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Abstract Background NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Methods Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Results Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P

Abstract The objective of this study was to investigate the culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery. The selected time points of the perioperative period included before the use of antibiotic eye drops, before eye wash (after the use of antibiotic eye drops), after eye wash, and immediately after surgery. Conjunctival specimens obtained at the four time points were cultured to detect the positivity and distribution of bacteria. Before prophylactic antibiotic eye drops were administered, 49 eyes (50%) had positive bacterial culture results, with 45 isolates (91.8%) identified as Staphylococcus epidermidis. The culture positivity rates of the conjunctival sac specimens before eye wash, after eye wash, and immediately after surgery were 19.4%, 3.1%, and 4.1%, respectively. The difference was significant before and after the use of antibiotics and before and after eye wash (both P 0.05). The judicious preoperative use of antibiotic eye drops combined with the surgical sterile eye wash procedure maximised the removal of conjunctival sac bacteria. Skilled surgical manipulations generally did not increase the risk of infection.

Background: Bridging repair has emerged as a promising and reliable treatment strategy for the massive rotator cuff tears (MRCTs). However, there remains a lack of evidence on which bridging graft provides the better repair results, and a dearth of animal studies comparing bridging repairs with different grafts. The purpose of this study was to evaluate the histological and biomechanical outcomes of commonly used grafts (autologous fascia lata (FL), acellular dermal matrix graft (ADM), and polyethylene terephthalate (PET) patch). Methods: A total of 66 male New Zealand White Rabbits were used to mimic a model of unilateral chronic MRCTs. The rabbits were randomly divided into three groups: (1) FL group, which underwent bridging repair with autologous FL; (2) ADM group, which underwent bridging with ADM; and (3) PET group, which underwent bridging with PET patch. Tissue samples were collected and subjected to histological analysis using Hematoxylin and eosin, Picrosirius red, Safranin O/Fast green staining, and Immunostaining. Collagen diameter and fibril density in the regenerated tendon was analyzed with transmission electron microscopy (TEM). Additionally, biomechanical tests were performed at 6 and 12 weeks after repair. Results: The regenerated tendon successfully reattached to the footprint in all experimental groups. At 6 weeks after repair, the FL group had a significantly higher Modified Tendon Histological Evaluation (MTHE) score at the regenerated tendon than the PET group (13.2 ± 1.64 vs 9.6 ± 1.95, respectively; P = 0.038). The picrosirius red staining results showed that the FL group had a significantly higher type I collagen content than the ADM and PET groups at 6 weeks, and this difference was sustained with the PET group at 12 weeks (P

Liquid cooling is widely used on high power motors. Optimal design of the coolant loop could help rise the power density. The coolant channels are placed across the stator core in this research. The heat dissipation performances of the coolant channel with different designs are compared and analyzed through simulation. Experiments were carried out to verify the simulation results and the feasibility of the cooling method. The results show that the coolant loop should be placed tightly close to the slots. The heat dissipation performance of the optimized coolant loop is efficient compared to the jacket cooling design. The coolant channels across the stator core could remain sealed under a 0.5 Mpa pressure at least according to the air proof test. The coolant pressure within the channels could be reduced efficiently through increasing the parallel loop number or moving the channels away from the slots properly. The winding temperature of the measured values and the simulated results of the motor with jacket cooling is within 2 °C.

This article investigates the complex dynamics of ammonia as an alternative fuel within the ambit of China's strategic initiatives aimed at attaining carbon neutrality. Given ammonia's distinctive characteristics as a fuel, this analysis delves into the nascent development status and the multifaceted challenges confronting this sector within China. Through a comprehensive examination of the plethora of new energy policies promulgated by the Chinese government, this article underscores the initial phase of accelerated growth in the ammonia fuel domain. The imposition of carbon emission restrictions, coupled with the momentum generated by technological innovations, positions green ammonia as an efficacious solution for hydrogen storage and utilization, thereby fostering a symbiotic relationship with the hydrogen energy industry chain. The proactive policy framework adopted by China significantly enhances the pivotal role of ammonia fuel technology, making it one of the principal technological pathways for China to realize its carbon neutrality ambitions in the future.

Abstract Background Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. Result This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. Conclusion This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.

Abstract Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer cells may preferentially rely on certain amino acids for rapid growth and metastasis. On the other hand, sufficient nutrient availability and uptake are necessary for mounting an effective T cell anti-tumor response in the tumor microenvironment (TME). Here we demonstrate that tumor cells outcompete T cells for cystine uptake due to high Slc7a11 expression. This competition induces T-cell exhaustion and ferroptosis, characterized by diminished memory formation and cytokine secretion, increased PD-1 and TIM-3 expression, as well as intracellular oxidative stress and lipid-peroxide accumulation. Importantly, either Slc7a11 deletion in tumor cells or intratumoral cystine supplementation improves T cell anti-tumor immunity. Mechanistically, cystine deprivation in T cells disrupts glutathione synthesis, but promotes CD36 mediated lipid uptake due to dysregulated cystine/glutamate exchange. Moreover, enforced expression of glutamate-cysteine ligase catalytic subunit (Gclc) promotes glutathione synthesis and prevents CD36 upregulation, thus boosting T cell anti-tumor immunity. Our findings reveal cystine as an intracellular metabolic checkpoint that orchestrates T-cell survival and differentiation, and highlight Gclc as a potential therapeutic target for enhancing T cell anti-tumor function.

Abstract Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.

Abstract Background The use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors. Methods Patients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not. Results In univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not. Conclusion In patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

Abstract N 6-methyladenosine (m6A) is an RNA modification that can be removed by demethylases [fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5)], which regulate gene expression and cell function. We show that m6A levels and m6A demethylase levels are altered in nasopharyngeal carcinoma (NPC) tissues vs. normal tissues. High FTO and ALKBH5 predict a poor prognosis in NPC patients. Silencing FTO and ALKBH5 inhibited the malignant behavior of patient-derived NPC cells in a short time. However, as time progressed, the inhibitory effect of FTO or ALKBH5 was weakened, and the cosilencing of FTO and ALKBH5 maintained a better inhibitory effect. Combined transcriptome and m6A-seq analysis revealed a downstream target gene that was jointly regulated by FTO and ALKBH5 in NPC, and ARHGAP35 was chosen to do further study. The synergistic silencing of FTO and ALKBH5 increased the methylation level on the mRNA CDS of a new transcription factor (ARHGAP35) and positively regulate the protein coding capacity and mRNA stability of ARHGAP35, thus leading to increased expression of ARHGAP35 and inhibition of the malignant phenotype of tumor cells. Our study revealed that the growth and metastasis of NPC can be stably inhibited through synergistic silencing of the demethylases FTO and ALKBH5, which play a positive role in the treatment of NPC by regulating the downstream transcript ARHGAP35 and increasing its m6A level.

