First Known Human Death After Infection With the Avian Influenza A/H3N8 Virus: Guangdong Province, China, March 2023.

Here, we report on a case of human infection with the H3N8 avian influenza virus. The patient had multiple myeloma and died of severe infection. Genome analysis showed multiple gene mutations and reassortments without mammalian-adaptive mutations. This suggests that avian influenza (A/H3N8) virus infection could be lethal for immunocompromised persons.

Membranes based on Covalent Organic Frameworks through Green and Scalable Interfacial Polymerization using Ionic Liquids for Antibiotic Desalination.

Covalent organic framework (COF) membranes featuring uniform topological structures and devisable functions, show huge potential in water purification and molecular separation. Nevertheless, the inability of uniform COF membranes to be produced on an industrial scale and their nonenvironmentally friendly fabrication method are the bottleneck preventing their industrial applications. Herein, we report a new green and industrially adaptable scraping-assisted interfacial polymerization (SAIP) technique to fabricate scalable and uniform TpPa COF membranes. The process used non-toxic and low-volatility ionic liquids (ILs) as organic phase instead of conventional organic solvents for interfacial synthesis of TpPa COF layer on a support membrane, which can simultaneously achieve the purposes of (i) improving the greenness of membrane-forming process and (ii) fabricating a robust membrane that can function beyond the conventional membranes. This approach yields a large-area, continuous COF membrane (19×25 cm2 ) with a thickness of 78 nm within a brief period of 2 minutes. The resulting membrane exhibited an unprecedented combination of high permeance (48.09 L m-2 h-1 bar-1 ) and antibiotic desalination efficiency (e.g., NaCl/adriamycin separation factor of 41.8), which is superior to the commercial benchmarking membranes.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination.

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

The porous hollow cobalt-based oxides encapsulated with bimetallic PdAu Nanoparticles of electrochemical biosensor for highly sensitive pesticides detection.

Efficient and portable electrochemical biosensors are received to evaluation of pesticides in the environment, which can make great significance for food safety. In this study, the Co-based oxides with a kind of hierarchical porous hollow and nanocages were constructed, in which the materials (Co3O4-NC) were encapsulated with PdAu nanoparticles (NPs). Due to the unique porous structure, the changeable valence state of cobalt and the synergistic effect of bimetallic PdAuNPs, PdAu@Co3O4-NC possessed excellent electron pathways, and showed more exposed active sites. Accordingly, the porous Co-based oxides have been applied to construct an acetylcholinesterase (AChE) electrochemical biosensor, which showed good performance for organophosphorus pesticides (OPs) detection. The optimum biosensing platform based on nanocomposites was applied to exhibit highly sensitive determination of omethoate and chlorpyrifos, with the relative low detection limit of 6.125 × 10-15M and 5.10 × 10-13M, respectively. And a wide detection range of 6.125 × 10-15∼ 6.125 × 10-6M and 5.10 × 10-13∼ 5.10 × 10-6M for these two pesticides were achieved. Therefore, the PdAu@Co3O4-NC may represent a powerful tool for ultrasensitive sensing of OPs, and have great potential application.

Theoretical study of protein adsorption on graphene/h-BN heterostructures.

The biological characteristics of planar heterojunction nanomaterials and their interactions with biomolecules are crucial for the potential application of these materials in the biomedical field. This study employed molecular dynamics (MD) simulations to investigate the interactions between proteins with distinct secondary structures (a single α-helix representing the minimal oligomeric domain protein, a single ß-sheet representing the WW structural domain of the Yap65 protein, and a mixed α/ß structure representing the BBA protein) and a planar two-dimensional heterojunction (a GRA/h-BN heterojunction consisting of a graphene nanoplate (GRA) and a hexagonal boron nitride nanoplate (h-BN)). The results indicate that all three kinds of protein can be quickly and stably adsorbed on the GRA/h-BN heterojunction due to the strong van der Waals interaction, regardless of their respective types, structures and initial orientations. Moreover, the proteins exhibit a pronounced binding preference for the hBN region of the GRA/h-BN heterojunction. Upon adsorption, the α-helix structure of the minimal oligomeric domain protein experiences partial or complete denaturation. Conversely, while the secondary structure of the single ß-sheet and mixed α/ß structure (BBA protein) undergoes slight changes (focus on the coil and turn regions), the main α-helix and ß-sheet structures remain intact. The initial orientation significantly impacts the degree of protein adsorption and its position on the GRA/h-BN heterojunction. However, regardless of the initial orientation, proteins can ultimately be adsorbed onto the GRA/h-BN heterojunction. Furthermore, the initial orientation has a minor influence on the structural changes of proteins. Significantly, the combination of different secondary structures helps mitigate the denaturation of a single α-helix structure to some extent. Overall, the adsorption of proteins on GRA/h-BN is primarily driven by van der Waals and hydrophobic interactions. Proteins with ß-sheet or mixed structures exhibit stronger biocompatibility on the GRA/h-BN heterojunction. Our research elucidated the biological characteristics of GRA/h-BN heterojunction nanomaterials and their interactions with proteins possessing diverse secondary structures. It offers a theoretical foundation for considering heterojunction nanomaterials as promising candidates for biomedical applications.

