Emerging strategies for tissue engineering in vascularized composite allotransplantation: A review.

Vascularized composite allotransplantation (VCA), which can effectively improve quality of life, is a promising therapy for repair and reconstruction after face or body trauma. However, intractable issues are associated with VCA, such as the inevitable multiple immunogenicities of different tissues that cause severe rejection, the limited protocols available for clinical application, and the shortage of donor sources. The existing regimens used to extend the survival of patients receiving VCAs and suppress rejection are generally the lifelong application of immunosuppressive drugs, which have side effects. Consequently, studies aiming at tissue engineering methods for VCA have become a topic. In this review, we summarize the emerging therapeutic strategies for tissue engineering aimed to prolong the survival time of VCA grafts, delay the rejection and promote prevascularization and tissue regeneration to provide new ideas for future research on VCA treatment.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature.

CONTEXT.­: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. OBJECTIVE.­: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. DESIGN.­: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. RESULTS.­: The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. CONCLUSIONS.­: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

pH buffer KH2PO4 boosts zinc ion battery performance via facilitating proton reaction of MnO2 cathode.

Zinc-ion batteries (ZIBs) are rapidly emerging as safe, cost-effective, nontoxic, and environmentally friendly energy storage systems. However, mildly acidic electrolytes with depleted protons cannot satisfy the huge demand for proton reactions in MnO2 electrodes and also cause several issues in ZIBs, such as rapidly decaying cycling stability and low reaction kinetics. Herein, we propose a pH-buffering strategy in which KH2PO4 is added to the electrolyte to overcome the problems caused by low proton concentrations. This strategy significantly improves the rate and cycle stability performance of zinc-manganese batteries, delivering a high capacity of 122.5 mAh/g at a high current density of 5 A/g and enabling 9000 cycles at this current density, with a remaining capacity of 70 mAh/g. Ex-situ X-ray diffraction and scanning electron microscopy analyses confirmed the generation/dissolution of Zn3PO4·4H2O and Zn4(OH)6(SO4)·5H2O, byproducts of buffer products and proton reactions. In-situ pH measurements and chemical titration revealed that the pH change during the electrochemical process can be adjusted to a low range of 2.2-2.8, and the phosphate distribution varies with the pH range. Those results reveal that H2PO4- provides protons to the cathode through the chemical balance of HPO42-, HPO42-, and Zn3PO4·4H2O. This study serves as a guide for studying the influences and mechanisms of buffering additives in Zn-MnO2 batteries.

ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma.

BACKGROUND: Immunocheckpoint inhibitors (ICIs) have been widely used in the clinical treatment of lung cancer. Although clinical studies and trials have shown that patients can benefit significantly after PD-1/PD-L1 blocking therapy, less than 20% of patients can benefit from ICIs therapy due to tumor heterogeneity and the complexity of immune microenvironment. Several recent studies have explored the immunosuppression of PD-L1 expression and activity by post-translational regulation. Our published articles demonstrate that ISG15 inhibits lung adenocarcinoma progression. Whether ISG15 can enhance the efficacy of ICIs by modulating PD-L1 remains unknown. METHODS: The relationship between ISG15 and lymphocyte infiltration was identified by IHC. The effects of ISG15 on tumor cells and T lymphocytes were assessed using RT-qPCR and Western Blot and in vivo experiments. The underlying mechanism of PD-L1 post-translational modification by ISG15 was revealed by Western blot, RT-qPCR, flow cytometry, and Co-IP. Finally, we performed validation in C57 mice as well as in lung adenocarcinoma tissues. RESULTS: ISG15 promotes the infiltration of CD4+ T lymphocytes. In vivo and in vitro experiments demonstrated that ISG15 induces CD4+ T cell proliferation and invalidity and immune responses against tumors. Mechanistically, we demonstrated that the ubiquitination-like modifying effect of ISG15 on PD-L1 increased the modification of K48-linked ubiquitin chains thus increasing the degradation rate of glycosylated PD-L1 targeting proteasomal pathway. The expression of ISG15 and PD-L1 was negatively correlated in NSCLC tissues. In addition, reduced accumulation of PD-L1 by ISG15 in mice also increased splenic lymphocyte infiltration as well as promoted cytotoxic T cell infiltration in the tumor microenvironment, thereby enhancing anti-tumor immunity. CONCLUSIONS: The ubiquitination modification of PD-L1 by ISG15 increases K48-linked ubiquitin chain modification, thereby increasing the degradation rate of glycosylated PD-L1-targeted proteasome pathway. More importantly, ISG15 enhanced the sensitivity to immunosuppressive therapy. Our study shows that ISG15, as a post-translational modifier of PD-L1, reduces the stability of PD-L1 and may be a potential therapeutic target for cancer immunotherapy.