Surgical repair or reconstruction of the lateral ligaments for patients with chronic ankle instability (CAI) could, logically, restore the proprioception of ankle through retensing receptors. To validate this hypothesis, seven databases were systematically searched, and thirteen studies comprising a total of 347 patients with CAI were included. Although five studies reported improved proprioceptive outcomes after surgeries, the other five studies with between-limb/group comparisons reported residual deficits at final follow-up, which does not consistently support proprioceptive recovery after existing surgical restabilization for CAI. More controlled studies are needed to provide evidence-based protocols to improve proprioceptive recovery after ankle restabilization for CAI.

Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.

This study reveals a novel understanding of the influence of annealing the feed powder, which alters the precipitate characteristics in the powder particles on the microstructure and mechanical properties of Haynes230 superalloy fabricated by laser powder bed fusion (LPBF) plus hot isostatic pressing (HIP) and solution treatment. Specifically, annealing Haynes230 superalloy powder at 1000°C for 1 h under vacuum resulted in the precipitation of M6C carbide instead of the typical M23C6 found in unannealed powder. The alloy fabricated by LPBF of the annealed powder plus HIP and heat treatment exhibited an increased number density of the carbide precipitates at grain boundaries, but a reduced number density of the intragranular carbide precipitates. Consequently, its ambient temperature tensile properties decreased clearly in terms of yield strength (406–383 MPa), ultimate tensile strength (936–841 MPa) and elongation to fracture (38.6% to 25%) compared to the alloy fabricated by LPBF of the as-received powder plus same post-print processing. However, the annealing of the feed powder had little effect on the tensile properties of the samples at 900°C. These findings underscore the significant impacts of feed powder microstructure on the mechanical properties of LPBF-processed superalloys.

Abstract While most nanomedicines primarily aim to stimulate the immune system against infections or tumors, there is a growing demand for inducing immune tolerance under certain conditions, such as allergic and autoimmune diseases. Researchers have explored nanotechnology‐based strategies to induce immune tolerance in a targeted and specific manner. One approach involves the use of nanoparticles (NPs) to encapsulate immunosuppressive drugs and/or antigens to educate naïve T cells and promote the generation of antigen‐specific regulatory T cells that inhibit immune responses. However, this approach has certain limitations. The hydrophobicity of proteins or peptides restricts the degree to which they can be encapsulated in NPs, which in turn, affects their loading efficiency and treatment efficacy. With the emergence of mRNA lipid nanoparticle (LNP) platforms, there is the possibility of overcoming the limitations of protein and peptide encapsulation. To date, mRNA LNP systems have been shown to provide organ, cellular, and subcellular targeting for the induction of immune tolerance. This method of drug delivery is flexible and scalable that can be customized for a specific patient, resulting in an effective means of administering relevant proteins or epitopes to induce antigen‐specific immune tolerance. With continued research and development, this technology could offer a safer and more effective alternative to current therapies, ultimately improving the quality of life of patients worldwide.

Tuberculosis (TB) remains a prevalent global infectious disease caused by genetically closely related tubercle bacilli in Mycobacterium tuberculosis complex (MTBC). For a century, the Bacillus Calmette-Guérin (BCG) vaccine has been the primary preventive measure against TB. While it effectively protects against extrapulmonary forms of pediatric TB, it lacks consistent efficacy in providing protection against pulmonary TB in adults. Consequently, the exploration and development of novel TB vaccines, capable of providing broad protection to populations, have consistently constituted a prominent area of interest in medical research. This article presents a concise overview of the novel TB vaccines currently undergoing clinical trials, discussing their classification, protective efficacy, immunogenicity, advantages, and limitations. In vaccine development, the careful selection of antigens that can induce strong and diverse specific immune responses is essential. Therefore, we have summarized the molecular characteristics, biological function, immunogenicity, and relevant studies associated with the chosen antigens for TB vaccines. These insights gained from vaccines and immunogenic proteins will inform the development of novel mycobacterial vaccines, particularly mRNA vaccines, for effective TB control.

ObjectiveThis study aimed to investigate the clinical manifestations and prognosis of lung transplant (LTx) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease (COVID-19) pandemic.MethodsThe research participants were LTx recipients who underwent surgery and were regularly followed up at our center. From 1 December 2022 to 28 February 2023, during the COVID-19 pandemic in China, research participants were interviewed either online or in person. SARS-CoV-2 nucleic acid or self-tested antigens were detected according to accessibility. Diagnosis and treatment were performed according to the Diagnosis and Treatment Plan for COVID-19 (10th edition) issued by the National Health Commission of the People's Republic of China. Hospitalized patients underwent chest imaging examinations, routine blood tests, biomarkers for infection and inflammation, and biochemical tests, all of which were taken and recorded. Data were analyzed to describe the features of COVID-19 in LTx recipients.ResultsIn total, 52 patients were enrolled in this study, comprising 48 men and 4 women, with a mean age of 51.71 ± 11.67 years. By 1 December 2022, the mean survival period was 33.87 ± 25.97 months, of which 84.61% of the patients (44/52) had a survival period longer than 12 months. The SARS-CoV-2 infection rate in these LTx recipients was 82.69% (43/52), with 3.85% (2/52) of the infected recipients being asymptomatic, 50.00% (26/52) of the infected recipients experiencing mild COVID-19, 11.54% (6/52) having moderate COVID-19, and 17.31% (9/52) having severe or critical COVID-19. The mortality rate among severe and critical patients was 66.67% (6/9).ConclusionLTx recipients in this cohort exhibited a notable susceptibility to SARS-CoV-2, with 82.69% of individuals diagnosed with COVID-19. Moreover, the mortality rate among critically ill patients was high.

