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Ischemia-reperfusion-induced acute kidney injury (IR-AKI) commonly occurs in situations such as hemorrhagic shock, kidney transplantation, and cardiovascular surgery. As one of the significant causes of AKI, IR-AKI is characterized by its high incidence and mortality rates. Currently, effective inflammation control is the key for the treatment of IR-AKI. In this study, we developed an ROS-responsive polymeric prodrugs (Zn-D/DTH) which could target the externalized PS of apoptotic cells, and then responsively released HDM (anti-inflammatory peptides) in the presence of intracellular ROS. Zn-D/DTH effectively ameliorated renal function and mitigated pathological alterations such as the loss of the brush border, tubular dilation, and accumulation of cellular debris within the tubular lumens. Furthermore, Zn-D/DTH greatly reduced the generation of pro-inflammatory factors like IL-6, COX-2, and iNOS in renal tissues, suggesting its protective role largely stems from suppression of the inflammatory response. Additional mechanism exploration revealed that Zn-D/DTH markedly decreased the expression levels of TLR4 and MyD88, as well as the phosphorylation of NF-κB in the damaged kidneys. This, in turn, reduced the number of apoptotic tubular cells and the activity of Caspase 9 and Caspase 3 caused by ischemia-reperfusion. Additionally, Zn-D/DTH treatment showed improvement in the long-term renal damage and fibrosis induced by ischemia-reperfusion. The experimental outcomes indicated that Zn-D/DTH attenuated renal ischemia-reperfusion injury and delayed the transition from acute kidney injury to chronic kidney disease by downregulating the TLR4/MyD88/NF-κB signaling pathway and reducing the expression of apoptotic caspases, thereby inhibiting inflammation and reducing cell apoptosis., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The effective treatment of acute lung injury (ALI) remains a significant challenge. Patients with ALI demonstrate an abundance of proinflammatory mediators in both bronchoalveolar lavage fluid (BALF) and circulating plasma. Bardoxolone methyl (BM) is a semi-synthetic triterpenoid derived from oleanolic acid, a natural product known for its ability to inhibit proinflammatory signaling. GSDMD is a signaling protein involved in pyroptosis, a form of programmed cell death. It has been reported that its upstream proteins play a role in the pathogenesis of ALI. However, there is currently no research examining whether the effect of BM on the occurrence and development of ALI is associated with changes in GSDMD protein. In this study, we prepared nanostructured lipid carriers loaded with BM and conjugated with anti-PECAM-1 antibody (PECAM@BM NLCs). PECAM@BM NLCs were designed to specifically bind to pulmonary vascular endothelial cells that highly express the PECAM-1 receptors. We also aimed to investigate the protective effects of PECAM@BM NLCs on ALI and elucidate the underlying molecular mechanisms. The results demonstrated that PECAM@BM NLCs accumulated in the lung tissues and significantly alleviated the inflammatory injury of ALI. This was evidenced by the changes in the lung wet/dry ratio, the total protein concentration, proinflammatory cytokines in BALF, and the histopathological progress. Additionally, we elucidated that PECAM@BM NLCs had the ability to inhibit the assembly of NLRP3 inflammasome and pro-caspase-1 complex, thereby suppressing the induction of pyroptosis. This mechanism resulted in the inhibition of N-terminal GSDMD expression and effectively prevented the progression of ALI., Competing Interests: Declaration of Competing Interest We state explicitly that no potential competing interests exist., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process and the detection of CTCs has been widely used clinically. In addition, cancer stem cells (CSCs) are the source of distant metastasis. However, the relationship between CTCs and CSCs in nasopharyngeal carcinoma (NPC) patients was largely unknown. A total of 93 NPC patients were enrolled in this study. The CTCs in the peripheral blood were detected. The expression of ALDH1A1 in the tumor tissues of the corresponding patients was detected using immunohistochemistry (IHC). The prognostic value of CTCs level and the correlation with the expression of ALDH1A1 was evaluated. Data showed that the detection of CTCs was positively correlated with metastasis (p<0.001). The positive detection of CTCs was also associated with poor overall survival (p=0.025). CTCs ≥2 demonstrated good specificity and sensitivity in predicting distant metastasis, while CTCs ≥8 demonstrated better specificity and sensitivity in predicting prognosis than CTCs ≥2. Furthermore, we found that there was a positive relationship between the detection of CTCs and the expression of ALDH1A1 (p=0.001). The prognosis analysis also demonstrated that high ALDH1A1 expression was correlated with poor overall survival (p=0.006). Our study demonstrated a positive correlation between the CTCs and the expression of CSCs, both were positively correlated with metastasis and poor prognosis. These results indicated that the CTCs might indirectly reflect the expression of CSCs.

