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A 4H‐SiC trench metal–oxide–semiconductor field‐effect‐transistor (MOSFET) design with an integrated merged PiN Schottky (MPS) diode is proposed. The Schottky contact is embedded on the bottom of the trench structure for the first time. The low electric field in the oxide and Schottky contact surface can be achieved simultaneously using the proposed integration design which enhances the oxide reliability and reduces leakage from the Schottky diode. The integration of the MPS diode reduces the total chip area and the required number of dies compared with the conventional method of using an external Schottky diode. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) often results in the production and accumulation of adenosine (ADO), a byproduct that negatively impacts the therapeutic effect as well as facilitates tumor development and metastasis. Here, an innovative strategy is elaborately developed to effectively activate ICD while avoiding the generation of immunosuppressive adenosine. Specifically, ZIF-90, an ATP-responsive consumer, is synthesized as the core carrier to encapsulate AB680 (CD73 inhibitor) and then coated with an iron-polyphenol layer to prepare the ICD inducer (AZTF), which is further grafted onto prebiotic bacteria via the esterification reaction to obtain the engineered biohybrid (Bc@AZTF). Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (αPD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism., (© 2024 Wiley‐VCH GmbH.)

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

Tertiary lymphoid structures (TLSs) primarily constructed by multiple immune cells can effectively enhance tumor immune responses, but expediting the formation of TLSs is still an enormous challenge. Herein, a stimulator of interferon gene (STING)-activating hydrogel (ZCCG) was elaborately developed by coordinating Zn 2+ with 4,5-imidazole dicarboxylic acid, and simultaneously integrating chitosan (a stimulant of STING pathway activation) and CpG (an agonist of toll-like receptor 9, TLR9) for initiating and activating cGAS-STING and TLR9 pathway-mediated immunotherapy. Moreover, the dual-pathway activation could effectively enhance the infiltration of immune cells and the expression of lymphocyte-recruiting chemokines in the tumor microenvironment (TME), thereby promoting the formation of TLSs and further strengthening tumoricidal immunity. Local administration of the hydrogel could prime systemic immune responses and long-term immune memory and improve the therapeutic effects of programmed death-1 antibody (αPD-1) to inhibit tumor progression, metastasis and recurrence. The engineered hydrogel lays the foundation for tumor immunotherapy strategies based on the enhanced formation of TLSs via the activation of the cGAS-STING and TLR9 pathways.

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO 3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8 + T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.

Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self-assembled from Fe(II), unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll-like receptor 9, induces the production of pro-inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune-related processes to achieve optimal antitumor immunotherapy., (© 2023 Wiley-VCH GmbH.)

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity, but specific activation of STING pathway is still an enormous challenge. Herein, a ferroptosis-induced mitochondrial DNA (mtDNA)-guided tumor immunotherapy nanoplatform (designated as HBMn-FA) was elaborately developed for activating and boosting STING-based immunotherapy. On the one hand, the high-levels of reactive oxygen species (ROS) in tumor cells induced by HBMn-FA-mediated ferroptosis elicited mitochondrial stress to cause the release of endogenous signaling mtDNA, which specifically initiate cGAS-STING pathway with the cooperation of Mn 2+ . On the other hand, the tumor-derived cytosolic double-stranded DNA (dsDNA) from debris of death cells caused by HBMn-FA further activated the cGAS-STING pathway in antigen-presenting cells (e.g., DCs). This bridging of ferroptosis and cGAS-STING pathway could expeditiously prime systemic antitumor immunity and enhance the therapeutic efficacy of checkpoint blockade to suppress tumor growth in both localized and metastatic tumor models. The designed nanotherapeutic platform paves the way for novel tumor immunotherapy strategies that are based on specific activation of STING pathway., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Heat shock proteins (HSPs), which have a variety of functions, are one of the stress protein families. In recent years, They have been reported to play a dual role in hepatitis B virus (HBV) which as persistent infection which is associated with, cirrhosis and liver cancer. In this article, we have summarized the regulatory mechanisms between HSPs and viruses, especially HBV and associated diseases based on HSP biological functions of in response to viral infections. In view of their potential as broad-spectrum antiviral targets, we have also discuss current progress and challenges in drug development based on HSPs, as well as the potential applications of agents that have been evaluated clinically in HBV treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: KIF23 is a member of kinesin family, recent researches indicate KIF23 plays an important role in the proliferation and migration of malignant cancer cells. While the function and specific molecule mechanism of KIF23 in triple negative breast cancer remains unclear., Methods: QRT-PCR and immunohistochemistry were conducted to analyze expression of KIF23 in triple negative breast cancer tissues and paired paracancer tissues. CCK-8 assay, colony formation assay, wound healing assay and transwell assay were applied for exploring phenotype changing of triple negative breast cancer cell lines MDA-MB-231 and BT549 after siRNA-induced knockdown of KIF23. Several bioinformatic databases were used for predicting miRNAs that combing with KIF23 mRNA and verified by dual luciferase reporter assay. Western blot assay was performed to explore downstream signaling pathway of KIF23., Results: KIF23 was overexpressed in triple negative breast cancer, knockdown of KIF23 by siRNA inhibited proliferation and migration of TNBC cell lines MDA-MB-231 and BT549. Mechanistically, knockdown of KIF23 resulted in the suppression of Epithelial-Mesenchymal Transition. Meanwhile, miR-195-5p was downregulated in TNBC, and dual luciferase reporter assay indicated miR-195-5p could combine with 3'UTR of KIF23 thus promoting degradation of KIF23., Conclusions: KIF23 is a potential oncogene in triple negative breast cancer, miR-195-5p could combine with 3'UTR of KIF23. Our study reveals a new sight into triple negative breast cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-19). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Antibiotics contribute a lot to human beings and can kill bacteria effectively. However, more and more studies show that antibiotics can disturb the intestinal microbial community. It has been widely reported that oral antibiotics can reduce the diversity of intestinal microflora, but the effect of intramuscular injection on intestinal microflora is less studied. In this study, we sequenced the intestinal microflora of mice treated with tetracycline by 16SrRNA method, and found that intramuscular injection of tetracycline (TET) can also reduce the intestinal microbial richness of mice. In addition, the results showed that within a certain range (3 mg), with the increase of TET injection concentration, the wind of intestinal microflora in mice decreased significantly. When the injection concentration reached saturation, although the amount of TET injection was increased, the degree of intestinal flora affected was not increased. The results showed that the degree of diversity decrease was in direct proportion to the amount of tetracycline injection in the saturated concentration, but not positively related to the high amount of TET injection after exceeding the saturated concentration.

