Adipocyte­rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator­activated receptor gamma/ABCG2 in epithelial ovarian cancer.

The effects of adipocyte­rich microenvironment (ARM) on chemoresistance have garnered increasing interest. Ovarian cancer (OVCA) is a representative adipocyte­rich associated cancer. In the present study, epithelial OVCA (EOC) was used to investigate the influence of ARM on chemoresistance with the aim of identifying novel targets and developing novel strategies to reduce chemoresistance. Bioinformatics analysis was used to explore the effects of ARM­associated mechanisms contributing to chemoresistance and treated EOC cells, primarily OVCAR3 cells, with human adipose tissue extracts (HATES) from the peritumoral adipose tissue of patients were used to mimic ARM in vitro. Specifically, the peroxisome proliferator­activated receptor Î³ (PPARγ) antagonist GW9662 and the ABC transporter G family member 2 (ABCG2) inhibitor KO143, were used to determine the underlying mechanisms. Next, the effect of HATES on the expression of PPARγ and ABCG2 in OVCAR3 cells treated with cisplatin (DDP) and paclitaxel (PTX) was determined. Additionally, the association between PPARγ, ABCG2 and chemoresistance in EOC specimens was assessed. To evaluate the effect of inhibiting PPARγ, using DDP, a nude mouse model injected with OVCAR3­shPPARγ cells and a C57BL/6 model injected with ID8 cells treated with GW9662 were established. Finally, the factors within ARM that contributed to the mechanism were determined. It was found that HATES promoted chemoresistance by increasing ABCG2 expression via PPARγ. Expression of PPARγ/ABCG2 was related to chemoresistance in EOC clinical specimens. GW9662 or knockdown of PPARγ improved the efficacy of chemotherapy in mice. Finally, angiogenin and oleic acid played key roles in HATES in the upregulation of PPARγ. The present study showed that the introduction of ARM­educated PPARγ attenuated chemoresistance in EOC, highlighting a potentially novel therapeutic adjuvant to chemotherapy and shedding light on a means of improving the efficacy of chemotherapy from the perspective of ARM.

Rapid, accurate, and novel diagnostic technique for respiratory pathogens: Clinical application of loop-mediated isothermal amplification assay in older patients with pneumonia, a multicenter prospective observational study.

Background: Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method using only one type of enzyme that can amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. Chips for Complicated Infection Detection (CCID) is based on LAMP. This study translate CCID into clinical application and evaluate its diagnostic value for pneumonia. Methods: Eighty one older patients with pneumonia were prospectively enrolled from January 1 to July 23, 2021, and 57 sputum/airway secretion and 35 bronchoalveolar lavage fluid samples were collected and analyzed by CCID and conventional microbiological tests (CMTs). Samples were collected, transported, monitored, and managed by a multidisciplinary team using a sample management information system. Results: CCID turnaround time was 50 min, and the detection limit was 500 copies/reaction. The percentage of positive samples was significantly higher using CCID than CMTs, especially for Klebsiella pneumoniae (odds ratio [OR], 9.0; 95% confidence interval [CI], 1.1-70.5; p < 0.05), Enterococcus faecalis (OR, ∞; p < 0.01), Stenotrophomonas maltophilia (OR, ∞; p < 0.01), fungi (OR, 26.0; 95% CI, 3.6-190.0; p < 0.01), and viruses (CCID only; p < 0.01). In addition, the percentage of positive results was significantly higher using CCID than CMTs in patients who used antibiotics for more than 3 days (91.9% vs. 64.9%; p < 0.01). Analyzing clinical impact, 55 cases (59.8%) benefited from CCID. Conclusion: CCID allows the rapid and accurate detection of pneumonia in older patients. Moreover, this technique is less affected by previous antibiotic treatment and can improve patient care.

Transmission of hepatitis E virus from rabbits to cynomolgus macaques.

The recent discovery of hepatitis E virus (HEV) strains in rabbits in the People's Republic of China and the United States revealed that rabbits are another noteworthy reservoir of HEV. However, whether HEV from rabbits can infect humans is unclear. To study the zoonotic potential for and pathogenesis of rabbit HEV, we infected 2 cynomolgus macaques and 2 rabbits with an HEV strain from rabbits in China. Typical hepatitis developed in both monkeys; they exhibited elevated liver enzymes, viremia, virus shedding in fecal specimens, and seroconversion. Comparison of the complete genome sequence of HEV passed in the macaques with that of the inoculum showed 99.8% nucleotide identity. Rabbit HEV RNA (positive- and negative-stranded) was detectable in various tissues from the experimentally infected rabbits, indicating that extrahepatic replication may be common. Thus, HEV is transmissible from rabbits to cynomolgus macaques, which suggests that rabbits may be a new source of human HEV infection.

Pattern formation of Rayleigh-Bénard convection of cold water near its density maximum in a vertical cylindrical container.

In order to understand the onset of convective instability and multiple stable convection patterns of buoyancy-driven convection of cold water near its density maximum in a vertical cylindrical container heated from below, a series of three-dimensional numerical simulations were performed. The aspect ratio of the container was 2 and Prandtl number of cold water was 11.57. The sidewall was considered to be perfectly adiabatic, and the density inversion parameter was fixed at 0.3. The result shows that the density inversion phenomenon in cold water has an important effect on the critical Rayleigh number for the onset of convection and the pattern formation at higher Rayleigh numbers. When the Rayleigh number varies from 3×10(3) to 1.2×10(5), eight stable, steady convection patterns are obtained under different initial conditions. The coexistence of multiple stable steady flow patterns is also observed within some specific ranges of the Rayleigh number.