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Background While the connection between monounsaturated fatty acid (MUFA) intake and non-alcoholic fatty liver disease (NAFLD) has received attention, research in Chinese populations remains scarce. Objective This study aims to evaluate the association between daily MUFA intake and the prevalence of NAFLD in a Chinese population and to estimate the probable threshold of MUFA intake for NAFLD risk. Methods This case-control study employed data from the Dryad database (https://doi.org/10.5061/dryad.8nn2j46), complying with Dryad's terms of service. We collected data from 534 NAFLD patients and 534 healthy controls who underwent medical tests at the First Hospital of Nanping Affiliated to Fujian Medical University between April 2015 and August 2017. A semi-quantitative food frequency questionnaire (SQFFQ) was used to collect individuals' typical food consumption information, and daily MUFA intake was computed. A thorough analytical technique, including baseline characteristics, multivariate statistics, non-linear relationship analysis, and subgroup research, was applied to study the correlation between daily MUFA intake and NAFLD prevalence. Multiple confounding factors, such as age, sex, lifestyle, and other dietary components, were evaluated to estimate the theoretical threshold of MUFA intake for NAFLD risk. Results In the adjusted model, daily MUFA intake was a significant risk factor for NAFLD (OR=1.04, 95%CI=1.02-1.07, P

Abstract Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating’s controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.

Abstract Skull-base chordoma is a rare, aggressive bone cancer with a high recurrence rate. Despite advances in genomic studies, its molecular characteristics and effective therapies remain unknown. Here, we conduct integrative genomics, transcriptomics, proteomics, and phosphoproteomics analyses of 187 skull-base chordoma tumors. In our study, chromosome instability is identified as a prognostic predictor and potential therapeutic target. Multi-omics data reveals downstream effects of chromosome instability, with RPRD1B as a putative target for radiotherapy-resistant patients. Chromosome 1q gain, associated with chromosome instability and upregulated mitochondrial functions, lead to poorer clinical outcomes. Immune subtyping identify an immune cold subtype linked to chromosome 9p/10q loss and immune evasion. Proteomics-based classification reveals subtypes (P-II and P-III) with high chromosome instability and immune cold features, with P-II tumors showing increased invasiveness. These findings, confirmed in 17 paired samples, provide insights into the biology and treatment of skull-base chordoma.

Abstract With the increase in high-rise buildings in cities, public flue exhaust systems have a direct impact on residential air quality and the living environment. Although existing studies have analyzed the problems in public flue exhaust systems through computational fluid dynamics (CFD) numerical simulations and experimental tests, these studies often lack an in-depth exploration of the specific impacts of individual components in the system. To solve this problem, this study not only thoroughly analyzes the key components in the public flue system, such as branch pipes, check valves, and tee pipes, but also develops a parametric public flue simulation system software based on C# and verifies the accuracy of the simulation through experiments. The study first determines the key parameters affecting the comprehensive resistance coefficient of the branch pipe, check valve, tee pipe, and other components through CFD simulation and experimental testing. Subsequently, a visualization program is developed using the C# language, which can quickly simulate and visualize the flow changes in the flue according to different building parameters such as the number of floors, height of floors, and size of the flue. The results confirm that the program can efficiently predict the flow distribution under different design options, providing a practical tool for the optimal design and performance evaluation of public flues, which is important for improving the air quality of the living environment.

Various studies have been conducted on applying intelligent recognition technology, especially speech recognition technology to improve English learning ability, mostly listening and speaking. However, few studies have touched on how image-to-text recognition technology can be used for writing. The present research was conducted to fill this gap by exploring the optimization of a deep-learning-based image captioning algorithm to facilitate English writing, so as to enable learners to break the time and space limitations and learn English writing (including sentence patterns, spelling, vocabulary, and grammar) anytime and anywhere by taking pictures. Therefore, this paper focused on image captioning based on CNN(Convolutional Neural Networks) and LSTM (Long Short-Term Memory), using DenseNet201 or Vision Transformer trained on the ImageNet-1K image classification dataset as the image encoder and LSTM as the decoder. First, pre-training was performed on the Flickr8k dataset. After selecting the best-trained model as the pre-trained weight model for the COCO dataset, fine-tuning optimization was performed on the COCO dataset, and the attention mechanism was used to design the ablation experiment. The BLEU-4, CIDEr, METEOR, and ROUGE evaluation indexes of the optimized model on the test set were 0.3437,1.121,0.2750, and 0.5117, respectively. The study results showed that the convergence of the model was accelerated and had better performance. The model was used to automatically caption 12 images that had never been used during the training process. The descriptions generated by the optimized image captioning algorithm have lexical and syntactic accuracy, and matched what the images expressed, showing that this improved algorithm could be used as a learning tool to help English learners improve lexical and syntactic acquisition to promote writing through the generated descriptions of the pictures taken anytime and anywhere in real-life situations.

