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Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor β (TGFβ) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFβ inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1 (as those levels found in patients’ synovial fluid). A monthly injection strategy was then designed of using poly lactic-co-glycolic acid (PLGA) microparticles and hyaluronic acid (HA) solution to enable a sustained release of PFD (the “PLGA-PFD + HA” strategy). This strategy effectively regulated OA progression in destabilization of the medial meniscus (DMM)- induced OA mice model, including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA, and reduced synovitis and pain with cartilage preservation effects. This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

Abstract The function of proteins depends on their correct structure and proper dynamics. Understanding the dynamics of target proteins facilitates drug design and development. However, dynamic information is often hidden in the spatial structure of proteins. It is important but difficult to identify the specific residues that play a decisive role in protein dynamics. Here, we report that a critical glycine residue (Gly463) dominates the motion of threonyl-tRNA synthetase (ThrRS) and the sensitivity of the enzyme to antibiotics. Obafluorin (OB), a natural antibiotic, is a novel covalent inhibitor of ThrRS. The binding of OB induces a large conformational change in ThrRS. Through five crystal structures, biochemical and biophysical analyses, and computational simulations, we found that Gly463 plays an important role in the dynamics of ThrRS. Mutating this flexible residue into more rigid residues did not damage the enzyme’s three-dimensional structure but significantly improved the thermal stability of the enzyme and suppressed its ability to change conformation. These mutations cause resistance of ThrRS to antibiotics that are conformationally selective, such as OB and borrelidin. This work not only elucidates the molecular mechanism of the self-resistance of OB-producing Pseudomonas fluorescens but also emphasizes the importance of backbone kinetics for aminoacyl-tRNA synthetase-targeting drug development.

Lepista sordida is a valuable edible mushroom rich in natural bioactive compounds. In the present study, a high-quality whole-genome of a domesticated strain of L. sordida was sequenced, revealing a 40.67 Mb genome in 13 contigs. Phylogenetic analysis revealed that L. sordida is evolutionarily closely related to edible mushroom Lyophyllum decastes and Hypsizygus marmoreus. Heat stress has a significant effect on the yield and quality of mushrooms, but the molecular basis for this is poorly understood in L. sordida. A label-free comparative proteomic analysis was performed under different heat stress conditions. The growth of L. sordida mycelia was inhibited, and nuclear apoptosis occurred under heat stress. Ca2+ and MAPK signaling pathways were found to be involved in heat stress signal transduction. It is hypothesized that the expression of various heat shock proteins plays a crucial role in the response to heat stress. In addition, the components of the ubiquitin-proteasome system and the thioredoxin system were upregulated, preventing the accumulation of misfolded proteins and possibly supporting the response to heat stress. In summary, these results provide a fundamental insight into the evolution and heat stress-responsive mechanisms in L. sordida and may facilitate the breeding of heat-tolerant strains for artificial cultivation.

Large rivers throughout the world have been transformed by anthropogenic stressors that are known to influence the structure and composition of fish assemblages. Management of large rivers requires balancing socio-economic and political considerations with biodiversity conservation efforts. By exchanging best management practices between rivers, management efforts can be improved. However, data limitations have largely prevented comparative analyses among fish assemblages in large rivers, potentially limiting the effectiveness of shared management strategies. To improve understanding of the similarities and differences between the Upper Mississippi and Yangtze Rivers, we (1) compared environmental variables and functional traits of fish assemblages between the two systems, (2) identified traits responsible for distinguishing functional groups from one another, and (3) investigated relationships between similar functional groups of fishes and environmental variables to establish expectations for how fish assemblages in large rivers might respond to anthropogenic stressors. Regional species pools in the Upper Mississippi and Upper Yangtze Rivers were characterized by a similar composition of functional traits; the majority of species were omnivorous, had affinities for gravel or sand substrates, and produced sinking eggs. Few species were pelagic, planktivorous, or herbivorous. Functional groups in both rivers were primarily distinguished according to species' trophic habits and substrate preferences, with secondary contributions from species’ water column positions and life history characteristics. Pelagic planktivores and small-bodied guarders with an affinity for structural habitat complexity tended to increase downriver in both systems, in direct association with total phosphorus concentrations, agricultural land use, and temperature. In contrast, proportions of lithophilic species with affinities for gravel or cobble substrates were highest in segments located furthest upriver. By highlighting the sensitivity of different groups of fishes to anthropogenic stressors, we provide insights into the functional ecology of fishes inhabiting the Mississippi and Yangtze Rivers.

In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie bandavirus (DBV), was first discovered in Henan, China. It is a tick-borne zoonotic virus with a fatality rate ranging from 6% to 30%. Currently, we lack safe and effective vaccines or antiviral drugs to treat SFTSV infection. Therefore, the development of a specific, sensitive, and cost-effective detection method is crucial. Using inactivated SFTSV and recombinant SFTSV nucleocapsid protein (SFTSV-NP), we repeatedly immunized mice with different adjuvants and obtained two monoclonal antibodies against SFTSV-NP, which were used to develop a colloidal gold immunochromatographic assay (ICA) rapid test kit for SFTSV. Compared with nucleic acid testing (gold standard), the ICA test strips are 97.67% accurate in testing clinical serum samples (36 cases of clinical serum samples and seven cases of whole blood samples). The test kit was 100% accurate in detecting different SFTSV strains. No false-positive results were generated when detecting other arboviruses. Therefore, our developed SFTSV test kit conveniently, rapidly, and effectively detects SFTSV.

