Novel insights into dimethylsulfoniopropionate cleavage by deep subseafloor fungi.

Dimethylsulfoniopropionate (DMSP), a key organic sulfur compound in marine and subseafloor sediments, is degraded by phytoplankton and bacteria, resulting in the release of the climate-active volatile gas dimethylsulfide (DMS). However, it remains unclear if dominant eukaryotic fungi in subseafloor sediments possess specific abilities and metabolic mechanisms for DMSP degradation and DMS formation. Our study provides the first evidence that fungi from coal-bearing sediments ∼2 km below the seafloor, such as Aspergillus spp., Chaetomium globosum, Cladosporium sphaerospermum, and Penicillium funiculosum, can degrade DMSP and produce DMS. In Aspergillus sydowii 29R-4-F02, which exhibited the highest DMSP-dependent DMS production rate (16.95 pmol/µg protein/min), two DMSP lyase genes, dddP and dddW, were identified. Remarkably, the dddW gene, previously observed only in bacteria, was found to be crucial for fungal DMSP cleavage. These findings not only extend the list of fungi capable of degrading DMSP, but also enhance our understanding of DMSP lyase diversity and the role of fungi in DMSP decomposition in subseafloor sedimentary ecosystems.

[Screw versus Kirschner wire fixation for lateral humeral condyle fractures in children:a meta analysis].

OBJECTIVE: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children. METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3. RESULTS: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22, 95%CI(0.09, 0.56), P=0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate(P>0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18, 95%CI(0.05, 0.65), P=0.009]. CONCLUSION: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

The potential role of subseafloor fungi in driving the biogeochemical cycle of nitrogen under anaerobic conditions.

Fungi represent the dominant eukaryotic group of organisms in anoxic marine sedimentary ecosystems, ranging from a few centimeters to ~ 2.5 km below seafloor. However, little is known about how fungi can colonize anaerobic subseafloor environments for tens of millions of years and whether they play a role in elemental biogeochemical cycles. Based on metabolite detection, isotope tracer and gene analysis, we examined the anaerobic nitrogen conversion pathways of 19 fungal species (40 strains) isolated from1.3 to 2.5 km coal-bearing sediments below seafloor. Our results show for the first time that almost all fungi possess anaerobic denitrification, dissimilatory nitrate reduction to ammonium (DNRA), and nitrification pathways, but not anaerobic ammonium oxidation (anammox). Moreover, the distribution of fungi with different nitrogen-conversion abilities in subseafloor sediments was mainly determined by in situ temperature, CaCO3, and inorganic carbon contents. These findings suggest that fungi have multiple nitrogen transformation processes to cope with their requirements for a variety of nitrogen sources in nutrient deficient anaerobic subseafloor sedimentary environments.

[Determination and Traceability Analysis of Phthalic Acid Esters in Garlic (Allium stivum L.) from Jiangsu Province, China].

Phthalic acid esters (PAEs) are ubiquitous environmental pollutants and are recognized as a threat to the environment and agricultural product safety across the world. In order to investigate the level of PAEs in garlic, soils, and agricultural films from Pizhou City, Jiangsu province, China, 11 garlic samples, 106 soil samples, and 4 agricultural film samples were collected and analyzed using GC-MS. In addition, the uptake and transport characteristics of six PAEs compounds classified as priority pollutants by the United States Environmental Protection Agency (EPA) in the garlic cultivar Daqingke were investigated under hydroponic conditions. The results indicated that dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were the dominant PAEs species in garlic cloves of the different garlic varieties from Pizhou City. The average contents of DBP and DEHP in garlic cloves were 0.611 mg·kg-1 and 0.167 mg·kg-1, respectively, which were significantly higher than those of the commercial varieties of garlic. The concentrations of DBP and DEHP differed in three tissues of garlic bulbs, ordered as the skin of garlic bulb>skin of garlic clove>garlic clove. Dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), DBP, and DEHP were the main PAEs species and were detected in all the surface soils collected from Pizhou City. Compared with the soil allowable concentrations of the six PAEs in the United States, the DMP and DBP concentrations in approximately 100% and 63.2% of soil samples exceeded the recommended allowable concentrations set by the EPA. However, the levels of DEP, DIBP, and DEHP in the soils were below the maximum allowable concentrations set by the EPA. Nevertheless, the average content of DEHP in soils was 486 µg·kg-1 and was found to be much higher than that in the other four PAEs. Six PAEs, including DMP, DEP, DIBP, DBP, butyl benzyl phthalate (BBP), and DEHP, were detected in all the agricultural film samples. Among them, the contents of DBP and DEHP in the agricultural films were the highest, accounting for 53.7%-63.2% of the total PAEs. The amount of PAEs present in the residual film was significantly lower than that in the new film, and all six PAEs were detected in garlic or soil samples, suggesting that agricultural film can be an important source of PAEs in garlic farming soils and garlic. Furthermore, the garlic plants absorbed DMP and DEP efficiently from the substrate and showed higher translocation factors (TFs) for DMP and DEP than those for DBP, BBP, DEHP, and di-n-octyl phthalate (DnOP), resulting in a higher accumulation of DMP and DEP in the over-ground parts of garlic. In contrast, DBP and BBP in roots of garlic displayed higher bioconcentration factors (57.4 and 81.5, respectively) compared to those of the other four PAEs, whereas the TFs of DBP and BBP were lower; this may have contributed to the high accumulation of DBP in garlic bulbs. The BCFs and TFs of DEHP and DnOP in garlic were relatively lower, but the DEHP had been detected in all garlic cloves, which may be a result of the higher DEHP contents in soils.

