Blocking the MIR155HG/miR-155 axis reduces CTGF-induced inflammatory cytokine production and α-SMA expression via upregulating AZGP1 in hypertrophic scar fibroblasts.

Hypertrophic scarring (HS) is a pathological condition characterized by excessive fibrosis and inflammation, resulting in excessive extracellular matrix formation in the skin. MIR155HG, a long non-coding RNA, is abnormally upregulated in fibrotic tissues; however, its underlying mechanism is poorly understood. Using single-cell sequencing data, we analyzed connective tissue growth factor (CTGF) expression in various cell types in HS and normal skin tissues and MIR155HG expression in clinical samples. To investigate the mechanism of fibrosis, an in vitro model using CTGF-treated hypertrophic scar fibroblasts (HSFBs) was established and qRT-PCR, western blotting and ELISA assays were performed to investigate the expression of interleukin (IL)-1ß, IL-6, and mesenchymal markers α-smooth muscle actin (α-SMA). CTGF stimulates MIR155HG level through phosphorylated STAT3 binding to the MIR155HG promoter. We analyzed the methylation of MIR155HG, assessed the levels of miR-155-5p/-3p in CTGF-treated HSFBs and identified differentially expressed genes among HS and NS samples using the Gene Expression Omnibus RNA sequencing data. The binding between miR-155-5p/-3p and AZGP1 was confirmed using a dual-luciferase assay and inflammatory cytokine production and α-SMA expression were investigated in rescue experiments. The findings revealed that CTGF elevated inflammatory cytokine production, α-SMA and MIR155HG expression in HSFBs. MIR155HG is upregulated in HS tissues due to low DNA methylation. Mechanistically, miR-155-5p/-3p was directly bound to MIR155HG 3'UTR. MIR155HG silencing inhibited cytokine production and α-SMA expression by repressing the generation of miR-155-5p/-3p in CTGF-treated HSFBs. Bioinformatics analysis and luciferase reporter assays revealed that miR-155-5p/-3p targets AZGP1. In addition, transfection with plasmids carrying AZGP1 cDNA significantly inhibited the signaling activity of miR-155-5p/-3 p-overexpressing HSFBs. Our findings highlight the importance of the MIR155HG/miR-155/AZGP1 axis in regulating cytokine production and α-SMA in HS.

Modifications on the coastal atmospheric sulfur and cloud condensation nuclei along the Eastern China seas by shipping fuel transition.

Marine fuel combustion from shipping releases SO2 and forms sulfate particles, which may alter low cloud characteristics. A series of strategies were implemented to control the sulfur content of ship fuel oil from 2018 to 2020, offering insights into the effects of the ship fuel oil transition on sulfur-related pollutants and the consequent cloud condensation nuclei (CCN) in the atmosphere. Compared to 2018 in the southeast China waters, shipping SO2 emission decreased by 78 % in 2020, resulting in a 76 % reduction in ship-related total sulfur concentration, and a decrease of 54 % in CCN number concentration under supersaturation 0.2 % (CCN0.2) contributed by shipping. The response of CCN0.2 to ship-related sulfate modification is more pronounced in relatively clean environments than polluted environments, highlighting the uneven changes in coastal CCN along the Eastern China Sea induced by the ship fuel policies. CCN can trigger the formation of cloud droplets, 2020 fuel regulation may have and will reduce the cooling radiative forcing effect with strong spatial heterogeneity. The study provides insights into the variations in coastal atmospheric sulfur-related pollutants and CCN in uneven response to changes in ship fuel oil, prompting the need for further comprehensive assessments of the climate effects resulting from potential shifts in ship fuel use in the future.

LncRNA LINC00466 Promotes the Progression of Breast Cancer via miR-4731-5p/EPHA2 Pathway.

BACKGROUND: Breast Cancer (BC) is a female malignancy with a high mortality rate. Novel diagnostic and prognostic biomarkers are valuable for reducing BC mortality. Our study is designed to undrape the precise role of the LINC00466/miR-4731-5p/EPHA2 axis in BC.

Arbitrary engineering of spatial caustics with 3D-printed metasurfaces.

