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Shear bands frequently appear in lattice architectures subjected to compression, leading to an unstable stress–strain curve and global deformation. This deformation mechanism reduces their energy absorption and loading-bearing capacity and causes the architectures to prioritize mechanical protection of external components at the expense of the entire structure. Here, we leverage the design freedom offered by additive manufacturing and the geometrical relation of dual-phase nanolamellar crystals to fabricate heterogeneous lamellar lattice architectures consisting of body-centered cubic (BCC) and face-centered cubic (FCC) unit cells in alternating lamella. The lamellar lattice demonstrates more than 10 and 9 times higher specific energy absorption and energy absorption efficiency, respectively, compared to the BCC lattice. The drastic improvement arises as the nucleation of shear bands is inhibited by the discrete energy threshold for plastic buckling of adjacent heterogeneous lattice lamella during loading. Despite its lower density than the FCC lattice, the lamellar lattice exhibits significant enhancement in plateau stress and crushing force efficiency, attributed to the strengthening effect induced by simultaneous deformation of unit cells in the BCC lattice lamella and the resulting cushion shielding effect. The design improves the global mechanical properties, making lamellar lattices compare favorably against numerous materials proposed for mechanical protection. Additionally, it provides opportunities to program the local mechanical response, achieving programmable internal protection alongside overall external protection. This work provides a different route to design lattice architecture by combining internal and external dual mechanical protection, enabling a generation of multiple mechanical protectors in aerospace, automotive, and transportation fields. [ABSTRACT FROM AUTHOR]

This study aimed to explore the key factors affecting pig farmers' willingness to participate in a pig manure outsourcing treatment project (PMOTP) from the perspectives of transaction costs and peer effects. Survey data from 512 pig farmers and the probit and Heckman probit models were used to estimate the impact of transaction costs and peer effects on farmers' participation in the PMOTP. The results demonstrate that more than 62% of farmers are willing to participate in the PMOTP, and the average willingness to pay reaches 7.2 yuan/ton. Farmers' willingness to participate in the PMOTP decreases with asset specificity, transaction frequency and uncertainty but increases with peer effects. Moreover, peer effects attenuate the inhibitory effect of transaction costs on farmers' participation in the PMOTP. Heterogeneity analysis showed that large-scale farmers without the self-breeding and self-rearing model are more affected by transaction costs and peer effects than other farmers. Moreover, asset specificity and peer effects are likely to increase farmers' willingness to pay for the project, which suggests that larger farms are more willing to invest in the PMOTP. These findings provide a useful reference for establishing a model for sustainable environmental service projects in the farming industry. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is a prevalent psychiatric disorder affecting about one-third of stroke survivors, significantly hindering recovery and quality of life. PSD also imposes a substantial burden on caregivers and healthcare systems. Aromatherapy has shown promise in alleviating depression, anxiety, and sleep disorders. This pilot randomized controlled trial aims to assess the feasibility and preliminary efficacy of mixed herb aromatherapy in treating PSD. Feasibility outcomes encompass recruitment, intervention adherence, assessment completion and safety assessment. Secondary outcomes include evaluations of depression, anxiety, cognitive function, sleep quality, quality of life, and brain function using EEG and fNIRS. Methods: This single-blind pilot randomized controlled trial will be conducted at the Second Rehabilitation Hospital of Shanghai, enrolling ninety-nine poststroke patients with PSD. Participants will be randomized into three groups: a Non-Active Control Group receiving standardized rehabilitation therapy, a CBT Group receiving conventional rehabilitation with bi-weekly CBT sessions, and an Aromatherapy Group receiving conventional rehabilitation with daily aromatic inhalation sessions. Interventions will last for four weeks, with efficacy assessed at baseline, post-intervention, and one month post-intervention. Rating scales will be used to measure changes in depression, sleep quality, cognitive function, and quality of life. EEG and fNIRS will specifically be used to measure changes in cerebral cortex activity and their correlations with depression. Feasibility will be evaluated through recruitment, intervention adherence, assessment completion and safety assessment. Discussion: This pilot study highlights the potential of mixed herb aromatherapy inhalation for treating PSD, addressing limitations of CBT by promoting selfmanagement. While demonstrating feasibility through recruitment, adherence, assessment completion and safety assessment, the study also acknowledges limitations such as unequal intervention times, the lack of physical function data. And the use of culturally relevant plant powders may enhance compliance but limits generalizability. Despite these constraints, the study provides valuable preliminary data and insights into the mechanisms of aromatherapy, encouraging further research and development of effective PSD treatments. [ABSTRACT FROM AUTHOR]

Additive manufacturing of fiber-reinforced polymer composites has garnered great interest due to its potential in fabricating functional products with lightweight characteristics and unique material properties. However, the major concern in polymer composites remains the presence of pore defects, as a thorough understanding of pore formation is insufficient. In this study, a powder-scale multiphysics framework has been developed to simulate the printing process of fiber-reinforced polymer composites in powder bed fusion additive manufacturing. This numerical framework involves various multiphysics phenomena such as particle flow dynamics of fiber-reinforced polymer composite powder, infrared laser--particle interaction, heat transfer, and multiphase fluid flow dynamics. The melt depths of one-layer glass fiber--reinforced polyamide 12 composite parts fabricated by selective laser sintering are measured to validate modelling predictions. The numerical framework is employed to conduct an in-depth investigation of pore formation mechanisms within printed composites. Our simulation results suggest that an increasing fiber weight fraction would lead to a lower densification rate, larger porosity, and lower pore sphericity in the composites. [ABSTRACT FROM AUTHOR]