Recent Advances in Flexible Ultrasonic Transducers: From Materials Optimization to Imaging Applications.

Ultrasonic (US) transducers have been widely used in the field of ultrasonic and photoacoustic imaging system in recent years, to convert acoustic and electrical signals into each other. As the core part of imaging systems, US transducers have been extensively studied and achieved remarkable progress recently. Imaging systems employing conventional rigid US transducers impose certain constraints, such as not being able to conform to complex surfaces and comfortably come into contact with skin and the sample, and meet the applications of continuous monitoring and diagnosis. To overcome these drawbacks, significant effort has been made in transforming the rigid US transducers to become flexible and wearable. Flexible US transducers ensure self-alignment to complex surfaces and maximize the transferred US energy, resulting in high quality detection performance. The advancement in flexible US transducers has further extended the application range of imaging systems. This review is intended to summarize the most recent advances in flexible US transducers, including advanced functional materials optimization, representative US transducers designs and practical applications in imaging systems. Additionally, the potential challenges and future directions of the development of flexible US transducers are also discussed.

PM2.5 source apportionment identified with total and soluble elements in positive matrix factorization.

Source apportionments of urban aerosols identified with positive matrix factorization (PMF) are sensitive to input variables. So far, total elements were frequently included as effective factors in PMF-based source apportionment. We investigated the advances to involve soluble parts of elements in the source apportionment with four data sets of PM2.5 composition observed at a coastal city (Qingdao) in northern China: water-soluble ions plus organic and elemental carbon (IC set), the IC set plus total elements (ICTE set), the IC set plus soluble elements (ICSE set), and the IC set plus both total elements and soluble elements (ICAE set). The apportionments of six sources, including secondary sulfate, secondary nitrate, secondary oxalate, sea salt, biomass burning and dust, were identified with the IC set. In comparison, pollutants from vehicle + coal combustion, ship emissions, waste incineration and industrial activities were also identified with the ICTE, ICSE, or ICAE sets. We found that the PMF solutions of the ICAE set could distinguish aged and fresh dust, and identify fly ash and aged pollutants from industrial sources. The profiles and corresponding time series of vehicle + coal combustion, secondary aerosols, ship emissions, sea salt, and biomass burning emissions identified with the four data sets were very similar, while discrepancies were encountered for waste incineration, dust, and industrial sources. These results indicate the benefits and potentials with total and soluble elements involved in PMF-based source apportionments.

Cantilever-enhanced photoacoustic spectroscopy for gas sensing: A comparison of different displacement detection methods.

Photoacoustic spectroscopy (PAS) combines the advantages of high sensitivity, high specificity and zero background, which is very suitable for trace gas detection. Cantilever-enhanced photoacoustic spectroscopy (CEPAS) utilizes highly sensitive mechanical cantilevers to further enhance the photoacoustic signal and shows a gas concentration detection limit of parts per trillion. This review is intended to summarize the recent advancements in CEPAS based on different displacement detection methods, such as Michelson interference, Fabry-Perot interference, light intensity detection, capacitive, piezoelectric and piezoresistive detection. Fundamental mechanisms and technical requirements of CEPAS are also provided in the literature. Finally, potential challenges and further opportunities are also discussed.

Efficiency of Multifunctional Antibacterial Hydrogels for Chronic Wound Healing in Diabetes: A Comprehensive Review.

