Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway

Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway

The effect of anti-PD-1/PD-L1 antibodies combined with VEGF receptor tyrosine kinase inhibitors versus bevacizumab in unresectable hepatocellular carcinoma

IntroductionImmune checkpoint inhibition (ICI) plus bevacizumab (BEV) is the standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of ICI plus bevacizumab and ICI plus receptor tyrosine kinase inhibitor (TKI) in this patient population.MethodsThis retrospective single-institution study enrolled 94 patients with uHCC who received ICI plus TKI or bevacizumab as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were used to evaluate treatment efficacy. RECIST v1.1 criteria were used to calculate the objective clinical response. Common Terminology Criteria for Adverse Events were used to report and categorize adverse events.ResultsBy the last follow-up interview on May 15, 2022, there were 57 deaths, and 19 patients did not develop disease progression. Thirty patients received sintilimab/atezolizumab plus bevacizumab (ICI + BEV group), and 64 received ICI plus TKI (ICI + TKI group). The median OS was 430 days (95% CI, 266-NA) in the ICI+TKI group and 498 days (95% CI, 349-NA) in the ICI+BEV group (HR, 1.20; 95% CI, 0.69-2.07; P = 0.52). There was no significant difference between the two groups in the median PFS (182 vs. 221 days, P=0.67). In the ICI+TKI group, the ORR and DCR were 28.1% and 67.2%, respectively. In the ICI+BEV group, the ORR and DCR were 26.7% and 66.7%, respectively. The overall incidence of adverse events was similar between the two groups. Palmar-plantar erythrodysesthesia syndrome (23[36%]) occurred only in the ICI + TKI group. Patients who received ICI+BEV were more prone to upper gastrointestinal bleeding (2 [7%]), with one patient with grade 4 requiring emergency DSA treatment.ConclusionThis study found that ICI+TKI and ICI+BEV as first-line treatments were similar in OS, PFS, and tumor response in uHCC. Different populations are suitable for different regimens because of the different adverse events

Pitch-based ribbon-shaped carbon-fiber-reinforced one-dimensional carbon/carbon composites with ultrahigh thermal conductivity

Ribbon-shaped carbon fibers have been prepared from mesophase pitch by melt-spinning, oxidative stabilization and further heat treatment. The internal graphitic layers of ribbon-shaped carbon fibers graphitized at 2800 C show a highly preferred orientation along the longitudinal direction. Parallel stretched and unidirectional arranged ribbon-shaped carbon fibers treated at about 450 C were sprayed with a mesophase pitch powder grout, and then hot-pressed at 500 C and subsequently carbonized and graphitized at various temperatures to produce one-dimensional carbon/carbon (C/C) composite blocks. The shape and microstructural orientation of ribbon fibers have been maintained in the process of hot-pressing and subsequent heat treatments and the main planes of the ribbon fibers are orderly accumulated along the hot-pressing direction. Microstructural analyses indicate that the C/C composite blocks have a typical structural anisotropy derived from the unidirectional arrangement of the highly oriented wide ribbon-shaped fibers in the composite block. The thermal conductivities of the C/C composites along the longitudinal direction of ribbon fibers increase with heat-treatment temperatures. The longitudinal thermal conductivity and thermal diffusivity at room temperature of the C/C composite blocks graphitized at 3100 C are 896 W/m K and 642 mm2/s, respectively.Key Program of Major Research Plan of the National Natural Science Foundation (grant No. 91016003) and the National Natural Science Foundation (grant No. 51372177) of China.http://www.elsevier.com/locate/carbonhb2014ai201

Analysis of the efficacy of Chinese medicine in the treatment of covid-19 and the study of medication pattern

In order to explore the efficacy and medication pattern of Chinese medicine in the treatment of COVID-19, we conducted statistics on the medication use of Chinese medicine based on some clinical data of novel coronavirus pneumonia (COVID-19) and related literature, and used the statistical method of frequency analysis to screen out the drugs with high frequency of use in patients with different types of novel coronavirus pneumonia (COVID-19). We used the statistical method of frequency analysis to screen out the core drugs with high frequency of use in patients with different types of novel coronavirus pneumonia (COVID-19) and the related main drug symptoms; Several drugs with good conversion effect were screened out by mean comparison method in terms of conversion time of drugs, and drug analysis was also conducted by data mining and other methods, so as to derive several groups of core drug combinations of Chinese medicine in the treatment of novel coronavirus pneumonia (COVID-19), and to provide data support and research directions for the effectiveness of Chinese medicine intervention in the treatment of novel coronavirus pneumonia (COVID-19)