A 13.5 kV 4H-SiC PiN rectifier with a considerable active area of 0.1 cm 2 is fabricated in this paper. Charge-field-modulated junction termination extension (CFM-JTE) has been proposed for satisfying the requirement of ultra-high reverse voltage, which enlarges the JTE dose tolerance window, making it approximately 2.8 times that of the conventional two-zone JTE. Besides, the CFM-JTE can be implemented through the conventional two-zone JTE process. The measured forward current is up to 100 A @ V F  = 5.2 V in the absence of carrier lifetime enhancement technology. The CFM-JTE structure accomplishes 96% of the theoretical breakdown voltage of the parallel plane junction with a relatively small terminal area of 400 μm, which contributes to achieving the Baliga's figure of merit of 58.8 GW/cm 2 .

In this study, we designed a novel ultra-wideband (UWB) absorber and numerically analyzed it to demonstrate that its light absorptivity was greater than 90% in the wavelength range of visible light and near-infrared (405-1505 nm). The structure of proposed novel UWB absorber consisted of four layers of films, including silica, titanium, magnesium fluoride, and aluminium, and the upper silica and titanium layers had rectangular cubes in them. For that, the excitations of propagating surface plasmon resonance (PSPR), local surface plasmon resonance (LSPR), and the resonance of Fabry-Perot (FP) cavity were generated at the same time and combined to reach the effect of perfect absorption and ultra-wideband. The proposed absorber had an average absorptivity of 95.14% in the wavelength range of 405 ∼ 1505 nm when the light was under normal incidence. In addition, the UWB absorber was large incident angle insensitive and polarization-independent. The absorber proposed in the paper had great prospects in the fields of thermal electronic equipment, solar power generation, and perfect cloaking.

Endometrial cancer (EC) is generally considered as a disease that affects older women. We attempt to explore the role of actin‑like protein 8 (ACTL8) in EC and how it achieves its function. Based on the data from The Cancer Genome Atlas (TCGA), we found that ACTL8 expression was up-regulated in EC tissues and correlated with shorter overall survival of EC patients. ACTL8 expression was significantly associated with age, clinical-stage, or grade. Cox proportional hazards model analysis revealed that ACTL8 expression, grade, and clinical-stage were promising independent prognostic factors of EC. Knockdown of ACTL8 repressed the proliferative, migrating and invading capabilities of human EC cell lines KLE and Ishikawa. Silencing ACTL8 up-regulated the negative cell cycle regulator p21 and epithelial marker E-cadherin, and down-regulated the positive cell cycle regulator Cyclin A, mesenchymal markers MMP-9 and N-cadherin in KLE cells. Collectively, these outcomes illustrated that ACTL8 might act as a tumor facilitator during EC progression.

