ELONGATED HYPOTCOTYL5 and SPINE BASE SIZE1 together mediate light-regulated spine expansion in cucumber.

Plant trichome development is influenced by diverse developmental and environmental signals, but the molecular mechanisms involved are not well understood in most plant species. Fruit spines (trichomes) are an important trait in cucumber (Cucumis sativus L.), as they affect both fruit smoothness and commercial quality. Spine Base Size1 (CsSBS1) has been identified as essential for regulating fruit spine size in cucumber. Here, we discovered that CsSBS1 controls a season-dependent phenotype of spine base size in wild-type plants. Decreased light intensity led to reduced expression of CsSBS1 and smaller spine base size in wild-type plants, but not in the mutants with CsSBS1 deletion. Additionally, knockout of CsSBS1 resulted in smaller fruit spine base size and eliminated the light-induced expansion of spines. Overexpression of CsSBS1 increased spine base size and rescued the decrease in spine base size under low light conditions. Further analysis revealed that ELONGATED HYPOTCOTYL5 (HY5), a major transcription factor involved in light signaling pathways, directly binds to the promoter of CsSBS1 and activates its expression. Knockout of CsHY5 led to smaller fruit spine base size and abolished the light-induced expansion of spines. Taken together, our study findings have clarified a CsHY5-CsSBS1 regulatory module that mediates light-regulated spine expansion in cucumber. This finding offers a strategy for cucumber breeders to develop fruit with stable appearance quality under changing light conditions.

Mycobacterium bovis BCG Given at Birth Followed by Inactivated Respiratory Syncytial Virus Vaccine Prevents Vaccine-Enhanced Disease by Promoting Trained Macrophages and Resident Memory T Cells.

Respiratory syncytial virus (RSV) infects more than 60% of infants in their first year of life. Since an experimental formalin-inactivated (FI) RSV vaccine tested in the 1960s caused enhanced respiratory disease (ERD), few attempts have been made to vaccinate infants. ERD is characterized by Th2-biased responses, lung inflammation, and poor protective immune memory. Innate immune memory displays an increased nonspecific effector function upon restimulation, a process called trained immunity, or a repressed effector function upon restimulation, a process called tolerance, which participates in host defense and inflammatory disease. Mycobacterium bovis bacillus Calmette-Guérin (BCG) given at birth can induce trained immunity as well as heterologous Th1 responses. We speculate that BCG given at birth followed by FI-RSV may alleviate ERD and enhance protection through promoting trained immunity and balanced Th immune memory. Neonatal mice were given BCG at birth and then vaccinated with FI-RSV+Al(OH)3. BCG/FI-RSV+Al(OH)3 induced trained macrophages, tissue-resident memory T cells (TRM), and specific cytotoxic T lymphocytes (CTL) in lungs and inhibited Th2 and Th17 cell immune memory, all of which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented the innate tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. Therefore, BCG given at birth to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants. IMPORTANCE RSV is the leading cause of severe lower respiratory tract infection of infants. ERD, characterized by Th2-biased responses, inflammation, and poor immune memory, has been an obstacle to the development of safe and effective killed RSV vaccines. Innate immune memory participates in host defense and inflammatory disease. BCG given at birth can induce trained immunity as well as heterologous Th1 responses. Our results showed that BCG/FI-RSV+Al(OH)3 induced trained macrophages, TRM, specific CTL, and balanced Th cell immune memory, which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. BCG at birth as an adjuvant to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants.

Genomic insights into the evolution and mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae co-harboring blaKPC and blaNDM: implications for public health threat mitigation.

BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) co-producing blaKPC and blaNDM poses a serious threat to public health. This study aimed to investigate the mechanisms underlying the resistance and virulence of CR-hvKP isolates collected from a Chinese hospital, with a focus on blaKPC and blaNDM dual-positive hvKP strains. METHODS: Five CR-hvKP strains were isolated from a teaching hospital in China. Antimicrobial susceptibility and plasmid stability testing, plasmid conjugation, pulsed-field gel electrophoresis, and whole-genome sequencing (WGS) were performed to examine the mechanisms of resistance and virulence. The virulence of CR-hvKP was evaluated through serum-killing assay and Galleria mellonella lethality experiments. Phylogenetic analysis based on 16 highly homologous carbapenem-resistant K. pneumoniae (CRKP) producing KPC-2 isolates from the same hospital was conducted to elucidate the potential evolutionary pathway of CRKP co-producing NDM and KPC. RESULTS: WGS revealed that five isolates individually carried three unique plasmids: an IncFIB/IncHI1B-type virulence plasmid, IncFII/IncR-type plasmid harboring KPC-2 and IncC-type plasmid harboring NDM-1. The conjugation test results indicated that the transference of KPC-2 harboring IncFII/IncR-type plasmid was unsuccessful on their own, but could be transferred by forming a hybrid plasmid with the IncC plasmid harboring NDM. Further genetic analysis confirmed that the pJNKPN26-KPC plasmid was entirely integrated into the IncC-type plasmid via the copy-in route, which was mediated by TnAs1 and IS26. CONCLUSION: KPC-NDM-CR-hvKP likely evolved from a KPC-2-CRKP ancestor and later acquired a highly transferable blaNDM-1 plasmid. ST11-KL64 CRKP exhibited enhanced plasticity. The identification of KPC-2-NDM-1-CR-hvKP highlights the urgent need for effective preventive strategies against aggravated accumulation of resistance genes.

Co-transfer of IncFII/IncFIB and IncFII plasmids mediated by IS26 facilitates the transmission of mcr-8.1 and tmexCD1-toprJ1.

PURPOSE: This study aimed to characterise the whole-genome structure of two clinical Klebsiella pneumoniae strains co-harbouring mcr-8.1 and tmexCD1-toprJ1, both resistant to colistin and tigecycline. METHODS: K. pneumoniae strains TGC-02 (ST656) and TGC-05 (ST273) were isolated from urine samples of different patients hospitalised at separate times in 2021. Characterisation involved antimicrobial susceptibility testing (AST), conjugation assays, whole-genome sequencing (WGS), and bioinformatics analysis. Comparative genomic analysis was conducted on mcr-8.1-carrying and tmexCD1-toprJ1-carrying plasmids. RESULTS: Both K. pneumoniae isolates displayed a multidrug-resistant phenotype, exhibiting resistance or reduced susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, aztreonam, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, apramycin, tigecycline and colistin. WGS analysis revealed that clinical strain TGC-02 carried the TmexCD1-toprJ1 gene on a 200-Kb IncFII/IncFIB-type plasmid, while mcr-8 was situated on a 146-Kb IncFII-type plasmid. In clinical strain TGC-05, TmexCD1-toprJ1 was found on a 300-Kb IncFIB/IncHI1B/IncR-type plasmid, and mcr-8 was identified on a 137-Kb IncFII/IncFIA-type plasmid. Conjugation experiments assessed the transferability of these plasmids. While transconjugants were not obtained for TGC-05 despite multiple screening with tigecycline or colistin, pTGC-02-tmex and pTGC-02-mcr8 from clinical K. pneumoniae TGC-02 demonstrated self-transferability through conjugation. Notably, the rearrangement of pTGC-02-tmex and pTGC-02-mcr8 via IS26-based homologous recombination was observed. Moreover, the conjugative and fusion plasmids of the transconjugant co-harboured the tmexCD1-toprJ1 gene cluster and mcr-8.1, potentially resulting from IS26-based homologous recombination. CONCLUSION: The emergence of colistin- and tigecycline-resistant K. pneumoniae strains is concerning, and effective surveillance measures should be implemented to prevent further dissemination.

Accuracy of Xpert Carba-R Assay for the Diagnosis of Carbapenemase-producing Organisms from Rectal Swabs in Asia: a Diagnostic Meta-analysis.