Abstract Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.

Abstract Understanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6130 UK Biobank (UKBB) participants’ T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as Unsupervised Deep learning derived Imaging Phenotypes (UDIPs). GWAS of these UDIPs in held-out UKBB subjects (n = 22,880 discovery and n = 12,359/11,265 replication cohorts for T1/T2) identified 9457 significant SNPs organized into 97 independent genetic loci of which 60 loci were replicated. Twenty-six loci were not reported in earlier T1 and T2 IDP-based UK Biobank GWAS. We developed a perturbation-based decoder interpretation approach to show that these loci are associated with UDIPs mapped to multiple relevant brain regions. Our results established unsupervised deep learning can derive robust, unbiased, heritable, and interpretable brain imaging phenotypes.

We obtained Peripheral blood mononuclear cells (PBMCs) from a peripheral blood sample of a 19-year-old male schizophrenia patient and successfully established induced pluripotent stem cell (iPSC) line using non-integrated reprogramming technology. This cell line possesses the correct karyotype, shape of an embryonic stem cell, the ability to express particular pluripotency markers, and the capacity to differentiate into three germ layers in vitro. This cell line will serve as an in vitro model for upcoming studies on the etiology of schizophrenia and the creation of novel treatment.

Sorafenib (SF), a multi-targeted tyrosine kinase inhibitor, serves as a primary therapeutic modality for advanced liver cancer. Nonetheless, its clinical efficacy is hindered by various obstacles, such as limited bioavailability and inadequate accumulation. This study introduces a novel biomimetic mineralization enzyme, known as BSA@Pt/Ce6/SF@M (PCFM). The PCFM incorporates platinum (Pt) as a catalytic agent, SF as a molecular-targeted therapeutic agent, and Ce6 as a photosensitizer within liver cancer cell membranes. This strategy enables the combination of various anti-tumor treatments, such as photodynamic therapy (PDT) and autophagy induction, leading to increased bioavailability of SF and achieving a multidimensional synergistic anticancer effect. The PDT effect produced by Ce6 in PCFM greatly enhances SF-induced autophagy, effectively promoting autophagic cell death. Furthermore, Pt dissociates from the biomineralization process, acquiring peroxidase properties through chemokinetic reactions. This facilitates the catalysis of significant oxygen generation, addressing the challenge of hypoxia in the tumor microenvironment and improving the efficacy of PDT. Moreover, the SF further enhances therapeutic efficacy by inducing autophagy in response to energy deprivation, as indicated by the reduced levels of HIF-1α, p62, along with increased levels of ROS and LC3-Ⅱ/Ι. This biomineralization-based nanoenzyme exhibits strong anti-tumor characteristics, offering a novel strategy for overcoming challenges in liver cancer treatment.

Cerebrospinal fluid-contacting neurons (CSF-cNs) represent a distinct group of interneurons characterized by their prominent apical globular protrusions penetrating the spinal cord’s central canal and their basal axons extending towards adjacent cells. Identified nearly a century back, the specific roles and attributes of CSF-cNs have just started to emerge due to the historical lack of definitive markers. Recent findings have confirmed that CSF-cNs expressing PKD2L1 possess attributes of neural stem cells, suggesting a critical function in the regeneration processes following spinal cord injuries. This review aims to elucidate the molecular markers of CSF-cNs as potential neural stem cells during spinal cord development and assess their roles post-spinal cord injury, with an emphasis on their potential therapeutic implications for spinal cord repair.

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis.

Multi-Label Classification refers to the classification task where a data sample is associated with multiple labels simultaneously, which is widely used in text classification, image classification, and other fields. Different from the traditional single-label classification, each instance in Multi-Label Classification corresponds to multiple labels, and there is a correlation between these labels, which contains a wealth of information. Therefore, the ability to effectively mine and utilize the complex correlations between labels has become a key factor in Multi-Label Classification methods. In recent years, research on label correlations has shown a significant growth trend internationally, reflecting its importance. Given that, this paper presents a survey on the label correlations in Multi-Label Classification to provide valuable references and insights for future researchers. The paper introduces multi-label datasets across various fields, elucidates and categorizes the concept of label correlations, emphasizes their utilization in Multi-Label Classification and associated subproblems, and provides a prospect for future work on label correlations.

As China accelerates its transition to a low-carbon society, its power system is facing growing challenges in terms of maintaining adequacy amid a rapidly evolving energy structure. The concept of adequacy, traditionally focused on power capacity and generation, has broadened to include dimensions like flexibility and inertia. Against this backdrop, optimizing the integration of coal power and renewable energy to meet the system’s needs for adequacy, flexibility, and frequency stability has become a critical research area. This paper introduces the concept of “Generalized Adequacy”, expanding the traditional understanding of adequacy, and proposes an optimization model for the coordinated development of coal power and renewable energy based on this concept. This study examines the effects of extreme weather, renewable energy penetration, wind–solar ratios, and generalized adequacy constraints using a case study from a central region of China. The findings reveal that extreme weather conditions drive an increase in photovoltaic installations, while higher renewable energy penetration leads to more wind power installations. Accounting for generalized adequacy constraints can moderate the retirement of coal-fired plants, reducing unnecessary inertia support in normal conditions and ensuring dynamic frequency stability during extreme weather events.

