Lanthanide Doping into All-Inorganic Heterometallic Halide Layered Double Perovskite Nanocrystals for Multimodal Visible and Near-Infrared Emission.

The introduction of lanthanide ions (Ln3+) into all-inorganic lead-free halide perovskites has captured significant attention in optoelectronic applications. However, doping Ln3+ ions into heterometallic halide layered double perovskite (LDP) nanocrystals (NCs) and their associated doping mechanisms remain unexplored. Herein, we report the first colloidal synthesis of Ln3+ (Yb3+, Er3+)-doped LDP NCs utilizing a modified hot-injection method. The resulting NCs exhibit efficient near-infrared (NIR) photoluminescence in both NIR-I and NIR-II regions, achieved through energy transfer down-conversion mechanisms. Density functional theory calculations reveal that Ln3+ dopants preferentially occupy the Sb3+ cation positions, resulting in a disruption of local site symmetry of the LDP lattices. By leveraging sensitizations of intermediate energy levels, we delved into a series of Ln3+-doped Cs4M(II)Sb2Cl12 (M(II): Cd2+ or Mn2+) LDP NCs via co-doping strategies. Remarkably, we observe a brightening effect of the predark states of Er3+ dopant in the Er3+-doped Cs4M(II)Sb2Cl12 LDP NCs owing to the Mn component acting as an intermediate energy bridge. This study not only advances our understanding of energy transfer mechanisms in doped NCs but also propels all-inorganic LDP NCs for a wider range of optoelectronic applications.

Type-I CdS/ZnS Core/Shell Quantum Dot-Gold Heterostructural Nanocrystals for Enhanced Photocatalytic Hydrogen Generation.

Developing Type-I core/shell quantum dots is of great importance toward fabricating stable and sustainable photocatalysts. However, the application of Type-I systems has been limited due to the strongly confined photogenerated charges by the energy barrier originating from the wide-bandgap shell material. In this project, we found that through the decoration of Au satellite-type domains on the surface of Type-I CdS/ZnS core/shell quantum dots, such an energy barrier can be effectively overcome and an over 400-fold enhancement of photocatalytic H2 evolution rate was achieved compared to bare CdS/ZnS quantum dots. Transient absorption spectroscopic studies indicated that the charges can be effectively extracted and subsequently transferred to surrounding molecular substrates in a subpicosecond time scale in such hybrid nanocrystals. Based on density functional theory calculations, the ultrafast charge separation rates were ascribed to the formation of intermediate Au2S layer at the semiconductor-metal interface, which can successfully offset the energy confinement introduced by the ZnS shell. Our findings not only provide insightful understandings on charge carrier dynamics in semiconductor-metal heterostructural materials but also pave the way for the future design of quantum dot-based hybrid photocatalytic systems.

Associations between the levels of circulating inflammatory adipokines and the risk of type 2 diabetes in Chinese male individuals: A case-control study.

BACKGROUND: Whether the levels of circulating inflammatory adipokines affect the progression of type 2 diabetes (T2D) remains unclear. This study aimed to assess the association between circulating inflammatory adipokine levels and risk of T2D. METHODS: This case-control study involved 130 individuals consisting of 66 healthy controls (Control group) and 64 patients with T2D (T2D group) in Lishui Municipal Central Hospital from January 2017 to June 2017. Multivariate logistic regression analysis was applied to assess the associations between circulating inflammatory adipokine levels and the risk of T2D. RESULTS: There were significant differences in the levels of adiponectin (p = 0.013) and visfatin (p < 0.001) between the T2D and Control groups. In contrast, no significant differences in leptin (p = 0.113), TNF-α (p = 0.632), and IL-6 (p = 0.156) levels were found between the groups. Multivariate logistic regression indicated that elevated visfatin level was associated with an increased risk of T2D (OR: 3.543; 95% CI: 1.771-7.088; p < 0.001), while adiponectin (OR: 1.946; 95% CI: 0.925-4.094; p = 0.079), leptin (OR: 3.723; 95% CI: 0.788-17.583; p = 0.097), TNF-α (OR: 1.081; 95% CI: 0.911-1.281; p = 0.373), and IL-6 (OR: 0.878; 95% CI: 0.657-1.173; p = 0.379) were not associated with the risk of T2D. CONCLUSIONS: This study found elevated visfatin levels are associated with an increased risk of T2D, while adiponectin, leptin, TNF-α, and IL-6 are not. These findings should be further verified by a large-scale prospective study.

