Function analysis of transcription factor OSR1 regulating osmotic stress resistance in maize.

BACKGROUND: Maize is a major cereal crop world widely, however, the yield of maize is frequently limited by dehydration and even death of plants, which resulted from osmotic stress such as drought and salinity. Dissection of molecular mechanisms controlling stress tolerance will enable plant scientists and breeders to increase crops yield by manipulating key regulatory components. METHODS: The candidate OSR1 gene was identified by map-based cloning. The expression level of OSR1 was verified by qRT-PCR and digital PCR in WT and osr1 mutant. Electrophoretic mobility shift assay, transactivation activity assay, subcellular localization, transcriptome analysis and physiological characters measurements were conducted to analyze the function of OSR1 in osmotic stress resistance in maize. RESULTS: The osr1 mutant was significantly less sensitive to osmotic stress than the WT plants and displayed stronger water-holding capacity, and the OSR1 homologous mutant in Arabidopsis showed a phenotype similar with maize osr1 mutant. Differentially expressed genes (DEGs) were identified between WT and osr1 under osmotic stress by transcriptome analysis, the expression levels of many genes, such as LEA, auxin-related factors, PPR family members, and TPR family members, changed notably, which may primarily involve in osmotic stress or promote root development. CONCLUSIONS: OSR1 may serve as a negative regulatory factor in response to osmotic stress in maize. The present study sheds new light on the molecular mechanisms of osmotic stress in maize.

Adsorption of LIBs Thermal Runaway Gases on TM-Decorated HfS2 Surface: A DFT Study.

With the wide application of lithium-ion batteries (LIBs) in different fields, safety accidents occur frequently. Therefore, it is necessary to monitor the thermal runaway gas for an early warning. In this article, the adsorption properties of the characteristic gases of LIBs thermal runaway gases are studied by density functional theory (DFT). The adsorption structure of TM (Co/Rh/Ir)-decorated HfS2 (TM@HfS2) is established, and its adsorption properties for C2H4, CH4, and CO are studied. The adsorption energy, charge transfer, band, DOS, charge difference density, work function, and recovery time are discussed in detail. The results show that Ir@HfS2 has the strongest adsorption performance for C2H4 and CO, so C2H4 and CO can be stably adsorbed on the surface of the Ir@HfS2 monolayer. The adsorption energy of CH4 on Co@HfS2 is stronger than those of Rh@HfS2 and Ir@HfS2, but the adsorption energy is still very small. By applying biaxial strain to Co@HfS2, we found that the adsorption energy increases with the increase in negative strain. This study provides a theoretical basis for the regulation of the adsorption properties of HfS2 by different transition metals.

Epidemiology and molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolated from neonatal intensive care units in General Hospital of Ningxia Medical University, China, 2017-2021.

OBJECTIVES: This study aimed to retrospectively investigate the epidemiology and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from neonatal intensive care units (NICU) between 2017 and 2021. METHODS: The antibacterial susceptibility of all strains was assessed using the VITEK 2 compact system. The presence of antibiotic resistance, virulence genes, sequence types (STs), capsular (K) types, and the wzi genes was determined through polymerase chain reaction (PCR). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme XbaI. Additionally, the virulence potential of peg344-positive strains was evaluated using the string test and mouse intraperitoneal infection models. Whole-genome sequencing was conducted on the DNB system and PacBio platforms. RESULTS: A total of 46 CRKP isolates were collected during the study period. Out of these, 93.47% (43/46) were identified as CRKP strains belonging to the ST76-K10 type carrying blaNDM-5. It was observed that CRKP infection resulted in more severe clinical symptoms compared to CRKP colonization. Among the CRKP strains, a hypervirulent CRKP strain called KP-63, belonging to the ST23 type, was identified. This strain exhibited high mortality in the mouse infection model and was found to possess virulence genes. Genomic alignment analysis revealed a significant similarity between the virulence plasmid from KP-63 strain (pKP-63) and pK2044 from the hypervirulent K. pneumoniae strain NTUH-2044. CONCLUSIONS: There has been a potential dissemination of ST76-K10 type CRKP carrying blaNDM-5 in the NICU at Ningxia Hospital. Neonatal CRKP infection has been found to cause more severe clinical symptoms than colonization. Furthermore, we have discovered a CR-hvKP strain of ST23 with serotype K1, which exhibits a significant resemblance in its virulent plasmid to pK2044. Therefore, it is crucial to enforce effective measures to restrict the spread and hinder the evolution of CRKP within the hospital.

