Corrigendum: Gut microbiome alterations during gastric cancer: evidence assessment of case-control studies.

[This corrects the article DOI: 10.3389/fmicb.2024.1406526.].

Corrigendum: Positive association between blood ethylene oxide levels and metabolic syndrome: NHANES 2013-2020.

[This corrects the article DOI: 10.3389/fendo.2024.1365658.].

Genome-wide identification of SAMS gene family in Cucurbitaceae and the role of ClSAMS1 in watermelon tolerance to abiotic stress.

S-Adenosyl-L-methionine (SAM) is widely involved in plant growth, development, and abiotic stress response. SAM synthetase (SAMS) is the key enzyme that catalyzes the synthesis of SAM from methionine and ATP. However, the SAMS gene family has not been identified and their functions have not been characterized in most Cucurbitaceae plants. Here, a total of 30 SAMS genes were identified in nine Cucurbitaceae species and they were categorized into 3 subfamilies. Physicochemical properties and gene structure analysis showed that the SAMS protein members are tightly conserved. Further analysis of the cis-regulatory elements (CREs) of SAMS genes' promoter implied their potential roles in stress tolerance. To further understand the molecular functions of SAMS genes, watermelon SAMSs (ClSAMSs) were chosen to analyze the expression patterns in different tissues and under various abiotic stress and hormone responses. Among the investigated genes, ClSAMS1 expression was observed in all tissues and found to be up-regulated by abiotic stresses including salt, cold and drought treatments as well as exogenous hormone treatments including ETH, SA, MeJA and ABA. Furthermore, knockdown of ClSAMS1 via virus-induced gene silencing (VIGS) decreased SAM contents in watermelon seedings. The pTRSV2-ClSAMS1 plants showed reduced susceptibility to drought, cold and NaCl stress, indicating a positive role of ClSAMS1 in abiotic stresses tolerance. Those results provided candidate SAMS genes to regulate plant resistance against abiotic stresses in Cucurbitaceae plants.

Positive association between blood ethylene oxide levels and metabolic syndrome: NHANES 2013-2020.

Purpose: The exposure of Ethylene oxide (EO) is linked to systemic inflammatory response and various cardiovascular risk factors. Hemoglobin's binding to ethylene oxide (HbEO) was used to measure serum EO level. This research aims to explore the association between metabolic syndrome (MetS) and HbEO, and between HbEO and components of metabolic syndrome. Method: This research included 1842 participants from 2013 to 2020 in National Health and Nutrition Examination Survey (NHANES) database. Weighted logistic regression models were used to analyze the relationship between HbEO and metabolic syndrome risk, using odds ratio (OR) and 95% confidence interval (CI). The restricted cubic spline plot explores whether there is a dose-response relationship between HbEO and MetS risk. Subgroup analysis was performed to analyze study heterogeneity. Results: Significant differences were found in gender, educational level, marital status, diabetes status and hypertension among different groups (P < 0.001, P = 0.007, P = 0.003, P < 0.001, P < 0.001, respectively). The serum HbEO level exhibited positive correlation with metabolic syndrome risk in Q2 level (OR=1.64, 1.04~2.48), Q3 level (OR=1.99, 1.29~3.08), and Q4 level (OR=2.89, 1.92~4.34). The dose-response association suggested a possible linear association between serum HbEO and metabolic syndrome risk (P-overall=0.0359, P-non-linear=0.179). L-shaped association was found between HbEO and the risk of MetS in female population, obese population and mid-age and elder population (P-overall<0.001, P-non-linear=0.0024; P-overall=0.0107, P-non-linear=0.0055 P-overall<0.001 P-non-linear=0.0157). Conclusion: This study indicates a linear correlation between MetS and HbEO, with MetS risk escalating as HbEO levels increase. The prevalence of MetS varies depending on BMI, age and gender, and these factors can also influence MetS prevalence when exposed to EO.

Gut microbiome alterations during gastric cancer: evidence assessment of case-control studies.

