Inactivation of chlorine-resistant bacteria (CRB) via various disinfection methods: Resistance mechanism and relation with carbon source metabolism.

With the widespread use of chlorine disinfection, chlorine-resistant bacteria (CRB) in water treatment systems have gained public attention. Bacterial chlorine resistance has been found positively correlated with extracellular polymeric substance (EPS) secretion. In this study, we selected the most suitable CRB controlling method against eight bacterial strains with different chlorine resistance among chloramine, ozone, and ultraviolet (UV) disinfection, analyzed the resistance mechanisms, clarified the contribution of EPS to disinfection resistance, and explored the role of carbon source metabolism capacity. Among all the disinfectants, UV disinfection showed the highest disinfection capacity by achieving the highest average and median log inactivation rates for the tested strains. For Bacillus cereus CR19, the strain with the highest chlorine resistance, 40 mJ/cm2 UV showed a 1.90 log inactivation, which was much higher than that of 2 mg-Cl2/L chlorine (0.67 log), 2 mg-Cl2/L chloramine (1.68 log), and 2 mg/L ozone (0.19 log). Meanwhile, the UV resistance of the bacteria did not correlate with EPS secretion. These characteristics render UV irradiation the best CRB controlling disinfection method. Chloramine was found to have a generally high inactivation efficiency for bacteria with high chlorine-resistance, but a low inactivation efficiency for low chlorine-resistant ones. Although EPS consumed up to 56.7% of chloramine which an intact bacterial cell consumed, EPS secretion could not explain chloramine resistance. Thus, chloramine is an acceptable CRB control method. Similar to chlorine, ozone generally selected high EPS-secreting bacteria, with EPS consuming up to 100% ozone. Therefore, ozone is not an appropriate method for controlling CRB with high EPS secretion. EPS played an important role in all types of disinfection resistance, and can be considered the main mechanism for bacterial chlorine and ozone disinfection resistance. However, as EPS was not the main resistance mechanism in UV and chloramine disinfection, CRB with high EPS secretion were inactivated more effectively. Furthermore, carbon source metabolism was found related to the multiple resistance of bacteria. Those with low carbon source metabolism capacity tended to have higher multiple resistance, especially to chlorine, ozone, and UV light. Distinctively, among the tested gram-negative bacteria, in contrast to other disinfectants, chloramine resistance was negatively correlated with EPS secretion and positively correlated with carbon source metabolism capacity, suggesting a special disinfection mechanism.

Spatial nanopores promote laccase degradation of bisphenol A and its analogs.

Bisphenol A (BPA) and its analogs are endocrine-disrupting chemicals that are frequently detected in environmental and human samples. However, the effective removal of BPA and its analogs has not yet been extensively studied. Herein, we introduce a novel enzyme reactor for the degradation of BPA and its analogs in water. The influence of pore size on the degradation efficiency of immobilized laccase in the spatial nanopores of hydrogel was investigated using BPA as a representative compound. This showed that nanopores enhance the activity of immobilized laccases in a pore size-dependent manner and increase their stability. Compared with the same amount of free laccase, the 50 mg/L BPA degradation performance of laccase immobilized in 76 nm nanopores increased to 300 %. Taking advantage of magnetic separation, this immobilized laccase can be reused, and its degradation capacity was maintained at over 73.7 % after ten reactions. Moreover, the degradation of seven BPA analogs was 1.03-5.88 times higher using laccase immobilized in nanopores compared with free laccase. Also, the biocatalyst could efficiently degrade BPA analogs in real water matrix. This study opens up a new avenue for the removal of BPA and its analogs by immobilizing laccase in nanopores, overcoming the key limitations introduced by the short enzyme life span and non-reusability.

Modeling and optimization of synergistic ozone-ultraviolet-chlorine process for reclaimed water disinfection: From laboratory tests to software simulation.