Caustics occur in diverse physical systems, spanning the nano-scale in electron microscopy to astronomical-scale in gravitational lensing. As envelopes of rays, optical caustics result in sharp edges or extended networks. Caustics in structured light, characterized by complex-amplitude distributions, have innovated numerous applications including particle manipulation, high-resolution imaging techniques, and optical communication. However, these applications have encountered limitations due to a major challenge in engineering caustic fields with customizable propagation trajectories and in-plane intensity profiles. Here, we introduce the "compensation phase" via 3D-printed metasurfaces to shape caustic fields with curved trajectories in free space. The in-plane caustic patterns can be preserved or morphed from one structure to another during propagation. Large-scale fabrication of these metasurfaces is enabled by the fast-prototyping and cost-effective two-photon polymerization lithography. Our optical elements with the ultra-thin profile and sub-millimeter extension offer a compact solution to generating caustic structured light for beam shaping, high-resolution microscopy, and light-matter-interaction studies.

PTPRO inhibits LPS-induced apoptosis in alveolar epithelial cells.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), represent critical clinical syndromes with multifactorial origins, notably stemming from sepsis within intensive care units (ICUs). Despite their high mortality rates, no selective cure is available beside ventilation support. Apoptosis plays a complex and pivotal role in the pathophysiology of acute lung injury. Excessive apoptosis of alveolar epithelial and microvascular endothelial cells can lead to disruption of lung epithelial barrier integrity, impairing the body's ability to exchange blood and gas. At the same time, apoptosis of damaged or dysfunctional cells, including endothelial and epithelial cells, can help maintain tissue integrity and accelerate recovery from organ pro-inflammatory stress. The balance between pro-survival and pro-apoptotic signals in lung injury determines patient outcomes, making the modulation of apoptosis an area of intense research in the quest for more effective therapies. Here we found that protein tyrosine phosphatase receptor type O (PTPRO), a poorly understood receptor-like protein tyrosine phosphatase, is consistently upregulated in multiple tissue types of mice under septic conditions and in the lung alveolar epithelial cells. PTPRO reduction by its selective short-interfering RNA (siRNA) leads to excessive apoptosis in lung alveolar epithelial cells without affecting cell proliferation. Consistently PTPRO overexpression by a DNA construct attenuates apoptotic signaling induced by LPS. These effects of PTPTO on cellular apoptosis are dependent on an ErbB2/PI3K/Akt/NFκB signaling pathway. Here we revealed a novel regulatory pathway of cellular apoptosis by PTPRO in lung alveolar epithelial cells during sepsis.

Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function.

BACKGROUND: Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. METHODS: Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni-NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. RESULTS: In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αß T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. CONCLUSION: Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Multi-Scale Masked Autoencoders for Cross-Session Emotion Recognition.

Affective brain-computer interfaces (aBCIs) have garnered widespread applications, with remarkable advancements in utilizing electroencephalogram (EEG) technology for emotion recognition. However, the time-consuming process of annotating EEG data, inherent individual differences, non-stationary characteristics of EEG data, and noise artifacts in EEG data collection pose formidable challenges in developing subject-specific cross-session emotion recognition models. To simultaneously address these challenges, we propose a unified pre-training framework based on multi-scale masked autoencoders (MSMAE), which utilizes large-scale unlabeled EEG signals from multiple subjects and sessions to extract noise-robust, subject-invariant, and temporal-invariant features. We subsequently fine-tune the obtained generalized features with only a small amount of labeled data from a specific subject for personalization and enable cross-session emotion recognition. Our framework emphasizes: 1) Multi-scale representation to capture diverse aspects of EEG signals, obtaining comprehensive information; 2) An improved masking mechanism for robust channel-level representation learning, addressing missing channel issues while preserving inter-channel relationships; and 3) Invariance learning for regional correlations in spatial-level representation, minimizing inter-subject and inter-session variances. Under these elaborate designs, the proposed MSMAE exhibits a remarkable ability to decode emotional states from a different session of EEG data during the testing phase. Extensive experiments conducted on the two publicly available datasets, i.e., SEED and SEED-IV, demonstrate that the proposed MSMAE consistently achieves stable results and outperforms competitive baseline methods in cross-session emotion recognition.

