Chromosome-level genome assembly of the western flower thrips Frankliniella occidentalis.

The western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) is a global invasive species that causes increasing damage by direct feeding on crops and transmission of plant viruses. Here, we assemble a previously published scaffold-level genome into a chromosomal level using Hi-C sequencing technology. The assembled genome has a size of 302.58 Mb, with a contig N50 of 1533 bp, scaffold N50 of 19.071 Mb, and BUSCO completeness of 97.8%. All contigs are anchored on 15 chromosomes. A total of 16,312 protein-coding genes are annotated in the genome with a BUSCO completeness of 95.2%. The genome contains 492 non-coding RNA, and 0.41% of interspersed repeats. In conclusion, this high-quality genome provides a convenient and high-quality resource for understanding the ecology, genetics, and evolution of thrips.

ß-Lactoglobulin-based aerogels: Facile preparation and sustainable removal of organic contaminants from water.

Economically and efficiently removing organic pollutants from water is still a challenge in wastewater treatment. Utilizing environmentally friendly and readily available protein-based natural polymers to develop aerogels with effective removal performance and sustainable regeneration capability is a promising strategy for adsorbent design. Here, a robust and cost-effective method using inexpensive ß-lactoglobulin (BLG) as raw material was proposed to fabricate BLG-based aerogels. Firstly, photocurable BLG-based polymers were synthesized by grafting glycidyl methacrylate. Then, a cross-linking reaction, including photo-crosslinking and salting-out treatment, was applied to prepared BLG-based hydrogels. Finally, the BLG-based aerogels with high porosity and ultralight weight were obtained after freeze-drying. The outcomes revealed that the biocompatible BLG-based aerogels exhibited effective removal performance for a variety of organic pollutants under perfectly quiescent conditions, and could be regenerated and reused many times via a simple and rapid process of acid washing and centrifugation. Overall, this work not only demonstrates that BLG-based aerogels are promising adsorbents for water purification but also provides a potential way for the sustainable utilization of BLG.

Ba2Ga2F6(IO3)(PO4): the first fluoride-containing iodate-phosphate with a 1D [Ga2F6(IO3)(PO4)]4- helix chain.

Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.

IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts.

BACKGROUND: Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms. METHODS: Cardiomyocyte-specific inositol-requiring enzyme 1α (IRE1α) knockout and overexpression mouse models were generated to explore its function in vivo. Neonatal rat ventricular myocytes were isolated and cultured to evaluate the role of IRE1α in cardiomyocyte growth in vitro. Mass spectrometry was conducted to identify novel interacting proteins of IRE1α. Ribosome sequencing and polysome profiling were performed to determine the molecular basis for the function of IRE1α in translational control. RESULTS: We show that IRE1α is required for cell growth in neonatal rat ventricular myocytes under prohypertrophy treatment and in HEK293 cells in response to serum stimulation. At the molecular level, IRE1α directly interacts with eIF4G and eIF3, 2 critical components of the translation initiation complex. We demonstrate that IRE1α facilitates the formation of the translation initiation complex around the endoplasmic reticulum and preferentially initiates the translation of transcripts with 5' terminal oligopyrimidine motifs. We then reveal that IRE1α plays an important role in determining the selectivity and translation of these transcripts. We next show that IRE1α stimulates the translation of epidermal growth factor receptor through an unannotated terminal oligopyrimidine motif in its 5' untranslated region. We further demonstrate a physiological role of IRE1α-governed protein translation by showing that IRE1α is essential for cardiomyocyte growth and cardiac functional maintenance under hemodynamic stress in vivo. CONCLUSIONS: These studies suggest a noncanonical, essential role of IRE1α in orchestrating protein synthesis, which may have important implications in cardiac hypertrophy in response to pressure overload and general cell growth under other physiological and pathological conditions.

Label-free white blood cells classification using a deep feature fusion neural network.