Objective: To explore the significance of the resistance to polymyxin resistance of the extensively drug resistant Acinetobacter baumannii (XDRAB) lipopolysaccharide (LPS) lpx A , lpx C , lpx D and to screen appropriate combination therapy., Methods: In the past two years, 72 XDRAB in the secretions of our patients were selected as the research object. According to the minimum inhibitory concentration (MIC) of the XDRAB strain on polymyxin, they were included in the drug resistance group and the sensitive group. The gene sequences of strains lpx A , lpx C , lpx D were compared with the standard strains to analyze gene mutations and compared the mutation rates in the drug resistant group and the sensitive group. The efficacy of the combination drugs was evaluated by microcheckerboard dilution method, including polymyxin+imipenem group, polymyxin+meropenem group, polymyxin+cefoperazone/sulbactam group, polymyxin+levofloxacin group, and polymyxin+fosfomycin group. Calculated the fractional inhibitory concentration (FIC) index of the combined medication regimen and compared the percentage of strains that exhibited synergistic, additive, irrelevant, and antagonistic effects., Results: Tentyone were in the drug resistant group, accounting for 21 (29.17%,) and 51 were in the sensitive group, accounting for 70.83%. Some strains had mutations in lpx A , lpx C , lpx D genes. The mutation rate in the drug resistant group was 90.48%, which was significantly higher than 11.76% in the sensitive group, the difference was statistically significant ( P <0.05). The combined drug sensitivity test showed, compared with the polymyxin+fosfomycin group, the mycotin+fosfomycin group had a higher percentage of strains with synergistic FIC index in the polymyxin+imipenem group, the difference was statistically significant ( P <0.01)., Conclusion: XDRAB is resistant to polymyxin, which is related to mutations in LPS lipid A biosynthesis genes lpx A , lpx C , lpx D . Clinical treatment should adopt a combination of polymyxin+imipenem/meropenem and other drug combination to reduce the secondary infection of drug resistant bacteria., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Nucleic acid aptamers have been widely used in various fields such as biosensing, DNA chip, and medical diagnosis. However, the high susceptibility of nucleic acids to ubiquitous nucleases reduces the biostability of aptamers and limits their applications in biological contexts. Therefore, improving the biostability of aptamers becomes an urgent need. Herein, we present a simple strategy to resolve this problem by directly replacing the d-DNA-based aptamers with left-handed l-DNA. By testing several reported aptamers against respective targets, we found that our proposed strategy stood up well for nonchiral small molecule targets (e.g., Hemin and cationic porphyrin) and chiral targets whose interactions with aptamers are chirality-independent (e.g., ATP). We also found that the l-DNA aptamers were indeed endowed with greatly improved biostability due to the extraordinary resistance of l-DNA to nuclease digestion. With respect to other small-molecule targets whose interactions with aptamers are chirality-dependent (e.g., kanamycin) and biomacromolecules (e.g., tyrosine kinase-7), however, the proposed strategy was not entirely effective likely due to the participation of the DNA backbone chirality into the target recognition. In spite of this limitation, this strategy indeed paves an easy way to screen highly biostable aptamers important for the applications in many fields.

Lymphoma is a malignant disease of the hematopoietic system that typically affects B cells. The up-regulation of miR-148b is associated with radiosensitization in B-cell lymphoma (BCL). This study aimed to explore the role of miR-148b in regulating the radiosensitivity of BCL cells and to investigate the underlying mechanism. miR-148b directly targeted Bcl-w, decreased the cell viability and colony formation, while promoted apoptosis, in irradiated BCL cells. These changes were accompanied by decreased mitochondrial membrane potential, release of cytochrome C, increased levels of the cleaved caspase 9 and caspase 3, and increased expression of other proteins related to the mitochondrial apoptosis pathway. These effects of miR-148b were effectively inhibited by Bcl-w. In addition, miR-148b inhibited the growth of tumors in nude mice implanted with xenografts of irradiated Raji cells. In patients with BCL, levels of miR-148b were downregulated, while levels of Bcl-w were upregulated; a significant negative correlation between levels of miR-148b and Bcl-w was confirmed. Taken together, these experiments showed that miR-148b promoted radiation-induced apoptosis in BCL cells by targeting anti-apoptotic Bcl-w. miR-148b might be used as a marker to predict the radiosensitivity of BCL., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

To investigate the effects of autophagy activator and autophagy inhibitor on the CNE2 radiation sensitivity of nasopharyngeal carcinoma cells. RNA interference technology was used to silence the atg5 gene and autophagy inhibition cell model was constructed. Rapamycin and chloroquine were treated respectively on cells with X-ray 5Gy irradiation. Cells' growth status were observed for 8 days and control group was set. The cell viability was detected by MTT assay and colony formation assay, and the cell cycle was analyzed by flow cytometry. Compared with the control group, the survival rate, clone formation rate and the survival rate of the irradiation of the other three groups were significantly lower. (P&lt;0.05) Most cells were detected in the G0/G1 phase in the other three groups except the control group, and cells of the other two periods were less than those in the G0/G1 phase. The autophagy inhibitor or activator and atg5 silencing can be increased by CNE2 radiation therapy, however, the sensitization effect increase of autophagy activator is better than others.

