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Extranodal NK/T cell lymphoma, nasal type (ENKTL) is an aggressive and heterogeneous disease. With standard treatment containing pegaspargase-based regimen, patients who were resistant to pegaspargase have rapidly disease progression and worse prognosis. Thus, there is an urgent requirement for constructing ENKTL cell line model to explore the mechanism of pegaspargase resistance and new molecular targeted drugs to improve prognosis. We report here on the establishment of a novel ENKTL cell line, NK-NJ. The cells were isolated from a 52-year-old Chinese man who was diagnosed with relapse/refractory (R/R) ENKTL and grow steadily in vitro. The NK-NJ cells express CD56, CD2, CD45RA with no expression of CD3, CD16, CD57, CD4, CD8, CD26, CD28, CD5, TCR, CD45RO and CD161 and showed a TCR gene unrearrangement, which suggested an origin in the NK-lineage but not T-lineage. The immunophenotypes of NK-NJ cells were consistent with the patient. Moreover, short tandem repeat (STR) profiling results also demonstrated that NK-NJ originated from the patient. NK-NJ showed complex karyotype. Target sequencing method indicated that the main mutation genes of the first-time disease progression of lymph nodal were the same as main mutation genes of the primary nasal lesions. Moreover, NK-NJ was recognized as latency I with EBER positivity and carried high EBV-DNA viral load. The chemosensitivity results suggested synthetic lethality of epigenetic drugs and PD-1 inhibitor for ENKTL patients by reasons of epigenetic drugs promoting PD-L1 expression. In conclusion, we established a new ENKTL cell line in the era of new targeted drugs. We hope that this cell line can help to further understand underlying pathogenesis of ENKTL especially for advanced ENKTL and the functional role of EBV in ENKTL pathogenetic process.

A chiral phosphine oxide-ligated Ni-Al bimetallic catalyst was used to realize an enantioselective C2-H alkylation of pyridines without the need of a C2-block. A wide range of pyridines, including unsubstituted pyridine, C3, C4, and C2-substituted pyridines, and even complex pyridine-containing bioactive molecules are well compatible with the reaction, providing up to 81% yield and up to 97% ee.

The fatigue crack initiation life of unwelded steel components accounts for the majority of the total fatigue life, and the accurate prediction of it is of vital importance. In this study, a numerical model utilizing the extended finite element method (XFEM) and Smith–Watson–Topper (SWT) model is established to predict the fatigue crack initiation life of notched details extensively used in orthotropic steel deck bridges. Using the user subroutine UDMGINI in Abaqus, a new algorithm was proposed to calculate the damage parameter of SWT under high-cycle fatigue loads. The virtual crack-closure technique (VCCT) was introduced to monitor crack propagation. Nineteen tests were performed, and the results were used to validate the proposed algorithm and XFEM model. The simulation results show that the proposed XFEM model with UDMGINI and VCCT can reasonably predict the fatigue lives of the notched specimens within the regime of high-cycle fatigue with a load ratio of 0.1. The error for the prediction of fatigue initiation life ranges from −27.5% to 41.1%, and the prediction of total fatigue life has a good agreement with the experimental results with a scatter factor of around 2.

[Formula: see text]-MIL-101(Al) material containing phenazine groups, i.e. 1-metal-organic framework (MOF) has been prepared and characterized via FT-IR, PXRD, TGA, SEM and [Formula: see text] adsorption and desorption isotherm in this work. 1-MOF can exhibit emission peaks at 447 nm (in pure aqueous solvent) and 595 nm (in pure organic solvents) under 327 nm ultraviolet excitation, respectively. Based on this interesting feature, 1-MOF has been effectively used as a ratiometric fluorescent probe to detect water content in organic solvents. The luminescence color of 1-MOF changed obviously from red to blue with the increasing of water content in organic solvents, which can be observed by the naked eyes. The route to detect water content in organic solvents is fast, accurate and possessing great application potential.

Ginkgo biloba seeds are important raw material for foods and medicines. A response surface method was used to obtain the following optimized extraction conditions for Ginkgo biloba seed extracts (GBSE) with the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability: 0.08 g/mL material-to-liquid ratio, 70% ethanol concentration, 47°C extraction temperature and extraction time of 22 min. Fourier transform infrared spectroscopy revealed the polysaccharide structure of GBSE from three varieties of Ginkgo biloba seeds (Fozhi, Maling and Yuanling seed varieties). The extract yield, polysaccharides, total phenolics and total flavonoids in the three varieties were 5.77–6.11%, 11.45–364.69 mg/g, 22.34–25.54 mg/g and 14.87–16.47 mg/g, respectively. The GBSE has good antioxidant ability, including DPPH-reducing activity (1842.73–2616.00 micromol [mmol] Trolox Equivalents [TE]/gram [g]), ABTS (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); 185.03–217.63 mmol TE/g) and ferric-reducing antioxidant power (FRAP; 220.46–230.77 mmol TE/g). This study provides a method for preparing GBSE with high antioxidant activity and improving the utilization value of Ginkgo biloba seeds.