Accurate diagnosis of isolated iliac vein thrombosis in third trimester pregnancy with clues on great saphenous vein reflux: a case report and review of literature.

BACKGROUND: Pregnancy is known to be a risk factor for venous thromboembolism (VTE). We report the case of a pregnant patient with difficult to diagnose iliac vein thrombosis, establishing a definite diagnosis by clues of great saphenous vein reflux. CASE PRESENTATION: A 37-year-old G1P0 woman at 35 weeks of assisted twin gestation presented with a complaint of persistent left lower limb edema and tenderness. A vascular ultrasound was used to examine the bilateral lower limb. Doppler of left lower extremity revealed continuous great saphenous vein reflux. Right saphenofemoral veins demonstrated venous stasis and no reflux. Unilateral continuous great saphenous vein reflux suggested left iliac veins obstruction or extrinsic compression. Anterograde venography showed a completely occlusive filling defect of the left external iliac vein, which is the definitive diagnosis of acute deep venous thrombosis. The patient underwent a cesarean delivery following inferior vena cava filter (IVCF) placement, and no signs of deep venous thrombosis (DVT) or pulmonary embolism (PE) were reported after delivery. CONCLUSION: In pregnant women with suspected deep vein thrombosis, it is imperative to assess the presence of unilateral continuous great saphenous vein reflux.

Molecular understanding of charge effect on desalination performance in lamellar MoS2 membranes.

Due to its advantages of superior oxidation resistance, excellent chemical stability and non-toxicity, molybdenum disulfide (MoS2) has shown prospects in seawater desalination applications. In this manuscript, molecular dynamics (MD) simulation has been employed to explore the effect of charge distribution in MoS2 nanosheets on the desalination performance of the lamellar MoS2 membrane. It is found that the model considering the atomic charge better describes the transport behavior of salt solution in the membranes. The water flux passing through the lamellar MoS2 membrane would be influenced little by the atomic charges in the MoS2 nanosheet. The lamellar MoS2 membrane considering the atomic charge distribution shows a screening effect between Na+ and Cl- ions.

Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells.

The tumor suppressor p53 is usually inactivated by somatic mutations in malignant neoplasms, and its reactivation represents an attractive therapeutic strategy for cancers. Here, we reported that a new quinolone compound RYL-687 significantly inhibited non-small cell lung cancer (NSCLC) cells which express wild type (wt) p53, in contract to its much weaker cytotoxicity on cells with mutant p53. RYL-687 upregulated p53 in cells with wt but not mutant p53, and ectopic expression of wt p53 significantly enhanced the anti-NSCLC activity of this compound. RYL-687 induced production of reactive oxygen species (ROS) and upregulation of Nrf2, leading to an elevation of the NAD(P)H:quinoneoxidoreductase-1 (NQO1) that can protect p53 by inhibiting its degradation by 20S proteasome. RYL-687 bound NQO1, facilitating the physical interaction between NQO1 and p53. NQO1 was required for RYL-687-induced p53 accumulation, because silencing of NQO1 by specific siRNA or an NQO1 inhibitor uridine, drastically suppressed RYL-687-induced p53 upregulation. Moreover, a RYL-687-related prodrug significantly inhibited tumor growth in NOD-SCID mice inoculated with NSCLC cells and in a wt p53-NSCLC patient-derived xenograft mouse model. These data indicate that targeting NQO1 is a rational strategy to reactivate p53, and RYL-687 as a p53 stabilizer bears therapeutic potentials in NSCLCs with wt p53.

Transcriptional regulation and small compound targeting of ACE2 in lung epithelial cells.