Abstract Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelope proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance. Inactivating NDP52 in hepatocytes results in decreased targeting of viral envelopes in the lysosome and increased levels of viral replication. NDP52 inhibits HBV at both viral entry and late replication stages. In contrast to NDP52-mediated bacterial autophagy, lysosomal degradation of HBV envelopes is independent of galectin 8 and ATG5. NDP52 forms complex with Rab9 and viral envelope proteins and links HBV to Rab9-dependent lysosomal degradation pathway. These findings reveal that NDP52 acts as a sensor for HBV infection, which mediates a unique antiviral response to eliminate the virus. This work also suggests direct roles for autophagy receptors in other lysosomal degradation pathways than canonical autophagy.

Abstract Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

Abstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. Methods The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. Results LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. Conclusions LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.

Abstract Background Myopia is a common eye disorder that results from gene-environment interactions. The prevalence of myopia varies across populations, and exposure to bright sunlight may prevent its development. We hypothesize that local adaptation to light environments during human migration played a role in shaping the genetic basis of myopia, and we aim to investigate how the environment influences the genetic basis of myopia. Method We utilized the whole-genome variant data of the 1000 Genomes Project for analysis. We searched myopia-associated loci that were under selection in Europeans using population branch statistics and the number of segregating sites by length statistics. The outliers of these statistics were enriched in the Kyoto Encyclopedia of Genes and Genomes pathways and the gene ontology biological process terms in searching for pathways that were under selection. We applied Bayesian inference to estimate the correlation between environmental factors and allele frequencies of the selected loci and performed causal inference of myopia using two-sample Mendelian randomization analysis. Results We detected signatures of adaptation in vision and light perception pathways, supporting our hypothesis of sunlight adaptation. We discovered a strong correlation between latitude and allele frequencies in genes that are under significant selection, and we found pleiotropic effects of pigmentation or circadian rhythm genes on myopia, indicating that sunlight exposure influences the genetic diversity of myopia. Conclusions Myopia genes involved in light perception showed signs of selection. Local adaptation during human migration shaped the genetic basis of myopia and may have influenced its global prevalence distribution.

Abstract Immunogenomic loci remain poorly understood because of their genetic complexity and size. Here, we report the de novo assembly of a cattle genome and provide a detailed annotation of the immunogenomic loci. The assembled genome contains 143 contigs (N50 ~ 74.0 Mb). In contrast to the current reference genome (ARS-UCD1.2), 156 gaps are closed and 467 scaffolds are located in our assembly. Importantly, the immunogenomic regions, including three immunoglobulin (IG) loci, four T-cell receptor (TR) loci, and the major histocompatibility complex (MHC) locus, are seamlessly assembled and precisely annotated. With the characterization of 258 IG genes and 657 TR genes distributed across seven genomic loci, we present a detailed depiction of immune gene diversity in cattle. Moreover, the MHC gene structures are integrally revealed with properly phased haplotypes. Together, our work describes a more complete cattle genome, and provides a comprehensive view of its complex immune-genome.

Abstract This paper presents a new method for accurately measuring the vocabulary size of second language (L2) learners. Traditional vocabulary size tests (VSTs) are limited in capturing a tester’s vocabulary and are often population-specific. To overcome these issues, we propose an intelligent vocabulary size measurement method that utilizes massive robot testers. They are equipped with randomized and word-frequency-based vocabularies to simulate L2 learners’ variant vocabularies. An intelligent vocabulary size test (IVST) is developed to precisely measure vocabulary size for any population. The robot testers “take” the IVST, which dynamically generates quizzes with varying levels of difficulty adapted to the estimated tester’s vocabulary size in real-time using an artificial neural network (ANN) through iterative learning. The effectiveness of the IVST is factually verified by their visible vocabularies. Additionally, we apply a long short-term memory (LSTM) model to further enhance the method’s performance. The proposed method has demonstrated high reliability and effectiveness, achieving accuracies of 98.47% for the IVST and 99.87% for the IVST with LSTM. This novel approach provides a more precise and reliable method for measuring vocabulary size in L2 learners compared to traditional VSTs, offering potential benefits to language learners and educators.

Study Design Single‐center, retrospective study. Objective Hemivertebra resection is the only treatment option for congenital cervical scoliosis (CCS). However, this procedure is complex and technically demanding. It often requires a considerably long operation, and there is substantial intraoperative bleeding. Therefore, we have attempted to treat CCS with a concave side distraction comprising a three‐dimensional (3D) printed titanium cage. The purpose of this study is to evaluate the safety and efficacy of this technique for the treatment of patients with CCS. Methods A series of 22 patients with CCS who underwent a concave side distraction technique between 2019 and 2021 were retrospectively reviewed and analyzed. Radiological measurements included the Cobb angle of the distraction segments, the kyphosis angle, the range of movement, and the distraction correction angle. Student's t‐test and Spearman correlation analysis were used for statistical analysis. p

Colorectal cancer (CRC) is one of the most common cancers and the second most deadly cancer across the globe. Colorectal cancer stem cells (CCSCs) fuel CRC growth, metastasis, relapse, and chemoresistance. A complete understanding of the modulatory mechanisms of CCSC biology is essential for developing efficacious CRC treatment. In the current study, we characterized the expression and function of GTP binding protein 2 (GTPBP2) in a chemical-induced mouse CRC model. We found that GTPBP2 was expressed at a higher level in CD133+CD44+ CCSCs compared with other CRC cells. Using a lentivirus-based Cas9/sgRNA system, GTPBP2 expression was ablated in CRC cells in vitro. GTPBP2 deficiency caused the following effects on CCSCs: 1) Significantly accelerating proliferation and increasing the proportions of cells at G1, S, and G2/M phase; 2) Impairing resistance to 5-Fluorouracil; 3) Weakening self-renewal but not impacting cell migration. In addition, GTPBP2 deficiency remarkably decreased β-catenin expression while increasing β-catenin phosphorylation in CCSCs. These effects of GTPBP2 were present in CCSCs but not in other CRC cell populations. The Wnt agonist SKL2001 completely abolished these changes in GTPBP2-deficient CCSCs. When GTPBP2-deficient CCSCs were implanted in nude mice, they exhibited consistent changes compared with GTPBP2-expressing CCSCs. Collectively, this study indicates that GTPBP2 positively modulates Wnt signaling to reinforce the quiescence, self-renewal, and chemoresistance of mouse CCSCs. Therefore, we disclose a novel mechanism underlying CCSC biology and GTPBP2 could be a therapeutic target in future CRC treatment.

