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NMR data in a mnova file format and HPLC traces forEnantioselective Nickel-Catalyzed Electrochemical Cross-Dehydrogenative Amination.&nbsp

Ischemia-reperfusion (I/R) injury is a common occurrence in various surgical procedures used to treat heart diseases. However, the role of insulin-like growth factor 2 receptor (IGF2R) during the process of myocardial I/R remains unclear. Therefore, this study aims to investigate the expression, distribution, and functionality of IGF2R in various I/R-associated models (such as reoxygenation, revascularization, and heart transplant). Loss-of-function studies (including myocardial conditional knockout and CRISPR interference) were performed to clarify the role of IGF2R in I/R injuries. Following hypoxia, IGF2R expression increased, but this effect was reversed upon restoration of oxygen levels. Loss of myocardial IGF2R was found to enhance the cardiac contractile functions, and reduced cell infiltration or cardiac fibrosis of I/R mouse models compared to the genotype control. CRISPR-inhibition of IGF2R decreased cell apoptotic death under hypoxia. RNA sequencing analysis indicated that myocardial IGF2R played a critical role in regulating the inflammatory response, innate immune response, and apoptotic process following I/R. Integrated analysis of the mRNA profiling, pulldown assays, and mass spectrometry identified granulocyte-specific factors as potential targets of myocardial IGF2R in the injured heart. In conclusion, myocardial IGF2R emerges as a promising therapeutic target to ameliorate inflammation or fibrosis following I/R injuries.

Background: Transcriptional reconfiguration is central to heart failure, the most common cause of which is dilated cardiomyopathy (DCM). The effect of 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive. Methods: We generated a compendium of 3-dimensional epigenome and transcriptome maps from 101 biobanked human DCM and nonfailing heart tissues through highly integrative chromatin immunoprecipitation (H3K27ac [acetylation of lysine 27 on histone H3]), in situ high–throughput chromosome conformation capture, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin using sequencing, and RNA sequencing. We used human induced pluripotent stem cell–derived cardiomyocytes and mouse models to interrogate the key transcription factor implicated in 3-dimensional chromatin organization and transcriptional regulation in DCM pathogenesis. Results: We discovered that the active regulatory elements (H3K27ac peaks) and their connectome (H3K27ac loops) were extensively reprogrammed in DCM hearts and contributed to transcriptional dysregulation implicated in DCM development. For example, we identified that nontranscribing NPPA-AS1 (natriuretic peptide A antisense RNA 1) promoter functions as an enhancer and physically interacts with the NPPA (natriuretic peptide A) and NPPB (natriuretic peptide B) promoters, leading to the cotranscription of NPPA and NPPB in DCM hearts. We revealed that DCM-enriched H3K27ac loops largely resided in conserved high-order chromatin architectures (compartments, topologically associating domains) and their anchors unexpectedly had equivalent chromatin accessibility. We discovered that the DCM-enriched H3K27ac loop anchors exhibited a strong enrichment for HAND1 (heart and neural crest derivatives expressed 1), a key transcription factor involved in early cardiogenesis. In line with this, its protein expression was upregulated in human DCM and mouse failing hearts. To further validate whether HAND1 is a causal driver for the reprogramming of enhancer–promoter connectome in DCM hearts, we performed comprehensive 3-dimensional epigenome mappings in human induced pluripotent stem cell–derived cardiomyocytes. We found that forced overexpression of HAND1 in human induced pluripotent stem cell–derived cardiomyocytes induced a distinct gain of enhancer–promoter connectivity and correspondingly increased the expression of their connected genes implicated in DCM pathogenesis, thus recapitulating the transcriptional signature in human DCM hearts. Electrophysiology analysis demonstrated that forced overexpression of HAND1 in human induced pluripotent stem cell–derived cardiomyocytes induced abnormal calcium handling. Furthermore, cardiomyocyte-specific overexpression of Hand1 in the mouse hearts resulted in dilated cardiac remodeling with impaired contractility/Ca 2+ handling in cardiomyocytes, increased ratio of heart weight/body weight, and compromised cardiac function, which were ascribed to recapitulation of transcriptional reprogramming in DCM. Conclusions: This study provided novel chromatin topology insights into DCM pathogenesis and illustrated a model whereby a single transcription factor (HAND1) reprograms the genome-wide enhancer–promoter connectome to drive DCM pathogenesis.

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodelling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signalling pathway. Inhibition and genetic ablation of BDR9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment. In addition, pharmacological inhibition of BRD9 significantly reduced the tumorigenesis in patient-derived xenografts mouse models and eliminated CSCs in tumours from pancreatic cancer patients. Mechanistically, inhibition of BRD9 disrupts enhancer-promoter looping and transcription of stemness genes in CSCs. Collectively, the data suggest BRD9 as a novel therapeutic target for PDAC treatment via modulation of CSC stemness.