Diabetic chronic wounds or amputation, which are complications of diabetes mellitus (DM), are a cause of great suffering for diabetics. In addition to the lack of oxygen, elevated reactive oxygen species (ROS) and reduced vascularization, microbial invasion is also a critical factor that induces non-healing chronic diabetic wounds, ie, wounds still remaining in the stage of inflammation, after which the wound tissue begins to age and becomes necrotic. To clear up the infection, alleviate the inflammation in the wound and prevent necrosis, many kinds of hydrogel have been fabricated to eliminate infections with pathogens. The unique properties of hydrogels make them ideally suited to wound dressings because they provide a moist environment for wound healing and act as a barrier against bacteria. This review article will mainly cover the recent developments and innovations of antibacterial hydrogels for diabetic chronic wound healing.

Mussel-inspired collagen-hyaluronic acid composite scaffold with excellent antioxidant properties and sustained release of a growth factor for enhancing diabetic wound healing.

Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 â€‹mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing.

Fertilizer stabilizers reduce nitrous oxide emissions from agricultural soil by targeting microbial nitrogen transformations.

Nitrous oxide (N2O) is a pollutant released from agriculture soils following N fertilizer application. N stabilizers, such as N-(n-butyl) thiophosphoric triamide (NBPT) and 3,4-dimethylpyrazole phosphate (DMPP) could mitigate these N2O emissions when applied with fertilizer. Here, field experiments were conducted to investigate the microbial mechanisms by which NBPT and DMPP mitigate N2O emissions following urea application. We determined dynamic N2O emissions and inorganic N concentrations for two wheat seasons and combined this with metagenomic sequencing. Application of NBPT, DMPP, and both NBPT and DMPP together with urea decreased mean N2O accumulative emissions by 77.8, 91.4 and 90.7%, respectively, compared with urea application alone, mainly via repressing the increase in NO2- concentration after N fertilization. Sequencing results indicated that urea application enriched microorganisms that were positively correlated with N2O production, whereas N stabilizers enriched microorganisms that were negatively correlated with N2O production. Furthermore, compared to urea application alone, NBPT with urea reduced the abundances of genes related to denitrification, including napA/nasA, nirS/nirK, and norBC, resulting in a higher soil NO3- pool. Conversely, DMPP application, either alone or together with NBPT, decreased the abundance of genes involved in ammonia oxidation and denitrification, including amoCAB, hao, napA/nasA, nirS/nirK, and norBC, and maintained a greater soil NH4+ pool. Both N stabilizers resulted in similar abundances of nirABD-which is related to NO2- reducers-as when no N fertilizer was applied, which could prevent NO2- accumulation, consequently mitigating N2O emissions. These findings suggest that the high effectiveness of N stabilizers on mitigating N2O emissions could be attributed to changes to soil microbial communities and N-cycling functional genes to control the by-product or intermediate products of microbial N-cycling processes in agricultural soils.

A Review of High-Frequency Ultrasonic Transducers for Photoacoustic Imaging Applications.

Photoacoustic imaging (PAI) is a new and rapidly growing hybrid biomedical imaging modality that combines the virtues of both optical and ultrasonic (US) imaging. The nature of the interaction between light and ultrasound waves allows PAI to make good use of the rich contrast produced by optics while retaining the imaging depths in US imaging. High-frequency US transducers are an important part of the PAI systems, used to detect the high-frequency and broad-bandwidth photoacoustic signals excited by the target tissues irradiated by short laser pulses. Advancement in high-frequency US transducer technology has influenced the boost of PAI to broad applications. Here, we present a review on high-frequency US transducer technologies for PAI applications, including advanced piezoelectric materials and representative transducers. In addition, we discuss the new challenges and directions facing the development of high-frequency US transducers for PAI applications.

A nomogram-based immune-serum scoring system predicts overall survival in patients with lung adenocarcinoma.