Characterization of a Novel Carbapenem-Resistant Klebsiella michiganensis Strain Coharboring the blaSIM-1, blaOXA-1, blaCTX-M-14, qnrS, and aac(6')-Ib-cr Genes.

Carbapenem-resistant Klebsiella michiganensis (CRKM) and Klebsiella oxytoca (CRKO) strains have occasionally been reported to cause severe infections. However, SIM-producing K. michiganensis strains have never been described. In this study, we phenotypically and genetically characterized 6 CRKM and CRKO strains isolated over the past 10 years at a Chinese tertiary hospital. All six strains were positive for the mCIM test, and five were positive for the MBL test. Carbapenemase-encoding genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-23, blaOXA-24, blaOXA-51, and blaOXA-58) and another 12 resistance genes were screened by PCR, and blaKPC, blaNDM, and blaIMP were identified in five strains. However, the CRKM strain KM41, which was resistant to IPM and MEM with minimum inhibitory concentrations (MICs) of 4 µg/ml and 16 µg/ml, respectively, had positive mCIM and MBL results but lacked the eight carbapenemase-encoding genes. Whole-genome sequencing of the KM41 strain revealed more than 20 drug resistance genes; in particular, blaSIM-1, blaOXA-1, blaCTX-M-14, qnrS, aac(6')-Ib-cr, aadA17, and aar-3 were found to be located in a single plasmid. To the best of our knowledge, this is the first description of a K. michiganensis strain coharboring blaSIM-1, blaOXA-1, blaCTX-M-14, qnrS, and aac(6')-Ib-cr in China.

Association of thyroid hormone with body fat content and lipid metabolism in euthyroid male patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: This study aimed to explore the associations of thyroid hormones with body fat content and lipid metabolism in euthyroid male patients with type 2 diabetes mellitus (T2DM). METHODS: In January 2017, a cross sectional study, 66 male patients with T2DM who met the World Health Organization diagnostic criteria of 1999 who were ≥ 18.0 years and had normal thyroid function were recruited at a tertiary hospital. The categories of thyroid hormones (free triiodothyronine [FT3], free thyroxine [FT4], and thyroid-stimulating hormone [TSH]) were divided into three groups according to tertiles of thyroid hormones. RESULTS: The mean FT3, FT4, and TSH of the patients were 2.56 pg/mL, 1.03 ng/dL, and 1.50 µIU/mL, respectively. Increased FT3 were associated with higher body mass index (BMI) (P <  0.001), body fat percentage (BFP) (P = 0.008), visceral fat content (VFC) (P = 0.019), adiponectin (P = 0.037), tumor necrosis factor alpha (TNF-α) (P <  0.001), and interleukin 6 (IL-6) (P = 0.015). There were significant differences among the different FT4 categories for BMI (P = 0.033), waist-hip ratio (WHR) (P = 0.030), low-density lipoprotein cholesterol (LDL-C) (P = 0.014), and IL-6 (P = 0.009). Increased TSH could increase the total cholesterol (TC) (P = 0.005) and high-density lipoprotein cholesterol (HDL-C) (P = 0.010). FT3 was positively correlated with BMI (r = 0.45; P <  0.001), WHR (r = 0.27; P = 0.028), BFP (r = 0.33; P = 0.007), VFC (r = 0.30; P = 0.014), adiponectin (r = 0.25; P = 0.045), TNF-α (r = 0.47; P <  0.001), and IL-6 (r = 0.32; P = 0.008). FT4 was positively correlated with HDL-C (r = 0.26; P = 0.038), LDL-C (r = 0.26; P = 0.036), and adiponectin (r = 0.28; P = 0.023). TSH was positively correlated with TC (r = 0.36; P = 0.003). CONCLUSION: This study found that the changes in thyroid hormones are associated with various body fat content and lipid metabolism in euthyroid male patients with T2DM.