Fibroblasts can be reprogrammed into cardiovascular progenitor cells (CPCs) using transgenic approaches, although the underlying mechanism remains unclear. We determined whether activation of endogenous genes such as Gata4, Nkx2.5, and Tbx5 can rapidly establish autoregulatory loops and initiate CPC generation in adult extracardiac fibroblasts using a CRISPR activation system. The induced fibroblasts (>80%) showed phenotypic changes as indicated by an Nkx2.5 cardiac enhancer reporter. The progenitor characteristics were confirmed by colony formation and expression of cardiovascular genes. Cardiac sphere induction segregated the early and late reprogrammed cells that can generate functional cardiomyocytes and vascular cells in vitro. Therefore, they were termed CRISPR-induced CPCs (ciCPCs). Transcriptomic analysis showed that cell cycle and heart development pathways were important to accelerate CPC formation during the early reprogramming stage. The CRISPR system opened the silenced chromatin locus, thereby allowing transcriptional factors to access their own promoters and eventually forming a positive feedback loop. The regenerative potential of ciCPCs was assessed after implantation in mouse myocardial infarction models. The engrafted ciCPCs differentiated into cardiovascular cells in vivo but also significantly improved contractile function and scar formation. In conclusion, multiplex gene activation was sufficient to drive CPC reprogramming, providing a new cell source for regenerative therapeutics.

A Pd-PEPPSI-IPr embedded conjugated microporous polymer (Pd-PEPPSI-CMP) was shown to be a highly efficient heterogeneous catalyst for the Suzuki–Miyaura-type coupling of aryl chlorides and arylboronic acids.

As the power density of electronic devices continuously increases, there is a growing demand to improve the heat conduction performance of thermal management materials for addressing heat dissipation issues. Single-/few-layer graphene is a promising candidate as a filler of a metal matrix due to its extremely high thermal conductivity (

Seed plants comprise angiosperms and gymnosperms. The latter includes gnetophytes, cycads, Ginkgo, and conifers. Conifers are distributed worldwide, with 630 species distributed across eight families and 70 genera. Their distinctiveness has triggered much debate on their origin, evolution, and phylogenetic placement among seed plants. To better understand the evolution of gymnosperms and their relation to other seed plants, we report here a high-quality genome sequence for a tree species, Chinese fir (Cunninghamia lanceolata), which has excellent timber quality and high aluminum adaptability and is a member of Cupressaceae with high levels of heterozygosity. We assembled an 11.24 Gb genome with a contig N50 value of 2.15 Mb and anchored the 10.89 Gb sequence to 11 chromosomes. Phylogenomic analyses showed that cycads sister to Ginkgo, which place to sister in all gymnosperm lineages, and Gnetales within conifers sister to Pinaceae. Whole-genome duplication (WGD) analysis showed that the ancestor of seed plants has differentiated into angiosperms and gymnosperms after having experienced a WGD event. The ancestor of extant gymnosperm has experienced a gymnosperm-specific WGD event and the extant angiosperms do not share a common WGD before their most recent common ancestor diverged into existing angiosperms lineages. Analysis of the MADS-box gene family ofC. lanceolatarevealed the developmental mechanism of the reproductive organs inC. lanceolata, which supported the (A)B(C) model of the development of gymnosperms reproductive organs. In addition, astringent seeds and shedding of whole branches (with withered leaves) might be a strategy ofC. lanceolatathat evolved during long-term adaptation to an aluminum-rich environment. The findings also reveal the molecular regulation mechanism of shade tolerance inC. lanceolataseedlings. Our results improve the resolution of ancestral genomic features within seed plants and the knowledge of genome evolution and diversification of gymnosperms.

AimsJunctophilin-2 is required for the development, maturation and integrity of the t-tubule system and the gating stability of RyR2 in cardiomyocytes. This study investigated whether and how junctophilin-2 maintained junctin, a scaffold protein stabilizing RyR2, to prevent cardiomyocyte death under stress.MethodsCardiomyocytes were exposed to conditions of stress including palmitate, doxorubicin, or hypoxia/re-oxygenation. Adenoviral vectors were employed to manipulate expression of junctophilin-2 and junctin in cardiomyocytes. Molecular/cellular/biochemical analyses were conducted.ResultsDifferent conditions of stress decreased junctophilin-2 expression through aberrant autophagy and concomitantly induced a reduction of junctin protein in cardiomyocytes. Over-expression of junctophilin-2 preserved the protein levels of junctin and attenuated cytosolic Ca2+and apoptosis in cardiomyocytes under stress. Knockdown of junctophilin-2 reproduced the detrimental phenotypes of stress in cardiomyocytes. Notably, over-expression of junctin prevented cardiomyocyte death under stress whereas knockdown of junctin offset the protective effects conferred by junctophilin-2 over-expression. Mechanistically, junctophilin-2 blocked MURF1-junctin interaction thereby preventing junctin ubiquitination and proteasome-dependent degradation. Mass spectrometry analysis identified multiple ubiquitination sites on the junctin protein and the non-ubiquitinated junctin mutant (K8A/K102A/K107A/K140A) was resistant to degradation.ConclusionsThis study uncovers an unrecognized role of junctophilin-2 in preventing junctin ubiquitination and degradation in maintaining cytosolic Ca2+homeostasis. Both junctophilin-2 and junctin represent two new survival factors of cardiomyocytes and thus, may be new therapeutic targets for cardiac protection.

