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Certain miRNAs, called oncomiRs, play a causal role in the onset and maintenance of cancer when overexpressed, thus, representing a potential new class of targets for therapeutic intervention. RNA-cleaving DNAzymes, mainly aimed at mRNA, have shown potential as therapeutic agents for various diseases. However, it's rarely reported that a DNAzyme was used for intracellular miRNA cleavage to suppress cell growth. Herein, we have developed a MnO2 nanosheet-mediated photo-controlled DNAzyme (NPD) for intracellular miRNA cleavage to suppress cell growth. MnO2 nanosheets adsorb photocaged DNAzymes, protect them from enzymatic digestion, and efficiently deliver them into cells. In the presence of intracellular glutathione (GSH), MnO2 nanosheets are reduced to Mn2+ ions, which serve as cofactors of the 8–17 DNAzyme for miRNA cleavage. Once the DNAzyme is activated by light, it can cyclically cleave endogenous miR-21 inside cells, which would suppress cancer cell migration and invasion, and finally induce cancer cell apoptosis. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a multifactoral and polygenic disease with high prevalence in Southeast Asia and Southern China. Environmental factors and genetic susceptibility play important roles in NPC pathogenesis. In the present study, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in nuclear factor-kappa B (NFκB) and its inhibitor (IκBα ) conferred consistent risks for NPC. Four putatively functional SNPs (NFκB1: rs28362491del>ins ATTG; NFκB2: rs12769316G>A; IκBα : rs2233406C>T and rs696G>A) were analyzed to evaluate their associations with NPC risk in total 1590 NPC cases and 1979 cancer-free controls. We found that the rs28362491 insATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of NPC (odds ratio [OR]=1.30, 95% confidence interval [CI]=1.09–1.55, and P=2.80×10-3) compared with the del/del homozygous genotype. The rs696AA variant in IκBα had an increased risk of NPC (OR=1.41, 95% CI=1.20–1.66, and P=2.28×10-5) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a. Furthermore, both adverse genotypes of NFκB/IκBα and their interaction also exerted an increased risk on NPC. Taken together, Our findings indicated that genetic variants in NFκB1 (rs28362491del>ins ATTG) and IκBα (rs696G>A) and their synergistic effect might contribute to NPC predisposition. [ABSTRACT FROM AUTHOR]

Lung inflammation is the major pathogenetic feature for both chronic obstructive pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFκB) and its inhibitor (IκB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFκB/ IκB confer consistent risks for COPD and lung cancer. Four putative functional SNPs ( NFκB1: −94del>insATTG; NFκB2: −2966G>A; IκBα: −826C>T, 2758G>A) were analyzed in southern and validated in eastern Chineses to test their associations with COPD risk in 1,511 COPD patients and 1,677 normal lung function controls, as well as lung cancer risk in 1,559 lung cancer cases and 1,679 cancer-free controls. We found that the −94ins ATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of COPD (OR 1.27, 95 % CI 1.06-1.52) and promoted COPD progression by accelerating annual FEV1 decline ( P = 0.015). The 2758AA variant in IκBα had an increased risk of lung cancer (OR 1.53, 95 % CI 1.30-1.80) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a but not hsa-miR-34b. Furthermore, both adverse genotypes exerted effect on increasing lung cancer risk in individuals with pre-existing COPD, while the −94del>insATTG did not in those without pre-existing COPD. However, no significant association with COPD or lung cancer was observed for −2966G>A and −826C>T. Our data suggested a common susceptible mechanism of inflammation in lung induced by genetic variants in NFκB1 (−94del>ins ATTG) or IκBα (2758G>A) to predict risk of COPD or lung cancer. [ABSTRACT FROM AUTHOR]