In this study, a single-outer-spiral electrode with inductance of 20 μH is employed to couple the energy input of a bipolar nanosecond pulse for the purpose of generating a large-scale atmospheric pressure plasma jet. When the spiral electrode is wrapped around a plasma jet tube with a length of 35 cm, the electrical field can be optimized, resulting in a stable laminar flow field, and a plasma jet with a length and diameter larger than 14 cm and 1.2 cm can be generated. A comparative study of the bipolar and unipolar pulse excitation voltages is also conducted, showing that the maximum lengths of the plasma jet excited by a bipolar pulse voltage, positive pulse voltage, and negative are 14 cm, 10 cm, and 7 cm, respectively. The temporal and spatially resolved spectra of the plasma jets excited by both bipolar and unipolar pulses are investigated, respectively, and the main physiochemical processes of the active species and the plasma dynamics’ evolution are discussed.

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.

The water jet nozzle is a penetrating drilling tool, which sends the pumped water to the nozzle through a high-pressure hose. It can work in a variety of working environments. When it dredges the blockage in the pipeline, its structural parameters will affect the jet flow field in the pipeline. Taking the self-propelled water jet nozzle as the research object, SolidWorks was used to establish the nozzle model with different parameter structures. Based on Fluent, the k-ε turbulence model was used to simulate the jet of nozzles with different nozzle sizes and arrangements in the pipeline. The distribution of the jet flow field and the change in velocity and displacement of nozzles with different parameters in the pipeline were compared, and then computational fluid dynamics (CFD) were used to process the simulation data for further research. The results show that when the inclination angle of the rear nozzle is 35°, the attenuation of the front jet velocity and the fluctuation of the wall fluid velocity are the smallest. When the nozzle aperture is increased from 2 mm to 3.5 mm, the vortex area inside the pipe is reduced, and the velocity attenuation of the front jet is also reduced, with the velocity attenuation rate decreasing by about 10%. This study provides a reference for the design and parameter optimization of self-propelled water jet nozzles.

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium graminearum, and curcumin (CUR) is a natural polyphenolic compound found in turmeric. However, the combined treatment of CUR and DON to explore the mitigating effect of CUR on DON and their combined mechanism of action is not clear. Therefore, in this study, we established four treatment groups (CON, CUR, DON and CUR + DON) to investigate their mechanism in the porcine intestinal epithelial cells (IPEC-J2). In addition, the cross-talk and alleviating potential of CUR interfering with DON-induced cytotoxic factors were evaluated by in vitro experiments; the results showed that CUR could effectively inhibit DON-exposed activated TNF-α/NF-κB pathway, attenuate DON-induced apoptosis, and alleviate DON-induced endoplasmic reticulum stress and oxidative stress through PERK/CHOP pathways, which were verified at both mRNA and protein levels. In conclusion, these promising findings may contribute to the future use of CUR as a novel feed additive to protect livestock from the harmful effects of DON.

The impact of contact between two elastic–plastic bodies is highly complex, with no established theoretical contact model currently available. This study investigates the problem of an elastic–plastic sphere impacting an elastic–plastic half-space at low speed and low energy using the finite element method (FEM). Existing linear contact loading laws exhibit significant discrepancies as they fail to consider the impact of elasticity and yield strength on the elastic–plastic sphere. To address this limitation, a novel linear contact loading law is proposed in this research, which utilizes the concept of equivalent contact stiffness rather than the conventional linear contact stiffness. The theoretical expressions of this new linear contact loading law are derived through FEM simulations of 150 sphere and half-space impact cases. The segmental linear characteristics of the equivalent contact stiffness are identified and fitted to establish the segmental expressions of the equivalent contact stiffness. The new linear contact loading law is dependent on various factors, including the yield strain of the half-space, the ratio of elastic moduli between the half-space and sphere, and the ratio of yield strengths between the half-space and sphere. The accuracy of the proposed linear contact loading law is validated through extensive Finite Element Method simulations, which involve an elastic–plastic half-space being struck by elastic–plastic spheres with varying impact energies, sizes, and material combinations.

Eriogyna pyretorum Westwood is a notorious defoliator of Camphora officinarum Nees that causes large economic and ecological losses in planted forests. To understand the importance of suppressing the population of E. pyretorum on natural parasitoids, a four-years investigation was conducted in the field. Four egg parasitoid species Ooencyrtus kuvanae Howard, Trichogramma chionis Ishii, Telenomus sp. and Anastatus dexingensis Sheng & Wang were captured in the wild. One of these is the dominant endoparasitoid species T. chionis, which has a quicker developmental time (8.33 d), more offspring (8.39/egg) and a greater parasitism rate (89.54%). With different elevation distributions, the parasitism rates for Kriechbaumerella longiscutellaris Qian & He, Gregopimpla himalayensis (Cameron), Theronia depressa (Gupta) and Xanthopimpla konowi (Krieger) were 17.29%, 2.10%, 4.23% and 0.83%, respectively. Female longevity (47.75 d), offspring (13.36/pupa) and sex ratio (1.16:1) were compared in four pupal parasitoids and K. longiscutellaris was the most abundant species of E. pyretorum in Fujian Province.

