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The general objective of the review is to explain the interaction between HIF-1 and mitochondria. On the one hand, this review describes the effects of HIF-1 on mitochondrial structure, including quantity, distribution, and morphology, as well as on mitochondrial metabolism and respiratory function. On the other hand, various factors, including mitochondrial activation of enzymes, the respiratory chain, complex and decoupling proteins, affect the stability and activity of HIF-1. It is possible to develop future molecular therapeutic interventions by understanding the interrelationships between HIF-1 and mitochondria.

Ag-Nb2AlC composite materials with a Nb2AlC volume percentage ranging from 10% to 40% were prepared using the spark plasma sintering method. The composite with 10% Nb2AlC achieved a high density of 99.2%. The microhardness exhibited a peak value of 84.8 HV at a Nb2AlC content of 30%. The conductivity of the composite material decreases linearly with an increase in Nb2AlC content, ranging from 0.134 MS·cm−1 to 0.086 MS·cm−1. A three-dimensional laser scanning microscope was employed to characterize the morphology following arc erosion, and the erosion area was subsequently measured. Results indicated that arc erosion was concentrated on the Ag-20 vol.% Nb2AlC composite material, resulting in a smaller circular erosion area. As Nb2AlC content increased to 30% and 40%, the arc shifted, leading to an expansion of the erosion area. Notably, the Ag-30 vol.% Nb2AlC composite material exhibited the highest arc energy (3.401 kJ). The eroded surface displayed spattered particles and a convex morphology. Additionally, EDS and Raman spectroscopic analyses revealed the formation of Nb2O5, Ag2O, and Al2O3 on the surface. The arc erosion mechanism was analyzed from an electrical perspective, indicating that the formation of the arc is attributed to the development of a positive streamer and air breakdown within a strongly nonuniform field. Consequently, the surface atoms of Ag-Nb2AlC absorb energy, leading to the formation of metal ions that combine with the ionized air to create oxides. This research lays a theoretical foundation for the application of silver-based electrical contact materials.

Despite significant advancements in CNN-based object detection technology, adverse weather conditions can disrupt imaging sensors’ ability to capture clear images, thereby adversely impacting detection accuracy. Mainstream algorithms for adverse weather object detection enhance detection performance through image restoration methods. Nevertheless, the majority of these approaches are designed for a specific degradation scenario, making it difficult to adapt to diverse weather conditions. To cope with this issue, we put forward a degradation type-aware restoration-assisted object detection network, dubbed DTRDNet. It contains an object detection network with a shared feature encoder (SFE) and object detection decoder, a degradation discrimination image restoration decoder (DDIR), and a degradation category predictor (DCP). In the training phase, we jointly optimize the whole framework on a mixed weather dataset, including degraded images and clean images. Specifically, the degradation type information is incorporated in our DDIR to avoid the interaction between clean images and the restoration module. Furthermore, the DCP makes the SFE possess degradation category awareness ability, enhancing the detector’s adaptability to diverse weather conditions and enabling it to furnish requisite environmental information as required. Both the DCP and the DDIR can be removed according to requirement in the inference stage to retain the real-time performance of the detection algorithm. Extensive experiments on clear, hazy, rainy, and snowy images demonstrate that our DTRDNet outperforms advanced object detection algorithms, achieving an average mAP of 79.38% across the four weather test sets.

Islands are important sources of environmental resources, and assessing their ecological status is important to ensure their sustainable use, conservation, and management. We use the Pressure-State-Response model to identify 12 risk sources, 7 risk receptors, and 2 risk responses, in a system that factors in the probability of risk occurrence and ecosystem fragility. An ecological risk identification matrix for island ecosystems is established, which, in combination with risk value computations and grading criteria, enables the determination of the risk level of island ecosystems. We report risk values for terrestrial ecosystems on North Changshan Island and the intertidal and coastal waters of Miao Island to be moderate (0.50), signifying that certain risks exist and that precautionary measures should be taken to prevent potential ecological problems. For North Changshan Island, this value for the intertidal and coastal waters is 0.74, because this environment is more sensitive to risks from aquaculture. The lower risk value for terrestrial ecosystems on Miao Island (0.40) indicates a reduced possibility of ecological problems. These findings provide data and technical support for the protection of island plant species, preservation of island ecosystems, ecological restoration and optimization of damaged islands, and the spatial development of islands.