Objectives: The altered neuromelanin in substantia nigra pars compacta (SNpc) is a valuable biomarker in the detection of early-stage Parkinson's disease (EPD). Diagnosis via visual inspection or single radiomics based method is challenging. Thus, we proposed a novel hybrid model that integrates radiomics and deep learning methodologies to automatically detect EPD based on neuromelanin-sensitive MRI, namely short-echo-time Magnitude (setMag) reconstructed from quantitative susceptibility mapping (QSM). Methods: In our study, we collected QSM images including 73 EPD patients and 65 healthy controls, which were stratified into training-validation and independent test sets with an 8:2 ratio. Twenty-four participants from another center were included as the external validation set. Our framework began with the detection of the brainstem utilizing YOLO-v5. Subsequently, a modified LeNet was applied to obtain deep learning features. Meanwhile, 1781 radiomics features were extracted, and 10 features were retained after filtering. Finally, the classified models based on radiomics features, deep learning features, and the hybrid of both were established through machine learning algorithms, respectively. The performance was mainly evaluated using accuracy, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The saliency map was used to visualize the model. Results: The hybrid feature-based support vector machine (SVM) model showed the best performance, achieving ACC of 96.3 and 95.8% in the independent test set and external validation set, respectively. The model established by hybrid features outperformed the one radiomics feature-based (NRI: 0.245, IDI: 0.112). Furthermore, the saliency map showed that the bilateral "swallow tail" sign region was significant for classification. Conclusion: The integration of deep learning and radiomic features presents a potent strategy for the computer-aided diagnosis of EPD. This study not only validates the accuracy of our proposed model but also underscores its interpretability, evidenced by differential significance across various anatomical sites. [ABSTRACT FROM AUTHOR]

BACKGROUND Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce. METHODS This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed. RESULTS After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype (P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure (n = 6, 16.7%), followed by mixed (n = 26, 30.6%) and vasodepressive (n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve (P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type (P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC = 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02). CONCLUSIONS Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC = 8.4 ms might benefit from CNA. [ABSTRACT FROM AUTHOR]

Increasing demands for livestock products have stimulated rapid increases in the number of livestock and the scale of farming, thus increasing pressure on resources and the environment. Coordinating the development of livestock production (LP) with residential consumption (RC), resources and the environmental carrying capacity (RECC) is important to ensure sustainable development. In this study, the entropy weight method and the improvedcoupling coordination degree (CCD) model were used to identify the spatial-- temporal coordination development characteristics of livestock productionresidential consumption-resource and environmental carrying capacity (LRRE). Furthermore, the spatial autocorrelation model (SAM) and gray model (GM) were used to analyze the spatial aggregation characteristics and future development trends of the CCDs of the LRRE in China. The findings show that the CCDs of the LRRE values in 31 Chinese provinces increased from 2005 to 2020, but no provinces reached a high coordination level. Specifically, the coordinated development level of LRRE is relatively high in the central, eastern and northeastern regions and relatively low in the western region. The spatial autocorrelation analysis confirmed that the high-high (H-H) aggregation areas were mainly distributed in the northeastern, eastern, and central regions, while low-high (L-H) agglomeration was distributed in the western region. This phenomenon is mainly attributed to the continuous expansion of the scale of livestock production in western China. Regions with relatively developed economies have more funds to invest in environmental protection projects. Using GM method, we find that the CCDs of LRRE in 31 provinces in China will increase from 2021 to 2030, and all provinces will reach the basic coordination level. However, most of the western regions will barely reach the basic coordination level. This result indicates that the low level of LRRE development in western China may be difficult to change in the short term. The level of coordinated LRRE development in the relatively developed eastern region is increasing. The spatial layout of China's livestock industry should be appropriately adjusted, its expansion rate in the western region should be decreased, and the ecological environment of the areas bordering the western and central regions should be improved. These findings have practical implications for other large livestock production countries. Promoting the coordinated development of LRRE is also an important condition for agricultural transformation in developing countries, especially for improving the environment in key areas of the livestock industry. [ABSTRACT FROM AUTHOR]

Chinese plum (Prunus salicina Lindl.) originates from China and makes a large contribution to the global production of plums. The P. salicina 'Wushancuili' has a green coloration and high fruit quality and is economically important in eliminating poverty and protecting ecology in the Yangtze River Three Gorges Reservoir. However, rain-induced cracking (rain-cracking, literally skin cracking caused by rain) is a limitation to 'Wushancuili' fruit production and causes severe losses. This study reported a high-quality 'Wushancuili' genome assembly consisting of a 302.17-Mb sequence with eight pseudo-chromosomes and a contig N50 of 23.59 Mb through the combination of Illumina sequencing, Pacific Biosciences HiFi III sequencing, and high-throughput chromosome conformation capture technology. A total of 25 109 protein-coding genes are predicted and 54.17% of the genome is composed of repetitive sequences. 'Wushancuili' underwent a remarkable orthoselection during evolution. Gene identification revealed that loss-of-function in four core MYB10 genes results in the anthocyanin deficiency and absence of red color, revealing the green coloration due to the residual high chlorophyll in fruit skin. Besides, the occurrence of cracking is assumed to be closely associated with cell wall modification and frequently rain-induced pathogen enrichment through transcriptomic analysis. The loss of MYB10 genes might render fruit more susceptible to pathogen-mediated cracking by weakening the epidermal strength and reactive oxygen species (ROS) scavenging. Our findings provided fundamental knowledge regarding fruit coloration and rain-cracking and will facilitate genetic improvement and cultivation management in Chinese plums. [ABSTRACT FROM AUTHOR]