Reactive oxygen species: Multidimensional regulators of plant adaptation to abiotic stress and development.

Reactive oxygen species (ROS) are produced as undesirable by-products of metabolism in various cellular compartments, especially in response to unfavorable environmental conditions, throughout the life cycle of plants. Stress-induced ROS production disrupts normal cellular function and leads to oxidative damage. To cope with excessive ROS, plants are equipped with a sophisticated antioxidative defense system consisting of enzymatic and non-enzymatic components that scavenge ROS or inhibit their harmful effects on biomolecules. Nonetheless, when maintained at relatively low levels, ROS act as signaling molecules that regulate plant growth, development, and adaptation to adverse conditions. Here, we provide an overview of current approaches for detecting ROS. We also discuss recent advances in understanding ROS signaling, ROS metabolism, and the roles of ROS in plant growth and responses to various abiotic stresses.

Direct balancing of lipid mobilization and reactive oxygen species production by the epoxidation of fatty acid catalyzed by a cytochrome P450 protein during seed germination.

Fatty acid (FA) ß-oxidation provides energy for oil seed germination but also produces massive byproduct reactive oxygen species (ROS), posing potential oxidative damage to plant cells. How plants overcome the contradiction between energy supply and ROS production during seed germination remains unclear. In this study, we identified an Arabidopsis mvs1 (methylviologen-sensitive) mutant that was hypersensitive to ROS and caused by a missense mutation (G1349 substituted as A) of a cytochrome P450 gene, CYP77A4. CYP77A4 was highly expressed in germinating seedling cotyledons, and its protein is localized in the endoplasmic reticulum. As CYP77A4 catalyzes the epoxidation of unsaturated FA, disruption of CYP77A4 resulted in increased unsaturated FA abundance and over accumulated ROS in the mvs1 mutant. Consistently, scavenging excess ROS or blocking FA ß-oxidation could repress the ROS overaccumulation and hypersensitivity in the mvs1 mutant. Furthermore, H2 O2 transcriptionally upregulated CYP77A4 expression and post-translationally modified CYP77A4 by sulfenylating its Cysteine-456, which is necessary for CYP77A4's role in modulating FA abundance and ROS production. Together, our study illustrates that CYP77A4 mediates direct balancing of lipid mobilization and ROS production by the epoxidation of FA during seed germination.

Multi-View Stereo Vision Patchmatch Algorithm Based on Data Augmentation.

In this paper, a multi-view stereo vision patchmatch algorithm based on data augmentation is proposed. Compared to other works, this algorithm can reduce runtime and save computational memory through efficient cascading of modules; therefore, it can process higher-resolution images. Compared with algorithms utilizing 3D cost volume regularization, this algorithm can be applied on resource-constrained platforms. This paper applies the data augmentation module to an end-to-end multi-scale patchmatch algorithm and adopts adaptive evaluation propagation, avoiding the substantial memory resource consumption characterizing traditional region matching algorithms. Extensive experiments on the DTU and Tanks and Temples datasets show that our algorithm is very competitive in completeness, speed and memory.

Geospatial epidemiology of Toxoplasma gondii infection in livestock, pets, and humans in China, 1984-2020.