The flame retardancy and smoke suppression performance of silicone rubber foam (SiFs) greatly affected its promotion and application in the field of high performance materials. Improving the flame retardancy and smoke suppression performance of SiFs had became a hot and difficult topic in recent years. The current research status of flame retardancy and smoke suppression of SiFs in flame retardant systems such as metal hydroxide flame retardants, boron- based flame retardants, phosphorus-and nitrogen-based flame retardants, platinum catalysts, microcapsule flame retardants, and ceramic-based flame retardants had been summarized with 67 references. Besides, the corresponding flame retardancy mechanisms had been expounded. Finally, the future research direction of flame retardancy and smoke suppression of SiFs was presented.

Objective To explore the impact of knocking down Sec31A on the malignant phenotype of head and neck squamous cell carcinoma(HNSCC) and its possible mechanisms. Methods Transcriptome sequencing data of HNSCC tissues and adjacent tissues were obtained from the TCGA database, and the expression levels of Sec31A were compared. Immunohistochemical staining was used to analyze the expression of Sec31A in HNSCC tissues. Kaplan-Meier survival analysis was used to compare the relationship between Sec31A and the prognosis of HNSCC patients. Small interfering plasmids si-Sec31A and si-NC were transfected into HNSCC cell lines HN6 and HN4, and the impact of knocking down Sec31A on the biological behavior of HNSCC cells was detected through CCK-8 experiments, plate cloning experiments, scratch healing experiments, and Transwell experiments. Changes in the expression levels of PI3K/AKT/mTOR pathway related proteins in cells were detected after knocking down Sec31A with HN6 and HN4 through Western Blot(WB)experiments. Stable transfected cell lines of HN6 siSec31A and HN6 siNC were constructed and inoculated subcutaneously in nude mice to further verify the tumorigenic effect of Sec31A in vivo. Results TCGA data showed that Sec31A was higher in HNSCC tissues than in adjacent normal tissues(P

Objective How to minimize postoperative pain following knee replacement surgery has been a great challenge. This study was performed to evaluate the effect of applying a topical nonsteroidal anti‐inflammatory drug (NSAID) lateral to the incision for postoperative pain following unicompartmental knee arthroplasty (UKA). Methods The randomized controlled trial enrolled 100 patients from August 2023 to January 2024. One hundred patients who underwent UKA were randomized into two groups. The intervention group received a topical NSAID lateral to the incision postoperatively, and the control group received a placebo lateral to the incision postoperatively. The primary outcome measures were the amount of opioid consumption and the visual analogue scale (VAS) score (12, 24, 36, 48, and 72 h after operation) for pain. The secondary outcome measures were the American Knee Society Score (AKSS, preoperation and 1‐month follow‐up after operation), the time of first analgesic demand, side effects of opioids, operation time, postoperative stay, surgery‐related complications, and postoperative incision healing grade. Independent sample t test and paired sample t test were used to compare continuous data. Chi‐square test and Fisher's precision probability tests were used to analyze the categorical data. Results Ninety‐eight patients (intervention group, 48 patients; control group, 50 patients) were analyzed. Opioid consumption was significantly lower in the intervention group than in the control group during the first 12 h, 12 to 24 h, and 24 to 48 h postoperatively (p

