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The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.

Visual Object Tracking plays an essential role in solving many basic problems in computer vision. In order to improve the tracking accuracy, the previous methods have prevented tracking failures from occurring by improving the ability to describe the target. However, few of them consider ways to relocate and track the target after a tracking failure. In this paper, we propose the use of a parallel dual network for visual object tracking. This is constructed from two networks and an adjustment module to enable judgement of tracking failures, as well as target relocation and tracking. Firstly, we employ the Siamese matching method and correlation filter method to build tracking network and inspecting network. Both networks track the target simultaneously to obtain two tracking results. Secondly, an adjustment module is constructed, which compares the overlap ratio of the two tracking results with a set threshold, then fuses them or selects the best one. Finally, the fusion or selection result is output and the tracker is updated. We perform comprehensive experiments on five benchmarks: VOT2016, UAV123, Temple Color-128, OTB-100 and OTB-50. The results demonstrate that, compared with other state-of-the-art algorithms, the proposed tracking method improves tracking precision while maintaining real-time performance.

Hydrolysis of lignocellulosic biomass produces the mixed sugars of glucose (60–70 %), xylose (20–30 %), and arabinose (2–20 %), etc. Using mixed sugars instead of pure glucose for microbial biosynthesis will reduce the cost of carbon source and maximize utilization of biomass. However, carbon catabolite repression and poor adaptation of metabolic pathways are obstacles in the synergistic utilization of mixed sugars, thus resulting in low carbon utilization efficiency. Here, we engineered the mixed sugar metabolic channels in Pseudomonas putida to achieve their synergistic utilization for producing vanillic acid, a valuable aromatic compound with broad applications in the food, pharmaceuticals, cosmetics, and chemical industries. Expressing O-methyltransferase (OMT) and deleting vanillate-O-demethylase (vanAB) realized vanillic acid accumulation in P. putida from glucose. Introducing the xylose isomerase pathway enabled the strain to produce vanillic acid from xylose. Deleting glucose dehydrogenase (gcd) and transcriptional regulator (hexR), together expressing two critical pentose phosphate pathway enzymes (transketolase and transaldolase) effectively balanced glucose-xylose metabolic channels for vanillic acid production. Further assembling the arabinose oxidation pathway established the efficient metabolism of three sugars. The final engineered strain (VA12) produced 2.75 g/L vanillic acid in fed-batch fermentation with 20 g/L glucose, 10 g/L xylose and 10 g/L arabinose. This study effectively reduces carbon catabolite repression in the synergistic utilization of mixed sugars, and represents the first case utilizing glucose-xylose-arabinose for vanillic acid production, illustrating the capability of transforming lignocellulose hydrolyzate into valuable chemical products.

Background: Essential tremor (ET) is a common movement disorder among elderly individuals worldwide and is occasionally associated with a high risk for mild cognitive impairment and dementia. This retrospective study aimed to determine the clinical outcome of unilateral magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in Chinese patients with ET. Methods: In total, 31 male and 17 female patients with drug-refractory ET were enrolled in this research study from January 2017 to September 2019. The severity of tremor and disability were assessed using the Clinical Rating Scale for Tremor (CRST) within a 2-year follow-up period. Results: The mean age of the participants was 59.14 ± 13.5 years. The mean skull density ratio (SDR) was 0.5 ± 0.1. The mean highest temperature was 57.0 ± 2.4°C. The mean number of sonications was 10.0 ± 2.6. The average maximum energy was 19,710.5 ± 8,624.9 J. The total CRST scores and sub-scores after MRgFUS thalamotomy significantly reduced during each follow-up ( p < 0.001). All but four (8.3%) of the patients had reversible adverse events (AEs) after the procedure. Conclusions: MRgFUS had sustained clinical efficacy 2 years after treatment for intractable ET. Only few patients presented with thalamotomy-related AEs including numbness, weakness, and ataxia for an extended period. Most Chinese patients were treated safely and effectively despite their low SDR.

