4'-O-methylbavachalcone alleviates ischemic stroke injury by inhibiting parthanatos and promoting SIRT3.

Cerebral ischemia-reperfusion injury (CIRI) can induce massive death of ischemic penumbra neurons via oxygen burst, exacerbating brain damage. Parthanatos is a form of caspase-independent cell death involving excessive activation of PARP-1, closely associated with intense oxidative stress following CIRI. 4'-O-methylbavachalcone (MeBavaC), an isoprenylated chalcone component in Fructus Psoraleae, has potential neuroprotective effects. This study primarily investigates whether MeBavaC can act on SIRT3 to alleviate parthanatos of ischemic penumbra neurons induced by CIRI. MeBavaC was oral gavaged to the middle cerebral artery occlusion-reperfusion (MCAO/R) rats after occlusion. The effects of MeBavaC on cerebral injury were detected by the neurological deficit score and cerebral infarct volume. In vitro, PC-12 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R), and assessed cell viability and cell injury. Also, the levels of ROS, mitochondrial membrane potential (MMP), and intracellular Ca2+ levels were detected to reflect mitochondrial function. We conducted western blotting analyses of proteins involved in parthanatos and related signaling pathways. Finally, the exact mechanism between the neuroprotection of MeBavaC and parthanatos was explored. Our results indicate that MeBavaC reduces the cerebral infarct volume and neurological deficit scores in MCAO/R rats, and inhibits the decreased viability of PC-12 cells induced by OGD/R. MeBavaC also downregulates the expression of parthanatos-related death proteins PARP-1, PAR, and AIF. However, this inhibitory effect is weakened after the use of a SIRT3 inhibitor. In conclusion, the protective effect of MeBavaC against CIRI may be achieved by inhibiting parthanatos of ischemic penumbra neurons through the SIRT3-PARP-1 axis.

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer.

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

Functional analysis, diversity, and distribution of the ean cluster responsible for 17ß-estradiol degradation in sphingomonads.

17ß-estradiol (E2) is a natural endocrine disruptor that is frequently detected in surface and groundwater sources, thereby threatening ecosystems and human health. The newly isolated E2-degrading strain Sphingomonas colocasiae C3-2 can degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway; the former is the primary pathway supporting the growth of this strain and the latter is a branching pathway. The novel gene cluster ean was found to be responsible for E2 degradation through the 4,5-seco pathway, where E2 is converted to estrone (E1) by EanA, which belongs to the short-chain dehydrogenases/reductases (SDR) superfamily. A three-component oxygenase system (including the P450 monooxygenase EanB1, the small iron-sulfur protein ferredoxin EanB2, and the ferredoxin reductase EanB3) was responsible for hydroxylating E1 to 4-hydroxyestrone (4-OH-E1). The enzymatic assay showed that the proportion of the three components is critical for its function. The dioxygenase EanC catalyzes ring A cleavage of 4-OH-E1, and the oxidoreductase EanD is responsible for the decarboxylation of the ring A-cleavage product of 4-OH-E1. EanR, a TetR family transcriptional regulator, acts as a transcriptional repressor of the ean cluster. The ean cluster was also found in other reported E2-degrading sphingomonads. In addition, the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 via the 9,10-seco pathway, but its encoding genes are not located within the ean cluster. These results refine research on genes involved in E2 degradation and enrich the understanding of the cleavages of ring A and ring B of E2.IMPORTANCESteroid estrogens have been detected in diverse environments, ranging from oceans and rivers to soils and groundwater, posing serious risks to both human health and ecological safety. The United States National Toxicology Program and the World Health Organization have both classified estrogens as Group 1 carcinogens. Several model organisms (proteobacteria) have established the 4,5-seco pathway for estrogen degradation. In this study, the newly isolated Sphingomonas colocasiae C3-2 could degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway. The novel gene cluster ean (including eanA, eanB1, eanC, and eanD) responsible for E2 degradation by the 4,5-seco pathway was identified; the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 through the 9,10-seco pathway. The TetR family transcriptional regulator EanR acts as a transcriptional repressor of the ean cluster. The cluster ean was also found to be present in other reported E2-degrading sphingomonads, indicating the ubiquity of the E2 metabolism in the environment.