Swimming ability of Schizothoracinae fishes in Yarlung Zangbo River of China.

The Yarlung Zangbo River is a river with abundant hydropower resources but fragile biodiversity in China. As an important benchmark for both research and ecological management, there is still a lack of knowledge about the swimming ability of fishes in the Yarlung Zangbo River. The induced flow velocity (Uind), critical swimming speed (Ucrit), and burst swimming speed (Uburst) of five Schizothoracinae species were tested in this study. Relative swimming ability related to body length and body shape was calculated. The results indicated that the average absolute swimming speeds (Uind-a, Ucrit-a, and Uburst-a) of all the experimental fish were 10.20 ± 0.01, 57.58 ± 3.28, and 69.54 ± 2.94 cm/s, respectively, and the corresponding relative Uind, Ucrit, and Uburst related to body length (Uind-l, Ucrit-l, Uburst-l) were 1.15 ± 0.07, 5.04 ± 0.26, and 7.23 ± 0.28 BL/s, respectively. Moreover, relative Uind, Ucrit, and Uburst related to body shape (Uind-s, Ucrit-s, and Uburst-s) were 0.80 ± 0.13, 2.49 ± 0.51, and 4.32 ± 0.57 cm-2/s, respectively. No significantly differences in relative swimming speeds existed among five species. Only Oxygymnocypris stewartii was significantly weaker in Uburst-s than Schizothorax o'connori. The body shape showed a stronger relationship with swimming speed than the body length did. Schizothoracinae fish in the Yarlung Zangbo River basin are less sensitive to the water flow and performed weaker Ucrit and Uburst compared to those in the Yangtze River basin, indicating that Schizothoracinae fish in the Yarlung Zangbo River may be more susceptible to threats from environmental changes. The paper enriched the research on the swimming ability of Schizothoracinae fishes and provided efficient data for the fish conservation in the Yarlung Zangbo River.

Immune responses induced by Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) upon co-administration with Bacillus Calmette-Guérin in mice.

OBJECTIVES: To preliminarily assess the immunogenicity of Mtb-HAg in mice and the synergistic effect provided by HAg when co-immunised with BCG. METHODS: Mice were randomly grouped for different immunisations and then spleens were aseptically removed and lymphocytes were extracted for immediate detection of cytokines transcript levels and stimulation index(SI), cytokine secretion and multifunctional antigen-specific T cells were detected after incubation for different times. RESULTS: HAg extracted from active Mtb is a group of mixed polypeptides with molecular weights of (10-14) kDa. It can significantly stimulate lymphocytes proliferation and increase SI. Injection of HAg alone and in combination with BCG induced significantly higher numbers of multifunctional antigen-specific T cells including CD4+ IFN-γ+, CD4+ IL-2+, CD8+ IFN-γ+, and CD8+ IL-2+ cells than that in BCG-treated mice. Co-immunisation induced the secretion of higher levels of IFN-γ, TNF-α, IL-2 and IL-4 and increased their mRNA expression levels. Significant increases in the transcription levels of IL-10, IL-12 and IL-17 were observed in the co-immunised group with the assistance of HAg. CONCLUSION: We demonstrated that HAg has favourable immunogenicity, triggers a stronger Th1-type immune response and proposed the hypothesis that HAg can be used as a BCG booster to further enhance the benefits of BCG.

Acute lung injury: a view from the perspective of necroptosis.

BACKGROUND: ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS. METHODS: The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented. CONCLUSION: Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms.

Cav3.2 channel regulates cerebral ischemia/reperfusion injury: a promising target for intervention.

JOURNAL/nrgr/04.03/01300535-202419110-00028/figure1/v/2024-03-08T184507Z/r/image-tiff Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury. Various calcium channels are involved in cerebral ischemia/reperfusion injury. Cav3.2 channel is a main subtype of T-type calcium channels. T-type calcium channel blockers, such as pimozide and mibefradil, have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury. However, the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear. Here, in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons. The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons. We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury. Cav3.2 knockout markedly reduced infarct volume and brain water content, and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury. Additionally, Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress, inflammatory response, and neuronal apoptosis. In the hippocampus of Cav3.2-knockout mice, calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury. These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling. Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

Revisiting the role and mechanism of ELF3 in circadian clock modulation.

