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Monolayer group IVA metal halides have attracted intensive attention for their excellent thermoelectric performance. Recently, the CdI2-type SnI2 monolayer has been successfully fabricated by molecular beam epitaxy for the first time. The universal two-dimensional growth behavior on different substrates, motivates strain engineering on its thermoelectric performance. Herein, the structure stability and thermoelectric properties of SnI2 monolayer under different strains are systematically investigated, based on first-principles calculations combined with Boltzmann transport theory. The investigation shows that the tensile strain can simultaneously induce phonon mode softening and band convergence, resulting in a significant enhancement in thermoelectric performance. The phonon mode softening for ZA and optical branches further enhances lattice anharmonicity and a reduced thermal conductivity of ∼0.14 Wm−1K−1 at 300 K (∼0.05 Wm−1K−1, 800 K) can be obtained. Additionally, band convergence in valence band improves the Seebeck coefficient and increases power factor. Under +2 % tensile strain, the optimal ZT values of SnI2 monolayer for p-type doping are substantially enhanced up to 3.05 (300 K) and 5.06 (800 K), which are increased by ∼98 % and ∼50 % compared to the case without strain. Our results reveal the close relationship between the phonon mode softening and enhanced anharmonicity, and provide the physical insights into the understanding of the modulation of thermoelectric properties of monolayer SnI2, shedding light on substantially optimizing the thermoelectric performance of monolayer group IVA metal halides family.

Abstract Background The chimeric antigen receptor (CAR)-T therapy has a limited therapeutic effect on solid tumors owing to the limited CAR-T cell infiltration into solid tumors and the inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Macrophage is an important component of the innate and adaptive immunity, and its unique phagocytic function has been explored to construct CAR macrophages (CAR-Ms) against solid tumors. This study aimed to investigate the therapeutic application of CAR-Ms in ovarian cancer. Methods In this study, we constructed novel CAR structures, which consisted of humanized anti-HER2 or CD47 scFv, CD8 hinge region and transmembrane domains, as well as the 4-1BB and CD3ζ intracellular domains. We examined the phagocytosis of HER2 CAR-M and CD47 CAR-M on ovarian cancer cells and the promotion of adaptive immunity. Two syngeneic tumor models were used to estimate the in vivo antitumor activity of HER2 CAR-M and CD47 CAR-M. Results We constructed CAR-Ms targeting HER2 and CD47 and verified their phagocytic ability to ovarian cancer cells in vivo and in vitro. The constructed CAR-Ms showed antigen-specific phagocytosis of ovarian cancer cells in vitro and could activate CD8+ cytotoxic T lymphocyte (CTL) to secrete various anti-tumor factors. For the in vivo model, mice with human-like immune systems were used. We found that CAR-Ms enhanced CD8+ T cell activation, affected tumor-associated macrophage (TAM) phenotype, and led to tumor regression. Conclusions We demonstrated the inhibition effect of our constructed novel HER2 CAR-M and CD47 CAR-M on target antigen-positive ovarian cancer in vitro and in vivo, and preliminarily verified that this inhibitory effect is due to phagocytosis, promotion of adaptive immunity and effect on tumor microenvironment.

Abstract Although there have been studies correlating DYRK2 with a number of human cancers, there has been no pan-cancer analysis. Therefore, through the TCGA database, we conducted a related study on the expression of DYRK2 in cancers.The expression of DYRK2 is obviously increased in some cancers, while the opposite is true in others, and there is a clear association between its expression and the prognosis of cancer patients.The mutation of DYRK2 is also significantly correlated with patients’ prognosis in certain human tumors. In addition, phosphorylation and methylation levels of DYRK2 are different between tumor tissues and adjacent normal tissues in various tumors. In the tumour microenvironment, the expression of DYRK2 correlates with cancer-associated fibroblast infiltration, such as BLCA or HNSC. In order to fully understand the role of DYRK2 in different tumors, we conducted a pan-cancer analysis.