The pursuit of high-performance is worth considerable effort in catalysis for energy efficiency and environmental sustainability. To develop redox catalysts with superior performance for soot combustion, a series of MnxCoy oxides were synthesized using MgO template substitution. This method greatly improves the preparation and catalytic efficiency and is more in line with the current theme of green catalysts and sustainable development. The resulting Mn1Co2.3 has a strong activation capability of gaseous oxygen due to a high concentration of Co3+ and Mn3+. The Mn doping enhanced the intrinsic activity by prompting oxygen vacancy formation and gaseous oxygen adsorption. The nanosheet morphology with abundant mesoporous significantly increased the solid-solid contact efficiency and improved the adsorption capability of gaseous reactants. The novel design of Mn1Co2.3 oxide enhanced its catalytic performance through a synergistic effect of Mn doping and the porous nanosheet morphology, showing significant potential for the preparation of high-performance soot combustion catalysts. [ABSTRACT FROM AUTHOR]

Objective: The causal relationship between Rheumatoid arthritis (RA) and hypothyroidism/hyperthyroidism remains controversial due to the limitations of conventional observational research, such as confounding variables and reverse causality. We aimed to examine the potential causal relationship between RA and hypothyroidism/hyperthyroidism using Mendelian randomization (MR). Method: We conducted a bidirectional two-sample univariable analysis to investigate the potential causal relationship between hypothyroidism/hyperthyroidism and RA. Furthermore, we performed a multivariate analysis to account for the impact of body mass index (BMI), smoking quantity, and alcohol intake frequency. Results: The univariable analysis indicated that RA has a causative influence on hypothyroidism (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.01-1.14, P=0.02) and hyperthyroidism (OR=1.32, 95% CI=1.15-1.52, P<0.001). When hypothyroidism/hyperthyroidism was considered as an exposure variable, we only observed a causal relationship between hypothyroidism (OR=1.21, 95% CI=1.05-1.40, P=0.01) and RA, whereas no such connection was found between hyperthyroidism (OR=0.91, 95% CI=0.83-1.01, P=0.07) and RA. In the multivariate MR analyses, after separately and jointly adjusting for the effects of daily smoking quantity, alcohol intake frequency, and BMI, the causal impact of RA on hypothyroidism/hyperthyroidism and hypothyroidism on RA remained robust. However, there is no evidence to suggest a causal effect of hyperthyroidism on the risk of RA (P >0.05). Conclusion: Univariate and multivariate MR analyses have validated the causal association between RA and hypothyroidism/hyperthyroidism. Hypothyroidism confirmed a causal relationship with RA when employed as an exposure variable, whereas no such relationship was found between hyperthyroidism and RA. [ABSTRACT FROM AUTHOR]

Synechococcus are widely distributed in the global ocean, from the pelagic zone to coastal waters. However, little is known about Synechococcus in coastal seawater due to limitations in isolation and culture conditions. In this study, a combination of metagenomic sequencing technology, flow cytometry sorting, and multiple displacement amplification was used to investigate Synechococcus in the coastal seawater of Xiamen Island. The results revealed 18 clades of Synechococcus and diverse metabolic genes that appear to contribute to their adaptation to the coastal environment. Intriguingly, some metabolic genes related to the metabolism of carbohydrates, energy, nucleotides, and amino acids were found in 89 prophage regions that were detected in 16,258 Synechococcus sequences. The detected metabolic genes can enable prophages to contribute to the adaptation of Synechococcus hosts to the coastal marine environment. The detection of prophages also suggests that the cyanophages have infected Synechococcus. On the other hand, the identification of 773 genes associated with antiviral defense systems indicates that Synechococcus in Xiamen have evolved genetic traits in response to cyanophage infection. Studying the community diversity and functional genes of Synechococcus provides insights into their role in environmental adaptation and marine ecosystems. [ABSTRACT FROM AUTHOR]

Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT. [ABSTRACT FROM AUTHOR]

Background: Noonan syndrome (NS) is characterized by typical facial features, short stature, congenital heart defects and other comorbidities. Lymphedema and chylous pleural effusions are also common in NS, but protein-losing enteropathy (PLE) is rarely reported. Case presentation: We present the case of a 19-year-old Chinese woman presenting with PLE. Small intestine biopsy showed obvious expansion of lymphatic vessels. The gene mutation results of the patient indicated a c.184T>G missense mutation (p. Tyr62Asp) in the PTPN11 gene (NM_002834.3). Conclusion: NS accompanied by PLE is not common, but hypoproteinemia attributable to PLE may be more common in patients with NS than previously thought. It remains uncertain whether mutation of the PTPN11 gene is related to PLE, indicating that further research is needed. [ABSTRACT FROM AUTHOR]

The article focuses on addressing challenges in training sequential recommendation models with implicit feedback data and the limitations of one-hot data representations. It introduces a novel optimization framework called Multi-View Smoothness (MVS) to enhance both data representations and model learning, addressing context and label smoothness, and model regularization.