The gene encoding EARLY FLOWERING3 (ELF3) is necessary for photoperiodic flowering and the normal regulation of circadian rhythms. It provides important information at the cellular level to uncover the biological mechanisms that improve plant growth and development. ELF3 interactions with transcription factors such as BROTHER OF LUX ARRHYTHMO (BOA), LIGHT-REGULATED WD1 (LWD1), PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), PHYTOCHROME-INTERACTING FACTOR 7 (PIF7), and LUX ARRHYTHMO (LUX) suggest a role in evening complex (EC) independent pathways, demanding further investigation to elucidate the EC-dependent versus EC-independent mechanisms. The ELF3 regulation of flowering time about photoperiod and temperature variations can also optimize crop cultivation across diverse latitudes. In this review paper, we summarize how ELF3's role in the circadian clock and light-responsive flowering control in crops offers substantial potential for scientific advancement and practical applications in biotechnology and agriculture. Despite its essential role in crop adaptation, very little is known in many important crops. Consequently, comprehensive and targeted research is essential for extrapolating ELF3-related insights from Arabidopsis to other crops, utilizing both computational and experimental methodologies. This research should prioritize investigations into ELF3's protein-protein interactions, post-translational modifications, and genomic targets to elucidate its contribution to accurate circadian clock regulation.

Dynamic transcriptome analysis provides molecular insights into underground floral differentiation in Adonis Amurensis Regel & Radde.

Understanding flower developmental processes is a prerequisite for improving flowering 'plants' production. Adonis amurensis is a fascinating spring ephemeral plant that develops its flower organs underground. Nevertheless, knowledge of the molecular mechanisms driving this particular process is scarce. Herein, we examined transcriptional changes during underground flower differentiation in A. amurensis and unveiled key differently regulated genes and pathways. High-throughput RNA sequencing of meristems at different flower developmental stages, including flower primordium (FP), sepal stage (SE), perianth primordium (PE), stamen stage (ST), and pistil stage (PI), identified 303,234 unigenes that showed 44.79% similarity with sequences in Aquilegia coerulea. Correlations, principal component, and differentially expressed genes (DEGs) analyses revealed that few molecular changes occurred during the transition from PE to ST. Many DEGs exhibited stage-specific regulations. Transcription factor (TF) and phytohormone family genes are critical regulators of the floral differentiation process in A. amurensis. The most differentially regulated TFs were MADS, FAR1, MYBs, AP2/ERF, B3, C2H2, and LOBs. We filtered out 186 candidate genes for future functional studies, including 18 flowering/circadian-related, 32 phytohormone-related, and TF family genes. Our findings deepen our understanding of the underground flower differentiation process and offer critical resources to dissect its regulatory network in A. amurensis. These findings establish a foundational platform for researchers dedicated to exploring the unique phenotypic characteristics of this specific flowering modality and delving into the intricate molecular mechanisms underpinning its regulation and expression.

Fungal community diversity and their contribution to nitrogen cycling in in-situ aerated landfills: Insights from field and laboratory studies.