Speleoticus Ballarin & Li, 2016 is a relatively small spider genus of the family Nesticidae, currently including five cave-dwelling species, distributed exclusively in East Asia, four of which are known from China.A new troglobitic spider of the genus Speleoticus from the limestone Cave Hanwang Dong, north-eastern Sichuan, China, is described under the name of S. hei Yu & Lin, sp. n. Detailed descriptions, photographs and a distribution map of the new species are provided.

Abstract Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.

Abstract Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5–6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64–30.36) and 11.60 (95% CI: 8.28–13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34–0.64, p

Pancorius Simon, 1902 is a relatively large genus of jumping spider family Salticidae and currently contains 42 valid species that are mainly distributed in South East Asia, 11 of which are recorded from China.A new spider species of the genus Pancorius from Guiyang City in southwest China, is described under the name of P. guiyang Yang, Gu & Yu, sp. nov. Detailed descriptions and photographs are provided. DNA barcodes (a partial fragment of the mitochondrial cytochrome oxidase subunit I gene, COI) of the species were obtained to confirm matching of the sexes and for future use in molecular studies.

Tmarus Simon, 1875 is a relatively large spider genus, currently includes 227 species distributed worldwide. Fanjing Mountain Nature Reserve is one of China’s most biodiverse regions. However, Tmarus can be regarded as being poorly represented in Fanjing Mountain, with only one species having been recorded so far: T. fanjing Yang & Yu, 2022.Recently, various expeditions to Fanjing Mountain Nature Reserve were carried out by the authors. In this paper, two Tmarus species were brought to light by those expeditions: T. fanjing Yang & Yu, 2022 and T. circinalis Song & Chai, 1990. T. fanjing is redescribed, based on new material and the female is described and illustrated for the first time. The supplementary micrographs of T. circinalis are given for the first time. The DNA barcodes and a distribution map of both species are provided for future use.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E–11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.

CRISPR-Cas12a has been used for genome editing and molecular diagnosis. The well-studied Cas12a orthologs have a T-rich PAM and are usually categorized as non-thermally stable enzymes. Here, we identified a new Cas12a ortholog from Clostridium thermobutyricum, which survives at 60 °C. This Cas12a ortholog is named as CtCas12a and exhibits low sequence similarity to the known Cas12a family members. CtCas12a is active in a wide temperature range from 17 to 77 °C. Moreover, this ortholog has a relaxed PAM of YYV (Y=C or T, V = A or C or G). We optimized the conditions for trans-cleavage and enabled its detection of nucleic acids. CtCas12a executed genome editing in human cells and generated up to 26% indel formation in the EGFP locus. With the ability to be active at high temperatures as well as having a relaxed PAM sequence, CtCas12a holds potential to be further engineered for pathogen detection and editing a wide range of genomic sequences.

The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment–specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca2+/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo. Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration.

Cryptomeria japonica var. sinensis Miquel in south China is currently overwhelmingly infested by a native caterpillar species, Dendrolimus houi (Lepidoptera), which is causing severe economic losses and ecological disasters in both planted and natural forests. Our results include report of five parasitoid species and eight parasitoid flies within D. houi and a dominant endoparasitoid species Kriechbaumerella dendrolimi, which attacks pupae of D. houi with a high parasitism rate. This result might be helpful to improve better identification and application in the future for potential biological control of D. houi in the forests of east Asia.

Abstract Chemical modifications of RNAs, known as the epitranscriptome, are emerging as widespread regulatory mechanisms underlying gene regulation. The field of epitranscriptomics advances recently due to improved transcriptome-wide sequencing strategies for mapping RNA modifications and intensive characterization of writers, erasers, and readers that deposit, remove, and recognize RNA modifications, respectively. Herein, we review recent advances in characterizing plant epitranscriptome and its regulatory mechanisms in post-transcriptional gene regulation and diverse physiological processes, with main emphasis on N 6-methyladenosine (m6A) and 5-methylcytosine (m5C). We also discuss the potential and challenges for utilization of epitranscriptome editing in crop improvement.