The ozone-ultraviolet (UV)-chlorine process is a highly effective method of disinfection in water reuse system, but currently still lacks precise quantification and accurate control. It is difficult to determine the dosage of each disinfectant because of the complex interactions that occur between disinfection units and the complicated mathematical calculation required. In this study, we proposed a dosage optimization model for ozone-UV-chlorine synergistic disinfection process. The model was able to identify the cost-effective doses of the disinfectants under the constraints of microbial inactivation, decolorization, and residual chlorine retention requirements. Specifically, the simulation of microbial inactivation rates during synergistic disinfection process was accomplished through quantification of the synergistic effects between disinfection units and the introduction of enhancement coefficients. In order to solve this optimization model rapidly and automatically, a MATLAB-based software program with graphical user interface was developed. This software consisted of calibration unit, prediction unit, assessment unit, and optimization unit, and was able to simulate synergistic ozone-UV-chlorine process and identify the optimal dose of ozone, UV, and chlorine. Validation experiments revealed good agreements between the experimental data and the results calculated by the developed software. The developed software is believed to help the water reclamation plants improve disinfection efficiency and reduce the operational costs of synergistic disinfection processes.

Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases.

Background: Hepatocellular carcinoma (HCC) is a common malignancy. Ferroptosis and cuproptosis promote HCC spread and proliferation. While fewer studies have combined ferroptosis and cuproptosis to construct prognostic signature of HCC. This work attempts to establish a novel scoring system for predicting HCC prognosis, immunotherapy, and medication sensitivity based on ferroptosis-related genes (FRGs) and cuproptosis-related genes (CRGs). Methods: FerrDb and previous literature were used to identify FRGs. CRGs came from original research. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases included the HCC transcriptional profile and clinical information [survival time, survival status, age, gender, Tumor Node Metastasis (TNM) stage, etc.]. Correlation, Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses were used to narrow down prognostic genes and develop an HCC risk model. Using "caret", R separated TCGA-HCC samples into a training risk set and an internal test risk set. As external validation, we used ICGC samples. We employed Kaplan-Meier analysis and receiver operating characteristic (ROC) curve to evaluate the model's clinical efficacy. CIBERSORT and TIMER measured immunocytic infiltration in high- and low-risk populations. Results: TXNRD1 [hazard ratio (HR) =1.477, P<0.001], FTL (HR =1.373, P=0.001), GPX4 (HR =1.650, P=0.004), PRDX1 (HR =1.576, P=0.002), VDAC2 (HR =1.728, P=0.008), OTUB1 (HR =1.826, P=0.002), NRAS (HR =1.596, P=0.005), SLC38A1 (HR =1.290, P=0.002), and SLC1A5 (HR =1.306, P<0.001) were distinguished to build predictive model. In both the model cohort (P<0.001) and the validation cohort (P<0.05), low-risk patients had superior overall survival (OS). The areas under the curve (AUCs) of the ROC curves in the training cohort (1-, 3-, and 5-year AUCs: 0.751, 0.727, and 0.743), internal validation cohort (1-, 3-, and 5-year AUCs: 0.826, 0.624, and 0.589), and ICGC cohort (1-, 3-, and 5-year AUCs: 0.699, 0.702, and 0.568) were calculated. Infiltration of immune cells and immunological checkpoints were also connected with our signature. Treatments with BI.2536, Epothilone.B, Gemcitabine, Mitomycin.C, Obatoclax. Mesylate, and Sunitinib may profit high-risk patients. Conclusions: We analyzed FRGs and CRGs profiles in HCC and established a unique risk model for treatment and prognosis. Our data highlight FRGs and CRGs in clinical practice and suggest ferroptosis and cuproptosis may be therapeutic targets for HCC patients. To validate the model's clinical efficacy, more HCC cases and prospective clinical assessments are needed.

Microalgae-derived carbon quantum dots mediated formation of metal sulfide nano-adsorbents with exceptional cadmium removal performance.

Metal sulfides are regarded as efficient scavengers for heavy metals. However, the heavy metal adsorption capacity of metal sulfides is far from its theoretical values due to the insufficient exposure of adsorption sites. Surface modification of metal sulfides is considered one of the most effective strategies for improving heavy metal removal performance. Here, microalgae-derived carbon quantum dots (CQDs) were used as a green modifier for mediating nano-MnS/FeS formation to enhance Cd2+ removal. With the addition of 1 wt% CQDs, the Cd2+ adsorption capacity of 1 %CQDs-MnS reached 481 mg/g at 25 °C and 648.6 mg/g at 45 °C, which surpassed most of the previously reported metal sulfides. Furthermore, the CQDs-modified MnS displayed a better Cd2+ removal capacity than the commercial modifier sodium alginate. The mechanism analysis suggested that decreasing the particle size to expose more adsorption sites and providing additional chelating sites derived from the CQDs are two main reasons why CQDs enhance the Cd2+ adsorption capacity of metal sulfides. This study presents an exceptional cadmium nano-adsorbent of 1 %CQDs-MnS and provides a new perspective on the enhancement of heavy metal removal by using CQDs as a promising and universal green modifier that mediates the formation of metal sulfides.