Abstract This study investigates the adaptive strategies of the Alashan Ground Squirrel (Spermophilus alashanicus) in response to habitat changes, as rodents are sensitive indicators of ecosystem changes. Despite its ecological importance, the genome and microbiome of this species have not been thoroughly studied. This research fills this gap by presenting the first comprehensive metagenomic and transcriptomic datasets of the species. Transcriptomic data was collected from five tissue types, including heart, liver, cecum, muscle, and blood, resulting in the assembly of 72,156 unigenes. Metagenomic sequencing identified predominant bacterial groups such as Firmicutes, Bacteroidetes, Verrucomicrobia, Urovircota, and Proteobacteria. Our workflow involved RNA and DNA extraction, library preparation, assembly, and annotation, yielding valuable insights into gene discovery, microbial composition, and further genome and microbial function studies. In conclusion, our findings have significant implications for understanding the adaptive mechanisms of this species in response to environmental changes.

Abstract Arteriovenous fistulas (AVFs) are the most common vascular access points for hemodialysis (HD), but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia (NIH). Our previous studies have revealed a highly conserved LncRNA-LncDACH1 as an important regulator of cardiomyocyte and fibroblast proliferation. Herein, we find that LncDACH1 regulates NIH in AVF in male mice with conditional knockout of smooth muscle cell-specific LncDACH1 and in male mice model of AVF with LncDACH1 overexpression by adeno-associated virus. Mechanistically, silence of LncDACH1 activates p-AKT through promoting the expression of heat shock protein 90 (HSP90) and serine/arginine-rich splicing factor protein kinase 1 (SRPK1). Moreover, LncDACH1 is transcriptionally activated by transcription factor KLF9 that binds directly to the promoter region of the LncDACH1 gene. In this work, during AVF NIH, LncDACH1 is downregulated by KLF9 and promotes NIH through the HSP90/ SRPK1/ AKT signaling axis.

We present two cases of cardiac metastases adjacent to the right ventricle in a 55-year-old male and a 61-year-old female, both treated with magnetic resonance (MR)-guided adaptive stereotactic radiation therapy (SBRT). The prescribed regimen was 30Gy delivered in 3 fractions using a 1.5 Tesla magnetic resonance linear accelerator (MR-linac). Patients exhibited favorable tolerance to the treatment, with no observed acute toxicity.

The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20 %, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives. Based on this conformation, we designed and synthesized four series of derivatives. By evaluating their affinity and anti-HCC effects, we confirmed that these compounds exert anti-HCC activity by inhibiting ULK1. The structure-activity relationship was summarized, with derivative A4 showing 10 times higher activity than XST-14 and superior efficacy to sorafenib against HCC. A4 has excellent effect on reducing tumor growth and enhancing sorafenib activity in HepG2 and HCCLM3 cells. Moreover, we verified the therapeutic effect of A4 in sorafenib-resistant HCC cells both in vivo and in vitro. These results suggest that inhibiting ULK1 to regulate autophagy may become a new treatment method for HCC and that A4 will be used as a lead drug for HCC in further research. Overall, A4 shows good drug safety and efficacy, offering hope for prolonging the survival of HCC patients.

To improve the interpretability of estimation processes in machine learning, we applied the Shapley additive explanation method to six tree-based models for predicting downstream salinity. Decision tree-based adaptive boosting (AdaBoost) demonstrated the highest performance, followed by extreme gradient boosting (XGBoost). Global post-decomposition in XGBoost identified water level, a major cause of salinity intrusion in actual environments, as the main contributor of salinity intrusion, while an interaction effect between water temperature and sea level pressure was identified as the main contributor in AdaBoost. Local post-decomposition in XGBoost enables visual interpretation of most of the salinity behaviors. However, the interaction effect between water level and sea level pressure identified as the main contributor by XGBoost was unlikely to drive the actual increase in salinity immediately after a heavy rainfall event. We conclude that highly accurate estimations are not necessarily interpretable and reliable and local post-decomposition can detect inconsistencies in estimation processes.