The objective of this study was to preliminarily analyze the differences in pathogenicity and physiologic races between Pyricularia oryzae isolates from indica and japonica rice varieties. Five to 7 isolates of P. oryzae from indica and japonica, having good sporulation capacity, were screened out in each experimental year. To determine the pathogenicity of P. oryzae, different kinds of rice varieties were inoculated with mixtures of indica and japonica isolates. A total of 46 isolates, including 23 indica isolates and 23 japonica isolates, were screened out in four years. In total, 1252 rice varieties, including 490 indica, 296 japonica and 466 indica-japonica hybrid rice varieties, were inoculated. Our results suggested that the degree of disease was more severe in most indica varieties infected with indica isolates than in those infected with japonica isolates. That is, indica isolates were more inclined to infect indica varieties. A majority of japonica and indica-japonica hybrid rice varieties infected with japonica isolates showed more severe infection than those infected with indica isolates. In other words, japonica isolates more easily infected japonica and indica-japonica hybrid rice varieties. The differences in quantity among the varieties indicated high resistance to rice blast in the corresponding kinds of rice inoculated with indica and japonica isolates, fully explaining the above viewpoint. Most of the 23 indica isolates belonged to indica races. Among the 23 japonica isolates, half were indica races and half were japonica races. In addition, there were significant differences between the isolates selected in the first two years and those selected in the second two years. The isolates in the first two years were all of indica races, and those of japonica races all appeared in the second two years. The results showed that the race of isolates shared little association with the kind of rice variety collected but was associated with the year of neck blast sample collection.

Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea. The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δbcpex8, Δbcpex10, and Δbcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δbcpex8, Δbcpex10, and Δbcpex12 strains. The mycelial growth rates of Δbcpex8, Δbcpex10, and Δbcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δbcpex8, Δbcpex10, and Δbcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8, BcPEX10, and BcPEX12 are indispensable for the development and pathogenicity of B. cinerea.

Background Cardiomyocyte death contributes to cardiac pathology of diabetes. Studies have shown that the RIPK3/MLKL necroptosis signaling is activated in diabetic hearts. Deletion of RIPK3 was reported to attenuate myocardial injury and heart dysfunction in streptozocin (STZ)-induced diabetic mice, suggesting a potential role of necroptosis in diabetic cardiomyopathy. This study characterized cardiomyocyte necroptosis in diabetic hearts and investigated whether MLKL-mediated necroptosis is a target for cardiac protection in diabetes. Methods Type 1 diabetes was induced in RIPK3 knockout, MLKL knockout and wild-type mice. Akita Type-1 diabetic mice were injected with shRNA for MLKL. Myocardial function was assessed by echocardiography. Immuno-histological analyses determined cardiomyocyte death and fibrosis in the heart. Cultured adult mouse cardiomyocytes were incubated with high glucose in the presence of various drugs. Cell death and phosphorylation of RIPK3 and MLKL were analysed. Results We showed that the levels of phosphorylated RIPK3 and MLKL were higher in high glucose-stimulated cardiomyocytes and hearts of STZ-induced type-1 diabetic mice, akita mice and type-1 diabetic monkeys when compared to non-diabetic controls. Inhibition of RIPK3 by its pharmacological inhibitor or gene deletion, or MLKL deletion prevented high glucose-induced MLKL phosphorylation and attenuated necroptosis in cardiomyocytes. In STZ-induced type-1 diabetic mice, cardiomyocyte necroptosis was present along with elevated cardiac troponin I in serum and MLKL oligomerization, and co-localized with phosphorylated MLKL. Deletion of RIPK3 or MLKL prevented MLKL phosphorylation and cardiac necroptosis, attenuated serum cardiac troponin I levels, reduced myocardial collagen deposition and improved myocardial function in STZ-injected mice. Additionally, shRNA-mediated down-regulation of MLKL reduced cardiomyocyte necroptosis in akita mice. Interestingly, incubation with anti-diabetic drugs (empagliflozin and metformin) prevented phosphorylation of RIPK3 and MLKL, and reduced cell death in high glucose-induced cardiomyocytes. Conclusions We have provided evidence that cardiomyocyte necroptosis is present in diabetic hearts and that MLKL-mediated cardiomyocyte necroptosis contributes to diabetic cardiomyopathy. These findings highlight MLKL-mediated necroptosis as a target for cardiac protection in diabetes.

Manipulating the interfacial structure is vital to enhancing the interfacial thermal conductance (

To obtain a better understanding the thermal stress of a rail, the thermal simulator was used to measure the expansion curves of different stresses loaded during the continuous cooling process of U75V rail. The transformation plasticity model was established. The experimental results show that stress can accelerate the transformation process of pearlite. While the same cooling rate is accelerated with the increase of stress, the transformation process of pearlite is accelerated, and the proportion of plastic strain transformation in total strain increases. At the same stress, the process of transformation of pearlite decreases with the increase in cooling rate, and the proportion of transformation plastic strain in total strain decreases. When considering the transformation plasticity, the axial residual stress is more consistent with the actual working condition, the accuracy of the transformation plasticity model is higher; during the continuous cooling process, and the loading stress has a significant influence on the structure. When the stress increases, the orientation of the pearlite lamellae becomes disordered, the pearlite lamellae are bent, the lamellae spacing is no longer uniform, and the hardness is improved.