OBJECTIVE: The immunoscore, which is used to quantify immune infiltrates, has greater relative prognostic value than tumor, node, and metastasis (TNM) stage and might serve as a new system for classification of colorectal cancer. However, a comparable immunoscore for predicting lung adenocarcinoma (LUAD) prognosis is currently lacking. METHODS: We analyzed the expression of 18 immune features by immunohistochemistry in 171 specimens. The relationship of immune marker expression and clinicopathologic factors to the overall survival (OS) was analyzed with the Kaplan-Meier method. A nomogram was developed by using the optimal features selected by least absolute shrinkage and selection operator (LASSO) regression in the training cohort (n = 111) and evaluated in the validation cohort (n = 60). RESULTS: The indicators integrated in the nomogram were TNM stage, neuron-specific enolase, carcino-embryonic antigen, CD8center of tumor (CT), CD8invasive margin (IM), FoxP3CT, and CD45ROCT. The calibration curve showed prominent agreement between the observed 2- and 5-year OS and that predicted by the nomogram. To simplify the nomogram, we developed a new immune-serum scoring system (I-SSS) based on the points awarded for each factor in the nomogram. Our I-SSS was able to stratify same-stage patients into different risk subgroups. The combination of I-SSS and TNM stage had better prognostic value than the TNM stage alone. CONCLUSIONS: Our new I-SSS can accurately and individually predict LUAD prognosis and may be used to supplement prognostication based on the TNM stage.

Characterization of a distinct low-grade oncocytic renal tumor (CD117-negative and cytokeratin 7-positive) based on a tertiary oncology center experience: the new evidence from China.

To examine the clinicopathologic and immunohistochemical features of a group of newly defined low-grade oncocytic renal tumors (LOT) that have the "CD117 negative/cytokeratin (CK)7 positive" immunoprofile. We have queried our hospital database and found 4456 consecutive renal tumors between 2016 and 2019. Among these renal tumors, eight (8) cases meet the morphologic and immunohistochemical characterization for low-grade oncocytic renal tumor (LOT). The eight (8) patients' mean age is 56.6 years (range 39-70 years old), and the male to female ratio is 1:1. Macroscopically, these LOTs generally present with tan-brown and solid cut surfaces and demonstrate similar solid, compact nested growth pattern microscopically. Tumor cells exhibit oncocytic cytoplasm and uniformly rounded to oval nuclei. There are areas of edematous stroma containing dispersed single or small clustered tumor cells. All tumors are negative for CD117 and positive for CK7. Uniform reactivity is also found for BerEP4, cyclin D1, and SDHB. Besides, CD10, vimentin, and AMACR are either negative or only focally positive. All of the tumors are negative for CA9 and TFE. The Ki-67 index is less than 5% in the seven (7) internal cases. Seven (7) of the eight (8) patients who are available for follow-up are alive and without disease recurrence (mean follow-up period of 21.6 months, ranging from 6 to 43 months). We described a group of low-grade oncocytic renal tumors identified retrospectively in a large tertiary cancer center, which was probably the first report originated from China or even Asia in the English literature so far. These tumors demonstrated eosinophilic cytoplasm and low-grade appearing nuclei with a "CD117 negative/CK7 positive" immunoprofile. The incidence rate was about 3.7% of the oncocytic renal tumors and 0.18% of all the renal tumors that were received in our lab during the four-year period. It is necessary to separate this group of tumors by its characteristic morphologic and immunophenotypic features.

Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases.

Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic regimens, including doxorubicin. LINC00472 is regulated by microRNAs and several signaling pathways. However, the significance of LINC00472 in human diseases has not been clearly established. In this review, we elucidate on the significance of LINC00472 in various human diseases, indicating that LINC00472 may be a diagnostic, prognostic as well as therapeutic target for these diseases.

Ethephon Reduces Maize Nitrogen Uptake but Improves Nitrogen Utilization in Zea mays L.