Summary: Rice stripe virus (RSV) establishes infection in the ovaries of its vector insect, Laodelphax striatellus. We demonstrate that RSV infection delays ovarian maturation by inhibiting membrane localization of the vitellogenin receptor (VgR), thereby reducing the vitellogenin (Vg) accumulation essential for egg development. We identify the host protein L. striatellus Rab1 protein (LsRab1), which directly interacts with RSV nucleocapsid protein (NP) within nurse cells. LsRab1 is required for VgR surface localization and ovarian Vg accumulation. RSV inhibits LsRab1 function through two mechanisms: NP binding LsRab1 prevents GTP binding, and NP binding LsRab1-GTP complexes stimulates GTP hydrolysis, forming an inactive LsRab1 form. Through this dual inhibition, RSV infection prevents LsRab1 from facilitating VgR trafficking to the cell membrane, leading to inefficient Vg uptake. The Vg-VgR pathway is present in most oviparous animals, and the mechanisms detailed here provide insights into the vertical transmission of other insect-transmitted viruses of medical and agricultural importance.

Objective: The current study aimed to investigate the potential therapeutic impact of allantoin on diabetes produced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Subjects and methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The effect of oral treatment of allantoin (200, 400 and 800 mg/kg/day) for 8 weeks was evaluated by calculating the alteration in metabolic parameters, biochemical indicators, the oral glucose tolerance tests (OGTT) and hyperinsulinemic-euglycemic clamp tests were performed. Histopathological studies were performed in the liver, kidney and pancreas. Next, the expressions of the MAPK and insulin signaling pathway were measured by Western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. Results: The administration of allantoin resulted in a significant decrease in fasting blood glucose (FBG) levels, glycogen levels, and glycosylated hemoglobin levels in diabetic rats. Additionally, allantoin therapy led to a dose-dependent increase in body weight growth and serum insulin levels. In addition, the administration of allantoin resulted in a considerable reduction in lipid profile levels and amelioration of histological alterations in rats with diabetes. The administration of allantoin to diabetic rats resulted in a notable decrease in Malondialdehyde (MDA) levels, accompanied by an increase in the activity of antioxidant enzymes in the serum, liver, and kidney. The findings of oral glucose tolerance and hyperinsulinemic-euglycemic clamp tests demonstrated a significant rise in insulin resistance following the administration of allantoin. The upregulation of IRS-2/PI3K/p-Akt/GLUT expression by allantoin suggests a mechanistic relationship between the PI3K/Akt signaling pathway and the antihyperglycemic activity of allantoin. Furthermore, it resulted in a reduction in the levels of TGF-β1/p38MAPK/Caspase-3 expression in the aforementioned rat tissues affected by diabetes. Conclusions: This study implies that allantoin treats type 2 diabetes by activating PI3K. Additionally, it reduces liver, kidney, and pancreatic apoptosis and inflammation-induced insulin resistance.re

To meet the expectation set by Moore’s law on transistors, the search for thickness-scalable high dielectric constant (k) gate layers has become an emergent research frontier. Previous investigations have failed to solve the “polarizability–scalability–insulation robustness” trilemma. In this work, we show that this trilemma can be solved by using a gate layer of a high k ferroelectric oxide in its superparaelectric (SPE) state. In the SPE, its polar order becomes local and is dispersed in an amorphous matrix with a crystalline size down to a few nanometers, leading to an excellent dimensional scalability and a good field-stability of the k value. As an example, a stable high k value (37±3) is shown in ultrathin SPE films of (Ba0.95,Sr0.05)(Zr0.2,Ti0.8)O3 deposited on LaNiO3-buffered Pt/Ti/SiO2/(100)Si down to a 4 nm thickness, leading to a small equivalent oxide thickness of ~0.46 nm. The aforementioned characteristic microstructure endows the SPE film a high breakdown strength (~10.5 MV·cm−1 for the 4 nm film), and hence ensures a low leakage current for the operation of the complementary metal oxide semiconductor (CMOS) gate. Lastly, a high electrical fatigue resistance is displayed by the SPE films. These results reveal a great potential of superparaelectric materials as gate dielectrics in the next-generation microelectronics.