Identification of cuproptosis and ferroptosis-related subgroups and development of a signature for predicting prognosis and tumor microenvironment landscape in hepatocellular carcinoma.

Background: Ferroptosis and cuproptosis play a crucial role in the progression and dissemination of hepatocellular carcinoma (HCC). The primary objective of this study was to develop a unique scoring system for predicting the prognosis and immunological landscape of HCC based on ferroptosis-related genes (FRGs) and cuproptosis-related genes (CRGs). Methods: As the training cohort, we assembled a novel HCC cohort by merging gene expression data and clinical data from The Cancer Genome Atlas (TCGA) database, and Gene Expression Omnibus (GEO) database. The validation cohort consisted of 230 HCC cases taken from the International Cancer Genome Consortium (ICGC) database. Multiple genomic characteristics, such as tumor mutation burden (TMB), and copy number variations were analyzed concurrently. On the basis of the expression of CRGs and FRGs, patients were classified into cuproptosis and ferroptosis subtypes. Then, we constructed a risk model using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression analysis based on ferroptosis and cuproptosis-related differentially expressed genes (DEGs). Patients were separated into two groups according to median risk score. We compared the immunophenotype, tumor microenvironment (TME), cancer stem cell index, and treatment sensitivity of two groups. Results: Three subtypes of ferroptosis and two subtypes of cuproptosis were identified among the patients. A greater likelihood of survival (P<0.05) was expected for patients in FRGcluster B and CRGcluster B. After that, a confirmed risk signature for ferroptosis and cuproptosis was developed and tested. Patients in the low-risk group had significantly higher survival rates than those in the high-risk group, according to our study (P<0.001). There was also a strong correlation between the signature and other variables including immunophenoscore, TMB, cancer stem cell index, immunological checkpoint genes, and sensitivity to chemotherapeutics. Conclusions: Through this comprehensive research, we identified a unique risk signature associated with HCC patients' treatment status and prognosis. Our findings highlight FRGs' and CRGs' significance in clinical practice and imply ferroptosis and cuproptosis may be therapeutic targets for HCC patients.

[Spatial heterogeneity and driving factors of ecosystem water yield service in Yunnan Province, China based on Geodetector]. / åŸºäºŽåœ°ç†æŽ¢æµ‹å™¨çš„äº‘å—çœç”Ÿæ€ç³»ç»Ÿäº§æ°´æœåŠ¡çš„ç©ºé—´å¼‚è´¨æ€§åŠé©±åŠ¨å› ç´ .

Water yield is an important ecosystem service. It is the key to maintain ecological security and sustainable development to accurately grasp the spatial heterogeneity characteristics and identify the key driving factors of water yield in different regions. Taking Yunnan Province with significant geospatial heterogeneity as the research area, we used InVEST model to simulate the temporal and spatial variations of water yield in Yunnan Province from 1992 to 2019. The spatial characteristics of driving factors, such as climate, vegetation, soil, terrain, land use, on water yield service were analyzed through Geodetector. The results showed that water yield of Yunnan Province showed a fluctuating trend of increasing at first and decreasing later from 1992 to 2019, with a similar spatial distribution pattern in each year, and an overall trend of gradually decreasing from northwest, west and southwest to central and east. Climatic factors (precipitation and actual evapotranspiration) were the main driving factors leading to spatial differentiation of water yield. In different watershed divisions, the impact of each driving factor on water yield had significant spatial heterogeneity: the watersheds dominated by precipitation were mainly distributed in the west of Yunling-Yuanjiang line, the Irrawaddy River, the upper reaches of Nujiang River, the lower reaches of Nujiang River, the upper reaches of Lancang River, the upper reaches of Jinsha River, Yuanjiang River and Lixian River areas. As for the east of Yunling-Yuanjiang line, in karst landform areas (Nanguang River, Chishui River, Wujiang River, Youjiang River and Panlong River) and the lower reaches of Jinsha River with high population density and shortage of cultivated land, actual evapotranspiration and land use type were the leading factors controlling the spatial pattern of water yield. The results could provide a reference for water resources management policy and ecological civilization construction in Yunnan Province, with a certain guiding significance to promote the optimization and sustainable development of ecosystem services in complex plateau-mountain area.