Objectives: The study aims to systematically identify the alterations in gut microbiota that observed in gastric cancer through comprehensive assessment of case-control studies. Methods: The systematic literature search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify case-control studies that compared the microbiomes of individuals with and without gastric cancer. Quality of included studies was evaluated with the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analyses utilized a random-effects model, and subgroup and sensitivity analyses were performed to assess study heterogeneity. All data analyses were performed using the "metan" package in Stata 17.0, and the results were described using log odds ratios (log ORs) with 95% confidence intervals (CIs). Results: A total of 33 studies involving 4,829 participants were eligible for analysis with 29 studies provided changes in α diversity and 18 studies reported ß diversity. Meta-analysis showed that only the Shannon index demonstrated statistical significance for α-diversity [-5.078 (-9.470, -0.686)]. No significant differences were observed at the phylum level, while 11 bacteria at genus-level were identified significant changed, e.g., increasing in Lactobacillus [5.474, (0.949, 9.999)] and Streptococcus [5.095, (0.293, 9.897)] and decreasing in Porphyromonas and Rothia with the same [-8.602, (-11.396, -5.808)]. Sensitivity analysis indicated that the changes of 9 bacterial genus were robust. Subgroup analyses on countries revealed an increasing abundance of Helicobacter and Streptococcus in Koreans with gastric cancer, whereas those with gastric cancer from Portugal had a reduced Neisseria. Regarding the sample sources, the study observed an increase in Lactobacillus and Bacteroides in the gastric mucosa of people with gastric cancer, alongside Helicobacter and Streptococcus. However, the relative abundance of Bacteroides decreased compared to the non-gastric cancer group, which was indicated in fecal samples. Conclusion: This study identified robust changes of 9 bacterial genus in people with gastric cancer, which were country-/sample source-specific. Large-scale studies are needed to explore the mechanisms underlying these changes. Systematic Review: Unique Identifier: CRD42023437426 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023437426.

cGMP functions as an important messenger involved in SlSAMS1-regulated salt stress tolerance in tomato.

Salt stress adversely affects the growth, development, and yield of tomato (Solanum lycopersicum). SAM Synthetase (SAMS), which is responsible for the biosynthesis of S-adenosylmethionine (SAM, a precursor of polyamine biosynthesis), participates in plant response to abiotic stress. However, the regulatory mechanism of SAMS-mediated salt stress tolerance remains elusive. In this study, we characterized a SAMS homologue SlSAMS1 in tomato. We found that SlSAMS1 is highly expressed in tomato roots, and its expression can be induced by salt stress. Crucially, overexpression of SlSAMS1 in tomato enhances salt stress tolerance. Through metabolomic profiling, we identified some differentially accumulated metabolites, especially, a secondary messenger guanosine 3',5'-cyclic monophosphate (cGMP) which may play a key role in SlSAMS1-regulated salt tolerance. A series of physiological and biochemical data suggest that cGMP alleviates salt stress-induced growth inhibition, and potentially acts downstream of the polyamine-nitric oxide (PA-NO) signaling pathway to trigger H2O2 signaling in response to salt stress. Taken together, the study reveals that SlSAMS1 regulates tomato salt tolerance via the PA-NO-cGMP-H2O2 signal module. Our findings elucidate the regulatory pathway of SlSAMS1-induced plant response to salt stress and indicate a pivotal role of cGMP in salt tolerance.

Identification and functional analysis of ABC transporter genes related to deltamethrin resistance in Culex pipiens pallens.