Natural killer (NK) cells constitute an active and potent anti-tumor effector population against multiple malignancies. NK cells exploit tumoricidal machinery to restrain colorectal carcinoma (CRC) expansion and invasion. Nonetheless, it is becoming increasingly evident that functional exhaustion considerably compromises the potency of NK cells in patients with CRC. To elucidate the factors that impair NK cell function in the context of CRC, we determined the role of zinc finger protein 335 (ZFP335) in modulating NK cell activity in mouse CRC induced by azoxymethane and dextran sulfate sodium. ZFP335 was profoundly decreased in NK cells in mesenteric lymph nodes of CRC-bearing mice. ZFP335 was especially diminished in NK cells that were both phenotypically and functionally exhausted. Besides, effective ZFP335 knockdown markedly undermined NK cell proliferation, tumoricidal protein production, degranulation, and cytotoxic efficacy on malignant cells, strongly suggesting that ZFP335 reinforces NK cell function. Importantly, ZFP335 knockdown lowered the expression of Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3), both of which play crucial roles in NK cell homeostasis and activation. Collectively, ZFP335 down-regulation is essential for NK cell exhaustion in mesenteric lymph nodes of mice with CRC. We discovered a new ZFP335-JAK1/3 signaling pathway that modulates NK cell exhaustion.

Brucella, an adept intracellular pathogen, causes brucellosis, a zoonotic disease leading to significant global impacts on animal welfare and the economy. Regrettably, there is currently no approved and effective vaccine for human use. The ability of Brucella to evade host defenses is essential for establishing chronic infection and ensuring stable intracellular growth. Brucella employs various mechanisms to evade and undermine the innate and adaptive immune responses of the host through modulating the activation of pattern recognition receptors (PRRs), inflammatory responses, or the activation of immune cells like dendritic cells (DCs) to inhibit antigen presentation. Moreover, it regulates multiple cellular processes such as apoptosis, pyroptosis, and autophagy to establish persistent infection within host cells. This review summarizes the recently discovered mechanisms employed by Brucella to subvert host immune responses and research progress on vaccines, with the aim of advancing our understanding of brucellosis and facilitating the development of more effective vaccines and therapeutic approaches against Brucella.

BackgroundThe relationship between plant-based diets and gallstone disease has been debated. This study aimed to shed light on the association between plant-based dietary index and the risk of developing gallstone disease.MethodsEligible participants were selected from National Health and Nutrition Examination Survey (NHANES) 2017-2020. Three plant-based diet indexes (PDI, healthy PDI, unhealthy PDI) were calculated using data from two NHANES 24-h dietary recall interviews. Restricted Cubic Spline and multivariate logistic regression were used to analyze the associations. Subgroup analysis was adopted to make the results more robust.ResultsA total of 5673 eligible participants were analyzed. After adjusting for various confounding variables, uPDI was positively associated with gallstone disease (OR = 1.53, 95%CI: 1.02-2.29). No association was found between PDI/hPDI and gallstone disease (p > 0.05). The results of subgroup analysis did not show any positive association between uPDI and gallstones in specific groups.ConclusionOur study shows that the elevated uPDI are linked to a higher risk of gallstone disease.

Abstract IGF2BP2 is a new identified N6‐methyladenosine (m6A) reader and associated with poor prognosis in many tumors. However, its role and related mechanism in breast cancer, especially in triple‐negative breast cancer (TNBC), remains unclear. In this study, it is found that IGF2BP2 is highly expressed in TNBC due to the lower methylation level in its promoter region. Functional and mechanical studies displayed that IGF2BP2 could promote TNBC proliferation and the G1/S phase transition of the cell cycle via directly regulating CDK6 in an m6A‐dependent manner. Surprising, the regulation of protein levels of CDK6 by IGF2BP2 is related to the changes in translation rate during translation initiation, rather than mRNA stability. Moreover, EIF4A1 is found to be recruited by IGF2BP2 to promote the translation output of CDK6, providing new evidence for a regulatory role of IGF2BP2 between m6A methylation and translation. Downregulation of IGF2BP2 in TNBC cell could enhance the sensitivity to abemaciclib, a CDK4/6 inhibitor. To sum up, our study revealed IGF2BP2 could facilitate the translation output of CDK6 via recruiting EIF4A1 and also provided a potential therapeutic target for the diagnosis and treatment of TNBC, as well as a new strategy for broadening the drug indications for CDK4/6 inhibitors.

The presence of endotoxemia is strongly linked to the development of endothelial dysfunction and disruption of myocardial microvascular reactivity. These factors play a crucial role in the progression of endotoxemic cardiomyopathy. Sepsis-related multiorgan damage involves the participation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However, whether DNA-PKcs contributes to endothelial dysfunction and myocardial microvascular dysfunction during endotoxemia remains unclear. Hence, we conducted experiments in mice subjected to lipopolysaccharide (LPS)-induced endotoxemic cardiomyopathy, as well as assays in primary mouse cardiac microvascular endothelial cells. Results showed that endothelial-cell-specific DNA-PKcs ablation markedly attenuated DNA damage, sustained microvessel perfusion, improved endothelial barrier function, inhibited capillary inflammation, restored endothelium-dependent vasodilation, and improved heart function under endotoxemic conditions. Furthermore, we show that upon LPS stress, DNA-PKcs recognizes a TQ motif in cofilin2 and consequently induces its phosphorylation at Thr25. Phosphorylated cofilin2 shows increased affinity for F-actin and promotes F-actin depolymerization, resulting into disruption of the endothelial barrier integrity, microvascular inflammation, and defective eNOS-dependent vasodilation. Accordingly, cofilin2-knockin mice expressing a phospho-defective (T25A) cofilin2 mutant protein showed improved endothelial integrity and myocardial microvascular function upon induction of endotoxemic cardiomyopathy. These findings highlight a novel mechanism whereby DNA-PKcs mediates cofilin2Thr25 phosphorylation and subsequent F-actin depolymerization to contribute to endotoxemia-related cardiac microvascular dysfunction.

