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Zi-Li Huang,1,2,* Ping-Bao Zhang,1,3,* Jun-Tao Zhang,4 Feng Li,5 Ting-Ting Li,6 Xiu-Yan Huang1 1Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Radiology, Xuhui District Central Hospital of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 5School of Materials of Science and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 6Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiu-Yan Huang, Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yi Shan Road, Shanghai, People’s Republic of China, Tel/Fax +86-21-64701361, Email xyhuang1119@163.comBackground: FAT atypical cadherin 1 (FAT1) acts as a tumor suppressor or oncogene, which regulates cell adherence, proliferation, motility, and actin kinetics. FAT1 gene expression is closely related to hepatocarcinogenesis; however, the function and mechanism of FAT1 in hepatocellular carcinoma (HCC) remain unclear.Methods: Here, we screened for the FAT1, which is intimately linked to the development and progression of HCC, both in circulating tumor cells (CTCs) and tumor tissues using next generation sequencing (NGS). Immunohistochemical staining was performed to detect FAT1 protein expression. To determine the impact of FAT1 on epithelial–mesenchymal transition (EMT), migration and invasion of HCC, an in vitro transwell assay and Western blot were performed. Moreover, Gene Set Enrichment Analysis was carried out to discover the underlying mechanism. Finally, animal experiments were conducted to confirm the effects of FAT1 on HCC metastasis and tumorigenicity.Results: Our results showed that FAT1 expression was decreased in HCC tissues, while in vitro and in vivo, the FAT1 knockdown facilitated invasion, cell motility, colony formation, and proliferation. FAT1 knockdown also resulted in decreased expression of E-cadherin and markedly elevated expression of N-cadherin, vimentin, and snail. We also confirmed our hypothesis from the analysis of group differences in the CTC phenotype and lung metastasis in nude mice.Conclusion: Our findings illustrated that FAT1 played a negative regulatory role in the HCC EMT and metastasis, providing further evidence for the role played by FAT1 in the formation and progression of HCC.Keywords: hepatocellular carcinoma, FAT1, epithelial-mesenchymal transition, circulating tumor cells, metastasis

The myophage possesses a contractile tail that penetrates its host cell envelope. Except for investigations on the bacteriophage T4 with a rather complicated structure, the assembly pattern and tail contraction mechanism of myophage remain largely unknown. Here, we present the fine structure of a freshwater Myoviridae cyanophage Pam3, which has an icosahedral capsid of ~680 Å in diameter, connected via a three-section neck to an 840-Å-long contractile tail, ending with a three-module baseplate composed of only six protein components. This simplified baseplate consists of a central hub-spike surrounded by six wedge heterotriplexes, to which twelve tail fibers are covalently attached via disulfide bonds in alternating upward and downward configurations. In vitro reduction assays revealed a putative redox-dependent mechanism of baseplate assembly and tail sheath contraction. These findings establish a minimal myophage that might become a user-friendly chassis phage in synthetic biology.

The RNA-targeting type III-E CRISPR-gRAMP effector forms a complex with a caspase-like protease TPR-CHAT, but the mechanistic details of their functional relationship remain unknown. Here, we report on cryo-EM structures of gRAMPcrRNA and gRAMPcrRNA-TPR-CHAT complexes, before and after either self or non-self RNA target binding, elucidating mechanisms underlying RNA-targeting and non-self RNA-induced protease activation. Noteworthy, the associated TPR-CHAT adopts a strikingly distinct conformation on self versus non-self RNA targets, with nucleotides at position −1 and −2 of crRNA serving as a sensor. Only binding of non-self RNA target activates TPR-CHAT protease, leading to the cleavage of Csx30 protein. Furthermore, given that TPR-CHAT structurally resembles eukaryotic separase, our results implicate an ancient mechanism for separase regulation. Our findings should not only facilitate the development of gRAMP-based RNA manipulation tools, but also lead to a mechanistic understanding of the virus-host discrimination process governed by a caspase-like protease during type III-E CRISPR-Caspase immunity.

BACKGROUND Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

Lenvatinib (LEN) is approved as one of the commonly used drugs in the treatment of hepatocellular carcinoma (HCC). It is recognized to be a novel therapeutic choice for the direct and targeted delivery of effective drugs to HCC tumor sites. The key to the proposed method lies in the requirement for efficient targeted drug delivery carriers with targeting performance to deliver effective drugs directly and safely to tumor lesions.