Increasing use of plant density or/and nitrogen (N) application has been introduced to maize production in the past few decades. However, excessive planting density or/and use of fertilizer may cause reduced N use efficiency (NUE) and increased lodging risks. Ethephon application improves maize lodging resistance and has been an essential measure in maize intensive production systems associated with high plant density and N input in China. Limited information is available about the effect of ethephon on maize N use and the response to plant density under different N rates in the field. A three-year field study was conducted with two ethephon applications (0 and 90 g ha-1), four N application rates (0, 75, 150, and 225 kg N ha-1), and two plant densities (6.75 plants m-2 and 7.5 plants m-2) to evaluate the effects of ethephon on maize NUE indices (N agronomic efficiency, NAE; N recovery efficiency, NRE; N uptake efficiency, NUpE; N utilization efficiency, NUtE; partial factor productivity of N, PFPN), biomass, N concentration, grain yield and N uptake, and translocation properties. The results suggest that the application of ethephon decreased the grain yield by 1.83-5.74% due to the decrease of grain numbers and grain weight during the three experimental seasons. Meanwhile, lower biomass, NO 3 - and NH 4 + fluxes in xylem bleeding sap, and total N uptake were observed under ethephon treatments. These resulted in lower NAE and NUpE under the ethephon treatment at a corresponding N application rate and plant density. The ethephon treatment had no significant effects on the N concentration in grains, and it decreased the N concentration in stover at the harvesting stage, while increasing the plant N concentration at the silking stage. Consequently, post-silking N remobilization was significantly increased by 14.10-32.64% under the ethephon treatment during the experimental periods. Meanwhile, NUtE significantly increased by ethephon.

ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression.

Our previous work demonstrated that Epithelial Splicing Regulatory Protein 1 (ESRP1) could inhibit the progression of lung adenocarcinoma (ADC). When ESRP1 was upregulated, the interferon (IFN) pathway was activated and Interferon-stimulated gene 15 (ISG15) expression increased exponentially in our microarray result. In this study, we aim to explore the function of ISG15 and its interactions with ESRP1 and to provide new insights for ADC treatment. ISG15 expression in lung ADC tissues was determined by immunohistochemistry (IHC) staining. The effect of ISG15 on lung ADC progression was examined by in vitro and in vivo assays. The mechanism of action on ESRP1 regulating ISG15 was investigated using Western blotting, RT-qPCR, immunofluorescence staining, chromatin immunoprecipitation, and a dual luciferase reporter system. The ISGylation between ISG15 and ESRP1 was detected by co-immunoprecipitation. Patients with high ISG15 expression were associated with higher survival rates, especially those with ISG15 expression in the nucleus. In vitro and in vivo experiments showed that upregulation of ISG15 inhibited EMT in lung ADC. ESRP1 upregulated the expression of ISG15 through CREB with enriched ISG15 in the nucleus. Importantly, ISG15 promoted ISGylation of ESRP1 and slowed the degradation of ESRP1, which demonstrated that ESRP1 and ISG15 formed a positive feedback loop and jointly suppressed EMT of lung ADC. In conclusion, ISG15 serves as an independent prognostic marker for long-term survival in lung ADC patients. We have revealed the protective effect of ISG15 against lung ADC progression and the combinatorial benefit of ISG15 and ESRP1 on inhibiting EMT. These findings suggest that reconstituting ISG15 and ESRP1 may have the potential for treating lung ADC.

Polymorphous Supercapacitors Constructed from Flexible Three-Dimensional Carbon Network/Polyaniline/MnO2 Composite Textiles.

Polymorphous supercapacitors were constructed from flexible three-dimensional carbon network/polyaniline (PANI)/MnO2 composite textile electrodes. The flexible textile electrodes were fabricated through a layer-by-layer construction strategy: PANI, carbon nanotubes (CNTs), and MnO2 were deposited on activated carbon fiber cloth (ACFC) in turn through an electropolymerization process, "dipping and drying" method, and in situ chemical reaction, respectively. In the fabricated ACFC/PANI/CNTs/MnO2 textile electrodes, the ACFC/CNT hybrid framework serves as a porous and electrically conductive 3D network for the rapid transmission of electrons and electrolyte ions, where ACFC, PANI, and MnO2 are high-performance supercapacitor electrode materials. In the electrolyte of H2SO4 solution, the textile electrode-based symmetric supercapacitor delivers superior areal capacitance, energy density, and power density of 4615 mF cm-2 (for single electrode), 157 µW h cm-2, and 10372 µW cm-2, respectively, whereas asymmetric supercapacitor assembled with the prepared composite textile as the positive electrode and ACFC as the negative electrode exhibits an improved energy density of 413 µW h cm-2 and a power density of 16120 µW cm-2. On the basis of the ACFC/PANI/CNTs/MnO2 textile electrodes, symmetric and asymmetric solid-state textile supercapacitors with a PVA/H2SO4 gel electrolyte were also produced. These solid-state textile supercapacitors exhibit good electrochemical performance and high flexibility. Furthermore, flexible solid-state fiber-like supercapacitors were prepared with fiber bundle electrodes dismantled from the above composite textiles. Overall, this work makes a meaningful exploration of the versatile applications of textile electrodes to produce polymorphous supercapacitors.