Most orthopteran insects are phytophagous and some are important pests in agriculture and forests. Many intestinal microflora of Orthoptera insects have been reported, primarily from Acridoidea and there have been few reports of other taxa. In this study, we collected 15 individuals representing five species (Ruspolia lineosa, Tetrix japonica, Erianthus versicolor, Gryllotalpa orientalis and Teleogryllus emma) belonging to five orthopteran superfamilies (Tettigonioidea, Tetrigoidea, Eumastacoidea, Gryllotalpoidea and Grylloidea) to characterise and compare the gut microbiota with greater taxonomic width by performing sequencing analysis of the 16S rRNA V4 region in gut material. A total of 606,053 high-quality sequences and 3,105 OTUs were acquired from 15 gut samples representing 24 phyla, 48 classes, 69 orders, 133 families and 219 genera. Firmicutes and bacteria were the most abundant phyla, followed by Bacteroidetes, Cyanobacteria, Actinobacteria and Acidobacteria. At the genus level, Serratia, Citrobacter, Wolbachia, Lactobacillus and Parabacteroides were the most predominant genera in R. lineosa, T. japonica, E. versicolor, G. orientalis and T. emma, respectively. Both Principal Coordinates Analysis (PCoA) and heatmap results revealed significant differences in bacterial community composition across species. Additionally, alpha diversity analysis indicated the bacterial richness was significantly different amongst the five species.

Mandibular defect becomes a prevalent maxillofacial disease resulting in mandibular dysfunctions and huge psychological burdens to the patients. Considering the routine presence of oral contaminations and aesthetic restoration of facial structures, the current clinical treatments are however limited, incapable to reconstruct the structural integrity and regeneration, spurring the need for cost-effective mandibular tissue engineering. Hydrogel systems possess great merit for mandibular reconstruction with precise involvement of cells and bioactive factors. In this review, current clinical treatments and distinct mode(s) of mandible formation and pathological resorption are summarized, followed by a review of hydrogel-related mandibular tissue engineering, and an update on the advanced fabrication of hydrogels with improved mechanical property, antibacterial ability, injectable form, and 3D bioprinted hydrogel constructs. The exploration of advanced hydrogel systems will lay down a solid foundation for a bright future with more biocompatible, effective, and personalized treatment in mandibular reconstruction.

Yellowfin tuna (Thunnus albacares) is a valuable pelagic migratory fish with potential for aquaculture. Despite this, there is limited understanding of the biological and physiological characteristics of this species, particularly regarding sex differences in growth performance. The liver, a crucial organ for digestion and metabolism, plays a significant role in regulating fish growth. This study aimed to compare liver enzyme activities and transcriptome profiles between female and male yellowfin tuna to uncover the molecular mechanisms underlying difference between the sexes. The results revealed that female yellowfin tuna exhibited higher amylase and lipid metabolism enzyme activities, while male yellowfin tuna showed higher glucose-6-phosphate dehydrogenase and antioxidant enzyme activities. Additionally, through Illumina sequencing technology, the study generated 37.74 Gb of clean data and identified 36,482 unique genes (UniGenes) in the liver transcriptome. A total of 2542 differentially expressed genes were found, with enriched Gene Ontology terms and pathways related to metabolic processes, particularly lipid metabolism and transport. These findings suggest that female yellowfin tuna have superior digestive enzyme activities and lipid metabolism, while male yellowfin tuna excel in sugar metabolism, ATP production, and antioxidant defense. This study provides valuable insights into sex differences in yellowfin tuna and could aid in advancing full-cycle aquaculture practices for this species.

In order to solve the ecological environment pollution caused by a large amount of coal gangue accumulation and the problems of poor conveying performance and low support strength of paste filling materials. Based on the standard slump test and uniaxial compressive strength test, the slump and compressive strength (post-coagulation) of gangue paste under different aggregate size aggregations were obtained through orthogonal experiments in this study. The results show that the slump of the gangue filling paste with four types of aggregate size gradations is negatively correlated with the mass fraction, and the slump of the filling paste with a coarser aggregate content is more obviously affected by the mass fraction The increase of fine aggregate content has a significant impact on the compressive strength of the filling paste, which shows a trend of first increasing and then decreasing. When the mixing ratio of coarse aggregate and fine aggregate is 5:5, the compressive strength of the paste reaches the best. In addition, different proportions of aggregate mixing cause the filling paste to form different skeleton structures, including the skeleton void structure at 7:3 or 6:4, the skeleton dense structure at 5:5, and the skeleton suspension structure at 4:6, which are decisive for the final performance of the paste. By analyzing the experimental results of the compressive strength and slump of the gangue filling paste, it was found that the relationship between the compressive strength and slump of the gangue filling paste is a power index function. Through data fitting, it was found that the regression coefficient of the fitting function is no less than 0.97, and the fitting effect is good for evaluating the strength of the filling paste under the aggregate size grading.

In this paper, bismuth (Bi) was successfully deposited on graphite felts to improve the electrochemical performances of vanadium redox flow batteries. Modified graphite felts with different Bi particle loadings were obtained through electrochemical deposition at voltages of 0.8 V, 1.2 V and 1.6 V in 0.1 M BiCl3 solution for 10 min. The optimal Bi particle loading was confirmed by scanning electron microscopy (SEM), single cells and electrochemical tests. The SEM images revealed the deposition of granular Bi particles on the fiber surface. The Bi-modified felts which were electro-chemically deposited at 1.2 V (Bi/TGF-1.2V) showed excellent electrochemical performances in cyclic voltammetry curves and impedance spectroscopy. Meanwhile, the single cells assembled with Bi/TGF-1.2V as negative electrodes exhibited higher voltage efficiencies than the others. The optimized Bi particle loading induced better catalysis of the V3+/V2+ reaction and hence significantly improved the cell performances. In addition, the prepared Bi-modified felts showed stable cell performances and slower charge–discharge capacity declines than the other electrodes at current densities between 20 mA/cm2 and 80 mA/cm2. Compared with the pristine felt, the voltage efficiency of the vanadium redox flow battery assembled with Bi/TGF-1.2V graphite felt was 9.47% higher at the current density of 80 mA/cm2. The proposed method has considerable potential and guiding significance for the future modification of graphite felt for redox flow batteries.