To describe the local experience of adult patients presenting with cannabinoid hyperemesis syndrome (CHS) to an urban ED in the outer northern suburbs of Melbourne.Retrospective chart review of adult patients presenting to the ED with a documented history of CHS or equivalent terminology from January 2015 to January 2021. Age, sex, cannabis use, clinical features, pathology results, imaging and symptomatic management were examined as well as outcomes regarding disposition, representation, morbidity and mortality.One hundred and forty-two adult presentations were included. Sixty-seven were unique presentations and 29 were patients who represented during the study period. Most represented within 3 months (37.8%) and most represented at least twice. Males were overrepresented (68.7%). Patients were young (median age 31 years, interquartile range 23-35 years) and all had a history of regular cannabis use (usually daily). Cyclical nausea and/or vomiting was the most common clinical feature compared to others in previously reported diagnostic criteria. Patients typically had elevated white cell counts with associated neutrophilia (75.8%) and mild hypokalaemia (57.9%). Lipase was not elevated, and C-reactive protein was typically less than 50 mmol/L (98.2%). Imaging was not commonly performed but largely normal. Treatment was supportive with anti-emetic use, intravenous fluids and analgesia. There were no deaths or admissions to intensive care.Cyclical nausea and vomiting was the most common feature observed in this cohort compared to other clinical features reported in prior studies. Serum lipase was normal and C-reactive protein only mildly elevated. Prospective studies are required to further assess these findings.

Additional file 1. PRISMA-P 2015 Checklist.

Dialogue-based language models mark a huge milestone in the field of artificial intelligence, by their impressive ability to interact with users, as well as a series of challenging tasks prompted by customized instructions. However, the prevalent large-scale dialogue-based language models like ChatGPT still have room for improvement, such as unstable responses to questions and the inability to think cooperatively like humans. Considering the ability of dialogue-based language models in conversation and their inherent randomness in thinking, we propose ChatLLM network that allows multiple dialogue-based language models to interact, provide feedback, and think together. We design the network of ChatLLMs based on ChatGPT. Specifically, individual instances of ChatGPT may possess distinct perspectives towards the same problem, and by consolidating these diverse viewpoints via a separate ChatGPT, the ChatLLM network system can conduct decision-making more objectively and comprehensively. In addition, a language-based feedback mechanism comparable to backpropagation is devised to update the ChatGPTs within the network. Experiments on two datasets demonstrate that our network attains significant improvements in problem-solving, leading to observable progress amongst each member.

Additional file 2. Search strategy.

The merging of human intelligence and artificial intelligence has long been a subject of interest in both science fiction and academia. In this paper, we introduce a novel concept in Human-AI interaction called Symbiotic Artificial Intelligence with Shared Sensory Experiences (SAISSE), which aims to establish a mutually beneficial relationship between AI systems and human users through shared sensory experiences. By integrating multiple sensory input channels and processing human experiences, SAISSE fosters a strong human-AI bond, enabling AI systems to learn from and adapt to individual users, providing personalized support, assistance, and enhancement. Furthermore, we discuss the incorporation of memory storage units for long-term growth and development of both the AI system and its human user. As we address user privacy and ethical guidelines for responsible AI-human symbiosis, we also explore potential biases and inequalities in AI-human symbiosis and propose strategies to mitigate these challenges. Our research aims to provide a comprehensive understanding of the SAISSE concept and its potential to effectively support and enhance individual human users through symbiotic AI systems. This position article aims at discussing poteintial AI-human interaction related topics within the scientific community, rather than providing experimental or theoretical results.