miR-519d-3p alleviates high glucose-induced human retinal microvascular endothelial cells dysfunction and inhibits angiogenesis by targeting hypoxia inducible factor 1 subunit alpha / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To clarify the effect of miR-519d-3p on high glucose-induced human retinal microvascular endothelial cells(HRMEC)dysfunction and angiogenesis, and to elucidate the regulatory mechanism of miR-519d-3p on hypoxia inducible factor 1 subunit alpha(HIF-1α).METHODS: The normal glucose(NG)and high glucose(HG)cell models were established by inducing HRMEC with 5 and 30 mmol/L glucose, respectively. Control group: HG cell model was transfected with negative control mimics; mannitol group: the control group was added with 25 mmol/L mannitol; miR-519d-3p overexpression group: HG cell model was transfected with miR-519d-3p mimics; miR-519d-3p combined with HIF-1α overexpression group: HG cell model was co-transfected with miR-519d-3p mimics and HIF-1α overexpression vector. The expression of miR-519d-3p in each group was tested by real-time fluorescence quantitative PCR. The expression of HIF-1α protein in each group was tested by Western blotting. The binding sites between miR-519d-3p and HIF-1α were detected by luciferase reporter gene assay. The cell proliferation of each group was detected by CCK-8. The cell apoptosis of each group was tested by Hoechst 33342 staining. The protein expression of extracellular fluid inflammatory factors tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in each group was tested by ELISA. The formation of new capillary lumen-like structures was detected by tubule formation assay.RESULTS: Compared with the NG, miR-519d-3p expression was significantly reduced in the HG cell model, while HIF-1α protein expression was significantly increased in the HG(all P<0.01). Compared with the control group, HIF-1α protein expression was significantly reduced in the miR-519d-3p overexpression group(P<0.01). The “CGUGAAA” sequence of miR-519d-3p could specifically bind to the “GCACUUU” sequence of HIF-1α 3'-untranslated region(3'-UTR). Compared with the control group, the miR-519d-3p overexpression group showed a significant increase in 24, 48 and 72h absorbance values, a significant decrease in cell apoptotic rate, a significant decrease in the concentrations of TNF-α, IL-1β and IL-6, and a significant decrease in the number of new capillary lumen-like structures(all P<0.01). Compared with the miR-519d-3p overexpression group, the miR-519d-3p combined with HIF-1α overexpression group showed a significant decrease in 24, 48 and 72h absorbance values, a significant increase in cell apoptotic rate, a significant increase in the concentrations of TNF-α, IL-1β and IL-6, and a significant increase in the number of new capillary lumen-like structures(all P<0.01). There was no difference between the control group and mannitol group in the comparison of the above indicators(all P>0.05).CONCLUSION: miR-519d-3p expression is down-regulated while HIF-1α protein expression is up-regulated in high glucose induced HRMEC model. HIF-1α is a target gene of miR-519d-3p. The miR-519d-3p targets HIF-1α to increase cell proliferation and reduce cell apoptosis and inflammation, thereby alleviating high glucose-induced HRMEC dysfunction and inhibiting angiogenesis.