Two robust Pinus taiwanensis Hayata tree-ring width chronologies were developed at high elevation sites in Jiulongshan Natural Conservation Area (JLS01), southeastern Zhejiang Province and Guniujiang (GNJ01), southern Anhui Province, China. The reliable period was 1884-2010 for JLS01 and 1837-2008 for GNJ01, based on subsample signal strength (SSS) threshold value of 0.8. Meteorological data were monthly mean temperature, monthly total precipitation and monthly mean relative humidity, monthly total cloud cover, as well as monthly sunshine duration. The data from the meteorological stations around the sampling sites were averaged to represent regional climate, which were used in the correlation analyses with the tree-ring chronologies. The correlation analyses indicated that summer (prior June-July and current June) hydrothermal condition was the main limiting factor on radial tree growth at the two high elevation sites. For JLS01 chronology, significant positive correlations were found with prior June-July temperature and sunshine duration, significant negative correlations with prior June-July and current June precipitation and relative hu- midity, and total cloud cover of prior July. GNJ01 chronology was significantly positively correlated with prior July temperature as well as prior July and current June sunshine duration, negatively correlated with prior July and current June precipitation and relative humidity, as well as total cloud cover of prior June. These results showed that relatively high temperature could promote radial growth, whereas high precipitation, together with high relative humidity, high cloud cover and low sunshine duration, could limit the photosynthesis and thus restrain the radial tree growth.

The present paper introduced the principle of clustering of variables around latent components method, and used this method in selecting spectrum range of the NIR quantitative analysis models. Taking tobacco samples as experiment materials, we dealed with 107 sample spectra, divided the spectra into 5 clusters, and explained the information reflected by each of these 5 clusters in terms of chemistry. On this basis, we chose the corresponding wavelength range to set up the quantitative models of the total sugar, reducing sugar and nicotine by PLS method. Compared with the model based on the full NIR spectral range, Rtraining of the models based on the chosen spectral range rose from 0.977 1, 0.917 2 and 0.987 4 to 0.995 5, 0.975 1 and 0.994 4; Rtest rose from 0.977 8, 0.941 2 and 0.993 2 to 0.992 7, 0.967 9 and 0.994 0; RMSECV dropped from 1.09, 1.43, 0.14 to 1.05, 1.05 and 0.13, RMSEP dropped from 0.92, 1.17 and 0.16 to 0.39, 0.63 and 0.11 and the D value dropped from 1.274%, 1.972% and 0.829% to 0.711%, 0.843% and 0.768% for the total sugar, reducing sugar and nicotine, respectively. These data indicated that this method can improve the forecasting precision and stability of the model, so offers certain guidance on practical application.

The effects of glycerol and high temperatures on structure and function of phycobilisomes (PBSs) in vivo were investigated in a chlL deletion mutant of the cyanobacterium Synechocystis sp. PCC 6803. When the mutant was grown under light-activated heterotrophic growth conditions, it contained intact and functional PBSs, but essentially no chlorophyll and photosystems. So the structural and functional changes of the mutant PBSs in vivo can be handily detected by measurement of low temperature (77 K) fluorescence emission spectra. High concentration glycerol induced an obvious disassembly of PBSs and the dissociation of phycocyanins in the rod substructures into their oligomers and monomers. PBSs also disassembled at high temperatures and allophycocyanins were more sensitive to heat stress than phycocyanins. Our results demonstrate that the chlL(-) mutant strain is an advantageous model for studying the mechanisms of assembly and disassembly of protein complexes in vivo.

The effects of benzoquinone analogues, phenyl-1,4-benzoquinone (PBQ) and 2,5-dibromo-3-methyl-6-isopropyl-1,4-benzoquinone (DBMIB), on state transitions in Synechocystis sp. PCC 6803 were investigated. PBQ induced a transition from state 2 to state 1 in the absence of actinic light whereas DBMIB caused a state 2 transition. 3-(3,4-Dichlorophenyl)-1,1-dimethyl urea could not eliminate the effects of PBQ and DBMIB. These results imply that the redox state of the plastoquinone pool controls the state transitions in vivo and cytochrome b6f complex is involved in this process. As a working hypothesis, we propose that the occupancy of the quinol oxidation site and the movement of the Rieske protein may be pivotal in this regulation.

Changes in the protein secondary structure and electron transport activity of the Triton X-100-treated photosystem I (PSI) and photosystem II (PSII) complexes after strong illumination treatment were studied using Fourier transform-infrared (FT-IR) spectroscopy and an oxygen electrode. Short periods of photoinhibitory treatment led to obvious decreases in the rates of PSI-mediated electron transport activity and PSII-mediated oxygen evolution in the native or Triton-treated PSI and PSII complexes. In the native PSI and PSII complexes, the protein secondary structures had little changes after the photoinhibitory treatment. However, in both Triton-treated PSI and PSII complexes, short photoinhibition times caused significant loss of alpha-helical content and increase of beta-sheet structure, similar to the conformational changes in samples of Triton-treated PSI and PSII complexes after long periods of dark incubation. Our results demonstrate that strong-light treatment to the Triton-treated PSI and PSII complexes accelerates destruction of the transmembrane structure of proteins in the two photosynthetic membranes.