Aberrations and clinical significance of BRAF in malignant melanoma: A series of 60 cases in Chinese Uyghur.

Malignant melanoma (MM) is a highly malignant melanocytic tumor, it occurs mostly in the skin, the mucous membrane close to the skin, but also in the tunicae rhagoides and the pia mater. The Uyghur is the largest ethnic group living in the Xinjiang Uyghur Autonomous Region of China, accounting for 46% of the total population of 20 million. Large-scale studies on MMs in Asian countries are limited. This study aimed to investigate BRAF mRNA expression and mutations in Chinese Uyghur patients with MMs and to identify the clinical features associated with these parameters.Formalin-fixed, paraffin wax-embedded tumor sections from 60 MMs were analyzed for BRAF expression using reverse transcription polymerase chain reaction (RT-PCR). Exons 11 and 15 of BRAF were analyzed for the presence of mutations using PCR and DNA sequencing. Sixty MMs were followed by mobile phone for survival analysis.BRAF mRNA expression was higher in MMs than in pigmented moles and normal skin tissues. Fourteen of 60 MMs had BRAF mutations. The frequency of BRAF mutations was significantly higher in patients younger than 60 years (10/28, 4/32, P = .02). A significant difference was observed in the frequency of BRAF mutations among specimens of mucosal, acral, chronic sun-induced damage (CSD), and non-CSD MMs (2/10, 3/19, 8/25, 1/6, P = .002). No significant association was found among BRAF mutations, sex, ulceration, or lymph node metastasis. MMs lymph node metastasis (hazard ratio 2.54 [95% confidence interval 1.062 - 6.066], P = .01) affected survival.This study indicated that BRAF mutations and expression might serve as independent adverse prognostic factors in melanoma.

TIR/BB-loop mimetic AS-1 attenuates cardiac ischemia/reperfusion injury via a caveolae and caveolin-3-dependent mechanism.

AS-1, the TIR/BB loop mimetic, plays a protective role in cardiac ischemia/reperfusion (I/R) but the molecular mechanism remains unclear. The muscle specific caveolin3 (Cav-3) and the caveolae have been found to be critical for cardioprotection. This study aimed to evaluate our hypothesis that caveolae and Cav-3 are essential for AS-1-induced cardioprotection against myocardial I/R injury. To address these issues, we analyzed the involvement of Cav-3 in AS-1 mediated cardioprotection both in vivo and in vitro. We demonstrate that AS-1 administration significantly decreased infarct size, improved cardiac function after myocardial I/R and modulated membrane caveolae and Cav-3 expression in the myocardium. For in vitro studies, AS-1 treatment prevented Cav-3 re-distribution induced by H/R injury. In contrast, disruption of caveolae by MCD treatment or Cav-3 knockdown abolished the protection against H/R-induced myocytes injury by AS-1. Our findings reveal that AS-1 attenuates myocardial I/R injury through caveolae and Cav-3 dependent mechanism.

Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications.

Long non-protein-coding RNAs (lncRNAs) are emerging as important gene expression regulators that are linked to various biological processes at the post-transcriptional and transcriptional levels. lncRNAs are known to be important in cell proliferation, cell differentiation, apoptosis and metastasis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a novel lncRNA, is highly conserved amongst mammals. In addition, it has been considered to act as an oncogene, depending on the tumor system. An increasing number of studies have indicated that MALAT-1 may be detected in certain types of human tumors, including lung and bladder cancer and hepatocellular carcinoma. MALAT-1 silencing may be an effective therapeutic approach against tumors. The present study reviews the current knowledge on the functional role of MALAT-1 in the control of various cancers.