Clinical analysis of 15 pregnant women complicated with moyamoya disease / 中华妇产科杂志

Objective: To explore the effects of pregnancy complicated with moyamoya disease on maternal and fetal outcomes. Methods: The general clinical data and maternal and fetal outcomes of 20 pregnancies of 15 patients with moyamoya disease admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2022 were retrospectively analyzed. Results: (1) General information: among the 20 pregnancies of 15 clearly diagnosed pregnant women complicated with moyamoya disease, 12 were diagnosed before pregnancy (60%, 12/20), 3 were diagnosed during pregnancy (15%, 3/20), and 5 were diagnosed during puerperal period (25%, 5/20). There were 7 cases of primipara (35%, 7/20) and 13 cases of multipara (65%, 13/20). (2) Pregnancy complications and maternal and infant outcomes: among the 20 pregnancies of 15 pregnant women with moyamoya disease, there were 9 pregnancy complications (45%, 9/20), including 5 gestational hypertension (25%, 5/20), 2 severe pre-eclampsia (10%, 2/20), 1 hyperlipidemia and 1 gestational diabetes mellitus (5%, 1/20). There were 2 case of drug abortion in the first trimester, 3 cases of labor induction in the second trimester, and 15 cases of delivery during the third trimester. All the 15 deliveries were cesarean section, of which 11 (11/15) were cesarean sections with medical indications, and 4 (4/15) were cesarean sections caused by personal factors. General anesthesia was used in 5 cases (5/15), epidural block anesthesia in 7 cases (7/15), and combined spinal and epidural anesthesia in 3 cases (3/15). The median gestational age of 15 neonates was 37.2 weeks (34.0 to 40.8 weeks), with 10 cases (10/15) were full-term infants, and 5 (5/15) were preterm infants (3 of which were associated with hypertensive disorder complicating pregnancy). The birth weight of 15 neonates was (2 853±454) g. Four neonates were admitted to neonatal intensive care unit (NICU), of which 3 cases were admitted to NICU due to premature delivery and 1 case was admitted to NICU due to neonatal jaundice. There was no neonatal asphyxia or death. All neonates were followed up from 4 months to 6 years after birth, and all grew well. (3) Neurological symptoms during pregnancy: 8 cases (40%, 8/20) had neurological symptoms during pregnancy, and 6 cases (30%, 6/20) had hemorrhagic symptoms, of which 3 cases occurred during the puerperal period (3/6). There were 2 cases of ischemic symptoms (10%, 2/20), all of which occurred during the puerperal period (2/2). (4) Analysis of factors related to the occurrence of cerebral hemorrhage: the incidence of cerebral hemorrhage in patients with moyamoya disease diagnosed before pregnancy was significantly lower than that in those without a clear diagnosis, and the incidence of cerebral hemorrhage in women with moyamoya disease was lower than that in primipara (all P<0.01). The incidence of cerebral hemorrhage in moyamoya patients without hypertensive disorder complicating pregrancy was lower than that in patients with hypertensive disorder complicating pregrancy, but the difference was not statistically significant (P>0.05). Conclusions: Pregnancy combined with moyamoya disease has adverse effects on maternal and infant outcomes, and the incidence of pregnancy complications increases. Cerebral hemorrhage occurres in prenatal and puperium, while cerebral ischemia occurres mainly in puperium.

Association and prognostic significance of alpha-L-fucosidase-1 and matrix metalloproteinase 9 expression in esophageal squamous cell carcinoma.

BACKGROUND: Alpha-L-fucosidase-1 (FUCA1) has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma. Moreover, recent studies reported that FUCA1 could decrease the invasion capability by downregulating matrix metalloproteinase 9 (MMP-9) expression. However, the potential role and prognostic significance of FUCA1 in esophageal squamous cell carcinoma (ESCC) have not yet been explored. AIM: To evaluate the status, association, and prognostic value of FUCA1 and MMP-9 expression in ESCC. METHODS: Patients who underwent esophagectomy for ESCC between January 1, 2014, and December 31, 2014 at Sun Yat-Sen University Cancer Center were enrolled. The expression status of FUCA1 and MMP-9 in cancerous tissues was detected using immunohistochemistry. In addition, the expression profiles of the FUCA1 and MMP-9 genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas (TCGA) database. RESULTS: High expression of FUCA1 and MMP-9 was found in 90 patients (75.6%) and 62 patients (52.1%), respectively. In the high FUCA1 expression group, the constituent ratios of patients with stage III disease (61.1% vs 37.9%, P = 0.029), lymphatic invasion (62.2% vs 31.0%, P = 0.003), and high MMP-9 expression (60.0% vs 27.6%, P = 0.002) were significantly higher than those in the low FUCA1 expression group. In Kaplan-Meier univariate analysis, advanced tumor-node-metastasis stage (III, P = 0.001), positive regional lymph node metastasis (N+, P = 0.002), high FUCA1 expression (P = 0.001), and high MMP-9 expression (P = 0.002) were potential predictors of shorter overall survival (OS), which was similar to the results analyzed based on the TCGA database. Further Cox multivariate regression analyses still demonstrated that FUCA1 and MMP-9 expression levels were independent prognostic factors of OS [hazard ratio (HR): 0.484, 95% confidence interval (CI): 0.239-0.979; P = 0.044; and HR: 0.591, 95%CI: 0.359-0.973, P = 0.039, respectively]. CONCLUSION: FUCA1 cooperation with MMP-9 may have a major role in affecting the ESCC invasion and metastatic capability, and serve as a valuable prognostic biomarker in ESCC.