Metabolic disorders (i.e., hyperglycemia, hyperlipidemia, and hyperinsulinemia) cause increased secretion of inflammatory cytokines/chemokines, leading to gradual loss of cardiac resident macrophage population and increased accumulation of inflammatory monocytes/macrophages in the heart. Such self-perpetuating effect may contribute to the development of cardiomyopathy during diabetes. Recent meta-analysis data reveal that lipocalin 10 (Lcn10) is significantly downregulated in cardiac tissue of patients with heart failure but is increased in the blood of septic patients. However, the functional role of Lcn10 in cardiac inflammation triggered by metabolic disorders has never been investigated. In this study, we demonstrate that the expression of Lcn10 in macrophages was significantly decreased under multiple metabolic stress conditions. Furthermore, Lcn10-null macrophages exhibited pro-inflammatory phenotype in response to inflammation stimuli. Next, using a global Lcn10-knockout (KO) mouse model to induce type-2 diabetes (T2D), we observed that loss of Lcn10 promoted more pro-inflammatory macrophage infiltration into the heart, compared to controls, leading to aggravated insulin resistance and impaired cardiac function. Similarly, adoptive transfer of Lcn10-KO bone marrow cells into X-ray irradiated mice displayed higher ratio of pro-/anti-inflammatory macrophages in the heart and worsened cardiac function than those mice received wild-type (WT) bone marrows upon T2D conditions. Mechanistically, RNA-sequencing analysis showed that Nr4a1, a nuclear receptor known to have potent anti-inflammatory effects, is involved in Lcn10-mediated macrophage activation. Indeed, we found that nuclear translocation of Nr4a1 was disrupted in Lcn10-KO macrophages upon stimulation with LPS + IFNγ. Accordingly, treatment with Cytosporone B (CsnB), an agonist of Nr4a1, attenuated the pro-inflammatory response in Lcn10-null macrophages and partially improved cardiac function in Lcn10-KO diabetic mice. Together, these findings indicate that loss of Lcn10 skews macrophage polarization to pro-inflammatory phenotype and aggravates cardiac dysfunction during type-2 diabetes through the disruption of Nr4a1-mediated anti-inflammatory signaling pathway in macrophages. Therefore, reduction of Lcn10 expression observed in diabetic macrophages may be responsible for the pathogenesis of diabetes-induced cardiac dysfunction. It suggests that Lcn10 might be a potential therapeutic factor for diabetic heart failure.

Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially

Multiple genome-wide association studies (GWAS) have identified specific genetic variants in the coiled-coil domain containing 92 (

Background: The increased vascular leakage seen in sepsis patients is well-recognized to be responsible for sepsis-triggered organ failure and patient mortality. Prior work suggests that lipocalin 10 (Lcn10), a member of the lipocalin superfamily, is significantly downregulated in the blood of non-survival septic patients when comparing to the survival group. Nonetheless, whether Lcn10 affects endothelial barrier integrity in sepsis remains unknown. Methods and Results: First, we observed that the expression of Lcn10 was remarkably down-regulated in the hearts of both endotoxin LPS- and cecal ligation/puncture (CLP)-induced septic mice, compared to their controls. Interestingly, further analysis of Lcn10 expression in different cell types isolated from LPS- and CLP-hearts showed that reduction of Lcn10 occurred only in cardiac endothelial cells (ECs) but not in cardiomyocytes or fibroblasts. Using a global Lcn10-knockout (KO) mouse model, we found that loss of Lcn10 greatly increased vascular permeability, which correlated with more severe cardiac depression and higher mortality following LPS challenge or CLP surgery, compared to LPS- or CLP-treated wild-type (WT) mice. By contrast, in vitro overexpression of Lcn10 in ECs provided greater resistance to LPS-caused monolayer leak, compared to control cells. A mechanistic analysis by RNA-sequencing and RT-qPCR revealed that both endogenous and exogenous elevation of Lcn10 in ECs could greatly upregulate slingshot homolog 1 (Ssh1) expression. Ssh1 is a phosphatase known to activate Cofilin, a key actin-binding protein that plays an essential role in controlling actin filament dynamics. Accordingly, phosphorylated Cofilin levels were significantly reduced and thereby, reorganized F-actin to cortical actin for stabilizing tight junction molecules in Lcn10-treated ECs, compared to control cells. Finally, knockdown of Ssh1 in ECs by siRNA greatly offsets Lcn10-induced reduction of monolayer leakage upon LPS insult. Conclusions: Endothelial Lcn10 is critical for protecting against sepsis-induced cardiovascular leakage, and its underlying mechanism involves the activation of Ssh1-Cofilin pathway. Our study suggests that Lcn10 could be a novel regulator of vascular barrier integrity.