Step-and-project is a popular method to simulate non-penetrating deformable bodies in physically based animation. The strategy is to first integrate the system in time without considering contacts and then resolve potential intersections, striking a good balance between plausibility and efficiency. However, existing methods can be defective and unsafe when using large time steps, taking risks of failure or demanding repetitive collision testing and resolving that severely degrade performance. In this article, we propose a novel two-way method for fast and reliable continuous collision handling. Our method launches an optimization from both ends of the intermediate time-integrated state and the previous intersection-free state. It progressively generates a piecewise linear path and eventually obtains a feasible solution for the next time step. The algorithm efficiently alternates between a forward step and a backward step until the result is conditionally converged. Thanks to a set of unified volume-based contact constraints, our method offers flexible and reliable handling of various codimensional deformable bodies, including volumetric bodies, cloth, hair, and sand. Experimental results demonstrate the safety, robustness, physical fidelity, and numerical efficiency of our method, making it particularly suitable for scenarios involving large deformations or large time steps. [ABSTRACT FROM AUTHOR]

HPV (Human papillomavirus) affects 600,000 people worldwide each year. Almost all cervical cancers are associated with a past HPV infection. In particular, the positivity to the high-risk type HPV16 is detected in most of the invasive cervical cancers. FDA has approved prophylactic vaccines that protect against new HPV16 infections, but do not induce immunity in those patients with established infections or neoplasms. To date, no therapeutic vaccine targeting HPV16-associated lesions has been authorized. We have developed an mRNAbased vaccine against the HPV16 late oncoproteins E6 and E7, which are abundantly and exclusively expressed in high-grade squamous intraepithelial lesions (HSILs), a stage of the cervical disease that precedes the progression to carcinoma. Our in vitro and in vivo studies demonstrated that the translated mRNA is functional and elicits an antigen-specific adaptive immune response. Upon immunization with the vaccine, mice with HPV16+ lesions exhibited tumor growth inhibition, extension of lifespan, and development of a protective immune memory. In light of these results and the remarkable clinical success of mRNA vaccines against SARS-CoV2, we believe that our mRNA-based therapeutic vaccine has the potential to offer a non-invasive treatment alternative to the current standard of care for HPV16+ HSILs. [ABSTRACT FROM AUTHOR]

Objective: To explore the high-efficiency and low-risk prevention and treatment strategies for stem cells from human exfoliated deciduous teeth (SHED) for high-altitude cerebral oedema. Methods: A low-pressure and low-oxygen tank mimicking high-altitude conditions was used to establish the high-altitude cerebral oedema animal model. The preventive effects of SHED for cerebral oedema were then evaluated by haematoxylin and eosin (H&E) and histological staining. In vitro, SHED was co-cultured with BV-2 to analyse the effects of SHED by western blot and immunofluorescence staining. Results: SHED can prevent and treat cerebral oedema in a high altitude rat animal model. Mechanistically, SHED treatment can protect brain cells from apoptosis induced by high altitude condition. Moreover, SHED treatment can inhibit M1-type polarisation and promote M2-type polarisation of microglia cells via the suppression of hypoxia inducible factor (HIF)-1α-mediated extracellular signal-regulated kinase (ERK) signalling activated in high altitude condition. Conclusion: SHED treatment can relieve high-altitude cerebral oedema via inhibiting HIF- 1α-mediated ERK signalling, which indicates that SHED is a promising alternative strategy to prevent and treat high-altitude cerebral oedema. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the optimal regimen for unresectable recurrent hepatocellular carcinoma (HCC), so this retrospective study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and PD-1 inhibitors (T-L-P) versus TACE combined with lenvatinib (T-L) or TACE alone. Method: Data were collected from 204 patients with unresectable recurrent HCC who received T-L-P, T-L, or TACE alone at three medical centers from January, 2019 to December, 2020 for analysis. The survival outcomes, tumor response, and adverse events were compared between three groups, and risk factors were further investigated. Results: The median overall survival in the T-L-P, T-L, and TACE alone groups were not reached, 25.6, and 15.7 months, respectively (p < 0.001). The median progression-free survival in the T-L-P, T-L, and TACE alone groups were 24.1, 17.3, and 13.7 months, respectively (p < 0.001). The best objective response rate in the T-L-P, T-L, and TACE alone groups were 70.4%, 48.9%, and 42.5%, respectively. The best disease control rate in the T-L-P, T-L, and TACE alone groups were 100.0%, 97.8%, and 87.5%, respectively. There was no significant difference between the T-L-P and T-L groups for Grade 3/4 adverse events. Conclusion: T-L-P regimen was safe and superior to T-L or TACE alone in improving survival for unresectable recurrent HCC patients. [ABSTRACT FROM AUTHOR]

The number of patients with hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection remains large, despite the remarkable effectiveness of antiviral drugs and vaccines for HBV in preventing and treating HBV infection. Necroptosis is closely related to the occurrence of inflammation, clearance of viral infection, and tumor progression. Presently, little is known about the changes in necroptosis-related genes in the progression from chronic HBV infection (CHI) to HBV-related hepatic fibrosis (HBV-HF) and HBV-related hepatocellular carcinoma (HBV-HCC). In this study, Cox regression analysis was performed using GSE14520 chip data and a necroptosis-related genes survival prognosis score (NRGPS) was established for HBV-HCC patients. NRGPS was constructed using three model genes (G6PD, PINK1 and LGALS3), and verified by data sequencing in the TCGA database. The HBV-HCC cell model was established by transfection of pAAV/HBV1.2C2, constructed by homologous recombination, into HUH7 and HEPG2 cells. The expression levels of G6PD, PINK1, and LGALS3 were detected using RT-qPCR. We further analyzed the expression of the model genes in GSE83148, GSE84044, and GSE14520 and found that LGALS3 was consistently highly expressed in CHI, high fibrosis score and high NRGPS. In addition, immune microenvironment analysis showed that LGALS3 was not only associated with the infiltration of regulatory T cells in the immune microenvironment but also with expression of CCL20 and CCR6. The expression levels of model genes, FOXP3 and CCR6, were analyzed using RTqPCR in peripheral blood mononuclear cells of 31 hepatitis B surface antibody positive patients, 30 CHI, 21 HBV-HF, and 20 HBV-HCC. In further cell-model experiments, we analyzed the expression of CCL20 by RT-qPCR and the changes in cell proliferation and migration by CCK8 and transwell assays, respectively, in HBV-HCC cell models after LGALS3 knockdown. The findings of this study suggest that LGALS3 could be a biomarker for adverse progression following chronic HBV infection and may also be involved in the regulation of the immune microenvironment, making it a potential therapeutic target. [ABSTRACT FROM AUTHOR]