Undercooked or raw meat containing cyst-stage bradyzoites and oocyst-contaminated pets are presumed to constitute a major source of human toxoplasmosis. As the geospatial epidemiology of Toxoplasma gondii (T. gondii) infection in livestock, pets, and humans is rarely studied in China, we undertook a geospatial analysis using GIS visualization techniques. The present study retrieved information from the PubMed, China National Knowledge Infrastructure, and Baidu Scholar databases from 1984 up to 2020. All the data about the seroprevalence of T. gondii in livestock (sheep and goats, pigs, cattle and yaks), pets (cats, dogs), and humans in China were collected. Geospatial epidemiology of T. gondii infection in these hosts was performed using GIS. Results revealed that the estimated pooled seroprevalence of T. gondii was ranged from 3.98 to 43.02% in sheep and goats in China, 0.75 to 30.34% in cattle and yaks, 10.45 to 66.47% in pigs, 2.50 to 60.00% in cats, 0.56 to 27.65% in dogs, and 0.72 to 23.41% in humans. The higher seroprevalences of T. gondii were observed in sheep and goats in the districts of Chongqing, Zhejiang, and Beijing. The infection rates of T. gondii in cattle and yaks were higher in Guizhou, Zhejiang, and Chongqing. Also, the pigs from Chongqing and Guizhou were most severely infected with T. gondii. For cats, the districts of Shanxi, Hebei, and Yunnan had higher seroprevalences of T. gondii and, the infections among dogs were higher in Yunnan and Hebei as well. Furthermore, higher infection pressure of T. gondii exists in the districts of Taiwan and Tibet in humans. The geographical and spatial distribution of toxoplasmosis indicated that infection with T. gondii was widely spread in China, with a wide range of variations among the different hosts and regions in the country. Our results suggested that livestock and pets are not only a reservoir for the parasite but also a direct source of T. gondii infection for humans. It is important to control T. gondii infections in these animals that would reduce the risk of toxoplasmosis in humans.

APB-13 improves the adverse outcomes caused by TGEV infection by correcting the intestinal microbial disorders in piglets.

Porcine transmissible gastroenteritis virus (TGEV) is an enteric coronavirus that has caused high morbidity and mortality of piglets worldwide. Previous studies have shown that the TGEV can lead to severe diarrhoea, vomiting and dehydration in 2-week-old piglets and weaned piglets, resulting in a large number of piglet deaths. Antimicrobial peptides have broad-spectrum antimicrobial activity and a strong killing effect on bacteria, especially on the drug-resistant pathogenic bacteria, and it has attracted broad concern. However, there are very few reports on the effect of APB-13 (an antimicrobial peptide) on the intestinal microbes of piglets infected with TGEV. In this study, 16S rRNA gene sequencing was used to compare the microbial phylum and the genus of piglet's enteric microorganism in different experimental groups, and to predict the metabolic function of the microbial flora. At the same time, the apparent digestibility of nutrients, digestive enzyme activity, daily weight gain and survival rate were also measured. TGEV infection could cause the imbalance of intestinal microbes in piglets, and increase of the relative abundance of Proteobacteria, and decrease of the relative abundance of Firmicutes, Bacteroidetes and Actinobacteri. With the addition of APB-13, this problem can be alleviated, which can reduce the relative abundance of Proteobacteria and improve the balance of intestinal microorganisms. At the microbial genus level, after adding APB-13, the relative abundance of Catenibacterium, Enterobacter and Streptococcus in the intestinal tract of piglets infected with TGEV showed significant decrease, while the relative abundance of Lactobacillus and Ruminococcus increased. Finally, we found that APB-13 can significantly increase the activity of digestive enzyme in the intestinal tract of piglet, thereby improving the apparent digestibility of nutrients and the growth performance of piglets. This study demonstrates that APB-13 can alleviate the adverse outcomes caused by TGEV infection by correcting the intestinal microbial disorders.

Expression of porcine interferon-α and its bioactivity analysis in vitro and in vivo.