Metabolic disorders (i.e., hyperglycemia, hyperlipidemia, and hyperinsulinemia) cause increased secretion of inflammatory cytokines/chemokines, leading to gradual loss of cardiac resident macrophage population and increased accumulation of inflammatory monocytes/macrophages in the heart. Such self-perpetuating effect may contribute to the development of cardiomyopathy during diabetes. Recent meta-analysis data reveal that lipocalin 10 (Lcn10) is significantly downregulated in cardiac tissue of patients with heart failure but is increased in the blood of septic patients. However, the functional role of Lcn10 in cardiac inflammation triggered by metabolic disorders has never been investigated. In this study, we demonstrate that the expression of Lcn10 in macrophages was significantly decreased under multiple metabolic stress conditions. Furthermore, Lcn10-null macrophages exhibited pro-inflammatory phenotype in response to inflammation stimuli. Next, using a global Lcn10-knockout (KO) mouse model to induce type-2 diabetes (T2D), we observed that loss of Lcn10 promoted more pro-inflammatory macrophage infiltration into the heart, compared to controls, leading to aggravated insulin resistance and impaired cardiac function. Similarly, adoptive transfer of Lcn10-KO bone marrow cells into X-ray irradiated mice displayed higher ratio of pro-/anti-inflammatory macrophages in the heart and worsened cardiac function than those mice received wild-type (WT) bone marrows upon T2D conditions. Mechanistically, RNA-sequencing analysis showed that Nr4a1, a nuclear receptor known to have potent anti-inflammatory effects, is involved in Lcn10-mediated macrophage activation. Indeed, we found that nuclear translocation of Nr4a1 was disrupted in Lcn10-KO macrophages upon stimulation with LPS + IFNγ. Accordingly, treatment with Cytosporone B (CsnB), an agonist of Nr4a1, attenuated the pro-inflammatory response in Lcn10-null macrophages and partially improved cardiac function in Lcn10-KO diabetic mice. Together, these findings indicate that loss of Lcn10 skews macrophage polarization to pro-inflammatory phenotype and aggravates cardiac dysfunction during type-2 diabetes through the disruption of Nr4a1-mediated anti-inflammatory signaling pathway in macrophages. Therefore, reduction of Lcn10 expression observed in diabetic macrophages may be responsible for the pathogenesis of diabetes-induced cardiac dysfunction. It suggests that Lcn10 might be a potential therapeutic factor for diabetic heart failure.

To compare the surgical outcomes of debridement, antibiotics, and single-stage total hip replacement (DASR) vs two-stage arthroplasty (two-stage arthroplasty) for chronic destructive septic hip arthritis (SHA).Cases of chronic destructive SHA treated by DASR or two-stage arthroplasty in our department from January 2008 to October 2021 were retrospectively reviewed. Patient demographic information, perioperative inflammation markers, intraoperative blood loss, microbial culture, and metagenomic new generation sequencing results were recorded. The perioperative complications, hospital stay, hospitalization cost, infection recurrence rate, and Harris Hip Score (HHS) at the last follow-up were compared between the two groups.A total of 28 patients were included in the study, including 11 patients who received DASR and 17 patients who received two-stage arthroplasty. There was no significant difference in demographic information, preoperative serum inflammatory markers, synovial fluid white blood cell count, or percentage of polymorphonuclear leukocytes between the two groups. The DASR group demonstrated significantly lower intraoperative blood loss [(368.2 ± 253.3) mL vs (638.2 ± 170.0) mL, p = 0.002], hospital stay [(22.6 ± 8.1) days vs (43.5 ± 13.2) days, p 0.0001], and hospitalization expenses [(81,269 ± 11,496) RMB vs (137,524 ± 25,516) RMB, p 0.0001] than the two-stage arthroplasty group. In the DASR group, one patient had dislocation as a complication. There were no cases with recurrence of infection. In the two-stage arthroplasty group, there was one case complicated with spacer fracture, one case with spacer dislocation, and one case with deep vein thrombosis of the lower limbs. There were no cases with recurrence of infection. There were no significant differences in the readmission rate, complication rate, or HHS at the last follow-up between the two groups.Both DASR and two-stage arthroplasty achieved a satisfactory infection cure rate and functional recovery for chronic destructive SHA, and DASR demonstrated significantly lower intraoperative blood loss, hospital stay, and hospitalization costs than two-stage arthroplasty. For appropriately indicated patients, if microbial data are available and a standardized debridement protocol is strictly followed, DASR can be a treatment option.

At present, the Corona Virus Disease 2019 (COVID-19) is ravaging the world, bringing great impact on people's life safety and health as well as the healthy development of economy and society, so the research on the prediction of the development trend of the epidemic is crucial. In this paper, we focus on the prevention and control of epidemic using the relevant technologies in the field of artificial intelligence and signal analysis. With the unknown principle of epidemic transmission, we first smooth out the complex and variable epidemic data through the empirical mode decomposition model to obtain the change trends of epidemic data at different time scales. On this basis, the change trends under different time scales are trained using an extreme learning machine to obtain the corresponding prediction values, and finally the epidemic prediction results are obtained by fitting through Adaptive Network-based Fuzzy Inference System. The experimental results show that the algorithm has good learning ability, especially in the prediction of time-series sequences can guarantee the accuracy rate while having low time complexity. Therefore, this paper not only plays a theoretical support for epidemic prevention and control, but also plays an important role in the construction of public emergency health system in the long run.

An epoxy resin/powder curing agent crack-repair material (EPCRM) was developed to overcome the limitations of the existing materials used to seal asphalt pavement cracks. The EPCRM was prepared by ...

A series of heterogeneous molecular catalysts by immobilizing nickel(ii) phthalocyanine (NiPc) onto different carbon supports were constructed to study the influence of the catalyst's microstructure on the performance of electrochemical carbon dioxide reduction reaction (CO2RR). The microporous structure of the electrocatalysts could influence CO2 transfer and therefore change the CO2 concentration at the surface of the catalyst, which singnificantly impacted the CO2RR performance.