The complex tectonic evolution in the Tibetan region has impacted climate, the Asian monsoon system, and the development of major biodiversity hotspots, especially since the onset of the India-Eurasia continental collision during the early Paleogene. Untangling the links between the geologic, climatic, and ecological history of the broader region can provide insights into these Earth system mechanisms, relevant for the future of our rapidly changing planet. To better understand environmental conditions across this critical time and place, we reconstruct the climatic and environmental history from a key sedimentary repository within the Lühe Basin, Yunnan, China, uniquely located between high elevation Tibet and low elevation coastal China. We investigate a 340-m long section using a multi-proxy organic geochemistry approach, complemented with sedimentological interpretations and climate model simulations. The complementary organic geochemical proxies, including n-alkanes, terpenoids, and hopanes, suggest that these thermally immature sediments were deposited in a dynamic environment that fluctuated between low energy floodplains and high energy fluvial systems. Our branched glycerol diakyl glycerol tetraether-based proxies indicate terrestrial temperatures of around 17°C ± 3 SD and our model-based temperatures indicate terrestrial temperatures for Chattian of around 19°C, consistent with the literature palaeobotany-based temperatures from the nearby Lühe town section. These combined palaeotemperatures match presentday values, suggesting that this area has not undergone significant temperature change since the early Oligocene. [ABSTRACT FROM AUTHOR]

Introduction: Itch is a common symptom of many skin and systemic diseases. Identifying novel endogenous itch mediators and the downstream signaling pathways involved will contribute to the development of new strategies for the treatment of chronic itch. In the present study, we adopted behavioral testing, patch clamp recording and metabonomics analysis to investigate the role of agmatine in itch and the underlying mechanism. Methods: Behavioral analysis was used to evaluate the establishing of acute and chronic itch mice model, and to test the effects of different drugs or agents on mice itch behavior. Western blotting analysis was used to test the effect of agmatine on phosphorylation of ERK (p-ERK) expression in the spinal cord. Patch clamp recording was used to determine the effect agmatine on the excitability of DRG neurons and the role of ASIC3. Finally, the metabonomics analysis was performed to detect the concentration of agmatine in the affected skin under atopic dermatitis or psoriasis conditions. Results: We fused a mouse model and found that an intradermal injection of agmatine (an endogenous polyamine) into the nape of the neck or cheek induced histamine-independent scratching behavior in a dose-dependent manner. In addition, the ablation of nociceptive C-fibers by resiniferatoxin (RTX) abolished agmatine-induced scratching behavior. However, agmatine-induced itch was not affected by the pharmacological inhibition of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1); similar results were obtained from TRPV1-/- or TRPA1-/- mice. Furthermore, agmatine-induced itch was significantly suppressed by the administration of acid-sensing ion channel 3 (ASIC3) inhibitors, APETx2 or amiloride. Agmatine also induced the upregulation of p-ERK in the spinal cord; this effect was inhibited by amiloride. Current clamp recording showed that the acute perfusion of agmatine reduced the rheobase and increased the number of evoked action potentials in acute dissociated dorsal root ganglion (DRG) neurons while amiloride reversed agmatine-induced neuronal hyperexcitability. Finally, we identified significantly higher levels of agmatine in the affected skin of a mouse model of atopic dermatitis (AD) when compared to controls, and the scratching behavior of AD mice was significantly attenuated by blocking ASIC3. Discussion: Collectively, these results provide evidence that agmatine is a novel mediator of itch and induces itch via the activation of ASIC3. Targeting neuronal ASIC3 signaling may represent a novel strategy for the treatment of itch. [ABSTRACT FROM AUTHOR]

Glass fibre (GF) and glass bead (GB)--reinforced polyamide1212 (PA1212) was additively manufactured by selective laser sintering. The effects of laser power and GF content on the tensile and tribological properties of the printed specimens with a base GB weight fraction of 40 wt.% were investigated. The strengthening mechanism of GFs/GBs was illustrated by analyzing the interfacial adhesion between the fillers and the PA1212 matrix. The specimens with 40 wt.% GBs and 10 wt.% GFs fabricated at a laser power of 30 W exhibited a strength of 52 MPa, a friction coefficient of 0.23, and a wear rate of 0.0011 mm³/N·m. The selected optimal laser power and GF addition contributed to the strong interfacial adhesion, which realised flat surface morphology and an adequate encapsulation of fillers in the specimen. The reinforcement of GBs/GFs in PA1212 can serve as a reference for a deeper understanding of the strengthening mechanisms for other additively manufactured engineering plastics. [ABSTRACT FROM AUTHOR]

The packing characteristics of fiber/polymer powder in powder bed fusion additive manufacturing exhibit a high correlation with the mechanical behaviours of printed composite parts such as homogeneity and anisotropy. A discrete element model has been developed to investigate the packing characteristics of glass fiber/polyamide 12 (PA12) powder, which include fiber orientations, fiber homogeneity, and packing density. The predicted probability distributions of fiber orientations in the powder bed are comparable with those measured in glass fiber--reinforced PA12 composites printed via multi jet fusion. Three types of fibers with different length distributions are adopted to study the effects of the fiber length distribution on their packing characteristics. The simulation results reveal that a large average fiber length is beneficial to fiber alignment in the powder spreading direction but lowers the fiber homogeneity and packing density of the powder bed. Furthermore, varying the fiber length can provide an effective way to regulate fiber orientations in the powder packing process, which would help achieve satisfactory anisotropic mechanical properties for composite parts. [ABSTRACT FROM AUTHOR]