Decoupling the Effect of Climate and Land-Use Changes on Carbon Sequestration of Vegetation in Mideast Hunan Province, China

Urbanization and global climate change are two important global environmental phenomena in the 21st century. Human activities and climate changes usually increase the uncertainties of the ecosystem functions and structures and can greatly affect regional landscape patterns and the carbon cycle. Consequently, it is critical to understand how various climate and land-use changes influence the carbon dynamics at a regional scale. In this study, we quantitatively analyzed the spatial and temporal changes of net primary productivity (NPP) and the effects of climate factors and human disturbance factors (i.e., land-use changes) on the “Chang–Zhu–Tan” (CZT) urban agglomeration region from 2000 to 2015. The Carnegie–Ames–Stanford Approach (CASA) model was combined with spatially explicit land-use maps, monthly climate data, and MODIS NDVI images to simulate the carbon dynamics in the CZT area. Based on our six different scenarios, we also analyzed the relative roles of climate change and land-use change in total production. Our results indicated that the annual NPP of the study area maintained an upward trend by 7.31 gC•m−2•yr−1 between 2000 and 2015. At the same time, the average annual NPP was 628.99 gC•m−2 in the CZT area. We also found that the NPP was lower in the middle of the north region than in others. In addition, land-use changes could contribute to a positive effect on the total production in the study area by 3.42 T gC. Meanwhile, the effect of climate changes on the total production amounted to −1.44 T gC in the same region and period. Temperature and precipitation had negative effects on carbon sequestration from 2000 to 2015. As forest land constituted over 62.60% of the total land use from 2000 to 2015, the negative effect of carbon sequestration caused by urbanization could be ignored in the CZT area. Although climate and land-use changes had simultaneously positive and negative effects during the period 2000–2015, prioritizing the protection of existing forest land could contribute to increasing carbon sequestration and storage at the regional scale. Our study assists in understanding the impact of climate changes and land-use changes on carbon sequestration while providing a scientific basis for the rational and effective protection of the ecological environment in mid-east Hunan Province, China

Simulation and Experiment of the Trapping Trajectory for Janus Particles in Linearly Polarized Optical Traps

The highly focused laser beam is capable of confining micro-sized particle in its focus. This is widely known as optical trapping. The Janus particle is composed of two hemispheres with different refractive indexes. In a linearly polarized optical trap, the Janus particle tends to align itself to an orientation where the interface of the two hemispheres is parallel to the laser propagation as well as the polarization direction. This enables a controllable approach that rotates the trapped particle with fine accuracy and could be used in partial measurement. However, due to the complexity of the interaction of the optical field and refractive index distribution, the trapping trajectory of the Janus particle in the linearly polarized optical trap is still uncovered. In this paper, we focus on the dynamic trapping process and the steady position and orientation of the Janus particle in the optical trap from both simulation and experimental aspects. The trapping process recorded by a high speed camera coincides with the simulation result calculated using the T-matrix model, which not only reveals the trapping trajectory, but also provides a practical simulation solution for more complicated structures and trapping motions.Science, Faculty ofNon UBCChemistry, Department ofReviewedFacultyResearcherOthe

Comparative Transcriptome Analysis Reveals the Molecular Immunopathogenesis of Chinese Soft-Shelled Turtle (Trionyx sinensis) Infected with Aeromonas hydrophila

Although hemorrhagic sepsis caused by Aeromonas hydrophila infection is the dominant disease in the aquaculture of Chinese soft-shelled turtle, information on its molecular pathology is seriously limited. In this study, ninety turtles intraperitoneally injected with A. hydrophila exhibited two different phenotypes based on the pathological symptoms, referred to as active and inactive turtles. Comparative transcriptomes of liver and spleen from these two groups at 6, 24, and 72 h post-injection (hpi) were further analyzed. The results showed that cytokine–cytokine receptor interaction, PRRs mediated signaling pathway, apoptosis, and phagocytosis enriched in active and inactive turtles were significantly different. Pro-inflammatory cytokines, the TLR signaling pathway, NLR signaling pathway, and RLR signaling pathway mediating cytokine expression, and apoptosis-related genes, were significantly up-regulated in inactive turtles at the early stage (6 hpi). The significant up-regulation of phagocytosis-related genes occurred at 24 hpi in inactive turtles and relatively lagged behind those in active turtles. The anti-inflammatory cytokine, IL10, was significantly up-regulated during the tested periods (6, 24, and 72 hpi) in active turtles. These findings offer valuable information for the understanding of molecular immunopathogenesis after A. hydrophila infection, and facilitate further investigations on strategies against hemorrhagic sepsis in Chinese soft-shelled turtle T. sinensis