Structural analysis of molybdate binding protein ModA from Klebsiella pneumoniae.

Klebsiella pneumoniae, a facultative anaerobe, relies on acquiring molybdenum to sustain growth in anaerobic conditions, a crucial factor for the pathogen to establish infections within host environments. Molybdenum plays a critical role in pathogenesis as it forms an essential component of cofactors for molybdoenzymes. K. pneumoniae utilizes the ABC (ATP-Binding-Cassette) transporter encoded by the modABC operon for uptake of the group VI elements molybdenum and tungsten. In this study, we determined the X-ray crystal structures of both the molybdenum-free and molybdenum-bound substrate-binding protein (SBP) ModA from Klebsiella pneumoniae to 2.00 Å and 1.77 Å resolution respectively. ModA crystallizes in the space group P222 with a single monomer in one asymmetric unit. The purified protein remained soluble and specifically bound molybdate and tungstate with Kd values of 6.3 nM and 5.2 nM, respectively. Tungstate competes with molybdate by binding to ModA, resulting in enhanced antimicrobial activity. These data provide a starting point for structural and functional analyses of molybdate transport in K. pneumoniae.

Fine particulate matter (PM2.5) trends from land surface changes and air pollution policies in China during 1980-2020.

High levels of fine particulate matter (PM2.5) pose a severe air pollution challenge in China. Both land use changes and anthropogenic emissions can affect PM2.5 concentrations. Only a few studies have addressed the long-term impact of land surface changes on PM2.5 in China. We conducted a comprehensive analysis of PM2.5 trends over China using the Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2) during 1980-2020. The monthly mean PM2.5 concentrations of MERRA-2 were evaluated across mainland China against independent surface measurements from 2013 to 2020, showing a good agreement. For the trend analysis, China was subdivided into six regions based on land use and ambient aerosols types. Our results indicate an overall significant PM2.5 increase over China during 1980-2020 with major changes in-between. Notwithstanding continued urbanization and associated anthropogenic activities, the PM2.5 reversed to a downward trend around 2007 over most regions except for the part of China that is most affected by desert dust. Statistical analysis suggests that PM2.5 trends during 1980-2010 were associated with urban expansion and deforestation over eastern and southern China. The trend reversal around 2007 is mainly attributed to Chinese air pollution control measures. A multiple linear regression analysis reveals that PM2.5 variability is linked to soil moisture and vegetation. Our results suggest that land use and land cover changes as well as pollution controls strongly influenced PM2.5 trends and that drought conditions affect PM2.5 particularly over desert and forest regions of China. This work contributes to a better understanding of the changes in PM2.5 over China.

Insight into the pollution characteristics of road and roof runoff in Changsha, China.

Non-point source pollution from rainwater runoff presents a serious challenge for urban water management in many cities undergoing urbanization and experiencing climate change. To alleviate water resource conflicts in Changsha, China, this study comprehensively evaluated the pollution characteristics and first flush effect (FFE) of runoff from asphalt roads and colored steel plate roofs under seven rainfall events in April-May 2022. The runoff was collected and purified using bioretention ponds. The results showed that the peak runoff pollutant concentrations occurred within the first 20 min of runoff generation and then decreased to relatively stable levels, with maximum total suspended solids (TSS) concentration and chemical oxygen demand (CODCr) reaching 873.5 and 207.32 mg/L, respectively, for road runoff and 162 and 73.31 mg/L for roof runoff, respectively. The main pollutants were TSS and CODCr, followed by ammonia nitrogen (NH4+-N), nitrate nitrogen (NO3--N), total phosphorus (TP), and nitrite nitrogen (NO2--N). Concentrations of pollutants and FFE for roof runoff were lower than those for road runoff. Road runoff had a more obvious FFE for TP and NH4+-N, whereas the roof runoff showed the presence of TP and NO3--N. An important implication is that treating the first 30% of surface runoff from rainfall events with long antecedent dry days or high rainfall amounts is necessary to improve water quality before discharge or utilization. The study also found that road and roof runoff, after treatment with bioretention ponds, exhibit good water quality, thus, allowing their use as reclaimed water or for miscellaneous purposes in urban areas. Overall, this study provides useful information for designing management measures to mitigate runoff pollution and reuse in Changsha.

Serum and tissue vascular endothelial growth factor predicts prognosis in hepatocellular carcinoma patients after partial liver resection.