Biodegradation of dibutyl phthalate by a novel endophytic Bacillus subtilis strain HB-T2 under in-vitro and in-vivo conditions.

The environmental prevalence and potential toxicity of dibutyl phthalate (DBP) motivate the attempt to develop feasible strategies to deal with DBP contamination. In this study, a strain of endphytic bacteria HB-T2 was isolated from sorrel roots and identified as Bacillus sp. by analysing its morphology, physiology, biochemistry and 16S rDNA sequence. The degradation efficiency of DBP by HB-T2 was almost identical under the temperature of 30∼40°C, but was significantly enhanced as the culture pH and inoculum size increases from 6.0 to 8.0, and 1% to 5% respectively. The degradation kinetics of DBP could be well described by the first-order kinetic model, with the degradation half-life ranging from 1.59 to 7.61 h when the initial concentrations of DBP were in the range of 5-20 mg/L. LC-MS analysis of the culture samples taken at varying intervals revealed monobutyl phthalate, phthalic acid and protocatechuic acid as the major metabolic intermediates during the degradation process. HB-T2 exhibited an excellent capability to degrade a wide range of phthalate esters (PAEs), especially butyl benzyl phthalate (BBP), dipentyl phthalate (DPP), and diisobutyl phthalate (DIBP). Inoculation of HB-T2 into Chinese cabbage (Brassica chinensis L.) growing in DBP-contaminated soils could significantly reduce the DBP levels in plant tissues and relieve the phytotoxic effects of DBP. Results of this study highlighted the great potential of this novel endophytic Bacillus subtilis strain HB-T2 for bioremediation of PAEs contamination and improvement of agricultural product safety by reducing PAEs accumulation in edible crops.

Causal Relations between Exposome and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose To explore the causal relationships of elements of the exposome with ischemic stroke and its subtypes at the omics level and to provide evidence for stroke prevention. Methods We conducted a Mendelian randomization study between exposure and any ischemic stroke (AIS) and its subtypes (large-artery atherosclerotic disease [LAD], cardioembolic stroke [CE], and small vessel disease [SVD]). The exposure dataset was the UK Biobank involving 361,194 subjects, and the outcome dataset was the MEGASTROKE consortium including 52,000 participants. @*Results@#We found that higher blood pressure (BP) (systolic BP: odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01 to 1.04; diastolic BP: OR, 1.03; 95% CI, 1.01 to 1.05; pulse pressure: OR, 1.03; 95% CI, 1.00 to 1.06), atrial fibrillation (OR, 1.18; 95% CI, 1.13 to 1.25), and diabetes (OR, 1.13; 95% CI, 1.07 to 1.18) were significantly associated with ischemic stroke. Importantly, higher education (OR, 0.69; 95% CI, 0.60 to 0.79) decreased the risk of ischemic stroke. Higher systolic BP (OR, 1.06; 95% CI, 1.02 to 1.10), pulse pressure (OR, 1.08; 95% CI, 1.02 to 1.14), diabetes (OR, 1.28; 95% CI, 1.13 to 1.45), and coronary artery disease (OR, 1.58; 95% CI, 1.25 to 2.00) could cause LAD. Atrial fibrillation could cause CE (OR, 1.90; 95% CI, 1.71 to 2.11). For SVD, higher systolic BP (OR, 1.04; 95% CI, 1.00 to 1.07), diastolic BP (OR, 1.06; 95% CI, 1.01 to 1.12), and diabetes (OR, 1.22; 95% CI, 1.10 to 1.36) were causal factors. @*Conclusions@#The study revealed elements of the exposome causally linked to ischemic stroke and its subtypes, including conventional causal risk factors and novel protective factors such as higher education.