BACKGROUND: Pathogens that reproduce or develop in mosquitoes can transmit several diseases, endanger human health, and overwhelm health systems. Synthetic pyrethroids are the most widely used insecticides against adult mosquitoes, but their widespread use has led to resistance. The adenosine triphosphate (ATP)-binding cassette (ABC) transporters are involved in the resistance monitoring of insects, but their role and underlying mechanisms in insecticide resistance have not been fully elucidated. In the present study, we identified ABC transporter genes in Culex pipiens and investigated their role in the development of insecticide resistance. RESULTS: We identified 63 ABC transporter genes in Cx. pipiens and classified them as per the ABC transporter subfamilies. We also performed phylogenetic analysis. The knockdown rate of the mosquitoes orally fed with the ABC transporter inhibitor verapamil increased after deltamethrin treatment compared with that of the control group. Several genes from the ABCB, ABCC, and ABCG subfamilies were highly expressed in resistant mosquitoes. Immunofluorescence analysis revealed that ABCG6032427 was expressed in the head, chest, abdomen, wings, and legs, and the expression was the highest in the legs. Subsequently, knockdown of ABCG6032427 using RNA interference (RNAi) increased the sensitivity of the mosquitoes to deltamethrin, and scanning and transmission electron microscopy revealed that ABCG6032427 knockdown reduced cuticle thickness and the cuticle became loose and irregular. CONCLUSIONS: ABCG6032427 may modulate cuticle thickness and structure, thus play an important role in the development of deltamethrin resistance in mosquitoes. Thus, it could be a potential target for deltamethrin resistance management in Cx. pipiens. © 2023 Society of Chemical Industry.

Toxic Effects of Perilla frutescens (L.) Britt. Essential Oil and Its Main Component on Culex pipiens pallens (Diptera: Culicidae).

Sustainable control of mosquitoes, vectors of many pathogens and parasites, is a critical challenge. Chemical insecticides are gradually losing their effectiveness because of development of resistance, and plant metabolites are increasingly being recognized as potential alternatives to chemical insecticides. This study aimed to analyze the main components of Perilla frutescens essential oil (PE-EO), investigate the specific activity of PE-EO as a botanical insecticide and mosquito repellent, and explore whether its main constituents are potential candidates for further research. The larvicidal activity assay showed that LC50 of PE-EO and 2-hexanoylfuran was 45 and 25 mg/L, respectively. In the ovicidal activity assay, both 120 mg/L PE-EO and 80 mg/L 2-hexanoylfuran could achieve 98% egg mortality. Moreover, PE-EO and 2-hexanoylfuran showed repellency and oviposition deterrence effects. Notably, 10% PE-EO maintained a high rate of protection for 360 min. Although PE-EO and its main component had certain toxic effects on zebrafish, no significant harmful effects were detected in human embryonic kidney cells. Therefore, perilla essential oil is an effective agent for mosquito control at several life stages and that its main component, 2-hexanoylfuran, is a potential candidate for developing novel plant biopesticides.

RUNX2 Reverses p53-Induced Chemotherapy Resistance in Gastric Cancer.

Objective: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance. Methods: First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed. Results: We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer. Conclusion: RUNX2 is a possible target for platinum-based chemotherapy resistance.

Effects of linalool on Botrytis cinerea growth and control of tomato gray mold.

We examined the antifungal characteristics of linalool against Botrytis cinerea using plate inhibition assay and spore germination assay, and assessed the capacity of linalool in controlling tomato gray mold disease via tomato pot inoculation assay. The results showed that linalool exhibited strong inhibitive effects on mycelial growth of B. cinerea, with an EC50 value of 0.581 mL·L-1. In the spore germination test, linalool treatment inhibited spore germination in a dose-dependent manner. The electric conductivity and the malondialdehyde (MDA) contents were significantly increased in linalool-treated B. cinerea than that of the control, indicating that linalool induced oxidative damage and destroyed the cell membrane integrity in B. cinerea. The activities of the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in the linalool-treated B. cinerea were decreased significantly by 27.4%, 68.9% and 26.0%, respectively, suggesting that linalool inhibited the antioxidant activity of B. cinerea. In the pot experiment, the diameter of lesions in linalool-treated tomatoes was significantly smaller than that of the control. The activities of SOD, POD, CAT, polyphenol oxidase, and phenylalnine ammonialyase in the linalool-treated tomatoes increased, while the MDA content decreased, suggesting that linalool could alleviate the oxidative damage caused by B. cinerea and promote plant disease resistance. In summary, linalool had inhibitory effect on the growth of B. cinerea and could control gray mold disease in tomatoes. These findings could lay the foundation for developing bota-nical antifungal agents for management of tomato gray mold disease.