Terrestrial laser scanning (TLS) is a promising technology for quantity checking huge grain stocks with low cost, light workload and high efficiency. Existing applications of TLS in bulk grain measurement and quantification lack the ability to capture complete structural information of grain bulks and thus will result in large errors. In this paper, we propose a bi-temporal TLS scheme for fast 3D modeling and accurate volume measurement of bulk grains stored in large warehouses. The scheme uses bi-temporal multi-site TLS datasets acquired under both empty and full or high loading conditions to obtain complete surface information about grain bulk’s structure. In order for a grain bulk’s all external surfaces and the 3D volumetric model reconstructed therefrom to be automatically derived from the bi-temporal TLS dataset, several dedicated methods are developed for the scheme. A fully automated marker-free strategy exploring structurally semantic information inherent in the large grain storehouses is adopted to register multi-scan TLS point cloud data captured in large-scale granary scenes. Also, a local minima-based region growing technique is devised to extract underlying surfaces from a granary scene point cloud model. Experiments show that the proposed 3D modeling and volume measurement scheme can work effectively and quickly in TLS-based granary field applications and repeated test data demonstrate its correctness, repeatability and accuracy. Compared with the conventional manual measurement approach, the bi-temporal TLS scheme can not only achieve much higher measurement precision, but also greatly improve efficiency by significantly reducing cost, workload, and manpower. It has good potential for use in the area of nation-wide grain inventory inspection in China.

ABSTRACT: miR-19b-3p is reported to undertake various biological role, while its function and action mechanism in chicken hepatic lipid metabolism is unclear. Conservation analysis and tissue expression pattern of miR-19b-3p and its target gene were evaluated, respectively. Dual luciferase reporter system and Western blot technologies were adopted to validate miR-19b-3p target gene. Overexpression and knockdown assays were done to explore the biological functions of miR-19b-3p and target gene in Leghorn Male Hepatoma cell line (LMH). Regulatory approaches of estrogen on miR-19b-3p and target gene expressions are analyzed through site-directed mutation combined with estrogen receptors antagonist treatment assays. The results showed that chicken miR-19b-3p mature sequences are highly conserved among Capra hircus, Columba livia, Rattus norvegicus, Mus musculus, Cricetulus griseus, Danio rerio, Danio novaehollandiae, Orycodylus porosus, Crocodylus porosus, Gadus morhua, and widely expressed in lung, ovary, spleen, duodenum, kidney, heart, liver, leg muscle, and pectoral muscle tissues. miR-19b-3p could significantly increase intracellular triglyceride (TG) content and decrease intracellular cholesterol (TC) content via targeting methylsterol monooxygenase 1 (MSMO1) and elongase of very long chain fatty acids 5 (ELOVL5), which are highly conserved among species, in both mRNA and protein levels. Estrogen could inhibit miR-19b-3p expression, but directly promoted MSMO1 transcription via estrogen receptor α (ERα) and indirectly regulated ELOVL5 expression at the transcription level. Meanwhile, estrogen could also upregulate MSMO1 and ELOVL5 expression through inhibiting miR-19b-3p expression at the post-transcription level. Taken together, these results highlight the role and regulatory mechanism of miR-19b-3p in hepatic lipid metabolism in chicken, and might produce useful comparative information for human obesity studies and biomedical research.

Abstract Background Collecting duct carcinoma (CDC) is a rare renal tumor, originating from the distal collecting duct. CDC rarely presents as a primary tumor outside the renal system. Case presentation In this study, we report a rare case of collecting duct carcinoma, with an initial presentation of retroperitoneal lymph node metastasis, and no identifiable primary renal tumor on CT, at the time of diagnosis. The patient was a 64-year-old man presenting with lower back pain. Preoperative CT showed a round, soft tissue mass, measuring 6.7 × 4.4 × 3.3 cm, in the left retroperitoneum with no exact occupying lesion in the left kidney. Clinically, ectopic pheochromocytoma was considered to be a differential diagnosis, and tumor resection was performed. Postoperative pathological results demonstrated that the mass was a fused lymph node, and the tumor cells were destroying the structure. The final diagnosis was lymph node metastatic collecting duct carcinoma, by histology and immunohistochemistry. No further treatment was performed as no space occupying lesion was found in the kidney. Three months later, CT was reexamined, and a mass of 3.6 cm in diameter, was found in the lower left kidney, along with multiple soft tissue masses, in the left renal hilum. Considering recurrence or metastasis, the patient was recommended to undergo surgical treatment, but the patient refused. Four months later, CT was re-examined. The tumor had rapidly progressed but the patient refused treatment again. As per the author’s press release (eleven months after the first discovery), the patient is still alive. Conclusion CDC is a rare malignant renal carcinoma, with a high chance of rapid progress, regional lymph nodes involvement and metastasis. It presents diagnostic challenges to clinicians and pathologists, particularly, in the absence of radiographically detectable intrarenal lesions. Definite diagnosis is based on pathological examination combined with immunohistochemical staining.

Abstract Multiple primary lung cancers (MPLCs) pose diagnostic and therapeutic challenges in clinic. Here, we orchestrated the cellular and spatial architecture of MPLCs by combining single-cell RNA-sequencing and spatial transcriptomics. Notably, we identified a previously undescribed sub-population of epithelial cells termed as CLDN2 + alveolar type II (AT2) which was specifically enriched in MPLCs. This subtype was observed to possess a relatively stationary state, play a critical role in cellular communication, aggregate spatially in tumor tissues, and dominate the malignant histopathological patterns. The CLDN2 protein expression can help distinguish MPLCs from intrapulmonary metastasis and solitary lung cancer. Moreover, a cell surface receptor−TNFRSF18/GITR was highly expressed in T cells of MPLCs, suggesting TNFRSF18 as one potential immunotherapeutic target in MPLCs. Meanwhile, high inter-lesion heterogeneity was observed in MPLCs. These findings will provide insights into diagnostic biomarkers and therapeutic targets and advance our understanding of the cellular and spatial architecture of MPLCs.