Nomogram for predicting the overall survival of the patients with oesophageal signet ring cell carcinoma.

BACKGROUND: The purpose of this study was to explore the prognostic factors of oesophageal signet ring cell (SRC) carcinoma and to construct a nomogram for predicting the outcome of SRC carcinoma of oesophagus. METHODS: A total of 968 cases of oesophageal SRC carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Cases were divided into training cohort and validation cohort. Univariate and multivariable Cox analyses was performed to select the predictors of overall survival (OS for the nomogram. The performance of nomogram was validated with Harrell's concordance index (C-index), calibration curves and decision curve analysis (DCA). RESULTS: The 1- and 5-year OS in the training cohort were 0.446 and 0.146, respectively, and the 1- and 5-year OS in the validation cohort were 0.459 and 0.138. The independent prognostic factors for establishing the nomogram were marital status, invasion of the surrounding tissue, lymph node metastasis, distant metastasis, surgery and chemotherapy. The Harrell's c-index value of the training cohort and validation cohort were 0.723 and 0.708. In the calibration curves, the predicted survival probability and the actual survival probability have a considerable consistency. DCA indicated the favourable potential clinical utility of the nomogram. CONCLUSIONS: A nomogram to predict the OS of patients with oesophageal SRC carcinoma was established. The validation of the nomogram fully demonstrates its great performance.

Log odds of positive lymph nodes is a better prognostic factor for oesophageal signet ring cell carcinoma than N stage.

BACKGROUND: Signet ring cell carcinoma is a rare type of oesophageal cancer, and we hypothesized that log odds of positive lymph nodes (LODDS) is a better prognostic factor for oesophageal signet ring cell carcinoma. AIM: To explore a novel prognostic factor for oesophageal signet ring cell carcinoma by comparing two lymph node-related prognostic factors, log odds of positive LODDS and N stage. METHODS: A total of 259 cases of oesophageal signet ring cell carcinoma after oesopha-gectomy were obtained from the Surveillance, Epidemiology, and End Results database between 2006 and 2016. The prognostic value of LODDS and N stage for oesophageal signet ring cell carcinoma was evaluated by univariate and multivariate analyses. The Akaike information criterion and Harrell's C-index were used to assess the value of two prediction models based on lymph nodes. External validation was performed to further confirm the conclusion. RESULTS: The 5-year cancer-specific survival (CSS) and 5-year overall survival (OS) rates of all the cases were 41.3% and 27.0%, respectively. The Kaplan-Meier method showed that LODDS had a higher score of log rank chi-squared (OS: 46.162, CSS: 41.178) than N stage (OS: 36.215, CSS: 31.583). Univariate analyses showed that insurance, race, T stage, M stage, TNM stage, radiation therapy, N stage, and LODDS were potential prognostic factors for OS (P < 0.1). The multivariate Cox regression model showed that LODDS was an significant independent prognostic factor for oesophageal signet ring carcinoma patients after surgical resection (P < 0.05), while N stage was not considered to be a significant prognostic factor (P = 0.122). Model 2 (LODDS) had a higher degree of discrimination and fit than Model 1 (N stage) (LODDS vs N stage, Harell's C-index 0.673 vs 0.656, P < 0.001; Akaike information criterion 1688.824 vs 1697.519, P < 0.001). The results of external validation were consistent with those in the study cohort. CONCLUSION: LODDS is a superior prognostic factor to N stage for patients with oesophageal signet ring cell carcinoma after oesophagectomy.

Baseline determination, susceptibility monitoring and risk assessment to triflumezopyrim in Nilaparvata lugens (Stål).