Hepacivirusgenus contains single-stranded positive-sense RNA viruses belonging to the family Flaviviridae, which contains 14 species. The 14 hepaciviruses were found in different mammals, such as primates, dogs, bats and rodents. To date, hepacivirus has not been reported in Crocidura animals. To study the prevalence and genetic evolution of hepacivirus in small mammals in Yunnan Province. Molecular detection of hepacivirus in small mammals from Yunnan Province during 2016- 2017 was performed by RT-PCR. Test results showed that the infection rate of hepacivirus in small mammals was 0.12% (2/1602), and the host animal was Crocidura dracula. Phylogenetic analysis and genetic analysis showed hepaciviruses obtained in this study don’t belong to any species of hepaciviruses, and form an independent clade. In general, a novel hepacivirus was identified for the first time in C. dracula specimens from Yunnan, China. And this study expanded the host range and viral diversity of hepaciviruses.

Stereolithography (SLA)-manufactured parts behave with anisotropic properties due to the varying interface orientations generated by the layer-based manufacturing process. Part build orientation is a very important factor of anisotropic mechanical properties. In this paper, the build orientation experiment was designed to study the anisotropic behaviour of the mechanical properties of the SLA parts based on the orientation relationship between the force and the layer. The results show that there are obvious brittle characteristics on the fracture surface of the specimens and microcracks perpendicular to the direction of the layer distributed on the side of the fracture. The mechanical properties under brittle fracture have different degrees of sensitivity to the build orientation. Among all the build orientations, whether a specimen is built flat or on an edge shows obvious difference in tensile strength, and the relative range distribution reaches 35%. The changes in elastic modulus and the elongation at break are the most obvious in different angles relative to the XY plane, and the relative range distribution reaches 62% and 56% respectively. In all the build orientations designed, the tensile strength is the largest when it is placed on the edge at 0° with Y-axis in the XY plane, the elastic modulus is the largest when it was placed vertically, and the elongation at break is the largest when it is placed flat at 45° with Y-axis in the XY plane.

BackgroundPolymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways.MethodsThe gene microarray data related to PM were downloaded from the Gene Expression Omnibus database. The analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were performed on differentially expressed genes (DEGs). The hub genes of PM were identified using weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) algorithm, and the diagnostic accuracy of hub markers for PM was assessed using the receiver operating characteristic curve. In addition, the level of infiltration of 28 immune cells in PM and their interrelationship with hub genes were analyzed using single-sample GSEA.ResultsA total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM.ConclusionWe identified the hub genes closely related to PM using WGCNA combined with LASSO algorithm, which helped clarify the molecular mechanism of PM development and might have great significance for finding new immunotherapeutic targets, and disease prevention and treatment.

Without an effective vaccine against SARS-CoV-2, the build-up of herd immunity through natural infection has been suggested as a means to control COVID-19. Although population immunity is typically estimated by the serological investigation of recovered patients, humoral immunity in asymptomatic subjects has not been well studied, although they represent a large proportion of all SARS-CoV-2 infection cases. In this study, we conducted a serosurvey of asymptomatic infections among food workers and performed serological and cellular response analyses of asymptomatic subjects in Wuhan, the original epicenter of the COVID-19 outbreak. Our data showed that up to 5.91% of the food workers carried SARS-CoV-2 IgG antibodies asymptomatically; however, in 90.4% of them, the antibody level declined over a 2-week period. IgM and IgG antibodies, including neutralizing antibodies, were significantly lower in asymptomatic subjects than in recovered symptomatic patients with similar disease courses. Furthermore, the asymptomatic subjects showed lymphopenia and a prominent decrease in the B-cell population, as well as a low frequency of antibody-secreting cells and a low cytokine response. These factors probably contributed to the low and unsustained antibody levels in asymptomatic subjects. Our results show that asymptomatic subjects are likely to be vulnerable to SARS-CoV-2 reinfection, and neither the proportion of population immunity nor the breadth of immune responses is sufficient for herd immunity.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

3D printing is a rapid prototyping technology in recent years. Computer aided design (CAD) combining with 3D printing in university is helpful for students to understand the design work. The history and characteristics of 3D printing technology were introduced. The technology and material used in 3D printer was summarized. The application of 3D printing technology in teaching was studied. Combining 3D printing technology and CAD design cases is helpful for students to understand the designed model directly and to master the three-view drawing of objects intuitively. Integrating 3D printing technology into mechanical design competition is an effective means to promote teaching effect. Apply 3D printing into CAD teaching could improve students’ subjective initiative in learning, expand students’ innovative thinking, and improve teaching quality.

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.