A-1(L) is a freshwater cyanophage with a contractile tail that specifically infects Anabaena sp. PCC 7120, one of the model strains for molecular studies of cyanobacteria. Although isolated for half a century, its structure remains unknown, which limits our understanding on the interplay between A-1(L) and its host. Here we report the 3.35 A cryo-EM structure of A-1(L) capsid, representing the first near-atomic resolution structure of a phage capsid with a T number of 9. The major capsid gp4 proteins assemble into 91 capsomers, including 80 hexons: 20 at the center of the facet and 60 at the facet edge, in addition to 11 identical pentons. These capsomers further assemble into the icosahedral capsid, via gradually increasing curvatures. Different from the previously reported capsids of known-structure, A-1(L) adopts a non-covalent chainmail structure of capsid stabilized by two kinds of mortise-and-tenon inter-capsomer interactions: a three-layered interface at the pseudo three-fold axis combined with the complementarity in shape and electrostatic potential around the two-fold axis. This unique capsomer construction enables A-1(L) to possess a rigid capsid, which is solely composed of the major capsid proteins with an HK97 fold. IMPORTANCE Cyanobacteria are the most abundant photosynthetic bacteria, contributing significantly to the biomass production, O2 generation, and CO2 consumption on our planet. Their community structure and homeostasis in natural aquatic ecosystems are largely regulated by the corresponding cyanophages. In this study, we solved the structure of cyanophage A-1(L) capsid at near-atomic resolution and revealed a unique capsid construction. This capsid structure provides the molecular details for better understanding the assembly of A-1(L), and a structural platform for future investigation and application of A-1(L) in combination with its host Anabaena sp. PCC 7120. As the first isolated freshwater cyanophage that infects the genetically tractable model cyanobacterium, A-1(L) should become an ideal template for the genetic engineering and synthetic biology studies.

A-1(L) is a freshwater cyanophage with a contractile tail that specifically infects Anabaena sp. PCC 7120, one of the model strains for molecular studies of cyanobacteria. Although isolated for half a century, its structure remains unknown, which limits our understanding on the interplay between A-1(L) and its host. Here we report the 3.35 Å cryo-EM structure of A-1(L) capsid, representing the first near-atomic resolution structure of a phage capsid with a T number of 9. The major capsid gp4 proteins assemble into 91 capsomers, including 80 hexons: 20 at the center of the facet and 60 at the facet edge, in addition to 11 identical pentons. These capsomers further assemble into the icosahedral capsid, via gradually increasing curvatures. Different from the previously reported capsids of known-structure, A-1(L) adopts a noncovalent chainmail structure of capsid stabilized by two kinds of mortise-and-tenon inter-capsomer interactions: a three-layered interface at the pseudo 3-fold axis combined with the complementarity in shape and electrostatic potential around the 2-fold axis. This unique capsomer construction enables A-1(L) to possess a rigid capsid, which is solely composed of the major capsid proteins with an HK97 fold. IMPORTANCE Cyanobacteria are the most abundant photosynthetic bacteria, contributing significantly to the biomass production, O(2) generation, and CO(2) consumption on our planet. Their community structure and homeostasis in natural aquatic ecosystems are largely regulated by the corresponding cyanophages. In this study, we solved the structure of cyanophage A-1(L) capsid at near-atomic resolution and revealed a unique capsid construction. This capsid structure provides the molecular details for better understanding the assembly of A-1(L), and a structural platform for future investigation and application of A-1(L) in combination with its host Anabaena sp. PCC 7120. As the first isolated freshwater cyanophage that infects the genetically tractable model cyanobacterium, A-1(L) should become an ideal template for the genetic engineering and synthetic biology studies.

A definition is given of the sandstone-fractured basement composite reservoir and its origin is analyzed at first; then take the SR oilfield as a case to describe its geological characteristics in terms of sand distribution, structural characteristics, oil-water contact, barrier distribution, and development degree of basement fractures; finally analyze the challenges of developing this type of reservoir and propose reasonable development strategy. The sandstone-fractured basement composite reservoir in Bongor Basin has a large thickness of sandstone but a limited horizontal distribution, a large reservoir structural relief, a unified oil-water system and the more developed fractures on the top of the basement. The challenges to face in the development include weak natural energy, high strata dip, extremely strong heterogeneity in basement reservoir, lack of stable barriers between sandstone and basement. This type of reservoirs requires prompt energy support through separated layer water flooding. An oil well should produce at a specific proration relative to the degree of fracture development, and at the same time, it is necessary to prevent the rapid breakthrough of injected water along the erosion surface of the basement.