White blood cell (WBC) classification is a valuable diagnostic approach for identifying diseases. However, conventional methods for WBC detection, such as flow cytometers, have limitations in terms of their high cost, large system size, and laborious staining procedures. As a result, deep learning-based label-free WBC image analysis methods are gaining popularity. Nevertheless, most existing deep learning WBC classification techniques fail to effectively utilize the subtle differences in the internal structures of WBCs observed under a microscope. To address this issue, we propose a neural network with feature fusion in this study, which enables the detection of label-free WBCs. Unlike conventional convolutional neural networks (CNNs), our approach combines low-level features extracted by shallow layers with high-level features extracted by deep layers, generating fused features for accurate bright-field WBC identification. Our method achieves an accuracy of 80.3 % on the testing set, demonstrating a potential solution for deep-learning-based biomedical diagnoses. Considering the proposed method simplifies the cell detection process and eliminates the need for complex operations like fluorescent staining, we anticipate that this automatic and label-free WBC classification network could facilitate more precise and effective analysis, and it could contribute to the future adoption of miniatured flow cytometers for point-of-care (POC) diagnostics applications.

Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway.

BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. METHODS: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway. CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.

Apolipoprotein O modulates cholesterol metabolism via NRF2/CYB5R3 independent of LDL receptor.

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.

Widespread Adoption of Microincision Vitrectomy Surgery Improves Visual Outcomes in Endogenous Endophthalmitis with Poor Initial Vision: A 21-Year Experience in Taiwan.

PURPOSE: To review the presentation and visual prognostic factors of patients with endogenous endophthalmitis before and after the introduction of microincision vitrectomy surgery (MIVS), at a tertiary referral hospital in Taiwan, over a 21-year period. METHODS: We retrospectively analyzed medical records of patients diagnosed with endogenous endophthalmitis before and after the introduction of MIVS between January 2002 and December 2022. RESULTS: Data were collected from 147 patients. Diabetes mellitus was the most common comorbidity (59.9%). Liver abscess (32.7%) was the leading source of infection, followed by urinary tract infection (15.0%), and infective endocarditis (5.4%). Klebsiella pneumoniae (50.4%) was the most common pathogen, followed by Staphylococcus aureus (13.5%), and Candida albicans (8.3%). Poor initial visual acuity worse than counting fingers (CF) (p < 0.001) and diabetes mellitus (p = 0.008) were significantly associated with poor visual outcomes. In the treatment of 98 patients with poor initial visual acuity worse than CF, the proportion of vitrectomy surgeries performed increased from 13/56 (23.2%) to 24/42 (57.1%) (p = 0.001) after the introduction of MIVS. Final visual acuity of CF or better increased from 7/56 (12.5%) to 12/42 (28.6%) after the introduction of MIVS (p = 0.046). Vitrectomy was a better prognostic factor for final visual outcome in patients with poor initial visual acuity of worse than CF (p = 0.011) than other factors. CONCLUSION: In endogenous endophthalmitis patients presenting with poor initial visual acuity, vitrectomy was a better visual prognostic factor. MIVS has allowed more patients to undergo vitrectomy and improved visual outcomes.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

Explaining the improving effect of dough crumb-sheet composite rolling on fresh noodle quality: From microstructure and moisture distribution perspective.

A new technique known as dough crumb-sheet composite rolling (DC-SCR) was used to improve the quality of fresh noodles. However, there is a dearth of theoretical investigations into the optimal selection of specific parameters for this technology, and the underlying mechanisms are not fully understood. Therefore, the effects of dough crumb addition times in DC-SCR on the texture, cooking, and eating quality of fresh noodles were first studied. Then, the underlying regulation mechanism of DC-SCR technology on fresh noodles was analyzed in terms of moisture distribution and microstructure. The study demonstrated that the most significant enhancement in the quality of fresh noodles was achieved by adding dough crumbs six times. Compared with fresh noodles made without the addition of dough crumbs, the initial hardness and chewiness of fresh noodles made by adding six times of dough crumbs increased by 25.32% and 46.82%, respectively. In contrast, the cooking time and cooking loss were reduced by 28.45% and 29.69%, respectively. This quality improvement in fresh noodles made by DC-SCR came from the microstructural differences of the gluten network between the inner and outer layers of the dough sheet. A dense structure on the outside and a loose structure on the inside could endow the fresh noodles made by DC-SCR with higher hardness, a shortened cooking time, and less cooking loss. This study would provide a theoretical and experimental basis for creating high-quality fresh noodles.