Diagnostic Value of Inflammatory Markers and Cytokines in Neonatal Sepsis.

Objective: To explore the diagnosis value of inflammatory markers and cytokines in neonatal sepsis. Methods: In this retrospective analysis, 90 cases of neonatal sepsis admitted to our hospital from April 2019 to April 2021 were included in the observation group, and 70 healthy neonates who received routine physical examinations in our hospital during the same period were recruited as the control group. Comparison and analysis of inflammatory markers and cytokines levels between the two groups were performed on days 1, 3, and 7 after the onset. Flow cytometry was used to measure the white blood cells (WBCs) and percentage of neutrophils (N%), immunoturbidimetry was used to determine C-reactive protein (CRP), immunochromatographic analysis was used to determine procalcitonin (PCT) in plasma, and the enzyme-linked immunosorbent assay was used to determine interleukin-27 (IL-27), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Results: Compared with healthy controls, neonatal sepsis resulted in significantly higher levels of WBC, N%, PCT, and CRP on days 1, 3, and 7 after onset. The levels of WBC, N%, and PCT were continuously decreased from day 1 to day 7, while the levels of CRP were increased on day 1 and day 3 but declined on day 7 (P < 0.05). Compared with healthy controls, patients with sepsis showed higher levels of IL-27, IL-6, IL-10, and TNF-α on days 1, 3, and 7 after the onset. The levels of IL-27, IL-6, and IL-10 were increased on day 1 and day 3 but decreased on day 7, and the levels of TNF-α were continuously decreased from day 1 to day 7 (all P < 0.05). Conclusion: Neonatal sepsis was associated with fluctuating levels of WBC, N%, PCT, CRP, IL-27, IL-6, IL-10, and TNF-α at different time points of disease. The joint detection of the above indices provides a new pathway for the early diagnosis of neonatal sepsis.

A case report of renal calyceal diverticulum with hypertension in children and review of literature.

BACKGROUND: Renal calyx diverticulum refers to a cystic lesion covered with the transitional epithelium in the renal parenchyma. Although there is no clear evidence that calyx diverticulum can cause hypertension, there exists a close association between the two, and there are few related reports. Herein, we reported the case of a child with renal calyx diverticulum complicated with hypertension and summarized the diagnosis and treatment. CASE PRESENTATION: Physical examination of the patient, an 11-year-old child, revealed a left renal cyst with hypertension (155/116 mmHg). There were no related symptoms. Routine urine and blood biochemical examinations showed no abnormalities. Imaging revealed left renal cyst compression causing the hypertension. She underwent renal cyst fluid aspiration and injection of a sclerosing agent into the capsule, but her blood pressure increased again 3 days postoperatively. Color Doppler ultrasonography showed that the size of the left renal cyst was the same as that preoperatively. To further confirm the diagnosis, cystoscopic retrograde ureteropyelography was performed to confirm the diagnosis of renal calyx diverticulum. Subsequently, renal calyceal diverticulum resection and calyx neck enlargement were performed. The operation went smoothly and the blood pressure returned to normal postoperatively. No abnormalities were noted at the 7-month postoperative follow-up. CONCLUSION: There exists an association between renal calyx diverticulum and hypertension. Therefore, hypertension can be considered a surgical indication for renal calyx diverticulum. Moreover, renal calyceal diverticulum in children can be easily misdiagnosed as a renal cyst. Therefore, it is important to be vigilant to prevent a series of complications, such as postoperative urine leakage, in such cases.

Duplex kidney complicated with preoperative inferior nephroblastoma rupture in children: a case report and literature review.