Locally advanced cervical rhabdomyosarcoma in adults: A case report.

BACKGROUND: Rhabdomyosarcoma is a soft tissue tumor of primitive mesenchymal cells origin, occurring predominantly in children and adolescents, but extremely rare in adults and the data regarding its treatment are sparse. Here, we would like to share our experience in the treatment of a locally advanced primary embryonal rhabdomyosarcoma of cervix in a 39-year-old female. CASE SUMMARY: The patient was admitted with symptoms of intermenstrual bleeding and postcoital bleeding for six months. Physical examination revealed a friable, polyp-like mass (5 cm × 5 cm) in her cervix protruding into the vagina, while the uterus was mobile and normal-sized. Colposcopy-directed biopsy was performed, and a pathological diagnosis of embryonal rhabdomyosarcoma was made. Magnetic resonance imaging of the pelvis showed that the cervical volume was significantly increased, with a hypointense and hyperintense soft tissue mass on the right side, invading the cervical stroma; the mass was 5 cm × 5 cm with a clear boundary and confined to the cervix; there were no obvious findings indicating tumor invasion in the vaginal wall, parametrium, or pelvic wall; no enlarged lymph nodes were observed in the pelvic cavity. Based on our findings, the tumor was classified as stage IA according to the intergroup rhabdomyosarcoma studies criteria and IB3 stage according to The International Federation of Gynecology and Obstetrics 2018. The patient underwent two courses of neoadjuvant chemotherapy and a partial remission was achieved. Subsequently, she underwent laparoscopic radical hysterectomy, bilateral salpingo-oophrectomy and pelvic lymph node dissection and there were no risk factors revealed by postoperative pathological examination. Adjuvant chemotherapy was performed after surgery. The patient was disease-free until the last follow-up, 49 mo after completing the entire treatment. CONCLUSION: Our experience suggests that neoadjuvant vincristine, dactinomycin, and cyclophosphamide chemotherapy followed by radical surgery and adjuvant chemotherapy might be reasonable therapeutic option for bulky cervical rhabdomyosarcoma in adults without fertility desire. Since large-scale studies on such rare conditions are rather impossible, further case reports and systematic reviews could help optimize the treatment of primary, bulky cervical rhabdomyosarcoma in adults.

Synthesis of pterodontic acid derivatives and the study of their anti-influenza A virus (H1N1) activity.

Laggera pterodonta (DC.) Benth, a folk herb widely distributes in southwest China, especially in Yunnan Province, demonstrates anti-pathogenic microorganisms, anti-inflammatory, inhibition of Helicobacter pylori activities in vitro et al. Interestingly, previous studies have shown that pterodontic acid (1), a eudesmane-type sesquiterpene isolated from L. pterodonta (DC.), displays excellent selective antiviral activity to H1N1 subtype of influenza A virus. At the same time, our group also discovered that the antiviral activity of 1 was relatively close to that activity of post-marketed ribavirin. Therefore, we consider that the synthesis of pterodontic acid (1) derivatives and evaluation of their anti-influenza A virus (H1N1) activities is of potential clinical significance. In this manuscript, a series of pterodontic acid derivatives were prepared and demonstrated significantly improved anti-influenza A virus (H1N1) activities, providing more opportunities for the treatment of respiratory viral diseases.

Yellow nutsedge WRI4-like gene improves drought tolerance in Arabidopsis thaliana by promoting cuticular wax biosynthesis.