Multi jet fusion (MJF), a powder-based additive manufacturing technology, is suitable for fabricating fibre-reinforced polymer composites. However, the types of reinforcement fibres applied in MJF are limited due to the incompatibility between the fibres and polymer. Herein, a simple and cost-effective surface modification method for Fe3O4-coated aramid fibres (Fe3O4@AF hybrids) is proposed to fabricate polyamide 12 (PA12) composites by MJF. The optimal fibre content for Fe3O4@AF/PA12 composites is 6 wt%, which resulted in 10.83% and 16.05% higher ultimate tensile strength and Young's modulus, respectively, compared with AF/PA12. The addition of Fe3O4@AF hybrids also improved the flame retardancy of AF/PA12 by reducing the peak heat release rate (PHRR) and postponing the temperature at PHRR. This practical surface modification method can be potentially applied to other reinforcement fibres for fabricating functional polymer composites by other powder-based manufacturing technologies. [ABSTRACT FROM AUTHOR]

Polymeric materials for powder bed fusion additive manufacturing have been attracting extensive research interest due to their vast potential for fabricating end-use functional parts. Here, a high-fidelity multiphysics approach combining the discrete element model with the computational fluid dynamics model has been developed to simulate the printing process of polymers in powder bed fusion, involving powder recoating, melting, and coalescence. The developed approach considers particle flow dynamics, the reflection, absorption, and transmission of infrared laser radiation, and the viscous flow of polymer melt. The pore formation mechanisms due to lack of fusion and gas entrapment in polyamide 12 parts printed via selective laser sintering are studied. The simulation results reveal that lower polymer viscosity would be beneficial to the densification rate of the printed parts. Excessively small powder particles would degrade powder bed quality due to the agglomeration of polymer powder, thus leading to high porosity in the printed parts. [ABSTRACT FROM AUTHOR]

Metal oxide nanorods exhibit promising potential as reinforcement fillers in various polymer matrices, but their application in the Multi Jet Fusion (MJF) technique is rarely reported. In this work, surface-modified zinc oxide nanorods (SMZnO) were synthesized and incorporated into polyamide 12 (PA12) powder to enhance the mechanical properties of the MJF-printed parts. Compared to ZnO, SMZnO exhibited better dispersion, resulting in markedly enhanced mechanical performances. The ultimate tensile strength and the Young's modulus of the MJFprinted SMZnO/PA12 nanocomposites were 62.02 MPa and 2.28 GPa in the X orientation and 64.07 MPa and 2.34 GPa in the Y orientation, equivalent to 27.85%, 59.44%, 29.12%, and 54.97% increments, respectively. The flexural strength and modulus demonstrated similar improvements in the X and Y orientations, confirming the uniform mechanical enhancement effect of homogenously distributed SMZnO. This work provides a novel and facile approach for the additive manufacturing of polymeric nanocomposites with superior mechanical performance. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) offers the advantages of direct near-net-shape production, reduced material waste, and shortened production lead time, showing great potential to revolutionise the manufacturing industry. The flexible movements of the deposition head and the build platform allow directed energy deposition (DED) to conduct the repair process of damaged high-value metallic parts. However, the resulting heterogeneous microstructure and its effect on the mechanical properties of the repaired parts have not been widely realised. In this work, the repair of Monel alloy parts, known for their excellent mechanical properties and high corrosion resistance, was conducted by the laser-DED process with low and high laser power settings, respectively. Different from the fine, equiaxed grains in the original part, the as-deposited Monel alloy consists of large columnar grains. The mechanical performance across the interface between the original and newly deposited material was tested and analysed along horizontal and vertical loading directions. The yield strength and elongation of repaired Monel alloy parts were 409.1 MPa and 35.2% along the horizontal loading direction, which both significantly surpass the corresponding values along the vertical loading direction. This study lays the groundwork for designing a laser-DED process to achieve high performance for repaired metallic parts. [ABSTRACT FROM AUTHOR]

Multi Jet Fusion (MJF) has attracted extensive attention because of its ability to print support-free complex structures. However, the mechanical properties of MJF-printed polymer parts are still unsatisfactory for certain industrial requirements. Herein, by leveraging the fibre reinforcement effect and high specific strength of polyimide (PI) fibres, this work developed PI/polyamide 12 (PA12) composites with largely enhanced mechanical performance via MJF. Specifically, the tensile strength and modulus were increased by 43% and 42%, and the flexural strength and modulus were improved by 39% and 46%, respectively, compared to those of the neat PA12 parts. Furthermore, the incorporation of lightweight PI fibres endowed the composites with high specific tensile strength (67.60 kN·m/kg) and specific flexural strength (93.70 kN·m/kg), which are superior to those of MJF-printed PA12 composites reinforced with other fibres. This work provides new insights into enhancing the mechanical performance of lightweight parts printed by MJF and other powder-based techniques. [ABSTRACT FROM AUTHOR]