Abstract Background SIRPB1 expression is upregulated in various tumor types, including gliomas, and is known to contribute to tumor progression; nevertheless, its function in the immune milieu of gliomas is still mainly unknown. Methods This study, we analyzed 1152 normal samples from the GTEx database and 670 glioma samples from the TCGA database to investigate the relationship between the expression of SIRPB1 and clinicopathological features. Moreover, SIRPB1 gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 and were induced into a co-culture of macrophages and glioma cells in vitro to learn more about the role of SIRPB1 in the glioma immune milieu. Lastly, we established a prognostic model to predict the effect of SIRPB1 on prognosis. Results Significantly higher levels of SIRPB1 expression were found in gliomas, which had an adverse effect on the immune milieu and correlated poorly with patient survival. SIRPB1 activation with certain antibodies results in SYK phosphorylation and the subsequent activation of calcium, MAPK, and NF-κB signaling pathways. This phenomenon is primarily observed in myeloid-derived cells as opposed to glioma cells. In vitro co-culture demonstrated that macrophages with SIRPB1 knockout showed decreased IL1RA, CCL2, and IL-8, which were recovered upon ectopic expression of SIRPB1 but reduced again following treatment with SYK inhibitor GS9973. Critically, a lower overall survival rate was linked to increased SIRPB1 expression. Making use of SIRPB1 expression along with additional clinicopathological variables, we established a nomogram that showed a high degree of prediction accuracy. Conclusions Our study demonstrates that glioma cells can be activated by macrophages via SIRPB1, subsequently reprogramming the TME, suggesting that SIRPB1 could serve as a promising therapeutic target for gliomas.

Abstract Background The triglyceride and glucose (TyG) index, a simple surrogate marker of insulin resistance, is related to cardiovascular disease. However, there is a lack of evidence for the relationship between the TyG index and chest pain. This study aimed to investigate the association of the TyG index with chest pain and to evaluate the relationship between the TyG index and all-cause mortality in participants with or without chest pain. Methods The present study utilized data from the 2001–2012 National Health and Nutrition Examination Survey (NHANES), employing a combination of cross-sectional and cohort study designs. The association between the TyG index and chest pain was investigated using weighted logistic regression models. Weighted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality. Restricted cubic spline analysis was used to explore linear or nonlinear relationships between the TyG index and chest pain or all-cause mortality. Results The findings revealed a positive correlation between the TyG index and chest pain, even after adjusting for potential confounding factors (quartile 4 versus quartile 1, odds ratio [OR] 1.42, 95% confidence interval [CI] 1.14–1.77, P = 0.002). During a mean follow-up time of 139 months, a total of 2286 individuals (27.43%) experienced mortality. Weighted multivariate Cox regression models indicated that for each one-unit increase in the TyG index, the adjusted hazard ratio (HR) for mortality was 1.14 (95% CI = 0.94–1.37) for participants with chest pain and 1.25 (95% CI = 1.09–1.43) for those without chest pain. Furthermore, restricted cubic spline analysis revealed a linear relationship between the TyG index and chest pain (P for nonlinearity = 0.902), whereas a nonlinear relationship was shown between the TyG index and all-cause mortality among populations regardless of chest pain (all P for nonlinearity

Abstract Neural ordinary differential equations (ODEs) (Neural ODEs) construct the continuous dynamics of hidden units using ODEs specified by a neural network, demonstrating promising results on many tasks. However, Neural ODEs still do not perform well on image recognition tasks. The possible reason is that the one‐hot encoding vector commonly used in Neural ODEs can not provide enough supervised information. A new training based on knowledge distillation is proposed to construct more powerful and robust Neural ODEs fitting image recognition tasks. Specially, the training of Neural ODEs is modelled into a teacher‐student learning process, in which ResNets are proposed as the teacher model to provide richer supervised information. The experimental results show that the new training manner can improve the classification accuracy of Neural ODEs by 5.17%, 24.75%, 7.20%, and 8.99%, on Street View House Numbers, CIFAR10, CIFAR100, and Food‐101, respectively. In addition, the effect of knowledge distillation is also evaluated in Neural ODEs on robustness against adversarial examples. The authors discover that incorporating knowledge distillation, coupled with the increase of the time horizon, can significantly enhance the robustness of Neural ODEs. The performance improvement is analysed from the perspective of the underlying dynamical system.