Efficacy and safety of adjunctive perampanel treatment in pediatric patients with epilepsy aged 4-12 years: a real-world study.

OBJECTIVE: To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12 years with epilepsy. METHODS: We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12 years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. RESULTS: (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12 months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12 months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. CONCLUSION: In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

Bilateral Production Shield Enabling Highly Efficient Perovskite Photovoltaics.

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

MyoVision-US: an Artificial Intelligence-Powered Software for Automated Analysis of Skeletal Muscle Ultrasonography.

Introduction/Aims: Muscle ultrasound has high utility in clinical practice and research; however, the main challenges are the training and time required for manual analysis to achieve objective quantification of morphometry. This study aimed to develop and validate a software tool powered by artificial intelligence (AI) by measuring its consistency and predictability of expert manual analysis quantifying lower limb muscle ultrasound images across healthy, acute, and chronic illness subjects. Methods: Quadriceps complex (QC [rectus femoris and vastus intermedius]) and tibialis anterior (TA) muscle ultrasound images of healthy, intensive care unit, and/or lung cancer subjects were captured with portable devices. Automated analyses of muscle morphometry were performed using a custom-built deep-learning model (MyoVision-US), while manual analyses were performed by experts. Consistency between manual and automated analyses was determined using intraclass correlation coefficients (ICC), while predictability of MyoVision -US was calculated using adjusted linear regression (adj.R 2 ). Results: Manual analysis took approximately 24 hours to analyze all 180 images, while MyoVision - US took 247 seconds, saving roughly 99.8%. Consistency between the manual and automated analyses by ICC was good to excellent for all QC (ICC:0.85-0.99) and TA (ICC:0.93-0.99) measurements, even for critically ill (ICC:0.91-0.98) and lung cancer (ICC:0.85-0.99) images. The predictability of MyoVision-US was moderate to strong for QC (adj.R 2 :0.56-0.94) and TA parameters (adj.R 2 :0.81-0.97). Discussion: The application of AI automating lower limb muscle ultrasound analyses showed excellent consistency and strong predictability compared with human analysis. Future work needs to explore AI-powered models for the evaluation of other skeletal muscle groups.

Optimization of Composite Enzymatic Extraction, Structural Characterization and Biological Activity of Soluble Dietary Fiber from Akebia trifoliata Peel.

In order to reduce the waste of Akebia trifoliata peel and maximize its utilization, in this study, on the basis of a single-factor experiment and the response surface method, the optimum technological conditions for the extraction of soluble dietary fiber from Akebia trifoliata peel with the compound enzyme method were obtained. The chemical composition, physical and chemical properties, structural characterization and biological activity of the purified soluble dietary fiber (AP-SDF) from the Akebia trifoliata peel were analyzed. We discovered that that the optimum yield was 20.87% under the conditions of cellulase addition 600 U/g, enzymolysis time 100 min, solid-liquid ratio 1:24 g/mL and enzymolysis temperature 51 °C. At the same time, AP-SDF was a porous network structure cellulose type I acidic polysaccharose mainly composed of arabinoxylan (36.03%), galacturonic acid (27.40%) and glucose (19.00%), which possessed the structural characteristic peaks of the infrared spectra of polysaccharides and the average molecular weight (Mw) was 95.52 kDa with good uniformity. In addition, the AP-SDF exhibited high oil-holding capacity (15.11 g/g), good water-holding capacity and swelling capacity, a certain antioxidant capacity in vitro, hypoglycemic activity in vitro for α-glucosidase inhibition and hypolipidemic activity in vitro for the binding ability of bile acids and cholesterol. These results will provide a theoretical basis for the development of functional products with antioxidant, hypoglycemic and hypolipidemic effects, which have certain application value in related industries.

Contemporary Views of the Extraction, Health Benefits, and Industrial Integration of Rice Bran Oil: A Prominent Ingredient for Holistic Human Health.