Owing to their advantages of superior inherent porosity, high chemical stability, light weight, and molecularly tunable optoelectronic properties, conjugated microporous polymers (CMPs) have been receiving increasing attention and research interest as promising alternatives to traditional inorganic semiconductors for heterogeneous photocatalysis. Herein, we report the concise synthesis of tetrathienoanthracene-based conjugated microporous polymers (TTA-CMP) via a bottom-up strategy. TTA-CMP was employed as metal-free visible-light solid organocatalyst for three prototypic organic reactions: the dehydrogenative coupling reaction, dehydrogenative-Mannich reaction, and photocatalytic synthesis of benzimidazoles. Indeed, TTA-CMP showed excellent photocatalytic activity (29 examples, 80–98% yield) and outstanding reusability (10–12 times) in these three reactions. The extended π-conjugation in TTA-CMP enhances its visible light absorption, therefore, TTA-CMP displays higher catalytic activity than the corresponding small molecular photocatalyst. This work reveals the bright future of TTA-CMP as an efficient solid organocatalyst for other photocatalytic syntheses.

In the title complex, [Ni(C16H13ClN2O3)(C3H4N2)], the NiII ion is coordinated by two O atoms and one N atom derived from the dianionic N′-[(1E)-1-(5-chloro-2-hydroxyphenyl)ethylidene]-4-methoxybenzohydrazide ligand and one N atom from the imidazole molecule. The N2O2 donor set defines an approximate square-planar geometry. The dihedral angles between the imidazole ring and the fused six-membered and methoxybenzene rings are 17.78 (14) and 13.23 (16)°, respectively; the dihedral angle between the C6 rings is 6.63 (12)°. The most prominent feature of the molecular packing is the formation of 41-helical chains (along the c axis) mediated by imidazole-N—H...O(phenoxide) hydrogen bonding; these are linked by methyl-C—H...Cl interactions.

NMR data in a mnova file format and HPLC traces forcatalytic stereodivergent total synthesis of amathaspiramide D. NMR data are available as .mnova files

Exploring arsenic (As) transformation during coal combustion is beneficial for reducing its pollution. Herein, combustion experiments were developed at 1100-1300 °C in a fixed-bed experimental system with 25 types of coal samples. The occurrences of As in coal and combustion products were characterized. All the original forms of As in coal were found to be unstable during combustion. As retained in ash existed as water-soluble and ion-exchangeable and residual forms, but only as residual form at combustion temperature above 1200 °C. The distribution of As in gaseous and solid combustion products varied widely by coal types, which resulted from the coupling effects of multi-minerals in coal. Co-combustion experiments were conducted using As model compounds and pure minerals, by which the interaction of Ca, Fe, Si and Al minerals to retain As was elucidated. The As transformation during coal combustion was primarily attributed to the coupling action of Ca, Fe, Si and Al minerals in coal. As a result, As was retained as Ca-Si-Al-As and Fe-Si-Al-As composite salts in the ash, which have little environmental hazard. Utilizing the coupling effects of multi-minerals during combustion help reduce As pollution from coal-fired plants.

Lipid overload contributes to cardiac complications of diabetes and obesity. However, the underlying mechanisms remain obscure. This study investigates the role of gamma-aminobutyrate transaminase (ABAT), the key enzyme involved in the catabolism of γ-aminobutyric acid (GABA), in lipid overload-induced cardiac injury. Microarray revealed a down-regulation of ABAT mRNA expression in high fat diet (HFD)-fed mouse hearts, which correlated with a reduction in ABAT protein level and its GABA catabolic activity. Transgenic mice with cardiomyocyte-specific ABAT over-expression (Tg-ABAT/tTA) were generated to determine the role of ABAT in lipid overload-induced cardiac injury. Feeding with a HFD to control mice for 4 months reduced ATP production and the mitochondrial DNA copy number, and induced myocardial oxidative stress, hypertrophy, fibrosis and dysfunction. Such pathological effects of HFD were mitigated by ABAT over-expression in Tg-ABAT/tTA mice. In cultured cardiomyocytes, palmitate increased mitochondrial ROS production, depleted ATP production and promoted apoptosis, all of which were attenuated by ABAT over-expression. With the inhibition of ABAT’s GABA catabolic activity, the protective effects of ABAT remained unchanged in palmitate-induced cardiomyocytes. Thus, ABAT protects the mitochondrial function in defending the heart against lipid overload-induced injury through mechanisms independent of its GABA catabolic activity, and may represent a new therapeutic target for lipid overload-induced cardiac injury.

Additional file 1. Supplementary Figures and Tables.

Supplemental Material, sj-pdf-1-dvr-10.1177_14791641221083396 for Association of triglyceride-glucose with cardiac hemodynamics in type 2 diabetes by Chenxi Wang, Zhicong Zhao, Xia Deng, Zhensheng Cai, Tian Gu, Lian Li, Chang Guo, Dong Wang, Ling Yang, Li Zhao and Guoyue Yuan in Diabetes and Vascular Disease Research