Craniopharyngioma (CP) is a rare benign tumor that develops from the residual epithelial cells of the craniopharynx, accounting for <5% of intracranial tumors. It is common for CPs to grow in the sellar/parasellar region and extend suprasellar. The pathology classifies CPs into adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). The PCP is mainly solid and occurs only in adults. ACP is predominantly cystic and more common in childhood and adolescent. Multilocular cystic ACP involving the anterior, middle, and posterior cranial fossa is rare in adults. Here, we report a case of a 46-year-old adult male patient who presented with recurrent headaches for 1 year with choking and hoarseness. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple cystic masses in the anterior, middle, and posterior cranial fossa. Initial hypotheses included the following: CP, colloid cyst, enterogenous cyst, epidermoid cyst, and dermoid cyst. Subsequently, the patient underwent surgery and postoperative histopathology diagnosed ACP. Adults with ACP involving the anterior, middle, and posterior cranial fossae are uncommon. This is a rare condition that radiologists should be aware of. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a progressive and irreversible brain degenerative disorder early. Among all diagnostic strategies, hippocampal atrophy is considered a promising diagnostic method. In order to proactively detect patients with early Alzheimer's disease, we built an Alzheimer's segmentation and classification (AL-SCF) pipeline based on machine learning. Methods: In our study, we collected coronal T1 weighted images that include 187 patients with AD and 230 normal controls (NCs). Our pipeline began with the segmentation of the hippocampus by using a modified U2-net. Subsequently, we extracted 851 radiomics features and selected 37 features most relevant to AD by the Hierarchical clustering method and Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. At last, four classifiers were implemented to distinguish AD from NCs, and the performance of the models was evaluated by accuracy, specificity, sensitivity, and area under the curve. Results: Our proposed pipeline showed excellent discriminative performance of classification with AD vs NC in the training set (AUC=0.97, 95% CI: (0.96-0.98)). The model was also verified in the validation set with Dice=0.93 for segmentation and accuracy=0.95 for classification. Discussion: The AL-SCF pipeline can automate the process from segmentation to classification, which may assist doctors with AD diagnosis and develop individualized medical plans for AD in clinical practice. [ABSTRACT FROM AUTHOR]

Since the COVID-19 outbreaks, masks have become one of the most controversial topics throughout the world. However, the pro-mask atmosphere seems to be formed smoothly in China, at least in the beginning and peak of epidemic. To understand the social construction of masks in China, this study examines the media framing of masks from 2001 to 2020 in two important newspapers, the People's Daily and the Southern Metropolis Daily. We found that pro-mask discourse portrayed wearing masks first as an emergent and undesired health strategy; later, as an inevitable measure against constant crises; and lastly, part of the new normality. The legalization of wearing masks lies in the severity of a certain health crisis, the effectiveness that masks can protect citizens from such crisis, a comparatively low cost that to exchange for normal lives under a crisis, and the fact that it could overall benefit China's national image and interests. Moreover, masks have been constructed as a financially promising business and a trendy fashion, which further justifies their existence. The counterdiscourses against masks appeared when the conditions that justified masks were questioned. [ABSTRACT FROM AUTHOR]

To characterize complex and heterogeneous side information in recommender systems, the heterogeneous information network (HIN) has shown superior performance and attracted much research attention. In HIN, the rich entities, relations, and paths can be utilized to model the correlations of users and items; such a task setting is often called HIN-based recommendation. Although HIN provides a general approach to modeling rich side information, it lacks special consideration on the goal of the recommendation task. The aggregated context from the heterogeneous graph is likely to incorporate irrelevant information, and the learned representations are not specifically optimized according to the recommendation task. Therefore, there is a need to rethink how to leverage the useful information from HIN to accomplish the recommendation task. To address the above issues, we propose a Curriculum pre-training based HEterogeneous Subgraph Transformer (called CHEST) with new data characterization, representation model, and learning algorithm. Specifically, we consider extracting useful information from HIN to compose the interaction-specific heterogeneous subgraph, containing highly relevant context information for recommendation. Then, we capture the rich semantics (e.g., graph structure and path semantics) within the subgraph via a heterogeneous subgraph Transformer, where we encode the subgraph into multi-slot sequence representations. Besides, we design a curriculum pre-training strategy to provide an elementary-to-advanced learning process. The elementary course focuses on capturing local context information within the subgraph, and the advanced course aims to learn global context information. In this way, we gradually capture useful semantic information from HIN for modeling user-item interactions. Extensive experiments conducted on four real-world datasets demonstrate the superiority of our proposed method over a number of competitive baselines, especially when only limited training data is available. [ABSTRACT FROM AUTHOR]

Objective: To explore whether hydrogen sulphide (H2S) could protect human periodontal ligament stem cells (PDLSCs)from senescence and the possible underlying mechanisms. Methods: Cell cycle assay and Ki-67 assay were used to measure proliferation of PDLSCs. Real-time polymerase chain reaction (PCR) was used to measure cellular senescence-related pl6 and p21. Calcium influx was detected by measurement ofCa2+ imaging. In addition, we analysed the possible mechanisms underlying H2S acting on PDLSCs by microarray. Results: The cell proliferation rate of aging PDLSCs decreased significantly. The expression of cellular senescence-related pi 6 and p21 significantly increased in aging PDLSCs. H2S donor (GYY4137) treatment increased the proliferation rate of senescence PDLSCs. Furthermore, the donor of H2S treatment effectively prevented cell cycle arrest of PDLSCs during the aging process and inhibited the expression of cellular senescence-related markers. Mechanically, H2S donor treatment could activate the calcium influx in PDLSCs. Moreover, pretreatment with TRPV4 inhibitors significantly attenuated the calcium influx induced by H2S donor treatment in PDLSCs. It also alleviated the protective effect of H2S on the senescence of PDLSCs. Conclusion: H2S alleviated the senescence of human PDLSCs by TRPV4 channel mediated calcium flux. These results provide a potential strategy to deal with cell aging and may facilitate cell therapy for oral diseases. [ABSTRACT FROM AUTHOR]