Fluorescent immunoassay for chloramphenicol based on the label-free polyadenine-mediated spherical nucleic acids triggered signal amplification.

A fluorescent immunosorbent assay incorporating signal amplification away from the surface of spherical nucleic acid (SNA) was developed for the detection of chloramphenicol (CAP). Through the conjugation of antibodies and poly-adenine (polyA) DNA onto the surface of gold nanoparticles (AuNPs), the fabrication of the nano-immunoprobe was achieved in a more straightforward and cost-effective manner. Moreover, a strategy utilizing the hybridization chain reaction (HCR) in the amplification step was devised, with particular attention given to the enzyme inhibition associated with SNA. The results demonstrated good performance on CAP detection with a linear range of 0.01-5 ng/L with a detection limit of 0.005 ng/L. The significance of this work mainly lies in the polyA-SNA-based immunoprobe and the thoughtful design to prevent enzyme inhibition.

Supergravity-Steered Generic Manufacturing of Nanosheets-Embedded Nanocomposite Hydrogel with Highly Oriented, Heterogeneous Architecture.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening.

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

[Develop the rural ecology in the New Era]. / 发展新时代的乡村生态学.

Rural ecology is a comprehensive field of study that takes the rural social-ecological-economic systems as the objective object and emphasizes spatial carrier governance. The development of rural ecology in the New Era embodies and implements comprehensively the core concepts of Xi Jinping Thought on Socialism with Chinese Cha-racteristics for a New Era, including harmonious coexistence between humans and nature, rural revitalization, green development, and the comprehensive construction of a socialist modernized nation. Under the goal of Chinese-style modernization, rural ecology exhibits characteristics distinct from the past, such as the integration of research objects, the intersectionality of basic theories, the computational feature of technical methods, and the orientation of exporting outcomes. To provide disciplinary support for modernization-oriented science to meet the new demands of country's rural development, effectively narrating the story of sustainable rural development in China and providing fundamental guarantees for the safety of rural systems, a number of issues such as paradigm innovation in research, improvement of data quality, and integration of comprehensive technologies, should be fully considered.

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling.

BACKGROUND: Colorectal cancer stem cells (CCSCs) are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer (CRC) patients. CCSCs are generally accepted to be important sources of CRC and are responsible for the progression, metastasis, and therapeutic resistance of CRC. Therefore, targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC. AIM: To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism. METHODS: CCSCs were enriched from CRC cell lines by in conditioned serum-free medium. Western blot, Aldefluor, transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs. The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis, colony formation, sphere formation, flow cytometry, and western blotting assessments in vitro and tumor growth, immunohistochemistry and immunofluorescence assessments in vivo. RESULTS: Compared with parental cells, sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumorigenesis, demonstrating that the CRC sphere cells displayed CSC features. VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells, as indicated by their proliferation, migration and clonality in vitro, and suppressed the tumor of CCSC-derived xenograft tumors in vivo. Besides, VX-509 suppressed the CSC characteristics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition (EMT) signaling in vitro. Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differentially expressed genes and CSC-related database information. VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression. Moreover, VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression. CONCLUSION: VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal, and inhibits the dedifferentiated self-renewal of CCSCs.

Rheumatoid arthritis and the intestinal microbiome: probiotics as a potential therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by swollen joints, discomfort, stiffness, osteoporosis, and reduced functionality. Genetics, smoking, dust inhalation, high BMI, and hormonal and gut microbiota dysbiosis are all likely causes of the onset or development of RA, but the underlying mechanism remains unknown. Compared to healthy controls, patients with RA have a significantly different composition of gut microbiota. It is well known that the human gut microbiota plays a key role in the initiation, maintenance, and operation of the host immune system. Gut microbiota dysbiosis has local or systematic adverse effects on the host immune system, resulting in host susceptibility to various diseases, including RA. Studies on the intestinal microbiota modulation and immunomodulatory properties of probiotics have been reported, in order to identify their potential possibility in prevention and disease activity control of RA. This review summarized current studies on the role and potential mechanisms of gut microbiota in the development and progression of RA, as well as the preventative and therapeutic effects and potential mechanisms of probiotics on RA. Additionally, we proposed the challenges and difficulties in the application of probiotics in RA, providing the direction for the research and application of probiotics in the prevention of RA.