BACKGROUND/AIMS: To explore the effect of vascular endothelial growth factor (VEGF) expression on prognosis of hepatocellular carcinoma (HCC) after partial liver resection. METHODOLOGY: The expression of VEGF in 64 preoperative serum and resection specimens of HCC, confirmed by pathology, was detected by enzymelinked immunosorbent assay (ELISA) and immunohistochemistry. Correlations of VEGF level to clinicopathological features were analyzed. Cox regression model was used to analyze the recurrence risk factors after hepatectomy. RESULTS: Serum level of VEGF in HCC patients was 334.50±247.62pg/mL, significantly higher than healthy control group (p<0.01); it was also significantly higher in recurrent group than in non-recurrent group (p<0.05). VEGF was expressed in cytoplasm of HCC specimens. The positive rates of VEGF was significantly higher in recurrent group than in non-recurrent group (85.0% vs. 54.5%, p<0.05). The 1-, 2- and 3-year disease-free survival rates were significantly higher in VEGF(-) group than in VEGF(+) group (81.3% vs. 52.2%, 68.8% vs. 33.3%, and 62.5% vs. 29.1%, p<0.01). The overall survival rates of VEGF(-) subgroup was borderline significant higher than that of VEGF(+) subgroup (p=0.068). Multivariate analysis revealed that preoperative macroscopically disseminated nodules, tumor micrometastasis, serum and tissue VEGF level were independent recurrence risk factors. CONCLUSIONS: Serum and tissue VEGF level of HCC patients ascends distinctly, correlates to the recurrence of HCC after partial liver resection which can be used to estimate the risk of postoperative recurrence of HCC.

Ala499Val (C>T) and Lys939Gln (A>C) polymorphisms of the XPC gene: their correlation with the risk of primary gallbladder adenocarcinoma--a case-control study in China.

Genetic variations in the gene XPC may be associated with increased risk for gallbladder cancer (GBC). In this study, we detected two non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) in 334 cases of GBC and 329 subjects of hospital-based age- and sex frequency-matched controls in China using a polymerase chain reaction-restriction fragment length polymorphism assay. Allelic association analysis for the two single-nucleotide polymorphisms (SNPs) showed that the risk allele T of Ala499Val was significantly associated with GBC [odds ratio (OR)=1.40, 95% confidence interval (CI): 1.11-1.76, P=0.005), with a population attributive risk of 5.3%. Logistic regression analysis revealed that Ala499Val CT heterozygote (OR=1.56, 95% CI: 1.13-2.14, P=0.002) and TT homozygote (OR=1.93, 95% CI: 1.04-3.55, P=0.048) had a significantly increased risk compared with CC homozygotes. Genetic analysis suggested that either the SNPs directly exert an effect or the linked functional gene impact of the disease trait likely follows an additive or dominant model. Gene interaction analysis demonstrated that the effects of XPC diplotypes (defined as the number of risk genotypes at the two SNP loci) were highly dependent on gallstone. The data from this case-control study indicated that XPC exonic variants contributed to the risk of GBC in this Chinese population.

Nodal regulates bladder cancer cell migration and invasion via the ALK/Smad signaling pathway.

BACKGROUND: Bladder cancer is the most common malignant tumor of the urinary tract. We aimed to explore the biological role and molecular mechanism of Nodal in bladder cancer. MATERIALS AND METHODS: The expression of Nodal in bladder cancer tissues and cells was determined by quantitative real-time polymerase chain reaction. The effect of silencing of Nodal on cell proliferation, clone formation, and migration and invasion was evaluated by MTT cell proliferation assay, colony formation, and transwell assays, respectively. Western blot analysis was employed to detect the expression of proliferation- and invasion-related proteins and proteins involved in ALK/Smad signaling. RESULTS: We found that the expression of Nodal was significantly increased in bladder cancer tissues and cell lines. Downregulation of Nodal effectively weakened cell proliferation, clone formation, and cell migration and invasion abilities. The protein expression levels of CDC6, E-cadherin, MMP-2, and MMP-9 were also altered by downregulation of Nodal. Knockdown of Nodal also blocked the expression of ALK4, ALK7, Smad2, and Smad4, which are involved in ALK/Smad signaling. Additionally, the ALK4/7 receptor blocker SB431542 reversed the promotive effects of Nodal overexpression on bladder cancer cell proliferation, migration, and invasion. CONCLUSION: Our study indicated that Nodal functions as an oncogene by regulating cell proliferation, migration, and invasion in bladder cancer via the ALK/Smad signaling pathway, thereby providing novel insights into its role in bladder cancer treatment.

hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population.