Background: Anti-programmed cell death ligand 1/vascular endothelial growth factor inhibition, coupled with chemotherapy, may potentiate antitumor immunity leading to enhanced clinical benefit, but it has not been investigated in advanced biliary tract cancer (BTC). Objectives: We investigated the efficacy and safety of atezolizumab, bevacizumab, and gemcitabine plus oxaliplatin (GEMOX) in advanced BTC and explore the potential biomarkers related to the response. Design: Multicenter, single-arm, retrospective study. Methods: Advanced BTC patients, who received a triple combination therapy at three medical centers between 18 March 2020 and 1 September 2021, were included. Treatment response was evaluated via mRECIST and RECIST v1.1. Endpoints included the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The whole exome sequencing of pathological tissues was conducted for bioinformatic analysis. Results: In all, 30 patients were enrolled. The best ORR was 76.7% and the DCR was 90.0%. The median PFS was 12.0 months, and the median OS was not reached. During the treatment, 10.0% (3/30) of patients suffered from ?grade 3 treatment-related adverse events (TRAEs). Furthermore, fever (73.3%), neutropenia (63.3%), increased aspartate transaminase and alanine aminotransferase levels (50.0% and 43.3%, respectively) are the most common TRAEs. Bioinformatics analysis revealed patients with altered ALS2CL had a higher ORR. Conclusion: The triple combination of atezolizumab, bevacizumab, and GEMOX may be efficacious and safe for patients with advanced BTC. ALS2CL may be a potential predictive biomarker for the efficacy of triple combination therapy. [ABSTRACT FROM AUTHOR]

Context: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. Objective: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. Methods: The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plantderived iridoids for depression. Results: Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. Discussion and conclusions: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications. [ABSTRACT FROM AUTHOR]

Contest: Isopsoralen, one of the main active and quality-control compounds in Psoralea corylifolia L. (Fabaceae), has antitumor and oestrogen-like effects. Previous studies demonstrated that isopsoralen induced hepatotoxicity and its long-term exposure led to cholestatic liver injury. Objective: This study investigates the effect of three- or seven-day exposure of low dose isopsoralen (80mg/kg) on bile acid homeostasis in C57BL/6J mice. Materials and methods: Forty-two C57BL/6J mice were randomly divided into control, three- and sevenday groups (n=14 per group, half female and half male). Isopsoralen suspension was administrated intragastrically at 80mg/kg once a day. Blood and liver samples were collected to measure biochemical indices and transport of BAs. The histopathology of the liver was also observed. HPLC-MS/MS was also used to measure the BAs profiles and transport activity. Results: In the study, isopsoralen increased the levels of serum AST, ALT in three- and seven-day groups, and caused vacuolar degeneration and swelling in the liver. Canalicular efflux transporters BSEP, OSTa, MRP2, MRP3, and basolateral uptake transporters NTCP, OATP4 were inhibited after seven-day-administration. Moreover, amino acid binding enzymes (BAAT and BACS) were also inhibited after seven-day-administration. The composition of BAs changed greatly and the concentration of some unconjugated-BAs which have stronger hydrophobicity, such as CA, CDCA, was significantly increased. Conclusions: Isopsoralen (80mg/kg) caused hepatotoxicity after short-term exposure by inhibiting the expression of efflux transporters, amino acid binding enzymes, and disrupting BAs spectrum. [ABSTRACT FROM AUTHOR]

Background: Proximal gastrectomy has gradually gained more attention due to its superiority in retaining the function of part of the stomach. The inevitable loss of the antireflux barrier and postoperative complications resulting from proximal gastrectomy can severely affect the quality of life. Continuous improvements in digestive tract reconstruction after proximal gastrectomy have yielded the development of a variety of methods with antireflux functions. Recently, our center attempted the left-open single-flap technique and initiated a multicenter, prospective, randomized controlled trial for patients undergoing proximal gastrectomy to reduce the difficulty of surgical anastomosis and the incidence of perioperative complications compared with the double-flap technique. These findings will provide more evidencebased medical research for the development of clinical guidelines. Methods/design: This study is a prospective, multicenter, randomized controlled clinical trial. We plan to recruit 250 patients who are eligible for proximal gastrectomy. After informed consent is obtained, patients will be randomly assigned to the trial group (left-open single-flap technique) and the control group (double-flap technique) in a 1:1 allocation ratio. Discussion: Increasingly, clinical studies have focused on the improvement of reconstruction modalities after proximal gastrectomy. Among these methods, the double-flap technique is a clinically effective method. The purpose of this study is to establish a prospective randomized controlled trial to compare the efficacy of the left-open single-flap technique versus the double-flap technique after proximal gastrectomy, aiming to provide more evidencebased medical studies for digestive tract reconstruction in proximal gastrectomy. [ABSTRACT FROM AUTHOR]

Transcription and replication of the influenza A virus (IAV) genome take place in the nucleus of infected cells, which rely on host factors to aid viral ribonucleoprotein (vRNP) to cross the nuclear pore complex (NPC) and complete the bidirectional nucleocytoplasmic trafficking. Here, we showed that nucleoporin 85 (NUP85), a component of NPC, interacted with RNP subunits polymerase basic 1 (PB1) and polymerase basic 2 (PB2) in an RNAdependent manner during IAV infection. Knockdown of NUP85 delayed the nuclear import of vRNP, PB1 and PB2, inhibiting polymerase activity and ultimately suppressing viral replication. Further analysis revealed that NUP85 assisted the binding of PB1 to nuclear transport factor Ran-binding protein 5 (RanBP5) and the binding of PB2 to nuclear transport factor importin α1 and importin α7. We also found that NUP85 expression was downregulated upon IAV infection. Together, our study demonstrated that NUP85 positively regulated IAV infection by interacting with viral PB1 and PB2, which may provide new insight into the process of vRNP nuclear import and a novel target for effective antivirals. [ABSTRACT FROM AUTHOR]