An ethyl acetate extract of a marine actinomycete strain, Nocardiopsis mentallicus SCSIO 53858, isolated from a deep-sea sediment sample in the South China Sea, exhibited anti-quorum-sensing (QS) activity against Chromobacterium violaceum CV026. Guided by the anti-QS activity, a novel active compound was isolated and purified from the extract and was identified as 2,3-dimethoxycinnamic acid (2,3-DCA) through spectral data analysis. At a concentration of 150 μg/mL, 2,3-DCA exhibited robust inhibitory effects on three QS-regulated traits of C. violaceum CV026: violacein production, swarming motility, and biofilm formation, with inhibition rates of 73.9%, 65.9%, and 37.8%, respectively. The quantitative reverse transcription polymerase chain reaction results indicated that 2,3-DCA can disrupt the QS system in C. violaceum CV026 by effectively suppressing the expression of QS-related genes, including cviR, vioA, vioB, and vioE. Molecular docking analysis revealed that 2,3-DCA hinders the QS system by competitively binding to the same binding pocket on the CviR receptor as the natural signal molecule N-hexanoyl-L-homoserine lactone. Collectively, these findings suggest that 2,3-DCA exhibits promising potential as an inhibitor of QS systems, providing a potential solution to the emerging problem of bacterial resistance.

Three pairs of enantiomers (1–3)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (5–7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2–5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals.

Non-thermal plasma driven ammonia synthesis has great potential for future industrial applications due to its low theoretical energy requirements. To achieve technological advancement and environmental sustainability, it is crucial to boost the energy yield in plasma-assisted ammonia synthesis. Therefore, optimizing energy transfer and utilization are key strategies for enhancing energy efficiency. In this study, dielectric barrier discharge driven by a nanosecond pulsed power supply is used to enhance plasma-assisted ammonia synthesis by controlling the energy transfer through the addition of noble gases. It was found that the addition of noble gases changed the plasma characteristics, significantly improved the uniformity of the discharge, and achieved a high energy yield for ammonia synthesis. The effects of additive amounts of argon (Ar) and helium (He), as well as the pulse parameters including the pulse voltage, pulse repetition frequency, pulse width, and pulse rise time on the energy yield of ammonia synthesis are discussed. The inclusion of noble gases expanded the pathway for gas-phase reactions, with the active components of critical reactions examined through optical emission spectra. This analysis revealed an increased presence of both N2+ and N2* particles in the reaction’s rate-limiting step, attributed to the addition of noble gases. Finally, a zero-dimensional (0D) plasma chemical kinetic model was established to investigate the influence of Ar addition on the reaction mechanism of ammonia synthesis.

The BRI1 EMS suppressor 1(BES1) transcription factor is a crucial regulator in the signaling pathway of Brassinosteroid (BR) and plays an important role in plant growth and response to abiotic stress. Although the identification and functional validation of BES1 genes have been extensively explored in various plant species, the understanding of their role in woody plants—particularly the endangered species Phoebe bournei (Hemsl.) Yang—remains limited. In this study, we identified nine members of the BES1 gene family in the genome of P. bournei; these nine members were unevenly distributed across four chromosomes. In our further evolutionary analysis of PbBES1, we discovered that PbBES1 can be divided into three subfamilies (Class I, Class II, and Class IV) based on the evolutionary tree constructed with Arabidopsis thaliana, Oryza sativa, and Solanum lycopersicum. Each subfamily contains 2–5 PbBES1 genes. There were nine pairs of homologous BES1 genes in the synteny analysis of PbBES1 and AtBES1. Three segmental replication events and one pair of tandem duplication events were present among the PbBES1 family members. Additionally, we conducted promoter cis-acting element analysis and discovered that PbBES1 contains binding sites for plant growth and development, cell cycle regulation, and response to abiotic stress. PbBES1.2 is highly expressed in root bark, stem bark, root xylem, and stem xylem. PbBES1.3 was expressed in five tissues. Moreover, we examined the expression profiles of five representative PbBES1 genes under heat and drought stress. These experiments preliminarily verified their responsiveness and functional roles in mediating responses to abiotic stress. This study provides important clues to elucidate the functional characteristics of the BES1 gene family, and at the same time provides new insights and valuable information for the regulation of resistance in P. bournei.