In centrifugal pump open cavitation tests, cavitation regulation valves are indispensable. During valve regulation, the irregular shape of the flow cross-section easily induces cavitation, significantly affecting the test results. This study investigates and designs a novel cavitation regulation valve. The valve core is composed of several identical valve flaps. By restricting the movement direction and distance of the valve flaps, the shape of the flow cross-section remains circular under different valve openings, ensuring optimal fluid flow conditions. This study examines the influence of the number of valve flaps on the flow state. The results indicate that, as the number of valve flaps increases, the flow cross-section approaches a circular shape, reducing the number of bubbles and improving the valve flow state. When the number of valve flaps increases to 20, the flow state shows no significant difference from a circular flow cross-section. Additionally, this study investigates the impact of the valve inlet and outlet shapes on the flow state. The findings reveal that the rounded corner structure experiences severe cavitation inside and at the rear end of the valve. The chamfered corner structure generates bubbles earlier than the initial valve structure but exhibits a stronger ability to resist pressure fluctuations. Both the chamfered inlet and chamfered outlet structures help suppress cavitation, with the chamfered outlet structure exhibiting lower-pressure fluctuations and stronger cavitation resistance. Therefore, the novel cavitation regulation valve with a circular flow cross-section can effectively enhance fluid flow conditions and suppress valve cavitation, demonstrating significant engineering application value.

Commercial live attenuated influenza vaccines (LAIVs) usually contain a high proportion of defective interfering particles (DIPs). Given that LAIVs are not sufficiently protective worldwide, the potential to enhance their efficacy by reducing the proportion of DIPs remains largely unknown. In this study, a prepared H3N2 cold-adapted LAIV with a low proportion of DIPs exhibits delayed yet improved replication in the upper respiratory tract of mice. The low DIPs LAIV induces an increase in goblet cells, microfold cells, and neutrophils, along with enhanced antigen presentation by dendritic cells. Compared to the commercially sourced high DIPs LAIV, the low DIPs LAIV elicits enhanced mucosal and humoral immune responses, facilitates cross-neutralization in mice, and provides complete protection against lethal challenges with H3N2, H1N1 or H1N1pdm09 strains. This study offers insights into optimizing commercial LAIVs and replicative RNA virus-based vaccines by controlling DIPs. Commercial live attenuated influenza vaccines (LAIVs), usually contain a high proportion of defective interfering particles (DIPs), are not sufficiently protective. With mice models, the authors here reveal that LAIV with low DIPs replicates better, enhances immune response and facilitates cross-neutralization protection against lethal challenge of influenza strains.

Background Maternal hemoglobin (Hb) is related to nutritional status, and it widely fluctuates during pregnancy. However, the relationship between Hb and blood pressure (BP) during pregnancy is unclear. This study aimed to estimate the associations between maternal Hb in various trimesters and its changes with BP during pregnancy. Methods We conducted this study by using data from the Electronic Medical Record System (EMRS) database of Zhoushan Maternal and Child Care Hospital in Zhejiang Province, China. The pregnancy duration was divided into seven periods: before 14th, 14 to 17th, 18 to 22nd, 23 to 27th, 28 to 31st, 32 to 35th, and 36 to delivery; generalized estimating equations (GEE) and multiple linear regressions were used for exploring their associations. Results 8168 pregnant women in the first trimester were included in this study. Hb level decreased significantly from the first to late-second trimester and then increased but did not return to the level of the first trimester. After adjustment for the potential confounders, compared with women with Hb 110 ~ 119 g/L, those with Hb < 110 g/L had low systolic BP (SBP) and diastolic BP (DBP) in the second and third trimesters and those with Hb ≥ 120 g/L had high SBP and DBP in various trimesters. Furthermore, the dose-response effect was observed between them; except that those with Hb < 100 g/L had high SBP in T1 ( β  = 2.85, P  = 0.012). Hb concentration changes during pregnancy were also positively associated with BP level. Furthermore, Hb had a higher effect on DBP than SBP. It is worth noting that the Hb concentration in > = 140 g/L groups had significantly higher SBP and DBP than the other groups. A significant nonlinear relationship was found between hemoglobin changes with both SBP and DBP in different gestational weeks ( P non-linear < 0.05). Conclusions This study found that maternal Hb was positively associated with BP during pregnancy and maternal Hb > 120 g/L during pregnancy and increased maternal Hb from the first to third trimesters should especially be given more attention.