The inability to effectively control invading bacteria or other pathogens is a major cause of multiple organ dysfunction and death in sepsis. As the first-line defense of the immune system, macrophages play a crucial role in the removal of pathogens during sepsis. In this study, we define secreted and transmembrane 1A (Sectm1a) as a novel ligand of glucocorticoid-induced TNFR (GITR) that greatly boosts macrophage phagocytosis and bactericidal capacity. Using a global Sectm1a knockout (KO) mouse model, we observed that Sectm1a deficiency significantly suppressed phagocytosis and bactericidal activity in both recruited macrophages and tissue-resident macrophages, which consequently aggravated bacterial burden in the blood and multiple organs and further increased systemic inflammation, leading to multiple organ injury and increased mortality during polymicrobial sepsis. By contrast, treatment of septic mice with recombinant Sectm1a protein (rSectm1a) not only promoted macrophage phagocytosis and bactericidal activity but also significantly improved survival outcome. Mechanistically, we identified that Sectm1a could bind to GITR in the surface of macrophages and thereby activate its downstream PI3K–Akt pathway. Accordingly, rSectm1a-mediated phagocytosis and bacterial killing were abolished in macrophages by either KO of GITR or pharmacological inhibition of the PI3K–Akt pathway. In addition, rSectm1a-induced therapeutic effects on sepsis injury were negated in GITR KO mice. Taken together, these results uncover that Sectm1a may represent a novel target for drug development to control bacterial dissemination during sepsis or other infectious diseases.

Aim Cardiac dysfunction is a prevalent comorbidity of disrupted inflammatory homeostasis observed in conditions such as sepsis (acute) or obesity (chronic). Secreted and transmembrane protein 1a (Sectm1a) has previously been implicated to regulate inflammatory responses, yet its role in inflammation-associated cardiac dysfunction is virtually unknown. Methods and results Using the CRISPR/Cas9 system, we generated a global Sectm1a-knockout (KO) mouse model and observed significantly increased mortality and cardiac injury after LPS injection, when compared to wild-type (WT) control. Further analysis revealed significantly increased accumulation of inflammatory macrophages in hearts of LPS-treated KO mice. Accordingly, ablation of Sectm1a remarkably increased inflammatory cytokines levels both in vitro [from bone marrow-derived macrophages (BMDMs)] and in vivo (in serum and myocardium) after LPS challenge. RNA-sequencing results and bioinformatics analyses showed that the most significantly downregulated genes in KO-BMDMs were modulated by LXRα, a nuclear receptor with robust anti-inflammatory activity in macrophages. Indeed, we identified that the nuclear translocation of LXRα was disrupted in KO-BMDMs when treated with GW3965 (LXR agonist), resulting in higher levels of inflammatory cytokines, compared to GW3965-treated WT-cells. Furthermore, using chronic inflammation model of high-fat diet (HFD) feeding, we observed that infiltration of inflammatory monocytes/macrophages into KO-hearts were greatly increased and accordingly, worsened cardiac function, compared to WT-HFD controls. Conclusion This study defines Sectm1a as a new regulator of inflammatory-induced cardiac dysfunction through modulation of LXRα signaling in macrophages. Our data suggest that augmenting Sectm1a activity may be a potential therapeutic approach to resolve inflammation and associated cardiac dysfunction. Translational perspective Better understanding on the interaction between inflammatory responses and cardiac health is prominent for the development of safer and more efficacious therapies for heart failure patients. The present study, using both acute (LPS) and chronic (high-fat diet) inflammation models, reiterated the adverse effects of abnormal macrophages activation on cardiac function. Our Sectm1a knockout mouse model showed exacerbated cardiac and systemic inflammatory responses, resulting in further aggravation of contractile dysfunction on the heart after endotoxin challenge. We also demonstrated Sectm1a as a new regulator of macrophage function through LXRα pathway. These data suggest a novel approach to regulate macrophage-elicited inflammation.

As a result of the evolution of Meso-Tethys, Early Cretaceous granitoids are widespread in the eastern Tengchong terrane, SW China, which is considered as the southern extension of the Tibetan Plateau. These igneous rocks are therefore very important for understanding the tectonic setting of Meso-Tethys and the formation of the Tibetan Plateau. In this paper, we present new zircon U-Pb dating, whole-rock elemental, and Nd isotopic data of granitoids obtained from the eastern Tengchong terrane. Our results show that these granitoids are composed of monzogranites and granodiorites and formed at ca. 124 Ma in the Early Cretaceous. Mineralogically and geochemically, these granitoids display metaluminous nature and affinity to I-type granites, which are derived from preexisting intracrustal igneous source rocks. The predominantly negative whole-rock εNd(t) values (−10.86 to −8.64) for all samples indicate that they are derived mainly from the partial melting of the Mesoproterozoic metabasic rocks in the lower crust. Integrating previous studies with the data presented in this contribution, we propose that the Early Cretaceous granitic rocks (135–110 Ma) also belong to I-type granites with minor high fractionation. Furthermore, in discriminant diagrams for source, granitoids are mainly derived from the partial melting of metaigneous rocks with minor sediments in the lower crust. The new identification of the Myitkyina Meso-Tethys ophiolitic suite in eastern Myanmar and mafic enclaves indicate that these Cretaceous igneous rocks were the products of the tectonic evolution of the Myitkyina Tethys Ocean, which was related to post-collisional slab rollback. Moreover, the Tengchong terrane is probably the southern extension of the South Qiangtang terrane.

