Arsenic trioxide (ATO) has been proved useful for the treatment of acute promyelocytic leukemia (APL). Apoptosis is the result of the cytotoxic effect of ATO, apoptotic mediated cell death confirmed ...by DNA fragmentation and Annexin V staining. Although signaling associated with ATO-induced apoptosis has been well defined, it is still unknown whether other forms of cell death are involved in ATO-induced cell death.
Western blotting, cytotoxicity assay, transmission electron microscopy were used to evaluate other forms of cell death in U251 cells.
We found that pyroptotic mediated cell death was observed in U251 cells after ATO treatment, which was confirmed by observing the increased gasdermin E (GSDME) cleavage, lactate dehydrogenase (LDH) release and transmission electron microscopy imaging. Consistent with previous results, caspase-3 was activated by ATO, which was also important for GSDME cleavage and subsequent pyroptosis.
We reported that GSDME mediated pyroptosis involved in ATO induced cell death in astroglioma cells.
Multi‐AXis Differential Optical Absorption Spectroscopy (MAX‐DOAS) observations were carried out from March 1, 2019 to February 29, 2020 in Qingdao, China, on the coast of the Yellow Sea (120.67°E, ...36.35°N). Atmospheric parameters retrieved from the MAX‐DOAS instrument included vertical profiles of aerosol extinction, gaseous aerosol precursors (NO2, SO2), and H2O. First, the seasonal relationship between aerosol optical depth (AOD) and the H2O vertical column density (VCD) was analyzed. The correlation coefficients (r) between AOD and H2O VCD were largest in the winter, followed by spring, autumn, and summer. In addition, the correlation during heavily polluted weather was much higher than that during clean weather or slightly polluted weather. Then, an analysis of the wind speed and direction, and trace gas VCDs during the months with frequent pollution (December 2019 and January 2020) found that heavy pollution episodes easily occurred in Qingdao due to a combination of high H2O concentrations and low wind speeds. Out of four pollution events (P1, P2, P3, P4), both the H2O concentration and pollution were highest during the first event (P1). The H2O VCD, AOD, sulfate AOD, and total column HNO3 simultaneously increased during P1, while the NO2 and SO2 VCDs decreased. These trends are consistent with liquid phase reactions. Finally, the 1,000 m backward trajectory for the wind and the gas profiles during P1 revealed that the pollutants increased in Qingdao due to the influence of a polluted air mass from the western inland regions.
Plain Language Summary
Water vapor and aerosols are important components of the atmosphere. An increase in H2O concentration will accelerate the liquid phase reactions of trace gas and aggravate haze pollution. In recent years, heavy haze pollution has frequently occurred in China, especially during the winter in the northern China. The relationship between H2O and the aerosol optical depth (AOD), and how this relationship impacts haze formation, are of great significance for understanding the mechanisms driving heavy air pollution. Multi‐AXis Differential Optical Absorption Spectroscopy (MAX‐DOAS) is a remote sensing method that can simultaneously measure H2O, aerosols, and gaseous precursors (NO2, SO2). MAX‐DOAS instruments are low‐cost, simple to operate, and provide high time resolution, making them well‐suited for atmospheric observations across large geographic regions. The ability of MAX‐DOAS observations to simultaneously constrain the vertical profiles of H2O, other trace gases, and aerosols provides a measurement framework for analyzing liquid‐phase reactions in heavily polluted conditions. When combined with a wind backward trajectory analysis, it is possible to study the transport of H2O and pollutants during haze events. This is crucial to understanding the causes of haze formation and informing regulatory policy.
Key Points
H2O vertical profiles were measured using Multi‐AXis Differential Optical Absorption Spectroscopy (MAX‐DOAS)
The correlation coefficient between the aerosol optical depth and the H2O VCD was higher during heavily polluted weather
Heavy air pollution easily occurred in Qingdao due to a combination of high H2O concentration and low wind speeds
A large-scale assay was performed by transfecting 29,910 individual cDNA clones derived from human placenta, fetus, and normal liver tissues into human hepatoma cells and 22,926 cDNA clones into ...mouse NIH 3T3 cells. Based on the results of colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806 cDNA species (8,237 clones) were found to possess the ability of either stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895 clones) were unigenes of uncharacterized structure and function. A comprehensive analysis of the genes and the potential mechanisms for their involvement in the regulation of cell growth is provided. The genes were classified into four categories: I, genes related to the basic cellular mechanism for growth and survival; II, genes related to the cellular microenvironment; III, genes related to host-cell systemic regulation; and IV, genes of miscellaneous function. The extensive growth-regulatory activity of genes with such highly diversified functions suggests that cancer may be related to multiple levels of cellular and systemic controls. The present assay provides a direct genomewide functional screening method. It offers a better understanding of the basic machinery of oncogenesis, including previously undescribed systemic regulatory mechanisms, and also provides a tool for gene discovery with potential clinical applications.