BACKGROUND: We admitted a child with a duplex kidney combined with preoperative rupture of nephroblastoma and used this case to discuss the clinical features and treatment of this disease. CASE PRESENTATION: We retrospectively analyzed the clinical data of a 5-year-old girl with preoperative duplex kidney rupture combined with inferior nephroblastoma who was admitted to the Fourth Hospital of Baotou. In addition, we reviewed the relevant literature. The patient's details were as follows: weight, 17 kg; height, 108 cm; and body surface area, 0.7 m2. Abdominal ultrasound for abdominal pain revealed the presence of a left-sided renal mass; enhanced abdominal computed tomography further confirmed it to be a left-sided duplex kidney measuring approximately 6 × 5 × 5 cm, with a rupture originating from the lower kidney. The PubMed database was searched from 2010 to 2020 for the terms "Wilms' tumor" and "Duplex" and "Wilms' tumor" and "Rupture." The treatment plan was preoperative chemotherapy (vincristine/dactinomycin, VA regimen) + left kidney tumor radical surgery + postoperative chemotherapy (actinomycin-D/VCR/doxorubicin, AVD regimen). Postoperative pathology revealed an International Society of Pediatric Oncology intermediate-risk stage-3 nephroblastoma (mixed type) in the left kidney. Literature review was performed with 71 cases meeting the set criteria with an aim to analyze and summarize the clinical characteristics and treatment of patients with ruptured nephroblastoma and duplex kidney combined with nephroblastoma. CONCLUSIONS: To our knowledge, no previous studies have reported preoperative duplex kidney combined with nephroblastoma rupture. In patients with this condition, preoperative chemotherapy is recommended when the vital signs are stable and tumor resection can be performed after the tumor has shrunk to prevent secondary spread. If the patient's vital signs are unstable, emergency exploratory surgery is needed. If the nephroblastoma rupture is old and limited, surgery can be performed when the tumor size is small.

Shape-Designable and Reconfigurable All-Paper Sensor through the Sandwich Architecture for Pressure/Proximity Detection.

All-paper sensors that are capable of free cutting and folding maximize the merits of papers, which fully utilize the unique potential of papers in cost effectiveness, flexibility, disposability, biodegradability, and a flexible design. However, most of the paper sensors have applied metals as the electrodes and polyimide/polydimethylsiloxane as the encapsulation/sensitive layers, limiting the advantages of the paper sensor. In this work, an all-paper, shape-designable, and reconfigurable capacitive pressure/proximity sensor is fabricated with multilayered tissue paper as the dielectric and polypyrrole printer paper as the electrode/encapsulation. Without the restriction of heterogeneous materials, the all-paper components enable the sensors' flexible shape design for freely cuttable and foldable 2D and 3D sensors including a 2D braille keyboard and even allow reconfiguration from a 3D box sensor to a 3D candy sensor. The all-paper sensor presents superior pressure-sensing performance (0.96 kPa-1 at <1.76 kPa and 0.09 kPa-1 at 1.76-22 kPa) and proximity-sensing ability. The sensing mechanism of the sensor is directly revealed from tissue paper changes using in situ 3D microscopy and dielectric measurement experiments. These results provide inspiration for realizing shape-designable and reconfigurable 3D sensors and fully demonstrate the application potential in omnidirectional perception, stretchable sensors, and green electronics.

Ultrasound-guided percutaneous microwave ablation of bilateral renal cell carcinomas: Focus upon safety and efficacy.

OBJECTIVE: To retrospectively review the safety and efficacy of ultrasound (US)-guided percutaneous microwave ablation (MWA) of bilateral renal cell carcinomas (BRCCs). PATIENTS AND METHODS: In this study, eight patients of BRCCs with 20 lesions seen from November 2012 to October 2018 were enrolled retrospectively. The patients were treated with US -guided percutaneous MWA and were followed up with contrast-enhanced US and computed tomography or magnetic resonance imaging. RESULTS: Technical success was achieved 20 tumors. The 18 lesions were performed to ablate 90%; 2 lesions were repeated because of detecting residual ablated tumor. Except six patients were noted fever, no severe complications occurred. The median follow-up time was 24 months (range 7-59 months). Among the eight patients, there was no local tumor recurrence in 6 of 8 completely ablated tumor lesions. One patient was retreated by MWA 6 months after ablation, and another was retreated after 19 months due to local tumor recurrence. No patients have obvious change of renal function and lost their life. CONCLUSION: US-guided percutaneous MWA is a beneficial treatment for BRCC.