Intracellular antigen labeling and manipulation by antibodies have been long-thought goals in the field of cell research and therapy. However, a central limitation for this application is that antibodies are not able to penetrate into the cytosol of living cells. Taking advantages of small sizes and unique structures of the single-domain antibodies, here, we presented a novel approach to rapidly deliver the nanobody/variable domain of heavy chain of heavy-chain antibody (VHH) into living cells via introducing its coding mRNA, which was generated by in vitro transcription. We demonstrated that actin-green fluorescent proteins (GFP) and Golgi-GFP can be recognized by the anti-GFP nanobody/VHH, vimentin can be recognized by the anti-vimentin nanobody/VHH, and histone deacetylase 6 (HDAC6) can be recognized by the anti-HDAC6 nanobody/VHH, respectively. We found that the anti-GFP nanobody expressed via in vitro-transcribed (IVT) mRNA can be detected in 3 h and degraded in 48 h after transfection, whereas the nanobody expressed via plasmid DNA, was not detected until 24 h after transfection. As a result, it is effective in delivering the nanobody through expressing the nanobody/VHH in living cells from its coding mRNA.

This study aims to explore the effects of exosomes, secreted by retinal pigment epithelial (RPE) cells under oxidative stress (OS), on apoptosis and inflammation of normal RPE cells. Exosomes secreted by normal RPE cells (named as exo) and rotenone (2.5 µmol/L) stimulated RPE cells (named as rot-exo) were isolated and extracted by multi-step differential centrifugation for morphology observation under a transmission electron microscopy. pcDNA3.1a, pcDNA3.1a-Apaf1, and p3xFlag-CMV-caspase-9 plasmids were constructed and transfected into ARPE-19 cells. Exosomes secreted by ARPE-19 cells were injected into the vitreous body of rats to verify the effect of Apaf1 and caspase-9 on cell apoptosis and inflammation. Co-immunoprecipitation was applied to clarify the interaction of Apaf1 with caspase-9. Exosomes secreted by rotenone stimulated ARPE-19 cells could induce cell apoptosis, oxidative injury, and inflammation in ARPE-19 cells. Exosomes secreted under OS can damage retinal functions of rats and have upregulated expression of Apaf1. Overexpression of Apaf1 in exosomes secreted under OS can cause the inhibition of cell proliferation, the increase of cell apoptosis and elicitation of inflammatory response in ARPE-19 cells. Exosomes derived from ARPE-19 cells under OS regulate Apaf1 expression to increase cell apoptosis and to induce oxidative injury and inflammatory response through a caspase-9 apoptotic pathway.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV., Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

Wu Yi,1 Tianxin Yang,2 Sisi Lin,1 Rui Hao,1 Jin Yu,1 Ying Wang,1,3 Xiangming Tong2,4 1Phase I Clinical Research Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Hematology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 4The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of ChinaCorrespondence: Xiangming TongThe Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13758183497, Email tongxiangmin@163.comAbstract: Extranodal NK/T cell lymphoma (ENKL) is a rare subtype of lymphoma that shows a poor clinical outcome. The most common sites are the nasal cavity, nasopharynx, paranasal sinuses, tonsils and larynx. Because of P-glycoprotein expression on ENKL cells, ENKL is resistant to anthracycline-based chemotherapy. L-asparaginase-based chemotherapy with or without radiotherapy shows promising outcomes for advanced ENKL, but has limited efficacy in relapsed/refractory ENKL. immune-checkpoint inhibitors, histone deacetylase inhibitors, and monoclonal antibodies are being investigated. In this review, we summarize the new treatments for ENKL.Keywords: extranodal NK/T cell lymphoma, pathway, PD-1, immunotherapy

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the most fatal diseases in the world. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the production of 5-methyltetrahydrofolate (5-CH3-THF), which is required for the de novo biosynthesis of methionine in bacteria. In this study, we identified Rv2172c as an MTHFR in M. tuberculosis through in vitro and in vivo analyses and determined that the protein was essential for the in vitro growth of the bacterium. Subsequently, we constructed rv2172c R159N and L214A mutants in M. tuberculosis, and found that these mutants were more sensitive to the antifolates para-aminosalicylic acid (PAS) and sulfamethoxazole (SMX). Combining biochemical and genetic methods, we found that rv2172c R159N or L214A mutation impaired methionine production, leading to increased susceptibility of M. tuberculosis to PAS, which was largely restored by adding exogenous methionine. Moreover, overexpression of rv2172c in M. tuberculosis could increase methionine production and lead to PAS resistance. This research was the first to identify an MTHFR in M. tuberculosis and revealed that the activity of this enzyme was associated with susceptibility to antifolates. These findings have particular value for anti-tubercular drugs design for the treatment of drug-resistant TB.

Additional file 5. Supplementary Table 1. Primers used for RT-PCR analysis.

