[Effect of Staphylococcal Nuclease and Tudor Domain Containing 1/SLC7A11 on the Occurrence and Development of Osteosarcoma by Inhibiting Ferroptosis].

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

[Characterization of Cell Subsets Associated With Prognosis of Osteosarcoma Based on Single-Cell Sequencing Data].

Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.

Forecast for peak infections in the second wave of the Omicron after the adjustment of zero-COVID policy in the mainland of China.

On December 7, 2022, the Chinese government optimized the current epidemic prevention and control policy, and no longer adopted the zero-COVID policy and mandatory quarantine measures. Based on the above policy changes, this paper establishes a compartment dynamics model considering age distribution, home isolation and vaccinations. Parameter estimation was performed using improved least squares and Nelder-Mead simplex algorithms combined with modified case data. Then, using the estimated parameter values to predict a second wave of the outbreak, the peak of severe cases will reach on 8 May 2023, the number of severe cases will reach 206,000. Next, it is proposed that with the extension of the effective time of antibodies obtained after infection, the peak of severe cases in the second wave of the epidemic will be delayed, and the final scale of the disease will be reduced. When the effectiveness of antibodies is 6 months, the severe cases of the second wave will peak on July 5, 2023, the number of severe cases is 194,000. Finally, the importance of vaccination rates is demonstrated, when the vaccination rate of susceptible people under 60 years old reaches 98%, and the vaccination rate of susceptible people over 60 years old reaches 96%, the peak of severe cases in the second wave of the epidemic will be reached on 13 July 2023, when the number of severe cases is 166,000.

Hydrodynamic Kelvin-Helmholtz instability on metallic surface.

Kelvin-Helmholtz instability on metallic surface is relevant to intense oblique impact in many physical processes such as explosive welding, Inertial Confinement Fusion and planetary impact events. Evolution of instability results in the formation of wavy morphology leading to material bonding or even mixing. However, mostly due to lack method to describe the dynamic behavior, instability mechanism controlled by elastoplastic properties of metal remains elusive. Here, we introduce a theory to reveal the evolution characteristics aroused by tangential velocity. Our simulations find that the unstable metallic surfaces exhibit amplitude growth and tangential motion by overcoming the depression of yield strength to generate wavy morphology. For diverse loading velocities, corrugated surfaces and material properties, an instability boundary distinguishes all unstable evolutions. Our analytical method with scale-independent variables reproducing numerical findings reveals plentiful characteristics of instability in strength materials. For designed loading velocities and material in oblique impact experiment in laboratory, the property of corrugated surfaces becomes an important factor to determine instability evolution.

Quantitative evaluation of the role of Fangcang shelter hospitals in the control of Omicron transmission: A case study of the outbreak in Shanghai, China in 2022.

Since Omicron began to spread in China, Shanghai has become one of the cities with more severe outbreaks. Under the comprehensive consideration of the vaccine coverage rate, the number of Fangcang shelter hospital beds and the number of designated hospital beds in Shanghai, this paper established a deterministic compartmental model and used the Nelder-Mead Simplex Direct Search Algorithm and chi-square values to estimate the model parameters. we calculate ℛ0 = 3.6429 when the number of beds in the Fangcang shelter hospital is relatively tight in the second stage and ℛ0 = 0.4974 in the fifth stage when there are enough beds in both Fangcang shelter hospital and designated hospital. Then we perform a sensitivity analysis on ℛ0 by using perturbation of fixed point estimation of model parameters in the fifth stage, and obtain three parameters that are more sensitive to ℛ0, which are transmission rate (ß 1d ), proportion of the infectious (η) and the hospitalization rate of asymptomatic infected cases (δ 1). Through simulation, we obtain that if the hospitalization rate of asymptomatic infections δ 2 > 0.9373 or the transmission rate ß 1b  < 0.0467, the second stage of Omicron transmission in Shanghai can be well controlled. Finally, we find the measure that converting the National Convention and Exhibition Center (NECC) into a Fangcang shelter hospital has played an important role in curbing the epidemic. Whether this temporary Fangcang shelter hospital is not built or delayed, the cumulative number of confirmed cases will both exceed 100,000, and the cumulative asymptomatic infections will both exceed 1 million. In addition, for a city of 10 million people, we obtain that if a permanent Fangcang shelter hospital with 17,784 beds is built ahead of epidemic, there will be no shortage of beds during the outbreak of Omicron. Our findings enrich the content of the impact of Fangcang shelter hospital beds on the spread of Omicron and confirm the correct policy adopted by the Chinese government.