Triflumezopyrim, a novel mesoionic chemical insecticide, is promoted as a powerful tool for control of susceptible and resistant hopper species in rice throughout Asia. For a newly commercialized insecticide it is important to establish susceptibility baseline, conduct susceptibility monitoring, and assess the risk of resistance via artificial selection to provide foundational information on designing resistance management strategy. The susceptibility baseline of triflumezopyrim was established for three rice planthopper species, Nilarpavata lugens (Stål), Sogatella furcifera (Horváth) and Laodelphax striatellus (Fallén). The LD50 of triflumezopyrim was 0.026, 0.032 and 0.094 ng/individual for the adults of the susceptible strains of S. furcifera, L. striatellus and N. lugens, respectively, determined by a topical application method. Using a rice stem (seedling) dipping method, the LC50 was determined as 0.042, 0.024 and 0.150 mg/L for the nymphs (3rd instar) of the three hopper species, respectively. In the meanwhile, the LC50 of Pyraxalt™ (triflumezopyrim 10% SC) was 0.064 mg/L for the N. lugens susceptible strain. Furthermore, the susceptibility of triflumezopyrim and other five neonicotinoid insecticides were monitored for N. lugens field populations collected from major rice production areas in China in 2015-2019. All monitored populations were susceptible to triflumezopyrim (0.5 to 3.9-fold resistance ratio), and showed no cross-resistance to the other five neonicotinoids. These results suggested that triflumezopyrim is a good option to control resistant N. lugens. In addition, a field-collected population of N. lugens was artificially selected with triflumezopyrim for 20 generations and resulted in 3.5-fold increase in LC50 from F0 and 6.0-fold increase from that of the susceptible strain. The realized heritability (h2) of resistance was estimated as 0.0451 by using threshold trait analysis. With this h2 value, the projected triflumezopyrim resistance development (a 10-fold increase in LC50) would be expected after 30.3 or 24.0 generations if 80% or 90% of the population was killed at each generation.

Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections.

Despite the growing global crisis caused by antimicrobial drug resistance among pathogenic bacteria, the number of new antibiotics, especially new chemical class of antibiotics under development is insufficient to tackle the problem. Our review focuses on an emerging class of antibacterial therapeutic agents that holds a completely novel mechanism of action, namely, inhibition of bacterial DNA polymerase IIIC. The recent entry of this new class into human trials may herald the introduction of novel drugs whose novel molecular target precludes cross-resistance with existing antibiotic classes. This review therefore examines the evolution of DNA pol IIIC inhibitors from the discovery of 6-(p-hydroxyphenylazo)uracil (HPUra) in the 1960s to the development of current first-in-class N7-substituted guanine drug candidate ACX-362E, now under clinical development for the treatment of Clostridioides difficile infection.

The role of plasma miRNAs in the diagnosis of pulmonary nodules.

BACKGROUND: In this study, we aimed to assess the clinical utility of detection of plasma microRNAs (miRNAs) in the diagnosis of pulmonary nodules. METHODS: Fifty-seven patients with pulmonary nodules who had undergone surgery were enrolled in our study from July 2016 to July 2017 at Sun Yat-sen University Cancer Center. We measured the expression levels of 12 miRNAs (miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210) in plasma samples of 57 patients, including 15 benign pulmonary nodules patients and 42 malignant pulmonary nodules patients. The levels of these miRNAs were detected by Real-time quantitative polymerase chain reaction (RT-PCR). The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of plasma miRNAs for non-small cell lung cancer (NSCLC). RESULTS: The expression levels of plasma miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210 are not associated with gender, age, pTNM stage, differentiation grade. The levels of miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miRNA-210 in NSCLC patients are significantly higher than those in benign pulmonary nodules patients (P<0.05). However, there are no significant differences for the expression levels of miRNA-155 and miRNA-126. For diagnosing NSCLC, the sensitivity and specificity was 66.7% and 80.0% for miRNA-17, 54.8% and 86.7% for miRNA-146a, 64.3% and 86.7% for miRNA-200b, 83.3% and 73.3% for miRNA-182, 54.8% and 80.0% for miRNA-221, 73.8% and 80.0% for miRNA-205, 78.6% and 73.3% for miRNA-7, 78.6% and 60.0% for miRNA-21, 78.6% and 73.3% for miRNA-145, 76.2% and 73.3% for miRNA-210. CONCLUSIONS: Plasma miRNAs (miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miRNA-210) have relatively high sensitivity and specificity for the diagnosis of NSCLC. These plasma miRNAs may be the potential biomarkers for early diagnosis of lung cancer.