Low reservoir maintaining pressure and rapid production rate are prone to occur when natural energy development is deployed in thick lithologic sandstone reservoirs. Water injection development can avoid these situations happening and enhance the development effects. The thick lithologic sandstone reservoir being studied is structured with a dip angle of 10° and therefore the water injection development process is highly affected by gravity differentiation, interlayer permeability heterogeneity and injection-production parameters. In order to improve the development effect, the key influencing factors during water injection should be sorted and optimized. The orthogonal test design method is chosen to investigate the water injection development parameters based on the numerical simulation models. In this study, 8 representative geological and development parameters are selected, 5 values are selected for each parameter and 50 simulation cases are designed to determine the relevance between parameters and the influence of each parameter on the development effect. The results indicates that the main influencing factor influencing water injection in thick sandstone reservoir is injection-production ratio, followed by oil recovery rate, horizontal permeability, dip angle and reservoir thickness. It is believed that this research can direct the water injection development in thick sandstone reservoir.

The dual porosity model is always applied in pressure transient well testing interpretation of fractured basement reservoir and there is no direct correlation between the interpretation results and fracture characteristic parameters. Fractures are important in fluid storage and flowing in basement reservoir, more details and information are needed in fractured reservoir well testing interpretation to guide the oil field development. The numerical well testing modeling is designed to solve the well testing interpretation problems in reservoir with regular fractures. But precise numerical well testing modeling of a dense system of randomly spaced, randomly distributed and oriented, interconnected and unconnected fractures would be very challenging. The numerical well testing modeling can simulate the impacts of well-hole connectivity, dip angle and fracture width on the interpretation results. It is supposed that the parameters in the regular fracture system that do not affect interpretation results do not work in nature fracture system. With this hypothesis, imaging logging data of 3 wells are selected to determine the fracture width, density and azimuth to calculate the fracture porosity and effective permeability and to build the simulation model. The pressure simulated from the model matches the pressure response of actual filed well testing and the effective permeability matches the real one too, which indicates that random fracture system can be replaced by simplified regular fracture system in this study to lower simulation difficulty. The sensitiveness of fracture parameters is also studied in this paper.

IWe have designed, simulated, and experimentally tested a broadband metamaterial absorber loaded with lumped resistors in the microwave range. Compared with an electric resonator structure absorber, the composite absorber loaded with lumped resistors has stronger absorptivity over an extremely extended bandwidth. The simulated results show that an effective absorption bandwidth covers from 7.12 to 8.61 GHz with the absorption rate more than 90% under normal incidence. For oblique incidence, the proposed absorber displays an absorption rate above 90% from 7.55 to 8.61 GHz when the incident angle is below 35° for the transverse electric polarization. About the transverse magnetic polarization, the absorber displays larger than 90% absorptance from 7.24 to 8.61 GHz when the incident angle is below 70°. During the entire design process, the absorber structure is fabricated and measured. The measured results show that the absorptivity is above 90% in the frequency range of 6.78–7.65 GHz and 8.20–9.31 GHz under normal incidence. Furthermore, the absorption mechanism and absorption properties are further researched.

Lake Chaohu, one of the five largest freshwater lakes in China, has been suffering from severe cyanobacterial blooms in the summer for many years. Cyanophages, the viruses that specifically infect cyanobacteria, play a key role in modulating cyanobacterial population, and thus regulate the emergence and decline of cyanobacterial blooms. Here we report a long-tailed cyanophage isolated from Lake Chaohu, termed Mic1, which specifically infects the cyanobacterium Microcystis aeruginosa. Mic1 has an icosahedral head of 88 nm in diameter and a long flexible tail of 400 nm. It possesses a circular genome of 92,627 bp, which contains 98 putative open reading frames. Genome sequence analysis enabled us to define a novel terminase large subunit that consists of two types of intein, indicating that the genome packaging of Mic1 is under fine control via posttranslational maturation of the terminase. Moreover, phylogenetic analysis suggested Mic1 and mitochondria share a common evolutionary origin of DNA polymerase γ gene. All together, these findings provided a start-point for investigating the co-evolution of cyanophages and its cyanobacterial hosts.