Interferon α (IFN-α) plays a crucial role in the host's immune response. In this study, the amino acid sequence of porcine interferon α (PoIFN-α) was analyzed. Seven substitutions, S38F, H40Q, F43L, N78D, Y86C, S151A, and R156T, were mutated and obtained by aligning the sequences of PoIFN-α subtypes. The PoIFN-α mutants were designed, expressed, and purified in E. coli. The antiviral activities of these PoIFN-αs were measured in Vero and swine testis cells against vesicular stomatitis virus (VSV). Their inhibitory abilities on pseudorabies virus (PRV) were also examined. Commercial PoIFN-α was used as a control. We found the ideal inducer concentration of isopropyl ß-D-thiogalactoside was 1 mM, and the best time-point for induction was 8 h. The PoIFN-α mutant named PoIFN-α-156s had the highest antiviral activity, which was about 200-fold more than that of PoIFN-α. PoIFN-α-156s could inhibit VSV and PRV replication in a dose-dependent manner in vitro. The half-life of PoIFN-α-156s was longer than that of PoIFN-α in mice, and the effective antiviral action was higher than PoIFN-α. Animal experiments showed that PoIFN-α-156s could decrease the viral load after infection with VSV. Overall, these results suggest that recombinant PoIFN-α-156s has the ability of antivirus, and is feasible for veterinary clinical applications and fundamental research.

Vitamin C-dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition.

Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domain-containing 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation.

Emerging medical therapies in crush syndrome - progress report from basic sciences and potential future avenues.

Crush injury is a disease that is commonly found in victims of earthquakes, debris flows, mine disasters, explosions, terrorist attacks, local wars, and other accidents. The complications that arise due to the crush injury inflicted on victims give rise to crush syndrome (CS). If not treated in time, the mortality rate of CS is very high. The most important measure that can be taken to reduce mortality in such situations is to immediately start treatment. However, the traditional treatment methods such as fluid resuscitation, diuresis, and hemodialysis are not feasible enough to be carried out at the disaster scene. So there is a need for developing new treatments that are efficient and convenient. Because it is difficult to diagnose in the disaster area and reach the treatment equipment and treat on time. It has become a new research needs to be directed into identifying new medical treatment targets and methods using the etiology and pathophysiological mechanisms of CS. In recent years, a large number of new anti-oxidant and anti-inflammatory drug therapies have been shown to be highly efficacious in CS rat/mouse models. Some of them are expected to become specific drugs for the emergency treatment of a large number of patients who may develop CS in the aftermath of earthquakes, wars, and other disasters in the future. Hence, we have reviewed the latest research on the medical therapy of CS as a source for anyone wishing to pursue research in this direction.

Simultaneous Decolorization and Biohydrogen Production from Xylose by Klebsiella oxytoca GS-4-08 in the Presence of Azo Dyes with Sulfonate and Carboxyl Groups.

Biohydrogen production from the pulp and paper effluent containing rich lignocellulosic material could be achieved by the fermentation process. Xylose, an important hemicellulose hydrolysis product, is used less efficiently as a substrate for biohydrogen production. Moreover, azo dyes are usually added to fabricate anticounterfeiting paper, which further increases the complexity of wastewater. This study reports that xylose could serve as the sole carbon source for a pure culture of Klebsiella oxytoca GS-4-08 to achieve simultaneous decolorization and biohydrogen production. With 2 g liter-1 of xylose as the substrate, a maximum xylose utilization rate (URxyl) and a hydrogen molar yield (HMY) of 93.99% and 0.259 mol of H2 mol of xylose-1, respectively, were obtained. Biohydrogen kinetics and electron equivalent (e- equiv) balance calculations indicated that methyl red (MR) penetrates and intracellularly inhibits both the pentose phosphate pathway and pyruvate fermentation pathway, while methyl orange (MO) acted independently of the glycolysis and biohydrogen pathway. The data demonstrate that biohydrogen pathways in the presence of azo dyes with sulfonate and carboxyl groups were different, but the azo dyes could be completely reduced during the biohydrogen production period in the presence of MO or MR. The feasibility of hydrogen production from industrial pulp and paper effluent by the strain if the xylose is sufficient was also proved and was not affected by toxic substances which usually exist in such wastewater, except for chlorophenol. This study offers a promising energy-recycling strategy for treating pulp and paper wastewaters, especially for those containing azo dyes.IMPORTANCE The pulp and paper industry is a major industry in many developing countries, and the global market of pulp and paper wastewater treatment is expected to increase by 60% between 2012 and 2020. Such wastewater contains large amounts of refractory contaminants, such as lignin, whose reclamation is considered economically crucial and environmentally friendly. Furthermore, azo dyes are usually added in order to fabricate anticounterfeiting paper, which further increases the complexity of the pulp and paper wastewater. This work may offer a better understanding of biohydrogen production from xylose in the presence of azo dyes and provide a promising energy-recycling method for treating pulp and paper wastewater, especially for those containing azo dyes.

