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Leptospirosis is a public health challenge in Sabah State of Malaysian Borneo. Rapid urbanization, rural-to-urban migration, and undocumented immigration in Sabah have increased the pressure on the urban garbage disposal system. Rodents and other small animals thrive under these conditions. We hypothesized that urban sanitation workers would be at risk of developing leptospirosis. see more In total, 303 urban sanitation workers with a mean age of 42.6 years were enrolled in this study. The serum samples collected from these workers were subjected to the microscopic agglutination test (MAT), PCR and nucleotide sequencing of the amplicons to confirm the presence of Leptospira. The phylogenetic analysis using the neighbor joining method was performed to assess whether they were pathogenic. In this study 43.8% (133/303) of the samples were MAT-seropositive and among them, 29 (21.8%) were positive by PCR. Nucleotide sequencing of the amplicons confirmed the presence of Leptospira. Phylogenetic analysis showed that our strains belonged to the pathogenic group of Leptospira. A high proportion of urban sanitation workers were seropositive for leptospirosis, and a considerable number were PCR positive for Leptospira, thereby indicating asymptomatic infections. Further research is needed to confirm whether this is a transient phenomenon or antibiotic therapy is required.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Intrinsic and acquired drug resistance represent fundamental barriers to the cure of high-grade serous ovarian carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian cancer deaths. Defects in homologous recombination (HR) DNA repair are key determinants of sensitivity to chemotherapy and poly-ADP ribose polymerase inhibitors. Restoration of HR is a common mechanism of acquired resistance that results in patient mortality, highlighting the need to identify new therapies targeting HR-proficient disease. We have shown promise for CX-5461, a cancer therapeutic in early phase clinical trials, in treating HR-deficient HGSC.

Herein, we screen the whole protein-coding genome to identify potential targets whose depletion cooperates with CX-5461 in HR-proficient HGSC.

We demonstrate robust proliferation inhibition in cells depleted of DNA topoisomerase 1 (TOP1). Combining the clinically used TOP1 inhibitor topotecan with CX-5461 potentiates a G2/M cell cycle checkpoint arrest in multiple HR-proficient HGSC cell lines. The combination enhances a nucleolar DNA damage response and global replication stress without increasing DNA strand breakage, significantly reducing clonogenic survival and tumour growth in vivo.

Our findings highlight the possibility of exploiting TOP1 inhibition to be combined with CX-5461 as a non-genotoxic approach in targeting HR-proficient HGSC.

Our findings highlight the possibility of exploiting TOP1 inhibition to be combined with CX-5461 as a non-genotoxic approach in targeting HR-proficient HGSC.Activated coke (AC) has great potential in the field of low-temperature NO removal (DeNOx), especially the branch prepared by blending modification. In this study, the AC-based pyrolusite and/or titanium ore blended catalysts were prepared and applied for DeNOx. The results show blending pyrolusite and titanium ore promoted the catalytic performance of AC (Px@AC, Tix@AC) clearly, and the co-blending of two of them showed a synergistic effect. The (P/Ti-1/2)15@AC performed the highest NO conversion of 66.4%, improved 16.9% and 16.0% respectively compared with P15@AC and Ti15@AC. For the (P/Ti-1/2)15@AC DeNOx, its relative better porous structure (SBET = 364 m2/g, Vmic = 0.156 cm3/g) makes better mass transfer and more active sites exposure, stronger surface acidity (C-O, 19.43%; C=O, 4.16%) is more favorable to the NH3 adsorption, and Ti, Mn and Fe formed bridge structure fasted the lactic oxygen recovery and electron transfer. The DeNOx of (P/Ti-1/2)15@AC followed both the E-R and L-H mechanism, both the gaseous and adsorbed NO reacted with the activated NH3 due to the active sites provided by both the carbon and titanium.Long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis of infectious diseases, but the role of lncRNAs in herpes simplex virus 1 (HSV-1) infection remains unknown. Using RNA sequencing analysis, we explored lncRNAs that were highly expressed in murine retinal photoreceptor cell-derived 661W cells infected with HSV-1. U90926 RNA (522 nucleotides) was the most upregulated lncRNA detected post HSV-1 infection. The level of U90926 RNA was continuously increased post HSV-1 infection, reaching a 100-fold increase at 24 h. Cellular fractionation showed that U90926 RNA was located in the nucleus post HSV-1 infection. Downregulation of U90926 expression by RNA interference markedly suppressed HSV-1 DNA replication (80% reduction at 12 h post infection) and HSV-1 proliferation (93% reduction at 12 h post infection) in 661W cells. The survival rates of U90926-knockdown cells were significantly increased compared to those of control cells (81% and 21%, respectively; p  less then  0.0001). Thus, lncRNA U90926 is crucial for HSV-1 proliferation in retinal photoreceptor cells and consequently leads to host cell death by promoting HSV-1 proliferation.In our previous study, we found that pyruvate kinase isoform M2 (PKM2) was secreted from the skeletal muscle and extended axons in the cultured neuron. Indirect evidence suggested that secreted PKM2 might relate to the recovery of motor function in spinal cord injured (SCI) mice. However, in vivo direct evidence has not been obtained, showing that extracellular PKM2 improved axonal density and motor function in SCI mice. In addition, the signal pathway of extracellular PKM2 underlying the increase in axons remained unknown. Therefore, this study aimed to identify a target molecule of extracellular PKM2 in neurons and investigate the critical involvement of extracellular PKM2 in functional recovery in the chronic phase of SCI. Recombinant PKM2 infusion to the lateral ventricle recovered motor function in the chronic phase of SCI mice. The improvement of motor function was associated with axonal increase, at least of raphespinal tracts connecting to the motor neurons directly or indirectly. Target molecules of extracellular PKM2 in neurons were identified as valosin-containing protein (VCP) by the drug affinity responsive target stability method.