Genetic Factors Associated with Enhanced blaKPC Expression in Tn3/Tn4401 Chimeras.

The expression of the blaKPC gene plays a key role in carbapenem resistance in Enterobacteriaceae However, the genetic regulators of the blaKPC gene have not been completely elucidated, especially the genes in Tn3-Tn4401 chimeras. Two novel Tn3-Tn4401 chimera isoforms were characterized in our hospital, isoform A (CTA), which harbors a 121-bp deletion containing the PX promoter and was present in 22.6% (54/239) of isolates, and isoform C (CTC), which harbors a 624-bp insertion and a P1 promoter deletion and was present in only 1 isolate. The carbapenem MICs of both isoforms were 2-fold or more higher than those of the wild type (Tn3-Tn4401 chimera, CTB), and blaKPC was most highly expressed in CTA. Bioinformatics and 5' rapid amplification of cDNA ends (5' RACE) experiments indicated a novel strong putative promoter, PY, at the 3' end of the ISKpn8 gene. PY mutation nearly abrogated blaKPC expression (P < 0.01) and restored carbapenem susceptibility in all 3 isoforms. Although the mutation of PX or P1 halved blaKPC expression in CTB (P < 0.05), PX deletion caused a 68% increase in blaKPC expression (P = 0.037) in CTA. The level of blaKPC mRNA in CTC was 8-fold higher than that in InCTC, which harbors P1 (P = 0.011). These results suggest that PY is a core promoter of the blaKPC gene in the chimeras and that the deletion of the PX and P1 promoters enhanced gene expression in CTA and CTC, respectively.

Unlocking the Drug Potential of the Bryostatin Family: Recent Advances in Product Synthesis and Biomedical Applications.

Bryostatins are a class of naturally occurring macrocyclic lactones with a unique fast developing portfolio of clinical applications, including treatment of AIDS, Alzheimer's disease, and cancer. This comprehensive account summarizes the recent progress (2014-present) in the development of bryostatins, including their total synthesis and biomedical applications. An emphasis is placed on the discussion of bryostatin 1, the most-studied analogue to date. This review highlights the synthetic and biological challenges of bryostatins and provides an outlook on their future development.

Comparative Analysis of blaKPC Expression in Tn4401 Transposons and the Tn3-Tn4401 Chimera.

Two basic structures that carry the blaKPC gene, the Tn4401 transposon and the Tn3-Tn4401 chimera, have been identified within and outside China. However, the different blaKPC expression levels and promoter activities of these two structures are not completely understood. We constructed Tn4401a, Tn4401b, and Tn3-Tn4401 chimera recombinants and found that the imipenem (IPM) and meropenem (MEM) MICs for the Escherichia coli transformants carrying the chimera were 2-fold higher than for those carrying Tn4401b but 2-fold lower than for those carrying Tn4401a In addition to the promoter P1, we characterized a novel potential promoter sequence (PX) in the chimera using 5' rapid amplification of cDNA ends (5' RACE), of which the -35 and -10 sequences were TTCAAA and TGAGACAAT, respectively. Although mutation of P1, P2, or PX significantly downregulated blaKPC mRNA expression in each structure (P < 0.05), the P2 mutation resulted in 2- and 3-fold greater decreases than the P1 mutation in Tn4401a and Tn4401b, respectively. Similarly, despite no significant difference in the PX and P1 mutations in the chimera, the carbapenem MIC and Klebsiella pneumoniae carbapenemase (KPC) production resulting from P2 mutations were significantly lower than those of P1 (P < 0.01) in the Tn4401 transposons. These studies indicate that the Tn3-Tn4401 chimera contains a novel potential blaKPC promoter, PX, and that its carbapenem resistance falls in between those of Tn4401a and Tn4401b.