Abstract A lipidome comprises thousands of lipid species, many of which are isomers and isobars. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), although widely used for lipidomic profiling, faces challenges in differentiating lipid isomers. Herein, we address this issue by leveraging the orthogonal separation capabilities of hydrophilic interaction liquid chromatography (HILIC) and trapped ion mobility spectrometry (TIMS). We further integrate isomer-resolved MS/MS methods onto HILIC-TIMS, which enable pinpointing double bond locations in phospholipids and sn-positions in phosphatidylcholine. This system profiles phospholipids at multiple structural levels with short analysis time (

Mechanical joint interfaces are widely found in mechanical equipment, and their contact stiffness directly affects the overall performance of the mechanical system. Based on the fractal and elastoplastic contact mechanics theories, the K-E elastoplastic contact model is introduced to establish the contact stiffness model for mechanical joint interfaces. This model considers the interaction effects between micro-asperities in the fully deformed state, including elasticity, first elastoplasticity, second elastoplasticity, and complete plastic deformation state. Based on this model, the effects of fractal parameters on normal contact stiffness and contact load are analyzed. It can be found that the larger fractal dimension D or smaller characteristic scale coefficient G will weaken the interaction between micro-asperities. The smoother processing surfaces lead to higher contact stiffness in mechanical joint interfaces. The applicability and effectiveness of the proposed model are verified by comparing it with the traditional contact model calculation results. Under the same load, the interaction between micro-rough surfaces leads to an increase in both overall deformation and contact stiffness. The accuracy of the predicted contact stiffness model is also validated by comparing it with experimental results.

Sodium-ion batteries (SIBs) have emerged as a promising alternative to lithium-ion batteries (LIBs) due to the abundance and low cost of sodium resources. Cathode material plays a crucial role in the performance of sodium ion batteries determining the capacity, cycling stability, and rate capability. Na3V2(PO4)3 (NVP) is a promising cathode material due to its stable three-dimensional NASICON structure, but its discharge capacity is low and its decay is serious with the increase of cycle period. We focused on modifying NVP cathode material by coating carbon and doping Nb5+ ions for synergistic electrochemical properties of carbon-coated NVP@C as a cathode material. X-ray diffraction analysis was performed to confirm the phase purity and crystal structure of the Nb5+ doped NVP material, which exhibited characteristic diffraction peaks that matched well with the NASICON structure. Nb5+-doped NVP@C@Nbx materials were prepared using the sol–gel method and characterized by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Raman and Brunauer -Emmett-Teller (BET) analysis. First-principles calculations were performed based on density functional theory. VASP and PAW methods were chosen for these calculations. GGA in the PBE framework served as the exchange-correlation functional. The results showed the NVP unit cell consisted of six NVP structural motifs, each containing octahedral VO6 and tetrahedral PO4 groups to form a polyanionomer [V2(PO4)3] along with the c-axis direction by PO4 groups, which had Na1(6b) and Na2(18e) sites. And PDOS revealed that after Nb doping, the d orbitals of the Nb atoms also contributed electrons that were concentrated near the Fermi surface. Additionally, the decrease in the effective mass after Nb doping indicated that the electrons could move more freely through the material, implying an enhancement of the electron mobility. The electrochemical properties of the Nb5+ doped NVP@C@Nb cathode material were evaluated through cyclic voltammetry (CV), galvanostatic charge-discharge tests, electrochemical impedance spectroscopy (EIS), and X-ray photoelectric spectroscopy (XPS). The results showed that NVP@C@Nb0.15 achieved an initial discharge capacity as high as 114.27 mAhg−1, with a discharge capacity of 106.38 mAhg−1 maintained after 500 cycles at 0.5C, and the retention rate of the NVP@C@Nb0.15 composite reached an impressive 90.22%. NVP@C@Nb0.15 exhibited low resistance and high capacity, enabling it to create more vacancies and modulate crystal structure, ultimately enhancing the electrochemical properties of NVP. The outstanding performance can be attributed to the Nb5+-doped carbon layer, which not only improves electronic conductivity but also shortens the diffusion length of Na+ ions and electrons, as well as reduces volume changes in electrode materials. These preliminary results suggested that the as-obtained NVP@C@Nb0.15 composite was a promising novel cathode electrode material for efficient sodium energy storage.

Piezoelectric material-based devices have garnered considerable attention from scientists and engineers due to their unique physical characteristics, resulting in numerous intriguing and practical applications. Among these, flexural-mode piezoelectric resonators (FMPRs) are progressively gaining prominence due to their compact, precise, and efficient performance in diverse applications. FMPRs, resonators that utilize one- or two-dimensional piezoelectric materials as their resonant structure, vibrate in a flexural mode. The resonant properties of the resonator directly influence its performance, making in-depth research into the resonant characteristics of FMPRs practically significant for optimizing their design and enhancing their performance. With the swift advancement of micro-nano electronic technology, the application range of FMPRs continues to broaden. These resonators, representing a domain of piezoelectric material application in micro-nanoelectromechanical systems, have found extensive use in the field of physical sensing and are starting to be used in micropower systems and biomedicine. This paper reviews the structure, working principle, resonance characteristics, applications, and future prospects of FMPRs.

This study employs the reflection symmetry decomposition (RSD) method to extract polarization scattering features from ground object images, aiming to determine the optimal data input scheme for deep learning networks in polarimetric synthetic aperture radar classification. Eight distinct polarizing feature combinations were designed, and the classification accuracy of various approaches was evaluated using the classic convolutional neural networks (CNNs) AlexNet and VGG16. The findings reveal that the commonly employed six-parameter input scheme, favored by many researchers, lacks the comprehensive utilization of polarization information and warrants attention. Intriguingly, leveraging the complete nine-parameter input scheme based on the polarization coherence matrix results in improved classification accuracy. Furthermore, the input scheme incorporating all 21 parameters from the RSD and polarization coherence matrix notably enhances overall accuracy and the Kappa coefficient compared to the other seven schemes. This comprehensive approach maximizes the utilization of polarization scattering information from ground objects, emerging as the most effective CNN input data scheme in this study. Additionally, the classification performance using the second and third component total power values (P2 and P3) from the RSD surpasses the approach utilizing surface scattering power value (PS) and secondary scattering power value (PD) from the same decomposition.