Summary Despite previous structural analyses of bacteriophages, quite little is known about the structures and assembly patterns of cyanophages. Using cryo-EM combined with crystallography, we solve the near-atomic-resolution structure of a freshwater short-tailed cyanophage, Pam1, which comprises a 400-A-long tail and an icosahedral capsid of 650 A in diameter. The outer capsid surface is reinforced by trimeric cement proteins with a β-sandwich fold, which structurally resemble the distal motif of Pam1's tailspike, suggesting its potential role in host recognition. At the portal vertex, the dodecameric portal and connected adaptor, followed by a hexameric needle head, form a DNA ejection channel, which is sealed by a trimeric needle. Moreover, we identify a right-handed rifling pattern that might help DNA to revolve along the wall of the ejection channel. Our study reveals the precise assembly pattern of a cyanophage and lays the foundation to support its practical biotechnological and environmental applications.

It is a common sense that innovations are easy to be created at the boundaries of different disciplines. Howerver, how to lead the postgraduate students, particualrly those are pursuing their master degree, to realize their cross-disciplinary innovations in their initial research life is a heavy task for their supervisors. In this paper, an advanced technology, electrospraying, is exploited as an excellent example to teach the postgraduate students to carry out their innovation processes, where the innovations happen not only in itself, but also in the selections of raw materials and the functional applications of the final products. The multiple disciplines, including polymer science, bioengineering, pharmaceutics, and food science, can collect together to the electrospraying processes for creating something new by crossing boundaries, and for thinking across them. Combining with the usage of modern advanced nanotechnology, and starting from the functional applications of nanomaterials, a series of similar innovations can be conceived along the approach demonstrated here.

Cyanobacteria are the most abundant photosynthetic microorganisms, the global distribution of which is mainly regulated by the corresponding cyanophages. A systematic screening of water samples in the Lake Chaohu enabled us to isolate a freshwater siphocyanophage that infects Microcystis wesenbergii, thus termed Mic1. Using cryoelectron microscopy, we solved the 3.5-Å structure of Mic1 capsid. The major capsid protein gp40 of an HK97-like fold forms two types of capsomers, hexons and pentons. The capsomers interact with each other via the interweaved N-terminal arms of gp40 in addition to a tail-in-mouth joint along the three-fold symmetric axis, resulting in the assembly of capsid in a mortise-and-tenon pattern. The novel-fold cement protein gp47 sticks at the two-fold symmetric axis and further fixes the capsid. These findings provide structural insights into the assembly of cyanophages, and set up a platform to explore the mechanism of specific interactions and co-evolution with cyanobacteria.

An efficient rare earth metal complex-catalyzed cycloaddition reaction of CO2 with propylene oxide using Hdpza (di(2-pyrazyl)amine) as a N-donor ligand has been accomplished in good to excellent yields with high selectivity. The effects of different rare earth metal salts, ligands and reaction conditions were examined. Catalytic reaction tests demonstrated that the incorporation of ErCl3 and Hdpza can significantly enhance the catalytic reactivity of the TBAB (nBu4NBr, tetra-n-butyl ammonium bromide) towards cycloaddition reaction of CO2 and propylene oxide that produce cyclic carbonates under mild conditions without any co-solvent.

The increase of the strength of gray cast iron is mainly depended on alloying. However, with the improvement of strength, its processing performance will always decrease. So three different gray cast irons are studied in this experiment, including adding 0.1% Nb elements, adding 0.2% Nb elements and adding 0.3% Nb elements, to investigate the Nbs effect to the mechanical performance of gray cast iron, we adopt Dynamic Strain Amplifier to measure cutting force to evaluate processing performance, use Optical Microscope and Electron Microscopy observe each samples organization, explains the relationship between Nbs content and the mechanical and processing performance of gray cast iron from micro-level. Finally, we draw the conclusion: when the Nb comes to 0.3 percent, the appearance of E-type graphite and Nb carbide durum granular will greatly decrease its processing performance.