[Effect of EDDS Application on Soil Cu/Cd Availability and Uptake/transport by Castor].

To investigate the effect of chelating agents on plant uptake of heavy metals, castor (Ricinus communis L.) was used as the test plant. Soil culture and pot experiments were conducted to study the effects of different concentrations of ethylenediamine disuccinic acid (EDDS) on the forms of Cu and Cd in soil and their absorption and transport by castor. The results showed that the application of EDDS significantly increased the content of available Cu and Cd. After 15 days of cultivation, the available Cu and Cd concentrations in the soil increased by 43.01%-103.55% and 51.78%-69.43%, respectively. EDDS promoted the conversion of reducible Cu to weak acid extractable and increased the mobility of Cu. Meanwhile, the application of EDDS promoted the absorption, transport, and enrichment of Cu in castor. Under the application of 2.5 mmol·kg-1 EDDS and 5.0 mmol·kg-1 EDDS, the Cu concentrations in the shoots were 4.88 times and 16.65 times higher than that of the control (P< 0.05), and the Cu concentrations in the roots were 2.89 times and 3.60 times higher than that of the control (P< 0.05), respectively. The Cu transport coefficient significantly increased by 72.73% and 381.82% when treated with EDDS 2.5 and EDDS 5.0. Simultaneously, the phytoextraction of Cu in shoots, roots, and their sum were 14.08, 2.16, and 4.70 times higher than that of the control (P<0.05), respectively, when treated with EDDS 5.0. Furthermore, EDDS significantly increased the Cd concentrations in castor. When treated with EDDS 2.5 the shoots and roots increased by 15.15% and 57.42%, respectively, and the phytoextraction of total Cd significantly increased by 13.44%. Generally, the EDDS treatment could increase the available Cu and Cd in soil, promote the uptake of Cu and Cd, and improve the phytoremediation efficiency of castor. Among them, the addition of 5.0 mmol·kg-1 EDDS had the best effect for Cu, whereas the addition of 2.5 mmol kg-1 EDDS had a higher increase in the phytoextraction of Cd.

RhNi Bimetallenes with Lattice-Compressed Rh Skin towards Ultrastable Acidic Nitrate Electroreduction.

Harvesting recyclable ammonia (NH3 ) from acidic nitrate (NO3 - )-containing wastewater requires the utilization of corrosion-resistant electrocatalytic materials with high activity and selectivity towards acidic electrochemical nitrate reduction (NO3 ER). Herein, ultrathin RhNi bimetallenes with Rh-skin-type structure (RhNi@Rh BMLs) are fabricated towards acidic NO3 ER. The Rh-skin atoms on the surface of RhNi@Rh BMLs experience the lattice compression-induced strain effect, resulting in shortened Rh-Rh bond and downshifted d-band center. Experimental and theoretical calculation results corroborate that Rh-skin atoms can inhibit NO2 */NH2 * adsorption-induced Rh dissolution, contributing to the exceptional electrocatalytic durability of RhNi@Rh BMLs (over 400 h) towards acidic NO3 ER. RhNi@Rh BMLs also reveal an excellent catalytic performance, boasting a 98.4% NH3 Faradaic efficiency and a 13.4 mg h-1 mgcat -1 NH3 yield. Theoretical calculations reveal that compressive stress tunes the electronic structure of Rh skin atoms, which facilitates the reduction of NO* to NOH* in NO3 ER. The practicality of RhNi@Rh BMLs has also been confirmed in an alkaline-acidic hybrid zinc-nitrate battery with a 1.39 V open circuit voltage and a 10.5 mW cm-2 power density. This work offers valuable insights into the nature of electrocatalyst deactivation behavior and guides the development of high-efficiency corrosion-resistant electrocatalysts for applications in energy and environment.