Sensing and cognition by homeowners and technicians for home maintenance are prime examples of human–building interaction. Damage, decay, and pest infestation present signals that humans interpret and then act upon to remedy and mitigate. The maintenance cognition process has direct effects on sustainability and economic vitality, as well as the health and well-being of building occupants. While home maintenance practices date back to antiquity, they readily submit to augmentation and improvement with modern technologies. This paper describes the use of networked smart technologies embedded with machine learning (ML) and presented in electronic formats to better inform homeowners and occupants about safety and maintenance issues, as well as recommend courses of remedial action. The demonstrated technologies include robotic sensing in confined areas, LiDAR scans of structural shape and deformation, moisture and gas sensing, water leak detection, network embedded ML, and augmented reality interfaces with multi-user teaming capabilities. The sensor information passes through a private local dynamic network to processors with neural network pattern recognition capabilities to abstract the information, which then feeds to humans through augmented reality and conventional smart device interfaces. This networked sensor system serves as a testbed and demonstrator for home maintenance technologies, for what can be termed Home Maintenance 4.0.

Low-alloy wear-resistant steel often requires the addition of trace alloy elements to enhance its performance while also considering the cost-effectiveness of production. In order to comparatively analyze the strengthening mechanisms of Mo and Cr elements and further explore economically feasible production processes, we designed two types of low-alloy wear-resistant steels, based on C-Mn series wear-resistant steels, with individually added Mo and Cr elements, comparing and investigating the roles of the alloying elements Mo and Cr in low-alloy wear-resistant steels. Utilizing JMatPro software to calculate Continuous Cooling Transformation (CCT) curves, conducting thermal simulation quenching experiments using a Gleeble-3800 thermal simulator, and employing equipment such as a metallographic microscope, transmission electron microscope, and tensile testing machine, this study comparatively investigated the influence of Mo and Cr on the microstructural transformation and mechanical properties of low-alloy wear-resistant steels under different cooling rates. The results indicate that the addition of the Mo element in low-alloy wear-resistant steel can effectively suppress the transformation of ferrite and pearlite, reduce the martensitic transformation temperature, and lower the critical cooling rate for complete martensitic transformation, thereby promoting martensitic transformation. Adding Cr elements can reduce the austenite transformation zone, decrease the rate of austenite formation, and promote the occurrence of low-temperature phase transformation. Additionally, Mo has a better effect on improving the toughness of low-temperature impact, and Cr has a more significant improvement in strength and hardness. The critical cooling rates of C-Mn-Mo steel and C-Mn-Cr steel for complete martensitic transition are 13 °C/s and 24 °C/s, respectively. With the increase in the cooling rate, the martensitic tissues of the two experimental steels gradually refined, and the characteristics of the slats gradually appeared. In comparison, the C-Mn-Mo steel displays a higher dislocation density, accompanied by dislocation entanglement phenomena, and contains a small amount of residual austenite, while granular ε-carbides are clearly precipitated in the C-Mn-Cr steel. The C-Mn-Mo steel achieves its best performance at a cooling rate of 25 °C/s, whereas the C-Mn-Cr steel only needs to increase the cooling rate to 35 °C/s to attain a similar comprehensive performance to the C-Mn-Mo steel.

The two existing clades of Galloanseres, orders Galliformes (landfowl) and Anseriformes (waterfowl), exhibit dramatically different evolutionary trends. Mitochondria serve as primary sites for energy production in organisms, and numerous studies have revealed their role in biological evolution and ecological adaptation. We assembled the complete mitogenome sequences of two species of the genus Aythya within Anseriformes: Aythya baeri and Aythya marila. A phylogenetic tree was constructed for 142 species within Galloanseres, and their divergence times were inferred. The divergence between Galliformes and Anseriformes occurred ~79.62 million years ago (Mya), followed by rapid evolution and diversification after the Middle Miocene (~13.82 Mya). The analysis of selective pressure indicated that the mitochondrial protein-coding genes (PCGs) of Galloanseres species have predominantly undergone purifying selection. The free-ratio model revealed that the evolutionary rates of COX1 and COX3 were lower than those of the other PCGs, whereas ND2 and ND6 had faster evolutionary rates. The CmC model also indicated that most PCGs in Anseriformes exhibited stronger selective constraints. Our study suggests that the distinct evolutionary trends and energy requirements of Galliformes and Anseriformes drive different evolutionary patterns in the mitogenome.

Abstract Aythya marila is one of the few species of Anatidae, and the only Aythya to live in the circumpolar. However, there is a relative lack of research on genetics of this species. In this study, we reported and assembled the first high-quality chromosome-level genome assembly of A. marila. This genome was assembled using Nanopore long reads, and errors corrected using Illumina short reads, with a final genome size of 1.14 Gb, scaffold N50 of 85.44 Mb, and contig N50 of 32.46 Mb. 106 contigs were clustered and ordered onto 35 chromosomes based on Hi-C data, covering approximately 98.28% of the genome. BUSCO assessment showed that 97.0% of the highly conserved genes in aves_odb10 were present intact in the genome assembly. In addition, a total of 154.94 Mb of repetitive sequences were identified. 15,953 protein-coding genes were predicted in the genome, and 98.96% of genes were functionally annotated. This genome will be a valuable resource for future genetic diversity and genomics studies of A. marila.

Background and objectives: The heterogeneity of pulmonary fibroblasts, a critical aspect of both murine and human models under physiological and pathological conditions, is well-documented. Yet, consensus remains elusive on the subtypes, lineage, biological attributes, signal transduction pathways, and plasticity of these fibroblasts. This ambiguity significantly impedes our understanding of the fibrotic processes that transpire in lung tissue during aging. This study aims to elucidate the transcriptional profiles, differentiation pathways, and potential roles of fibroblasts within aging pulmonary tissue.Methods: We employed single-cell transcriptomic sequencing via the 10x Genomics platform. The downstream data were processed and analyzed using R packages, including Seurat. Trajectory and stemness of differentiation analyses were conducted using the Monocle2 and CytoTRACE R packages, respectively. Cell interactions were deciphered using the CellChat R package, and the formation of collagen and muscle fibers was identified through Masson and Van Geison staining techniques.Results: Our analysis captured a total of 22,826 cells, leading to the identification of fibroblasts and various immune cells. We observed a shift in fibroblasts from lipogenic and immune-competent to fibrotic and myofibroblast-like phenotype during the aging process. In the aged stage, fibroblasts exhibited a diminished capacity to express chemokines for immune cells. Experimental validation confirmed an increase of collagen and muscle fiber in the aged compared to young lung tissues. Furthermore, we showed that TGFβ treatment induced a fibrotic, immunodeficient and lipodystrophic transcriptional phenotype in young pulmonary fibroblasts.Conclusion: We present a comprehensive single-cell transcriptomic landscape of lung tissue from aging mice at various stages, revealing the differentiation trajectory of fibroblasts during aging. Our findings underscore the pivotal role of fibroblasts in the regulation of immune cells, and provide insights into why age increases the risk of pulmonary fibrosis.