Background The nuclear distribution E homologue 1 (NDE1) is a crucial dynein binding partner. The NDE1 protein has the potential to disrupt the normal functioning of centrosomes, leading to a compromised ability to generate spindles and ensure precise separation of chromosomes during cell division. The potential consequences of this phenomenon include genomic instability, malignant transformation and the proliferation of neoplastic growths. However, studies examining the connection between NDE1 and cancer is still very rare. Methods The expression level, prognostic impact, gene change, DNA methylation, protein interaction, mRNA m6A modification, ceRNA network, associated gene and function enrichment, and immune‐related effects of NDE1 in pan‐cancer were examined using a range of online analytic tools and the R software package. The CCK‐8 test, transwell assay, scratch assay and colony formation assay were used to confirm the effects of NDE1 on the proliferation, invasion and metastasis of bladder cancer cells. Results Numerous tumour types have elevated NDE1, which is linked to a bad prognosis. NDE1 is an excellent diagnostic tool for many different types of cancer. Numerous malignancies have been linked to genetic changes in NDE1. NDE1 was connected to TMB, MSI, several immunological checkpoint genes and immune cell infiltration. NDE1 is linked to a number of immunological subtypes. NDE1 could affect how well immunotherapy works to treat different types of cancer. NDE1 was mostly associated with cell cycle, chromosomal segregation, DNA replication and mitotic segregation, according to GO and KEGG analyses. NDE1 physically binds to PAFAH1B1 and DCTN1, respectively. The proliferation, invasion and metastasis of bladder cancer cells may be prevented by NDE1 knockdown. Furthermore, knockdown of NDE1 promoted the apoptosis of bladder cancer cells. Conclusion High expression of NDE1 is present in a variety of tumours, which is linked to a bad prognosis for cancer. Knockdown of NDE1 inhibited the proliferation, invasion and metastasis of bladder cancer cells, and promoted the apoptosis. For a number of malignancies, NDE1 may be a biomarker for immunotherapy and prognosis.

Polymer flooding is an effective method widely applied for enhancing oil recovery (EOR) by reducing the mobility ratio between the injected water and crude oil. However, traditional polymers encounter challenges in high salinity reservoirs due to their salt sensitivity. To overcome this challenge, we synthesized a zwitterion polymer (PAMNS) with salt-induced tackifying property through copolymerization of acrylamide and a zwitterion monomer, methylacrylamide propyl-N, N-dimethylbutylsulfonate (NS). NS monomer is obtained from the reaction between 1,4-butanesultone and dimethylamino propyl methylacrylamide. In this study, the rheological properties, salt responsiveness, and EOR efficiency of PAMNS were evaluated. Results demonstrate that PAMNS exhibits desirable salt-induced tackifying characteristics, with viscosity increasing up to 2.4 times as the NaCl concentration reaches a salinity of 30 × 104 mg L−1. Furthermore, high valence ions possess a much stronger effect on enhancing viscosity, manifested as Mg2+ > Ca2+ > Na+. Molecular dynamics simulations (MD) and fluid dynamics experiment results demonstrate that PAMNS molecules exhibit a more stretched state and enhanced intermolecular associations in high-salinity environments. It is because of the salt-induced tackifying, PAMNS demonstrates superior performance in polymer flooding experiments under salinity ranges from 5 × 104 mg L−1 to 20 × 104 mg L−1, leading to 10.38–19.83% higher EOR than traditional polymers. A novel polymer (PAMNS) with salt-induced tackifying property was synthesized by using the anti-polyelectrolyte behaviors of zwitterionic monomer (NS). Additionally, the performance and application prospects of PAMNS in high-salt reservoirs were systematically studied. [Display omitted] •Zwitterionic copolymers display anti-polyelectrolyte behaviors.•Zwitterionic polymers show great promise for applications in high-salinity/ultra-high-salinity reservoirs.•A novel zwitterionic polymer (PAMNS) with salt-induced tackifying properties was successfully synthesized.•The properties and future direction of zwitterionic polymer (PAMNS) for practical applications are discussed.

Renal fibrosis is a prevalent pathological alteration that occurs throughout the progression of primary and secondary renal disorders towards end‐stage renal disease. As a complex and irreversible pathophysiological phenomenon, it includes a sequence of intricate regulatory processes at the molecular and cellular levels. Exosomes are a distinct category of extracellular vesicles that play a crucial role in facilitating intercellular communication. Multiple pathways are regulated by exosomes produced by various cell types, including tubular epithelial cells and mesenchymal stem cells, in the context of renal fibrosis. Furthermore, research has shown that exosomes present in bodily fluids, including urine and blood, may be indicators of renal fibrosis. However, the regulatory mechanism of exosomes in renal fibrosis has not been fully elucidated. This article reviewed and analysed the various mechanisms by which exosomes regulate renal fibrosis, which may provide new ideas for further study of the pathophysiological process of renal fibrosis and targeted treatment of renal fibrosis with exosomes. Multiple pathways are regulated by exosomes produced by various cell types, including tubular epithelial cells and mesenchymal stem cells, in the context of renal fibrosis. The study of exosomes will explore their potential in translational medicine and provide new ideas and ways for creating effective clinical treatment strategies.