Detection of Liquid Penetration of a Micropillar Surface Using the Quartz Crystal Microbalance.

A quantitative characterization of the wetting states of droplets on hydrophobic textured surfaces requires direct measurement of the liquid penetration into surface cavities, which is challenging. Here, the use of quartz crystal microbalance (QCM) technology is reported for the characterization of the liquid penetration depth on a micropillar-patterned surface. The actual liquid-air interface of the droplet was established by freezing the droplet and characterizing it using a cryogenically focused ion beam/scanning electron microscope (cryo FIB-SEM) technique. It was found that a direct correlation exists between the liquid penetration depth and the responses of the QCM. A very small frequency shift of the QCM (1.5%) was recorded when the droplet was in the Cassie state, whereas a significant frequency shift was observed when the wetting state changed to the Wenzel state (where full liquid penetration occurs). Furthermore, a transition from the Cassie to the Wenzel state can be captured by the QCM technique. An acoustic-structure-interaction based numerical model was developed to further understand the effect of penetration. The numerical model was validated by experimentally measured responses of micropillar-patterned QCMs. The results also show a nonlinear response of the QCM to the increasing liquid penetration depth. This research provides a solid foundation for utilizing QCM sensors for liquid penetration and surface wettability characterization.

Epidemiology and Azole Resistance of Clinical Isolates of Aspergillus fumigatus from a Large Tertiary Hospital in Ningxia, China.

Purpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023. Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms. Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region. Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.

ZIF-67-derived Co/CoSe ultrafine nanocrystal Schottky heterojunction decorated hollow carbon nanospheres as new-type anodes for potassium-ion batteries.

Metal-organic frameworks (MOFs) have the advantages of controllable chemical properties, rich pore structures and reaction sites and are expected to be high-performance anode materials for the next generation of potassium-ion batteries (PIBs). However, due to the large radius of potassium ions, the pure MOF crystal structure is prone to collapse during ion insertion and processing, so its electrochemical performance is quite limited. In this work, a hollow carbon sphere-supported MOF-derived Co/CoSe heterojunction anode material for potassium-ion batteries was developed by a hydrothermal method. The anode has high potassium storage capacity (461.9 mA h/g after 200 cycles at 1 A/g), excellent cycling stability and superior rate performance. It is worth noting that the potassium ion storage capacity of the anode material shows a gradual upward trend with the charge-discharge cycle, which is 145.9 mA h/g after 3000 cycles at a current density of 10 A/g. This work demonstrates that MOF-derived CoSe anodes with high capacity and low cost may be promising candidates for the introduction of potassium ion storage.

Sustained release of a highly specific GSK3ß inhibitor SB216763 in the PCL scaffold creates an osteogenic niche for osteogenesis, anti-adipogenesis, and potential angiogenesis.