Harmonic amide bond density as a game-changer for deciphering the crosslinking puzzle of polyamide.

It is particularly essential to analyze the complex crosslinked networks within polyamide membranes and their correlation with separation efficiency for the insightful tailoring of desalination membranes. However, using the degree of network crosslinking as a descriptor yields abnormal analytical outcomes and limited correlation with desalination performance due to imperfections in segmentation and calculation methods. Herein, we introduce a more rational parameter, denoted as harmonic amide bond density (HABD), to unravel the relationship between the crosslinked networks of polyamide membranes and their desalination performance. HABD quantifies the number of distinct amide bonds per unit mass of polyamide, based on a comprehensive segmentation of polyamide structure and consistent computational protocols derived from X-ray photoelectron spectroscopy data. Compared to its counterpart, HABD overcomes the limitations and offers a more accurate depiction of the crosslinked networks. Empirical data validate that HABD exhibits the expected correlation with the salt rejection and water permeance of reverse osmosis and nanofiltration polyamide membranes. Notably, HABD is applicable for analyzing complex crosslinked polyamide networks formed by highly functional monomers. By offering a powerful toolbox for systematic analysis of crosslinked polyamide networks, HABD facilitates the development of permselective membranes with enhanced performance in desalination applications.

Supported Ionic Liquid Membrane with Highly-permeable Polyamide Armor by In Situ Interfacial Polymerization for Durable CO2 Separation.

Supported ionic liquid membranes (SILMs), owing to their capacities in harnessing physicochemical properties of ionic liquid for exceptional CO2 solubility, have emerged as a promising platform for CO2 extraction. Despite great achievements, existing SILMs suffer from poor structural and performance stability under high-pressure or long-term operations, significantly limiting their applications. Herein, a one-step and in situ interfacial polymerization strategy is proposed to elaborate a thin, mechanically-robust, and highly-permeable polyamide armor on the SILMs to effectively protect ionic liquid within porous supports, allowing for intensifying the overall stability of SILMs without compromising CO2 separation performance. The armored SILMs have a profound increase of breakthrough pressure by 105% compared to conventional counterparts without armor, and display high and stable operating pressure exceeding that of most SILMs previously reported. It is further demonstrated that the armored SILMs exhibit ultrahigh ideal CO2 /N2 selectivity of about 200 and excellent CO2 permeation of 78 barrers upon over 150 h operation, as opposed to the full failure of CO2 separation performance within 36 h using conventional SILMs. The design concept of armor provides a flexible and additional dimension in developing high-performance and durable SILMs, pushing the practical application of ionic liquids in separation processes.

Analysis of the clinical diagnosis and treatment of fetal meconium peritonitis.

BACKGROUND: The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis (FMP), as well as the diagnostic efficacy of ultrasound for FMP. METHODS: The clinical data of 41 infants and pregnant women diagnosed with meconium peritonitis (MP) and treated at the Fujian Maternal and Child Health Hospital from January 2013 to January 2020 were analyzed retrospectively. Clinical data, imaging data, complications, treatment strategies, pregnancy outcomes, neonatal prognoses, and follow-up outcomes were all analyzed. RESULTS: The MP prenatal diagnosis rate was 56.1% (23/41), the neonatal surgery rate was 53.7% (22/41), and the survival rate was 85.4% (35/41). Intraperitoneal calcification (23 pregnant women, 56.1%), intestinal dilatation (13 pregnant women, 31.7%), peritoneal effusion (22 pregnant women, 53.7%), intraperitoneal pseudocyst (7 pregnant women, 17.1%), and polyhydramnios were diagnosed via prenatal ultrasound (18 pregnant women, 43.9%). Twenty-two pregnant women were assigned to the surgical treatment (operation) group, while 18 were assigned to the conservative treatment group. In the operation group, there were 9 cases of ileal atresia (40.9%), 7 cases of jejunal atresia (31.8%), 2 cases of atresia at the jejunum-ileum junction (9.1%), 2 cases of ileal perforation (9.1%), 1 case of ileal necrosis (4.5%), and 1 case of adhesive obstruction (4.5%). There was no statistically significant difference (p > .05) in the occurrence of various prenatal ultrasound findings by etiology. CONCLUSION: Multiple prenatal ultrasound markers have been identified for MP. To improve the efficacy of newborn treatment for FMP and reduce neonatal mortality, dynamic monitoring of ultrasound image alterations and strengthened integrated perinatal management are necessary.