Endowing Covalent Organic Frameworks with Photoresponsive Active Sites for Controllable Propylene Adsorption.

Photoresponsive covalent organic frameworks (PCOFs) have emerged as attractive candidates for adsorption, but it is challenging to construct PCOF adsorbents due to structural order loss of covalent organic frameworks (COFs) after introducing photoresponsive motifs and/or tedious steps of postmodification. Here, a facile strategy is developed, by dispersing photoresponsive metal-organic polyhedra (PMOP) into COFs, to endow COFs with photoresponsive adsorption sites. As a proof-of-concept study, a COF with pore size of 4.5 nm and PMOP with suitable molecular size (4.0 and 3.1 nm for trans and cis configuration, respectively) are selected to meet the requirements of proper accommodation space, good guest dispersion, and free isomerization. The structure of COF is well preserved after introducing PMOPs. Interestingly, the obtained photoresponsive host-guest composite (PHGC) adsorbents exhibit photomodulated adsorption capacity on propylene (C3 H6 ) and the change in adsorption capacity can reach up to 43.3% and is stable during multiple cycles. Density functional theory calculations reveal that visible-light irradiation drives the azobenzene motifs in PHGCs to the trans configuration and the adsorption sites are fully open and interact with C3 H6 . UV-light irradiation makes the azobenzene motifs transform to the cis configuration, leading to the shield of the adsorption sites and the consequent release of C3 H6 .

Linear analysis of Atwood number effects on shear instability in the elastic-plastic solids.

The evolution of shear instability between elastic-plastic solid and ideal fluid which is concerned in oblique impact is studied by developing an approximate linear theoretical model. With the velocities expressed by the velocity potentials from the incompressible and irrotational continuity equations and the pressures obtained by integrating momentum equations with arbitrary densities, the motion equations of the interface amplitude are deduced by considering the continuity of normal velocities and the force equilibrium with the perfectly elastic-plastic properties of solid at interface. The completely analytical formulas of the growth rate and the amplitude evolution are achieved by solving the motion equations. Consistent results are performed by the model and 2D Lagrange simulations. The characteristics of the amplitude development and Atwood number effects on the growth are discussed. The growth of the amplitude is suppressed by elastic-plastic properties of solids in purely elastic stage or after elastic-plastic transition, and the amplitude oscillates if the interface is stable. The system varies from stable to unstable state as Atwood number decreasing. For large Atwood number, elastic-plastic properties play a dominant role on the interface evolution which may influence the formation of the wavy morphology of the interface while metallic plates are suffering obliquely impact.

Abscisic acid (ABA)-importing transporter 1 (AIT1) contributes to the inhibition of Cd accumulation via exogenous ABA application in Arabidopsis.

Soil cadmium (Cd) accumulation presents risks to crop safety and productivity. However, through an exogenous application of abscisic acid (ABA), its accumulation in plants can be reduced and its toxicity mitigated, thereby providing an alternative strategy to counteract Cd contamination of arable soil. In the present study, we demonstrated that exogenous ABA application alleviates Cd-induced growth inhibition and photosynthetic damage in wild-type (Col-0) Arabidopsis plants. However, these positive effects were weakened in the ABA-importing transporter (AIT1)-deficient mutant (ait1). Through further analysis, we found that upon ABA application, the decrease in Cd level significantly differed among ait1, Col-0, and the two AIT1-overexpressing transgenic plants (AIT1ox-1 and AIT1ox-2), suggesting that AIT1 mediates the Cd-reducing effects of ABA. ABA application also inhibited the expression of IRT1, ZIP1, ZIP4, and Nramp1 in Col-0 plants subjected to Cd stress. However, significant differences among the genotypes (ait1, Col-0 and AIT1ox) were only observed in terms of IRT1 expression. Overall, our findings suggest that the suppression of Cd accumulation and restoration of plant growth by exogenous ABA require the ABA-importing activity of AIT1 to inhibit IRT1 expression.