Strategy to combine two functional components: Efficient nano material development for iodine immobilization.

The development of effective radioactive iodine adsorption materials from nuclear waste remains a significant challenge due to the drawbacks of the previous technologies such as complex synthesis process, high cost, and low stability. In this work, a Metal Oxidation-Carbon (MOC) composite material was designed and synthesized to solve this problem. The structure, composition, and physicochemical properties of this MOC were characterized to reveal its mesoporous material properties. Experiment results showed that this MOC material contain great physical and chemical adsorption efficiency towards iodine vapor, the adsorption capacity could up to 2647.54 mg/g. And the average desorption rate of 86.57% (in absolute ethanol) further proved its advanced recyclability. Moreover, this mesoporous material has great prospects in industrialization due to its simple one-step synthesis method, well-defined adsorption mechanism, and competitive application property.

Potassium application promote cotton acclimation to soil waterlogging stress by regulating endogenous protective enzymes activities and hormones contents.

To investigate the effect of potassium application on cotton damage mitigation after waterlogging stress, experiments were conducted under two potassium application levels (0 and 150 kg K2O hm-2) with three types of soil waterlogging treatments (0d, 3d and 6d) during cotton flowering stage. The results showed that: (a) under simple soil waterlogging stress, the increments of endogenous hormones contents of IAA, GA3 and ZR in cotton leaves were decreased as days of soil waterlogging. On the contrary, the soluble protein, MDA and ABA contents were significantly increased, while ZR/ABA, IAA/ABA and GA3/ABA were decreased. CAT and POD enzyme activities were increased although SOD activity decreased with the duration of soil waterlogging. (b) Potassium application combined with soil waterlogging significantly affected the antioxidant enzymes activity and endogenous hormones balance compared with soil waterlogging alone, leading to a significant increase in soluble protein and a pronounced decrease in H2O2 content, O2- generation rate, and MDA content, a significant increase in IAA, GA3 and ZR contents while a decrease in ABA content. Besides, it also kept higher SOD, CAT activities and slowly increased POD activity. (c) There was an obvious compensatory effect in cotton after 3d soil waterlogging under potassium application, which promoted rapidly recovery of physiological enzymes activities and ABA content. However, 6d soil waterlogging required a longer time for recovery. These findings were expected to provide a scientific and theoretical basis for reducing flood damage and improving cotton yield.

Outbreak of KPC-producing Klebsiella pneumoniae ST15 strains in a Chinese tertiary hospital: resistance and virulence analyses.

Introduction. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of clinical infection. However, K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae ST15 strains are occasionally identified and have seldom been reported to cause hospital outbreaks in PR China.Hypothesis/Gap Statement. In this study, we describe nosocomial outbreaks caused by KPC-producing K. pneumoniae ST15 strains in a Chinese tertiary hospital.Aim. To characterize the molecular relationship, resistance and virulence factors of the 32 KPC-producing K. pneumoniae ST15 strains isolated in a Chinese hospital.Methodology. A total of 102 non-repetitive carbapenem-resistant Enterobacteriaceae (CRE) strains were collected from a Chinese tertiary hospital in 2018. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to characterize the clonal relationship of the K. pneumoniae isolates, and the ST15 strains were selected for further study. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Fifteen carbapenem resistance genes, bla KPC genetic structures and 12 virulence factors were detected by PCR. Whole-genome sequencing (WGS) was performed using next-generation sequencing combined with single-molecule real-time sequencing.Results. Thirty-two K. pneumoniae ST15 strains were characterized, and 31 of them presented a PFGE similarity of >92 %, indicating clonal spread. In 81.3 % (26/32) of strains, the imipenem (IPM) and meropenem (MEM) MICs were ≤8 and≤16 µg ml-1, while only 1 isolate (KP18069) exhibited ≥64 µg ml-1 for both agents. The bla KPC-2 gene embedded in the Tn3-Tn4401 chimaera and synonymous mutations of the ompK35 gene were detected in all the strains. However, a nonsense mutation at amino acid position 248 (K248X) of OmpK36 was found in the highly carbapenem-resistant strain KP18069. No virulence gene was detected in any of the ST15 strains. WGS analyses further confirmed the genetic characteristics of the K. pneumoniae KP18069 strain.Conclusion. Nosocomial outbreaks caused by the clonal spread of K. pneumoniae ST15 strains were characterized in a Chinese tertiary hospital, and strict monitoring of highly resistant CRKP is required.