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND: Aberrant expression of programmed cell death-ligand 1 (PD-L1) and protein 53 (P53) has been observed in various malignancies, and recently, the mechanism of PD-L1 regulation by P53 has been elucidated. We aimed to explore possible correlations between PD-L1 and P53 expression and the prognosis of patients with resected pulmonary lymphoepithelioma-like carcinoma (LELC). METHODS: A total of 67 consecutive patients with primary pulmonary LELC who underwent radical resection from January 2003 to December 2014 were enrolled in our study. Membranous PD-L1 and nuclear P53 expression were detected by immunohistochemical staining (IHC). RESULTS: Positive expression of PD-L1 in tumor cells (TCs), PD-L1 in tumor-infiltrating lymphocytes (TILs) and P53 was investigated in 44 patients (65.7%), 37 patients (55.2%), and 34 patients (50.7%), respectively. Using univariate and multivariable analysis, both PD-L1 (+) in TCs and P53 (+) were observed to be significantly independent prognostic factors associated with longer disease-free survival (DFS, P=0.037 and 0.039, respectively), along with early stage LELC (P=0.037), but had no association with overall survival (OS) (P>0.05). In the P53 (+) group, the rate of patients with PD-L1 (+) in TCs was significantly higher than in the P53 (-) group (85.3% vs. 45.5%, P=0.001). In addition, among the 45 patients who underwent adjuvant chemotherapy, DFS was significantly longer in patients with either PD-L1 (+) in TCs or P53 (+) (P=0.036 and 0.044, respectively). CONCLUSIONS: PD-L1 and P53 may be potential therapeutic targets for primary pulmonary LELC. PD-L1 (+) in TCs and P53 (+) were reliable predictors for longer DFS and benefits from adjuvant therapy in resected cases. Routine detection of these two indices in lung LELC may be warranted.

Tumor-stroma ratio (TSR) in non-small cell lung cancer (NSCLC) patients after lung resection is a prognostic factor for survival.

BACKGROUND: In recent years, the tumor-stroma ratio (TSR) has been considered to a new and independent predictive variable for the prognosis of some kinds of neoplasms. The objective of this study was to assess the prognostic significance of the TSR in non-small cell lung cancer (NSCLC). METHODS: A cohort of 261 NSCLC patients who underwent radical surgery of lung cancer were included in the present study. Two independent observers visually estimated the TSR on hematoxylin-eosin (H&E) stained tissue pathological slices. According to the proportion of stroma ≥50% or <50%, We separate the patients into two groups: those with stroma-poor and those with stroma-rich tumors. RESULTS: Both univariate and multivariate analyses disclosed that the TSR was associated with overall survival (OS) [hazard ratio (HR), 1.741; 95% confidence intervals (CI), 1.040-2.913 and HR, 1.904; 95% CI, 1.132-3.202, respectively]. The HR values for disease-free survival (DFS) were 1.795 (95% CI, 1.073-3.005) and 2.034 (95% CI, 1.210-3.420). The OS and DFS of patients with stroma-poor tumors were better than those with stroma-rich tumors. CONCLUSIONS: These results demonstrated that the TSR is a new prognostic factor for NSCLC. Stroma-poor tumors were associated with longer disease-free period and better prognosis than were stroma-rich tumors in NSCLC patients. The TSR may contribute to the development of individualized treatment for NSCLC in the future.

Presence, distribution and risk assessment of polycyclic aromatic hydrocarbons in rice-wheat continuous cropping soils close to five industrial parks of Suzhou, China.

Polycyclic aromatic hydrocarbons (PAHs) accumulated in agricultural soils are likely to threaten human health and ecosystem though the food chain, therefore, it is worth to pay more attention to soil contamination by PAHs. In this study, the presence, distribution and risk assessment of 16 priority PAHs in rice-wheat continuous cropping soils close to industrial parks of Suzhou were firstly investigated. The concentrations of the total PAHs ranged from 125.99 ng/g to 796.65 ng/g with an average of 352.94 ng/g. Phenanthrene (PHE), fluoranthene (FLT), benzo [a] anthracene (BaA) and pyrene (PYR) were the major PAHs in those soil samples. The highest level of PAHs was detected in the soils around Chemical plant and Steelworks, followed by Printed wire board, Electroplate Factory and Paper mill. The composition of PAHs in the soils around Chemical plant was dominated by 3-ring PAHs, however, the predominant compounds were 4, 5-ring PAHs in the soils around other four factories. Meanwhile, the concentration of the total PAHs in the soils close to the factories showed a higher level of PAHs in November (during rice harvest) than that in June (during wheat harvest). Different with other rings of PAHs, 3-ring PAHs in the soils around Chemical plant and Steelworks had a higher concentration in June. The results of principal component analysis and isomeric ratio analysis suggested that PAHs in the studied areas mainly originated from biomass, coal and petroleum combustion. The risk assessment indicated that higher carcinogenic risk was found in those sites closer to the industrial park.

Rifampicin-Resistance Mutations in the rpoB Gene in Bacillus velezensis CC09 have Pleiotropic Effects.