Raoultella ornithinolytica is a poorly understood opportunistic pathogen, and the underlying mechanisms of its multidrug resistance and pathogenicity have not yet been comprehensively investigated. The multidrug‐resistant (MDR) strain WM1 was isolated from the blood of a male patient in Tianjin, China, in 2018. Here, we describe the complete genome and provide a genomic analysis of R. ornithinolytica WM1. The isolate was resistant to all tested antimicrobials except amikacin, tobramycin, and tigecycline. Two plasmids, pWM1‐1 (IncHI5) and pWM1‐2 (IncR), carried multidrug‐resistance regions. A large antimicrobial resistance island region resided on pWM1‐1 and exhibited mosaic structures resulting from the acquisition of complex integrations of variable regions, including genes conferring resistance to multiple classes of antimicrobials. Moreover, WM1 possessed virulence‐related elements that encode several virulence factors, including type I fimbriae, Escherichia coli common pilus, type II and VI secretion systems, yersiniabactin, enterobactin, and surface polysaccharide, indicating pathogenic potential. Furthermore, the core genome phylogeny and pan‐genome analyses revealed extensive genetic diversity. Our analysis indicates the need for stringent infection control, antimicrobial stewardship, periodic resistance monitoring, and rational medication to address potential threats posed by MDR R. ornithinolytica strains. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polyhydroxy alcohols can make the MP structure more compact. • Polyhydroxy alcohols can form interfacial layer to protect MP. • Polyhydroxy alcohols interact with actin especially by hydrogen bonds. • Polyhydroxy alcohol-mediated curing can be a novel curing method. This study aimed to investigate the structural and functional changes in polyhydroxy alcohol-mediated curing on pork myofibrillar proteins (MP). The results obtained from total sulfhydryl groups, surface hydrophobicity, fluorescence and Raman spectroscopies, and solubility demonstrated that the polyhydroxy alcohols (especially xylitol) significantly modified the MP tertiary structure, making this structure more hydrophobic and tighter. However, no significant differences were detected in the secondary structure. Furthermore, the thermodynamic analysis revealed that polyhydroxy alcohols could develop an amphiphilic interfacial layer on the MP surface, significantly increasing the denaturation temperature and enthalpy of denaturation (P < 0.05). On the other hand, the molecular docking and dynamics simulations showed that polyhydroxy alcohols interact with actin mainly through hydrogen bonds and van der Waals forces. Therefore, this could help reduce the effect of high-content salt ions on MP denaturation and improve the cured meat quality. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, we constructed a viable therapeutic vaccine of recombinant M. smegmatis mediated IL-12/GLS (granulysin) gene transfer into murine macrophages to exert the immunotherapy effects on the Mycobacterium tuberculosis infection. We tested this recombinant therapeutic vaccine in an in vivo study to determine its capability of stimulating host specific immune responses against M. tuberculosis. BALB/c mice intranasally immunized with the therapeutic vaccine developed an efficient Th1 protective immune response against M. tuberculosis which was equal to that of the BCG strain. Inoculation intranasally with this viable vaccine induced high level of serum IFN-gamma, IL-12 and IgG2a. The viable vaccine was capable of inducing purified protein derivative (PPD) antigen-specific splenocytes proliferation and IFN-gamma production from T cells in spleens of the immunized mice. In addition, intranasally inoculation with the viable vaccine can induce PPD antigen-specific sIgA production in the broncho-alveolar lavage fluid (BALF) of the immunized mice. No change of IL-4 level was found in all groups. The therapeutic mechanism of this viable vaccine against M. tuberculosis infection observed here appeared to be a result of the specific Th1 immune response activated by mycobacterium antigen from M. smegmatis and the expression of sIL-12/GLS in alveolar macrophages via the M. smegmatis-mediated gene transfer method. This research demonstrates that the therapeutic gene can be introduced into a host by viable mycobacteria works to induce the host specific immune response against M. tuberculosis infection in vivo. Since this therapeutic vaccine can strongly induce specific Th1 responses against M. tuberculosis in BALB/c mice and has no obviously harmfulness to the host simultaneously, the recombinant vaccine might be a potential candidate therapeutic vaccine against tuberculosis. [Copyright &y& Elsevier]

• An integrated process was proposed to treat highly concentrated toilet wastewater. • The integrated process significantly improved the COD and nitrogen removal compared with AAO. • EC can ensure that the effluent quality meets the mandated requirements. • The economic analysis confirmed that the integrated process was feasible. Low-flush toilets have received increasing attention in relation to the water crisis in water-scarce regions because the vacuum flushing system (VFS) can reduce the amount of water required for flushing by approximately 80%. However, low-flush toilet wastewater exhibits the characteristics of high pollutant concentrations and cannot be directly discharged into urban pipe networks; therefore, decentralized wastewater treatment is necessary. Traditional control process (mainly consisting of hydrolysis acidification tank (HAT), anaerobic-anoxic–oxic (AAO) tank, coagulation sedimentation filtration tank and UV disinfection) was unsatisfactory for treating this type of wastewater. Therefore, a newly designed integrated biological-electrocatalytic (AAIE) process (mainly consisting of anaerobic baffled reactor (ABR), alternating internal circulation activated sludge process (AICS), and electrocatalytic oxidation (EC)) was introduced. ABR achieved large amounts of organic matter removal, the organic biodegradation kinetics revealed that the maximum specific degradation rate of the ABR was 0.050 to 0.082 d−1; AICS further removed COD and nitrogen, the denitrification rate and growth rate of nitrifying bacteria in the AICS were in the range of 0.079–0.121 kg/(kg·d) and 0.32–1.54 d−1, respectively. The temperature and organic loading rate were identified as two key parameters for ABR and AICS to remove pollutants, therefore, EC was the guarantee to make the effluent quality met the directly discharge standard of China (GB 18918-2002), especially in winter. The results showed that the AAIE process presented COD, colority, ammonia and total nitrogen removal rates of 98.5 ± 0.7%, 98.8 ± 0.6%, 97.0 ± 0.4% and 93.4 ± 2.6%, respectively, which were considerably higher than those of the control process. Furthermore, the economic analysis indicated that the AAIE process was feasible and may help to pave the way for wide application of biological-electrocatalytic processes for highly concentrated toilet wastewater treatment. [ABSTRACT FROM AUTHOR]