The Cepheid Xpert Carba-R assay has been demonstrated to be reliable for rapid detection of carbapenemase-producing orgnisms (CPO) directly from rectal swabs but the performance of which remains unclear in Asia.We searched PubMed, EMBASE and Cochrane Library databases to identify studies according to predetermined criteria. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under the summary receiver operating characteristic curves (AUC). QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. A total of 5 unique studies involving 10807 samples met the inclusion criteria. The pooled sensitivity, specificity, PLR, NLR, and the AUC with 95% CIs of Xpert Carba-R were 0.91 (0.72-0.97), 0.99 (0.96-1.00), 71.24 (25.41-199.73), 0.09 (0.03-0.32), 0.99 (0.98-1.00), respectively. Deeks'funnel plot showed no publication bias.The present meta-analysis showed the Xpert Carba-R assay had good sensitivity and perfect specificity for detecting CPOs on rectal swabs.

SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.

Objective: SOX11 is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of SOX11 in tumorgenesis. Methods: SOX11 expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. SOX11's impact on proliferation and migration was studied in HepG2 and HuH7 cell lines. Results: SOX11 was significantly elevated in HCC tumors compared to controls. SOX11-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between SOX11 levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. SOX11 levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. SOX11 expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between SOX11 and ferroptosis-associated genes. Decreased SOX11 levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration. Conclusions: SOX11 was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.

Antimicrobial resistance and molecular epidemiology of carbapenem-resistant Escherichia coli from urinary tract infections in Shandong, China.

OBJECTIVES: Urinary tract infection (UTI) is one of the most common extraintestinal infections, and uropathogenic Escherichia coli (UPEC) is the main cause of UTIs. However, the ability to treat UTI has been compromised by the increase in antimicrobial resistance, especially carbapenem resistance. Here, we aimed to characterize the antimicrobial resistance and molecular epidemiology of carbapenem-resistant UPEC isolated in Shandong, China. METHODS: In total, 17 carbapenem-resistant UPEC (CR-UPEC) isolates were collected from July 2017 to May 2020 in the Shandong Provincial Hospital. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of CR-UPEC. Phylogenetic groups, drug resistance genes, biofilm formation, and virulence-related gene profiles of the isolates were analyzed. Plasmid profiling and conjugation assay were performed to evaluate the ability to transfer carbapenem resistance-related genes to other E. coli isolates. Biofilm formation was also evaluated, as it is important for the persistence of infectious diseases. RESULTS: We observed that 15 out of 17 CR-UPEC strains were blaNDM producers, among which 4 isolates could transfer blaNDM to recipient cells. The predominant sequence type was ST167 (6/17), followed by ST410 (3/17). The most prevalent phylogenetic group was phylogenetic group A (10/17), followed by phylogenetic group C (3/17). One isolate was resistant to polymyxin, which was caused by the carriage of a transferable plasmid harboring mcr-1. Statistical analysis did not reveal any significant difference in the carriage rate of fimbriae-coding genes between strong and weak biofilm producers. CONCLUSIONS: Our observations may assist in developing new therapeutic methods for drug-resistant organisms.

A novel HD-Zip I/C2H2-ZFP/WD-repeat complex regulates the size of spine base in cucumber.

Fruit spine is an important trait in cucumber, affecting not only commercial quality, but also fruit smoothness, transportation and storage. Spine size is determined by a multi-cellular base. However, the molecular mechanism underlying the regulation of cucumber spine base remains largely unknown. Here, we report map-based cloning and characterization of a spine base size 1 (SBS1) gene, encoding a C2H2 zinc-finger transcription factor. Near-isogenic lines of cucumber were used to map, identify and quantify cucumber spine base size 1 (CsSBS1). Yeast-hybrid, bimolecular fluorescence complementation (BiFC), co-immunoprecipitation (Co-IP) and RNA-sequencing assays were used to explore the molecular mechanism of CsSBS1 in regulating spine base size development. CsSBS1 was specifically expressed in cucumber ovaries with particularly high expression in fruit spines. Overexpression of CsSBS1 resulted in large fruit spine base, while RNA-interference silencing of CsSBS1 inhibited the expansion of fruit spine base. Sequence analysis of natural cucumber accessions revealed that CsSBS1 was lost in small spine base accessions, resulting from a 4895 bp fragment deletion in CsSBS1 locus. CsSBS1 can form a trimeric complex with two positive regulators CsTTG1 and CsGL1 to regulate spine base development through ethylene signaling. A novel regulator network is proposed that the CsGL1/CsSBS1/CsTTG1 complex plays a significant role in regulating spine base formation and size, which offers a strategy for cucumber breeders to develop smooth fruit.