Machine Learning Topological Phases with a Solid-State Quantum Simulator.

We report an experimental demonstration of a machine learning approach to identify exotic topological phases, with a focus on the three-dimensional chiral topological insulators. We show that the convolutional neural networks-a class of deep feed-forward artificial neural networks with widespread applications in machine learning-can be trained to successfully identify different topological phases protected by chiral symmetry from experimental raw data generated with a solid-state quantum simulator. Our results explicitly showcase the exceptional power of machine learning in the experimental detection of topological phases, which paves a way to study rich topological phenomena with the machine learning toolbox.

FKBP51 is associated with early postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgery.

Enhanced inflammation response was increasingly reported in association with postoperative cognitive dysfunction (POCD). Glucocorticoid receptor (GR) signal plays a key role in suppression of inflammation. This prospective cohort study aimed to evaluate GR signaling in elderly patients undergoing selective operation.One hundred twenty-six elderly patients were scheduled for hip fracture surgery with general anesthesia. Plasma cortisol levels and the expression levels of GR and FK506 binding protein 51 (FKBP51) in leukocytes were determined at 1 day preoperatively and 7 days. Postoperatively postoperative pain was assessed following surgery using visual analog pain scale (VAS). Neuropsychological tests were performed before surgery and 1 week postoperation. A decline of 1 or more standard deviations in 2 or more tests was considered to reflect POCD.POCD incidence in participants was 28.3% at 1 week after surgery. POCD patients presented significantly higher cortisol and FKBP51 levels compared with non-POCD patients (P < .05). Compared with non-POCD patients, VAS scores at 12 hours after surgery were higher in POCD patients (P < .05). No significant difference in expression levels of GR was found between groups POCD and non-POCD patients.High expression of FKBP51 in leukocytes and glucocorticoid resistance were associated with POCD in aged patients following hip fracture surgery.

Weyl Exceptional Rings in a Three-Dimensional Dissipative Cold Atomic Gas.

Three-dimensional topological Weyl semimetals can generally support a zero-dimensional Weyl point characterized by a quantized Chern number or a one-dimensional Weyl nodal ring characterized by a quantized Berry phase in the momentum space. Here, in a dissipative system with particle gain and loss, we discover a new type of topological ring, dubbed a Weyl exceptional ring consisting of exceptional points at which two eigenstates coalesce. Such a Weyl exceptional ring is characterized by both a quantized Chern number and a quantized Berry phase, which are defined via the Riemann surface. We propose an experimental scheme to realize and measure the Weyl exceptional ring in a dissipative cold atomic gas trapped in an optical lattice.

Quantum Supremacy for Simulating a Translation-Invariant Ising Spin Model.

We introduce an intermediate quantum computing model built from translation-invariant Ising-interacting spins. Despite being nonuniversal, the model cannot be classically efficiently simulated unless the polynomial hierarchy collapses. Equipped with the intrinsic single-instance-hardness property, a single fixed unitary evolution in our model is sufficient to produce classically intractable results, compared to several other models that rely on implementation of an ensemble of different unitaries (instances). We propose a feasible experimental scheme to implement our Hamiltonian model using cold atoms trapped in a square optical lattice. We formulate a procedure to certify the correct functioning of this quantum machine. The certification requires only a polynomial number of local measurements assuming measurement imperfections are sufficiently small.