Solid-state, liquid-free ion-conducting elastomers: rising-star platforms for flexible intelligent devices.

Soft ionic conductors have emerged as a powerful toolkit to engineer transparent flexible intelligent devices that go beyond their conventional counterparts. Particularly, due to their superior capacities of eliminating the evaporation, freezing and leakage issues of the liquid phase encountered with hydrogels, organohydrogels and ionogels, the emerging solid-state, liquid-free ion-conducting elastomers have been largely recognized as ideal candidates for intelligent flexible devices. However, despite their extensive development, a comprehensive and timely review in this emerging field is lacking, particularly from the perspective of design principles, advanced manufacturing, and distinctive applications. Herein, we present (1) the design principles and intriguing merits of solid-state, liquid-free ion-conducting elastomers; (2) the methods to manufacture solid-state, liquid-free ion-conducting elastomers with preferential architectures and functions using advanced technologies such as 3D printing; (3) how to leverage solid-state, liquid-free ion-conducting elastomers in exploiting advanced applications, especially in the fields of flexible wearable sensors, bioelectronics and energy harvesting; (4) what are the unsolved scientific and technical challenges and future opportunities in this multidisciplinary field. We envision that this review will provide a paradigm shift to trigger insightful thinking and innovation in the development of intelligent flexible devices and beyond.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease with a poor prognosis. We previously found that p62 presented a marked nuclear-cytoplasmic translocation in ESCC cells as compared that in normal esophageal epithelial cells, but its effects on ESCC cells remain unclear. This study aims to clarify the impacts of different cellular localization of p62 on the function of ESCC cells and the underlying molecular mechanisms. We here demonstrated that cytoplasmic p62 enhances the migration and invasion abilities of esophageal cancer cells, whereas nuclear p62 has no effect. We further explored the interaction protein of p62 by using GST pull-down experiment and identified EPLIN as a potential protein interacting with p62. In addition, reducing EPLIN expression significantly inhibited the migration and invasion of ESCC cells, which were rescued when EPLIN expression was restored after the p62 knockdown. At a molecular level, p62 in cytoplasm positively regulated the expression of EPLIN via enhancing its protein stability. Data from the TCGA and GEO database displayed a significant up-regulation of EPLIN mRNA expression in ESCC tissues compared with corresponding paired esophageal epithelial samples. Our findings present evidence that the nuclear-cytoplasmic translocation of p62 protein contributes to an aggressive malignancy phenotype, providing candidate molecular biomarkers and potential molecular targets for the diagnosis and treatment of ESCC.

A Chimeric Classical Insect-Specific Flavivirus Provides Complete Protection Against West Nile Virus Lethal Challenge in Mice.

West Nile virus (WNV), an arthropod-borne flavivirus, can cause severe symptoms, including encephalitis, and death, posing a threat to public health and the economy. However, there is still no approved treatment or vaccine available for humans. Here, we developed a novel vaccine platform based on a classical insect-specific flavivirus (cISF) YN15-283-02, which was derived from Culicoides. The cISF-WNV chimera was constructed by replacing prME structural genes of the infectious YN15-283-02 cDNA clone with those of WNV and successfully rescued in Aedes albopictus cells. cISF-WNV was nonreplicable in vertebrate cells and nonpathogenic in type I interferon receptor (IFNAR)-deficient mice. A single-dose immunization of cISF-WNV elicited considerable Th1-biased antibody responses in C57BL/6 mice, which was sufficient to offer complete protection against lethal WNV challenge with no symptoms. Our studies demonstrated the potential of the insect-specific cISF-WNV as a prophylactic vaccine candidate to prevent infection with WNV.