BACKGROUND: Cuticular wax plays important role in protecting plants from drought stress. In Arabidopsis WRI4 improves drought tolerance by regulating the biosynthesis of fatty acids and cuticular wax. Cyperus esculentus (yellow nutsedge) is a tough weed found in tropical and temperate zones as well as in cooler regions. In the current study, we report the molecular cloning of a WRI4-like gene from Cyperus esculentus and its functional characterization in Arabidopsis. RESULTS: Using RACE PCR, full-length WRI-like gene was amplified from yellow nutsedge. Phylogenetic analyses and amino acid comparison suggested it to be a WRI4-like gene. According to the tissue-specific expression data, the highest expression of WRI4-like gene was found in leaves, followed by roots and tuber. Transgenic Arabidopsis plants expressing nutsedge WRI4-like gene manifested improved drought stress tolerance. Transgenic lines showed significantly reduced stomatal conductance, transpiration rate, chlorophyll leaching, water loss and improved water use efficiency (WUE). In the absence of drought stress, expression of key genes for fatty acid biosynthesis was not significantly different between transgenic lines and WT while that of cuticular wax biosynthesis genes was significantly higher in transgenic lines than WT. The PEG-simulated drought stress significantly increased expression of key genes for fatty acid as well as wax biosynthesis in transgenic Arabidopsis lines but not in WT plants. Consistent with the gene expression data, cuticular wax load and deposition was significantly higher in stem and leaves of transgenic lines compared with WT under control as well as drought stress conditions. CONCLUSIONS: WRI4-like gene from Cyperus esculentus improves drought tolerance in Arabidopsis probably by promoting cuticular wax biosynthesis and deposition. This in turn lowers chlorophyll leaching, stomatal conductance, transpiration rate, water loss and improves water use efficiency under drought stress conditions. Therefore, CeWRI4-like gene could be a good candidate for improving drought tolerance in crops.

Safety of the Xuesaitong injection in China: results from a large-scale multicentre post-marketing surveillance study in a real-world setting.

OBJECTIVE: The safety profile of traditional Chinese medicine injections has emerged as the greatest challenge to their clinical application. The authors aimed to perform a post-marketing surveillance study in a real-world setting to evaluate the safety of the Xuesaitong (XST) injection in China. METHODS: This multi-centre, post-marketing, observational study enrolled patients who received XST injections in 42 centres in China between March 2015 and November 2017. Adverse drug reactions (ADRs) and adverse drug events (ADEs) were collected and evaluated in a post-marketing database. Logistic regression analysis was performed to analyse the risk factors for ADRs. RESULTS: A total of 30,008 consecutive patients with a mean age of 62.29 ± 14.58 years were included in this post-marketing study. The incidences of ADEs and ADRs were 0.5% and 0.33%, respectively. The most common clinical manifestations were damage to skin and appendages (47.66%). There were four new kinds of ADEs found in the present monitoring study. The majority of ADRs were type B (62.62%) and occurred within 24 h after XST injection treatment. No severe ADRs were reported in this analysis. Multivariate logistic regression analysis showed that the hospital level (OR = 0.607; 95% CI = 0.407-0.906; p = .0144), hypertension (OR = 1.979; 95% CI, 1.323-2.959; p = .0009) and solvent type (OR = 2.951; 95% CI, 1.608-5.417; p = .0005) were risk factors for ADR occurrence. CONCLUSION: XST injection is well tolerated and has a favourable safety profile for patients in a real-world setting. This post-marketing study provided further evidence of the safety of XST injections for clinical applications.

Selenium nanoparticle prepared by femtosecond laser-induced plasma shock wave.

A novel approach for the production of both amorphous and crystalline selenium nanoparticles (SeNPs) using femtosecond laser-induced plasma shock wave on the surface of Bi2Se3 topological insulators at room temperature and ambient pressure is demonstrated. The shape and size of SeNPs can be reliably controlled via the kinetic energy obtained from laser pulses, so these are applicable as active components in nanoscale applications. Importantly, the rapid, low-cost and eco-friendly synthesis strategy developed in this study could also be extendable to other systems.

Transcriptomic analysis of Eruca vesicaria subs. sativa lines with contrasting tolerance to polyethylene glycol-simulated drought stress.