BackgroundLifestyle modification is the cornerstone of non-alcoholic fatty liver disease (NAFLD) prevention and treatment. Short video platforms can facilitate easier access to health information for patients, thereby influencing lifestyle changes. An increasing number of individuals rely on online platforms to acquire health-related information about NAFLD. However, the quality of information regarding NAFLD on these platforms remains unclear.ObjectiveThis study aimed to investigate the quality of information about NAFLD on TikTok.MethodsA total of 497 videos were retrieved from TikTok. The basic video information, including the video source, was extracted. Two independent raters evaluated the quality and reliability of the videos using the Global Quality Score system and a modified DISCERN tool. Propensity score matching (PSM) was used to compare video quality across sources.ResultsNAFLD-related videos on TikTok were divided into three groups according to the uploader: health professionals, medical institutions, and science bloggers. Overall, the quality of NAFLD videos on TikTok was not satisfactory. Before PSM, there were no significant differences in video quality or content between the three groups. After PSM, the quality of NAFLD videos from health professionals was significantly better than the videos created by other groups. Besides, the videos of health professionals outperformed those of medical institutions and science bloggers in terms of the definition of disease, risk factors, and treatment, but were inferior to those of medical institutions considering the symptoms and tests of NAFLD.ConclusionThe quality of NAFLD-related videos on TikTok needs improvement. Compared with videos created by science bloggers and medical institutions, videos from health professionals may provide accurate guidance on the treatment and prevention of NAFLD.

Summary: Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma (LUAD) biomarkers, we showcased the superior performance of SRS compared to current state-of-the-art AI approaches. These findings suggest that AI tools, built on the ROB concept, can achieve enhanced molecular biomarker prediction accuracy from pathological images.

Abstract Progressive massive pulmonary fibrosis among coal miners has unexpectedly increased. It would likely due to the greater generation of smaller rock and coal particles produced by powerful equipment used in modern mines. There is limited understanding of the relationship between micro- or nanoparticles with pulmonary toxicity. This study aims to determine whether the size and chemical characteristics of typical coal-mining dust contribute to cellular toxicity. Size range, surface features, morphology, and elemental composition of coal and rock dust from modern mines were characterized. Human macrophages and bronchial tracheal epithelial cells were exposed to mining dust of three sub- micrometer and micrometer size ranges at varying concentrations, then assessed for cell viability and inflammatory cytokine expression. Coal had smaller hydrodynamic size (180–3000 nm) compared to rock (495–2160 nm) in their separated size fractions, more hydrophobicity, less surface charge, and consisted of more known toxic trace elements (Si, Pt, Fe, Al, Co). Larger particle size had a negative association with in-vitro toxicity in macrophages (p

Abstract Baer’s pochard (Aythya baeri) is a critically endangered species historically widespread throughout East Asia, whose population according to a recent estimate has decreased to between 150 and 700 individuals, and faces a long-term risk of extinction. However, the lack of a reference genome limits the study of conservation management and molecular biology of this species. We therefore report the first high-quality genome assembly of Baer’s pochard. The genome has a total length of 1.14 Gb with a scaffold N50 of 85,749,954 bp and a contig N50 of 29,098,202 bp. We anchored 97.88% of the scaffold sequences onto 35 chromosomes based on the Hi-C data. BUSCO assessment indicated that 97.00% of the highly conserved Aves genes were completely present in the genome assembly. Furthermore, a total of 157.06 Mb of repetitive sequences were identified and 18,581 protein-coding genes were predicted in the genome, of which 99.00% were functionally annotated. This genome will be useful for understanding Baer’s pochard genetic diversity and facilitate the conservation planning of this species.

Abstract Background Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB. Methods This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days. Results Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26–1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log10 copies/mL, respectively. Conclusions Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection. Trial registration ClinicalTrials.gov, number NCT05470829).

Abstract Background Esophageal squamous carcinoma (ESCC) is a common malignancy that originates in the digestive tract. Lymph node metastasis (LNM) is a complicated process, and tumor lymphangiogenesis has been reported to be associated with the spread of tumor cells to lymph nodes (LNs), including in ESCC. However, little is currently known about the mechanisms involved in lymphangiogenesis in ESCC tumors. According to previous literature, we know that hsa_circ_0026611 expresses at a high level in serum exosomes of patients with ESCC and shows a close association with LNM and poor prognosis. However, details on the functions of circ_0026611 in ESCC remain unclear. We aim to explore the effects of circ_0026611 in ESCC cell-derived exosomes on lymphangiogenesis and its potential molecular mechanism. Methods We firstly examined how circ_0026611 may express in ESCC cells and exosomes by quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The potential effects circ_0026611 may exert on lymphangiogenesis in ESCC cell-derived exosomes were assessed afterward via mechanism experiments. Results circ_0026611 high expression pattern was confirmed in ESCC cells and exosomes. ESCC cell-derived exosomes promoted lymphangiogenesis by transferring circ_0026611. Besides, circ_0026611 interacted with N-α-acetyltransferase 10 (NAA10) to inhibit NAA10-mediated prospero homeobox 1 (PROX1) acetylation with subsequent ubiquitination and degradation. Furthermore, circ_0026611 was verified to promote lymphangiogenesis in a PROX1-mediated manner. Conclusions Exosomal circ_0026611 inhibited PROX1 acetylation and ubiquitination to promote lymphangiogenesis in ESCC. Graphical Abstract