The human oxoguanine glycosylase 1(hOGG1) gene encodes a DNA glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2-deoxyguanine) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in the risk for adenocarcinoma of the gallbladder, we tested the association of this polymorphism with gallbladder cancer in a Chinese population-based, case control study of 204 cases and 209 controls. The subjects were genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) assay. The association between the genetic polymorphism of this gene and risk of the cancer was examined by using a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 37.3%; Ser/Cys, 53.6% and Cys/Cys, 9.1%) was significantly different from that among gallbladder cancer cases (Ser/Ser, 43.1%; Ser/Cys, 36.3% and Cys/Cys, 20.6%). Significantly increased risk for gallbladder cancer was both the hOGG1 326Ser/Cys (Odds ratio [OR] = 1.9, 95% confidence interval (CI) = 1.0-3.7) and hOGG1 326Cys/Cys genotypes (OR = 4.5, 95% CI = 1.1-22.4). We observed no statistically significant association between hOGG1 genotype and gallbladder cancer association in gallstone absence. In contrast, a near-significant increase in risk for gallbladder cancer was observed for gallstone presence with the hOGG1 326Ser/Cys genotype (OR = 2.2, CI = 1.4-3.5) whereas a significant increase in association for gallbladder cancer was observed for gallstone presence with the 326Cys/Cys genotype (OR = 6.1, CI = 2.1-27.2). These data corresponded with the fact that a significant trend towards increased association for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallstone presence(p < 0.001, chi(2) trend test)but not in gallstone absence(p = 0.89, chi(2) trend test). A significant increase in risk for gallbladder cancer was observed for larger gallstone (those with stone diameters 2 cm or greater) with the hOGG1 326Ser/Cys(OR = 1.9, 95% CI = 1.1-2.9) and hOGG1 326Cys/Cys genotypes(OR = 5.9, 95% CI = 1.6-18.0). These data are consistent with the observation that a significant trend towards increased risk for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallbladder cancer patients with larger gallstone (p < 0.001, chi(2) trend test). However, we observed no statistically significant association between hOGG1 genotype and gallbladder cancer risk in gallbladder cancer patients with smaller gallstone (those with stone diameters 2 cm smaller) (hOGG1 326Ser/Cys:OR = 2.2, 95% CI = 0.8-4.0; hOGG1 326Cys/Cys:OR = 2.9, 95% CI = 0.6-29.4; p = 0.06, chi(2) tread test). These results suggest that hOGG1 Ser326Cys polymorphism is associated with gallbladder cancer risk.

[Influence of preoperative transcatheter arterial chemoembolism on immunity after hepatectomy in patients with liver cancer].

BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolism (TACE) is one of important therapeutic method for hapatocarcinoma. Post-operative TACE could reduce recurrent rate definitely. However, there were much debate about the function and effect of preoperative TACE. This study was conducted to evaluate the effect of preoperative TACE on immunity of the patients with recurrent hepatocarcinoma who performed combined treatment. METHODS: The patients with primary hepatocarcinoma who performed operative TACE were collected. The dynamic changes of cellular immunity and humoral immunity in pre-intervention, pre-operation, combined treatment after recurrence periods were determined by flow cytometry and ELISA, and were compared with the data of the recurrent patients after simple operation. RESULTS: In TACE group: CD3, CD4, CD56 decreased slightly; serum IgM increased slightly, with no significant difference compared to pre-intervention (P < 0.05); At the time of combined treatment after recurrence, CD8 increased and CD4/CD8 decreased (0.8 +/- 0.3%), the immune suppression was slight. In sample operation group, CD3, CD4, CD56 were 49.0 +/- 9.1%, 19.0 +/- 4.8%, 18.6 +/- 9.9%; the immune suppression was severe. The operation significantly decreased the patients' CD3, CD4, and CD19. The pathologic results showed that the tumor capsule, intrahepatic daughter foci, tumor thrombus, and the radical degree in preoperative group were much better than those in simple operation group. CONCLUSION: The preoperative TACE do not obviously influence the immunity; furthermore, it can relieve the immune depression after operation and is a remedy of the surgical treatment. It is important to grasp the indication of preoperative TACE.