extensively. In this study, we aimed to investigate whether HTSFs-derived exosomes can change the fibrosis-related signaling pathways in human normal fibroblasts (HNFs). HTSFs and HNFs were isolated from human hypertrophic scar tissues. HTSFs-derived exosomes were extracted and treated to HNFs. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect mRNA and protein expression, respectively, and cell proliferation and mobility were also assessed. Exosome treatment markedly increased cell proliferation and migration, and induced small mother against decapentaplegic (SMAD) signaling by increasing the levels of phosphorylated SMAD2 and SMAD1/5/8. The levels of TAK1 signaling components were also increased after exosome treatment to HNFs, including phosphorylated TAK1, p38, ERK, and JNK. HTSFs-derived exosomes further induced the epithelial-mesenchymal transition by decreasing the expression level of E-cadherin and increasing the expression levels of N-cadherin and vimentin. Consequently, the expression levels of fibronectin, type Ⅰ collagen, and type Ⅲ collagen were increased. Our results demonstrate the fibrotic property of HTSFs-derived exosomes, which suggests a potential functional role in hypertrophic scar development and a new therapeutic target.

Tryptophan depletion results in tryptophan-to-phenylalanine substitutants.

Activated T cells secrete interferon-γ, which triggers intracellular tryptophan shortage by upregulating the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme1-4. Here we show that despite tryptophan depletion, in-frame protein synthesis continues across tryptophan codons. We identified tryptophan-to-phenylalanine codon reassignment (W>F) as the major event facilitating this process, and pinpointed tryptophanyl-tRNA synthetase (WARS1) as its source. We call these W>F peptides 'substitutants' to distinguish them from genetically encoded mutants. Using large-scale proteomics analyses, we demonstrate W>F substitutants to be highly abundant in multiple cancer types. W>F substitutants were enriched in tumours relative to matching adjacent normal tissues, and were associated with increased IDO1 expression, oncogenic signalling and the tumour-immune microenvironment. Functionally, W>F substitutants can impair protein activity, but also expand the landscape of antigens presented at the cell surface to activate T cell responses. Thus, substitutants are generated by an alternative decoding mechanism with potential effects on gene function and tumour immunoreactivity.

Normalization-free displacement reconstruction method based on fringe scaling.

The knotty problems in the displacement reconstruction based on the self-mixing (SM) technique are the estimation of the self-mixing interferometry parameters and the normalization of SM signals (SMSs) since they are all very time-consuming and based on complex algorithms. This has an unfavorable effect on the real-time and low-cost natures of the SM displacement sensor. In the paper, we have presented a simple method of displacement retrieval with a high resolution, which does not require the parameter estimation and normalization. The proposed method is based on the scaling of individual fringes in SMSs and speckle noise proof. The simplicity of the method will make a great contribution to lowering the cost of the SM displacement sensor and improving the reliability and resolution of the sensor.

ADT-OH inhibits malignant melanoma metastasis in mice via suppressing CSE/CBS and FAK/Paxillin signaling pathway.

Hydrogen sulfide (H2S) is widely recognized as the third endogenous gas signaling molecule and may play a key role in cancer biological processes. ADT-OH (5-(4-hydroxyphenyl)-3H-1,2-dithiocyclopentene-3-thione) is one of the most widely used organic donors for the slow release of H2S and considered to be a potential anticancer compound. In this study, we investigated the antimetastatic effects of ADT-OH in highly metastatic melanoma cells. A tail-vein-metastasis model was established by injecting B16F10 and A375 cells into the tail veins of mice, whereas a mouse footpad-injection model was established by injecting B16F10 cells into mouse footpads. We showed that administration of ADT-OH significantly inhibited the migration and invasion of melanoma cells in the three different animal models. We further showed that ADT-OH dose-dependently inhibited the migration and invasion of B16F10, B16F1 and A375 melanoma cells as evaluated by wound healing and Transwell assays in vitro. LC-MS/MS and bioinformatics analyses revealed that ADT-OH treatment inhibited the EMT process in B16F10 and A375 cells by reducing the expression of FAK and the downstream response protein Paxillin. Overexpression of FAK reversed the inhibitory effects of ADT-OH on melanoma cell migration. Moreover, after ADT-OH treatment, melanoma cells showed abnormal expression of the H2S-producing enzymes CSE/CBS and the AKT signaling pathways. In addition, ADT-OH significantly suppressed the proliferation of melanoma cells. Collectively, these results demonstrate that ADT-OH inhibits the EMT process in melanoma cells by suppressing the CSE/CBS and FAK signaling pathways, thereby exerting its antimetastatic activity. ADT-OH may be used as an antimetastatic agent in the future.