Angiotensin-converting enzyme 2 (ACE2) is the receptor of COVID-19 pathogen SARS-CoV-2, but the transcription factors (TFs) that regulate the expression of the gene encoding ACE2 (ACE2) have not been systematically dissected. In this study we evaluated TFs that control ACE2 expression, and screened for small molecule compounds that could modulate ACE2 expression to block SARS-CoV-2 from entry into lung epithelial cells. By searching the online datasets we found that 24 TFs might be ACE2 regulators with signal transducer and activator of transcription 3 (Stat3) as the most significant one. In human normal lung tissues, the expression of ACE2 was positively correlated with phosphorylated Stat3 (p-Stat3). We demonstrated that Stat3 bound ACE2 promoter, and controlled its expression in 16HBE cells stimulated with interleukin 6 (IL-6). To screen for medicinal compounds that could modulate ACE2 expression, we conducted luciferase assay using HLF cells transfected with ACE2 promoter-luciferase constructs. Among the 64 compounds tested, 6-O-angeloylplenolin (6-OAP), a sesquiterpene lactone in Chinese medicinal herb Centipeda minima (CM), represented the most potent ACE2 repressor. 6-OAP (2.5 µM) inhibited the interaction between Stat3 protein and ACE2 promoter, thus suppressed ACE2 transcription. 6-OAP (1.25-5 µM) and its parental medicinal herb CM (0.125%-0.5%) dose-dependently downregulated ACE2 in 16HBE and Beas-2B cells; similar results were observed in the lung tissues of mice following administration of 6-OAP or CM for one month. In addition, 6-OAP/CM dose-dependently reduced IL-6 production and downregulated chemokines including CXCL13 and CX3CL1 in 16HBE cells. Moreover, we found that 6-OAP/CM inhibited the entry of SARS-CoV-2 S protein pseudovirus into target cells. These results suggest that 6-OAP/CM are ACE2 inhibitors that may potentially protect lung epithelial cells from SARS-CoV-2 infection.

Charge Transfer in Patterned Bilayer Film of Ag/ZnS Composite by Magnetron Control Sputtering.

Ordered heterojunction nanocap arrays composed of the bilayer film Ag/ZnS were prepared onto ordered two-dimensional polystyrene bead arrays by magnetron control sputtering, and the surface morphologies were tuned by changing the ZnS thickness. When the ZnS thickness varied from 10 to 30 nm with a Ag thickness of 5 nm, the roughness of the bilayer film Ag/ZnS increased obviously. The UV-VIS spectra showed the shifted LSPR peaks with ZnS thickness, which was attributed to the changes of the electron density as confirmed by Hall effect analysis. SERS observations confirmed the charge transfer process for the varied electromagnetic couplings when the ZnS thickness changed.

Pore Formation Mechanism of A-Beta Peptide on the Fluid Membrane: A Combined Coarse-Grained and All-Atomic Model.

In Alzheimer's disease, ion permeability through the ionic channel formed by Aß peptides on cellular membranes appears to underlie neuronal cell death. An understanding of the formation mechanism of the toxic ionic channel by Aß peptides is very important, but remains unclear. Our simulation results demonstrated the dynamics and mechanism of channel formation by Aß1-28 peptides on the DPPC and POPC membrane by the coarse-grained method. The ionic channel formation is driven by the gyration of the radius and solvent accessible molecular surface area of Aß1-28 peptides. The ionic channel formation mechanism was explored by the free energy profile based on the distribution of the gyration of the radius and solvent accessible molecular surface area of Aß1-28 peptides on the fluid membrane. The stability and water permeability of the ionic channel formed by Aß peptides was investigated by all-atomic model simulation. Our simulation showed that the ionic channel formed by Aß1-28 peptides is very stable and has a good water permeability. This could help us to understand the pore formation mechanism by Aß1-28 peptides on the fluidic membrane. It also provides us with a guideline by which to understand the toxicity of Aß1-28 peptides' pores to the cell.

Simultaneous binding mechanism of multiple substrates for multidrug resistance transporter P-glycoprotein.

P-glycoprotein (P-gp), a member of ATP-binding cassette (ABC) transporters, is a multidrug resistance pump. Its promiscuous nature is the main cause of multidrug resistance in cancer cells. P-gp can bind multiple drug molecules simultaneously; however, the binding mechanism is still not clear. Furthermore, the upper limit of the number of substrates that can be accommodated by the binding pocket is not fully understood. In this work, we explore the dynamic process of P-gp binding to multiple substrates by using molecular dynamics (MD) simulations. Our results show that P-gp possesses the ability for simultaneous binding, and that the number of substrates has an upper limit. The accommodating ability of P-gp relates to the size of the binding drugs, and conforms to induced fit theory. In the binding process, the residues 339PHE, 982MET and 986GLN are essential. The pocket of P-gp presents strong flexibility and adaptability features according to the mutation results in this work. Drug molecules tend to gather in the pocket during binding, and interactions between these molecules are beneficial to simultaneous binding. These findings provide new insights into the mechanism of the promiscuous nature of P-gp, and may give us a guideline for inhibiting the process of multidrug resistance.

NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. METHODS: We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. RESULTS: After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. CONCLUSIONS: NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

Molecular modeling evaluation of the binding effect of five protease inhibitors to COVID-19 main protease.

Coronavirus disease 2019 (COVID-19) has caused more than 840,000 deaths as of 31 August 2020 in the whole world. The COVID-19 main protease (Mpro) has been validated as an attractive target for drug design. In this work, the binding mechanisms of five protease inhibitors (e.g., danoprevir, darunavir, ASC09, lopinavir and ritonavir) to COVID-19 Mpro were investigated. Based on the docking score, five protease inhibitors structures were selected for further evaluation. It is found that most of the selected drug molecules bind stably to the COVID-19 Mpro from the molecular dynamics simulation. Moreover, the MM/PBSA free energy calculations suggest that lopinavir with positive charge might be most active against COVID-19 Mpro.

An ABA Functional Analogue B2 Enhanced Salt Tolerance by Inducing the Root Elongation and Reducing Peroxidation Damage in Maize Seedlings.

Salt stress negatively affects maize growth and yield. Application of plant growth regulator is an effective way to improve crop salt tolerance, therefore reducing yield loss by salt stress. Here, we used a novel plant growth regulator B2, which is a functional analogue of ABA. With the aim to determine whether B2 alleviates salt stress on maize, we studied its function under hydroponic conditions. When the second leaf was fully developed, it was pretreated with 100 µM ABA, 0.01 µM B2, 0.1 µM B2, and 1 µM B2, independently. After 5 days treatment, NaCl was added into the nutrient solution for salt stress. Our results showed that B2 could enhance salt tolerance in maize, especially when the concentration was 1.0 µMol·L-1. Exogenous application of B2 significantly enhanced root growth, and the root/shoot ratio increased by 7.6% after 6 days treatment under salt stress. Compared with control, the ABA level also decreased by 31% after 6 days, which might have resulted in the root development. What is more, B2 maintained higher photosynthetic capacity in maize leaves under salt stress conditions and increased the activity of antioxidant enzymes and decreased the generation rate of reactive oxygen species by 16.48%. On the other hand, B2 can enhance its water absorption ability by increasing the expression of aquaporin genes ZmPIP1-1 and ZmPIP1-5. In conclusion, the novel plant growth regulator B2 can effectively improve the salt tolerance in maize.

High-coverage SARS-CoV-2 genome sequences acquired by target capture sequencing.

In this study, we designed a set of SARS-CoV-2 enrichment probes to increase the capacity for sequence-based virus detection and obtain the comprehensive genome sequence at the same time. This universal SARS-CoV-2 enrichment probe set contains 502 120 nt single-stranded DNA biotin-labeled probes designed based on all available SARS-CoV-2 viral sequences and it can be used to enrich for SARS-CoV-2 sequences without prior knowledge of type or subtype. Following the CDC health and safety guidelines, marked enrichment was demonstrated in a virus strain sample from cell culture, three nasopharyngeal swab samples (cycle threshold [Ct ] values: 32.36, 36.72, and 38.44) from patients diagnosed with COVID-19 (positive control) and four throat swab samples from patients without COVID-19 (negative controls), respectively. Moreover, based on these high-quality sequences, we discuss the heterozygosity and viral expression during coronavirus replication and its phylogenetic relationship with other selected high-quality samples from the Genome Variation Map. Therefore, this universal SARS-CoV-2 enrichment probe system can capture and enrich SARS-CoV-2 viral sequences selectively and effectively in different samples, especially clinical swab samples with a relatively low concentration of viral particles.

Atomistic insights into the separation mechanism of multilayer graphene membranes for water desalination.