The hot deformation behavior of Mg-3.5Zn-0.6Y-0.5Zr alloy was investigated by compressive tests of strain rate ranges of 0.002~1 s-1and deformation temperature ranges of 300~450 °C using a Gleeble 1500D thermal simulator. The flow stresses in different deformation conditions are measured. The results show that flow stress is significantly affected by both deformation temperature and strain rate, the flow stress increases with increase in strain rate and decreases in deformation temperature during the hot compression process. The constitutive equation established on the basis of data of activation energy and stress exponent is a hyperbolic sine function.

The formation of the microstructure of gray cast iron is a complex process. There remains many unanswered questions about the process. Using annealing method, the first crystallized primary austenite dendrites from the molten iron was displayed. The room temperature microstructures of gray cast iron with and without Cu, Cr addition were studied. The relationship between microstructure and mechanical property was discussed. The results show that the amount of primary austenite dendrites of the multi-alloyed gray cast iron increases significantly and the secondary dendrite arm spacing seems narrow. The microstructure at room temperature is fine and homogeneous. Tensile strength increases significantly, up to 300MPa with adding 0.58%Cu and 0.29%Cr.

Aero-heating analysis is very important for the thermal protection system design of blunted waverider. In this paper, the heat flux distributions on the nose region and leading edge, the upper surface and the lower surface are studied with numerical and experiment methods, including the effects of attack angle and sideslip angle. The results show that high heat flux is limited in a small region around the stagnation point, and the influence of attack angle on the aero-heating of nose region can be neglected. Because even small sideslip angle may induce great enhanced aero-heating on the windward side of blunted waverider, zero degree sideslip angle is suggested in the present paper. With this assumption, the thermal materials of nose region, leading edge and upper surface can be chosen based on their aero-heating under on-design condition; while for the lower surface, the thermal materials should be determined by the aero-heating under maximum angle of attack.

Purpose: To investigate the association of interleukin (IL)-6 with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D) in a Chinese population. Methods: Two subtypes of the IL-6 promoter (-174 and -572 G/C) were genotyped in 215 T2D patients with PDR and 207 T2D patients with a normal retinal function (controls) using the PCR-RFLP method. The mRNA and protein expression of IL-6 was examined by real-time PCR. Results: T2D patients with PDR had a significantly higher frequency of IL-6 -174 GC (OR 0.58; 95% CI 0.34-0.99; p = 0.011) and IL-6 -572 GG (OR 0.53; 95% CI 0.24-1.14; p = 0.016) than T2D controls. The mRNA expressions of the rs1800795 GC and rs1800796 GG genotype were significantly increased compared to other cases (Fsig = 0.002, p = 0.001, respectively), followed by a relative increase in IL-6 in protein. Conclusions: IL-6 genotypes of rs1800795 GC and rs1800796 GG might point to a relatively high risk for T2D patients suffering from PDR in a Chinese population and they were associated with elevation of IL-6 expression in both mRNA and protein.

To establish the rapid PCR amplification program and system and to verify the technical indexes.PCR multiplex and capillary electrophoresis detection of 24 autosomal STR loci and one Y-STR loci using the 6-color fluorescence marking technology, as well as A melogenin and Y-InDel. Meanwhile, sensitivity, specificity, identity, stability, mixing and a batch of sample tests were investigated, and the genotype of various routine samples and degraded, exfoliated cell samples were observed.The sensitivity of the system was 0.062 5 ng. In addition, the genotype could be detected accurately only around 65 min via rapid amplification. The species-specificity was high and the genotyping of all kinds of dry blood specimens of filter paper and mixed, degraded, exfoliated cell samples were accurate.The rapid amplification system can significantly improve the detection rate, and obtain accurate and stable genotyping results, which may be important implications for the establishment of STR database and study on population genetics and forensic identification.

A facile and improved route for the synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677 was described. The key step adopted the Fischer indole/reduction strategy. The preparation of the key intermediates N-protected piperidine carboxaldehyde 5 and the N-Boc-O-benzyl- d -serine (2) are also optimized.

When project accidents happened, engineers will always become to the scapegoat, because the professional ethics of engineers require they to take the construction quality and public safety in the first place. However, a game analysis of every parties involved in the construction found that the business ethics and supervision system are equally important. So, it is unreasonably to attribute engineering accidents to the professional ethics of engineers unilateral and isolated. In order to solve the engineering accidents fundamentally, institutional building and ethics construction must be combined to a whole.