A deep understanding of the shaping technique is urgently required to precisely tailor the pore structure of a graphene aerogel (GA) in order to fit versatile application backgrounds. In the present study, the microstructure and properties of GA were regulated by freeze-casting using an ice crystal template frozen from -10 °C to -196 °C. The phase field simulation method was applied to probe the microstructural evolution of the graphene-H2O system during freezing. Both the experimental and simulation results suggested that the undercooling degree was fundamental to the nucleation and growth of ice crystals and dominated the derived morphology of GA. The pore size of GA was largely regulated from 240 to 6 μm via decreasing the freezing temperature from -10 °C to -196 °C but with a constant density of 8.3 mg cm-3. Rapid freeze casting endowed GA with a refined pore structure and therefore better thermal, electrical, and compressive properties, whereas the GA frozen slowly had superior absorption properties owing to the continuous and tube-like graphene lamellae. The GA frozen at -196 °C exhibited the highest Young's modulus of 327 kPa with similar densities to those reported in the literature. These findings demonstrate the diverse potential applications of GA with regulated pore morphologies and also contribute to cryogenic-induced phase separation methods.

Late Cretaceous–Eocene granites are widespread in the Tengchong terrane and related to subduction and closure of the Neo–Tethyan Ocean. However, the reason of their compositional and spatial variat...

The 3D printing technology has evolved impressively over the last decade in its ability to fabricate structures with complex architectures at the micro- and macroscale. 3D printing of high explosive would reduce the unnecessary process for excessive handling, post-processing, and stockpiling confers benefits to safety, cost, waste, and flexibility. To truly take advantage of direct writing technology, materials and inks are allowed for fast and reliable deposition. Herein, 3D printable ink based on CL-20/HTPB was designed and printed. The explosive ink exhibited high performance, validating the potential of fully 3D printed structures with high performance of combustion. The method can print complex geometries with well-defined dimensions. To achieve high-quality printing with continuous ink, the uniformities were further optimized by tuning the concentrations of the CL-20, and the binder rate to curing agent. With the aid of 3D printing, various novel applications and functionalities became accessible, which is beyond the limits of conventional charge process (press loading and casting curing). This approach makes printing of diverse patterns possible, which open new avenues to fabricate gradient structure explosive and propellant with tunable safe combustion and detonation properties.

In this work, in situ growth of a titanium dioxide microplug (TDMP) having mesoporous channels at the tip of a glass micropipette induced by space-confined evaporation is reported. Moreover, clear ...

Calpains have been implicated in heart diseases. While calpain-1 has been detrimental to the heart, the role of calpain-2 in cardiac pathology remains controversial. In this study we investigated whether sustained over-expression of calpain-2 had any adverse effects on the heart and the underlying mechanisms. Double transgenic mice (Tg-Capn2/tTA) were generated, which express human CAPN2 restricted to cardiomyocytes. The mice were subjected to echocardiography at age 3, 6, 8 and 12 months, and their heart tissues and sera were collected for analyses. We showed that transgenic mice over-expressing calpain-2 restricted to cardiomyocytes had normal heart function with no evidence of cardiac pathological remodeling at age 3 months. However, they exhibited features of dilated cardiomyopathy including increased heart size, enlarged heart chambers and heart dysfunction from age 8 months; histological analysis revealed loss of cardiomyocytes replaced by myocardial fibrosis and cardiomyocyte hypertrophy in transgenic mice from age 8 months. These cardiac alterations closely correlated with aberrant autophagy evidenced by significantly increased LC3BII and p62 protein levels and accumulation of autophagosomes in the hearts of transgenic mice. Notably, injection of 3-methyladenine, a well-established inhibitor of autophagy (30 mg/kg, i.p. once every 3 days starting from age 6 months for 2 months) prevented aberrant autophagy, attenuated myocardial injury and improved heart function in the transgenic mice. In cultured cardiomyocytes, over-expression of calpain-2 blocked autophagic flux by impairing lysosomal function. Furthermore, over-expression of calpain-2 resulted in lower levels of junctophilin-2 protein in the heart of transgenic mice and in cultured cardiomyocytes, which was attenuated by 3-methyladenine. In addition, blockade of autophagic flux by bafilomycin A (100 nM) induced a reduction of junctophilin-2 protein in cardiomyocytes. In summary, transgenic over-expression of calpain-2 induces age-dependent dilated cardiomyopathy in mice, which may be mediated through aberrant autophagy and a reduction of junctophilin-2. Thus, a sustained increase in calpain-2 may be detrimental to the heart.

To investigate the mean preputial microvessel density (mMVD) and features of hypospadias and their relationship with the severity and early postoperative complications of the disease.Sixty children with hypospadias and another 14 age-matching ones with phimosis (the control group) underwent penile curvature correction, Snodgrass procedure or staged surgery, the excessive dorsal foreskin trimmed and retained. We determined the mMVD in the prepuce tissue of the patients by immunohistochemistry, and followed up those treated by Snodgrass procedure.The mMVD was significantly lower in the patients with severe hypospadias than in those with mild hypospadias and the controls (15.51 ± 3.53 vs 19.27 ± 4.42 and 22.09 ± 6.15, P0.05), with a median of 21.8 in the control group. The incidence of postoperative complications was obviously lower in the high mMVD (≥ 21.8) than in the low mMVD (21.8) group.The preputial mMVD is significantly lower in patients with severe hypospadias than in normal children, decreasing in a severity-dependent manner. The lower the preputial mMVD, the higher the incidence rate of postoperative complications. The preputial mMVD of 21.8 can be used as a reference index for evaluating the prognosis of surgery clinically. ?