Since the implementation of changing coal into clean energy heating in the Beijing–Tianjin–Hebei region, there has been a tremendous change in terms of air quality during the winter in the north. On the basis of field research for resort sample room setting up in the Yanqing district , Beijing, this paper mainly expounds the cold and heat sources and system solutions used by resort villas to meet the needs of hot water, heating, and cooling throughout the year, and introduces a new type of solar energy ‘The heat pump direct floor radiant heating system’ (called “Trinity”), which can combine air source heat pump-solar system and direct floor radiant heating to ensure the efficient and stable operation of the heating system while making full use of solar energy. Moreover, with the combination of modeling analysis on the annual load via DeST software, the result of actual measurement sees “Trinity” system as the optimal solution not only by means of comparing the heating scheme of the original single air source heat pump unit and the solar energy + air source heat pump unit’s simulation comparison, it was concluded that the initial investment of scheme two was 16,969 yuan and the initial investment of scheme two was 17,352 yuan. The annual operating cost of the second option is 3577.8 yuan, and the annual operating cost of the second option is only about one-half of the annual operating cost of the second option. Based on the calculation of the investment recovery period, the cost savings of the second option after only 0.15 years is net income. Therefore, the “Trinity” scheme is selected as the best scheme.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a significant and far-reaching impact on mental health. The psychiatric emergency department (PED) is pivotal in the management of acute and severe mental illnesses, especially anxiety-and stress-related disorders.AimsThis study aimed to evaluate whether changes in the frequency or patients’ demographics of visiting the PED occurred during the COVID-19 pandemic among individuals with anxiety and stress-related disorders.MethodsThis cross-sectional study used data on PED visit counts from the largest psychiatric hospital in China between 2018 and 2020 (before and during the COVID-19 pandemic). Data from 2020, representing the COVID-19 pandemic period, were extracted from electronic medical records and compared using descriptive statistics for the same periods in 2018 and 2019.ResultsThe number of PED visits related to anxiety and stress disorders per year increased from 83 in 2018 to 136 (63.9% increase) in 2019 and 239 (188.0% increase) in 2020. Compared to that in 2018 and 2019, the proportion of PED visits in 2020 among patients with anxiety and stress disorders increased significantly. Patients with anxiety-and stress-related disorders during PED visits in 2020 were younger than those in 2018 and 2019 (three-year groups: F = 9.124, df = 2, p

Background: Accumulating evidence shows that DNA methylation plays a role in antipsychotic response. However, the mechanisms by which DNA methylation changes are associated with antipsychotic responses remain largely unknown.Methods: We performed a methylome-wide association study (MWAS) to evaluate the association between DNA methylation and the response to risperidone in schizophrenia. Genomic DNA methylation patterns were assessed using the Agilent Human DNA Methylation Microarray.Results: We identified numerous differentially methylated positions (DMPs) and regions (DMRs) associated with antipsychotic response. CYP46A1, SPATS2, and ATP6V1E1 had the most significant DMPs, with p values of 2.50 × 10–6, 3.53 × 10–6, and 5.71 × 10–6, respectively. The top-ranked DMR was located on chromosome 7, corresponding to the PTPRN2 gene with a Šidák-corrected p-value of 9.04 × 10–13. Additionally, a significant enrichment of synaptic function and neurotransmitters was found in the differentially methylated genes after gene ontology and pathway analysis.Conclusion: The identified DMP- and DMR-overlapping genes associated with antipsychotic response are related to synaptic function and neurotransmitters. These findings may improve understanding of the mechanisms underlying antipsychotic response and guide the choice of antipsychotic in schizophrenia.

PU.1, a transcription factor member of the E26 transformation-specific family, affects the function of a variety of immune cells in several physiological and pathological conditions. Previous studies studying the role of PU.1 in pathological conditions have mainly focused on immune system-related cancers, and a series of articles have confirmed that PU.1 mutation can induce a variety of immune cell-related malignancies. The underlying mechanism has also been extensively validated. However, the role of PU.1 in other major immune system-related diseases, namely, systemic autoimmune diseases, is still unclear. It was only in recent years that researchers began to gradually realize that PU.1 also played an important role in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE). This review article summarizes the findings of recent studies that investigated the role of PU.1 in various autoimmune diseases and the related underlying mechanisms. Furthermore, it presents new ideas and provides insight into the role of PU.1 as a potential treatment target for autoimmune diseases and highlights existing research problems and future research directions in related fields.

Crocin, the main biologically active carotenoid of saffron, generally is derived from the dried trifid stigma of Crocus sativus L. Many studies have demonstrated that crocin has several therapeutic effects on biological systems through its anti-oxidant and anti-inflammatory properties. The wide range of crocin activities is believed to be because of its ability to anchor to many proteins, triggering some cellular pathways responsible for cell proliferation and differentiation. It also has therapeutic potentials in arthritis, osteoarthritis, rheumatoid arthritis, and articular pain probably due to its anti-inflammatory properties. Anti-apoptotic effects, as well as osteoclast inhibition effects of crocin, have suggested it as a natural substance to treat osteoporosis and degenerative disease of bone and cartilage. Different mechanisms underlying crocin effects on bone and cartilage repair have been investigated, but remain to be fully elucidated. The present review aims to undertake current knowledge on the effects of crocin on bone and cartilage degenerative diseases with an emphasis on its proliferative and differentiative properties in mesenchymal stem cells.