Spermatid elongation is a crucial event in the late stage of spermatogenesis in the Drosophila testis, eventually leading to the formation of mature sperm after meiosis. During spermatogenesis, significant structural and morphological changes take place in a cluster of post-meiotic germ cells, which are enclosed in a microenvironment surrounded by somatic cyst cells. Microtubule-based axoneme assembly, formation of individualization complexes and mitochondria maintenance are key processes involved in the differentiation of elongated spermatids. They provide important structural foundations for accessing male fertility. How these structures are constructed and maintained are basic questions in the Drosophila testis. Although the roles of several genes in different structures during the development of elongated spermatids have been elucidated, the relationships between them have not been widely studied. In addition, the genetic basis of spermatid elongation and the regulatory mechanisms involved have not been thoroughly investigated. In the present review, we focus on current knowledge with regard to spermatid axoneme assembly, individualization complex and mitochondria maintenance. We also touch upon promising directions for future research to unravel the underlying mechanisms of spermatid elongation in the Drosophila testis.

Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal models. To overcome these limitations, we performed flavivirus genome recoding using the contrary approach of codon optimisation. The genomes of flaviviruses such as dengue virus type 2 (DENV2) and Zika virus (ZIKV) contain functional RNA elements that regulate viral replication. We hypothesised that flavivirus genome recoding by codon optimisation would introduce silent mutations that disrupt these RNA elements, leading to decreased replication efficiency and attenuation. We chose DENV2 and ZIKV as representative flaviviruses and recoded them by codon optimising their genomes for human expression. Our study confirms that this recoding approach of codon optimisation does translate into reduced replication efficiency in mammalian, human, and mosquito cells as well as in vivo attenuation in both mice and mosquitoes. In silico modelling and RNA SHAPE analysis confirmed that DENV2 recoding resulted in the extensive disruption of genomic structural elements. Serial passaging of recoded DENV2 resulted in the emergence of rescue or adaptation mutations, but no reversion mutations. These rescue mutations were unable to rescue the delayed replication kinetics and in vivo attenuation of recoded DENV2, demonstrating that recoding confers genetically stable attenuation. Therefore, our recoding approach is a reliable attenuation method with potential applications for developing flavivirus vaccines.

The mitochondrial genomes of six Phylloscopus species—small insectivores belonging to the Phylloscopidae family—were obtained using the Illumina sequencing platform. The mitogenomes were closed circular molecules 16,922–17,007 bp in size, containing 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two control regions (CR1 and remnant CR2). The gene orders were conserved in 35 sampled Phylloscopus mitogenomes in the GenBank database, with a gene rearrangement of cytb-trnT-CR1-trnP-nad6-trnE-remnant CR2-trnF-rrnS. The average base compositions of the six Phylloscopus mitogenomes were 29.43% A, 32.75% C, 14.68% G, and 23.10% T, with the A+T content slightly higher than that of G+C. ATG and TAA were the most frequent initiating and terminating codons, respectively. Several conserved boxes were identified in CR1, including C-string in domain I; F, E, D, and C boxes, as well as bird similarity and B boxes, in domain II; and CSB1 in domain III. Tandem repeats were observed in remnant CR2 of the Phylloscopus fuscatus and Phylloscopus proregulus mitogenomes. A phylogenetic analysis with maximum likelihood (ML) and Bayesian inference (BI) methods, based on 13 protein-coding genes and two rRNA genes, indicated that the Phylloscopus species was divided into two larger clades, with a splitting time approximately 11.06 million years ago (mya). The taxa of Phylloscopus coronatus/Phylloscopus burkii and Phylloscopus inornatus/P. proregulus were located at the basal position of the different clades. The phylogenetic result of the cox1 gene showed that Seicercus was nested within Phylloscopus. The complete set of mitogenomes of the Phylloscopus species provides potentially useful resources for the further exploration of the taxonomic status and phylogenetic history of Phylloscopidae.

Viruses existed in wastewaters might pose a biosecurity risk to human and animal health. However, it is generally difficult to detect viruses in wastewater directly as they usually occur in low numbers in water. Therefore, processing large volumes of water to concentrate viruses in a much smaller final volume for detection is necessary. Glass wool has been recognized as an effective material to concentrate multiple in water, and in this study, we assessed the use of glass wools on concentrating pseudorabies virus (PRV), African swine fever virus (ASFV), and porcine epidemic diarrhea virus (PEDV) in water samples. The influence of pH values, water matrix, water volume, filtration rate, temperature on the effect of the method concentrating these viruses for detection was evaluated in laboratory. Our results revealed that glass wool was suitable for the concentration of above-mentioned viruses from different water samples, and demonstrated a good application effect for water with pH between 6.0–9.0. Furthermore, glass wool also showed a good recovery effect on concentrating viral nucleic acids and viral particles, as well as living viruses. In addition, combining use of glass wool with skim milk, polyethylene glycol (PEG)-NaCl, or ultracentrifuge had good effects on concentrating ASFV, PRV, and PEDV. Detection of wastewater samples (n = 70) collected from 70 pig farms in 13 regions across Hubei Province in Central China after glass-wool-concentration determined one sample positive for ASFV, eighteen samples positive for PRV, but no sample positive for PEDV. However, these positive samples were detected to be negative before glass wool enrichment was implemented. Our results suggest that glass wool-based water concentration method developed in this study represents an effective tool for detecting viruses in wastewater.