Rifampicin resistance (Rifr) mutations in the RNA polymerase ß subunit (rpoB) gene exhibit pleiotropic phenotypes as a result of their effects on the transcription machinery in prokaryotes. However, the differences in the effects of the mutations on the physiology and metabolism of the bacteria remain unknown. In this study, we isolated seven Rifr mutations in rpoB, including six single point mutations (H485Y, H485C, H485D, H485R, Q472R, and S490L) and one double point mutation (S490L/S617F) from vegetative cells of an endophytic strain, Bacillus velezensis CC09. Compared to the wild-type (WT) strain (CC09), the H485R and H485D mutants exhibited a higher degree of inhibition of Aspergillus niger spore germination, while the H485Y, S490L, Q472R, and S490L/S617F mutants exhibited a lower degree of inhibition due to their lower production of the antibiotic iturin A. These mutants all exhibited defective phenotypes in terms of pellicle formation, sporulation, and swarming motility. A hierarchical clustering analysis of the observed phenotypes indicated that the four mutations involving amino acid substitutions at H485 in RpoB belonged to the same cluster. In contrast, the S490L and Q472R mutations, as well as the WT strain, were in another cluster, indicating a functional connection between the mutations in B. velezensis and phenotypic changes. Our data suggest that Rifr mutations cannot only be used to study transcriptional regulation mechanisms, but can also serve as a tool to increase the production of bioactive metabolites in B. velezensis.

Systematic review of the association of diuretics with falls in the elderly / 中华护理杂志

Objective To systematically evaluate the association of diuretics with falls in the elderly. Methods Data of case-control studies and cohort studies of diuretics with falls in the elderly were collected by searching eleven electronic databases:MEDLINE,Embase,CENTRAL,AMED,CINAHL,Web of Science,Wiley online library, CBM,CNKI,VIP and WanFang Data from inception to July 2017. Study quality was assessed by the NOS scale. Meta-analysis was conducted by RevMan 5.3 software. Results A total of 17 studies involving 78284 patients were included(seven case-control studies and ten cohort studies). Meta-analysis showed that:①Case-control studies:crude OR showed that diuretics would not increase the risk of falls in elderly patients [OR=0.95,95%CI (0.66,1.38),P=0.80];adjusted OR showed that diuretics would increase the risk of falls in elderly patients[adjusted OR=1.25,95%CI (1.15,1.36),P<0.05]. ②Cohort studies:crude OR showed that diuretics would increase the risk of falls in elderly patients[OR=1.16,95%CI(1.02,1.32),P=0.03];adjusted OR showed that diuretics would not increase the risk of falls in elderly patients[adjusted OR=1.06,95%CI(0.92,1.22),P=0.43]. ③There was no statistically sig-nificant difference in the risk of falls among the elderly at different places,and there was no significant difference in the risk of falls among various diuretics (P>0.05). Conclusion Based on meta-analysis results of cohort studies that controlled confounders,and the results of diuretics in different places and different kinds,diuretics will not in-crease the risk of falls in older adults. Due to limited quantity and quality of included studies,the results need to be further confirmed by more rigorous clinical trials in the future.

The role of postoperative adjuvant chemotherapy for lymph node-positive esophageal squamous cell carcinoma: a propensity score matching analysis.

The prognosis of patients with lymph node-positive esophageal squamous cell carcinoma (ESCC) who primarily receive radical esophagectomy remains poor. In this study, we aimed to retrospectively investigate the role of postoperative adjuvant chemotherapy with docetaxel- or paclitaxel-based regimens in these patients. A total of 434 consecutive patients were included in this study who underwent radical esophagectomy and were pathologically confirmed to have lymph node-positive ESCC from January 2005 to December 2010 in our institution. Among these patients, 113 patients received postoperative adjuvant chemotherapy (Group SC), and 321 patients underwent surgery alone (Group S). Propensity score matching and multivariate analyses were used to compensate for differences in some baseline characteristics. After matching, Group SC had significantly longer median disease-free survival (DFS) than that in Group S (23.63 months vs. 16.70 months; p = 0.006); further subset analysis revealed that a benefit regarding DFS was only associated with patients with N1 stage and with tumor length <4.5 cm. The median overall survival (OS) was similar between the two groups (38.57 months for Group SC vs. 25.27 months for Group S; p = 0.05). Multivariate analysis showed that postoperative chemotherapy, length of the tumor, T status, and N category were significantly independent predictive factors of tumor recurrence (p < 0.05). Our data suggested that adjuvant chemotherapy with docetaxel- or paclitaxel-based regimens could significantly improve DFS for patients with N1 stage and tumor length <4.5 cm ESCC and that it could potentially prolong OS for patients with lymph node-positive ESCC after surgery, compared with surgery alone. These results warrant further confirmation in prospective, randomized trials.