The safe and effective use of Wnt signaling is a hot topic in developing osteogenic drugs. SB216763 (S33) is a widely used highly specific GSK3ß inhibitor. Here, we show that S33 initiates canonical Wnt signaling by inhibiting GSK3ß activity in the bone marrow stromal cell line ST2 and increases osteoblast marker alkaline phosphatase activity, osteoblast marker gene expression including Alpl, Col1α1, and Runx2, promoting osteogenic differentiation and mineralization of ST2 cells. In addition, S33 suppressed the expression of adipogenic transcription factors Pparg and Cebpa in ST2 cells to suppress adipogenesis. ICRT-14, a specific transcriptional inhibitor of Wnt signaling, reversed the effects of S33 on the differentiation of ST2 cells. S33 also increased the expression of osteoclast cytokines RANKL and Opg but decreased the RANKL/Opg ratio and had the potential to inhibit osteoclast differentiation. In addition, we printed the PSCI3D (polycaprolactone, S33, cell-integrated 3D) scaffolds using a newly established integrated 3D printing system for hard materials and cells. S33 sustained release in the hydrogel of the scaffold with 25.4% release on day 1% and 81.7% release over 7 days. Cells in the scaffolds had good cell viability. The ratio of live/dead cells remained above 94% for 7 days, while the cells in the scaffolds proliferated linearly, and the proliferative activity of the PSCI3D scaffold group increased 1.4-fold and 1.7-fold on days 4 and 7, respectively. Similarly, in PSCI3D scaffolds, osteogenic differentiation of st2 cells was increased. The alkaline phosphatase activity increased 1.4- and 4.0-fold on days 7 and 14, respectively, and mineralization increased 1.7-fold at 21 days. In addition, PSCI3D conditioned medium promoted migration and tubulogenesis of HUVECs, and S33 upregulated the expression of Vegfa, a key factor in angiogenesis. In conclusion, our study suggests that S33 functions in osteogenesis, anti-adipogenesis, and potential inhibition of osteoclast differentiation. And the sustained release of S33 in PSCI3D scaffolds creates a safe osteogenic niche, which promotes cell proliferation, osteogenesis, and angiogenesis and has application prospects.

Delayed step-by-step decompression with DSF alleviates skeletal muscle crush injury by inhibiting NLRP3/CASP-1/GSDMD pathway.

Crush injury (CI) is a common disease in earthquake and traffic accidents. It refers to long-term compression that induces ischemia and hypoxia injury of skeletal muscle rich parts, leading to rupture of muscle cells and release of contents into the blood circulation. Crush syndrome (CS) is the systemic manifestation of severe, traumatic muscle injury. CI rescue faces a dilemma. Ischemic reperfusion due to decompression is a double-edged sword for the injured. Death often occurs when the injured are glad to be rescued. Programmed cell death (PCD) predominates in muscle CI or ischemia-reperfusion injury. However, the function and mechanism of pyroptosis and apoptosis in the pathogenesis of skeletal muscle injury in CI remain elusive. Here, we identified that pyroptosis and apoptosis occur independently of each other and are regulated differently in the injured mice's skeletal muscle of CI. While in vitro model, we found that glucose-deprived ischemic myoblast cells could occur pyroptosis. However, the cell damage degree was reduced if the oxygen was further deprived. Then, we confirmed that delayed step-by-step decompression of CI mice could significantly reduce skeletal muscle injury by substantially inhibiting NLRP3/Casp-1/GSDMD pyroptosis pathway but not altering the Casp-3/PARP apoptosis pathway. Moreover, pyroptotic inhibitor DSF therapy alone, or the combination of delayed step-by-step decompression and pyroptotic inhibitor therapy, significantly alleviated muscle injury of CI mice. The new physical stress relief and drug intervention method proposed in this study put forward new ideas and directions for rescuing patients with CI, even CS-associated acute kidney injury (CS-AKI).

A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis.

Cell source is the key to decellularized matrix (DM) strategy. This study compared 3 cell types, osteocytes with/without dominant active Wnt/ß-catenin signaling (daCO and WTO) and bone marrow stromal cells (BMSCs) for their DMs in bone repair. Decellularization removes all organelles and >95% DNA, and retained >74% collagen and >71% GAG, maintains the integrity of cell basement membrane with dense boundaries showing oval and honeycomb structure in osteocytic DM and smooth but irregular shape in the BMSC-DM. DM produced higher cell survival rate (90%) and higher proliferative activity. In vitro, daCO-DM induces more and longer stress fibers in BMSCs, conducive to cell adhesion, spreading, and osteogenic differentiation. 8-wk after implantation of the critical-sized parietal bone defect model, daCO-DM formed tight structures, composed of a large number of densely-arranged type-I collagen under polarized light microscope, which is similar to and integrated with host bone. BV/TV (>54%) was 1.5, 2.9, and 3.5 times of WTO-DM, BMSC-DM, and none-DM groups, and N.Ob/T.Ar (3.2 × 102/mm2) was 1.7, 2.9, and 3.3 times. At 4-wk, daCO-DM induced osteoclastogenesis, 2.3 times higher than WTO-DM; but BMSC-DM or none-DM didn't. daCO-DM increased the expression of RANKL and MCSF, Vegfa and Angpt1, and Ngf in BMSCs, which contributes to osteoclastogenesis, angiogenesis, and neurogenesis, respectively. daCO-DM promoted H-type vessel formation and nerve markers ß3-tubulin and NeuN expression. Conclusion: daCO-DM produces metabolic and neurovascularized organoid bone to accelerate the repair of bone defects. These features are expected to achieve the effect of autologous bone transplantation, suitable for transformation application.