MicroRNA­199a­3p suppresses high glucose­induced apoptosis and inflammation by regulating the IKKß/NF­κB signaling pathway in renal tubular epithelial cells.

Renal tubular epithelial cells (RTEC) injury induced by hyperglycemia is considered a major contributor to the pathogenesis of diabetic nephropathy (DN). However, few studies have focused on the role of microRNAs (miRNAs/miRs) in RTEC injury. Therefore, the present study aimed to investigate the role and mechanisms of miRNAs in RTEC injury. In the study, miRNAs expression profiles were determined via microarray assay in the peripheral blood samples of patients with DN. High glucose (HG)­induced injury in HK­2 cells was used as a cell model to examine the potential role of miR­199a­3p in DN. The expression of miR­199a­3p was validated using reverse transcription­quantitative PCR. The expressions of TNF­α, IL­1ß and IL­6, were detected via ELISA. The protein levels of apoptosis­related proteins were determined using western blotting. Cell apoptosis and caspase 3 activity were evaluated via flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR­199a­3p and IKKß. miR­199a­3p was found to be significantly downregulated in the peripheral blood samples, and there was a negative correlation between miR­199a­3p expression and proteinuria in patients with DN. It was identified that miR­199a­3p expression was time­dependently decreased in the HG­induced cell damage model. Moreover, miR­199a­3p overexpression significantly improved HG­induced cell injury, as evidenced by the decrease in cell apoptosis and inflammation. Subsequent analyses demonstrated that miR­199a­3p directly targeted IKKß, whose expression was increased, and negatively correlated with miR­199a­3p expression in patients with DN. The protective effects of miR­199a­3p overexpression on HG­treated HK­2 cells were partially reversed by IKKß overexpression. In addition, activation of the NF­κB pathway by HG was blocked by miR­199a­3p mimics transfection in HK­2 cells. Collectively, the present findings indicated that miR­199a­3p protected HK­2 cells against HG­induced injury via inactivation of the IKKß/NF­κB pathway, suggesting enhanced expression of miR­199a­3p as a potential therapeutic strategy for patients with DN.

Effects of deferoxamine on the osteogenic differentiation of human periodontal ligament cells.

Hypoxia regulates a number of cell biological processes, including cell survival, development and differentiation. Deferoxamine (DFO), an oral chelator for blood transfusion patients, has been demonstrated to induce hypoxia and is frequently used as a hypoxia­mimicking agent. The purpose of the present study was to investigate the influence of DFO on the proliferation, migration and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The effects of DFO on hPDLC viability and migration were measured using an MTT and wound healing assay. To characterize the hypoxia microenvironment, the expression of hypoxia­inducible factor­1α (HIF­1α) in hPDLCs treated with DFO was quantified using the reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Subsequently, the osteogenic differentiation potential of DFO was determined by RT­qPCR of the mRNA of osteogenic markers (runt­related transcription factor 2 [Runx­2], osteopontin [OPN] and collagen type I [Col­1]). The alkaline phosphatase activity and mineral deposition were analyzed using alizarin red S staining. The MTT and wound healing assays demonstrated that low­concentrations of DFO had little impact on hPDLC viability and migration 48 h into the treatment. DFO upregulated the expression of hPDLC genes specific for osteogenic differentiation: HIF­1α, Runx­2, OPN and Col­1. Furthermore, formation of mineralized nodules was enhanced by DFO. The present study suggests that DFO provided favorable culture conditions to promote the osteogenic differentiation and mineralization of hPDLCs. The mechanism underlying these alterations remains to be elucidated.

MicroRNA-455-3p functions as a tumor suppressor by targeting eIF4E in prostate cancer.