Abstract Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

Abstract Sakuranetin plays a key role as a phytoalexin in plant resistance to biotic and abiotic stresses, and possesses diverse health-promoting benefits. However, mature rice seeds do not contain detectable levels of sakuranetin. In the present study, a transgenic rice plant was developed in which the promoter of an endosperm-specific glutelin gene OsGluD-1 drives the expression of a specific enzyme naringenin 7-O-methyltransferase (NOMT) for sakuranetin biosynthesis. The presence of naringenin, which serves as the biosynthetic precursor of sakuranetin made this modification feasible in theory. Liquid chromatography tandem mass spectrometry (LC–MS/MS) validated that the seeds of transgenic rice accumulated remarkable sakuranetin at the mature stage, and higher at the filling stage. In addition, the panicle blast resistance of transgenic rice was significantly higher than that of the wild type. Specially, the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging was performed to detect the content and spatial distribution of sakuranetin and other nutritional metabolites in transgenic rice seeds. Notably, this genetic modification also did not change the nutritional and quality indicators such as soluble sugars, total amino acids, total flavonoids, amylose, total protein, and free amino acid content in rice. Meanwhile, the phenotypes of the transgenic plant during the whole growth and developmental periods and agricultural traits such as grain width, grain length, and 1000-grain weight exhibited no significant differences from the wild type. Collectively, the study provides a conceptual advance on cultivating sakuranetin-rich biofortified rice by metabolic engineering. This new breeding idea may not only enhance the disease resistance of cereal crop seeds but also improve the nutritional value of grains for human health benefits.

Abstract Outcome-guided behavior requires knowledge about the identity of future rewards. Previous work across species has shown that the dopaminergic midbrain responds to violations in expected reward identity and that the lateral orbitofrontal cortex (OFC) represents reward identity expectations. Here we used network-targeted transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) during a trans-reinforcer reversal learning task to test the hypothesis that outcome expectations in the lateral OFC contribute to the computation of identity prediction errors (iPE) in the midbrain. Network-targeted TMS aiming at lateral OFC reduced the global connectedness of the lateral OFC and impaired reward identity learning in the first block of trials. Critically, TMS disrupted neural representations of expected reward identity in the OFC and modulated iPE responses in the midbrain. These results support the idea that iPE signals in the dopaminergic midbrain are computed based on outcome expectations represented in the lateral OFC.

IntroductionMembers of the plant-specific B3 transcription factor superfamily play crucial roles in various plant growth and developmental processes. Despite numerous valuable studies on B3 genes in other species, little is known about the B3 superfamily in pearl millet.Methods and resultsHere, through comparative genomic analysis, we identified 70 B3 proteins in pearl millet and categorized them into four subfamilies based on phylogenetic affiliations: ARF, RAV, LAV, and REM. We also mapped the chromosomal locations of these proteins and analyzed their gene structures, conserved motifs, and gene duplication events, providing new insights into their potential functional interactions. Using transcriptomic sequencing and real-time quantitative PCR, we determined that most PgB3 genes exhibit upregulated expression under drought and high-temperature stresses, indicating their involvement in stress response regulation. To delve deeper into the abiotic stress roles of the B3 family, we focused on a specific gene within the RAV subfamily, PgRAV-04, cloning it and overexpressing it in tobacco. PgRAV-04 overexpression led to increased drought sensitivity in the transgenic plants due to decreased proline levels and peroxidase activity.DiscussionThis study not only adds to the existing body of knowledge on the B3 family’s characteristics but also advances our functional understanding of the PgB3 genes in pearl millet, reinforcing the significance of these factors in stress adaptation mechanisms.