Globally, 50% of people consume rice (Oryza sativa), which is among the most abundant and extensively ingested cereal grains. Rice bran is a by-product of the cereal industry and is also considered a beneficial waste product of the rice processing industry. Rice bran oil (RBO) is created from rice bran (20-25 wt% in rice bran), which is the outermost layer of the rice kernel; has a lipid content of up to 25%; and is a considerable source of a plethora of bioactive components. The main components of RBO include high levels of fiber and phytochemicals, including vitamins, oryzanols, fatty acids, and phenolic compounds, which are beneficial to human health and well-being. This article summarizes the stabilization and extraction processes of rice bran oil from rice bran using different techniques (including solvent extraction, microwaving, ohmic heating, supercritical fluid extraction, and ultrasonication). Some studies have elaborated the various biological activities linked with RBO, such as antioxidant, anti-platelet, analgesic, anti-inflammatory, anti-thrombotic, anti-mutagenic, aphrodisiac, anti-depressant, anti-emetic, fibrinolytic, and cytotoxic activities. Due to the broad spectrum of biological activities and economic benefits of RBO, the current review article focuses on the extraction process of RBO, its bioactive components, and the potential health benefits of RBO. Furthermore, the limitations of existing studies are highlighted, and suggestions are provided for future applications of RBO as a functional food ingredient.

Classical swine fever virus non-structural protein 4A recruits dihydroorotate dehydrogenase to facilitate viral replication.

Mitochondria are energy producers in cells, which can affect viral replication by regulating the host innate immune signaling pathways, and the changes in their biological functions are inextricably linked the viral life cycle. In this study, we screened a library of 382 mitochondria-targeted compounds and identified the antiviral inhibitors of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo synthesis pathway of pyrimidine ribonucleotides, against classical swine fever virus (CSFV). Our data showed that the inhibitors interfered with viral RNA synthesis in a dose-dependent manner, with half-maximal effective concentrations (EC50) ranging from 0.975 to 26.635 nM. Remarkably, DHODH inhibitors obstructed CSFV replication by enhancing the innate immune response including the TBK1-IRF3-STAT1 and NF-κB signaling pathways. Furthermore, the data from a series of compound addition and supplementation trials indicated that DHODH inhibitors also inhibited CSFV replication by blocking the de novo pyrimidine synthesis. Remarkably, DHODH knockdown demonstrated that it was essential for CSFV replication. Mechanistically, confocal microscopy and immunoprecipitation assays showed that the non-structural protein 4A (NS4A) recruited and interacted with DHODH in the perinuclear. Notably, NS4A enhanced the DHODH activity and promoted the generation of UMP for efficient viral replication. Structurally, the amino acids 65-229 of DHODH and the amino acids 25-40 of NS4A were pivotal for this interaction. Taken together, our findings highlight the critical role of DHODH in the CSFV life cycle and offer a potential antiviral target for the development of novel therapeutics against CSF. IMPORTANCE: Classical swine fever remains one of the most economically important viral diseases of domestic pigs and wild boar worldwide. dihydroorotate dehydrogenase (DHODH) inhibitors have been shown to suppress the replication of several viruses in vitro and in vivo, but the effects on Pestivirus remain unknown. In this study, three specific DHODH inhibitors, including DHODH-IN-16, BAY-2402234, and Brequinar were found to strongly suppress classical swine fever virus (CSFV) replication. These inhibitors target the host DHODH, depleting the pyrimidine nucleotide pool to exert their antiviral effects. Intriguingly, we observed that the non-structural protein 4A of CSFV induced DHODH to accumulate around the nucleus in conjunction with mitochondria. Moreover, NS4A exhibited a strong interaction with DHODH, enhancing its activity to promote efficient CSFV replication. In conclusion, our findings enhance the understanding of the pyrimidine synthesis in CSFV infection and expand the novel functions of CSFV NS4A in viral replication, providing a reference for further exploration of antiviral targets against CSFV.

ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis.