A novel nomogram for predicting cancer-specific survival in women with uterine sarcoma: a large population-based study.

BACKGROUND: Uterine sarcoma (US) is a rare malignant uterine tumor with aggressive behavior and rapid progression. The purpose of this study was to constructa comprehensive nomogram to predict cancer-specific survival (CSS) of patients with US-based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective population-based study was conducted using data from patients with US between 2010 and 2015 from the SEER database. They were randomly divided into a training cohort and a validation cohort ata 7-to-3 ratio. Multivariate Cox analysis was performed to identify independent prognostic factors. Subsequently, a nomogram was established to predict patient CSS. The discrimination and calibration of the nomogram were evaluated by the concordance index (C-index) and the area under the curve (AUC). Finally, net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the benefits of the new prediction model. RESULTS: A total of 3861 patients with US were included in our study. As revealed in multivariate Cox analysis, age at diagnosis, race, marital status, insurance record, tumor size, pathology grade, histological type, SEER stage, AJCC stage, surgery status, radiotherapy status, and chemotherapy status were found to be independent prognostic factors. In our nomogram, pathology grade had strongest correlation with CSS, followed by age at diagnosis and surgery status. Compared to the AJCC staging system, the new nomogram showed better predictive discrimination with a higher C-index in the training and validation cohorts (0.796 and 0.767 vs. 0.706 and 0.713, respectively). Furthermore, the AUC value, calibration plotting, NRI, IDI, and DCA also demonstrated better performance than the traditional system. CONCLUSION: Our study validated the first comprehensive nomogram for US, which could provide more accurate and individualized survival predictions for US patients in clinical practice.

Olaparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation: SOLO1 China cohort.

PURPOSE: Maintenance therapy with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib provided a substantial progression-free survival (PFS) benefit compared with placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (BRCAm) who were in clinical complete or partial response following platinum-based chemotherapy in the Phase III SOLO1 global study. This led to the approval of maintenance olaparib in China, USA, EU, Japan and other countries, in the newly diagnosed setting. This separate China cohort of the SOLO1 study investigated the efficacy and safety of maintenance olaparib within the Chinese population. PATIENTS AND METHODS: In this double-blind, multicentre study, patients were randomized 2:1 to receive oral olaparib tablets (300 mg twice daily) or placebo. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). RESULTS: Of the 64 randomized patients, 44 received olaparib and 20 placebo. Olaparib reduced the risk of disease progression or death by 54% compared with placebo (HR 0.46, 95% Cl 0.23-0.97; median PFS was not reached in the olaparib arm vs 9.3 months in the placebo arm). The most common AEs in the olaparib arm were nausea (63.6 vs 25.0% with placebo), anaemia (59.1 vs 15.0%) and leukopenia (54.5 vs 20.0%). Grade ≥3 AEs were experienced by 56.8% of olaparib patients and 30.0% of placebo patients. CONCLUSIONS: Results in the SOLO1 China cohort support the use of olaparib as maintenance treatment for Chinese patients with newly diagnosed advanced ovarian cancer who have a BRCAm and are in complete or partial response after platinum-based chemotherapy.

A Multiscale Spatio-Temporal Convolutional Deep Belief Network for Sensor Fault Detection of Wind Turbine.