PurposeThe purpose of this study is to summarize the design and methodology of a large-scale trial in northern China, the Beijing Angle Closure Progression Study (BAPS). This trial is designed to explore the 5-year incidence of primary angle-closure suspect (PACS) progressing to primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) and to determine the possible risk factors of disease progression.Methods/designThe BAPS is a clinic-based, multicenter, noninterventional trial conducted on a sample of urban Chinese adults. Consecutive eligible patients who meet PACS diagnostic criteria will be recruited from eight participating centers, with the trial commencing on August 4, 2022. The target sample size is set at 825 subjects, with follow up planned for a minimum period of 5 years. Baseline examination will include presenting visual acuity, best corrected visual acuity, intraocular pressure (IOP), undilated slit-lamp biomicroscopy, stereoscopic evaluation of the optic disc, visual field test, optical coherence tomography evaluation of retinal nerve fiber layer, ultrasound biomicroscopy and IOLMaster. Questionnaires will also be used to collect detailed personal history. Patients are scheduled to visit the glaucoma clinic every 12 months and may visit the emergency room in case of acute attack of angle closure. Study endpoints include acute PAC episodes, elevated IOP, peripheral anterior synechiae, glaucomatous visual field defect, or glaucomatous abnormality of optic nerve.DiscussionThe BAPS will provide data on the 5-year incidence of PACS progressing to PAC or PACG and determine the risk factors for disease progression. This study will also help redefine high-risk patients with PACS.

IntroductionPolyetheretherketone (PEEK) lumbar fusion rods have been successfully used in short-segment posterior instrumentation to prevent adjacent segment degeneration. However, limited studies have reported their application in lumbar long-segment instrumentation. This study aimed to compare the biomechanical performances of PEEK rods and titanium rods in lumbar long-segment instrumentation using finite element (FE) models, with the expectation of providing clinical guidance.MethodsA lumbar FE model (A) and four lumbar fixation FE models (BI, CI, BII, CII) of the L1–S1 vertebral body were developed using CT image segmentation (A: intact model; BI: intact model with L2–S1 PEEK rod internal fixation; CI: intact model with L2–S1 titanium rod internal fixation; BII: intact model with L3–S1 PEEK rod internal fixation; CII: intact model with L3–S1 titanium rod internal fixation). A 150-N preload was applied to the top surface of L1, similar to the intact model. The stresses on the lumbar intervertebral disc, facet joint, pedicle screws, and rods were calculated to evaluate the biomechanical effect of the different fixation procedures in lumbar long-segment instrumented surgery.ResultsUnder the four physiological motion states, the average stresses on the adjacent segment intervertebral disc and facet joint in all fixation models were greater than those in the intact model. Furthermore, the average stresses on the adjacent segment intervertebral disc and facet joint were greater in models CI and CII than in models BI and BII, respectively. The average stresses on the pedicle screws and rods were decreased in models BI and BII compared with models CI and CII under the four physiological motion states, respectively.DiscussionThe PEEK rod internal fixation system may have better biomechanical properties than the titanium rod internal fixation system in delaying adjacent segment degeneration, improving the lumbar function of postoperative patients, and reducing the risk of screw loosening and breakage in lumbar long-segment instrumentation.

Major depressive disorder (MDD) is a debilitating mental health condition that poses significant risks and burdens. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a promising tool in investigating the neural mechanisms underlying MDD. However, a comprehensive bibliometric analysis of resting-state fMRI in MDD is currently lacking. Here, we aimed to thoroughly explore the trends and frontiers of resting-state fMRI in MDD research. The relevant publications were retrieved from the Web of Science database for the period between 1998 and 2022, and the CiteSpace software was employed to identify the influence of authors, institutions, countries/regions, and the latest research trends. A total of 1501 publications met the search criteria, revealing a gradual increase in the number of annual publications over the years. China contributed the largest publication output, accounting for the highest percentage among all countries. Particularly, the University of Electronic Science and Technology of China, Capital Medical University, and Harvard Medical School were identified as key institutions that have made substantial contributions to this growth. Neuroimage, Biological Psychiatry, Journal of Affective Disorders, and Proceedings of the National Academy of Sciences of the United States of America are among the influential journals in the field of resting-state fMRI research in MDD. Burst keywords analysis suggest the emerging research frontiers in this field are characterized by prominent keywords such as dynamic functional connectivity, cognitive control network, transcranial brain stimulation, and childhood trauma. Overall, our study provides a systematic overview into the historical development, current status, and future trends of resting-state fMRI in MDD, thus offering a useful guide for researchers to plan their future research.