Immune microenvironment could affect the biological progress in prostate cancer (PCa) through N6 methyl adenosine (m6A) methylation. The purpose of this study was to investigate the crosstalk between m6A methylation and immune microenvironment and explore potential biomarkers to improve the immunotherapeutic response. Firstly, according to 11 differentially expressed m6A genes between normal and tumor samples, PCa patients were divided into immune microenvironment subtype 1 (IMS1) and IMS2 based on m6A gene profiles extracted from The Cancer Genome Atlas (TCGA) database. IMS2 showed an immune “cold” phenotype with worse prognoses, and HNRNPC was identified as the biomarker of IMS2 by the protein‐protein interaction network. Furthermore, through bioinformatics analyses and in vitro experiments, we found that HNRNPC‐high patients showed a suppressive immune‐infiltrating tumor microenvironment with a higher infiltration of regulatory T (Treg) cells. Finally, we cocultured transfected PCa cells with peripheral blood mononuclear cells (PBMC) and verified that HNRNPC inhibits tumor immunity by elevating the activation of Treg cells and suppression of effector CD8 T cell. In conclusion, we identified a “cold” immune phenotype in PCa, and HNRNPC regulating the activation of Treg cells. Activation of the immune microenvironment through targeting HNRNPC may be a potential therapeutic option for advanced PCa. Harboring a high expression level of m6A reader HNRNPC, progressed prostate cancer (PCa) exhibited a “cold” immune phenotype, which was mainly induced by increasing Treg abundance. Targeting HNRNPC may help activate the immune microenvironment or elevate the sensitiveness to anti‐CTLA4 therapies.

Tuberculosis (TB) caused by Mycobacterium tuberculosis ( Mtb ) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb , the role of calcium (Ca 2+ ) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb -infected mice and macrophages. The target of miR-27a is the ER-located Ca 2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca 2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb . Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca 2+ -associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches. How Mycobacterium tuberculosis ( Mtb ) escapes autophagy-mediated clearance is poorly understood. Here, Liu et al. show that Mtb-induced MicroRNA-27a targets the ER-associated calcium transporter CACNA2D3, leading to suppression of antimicrobial autophagy and to enhanced intracellular survival of Mtb .

Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis ( M. tuberculosis ), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene β-defensin 4 ( Defb4 ) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis . In this work, authors mechanistically investigate the reduced induction of antimicrobial peptides in Mycobacterium tuberculosis infected macrophages.

The stainless steel/aluminum multilayer composites were prepared by one-step explosive welding using ammonium nitrate explosive with two different thicknesses. The microstructure and mechanical properties of the multilayer composites were examined. There is a thin metallurgical melting zone at each bonding interface, consisting mostly of iron and aluminum elements. However, the micro-crack appears in the second metallurgical bonding zone obtained using the explosive of 24 mm thickness. The micro-hardness values at the four bonding interfaces are higher than those of bulk 1060 aluminum and 304 stainless steel. The yield strength of the multilayer composites obtained in the two cases is higher than that of the original 304 stainless steel while the tensile strength is between those of the original 1060 aluminum and 304 stainless steel. Meanwhile, the tensile strength and yield strength of multilayer composites obtained by explosive welding with explosive of 20 mm thickness are relatively higher.

The stainless steel/aluminum multilayer composites were prepared by one-step explosive welding using ammonium nitrate explosive with two different thicknesses. The microstructure and mechanical properties of the multilayer composites were examined. There is a thin metallurgical melting zone at each bonding interface, consisting mostly of iron and aluminum elements. However, the micro-crack appears in the second metallurgical bonding zone obtained using the explosive of 24 mm thickness. The micro-hardness values at the four bonding interfaces are higher than those of bulk 1060 aluminum and 304 ­stainless steel. The yield strength of the multilayer composites obtained in the two cases is higher than that of the original 304 stainless steel while the tensile strength is between those of the original 1060 aluminum and 304 stainless steel. Meanwhile, the tensile strength and yield strength of multilayer composites obtained by explosive welding with explosive of 20 mm thickness are relatively higher.

Background This study evaluated the prognostic implications of pathological responses of primary tumors (PTs) and lymph nodes (LNs) among locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients received neoadjuvant immunotherapy combined with chemotherapy (nICT). Methods This study enrolled patients with LA-ESCC who underwent nICT combined with esophagectomy at Jiangsu Cancer Hospital. Two senior pathologists independently and systematically evaluated the postoperative pathological specimens in a double-blind manner. Tumor regression in PTs was assessed using the Becker criteria, while LNs regression grading was optimized using Harrell’s concordance index and the Akaike Information Criterion. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with recurrence patterns as the secondary endpoint. Results A total of 141 patients with 141 PTs and 2,316 LNs were reviewed. LNs regression classified as LNs complete response (LN-CR); Partial/Poor response (LN-PR); and Truly negative LNs (LNN). The ypT0N0 rate was 21.3%. With median 41-months follow-up (IQR 22–55), the 3-year OS and PFS rates were 61.7% (95% CI 53.3–69.1%) and 48.2% (95% CI 40.2–56.4%), respectively. PTs regression grade was an independent prognostic factor for both OS and PFS ( P  < 0.05). Multivariable analysis demonstrated that a poorer tumor regression grade (TRG) was significantly associated with increased risks of OS and PFS ( P  < 0.05). Furthermore, while complete LN-CR correlated with improved PFS compared to LN-PR ( P  = 0.037), this association did not retain statistical significance in the multivariate analysis. Non-ypT0N0 patients exhibited higher recurrence rates than ypT0N0 (52.3% vs 33.3%, P  = 0.047), primarily manifested as mixed progression. Conclusions PTs response may constitute a more prominent determinant of both OS and PFS than LNs status, and combining these factors enhances prognostic prediction.