Characterization of a carbapenem-resistant Citrobacter amalonaticus coharbouring bla IMP-4 and qnrs1 genes.

Introduction. Members of the genus Citrobacter are facultative anaerobic Gram-negative bacilli belonging to the Enterobacterales [Janda J Clin Microbiol 1994; 32(8):1850-1854; Arens Clin Microbiol Infect 1997;3(1):53-57]. Formerly, Citrobacter species were occasionally reported as nosocomial pathogens with low virulence [Pepperell Antimicrob Agents Chemother 2002;46(11):3555-60]. Now, they are consistently reported to cause nosocomial infections of the urinary tract, respiratory tract, bone, peritoneum, endocardium, meninges, intestines, bloodstream and central nervous system. Among Citrobacter species, the most common isolates are C. koseri and C. freundii, while C. amalonaticus has seldom been isolated [Janda J Clin Microbiol 1994; 32(8):1850-1854; Marak Infect Dis (Lond) 2017;49(7):532-9]. Further, Citrobacter spp. are usually susceptible to carbapenems, aminoglycosides, tetracyclines and colistin [Marak Infect Dis (Lond) 2017;49(7):532-9].Hypothesis/Gap Statement. As C. amalonaticus is rare, only one clinical isolate, coharbouring carbapenem resistance gene bla IMP-4 and quinolone resistance gene qnrs1, has been reported.Aim. To characterize a carbapenem-resistant C. amalonaticus strain from PR China coharbouring bla IMP-4 and qnrs1.Methodology. Three hundred and forty nonrepetitive carbapenem-resistant Enterobacterales (CRE) strains were collected during 2011-2018. A carbapenem-resistant C. amalonaticus strain was detected and confirmed using a VITEK mass spectrometry-based microbial identification system and 16S rRNA sequencing. Minimum inhibitory concentrations (MICs) for clinical antimicrobials were obtained by the broth microdilution method. Whole-genome sequencing (WGS) was performed for antibiotic resistance gene analysis, and a phylogenetic tree of C. amalonaticus strains was constructed using the Bacterial Pan Genome Analysis (BPGA) tool. The transferability of the resistance plasmid was verified by conjugal transfer.Results. A rare carbapenem-resistant C. amalonaticus strain (CA71) was recovered from a patient with cerebral obstruction and the sequences of 16S rRNA gene shared more than 99 % similarity with C. amalonaticus CITRO86, FDAARGOS 165. CA71 is resistant to ß-lactam, quinolone and aminoglycoside antibiotics, and even imipenem and meropenem (MICs of 2 and 4 mg l-1 respectively), and is only sensitive to polymyxin B and tigecycline. Six antibiotic resistance genes were detected via WGS, including the ß-lactam genes bla IMP-4, bla CTX-M-18 and bla Sed1, the quinolone gene qnrs1, and the aminoglycoside genes AAC(3)-VIIIa, AadA24. Interestingly, bla IMP-4 and qnrs1 coexist on an IncN1-type plasmid (pCA71-IMP) and successfully transferred to Escherichia coli J53 via conjugal transfer. Phylogenetic analysis showed that CA71 is most similar to C. amalonaticus strain CJ25 and belongs to the same evolutionary cluster along with seven other strains.Conclusion. To the best of our knowledge, this is the first report of a carbapenem-resistant C. amalonaticus isolate coharbouring bla IMP-4 and qnrs1.

Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations.