Background Neurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI. Methods Spinal cord transection at the T10–T11 level was used to construct the SSCI model in rats (10–week–old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1–3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed. Results Bladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1–3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1–3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the “Chemokine signaling pathway”, the “IL-17 signaling pathway”, and the “TGF-beta signaling pathway” suggests their potential involvement in regulating biological processes. The circRNA–miRNA–mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239–miRNA–mRNA–mediated network may play a critical role in the pathogenesis of SSCI-induced NB. Conclusions This study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets.

The extracellular matrix (ECM) plays a vital role in the progression and metastasis of glioma and is an important part of the tumor microenvironment. The matrisome is composed of ECM components and related proteins. There have been several studies on the effects of matrisomes on the glioma immune microenvironment, but most of these studies were performed on individual glioma immune‐related matrisomes rather than integral analysis. Hence, an overall analysis of all potential immune‐related matrisomes in gliomas is needed. Here, we divided 667 glioma patients in The Cancer Genome Atlas (TCGA) database into low, moderate, and high immune infiltration groups. Immune‐related matrisomes differentially expressed among the three groups were analyzed, and a risk signature was established. Eight immune‐related matrisomes were screened, namely, LIF, LOX, MMP9, S100A4, SRPX2, SLIT1, SMOC1, and TIMP1. Kaplan–Meier analysis, operating characteristic curve analysis, and nomogram were constructed to analyze the relationships between risk signatures and the prognosis of glioma patients. The risk signature was significantly correlated with the overall survival of glioma patients. Both high‐ and low‐risk signatures were also associated with some immune checkpoints. In addition, analysis of somatic mutations and anti‐PD1/L1 immunotherapy responses in the high‐ and low‐risk groups showed that the high‐risk group had worse prognosis and a higher response to anti‐PD1/L1 immunotherapy. Our analysis of immune‐related matrisomes may improve understanding of the characteristics of the glioma immune microenvironment and provide direction for glioma immunotherapy development in the future.

A field trial in Changsha, China, involving the release of a triple Wolbachia-infected strain of the mosquito, Aedes albopictus, demonstrates the feasibility of using an incompatible insect technique to suppress disease vector mosquito populations in urban subtropic environments.

A Neisseria cinerea Cas9 variant is characterised in PAM preference, editing efficiency (for both nuclease and base editing) and anti-CRISPR protein blocking, with a PAM of (N)4GYAT reported alongside a mouse zygote assay.

Abstract Disseminated intravascular coagulation (DIC) is a complex, life-threatening syndrome associated with the end-stage of different coagulation disorders. Early prediction of the risk of DIC development is an urgent clinical need to reduce adverse outcomes. However, effective approaches and models to identify early DIC are still lacking. In this study, a novel interpretable deep learning based time series is used to predict the risk of DIC. The study cohort included ICU patients from a 4300-bed academic hospital between January 1, 2019, and January 1, 2022. Experimental results show that our model achieves excellent performance (AUC: 0.986, Accuracy: 95.7%, and F1:0.935). Gradient-weighted Class Activation Mapping (Grad-CAM) was used to explain how predictive models identified patients with DIC. The decision basis of the model was displayed in the form of a heat map. The model can be used to identify high-risk patients with DIC early, which will help in the early intervention of DIC patients and improve the treatment effect.

The corticalis group is one of most diverse species-group in genus Clubiona Latreille, 1804. Currently, a total of 81 corticalis group species are known worldwide, amongst them 67 were recorded from China. However, the diversity of this group in China is still insufficiently known.Clubiona xianning sp. nov. is described as a new species of the C. corticalis species-group collected from Hubei Province, China.

Abstract Background Transposable elements (TEs) have been likened to parasites in the genome that reproduce and move ceaselessly in the host, continuously enlarging the host genome. However, the Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of TE invasion by imposing small-RNA-mediated silencing. Here we compare the TE activity of two grasshopper species with different genome sizes in Acrididae (Locusta migratoria manilensis♀1C = 6.60 pg, Angaracris rhodopa♀1C = 16.36 pg) to ascertain the influence of piRNAs. Results We discovered that repetitive sequences accounted for 74.56% of the genome in A. rhodopa, more than 56.83% in L. migratoria, and the large-genome grasshopper contained a higher TEs proportions. The comparative analysis revealed that 41 TEs (copy number > 500) were shared in both species. The two species exhibited distinct “landscapes” of TE divergence. The TEs outbreaks in the small-genome grasshopper occurred at more ancient times, while the large-genome grasshopper maintains active transposition events in the recent past. Evolutionary history studies on TEs suggest that TEs may be subject to different dynamics and resistances in these two species. We found that TE transcript abundance was higher in the large-genome grasshopper and the TE-derived piRNAs abundance was lower than in the small-genome grasshopper. In addition, we found that the piRNA methylase HENMT, which is underexpressed in the large-genome grasshopper, impedes the piRNA silencing to a lower level. Conclusions Our study revealed that the abundance of piRNAs is lower in the gigantic genome grasshopper than in the small genome grasshopper. In addition, the key gene HENMT in the piRNA biogenesis pathway (Ping-Pong cycle) in the gigantic genome grasshopper is underexpressed. We hypothesize that low-level piRNA silencing unbalances the original positive correlation between TEs and piRNAs, and triggers TEs to proliferate out of control, which may be one of the reasons for the gigantism of grasshopper genomes.