The application of in-situ aeration technology in landfills has been reported to promote fungal growth, but the community diversity and function of fungi in the aerated landfill system remain unknown. This study firstly investigated an in-situ aerated remediation landfill site to characterize the fungal community diversity in refuse. And to further reveal the fungal involvement in the nitrogen cycling system, laboratory-scale simulated aerated landfill reactors were then constructed. The results in the aerated landfill site showed a significant correlation between fungal community structure and ammonia nitrogen content in the refuse. Dominant fungi in the fungal community included commonly found environmental fungi such as Fusarium, Aspergillus, Gibberella, as well as unique fungi in the aerated system like Chaetomium. In the laboratory-scale aerated landfill simulation experiments, the fungal system was constructed using bacterial inhibitor, and nitrogen balance analysis confirmed the significant role of fungal nitrification in the nitrogen cycling process. When ammonia nitrogen was not readily available, fungi converted organic nitrogen to nitrate, serving as the main nitrification mechanism in the system, with a contribution rate ranging from 62.71 % to 100 % of total nitrification. However, when ammonia nitrogen was present in the system, autotrophic nitrification became the main mechanism, and the contribution of fungal nitrification to total nitrification was only 15.96 %. Additionally, fungi were capable of directly utilizing nitrite for nitrate production with a rate of 4.65 mg L-1 d-1. This research article contributes to the understanding of the importance of fungi in the aerated landfill systems, filling a gap in knowledge.

Canopy nitrogen deposition enhances soil ecosystem multifunctionality in a temperate forest.

Nitrogen (N) deposition affects ecosystem functions crucial to human health and well-being. However, the consequences of this scenario for soil ecosystem multifunctionality (SMF) in forests are poorly understood. Here, we conducted a long-term field experiment in a temperate forest in China, where N deposition was simulated by adding N above and under the canopies. We discover that canopy N addition promotes SMF expression, whereas understory N addition suppresses it. SMF was regulated by fungal diversity in canopy N addition treatments, which is largely due to the strong resistance to soil acidification and efficient resource utilization characteristics of fungi. While in understory N addition treatments, SMF is regulated by bacterial diversity, which is mainly because of the strong resilience to disturbances and fast turnover of bacteria. Furthermore, rare microbial taxa may play a more important role in the maintenance of the SMF. This study provides the first evidence that N deposition enhanced SMF in temperate forests and enriches the knowledge on enhanced N deposition affecting forest ecosystems. Given the divergent results from two N addition approaches, an innovative perspective of canopy N addition on soil microbial diversity-multifunctionality relationships is crucial to policy-making for the conservation of soil microbial diversity and sustainable ecosystem management under enhanced N deposition. In future research, the consideration of canopy N processes is essential for more realistic assessments of the effects of atmospheric N deposition in forests.

Inhibition of Drp1- Fis1 interaction alleviates aberrant mitochondrial fragmentation and acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common clinical disorder with complex etiology and poor prognosis, and currently lacks specific and effective treatment options. Mitochondrial dynamics dysfunction is a prominent feature in AKI, and modulation of mitochondrial morphology may serve as a potential therapeutic approach for AKI. METHODS: We induced ischemia-reperfusion injury (IRI) in mice (bilateral) and Bama pigs (unilateral) by occluding the renal arteries. ATP depletion and recovery (ATP-DR) was performed on proximal renal tubular cells to simulate in vitro IRI. Renal function was evaluated using creatinine and urea nitrogen levels, while renal structural damage was assessed through histopathological staining. The role of Drp1 was investigated using immunoblotting, immunohistochemistry, immunofluorescence, and immunoprecipitation techniques. Mitochondrial morphology was evaluated using confocal microscopy. RESULTS: Renal IRI induced significant mitochondrial fragmentation, accompanied by Dynamin-related protein 1 (Drp1) translocation to the mitochondria and Drp1 phosphorylation at Ser616 in the early stages (30 min after reperfusion), when there was no apparent structural damage to the kidney. The use of the Drp1 inhibitor P110 significantly improved kidney function and structural damage. P110 reduced Drp1 mitochondrial translocation, disrupted the interaction between Drp1 and Fis1, without affecting the binding of Drp1 to other mitochondrial receptors such as MFF and Mid51. High-dose administration had no apparent toxic side effects. Furthermore, ATP-DR induced mitochondrial fission in renal tubular cells, accompanied by a decrease in mitochondrial membrane potential and an increase in the translocation of the pro-apoptotic protein Bax. This process facilitated the release of dsDNA, triggering the activation of the cGAS-STING pathway and promoting inflammation. P110 attenuated mitochondrial fission, suppressed Bax mitochondrial translocation, prevented dsDNA release, and reduced the activation of the cGAS-STING pathway. Furthermore, these protective effects of P110 were also observed renal IRI model in the Bama pig and folic acid-induced nephropathy in mice. CONCLUSIONS: Dysfunction of mitochondrial dynamics mediated by Drp1 contributes to renal IRI. The specific inhibitor of Drp1, P110, demonstrated protective effects in both in vivo and in vitro models of AKI.