BACKGROUND: Eruca vesicaria subsp. sativa is one of the Cruciferae species most tolerant to drought stress. In our previous study some extremely drought-tolerant/sensitive Eruca lines were obtained. However little is known about the mechanism for drought tolerance in Eruca. METHODS: In this study two E. vesicaria subs. sativa lines with contrasting drought tolerance were treated with liquid MS/PEG solution. Total RNA was isolated from 7-day old whole seedlings and then applied to Illumina sequencing platform for high-throughput transcriptional sequencing. RESULTS: KEGG pathway analysis indicated that differentially expressed genes (DEGs) involved in alpha-Linolenic acid metabolism, Tyrosine metabolism, Phenylalanine, Tyrosine and tryptophan biosynthesis, Galactose metabolism, Isoquinoline alkaloid biosynthesis, Tropane, Piperidine and pyridine alkaloid biosynthesis, Mineral absorption, were all up-regulated specifically in drought-tolerant (DT) Eruca line under drought stress, while DEGs involved in ribosome, ribosome biogenesis, Pyrimidine metabolism, RNA degradation, Glyoxylate and dicarboxylate metabolism, Aminoacyl-tRNA biosynthesis, Citrate cycle, Methane metabolism, Carbon fixation in photosynthetic organisms, were all down-regulated. 51 DEGs were found to be most significantly up-regulated (log2 ratio ≥ 8) specifically in the DT line under PEG treatment, including those for ethylene-responsive transcription factors, WRKY and bHLH transcription factors, calmodulin-binding transcription activator, cysteine-rich receptor-like protein kinase, mitogen-activated protein kinase kinase, WD repeat-containing protein, OPDA reductase, allene oxide cyclase, aquaporin, O-acyltransferase WSD1, C-5 sterol desaturase, sugar transporter ERD6-like 12, trehalose-phosphate phosphatase and galactinol synthase 4. Eight of these 51 DEGs wre enriched in 8 COG and 17 KEGG pathways. CONCLUSIONS: DEGs that were found to be most significantly up-regulated specifically in the DT line under PEG treatment, up-regulation of DEGs involved in Arginine and proline metabolism, alpha-linolenic acid metabolism and down-regulation of carbon fixation and protein synthesis might be critical for the drought tolerance in Eruca. These results will be valuable for revealing mechanism of drought tolerance in Eruca and also for genetic engineering to improve drought tolerance in crops.

Effect of Dahuang Danpi Decoction on Lactobacillus bulgaricus growth and metabolism: In vitro study.

Gut flora plays an essential role in disease and health. A traditional Chinese herb formula, Dahuang Danpi Decoction (DDD) can alleviate several gastrointestinal diseases.In the present study, we assessed the effect of DDD on the growth and metabolism of Lactobacillus bulgaricus. L bulgaricus was cultured in MRS with 40 mg/ml (high), 10 mg/ml (medium), and 2.5 mg/ml (low) of DDD, Ceftriaxone and blank (control). The growth of L bulgaricus was measured by optical density. The levels of L-lactic acid and D-lactic acid were also measured.Compared to the control group, the concentrations of L bulgaricus in the medium and the high concentrations DDD groups were significantly higher (P < .001 for all), while the concentrations of L bulgaricus in the ceftriaxone groups were significantly lower. In the 3 DDD groups, the L- lactic acid levels were significantly higher than those in the control group and the ceftriaxone groups (P < .001 for all), and the L-lactic acid level was the highest in the high DDD group. Similarly, the D-lactic acid level in the high concentration DDD group was significantly higher than those in the medium and low concentration DDD groups, the control group and the ceftriaxone groups. Both the L-lactic acid and D-lactic acid levels were lower than those in the control group and the DDD groups.DDD could dose-dependently promote the growth of L bulgaricus and enhance the secretion of L-lactic acid and D-lactic acid, which suggests DDD may be able to interact with the probiotics, improve the gut microbiota, and serve in the prevention and treatment of dysbiosis.

Molecular dynamics simulations and linear response theories jointly describe biphasic responses of myoglobin relaxation and reveal evolutionarily conserved frequent communicators.

In this study, we provide a time-dependent mechanical model, taking advantage of molecular dynamics simulations, quasiharmonic analysis of molecular dynamics trajectories, and time-dependent linear response theories to describe vibrational energy redistribution within the protein matrix. The theoretical description explained the observed biphasic responses of specific residues in myoglobin to CO-photolysis and photoexcitation on heme. The fast responses were found to be triggered by impulsive forces and propagated mainly by principal modes <40 cm-1. The predicted fast responses for individual atoms were then used to study signal propagation within the protein matrix and signals were found to propagate ~8 times faster across helices (4076 m/s) than within the helices, suggesting the importance of tertiary packing in the sensitivity of proteins to external perturbations. We further developed a method to integrate multiple intramolecular signal pathways and discover frequent "communicators". These communicators were found to be evolutionarily conserved including those distant from the heme.

Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families.

BACKGROUND: Many X-linked non-syndromic hearing loss (HL) cases are caused by various mutations in the POU domain class 3 transcription factor 4 (POU3F4) gene. This study aimed to identify allelic variants of this gene in two Chinese families displaying X-linked inheritance deafness-2 (DFNX2) and one sporadic case with indefinite inheritance pattern. METHODS: Direct DNA sequencing of the POU3F4 gene was performed in these families and in 100 Chinese individuals with normal hearing. RESULTS: There are characteristic imaging findings in DFNX2 Chinese families with POU3F4 mutations. The temporal bone computed tomography (CT) images of patients with DFNX2 are characterized by a thickened stapes footplate, hypoplasia of the cochlear base, absence of the bony modiolus, and dilated internal acoustic meatus (IAM) as well as by abnormally wide communication between the IAM and the basal turn of the cochlea. We identified three causative mutations in POU3F4 for three probands and their extended families. In family 1468, we observed a novel deletion mutation, c.973delT, which is predicted to result in a p.Trp325Gly amino acid frameshift. In family 2741, the mutation c.927delCTC was identified, which is predicted to result in the deletion of serine at position 310. In both families, the mutations were located in the POU homeodomain and are predicted to truncate the C-terminus of the POU domain. In the third family, a novel de novo transversion mutation (c.669 T > A) was identified in a 5-year-old boy that resulted in a nonsense mutation (p.Tyr223*). The mutation created a new stop codon and is predicted to result in a truncated POU3F4 protein. CONCLUSIONS: Based on characteristic radiological findings and clinical features, POU3F4 gene mutation analysis will increase the success rate of stapes operations and cochlear implantations, and improve molecular diagnosis, genetic counseling, and knowledge of the molecular epidemiology of HL among patients with DFNX2.

Progress in the Study of Lymph Node Metastasis in Early-stage Cervical Cancer.

Spread into regional lymph node is the major route of metastasis in cervical cancer. Although lymph node status is not involved in the International Federation of Gynecology and Obstetrics staging system of uterine cervical cancer, the presence or absence of lymph node metastasis provides important information for prognosis and treatment. In this review, we have attempted to focus on the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. In addition, the preoperative prediction of lymph node status, as well as the intraoperative assessment by sentinel nodes will be reviewed. Finally, lymph node micrometastasis also will be discussed.

Diurnal variation of CO2, CH4, and N2O emission fluxes continuously monitored in-situ in three environmental habitats in a subtropical estuarine wetland.

Wetlands play a crucial role in modulating atmospheric concentrations of greenhouse gases (GHGs) such as carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). The key factors controlling GHG emission from subtropical estuarine wetlands were investigated in this study, which continuously monitored the uptake/emission of GHGs (CO2, CH4, and N2O) by/from a subtropical estuarine wetland located in the Minjiang estuary in the coastal region of southeastern China. A self-designed floating chamber was used to collect air samples on-site at three environmental habitats (Phragmites australis marsh, mudflats, and river water). The CO2, CH4, and N2O concentrations were then measured using an automated nondispersive infrared analyzer. The magnitudes of the CO2 and N2O emission fluxes at the three habitats were ordered as river water>P. australis>mudflats. P. australis emitted GHGs through photosynthesis and respiration processes. Emissions of CH4 from P. australis and the mudflats were revealed to be slightly higher than those from the river water. The total GHG emission fluxes at the three environmental habitats were quite similar (4.68-4.78gm-2h-1). However, when the total carbon dioxide equivalent fluxes (CO2-e) were considered, the river water was discovered to emit the most CO2-e compared with P. australis and the mudflats. Based on its potential to increase global warming, N2O was the main contributor to the total GHG emission, with that emitted from the river water being the most considerable. Tidal water carried onto the marsh had its own GHG content and thus has acted as a source or sink of GHGs. However, water quality had a large effect on GHG emissions from the river water whereas the tidal water height did not. Both high salinity and large amounts of sulfates in the wetlands explicitly inhibited the activity of CH4-producing bacteria, particularly at nighttime.