Sensor fault detection of wind turbines plays an important role in improving the reliability and stable operation of turbines. The supervisory control and data acquisition (SCADA) system of a wind turbine provides promising insights into sensor fault detection due to the accessibility of the data and the abundance of sensor information. However, SCADA data are essentially multivariate time series with inherent spatio-temporal correlation characteristics, which has not been well considered in the existing wind turbine fault detection research. This paper proposes a novel classification-based fault detection method for wind turbine sensors. To better capture the spatio-temporal characteristics hidden in SCADA data, a multiscale spatio-temporal convolutional deep belief network (MSTCDBN) was developed to perform feature learning and classification to fulfill the sensor fault detection. A major superiority of the proposed method is that it can not only learn the spatial correlation information between several different variables but also capture the temporal characteristics of each variable. Furthermore, this method with multiscale learning capability can excavate interactive characteristics between variables at different scales of filters. A generic wind turbine benchmark model was used to evaluate the proposed approach. The comparative results demonstrate that the proposed method can significantly enhance the fault detection performance.

miR-603 targeted hexokinase-2 to inhibit the malignancy of ovarian cancer cells.

The Warburg effect, characterized by energy production through a high rate of aerobic glycolysis, is a metabolic hallmark of cancer cells. We previously found that ginsenoside 20(S)-Rg3 upregulated miR-603 and impaired the malignancy of ovarian cancer cells by inhibiting the Warburg effect. However, the precise functional role of miR-603 in ovarian cancer progression remains poorly defined. Here, we report that the level of miR-603 in ovarian cancer tissues is significantly lower than that in para-tumor tissues. Overexpression of miR-603 in ovarian cancer cells inhibits the Warburg effect as evidenced by a decrease in glucose consumption, lactate production and hexokinase-2 (HK2) expression, reduces cell proliferation in vitro, and weakens their migration and invasion. Further, miR-603 directly targets HK2 as indicated in a luciferase reporter assay. In contrast to agomiR-NC, agomiR-603 treatment significantly inhibits tumor growth in vivo and the Warburg effect, which is illustrated by a decreased uptake of 18F-FDG in subcutaneous xenografts and HK2 downregulation. Finally, miR-603 is negatively regulated by DNMT3A-mediated DNA methylation in the promoter region of its precursor gene, suggesting that 20(S)-Rg3 antagonizes DNMT3A-mediated DNA methylation to impair growth, migration and invasion of ovarian cancer cells. In conclusion, miR-603 is a tumor suppressor targeting HK2 in ovarian cancer and its low level may result from DNMT3A-mediated methylation.

Expression of N-Myc Downstream-Regulated Gene 2 in Bladder Cancer and Its Potential Utility as a Urinary Diagnostic Biomarker.

BACKGROUND Initial diagnosis of carcinoma of the urinary bladder remains challenging. N-Myc downstream-regulated gene 2 (NDRG2) has been reported to be closely correlated with cell differentiation and proliferation in various cancers. However, its clinical significance in diagnosis of bladder cancer remains unclear. The purpose of this study was to detect the expression of NDRG2 and investigate its diagnostic value in bladder cancer. MATERIAL AND METHODS We recruited 127 patients with bladder cancer and 97 healthy controls. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analysis were conducted to measure the NDRG2 expression levels in urine of patients with bladder cancer, bladder cancer cell lines, and healthy controls. The correlations between NDRG2 expression and clinicopathological characteristics were analyzed by chi-square test, and the diagnostic value of NDRG2 was estimated by establishing a receiver operating characteristic (ROC) curve. RESULTS The relative NDRG2 expression were significantly downregulated both at mRNA and protein levels in urine of patients with bladder cancer and in cell lines, and its low expression was distinctively correlated with tumor grade and stage. The ROC curve showed NDRG2 could be a good diagnostic marker, with an AUC of 0.888, indicating high sensitivity and specificity. CONCLUSIONS NDRG2 was decreased in patients with bladder cancer and might be involved in the progression of this malignancy. Moreover, NDRG2 could be a potential independent diagnostic biomarker for bladder cancer.

MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression.

Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4+ T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4+ T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation. In the model, MBD2 and IRF4 protein expression increased in the lung and spleen cells. Under overexpression or silencing of the MBD2 and IRF4 gene, the differentiation of Th17 cells and IL-17 secretion showed positive changes. IRF4 protein expression showed a positive change with overexpression or silencing of the MBD2 gene, whereas there was no significant difference in the expression of MBD2 under overexpression or silencing of the IRF4 gene. These data provide novel insights into epigenetic regulation of severe asthma.

Statistical study to identify the key factors governing ground water recharge in the watersheds of the arid Central Asia.

Understanding the source and recharge of ground waters is of great significance to our knowledge in hydrological cycles in arid environments over the world. Northern Xinjiang in northwestern China is a significant repository of information relating to the hydrological evolution and climatic changes in central Asia. In this study, two multivariate statistical techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to assess the ground water recharge and its governing factors, with the principal idea of exploring the above techniques to utilize all available hydrogeochemical variables in the quality assessment, which are not considered in the conventional techniques like Stiff and Piper diagrams. Q-mode HCA and R-mode PCA were combined to partition the water samples into seven major water clusters (C1-C7) and three principal components (PC1-PC3, PC1 salinity, PC2 hydroclimate, PC3 contaminant). The water samples C1 + C4 were classified as recharge area waters (Ca-HCO3 water), C2 + C3 as transitional zone waters (Ca-Mg-HCO3-SO4 water), and C5 + C6 + C7 as discharge area waters (Na-SO4 water). Based on the Q-mode PCA scores, three groups of geochemical processes influencing recharge regimes were identified: geogenic (i.e., caused by natural geochemical processes), geomorphoclimatic (caused by topography and climate), and anthropogenic (caused by ground water contamination). It is proposed that differences in recharge mechanism and ground water evolution, and possible bedrock composition difference, are responsible for the chemical genesis of these waters. These will continue to influence the geochemistry of the northern Xinjiang drainage system for a long time due to its steady tectonics and arid climate. This study proved that the chemistry differentiation of ground water can effectively support the identification of ground water recharge and evolution patterns.

Parecoxib Protects Mouse Cortical Neurons Against OGD/R Induced Neurotoxicity by Up-Regulating Bcl-2.

Ischemic stroke remains a significant problem that is the major cause of death and disability worldwide. Parecoxib is clinically used for short-term management of postoperative pain. Administration of parecoxib in rats has been reported to protect against the cerebral ischemia/reperfusion. However, the neuroprotective mechanism of parecoxib is still largely unknown. In this study, we found parecoxib could protect against neurotoxicity induced by 4 h oxygen-glucose deprivation (OGD) plus reoxgenation for 20 h, a widely used in vitro model of ischemia/reperfusion. In addition, we characterized the molecular mechanism of parecoxib's neuroprotection. We found parecoxib was able to activate CREB, and subsequently maintained the expression of Bcl-2, which is an important mitochondria-associated protein. Inhibition of endogenous Bcl-2 expression by transfection of Bcl-2-shRNA significantly attenuated the neuroprotective effects of parecoxib treatment. Furthermore, ATP production assay and mitochondrial membrane potential (ΔΨm) assay suggested that parecoxib exerted neuroprotective effect against OGD/R by maintaining the function of mitochondria. These data suggested that parecoxib treatment is a potential therapeutic approach for protecting against ischemia/reperfusion injury.

Radical hysterectomy with adjuvant radiotherapy versus radical radiotherapy for FIGO stage IIB cervical cancer.