Deep learning-based control framework for dynamic contact processes in humanoid grasping.

Humanoid grasping is a critical ability for anthropomorphic hand, and plays a significant role in the development of humanoid robots. In this article, we present a deep learning-based control framework for humanoid grasping, incorporating the dynamic contact process among the anthropomorphic hand, the object, and the environment. This method efficiently eliminates the constraints imposed by inaccessible grasping points on both the contact surface of the object and the table surface. To mimic human-like grasping movements, an underactuated anthropomorphic hand is utilized, which is designed based on human hand data. The utilization of hand gestures, rather than controlling each motor separately, has significantly decreased the control dimensionality. Additionally, a deep learning framework is used to select gestures and grasp actions. Our methodology, proven both in simulation and on real robot, exceeds the performance of static analysis-based methods, as measured by the standard grasp metric Q1. It expands the range of objects the system can handle, effectively grasping thin items such as cards on tables, a task beyond the capabilities of previous methodologies.

Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event. METHODS: All ACS patients were screened at the Second Affiliated Hospital of Xi'an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded. RESULTS: The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan-Meier survival analysis (HR = 1.282, log-rank test: P > 0.05). CONCLUSIONS: FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.

Mechanical quenching phenomenon in diamond.

The structure of dislocation cores, the fundamental knowledge on crystal plasticity, remains largely unexplored in covalent crystals. Here, we conducted atomically resolved characterizations of dislocation core structures in a plastically deformed diamond anvil cell tip that was unloaded from an exceptionally high pressure of 360 GPa. Our observations unveiled a series of nonequilibrium dislocation cores that deviate from the commonly accepted "five-seven-membered ring" dislocation core model found in FCC-structured covalent crystals. The nonequilibrium dislocation cores were generated through a process known as "mechanical quenching," analogous to the quenching process where a high-energy state is rapidly frozen. The density functional theory-based molecular dynamic simulations reveal that the phenomenon of mechanical quenching in diamond arises from the challenging relaxation of the nonequilibrium configuration, necessitating a large critical strain of 25% that is difficult to maintain. Further electronic-scale analysis suggested that such large critical strain is spent on the excitation of valance electrons for bond breaking and rebonding during relaxation. These findings establish a foundation for the plasticity theory of covalent materials and provide insights into the design of electrical and luminescent properties in diamond, which are intimately linked to the dislocation core structure.

Mycobacterium tuberculosis PE_PGRS45 (Rv2615c) Promotes Recombinant Mycobacteria Intracellular Survival via Regulation of Innate Immunity, and Inhibition of Cell Apoptosis.

Tuberculosis (TB), a bacterial infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is a significant global public health problem. Mycobacterium tuberculosis expresses a unique family of PE_PGRS proteins that have been implicated in pathogenesis. Despite numerous studies, the functions of most PE_PGRS proteins in the pathogenesis of mycobacterium infections remain unclear. PE_PGRS45 (Rv2615c) is only found in pathogenic mycobacteria. In this study, we successfully constructed a recombinant Mycobacterium smegmatis (M. smegmatis) strain which heterologously expresses the PE_PGRS45 protein. We found that overexpression of this cell wall-associated protein enhanced bacterial viability under stress in vitro and cell survival in macrophages. MS_PE_PGRS45 decreased the secretion of pro-inflammatory cytokines such as IL-1ß, IL-6, IL-12p40, and TNF-α. We also found that MS_PE_PGRS45 increased the expression of the anti-inflammatory cytokine IL-10 and altered macrophage-mediated immune responses. Furthermore, PE_PGRS45 enhanced the survival rate of M. smegmatis in macrophages by inhibiting cell apoptosis. Collectively, our findings show that PE_PGRS45 is a virulent factor actively involved in the interaction with the host macrophage.