Toxoplasmosis, an infectious zoonotic disease caused by the apicomplexan parasite Toxoplasma gondii (T. gondii), is a major worldwide health problem. However, there are currently no effective options (chemotherapeutic drugs or prophylactic vaccines) for treating chronic latent toxoplasmosis infection. Accordingly, seeking more effective and safer chemotherapeutics for combating this disease remains a long-term and challenging objective. In this paper, we summarize possible molecular biotargets, with an emphasis on those that are druggable and promising, including, without limitation, calcium-dependent protein kinase 1, bifunctional thymidylate synthase-dihydrofolate reductase, and farnesyl diphosphate synthase. Meanwhile, as important components of medicinal chemistry, the binding modes and structure-activity relationship profiles of the corresponding inhibitors were also illuminated. We anticipate that this information will be helpful for further identification of more effective chemotherapeutic interventions to prevent and treat zoonotic infections caused by T. gondii.

MicroRNA-155-5p suppresses PD-L1 expression in lung adenocarcinoma.

MiR-155-5p is a key oncogenic microRNA that maintains immune homeostasis and mediates cross-talk between inflammation and tumorigenesis. High expression of programmed death ligand-1 (PD-L1) also plays an important role in immune tolerance in tumors. The present study aimed to explore the relationship between miR-155-5p and PD-L1 in lung adenocarcinoma (LUAD) cells A549 and H1650. The expression levels of miR-155-5p and PD-L1 in LUAD patients were detected by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and mimics of miR-155-5p were used to model increased expression in A549 or H1650 cells. After 24 h, we measured levels of PD-L1 by qRT-PCR, western blotting and flow cytometry. In addition, we identified two sites in the PD-L1 3'-UTR (5'-AGCAUUA-3' and 5'-GCAUUAA-3') that can be bound by miR-155-5p using TargetScan (http://www.targetscan.org). Compared to normal tissue, miR-155-5p was overexpressed in tumor tissue (P = 0.0456), whereas the expression of PD-L1 was not significantly different (P = 0.1349). The expression levels of miR-155-5p and PD-L1 were negatively correlated (r = -0.6409, P = 0.0459 and r = -0.7544, P = 0.0117). Exogenous overexpression of miR-155-5p decreased the mRNA, total protein and membrane protein expression levels of PD-L1 both in A549 and H1650 cells (P < 0.05). Taken together, our data suggest that miR-155-5p may suppress the expression of PD-L1 in LUAD.

Further Spread of a blaKPC-Harboring Untypeable Plasmid in Enterobacteriaceae in China.

The wide spread of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae is great threat to public health in China. Plasmids are among the major factors mediating blaKPC gene dissemination. A total of 156 carbapenem-resistant Enterobacteriaceae (CRE) isolates were identified in a tertiary hospital in China. Six KPC-producing isolates, namely, E. coli (n = 2), E. asburiae (n = 1), C. freundii (n = 1), C. portucalensis (n = 1), and C. koseri (n = 1), tested positive for the pCKPC18-1-like untypeable plasmid, which was described recently in C. freundii. All 6 plasmids could be easily transferred into E. coli by chemical transformation or conjugation and were confirmed by sequencing to harbor blaKPC-2. Multilocus PCRs and EcoRI-RFLP revealed that the 6 untypeable plasmids belonged to 2 isoforms. High-throughput sequencing of representative plasmids (pCP40 and pEC86) led to the identification of 2 plasmids that shared the common backbone genes repA, DnaJ, StpA, and yafB, which were characteristic of the untypeable plasmid, and had similar blaKPC-2 genetic contexts of the Tn3-Tn4401 chimera. Nucleotide comparison revealed high sequence identity of the 2 plasmids with previously reported blaKPC-2-carrying untypeable plasmids. In particular, the pCP40 plasmid from C. portucalensis and the pHS062105-3 plasmid from K. pneumoniae differed by only 20 single-nucleotide polymorphisms (SNPs). To the best of our knowledge, this is the first report of a blaKPC-harboring untypeable plasmid spread into E. coli, E. asburiae, and C. koseri strains in China.