Graphene-based membranes have been extensively explored owing to their excellent separation properties. In this paper, multiple factors regarding desalination performance were investigated by molecular dynamics (MD) simulations. These factors include the interlayer spacing distance (H), the gap width (dG), offset (O), and the number of gaps and layers in a multilayer graphene membrane (MGM). It is found that salt rejection is influenced significantly by the interlayer spacing distance owing to the largest free energy between ions and graphene sheets as well as the relatively larger size of the hydration layer around the ions. The optimal desalting parameter (dG = 1 nm, H = 0.8 nm) was selected; MGM systems based on the optimized parameter exhibited excellent salt rejection for NaCl, MgCl2 and CaCl2 solutions. These results can provide some ideas for the future design of graphene-based membranes.

[Clinical features and follow-up results of boys and girls with systemic lupus erythematosus: a comparative analysis].

OBJECTIVE: To compare the clinical features and follow-up results of systemic lupus erythematosus (SLE) between boys and girls. METHODS: A retrospective analysis was performed for the clinical data of 79 children (18 boys and 61 girls), aged ≤14 years, who were diagnosed with SLE from 2008 to 2018. The boys and the girls were compared in terms of initial and major clinical symptoms, injury of organs/systems, related laboratory markers, and follow-up results. RESULTS: As for the initial and non-initial symptoms, fever had the highest incidence rate in the boys, while facial erythema had the highest incidence rate in the girls. The boys tended to develop renal injury and hematological damage (P<0.05), with a significantly higher incidence rate of proteinuria than the girls (P<0.05), while the girls tended to develop joint pain (P<0.05). There were high abnormal rates (>80%) of anti-nuclear antibody, dsDNA, complement C3, and erythrocyte sedimentation rate in both boys and girls (P>0.05). The boys had a significantly higher disease activity than the girls at the first visit and in year 9 of follow-up (P<0.05). A one-month to ten-year follow-up showed that among the boys, 3 were lost to follow-up, 1 died, 7 were well controlled but required oral administration of large doses of hormones or immunosuppression, 2 progressed to chronic renal failure, and 1 developed lupus encephalopathy. Among the girls, 3 were lost to follow-up; 5 died; 34 were well controlled, among whom 5 were maintained on oral prednisone acetate with a dose of <10 mg, 1 was withdrawn from the drug for 1 year, and 2 were withdrawn from the drug for 2 years; 4 developed lupus encephalopathy; 1 developed depression and anxiety and had suicidal tendency in the 7th year after disease onset; 2 experienced impaired vision, blurred vision, and chloropsia; 1 developed a vascular necrosis of both femoral heads in the 3rd year of hormone administration. CONCLUSIONS: There are differences in clinical features, several laboratory markers, and prognosis between boys and girls with SLE. Boys tend to have a high severity at disease onset, develop renal injury and hematological damage, and have poor long-term prognosis, while girls tend to have joint involvement.

Safety and efficacy of PD-1 blockade-activated multiple antigen-specific cellular therapy alone or in combination with apatinib in patients with advanced solid tumors: a pooled analysis of two prospective trials.

BACKGROUND: The lethal effects of multiple antigen-specific cellular therapy (MASCT) may be enhanced by blocking PD-1 in vitro and vascular endothelial growth factor receptor 2 inhibitor (apatinib). We analyzed the pooled data from our phase I/II trials to determine the toxicity and efficacy of PD-1 blockade (SHR-1210)-activated MASCT (aMASCT) alone or in combination with apatinib in advanced solid tumors. METHODS: Patients with advanced solid tumors received aMASCT alone (n = 32) or aMASCT plus apatinib (500 mg q.d., n = 38) after standard treatment. The safety profile was the primary end point. The secondary end points were antitumor response, progression-free survival (PFS), and overall survival (OS). The circulating T cells were quantified before and after aMASCT infusion. RESULTS: Treatment-related adverse events (AEs) occurred in 18/32 (56.3%) and 25/38 (65.8%) patients in the aMASCT and aMASCT plus apatinib groups, respectively. No serious AEs were reported, and apatinib did not increase immunotherapy-related toxicity. The objective response rate (34.2% and 18.8%) and PFS (median 6.0 and 4.5 months, P = 0.002) were improved in the aMASCT plus apatinib group compared with the aMASCT group; however, the OS was not improved (median 10.0 and 8.2 months, P = 0.098). Multivariate analyses indicated that two or more cycles of aMASCT treatment was an independent and favorable prognostic factor of PFS and OS. The circulating T cells increased and Tregs decreased in both groups after one cycle of aMASCT treatment. CONCLUSIONS: Treatment with aMASCT plus apatinib was safe and effective for the management of advanced solid tumors.

Molecular Evolution, Diversity, and Adaptation of Influenza A(H7N9) Viruses in China.

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016-17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015-2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.