Sodium butyrate (SB) ameliorated inflammation of COPD induced by cigarette smoke through activating the GPR43 to inhibit NF-κB/MAPKs signaling pathways.

Cigarette smoke is recognized as a major trigger for individuals with chronic obstructive pulmonary disease (COPD), leading to an amplified inflammatory response. The onset and progression of COPD are affected by multiple environmental and genetic risk factors, such as inflammatory mechanisms, oxidative stress, and an imbalance between proteinase and antiprotease. As a result, conventional drug therapies often have limited effectiveness. This study aimed to investigate the anti-inflammatory effect of sodium butyrate (SB) in COPD and explore its molecular mechanism, thereby deepening our understanding of the potential application of SB in the treatment of COPD. In our study, we observed an increase in the mRNA and protein expressions of inflammatory factors interleukin-1beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Matrix metallopeptidase 9 (MMP9) and MMP12 in both NR8383 cell and rat models of COPD. However, these expressions were significantly reduced after SB treatment. Meanwhile, SB treatment effectively decreased the phosphorylation levels of nuclear transcription factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear translocation of these proteins in the COPD cells, leading to a reduction in the expression of various inflammatory cytokines. Additionally, SB also inhibited the expression level of the Nod-like receptor pyrin domain 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 in the cigeratte smoke extract (CSE)-stimulated cells. Our results showed that CSE down-regulated the mRNA levels of G-protein-coupled receptor 43 (GPR43) and GPR109A, while SB only up-regulated the expression of GPR43 and had no effect on GPR109A. Moreover, additional analysis demonstrated that the knockdown of GPR43 diminishes the anti-inflammatory effects of SB. It is evident that siRNA-mediated knockdown of GPR43 prevented the reduction in mRNA expression of IL-1ß, IL-6, TNF-α, MMP9, and MMP12, as well as the expression of phosphorylated proteins NF-κB p65, JNK, and p38 MAPKs with SB treatment. These findings revealed a SB/GPR43 mediated pathway essential for attenuating pulmonary inflammatory responses in COPD, which may offer potential new treatments for COPD.

The global mismatch between equitable carbon dioxide removal liability and capacity.

Limiting climate change to 1.5°C and achieving net-zero emissions would entail substantial carbon dioxide removal (CDR) from the atmosphere by the mid-century, but how much CDR is needed at country level over time is unclear. The purpose of this paper is to provide a detailed description of when and how much CDR is required at country level in order to achieve 1.5°C and how much CDR countries can carry out domestically. We allocate global CDR pathways among 170 countries according to 6 equity principles and assess these allocations with respect to countries' biophysical and geophysical capacity to deploy CDR. Allocating global CDR to countries based on these principles suggests that CDR will, on average, represent ∼4% of nations' total emissions in 2030, rising to ∼17% in 2040. Moreover, equitable allocations of CDR, in many cases, exceed implied land and carbon storage capacities. We estimate ∼15% of countries (25) would have insufficient land to contribute an equitable share of global CDR, and ∼40% of countries (71) would have insufficient geological storage capacity. Unless more diverse CDR technologies are developed, the mismatch between CDR liabilities and land-based CDR capacities will lead to global demand for six GtCO2 carbon credits from 2020 to 2050. This demonstrates an imperative demand for international carbon trading of CDR.