BACKGROUND: The goal of this study was to compare treatment outcomes for Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical carcinoma patients receiving radical surgery followed by adjuvant postoperative radiotherapy versus radical radiotherapy. METHODS: Medical records of FIGO stage IIB cervical cancer patients treated between July 2008 and December 2011 were retrospectively reviewed. A total of 148 patients underwent radical hysterectomy with pelvic lymph node dissection followed by adjuvant radiotherapy (surgery-based group). These patients were compared with 290 patients that received radical radiotherapy alone (RT-based group). Recurrence rates, progression-free survival (PFS), overall survival (OS), local control rates, and treatment-related complications were compared for these two groups. RESULTS: Similar rates of recurrence (16.89% vs. 12.41%, p = 0.200), PFS (log-rank, p = 0.211), OS (log-rank, p = 0.347), and local control rates (log-rank, p = 0.668) were observed for the surgery-based group and the RT-based group, respectively. Moreover, the incidence of acute grade 3-4 gastrointestinal reactions and late grade 3-4 lower limb lymphedema were significantly higher for the surgery-based group versus the RT-based group. Cox multivariate analyses found no significant difference in survival outcome between the two groups, and tumor diameter and histopathology were identified as significant prognostic factors for OS. CONCLUSIONS: Radical radiotherapy was associated with fewer treatment-related complications and achieved comparable survival outcomes for patients with FIGO stage IIB cervical cancer compared to radical hysterectomy followed by postoperative radiotherapy.

A promoter that drives gene expression preferentially in male transgenic rats.

Gender-preferential gene expression is a widespread phenomenon in humans. It is important to study how gender differences influence the pathogenesis of various diseases and response to specific drugs. The aim of this study is to determine if the mouse albumin enhancer/promoter may serve as the promoter to introduce gender-preferential gene expression in transgenic animals. We created four independent transgenic rat lines in which the human C-reactive protein transgene was under the control of mouse albumin enhancer/promoter. Quantitative real time RT-PCR analysis showed that transgene expression in the liver of male rats was significantly higher than transgene expression in the female rats (P < 0.05).There was a 5.3-fold (male/female) difference in line-519, and a 12.2-fold (male/female) difference in line-488. Enzyme-linked immunosorbent assay showed that the serum of male transgenic rats had a 13- to 679-fold difference at the protein level on transgene production compared with female transgenic rats. The male-to-female difference in gene expression was 10- to 17-fold in the liver of transgenic rats. Orchiectomy dramatically reduced protein production from the transgene in the liver. Testosterone administration into female rats did not increase the transgene expression, but estrogen administration into the male rats reduced transgene expression. This study provides a valuable tool for investigating the pathological roles of genes that are expressed in a gender-preferential manner in human disease.

Uterine prolapse complicated by vaginal cancer: a case report and literature review.

Primary vaginal cancer is not common, representing 1-2% of all female genital malignancies. We present a case of a third-degree uterine prolapse complicated by an isolated primary vaginal cancer and its surgical treatment. The cervix was clinically normal, but on the nearby prolapsed vaginal wall, a large exogenous hard lesion had developed. A biopsy of the lesion revealed a squamous carcinoma. The patient was asymptomatic and had no recurrence during the last 4 years of follow-up after surgical treatment with radiotherapy. The surgical treatment with or without radiotherapy is the optimum treatment for uterine prolapse with early-stage vaginal squamous cell carcinoma, although the majority of vaginal malignancies are treated with radiotherapy. We recommend always performing a biopsy prior to surgery in prolapse-induced ulceration.

[Effect of Sox2 on proliferation of cervical squamous cancer cell line SiHa].

OBJECTIVE: To investigate the effect and its mechanism of stem cell related transcription factor Sox2 on the proliferation of cervical squamous carcinoma cell line SiHa. METHODS: Plasmid pIRES-EGFP-Sox2 or empty plasmid (pIRES-EGFP-empty) was stably transfected into SiHa cells. The expression of Sox2 was detected by both RT-PCT and Western blot. The effects of Sox2 on cellular proliferation and cell cycle were studied by MTT assay and flow cytometry (FCM) respectively. The expression of cell cycle related protein CyclinD1 was detected by Western blot. RESULTS: Compared to SiHa-EGFP cells, the expression of Sox2 was obviously up-regulated in SiHaSox2 cells (P < 0.01). MTT result showed that SiHa-Sox2 cells grew faster than the control cells. The over expression of Sox2 increased the proportion of transfected cells in phase S. The increased expression of CyclinD1 was further detected after the successful expression of Sox2 (P < 0.05). CONCLUSION: Sox2 could enhance the proliferation of cervical squamous cancer cells in the manner of up-regulating CyclinD1 expression.