B‐cell lymphoma‐6 (Bcl6) is a transcriptional repressor that plays important roles in various physiological activities such as innate and adaptive immune response, lymphocyte differentiation, and ...cell cycle regulation in mammals. Two homologs of Bcl6a, namely Bcl6aa and Bcl6ab, are identified in teleost fish including medaka Oryzias latipes. The expression profiles of bcl6aa and bcl6ab in medaka were studied using reverse‐transcription polymerase chain reaction and in situ hybridization. The transcripts of bcl6aa and bcl6ab were detected from very early embryos such as the four‐cell stage until hatching. Bcl6aa and bcl6ab were clearly detected in the embryonic body from 5 days postfertilization onward by in situ hybridization. Bcl6aa was specifically expressed in the retina, whereas bcl6ab was expressed in entire embryonic body. The results referred to that both bcl6aa and bcl6ab originate maternally in the zygotes and may play major roles in embryogenesis of medaka. The transcripts of bcl6aa and bcl6ab were detected in all examined adult tissues, including immune organs such as the gill, spleen, kidney, liver, and intestine. The expression of bcl6aa and bcl6ab in the liver, spleen, head–kidney, and intestine could be upregulated or downregulated by lipopolysaccharide and polyriboinosinic–polyribocytidylic acid. These results indicate that both bcl6aa and bcl6ab may be involved in immune response in medaka.
Bcl6aa and bcl6ab is duplicated homologs of BCL6 in fish. Medaka bcl6aa is located in the chromosome 4, bcl6ab is located in the chromosome 17. Bcl6aa & bcl6ab exist everywhere in adult tissues. Bcl6aa & bcl6ab are maternal origin and can be detected in very early embryos such as four‐cell stage, and are primarily detected in the yolk. From 5 dpf, bcl6aa is expressed in the eye only, whereas bcl6ab is expressed in the whole embryonic body. After stimulation by intraperitoneal injection of lipopolysaccharide and polyriboinosinic–polyribocytidylic acid, the expression level of bcl6aa and bcl6ab can be increased or decreased in the immune organs such as liver or spleen.
Only limited data are available on the real-life clinical utilization of aerosolized medications in intensive care unit (ICU) patients. Exploring the utilization of aerosolized medications in the ICU ...may contribute to develop appropriate education and improve the quality of aerosol therapy.
A 2-week, prospective, multicenter, observational, cohort study was conducted to record how the aerosolized medications were utilized in the Chinese ICUs, including indications, medications used in solo or combination, dosage, and side-effects in adult patients.
A total of 1006 patients from 28 ICUs were enrolled, of which 389 (38.7%) received aerosol therapy. The most common indications for aerosol therapy were difficulty in secretion management (23.1%) and chronic obstructive pulmonary disease exacerbation (18.5%). The combination of inhaled corticosteroids and short-acting muscarinic antagonist was the most commonly used medication (19.5%, 76/389). Ninety-two percent (358/389) of the patients did not have any side effects during aerosol therapy. More patients in the group with mechanical ventilation received bronchodilators than spontaneous breathing patients (81.3% vs. 55.5%,
< 0.001), and more patients who breathed spontaneously through a tracheostomy received mucus-regulating agents than other patients (70% vs. 37.9%,
= 0.004).
In mainland China, more than one-third of adult ICU patients received aerosol therapy. Medications utilized during aerosol therapy were variable in patients with different respiratory support. To promote appropriate use of aerosolized medications, high-quality randomized, controlled trials and clinical guidance on aerosolized medication indications and dosing are needed to improve clinical outcomes.
Purpose
To demonstrate the efficacy and safety of ranibizumab 0.5 mg pro re nata (PRN) versus laser photocoagulation for the treatment of Chinese patients with visual impairment due to diabetic ...macular edema (DME).
Methods
REFINE was a phase III, 12-month, double-masked, multicenter, laser-controlled study in patients (aged ≥ 18 years) with DME. Patients were randomized 4:1 to receive either ranibizumab 0.5 mg or laser dosing regimen. Efficacy was evaluated as mean average change in best-corrected visual acuity (BCVA) from Months 1 to 12 versus baseline (primary endpoint), anatomical outcomes, treatment exposure, and safety were also assessed.
Results
Ranibizumab was statistically superior (
p
< 0.001) to laser treatment, with a mean average BCVA gain of 6.8 letters (ranibizumab) over 12 months versus 1.1 letters (laser). At Month 12, mean BCVA gain was 7.8 letters (ranibizumab) and 2.5 letters (laser) from baseline. Patients in the ranibizumab arm received a mean number of 7.9 intravitreal injections, whereas those in the laser arm received a mean of 2.1 treatments. There were no new safety signals.
Conclusion
Ranibizumab 0.5 mg PRN demonstrated a statistically significant and clinically meaningful treatment effect versus laser and was well tolerated in Chinese patients with visual impairment due to DME over 12 months.
Protein degradation in eukaryotic cells is mainly carried out by the 26
proteasome, a macromolecular complex not only present in the cytosol and nucleus but also associated with various membranes. ...How proteasomes are anchored to the membrane and the biological meaning thereof have been largely unknown in higher organisms. Here, we show that
-myristoylation of the Rpt2 subunit is a general mechanism for proteasome-membrane interaction. Loss of this modification in the Rpt2-G2A mutant cells leads to profound changes in the membrane-associated proteome, perturbs the endomembrane system, and undermines critical cellular processes such as cell adhesion, endoplasmic reticulum-associated degradation and membrane protein trafficking. Rpt2
homozygous mutation is embryonic lethal in mice and is sufficient to abolish tumor growth in a nude mice xenograft model. These findings have defined an evolutionarily conserved mechanism for maintaining membrane protein homeostasis and underscored the significance of compartmentalized protein degradation by myristoyl-anchored proteasomes in health and disease.
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