MicroRNAs (miRNAs) are strongly implicated in various cancers, including prostate cancer. Recently, microRNA-455-3p (miR-455-3p) has been shown to be aberrantly expressed in many tumor tissues, but its functions in tumorigenesis remain unknown. In this study, we investigated the role of miR-455-3p in prostate cancer. We found that miR-455-3p is markedly downregulated in prostate cancer cell lines and clinical tumor specimens. Gain-of-function and loss-of-function studies showed that miR-455-3p promotes prostate cancer cell growth both in vitro and in vivo. Bioinformatics analysis and Luciferase reporter assays demonstrated that miR-455-3p directly targets and suppresses eIF4E, the rate-limiting factor for cap-dependent translation, which plays important roles in the initiation and progression of prostate cancers. Further studies demonstrated that miR-455-3p inhibits cap-dependent translation and the proliferation of prostate cancer cells through targeting eIF4E. Taken together, our findings suggest that miR-455-3p functions as a tumor suppressor by directly targeting eIF4E in prostate carcinogenesis and may be used as a potential target for therapeutic intervention in prostate cancer.

Targeting Swine Leukocyte Antigen Class I Molecules for Proteasomal Degradation by the nsp1α Replicase Protein of the Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Strain JXwn06.

UNLABELLED: Porcine reproductive and respiratory syndrome virus (PRRSV) is a critical pathogen of swine, and infections by this virus often result in delayed, low-level induction of cytotoxic T lymphocyte (CTL) responses in pigs. Here, we report that a Chinese highly pathogenic PRRSV strain possessed the ability to downregulate swine leukocyte antigen class I (SLA-I) molecules on the cell surface of porcine alveolar macrophages and target them for degradation in a manner that was dependent on the ubiquitin-proteasome system. Moreover, we found that the nsp1α replicase protein contributed to this property of PRRSV. Further mutagenesis analyses revealed that this function of nsp1α required the intact molecule, including the zinc finger domain, but not the cysteine protease activity. More importantly, we found that nsp1α was able to interact with both chains of SLA-I, a requirement that is commonly needed for many viral proteins to target their cellular substrates for proteasomal degradation. Together, our findings provide critical insights into the mechanisms of how PRRSV might evade cellular immunity and also add a new role for nsp1α in PRRSV infection. IMPORTANCE: PRRSV infections often result in delayed, low-level induction of CTL responses in pigs. Deregulation of this immunity is thought to prevent the virus from clearance in an efficient and timely manner, contributing to persistent infections in swineherds. Our studies in this report provide critical insight into the mechanism of how PRRSV might evade CTL responses. In addition, our findings add a new role for nsp1α, a critical viral factor involved in antagonizing host innate immunity.

Factors associated with one year retention to methadone maintenance treatment program among patients with heroin dependence in China.

OBJECTIVE: The aim of this study was to evaluate the risk factors associated with dropout from Methadone Maintenance Treatment (MMT) clinics within a 1 year follow-up cohort study in China. METHODS: A data analysis is to explore the adherence of MMT during one year from three hundred and twenty patients with heroin dependence at five clinics (3 in Shanghai, 2 in Kunming) in China. All participants were from the part of China-United States cooperation project entitled "Research about improving the compliance and efficacy of methadone maintenance treatment in China". Our data analysis includes the patients' attendance in the 6 months clinical study and the data in another 6 months afterward. The data of patients at baseline were collected with the Addiction Severity Index (ASI) which is a semi-structured questionnaire covering socio-demographic characteristics and drug use history. The one year attendance after recruitment at the clinics and daily dose were abstracted from the MMT clinic register system. The Cox proportional hazards model were used to explore the risk factor of dropout, defined as seven consecutive days without methadone. RESULTS: By the end of 1 year of treatment 86 patients still remained in MMT without dropout (87% in Shanghai and 13% patients in Kunming). Over the entire 1-year period the median days of remaining in the program were 84 days (in Shanghai and Kunming were 317 days and 22 days).The factors associated with retention included age (HR=0.98, 95%C.I.:0.96-0.99, P=0.0062) and ASI alcohol scores (HR=5.72, 95%C.I.:1.49-21.92, P=0.0109) at baseline. CONCLUSION: One year retention of newly recruited patients with heroin dependence was related to age and ASI alcohol scores at baseline. The adherence is poorer for the patients who are young and having more serious alcohol problems.