Herein, we elucidate the potential role of ANO6 (TMEM16F) in gastrointestinal stromal tumors (GISTs). ANO6 expression in GIST and adjacent normal tissues was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation, apoptosis, and pyroptosis were examined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining, and flow cytometry. In addition, the total iron and Fe2+ levels were assessed. IL-18 and IL-1ß levels were also evaluated. Lipid reactive oxygen species (ROS), cystine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were evaluated using appropriate kits. Ferroptotic markers, including Ptgs2, Chac1, SLC7A11, and SLC3A2, were analyzed by RT-qPCR, western blotting, and immunohistochemistry. ANO6 expression decreased in GIST tissues. ANO6-plasmid inhibits proliferation, induces apoptosis, and promotes pyroptosis in GIST-T1 and GIST-T1 IR cells. The ANO6-plasmid induced ferroptosis, as confirmed by enhanced lipid ROS levels, increased intracellular concentrations of total iron and Fe2+, promoted Ptgs2 and Chac1 expression, reduced Cys, GSH, and GPX4 levels, and downregulated SLC7A11 and SLC3A2 expression after in vitro and in vivo treatment with ANO6-plasmid. Moreover, the ANO6-plasmid inhibited GIST growth in vivo. Therefore, ANO6 may be a promising therapeutic target for blocking the development of GIST via the induction of apoptosis, pyroptosis, and ferroptosis.

Identification and epidemiology of a novel Hepacivirus in domestic ducks in Hunan province, China.

The genus Hepacivirus comprises a diverse range of genetically distinct viruses that infect both mammalian and non-mammalian hosts, with some posing significant risks to human and animal health. Members of the genus Hepacivirus are typically classified into fourteen species (Hepacivirus A-N), with ongoing discoveries of novel hepaciviruses like Hepacivirus P and Hepacivirus Q. In this study, a novel Hepacivirus was identified in duck liver samples collected from live poultry markets in Hunan province, China, using unbiased high-throughput sequencing and meta-transcriptomic analysis. Through sequence comparison and phylogenetic analysis, it was determined that this newly discovered Hepacivirus belongs to a new subspecies of Hepacivirus Q. Moreover, molecular screening revealed the widespread circulation of this novel virus among duck populations in various regions of Hunan province, with an overall prevalence of 13.3%. These findings significantly enhence our understanding of the genetic diversity and evolution of hepaciviruses, emphasizing the presence of genetically diverse hepaciviruses duck populations in China. Given the broad geographical distribution and relatively high positive rate, further investigations are essential to explore any potential associations between Hepacivirus Q and duck-related diseases.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Frailty and risk of systemic atherosclerosis: A bidirectional Mendelian randomization study.

BACKGROUND: Numerous observational studies have reported an association between frailty and atherosclerosis. However, the causal relationship between frailty and the occurrence of atherosclerosis in different anatomical sites remains unclear. we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causal relationship between the frailty index (FI), and both systemic atherosclerosis and lipids. METHODS: We obtained summary statistics from large-scale genome-wide association studies (GWAS) of various phenotypes, including frailty (n = 175,226), coronary atherosclerosis (n = 56,685), cerebral atherosclerosis (n = 150,765), peripheral arterial disease (PAD) (n = 361,194), atherosclerosis at other sites (n = 17,832), LDL-C (n = 201,678), HDL-C (n = 77,409), and triglycerides (n = 78,700). The primary MR analysis employed the inverse variance weighted (IVW) method. Furthermore, to assess reverse causality, we employed inverse MR and multivariate MR analysis. RESULTS: Genetically predicted FI showed positive associations with the risk of coronary atherosclerosis (OR = 1.47, 95% CI 1.12-1.93) and cerebral atherosclerosis (OR = 1.99, 95% CI 1.05-3.78), with no significant association (p >0.05) applied to peripheral arterial disease and atherosclerosis at other sites. Genetically predicted FI was positively associated with the risk of triglycerides (OR = 1.31, 95% CI 1.08-1.59), negatively associated with the risk of LDL-C (OR = 0.87, 95% CI 0.78-0.97), and showed no significant association with the risk of HDL-C (p >0.05). Furthermore, both reverse MR and multivariate MR analyses demonstrated a correlation between systemic atherosclerosis, lipids, and increased FI. CONCLUSION: Our study elucidated that genetically predicted FI is associated with the risk of coronary atherosclerosis and cerebral atherosclerosis by the MR analysis method, and they have a bidirectional causal relationship. Moreover, genetically predicted FI was causally associated with triglyceride and LDL-C levels. Further understanding of this association is crucial for optimizing medical practice and care models specifically tailored to frail populations.