A new and simple method based on the frequency-sweep method for measuring the frequency response of broadband optoelectronic devices is demonstrated. The electro-absorption modulator (EAM) can function as both modulator and receiver with the same frequency response. With this property, the frequency responses of a distributed feedback (DFB) laser at different bias currents were measured from dc to 20 GHz by the method. The results were quite identical with the results measured by the frequency-sweep method with broadband photodetector. Besides, the measurement bandwidth is not limited by the bandwidths of the devices, and the results are not influenced by the bandwidths of the EAM or other devices.

Recent experiments indicated that both layered Bi _2 O _2 Se and Bi _2 O _2 Te are promising thermoelectric materials with low thermal conductivities. However, theoretical study on the thermoelectric properties, especially the phonon transport properties, is rare. In order to understand the thermoelectric transport mechanism, we here investigate the electron and phonon transport properties by using the first-principles calculations combined with the Boltzmann transport theory. Our results indicate that both Bi _2 O _2 Se and Bi _2 O _2 Te are semiconductors with indirect energy gaps of 0.87 eV and 0.21 eV within spin–orbit coupling, respectively. Large Seebeck coefficient and power factor are found in the p -type than the n -type for both compounds. Low lattice thermal conductivities at room temperature are obtained, 1.14 W m ^−1 K ^−1 for Bi _2 O _2 Se and 0.58 W m ^−1 K ^−1 for Bi _2 O _2 Te, which are close to the experimental values. It is found that the low-frequency optical phonon branches with higher group velocity and longer lifetime also make a main contribution to the lattice thermal conductivity. Interestingly, the lattice thermal conductivity exhibits obvious anisotropy especially for Bi _2 O _2 Te. These results are helpful for the understanding and optimization of thermoelectric performance of layered Bi _2 O _2 Se and Bi _2 O _2 Te.

The purpose of the present study was to determine the in vitro and in vivo anti-cancer activity and pharmacological properties of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, KCN1. In the present study, we investigated the in vitro activity of KCN1 on cell proliferation and cell cycle distribution of pancreatic cancer cells, using the MTT and BrdUrd assays, and flow cytometry. The in vivo anti-cancer effects of KCN1 were evaluated in two distinct xenograft models of pancreatic cancer. We also developed an HPLC method for the quantitation of the compound, and examined its stability in mouse plasma, plasma protein binding, and degradation by mouse S9 microsomal enzymes. Furthermore, we examined the pharmacokinetics of KCN1 following intravenous or intraperitoneal injection in mice. Results showed that, in a dose-dependent manner, KCN1 inhibited cell growth and induced cell cycle arrest in human pancreatic cancer cells in vitro, and showed in vivo anticancer efficacy in mice bearing Panc-1 or Mia Paca-2 tumor xenografts. The HPLC method provided linear detection of KCN1 in all of the matrices in the range from 0.1 to 100 µM, and had a lower limit of detection of 0.085 µM in mouse plasma. KCN1 was very stable in mouse plasma, extensively plasma bound, and metabolized by S9 microsomal enzymes. The pharmacokinetic studies indicated that KCN1 could be detected in all of the tissues examined, most for at least 24 h. In conclusion, our preclinical data indicate that KCN1 is a potential therapeutic agent for pancreatic cancer, providing a basis for its future development.

Expression of p53 appears to be correlated to prognosis in patients with malignancy, but its role in gastric carcinoma has remained controversial. Recently we reported that JWA, an ADP-ribosylation-like factor 6 interacting protein 5 (ARL6ip5), was both prognostic for overall survival and predictive for platinum-based treatment of gastric cancer. In this study, we aimed to investigate p53 expression as a prognostic and predictive marker in resectable gastric cancer, alone and in combination with JWA. Expression of p53 was examined in three large patient cohorts (total n=1155) of gastric cancer. High expression of p53 was significantly correlated with unfavorable clinicopathologic parameters and decreased overall patient survival. Furthermore, patients with high p53 expression in tumors acquired remarkable survival benefit from adjuvant first-line platinum-based-chemotherapy. The synergy between p53 and JWA in predicting patient outcome was demonstrated, while no significantly elevated predictive value concerning chemotherapy was observed. Thus, p53 expression is a potent prognostic and predictive factor for resectable gastric cancer with adjuvant platinum-based chemotherapy. A combined effect of p53 with JWA as efficient prognostic indicators was found for the first time.