Additional file 1. Additional figures.

Cannabidiol (CBD), derived from the plant cannabis, can be used in the cosmetics industry for its antioxidant, anti-inflammatory, anti-wrinkle and whitening effects. However, CBD is purified from the hemp plant extract, its source is very limited and under strict control. So in this study, computational and experimental methods were combined to search for novel CBD substitutes with high biology potencies. The action mode between CBD and target protein cannabidiol receptor 1 was studied to find the key skeleton, which was used to virtually screen a natural products database to search for compounds with 70% similarity. The hit compounds with high docking scores were selected for the ABTS and DPPH free radical scavenging experiments for antioxidant evaluation. The effects on the expressions of nitric oxide (NO), interleukin-6 (IL-6), COX-2 and iNOS in RAW264.7 cell line were detected to demonstrate their anti-inflammatory abilities. The effect of anti-wrinkle ability were evaluated by detecting the extracellular matrix, such as collagen, elastin, fibronectin and reactive oxygen species (ROS) in HFF-1. The effects on melanin production and tyrosinase activity in Bb16F10 were also detected. As a result, two compounds were found to be superior to cannabidiol, in terms of antioxidant, anti-wrinkle and whitening efficacy with a lower cytotoxicity.

The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of 2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-CoV-2 epidemics in several large cities or provinces of China. However, information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-CoV-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-CoV-2 transmission profiles. Genomic epidemiology revealed multiple SARS-CoV-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size. Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-CoV-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-CoV-2 strains during the early COVID-19 epidemic in China.

AIM: To compare the clinical outcomes of wavefront guided femtosecond LASIK (WFG LASIK) and conventional femtosecond LASIK (NWFG LASIK) in eyes with myopia and myopia astigmatism. METHODS: This was a retrospective, nonrandomized, comparative investigation enrolling 236 eyes of 122 patients (18-50y) with low & moderate and high myopia. The WFG group including 97 eyes (50 patients) undergone WFG LASIK and the NWFG group including 139 eyes (72 patients) undergone conventional LASIK. Mean efficacy index, high order aberrations (HOAs), pupil size and the quality of visual questionnaire were evaluated 6mo postoperatively. RESULTS: There is no difference between WFG group (-0.054±0.049 in logMAR) and NWFG group (-0.040±0.056) in uncorrected distance visual acuity (UDVA) postoperatively. The myopia astigmatism is higher in WFG group than that in NWFG group (P

Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.

[Objectives] During the discharging of ship-used steam power,steam jet condensation was a common physical process. In order to fully grasp the fundamental physical phenomena within steam submerged jet and condensation under open space,CFD simulation with Mixture multiphase model was carried out.[Methods] With the experimental results,heat transfer model was modified. Vapor volume fraction 0.95 was regarded as the critical value to measure the length of plume. Spatial distribution of plume,velocity,temperature and pressure fields for steam submerged jet and condensation under different inlet pressure and condensed water temperature conditions were studied.[Results] Simulation results show that different initial state would affect the plume shapes. Within stable steam submerged jet and condensation,a relatively lower temperature area is appeared in the core of plume. Pressure distribution along the axial direction is present in a fluctuating form,verifies the existence of the expand-compress wave inside the plume,amplitude and spatial wavelength of the pressure fluctuation are increased with increasing inlet pressure.[Conclusions] Study in this paper could provide guidance for the optimal design of steam submerged jet and condensation.

Angiogenesis is a complex process, which involves the sprouting of new blood vessels from pre-existing vasculature. Pathological retinal angiogenesis can lead to vision loss and even blindness. Cyclin-dependent kinase 1 (CDK1) is involved in regulation of the cell cycle and is reported to contribute to tumor progression. However, the role of CDK1 in retinal angiogenesis is largely unknown. The purpose of the present study was to investigate the role of CDK1 in retinal angiogenesis. Western blotting, reverse transcription-quantitative PCR (RT-qPCR) analysis, immunofluorescence and immunohistochemistry were used to evaluate the expression of CDK1 in pathological angiogenesis using an oxygen-induced retinopathy (OIR) mouse model. Small interfering (si)RNA sequences against CDK1 were synthesized and incubated with retinal cells. The efficiency of knockdown was confirmed by western blot and RT-qPCR assays. The effect of CDK1 siRNAs on angiogenesis in vitro was investigated using EdU cell proliferation, cell migration and tube formation assays. Subsequently, flow cytometry was used to assess the effects of CDK1 siRNAs on cell cycle distribution and on the induction of apoptosis. The expression levels of cell cycle- and apoptosis-related genes were detected using western blotting. CDK1 was overexpressed in pathological retinal angiogenesis. CDK1 siRNAs inhibited human umbilical vein endothelial cell proliferation, migration and tube formation. The possible mechanisms involved the induction of cell cycle arrest at the G2/M phase and the induction of apoptosis via an increase in the expression levels of p21 and p53. In conclusion, the data indicated that CDK1 was overexpressed in the OIR model and that silencing of CDK1 inhibited angiogenesis in vitro. CDK1 may be a novel therapeutic target for pathological retinal angiogenesis.

We theoretically investigate the high-order harmonic generation (HHG) of H 2 + molecule in the counter-rotating two-color circularly polarized laser pulse by numerically solving the two-dimensional (2D) time-dependent Schrodinger equation (TDSE). The results show that the even harmonics are suppressed with the fundamental laser wavelength 800 nm for the ratio of the second laser frequency and the fundamental laser frequency 3 or 5. In order to investigate the contributions of the HHG from two nuclei, the HHG is separated into two parts, which is originated from nucleus 1 and nucleus 2. The underlying physical mechanism of enhancing and suppressing high-order harmonic generation is illustrated by the interference effect of the HHG spectra originating from two nuclei. Meanwhile, the difference of the HHG spectra is investigated with the fundamental laser wavelength 1600 nm and 2400 nm.

A field growing/non-growing season asymmetric warming experiment (C: control, i.e., no warming in the entire year; GLNG: growing season warming lower than non-growing season warming; GHNG: growing season warming higher than non-growing season warming) was conducted in an alpine meadow of the Northern Tibetan Plateau in early June 2015. The effects of growing/non-growing season asymmetric warming on the normalized difference vegetation index (NDVI), soil adjusted vegetation index (SAVI), aboveground biomass (AGB) and gross primary production (GPP) in 2015–2017 were examined. The ‘GLNG’ and ‘GHNG’ treatments significantly increased the annual mean air temperature (Ta) by 2.95 °C and 2.76 °C, and the vapor pressure deficit (VPD) by 0.23 kPa and 0.28 kPa but significantly reduced the annual mean soil moisture (SM) by 0.02 m3 m−3 and 0.02 m3 m−3 respectively; however, changes in the annual mean Ta, VPD and SM were the same between the ‘GLNG’ and ‘GHNG’ treatments over the three years in 2015–2017. There were no significant differences in the SAVI and GPP among the ‘C', ‘GLNG’ and ‘GHNG’ treatments over the three growing seasons in 2015–2017. The ‘GLNG’ and ‘GHNG’ treatments did not significantly affect the NDVI and AGB compared to ‘C’, whereas the NDVI and AGB under the ‘GLNG’ treatment were significantly greater than those under the ‘GHNG’ treatment over the three growing seasons in 2015–2017. The significant differences in NDVI and AGB between the ‘GLNG’ and ‘GHNG’ treatments may be attributed to the different effects under the ‘GLNG’ and ‘GHNG’ treatments on the non-growing season Ta, growing season water availability and soil nitrogen availability. Therefore, the non-growing season with a higher warming magnitude may have stronger effects on the aboveground plant production than did the growing season with a higher warming magnitude in the alpine meadow of the Northern Tibetan Plateau.

This article mainly describes the chemical and crystal structure of attapulgite as its unique crystal structure possess special physicochemical properties such as large specific surface area, adsorption performance, and cation exchangeability. By modification of attapulgite, such as purification, high temperature roasting and other physical modification or acid–base salt modification, organic modification, surfactant modification and other chemical modification can further improve its physicochemical properties. In this article, the modification methods of two aspects of physical modification and chemical modification are summarized, at the same time, the research progress and achievements of many scholars in attapulgite modification are reviewed. Through modified attapulgite the number of pores increased, channel become loose, pore diameter increases, pore volume increases, interlayer spacing increases, specific surface area increases, chargeability and adsorption activity change, and the adsorption performance of attapulgite is greatly improved. Many scholars have applied modified attapulgite to the treatment of radionuclides, and achieved remarkable results. It has been found that modified attapulgite has U(VI), Eu(III), Cs(III), Th(IV), both Eu(III) and Sr(II) have good adsorption properties, and the adsorption rate and adsorption capacity are greatly improved compared with the original soil. Based on the Summary of the attapulgite modification method and its application in the treatment of radionuclide, some suggestions on the research and application of attapulgite modification and the possible key research directions in the future are further proposed.