Objectives: Degenerative changes of endplates in older patients and tilting of vertebral body in lumbosacral lordosis could make an accurate identification of endplates for the Cobb measurement difficult. Pedicles have been proposed as alternative landmarks because they are usually better visualized, and offer similar clinical validity to the endplates. The objective of this study was to investigate the reliability of the pedicle method of Cobb measurement in degenerative lumbar scoliosis and compare it with the traditional endplate method., Methods: Two hundred and eighty-four radiographs of degenerative lumbar scoliosis were evaluated. The radiographs were classified into groups based on the patient's age (< 60 years, 60 to 80 years, and > 80 years), level of lower end vertebra (LEV) (LEV at L5, and LEV at or above L4), and curve severity (< 20°, 20° to 40°, and > 40°). Three observers independently measured the radiographs using the endplate and pedicle methods twice with an interval of 1 week. The intra- and interobserver reliabilities were calculated using intraclass correlation coefficients (ICC)., Results: The intra- and interobserver ICC values were better for all observers in the > 80 years age group using the pedicle method. The intraobserver ICC values of pedicle method were also better in the LEV at L5 group, and the interobserver ICC values showed a slightly better consistency with the pedicle method. For patients with > 40° curves, the intraobserver ICC values for all observers as well as interobserver ICC values were better using the endplate method., Conclusion: The reliabilities of the endplate and pedicle methods for degenerative lumbar scoliosis were both excellent. The pedicle method might be better in older patients (> 80 years) and those with LEV at L5; while the endplate method could have some strength in severe cases (> 40°).

The title salt, (C(6)H(11)N(2))(2)[Cd(C(7)H(3)NO(4))(2)], displays a discrete mononuclear structure, in which the central Cd(II) atom is six-coordinated in a distorted octa-hedral coordination geometry by two N and four O atoms from two different pyridine-2,6-dicarboxyl-ate anions in an O(2),N,O(6)-tridentate chelation mode. The crystal packing is stabilized by N-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance = 3.576 (5) Å].

The title compouand {[Zn(C(4)H(4)O(6))(C(12)H(8)N(2))]·6H(2)O}(n), has a linear chain structure parallel to [100] with Zn(C(4)H(4)O(6))(C(12)H(8)N(2)) repeat units; the asymmetric unit consists of one Zn(2+) cation, one l-tartrate dianion, one 1,10-phenanthroline and six free water mol-ecules. The Zn atom is in a distorted octa-hedral ZnN(2)O(4) coordination environment. The crystal structure is stabilized by O-H⋯O hydrogen bonds and π-π stacking of the phenanthroline units [centroid-centroid distances in the range 3.552 (2)-3.625 (2)Å] occurs between the chains. The title compound is isotypic with the Cu and Mn analogues.

In the pseudo-centrosymmetric mol-ecule of the title compound, C(18)H(16)N(4), two benzimidazole fragments form the dihedral angles of 83.49 (7) and 79.37 (7)°, with the mean plane of the linking butene chain. No classical inter-molecular inter-actions are observed. The porous crystal packing exhibits voids of 85 Å(3).

In the title compound, [Mn(C(10)H(10)N(2))(6)](ClO(4))(2), the Mn(II) ion, located on an inversion center, is coordinated by six N atoms from three pairs of symmetry-related 1-benzyl-1H-imidazole ligands in a distorted octa-hedral geometry. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the complex cations and perchlorate anions.

In the dication of the title compound, C(16)H(20)N(4) (2+)·C(10)H(4)O(8) (2-)·H(2)O, the dihedral angles formed by mean planes of the imidazolium rings and the benzene ring are 69.05 (18) and 89.1 (2)°. In the crystal, the components are linked into a three-dimensional network by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds.

The title compound, [Cu(2)(C(7)H(3)NO(4))(2)(C(12)H(12)N(6))(H(2)O)(2)]·H(2)O, displays a discrete dinuclear structure, in which the central Cu(II) atom is five-coordinated in a distorted square-based pyramidal coordination geometry and the flexible ligand 1,4-bis-(1,2,4-triazol-1-ylmeth-yl)benzene adopts a bis-monodentate bridging mode linking the Cu(II) atoms. It is further assembled by O-H⋯O hydrogen-bond inter-actions involving both the coordinated and uncoordinated water molecules. The latter exhibits half-occupancy.

In the title compound, C(14)H(14)N(4), the center of the phenyl-ene group is a crystallographic center of inversion. The compound is composed of three aromatic rings displaying a Z-like conformation. The dihedral angle between the pyrazole rings and the central phenyl ring is 83.84 (9)°.

Objective: This study intends to summarize 5 years of intraoperative hybrid procedure (IHP) experience with neonates and young children having congenital heart disease (CHD)., Methods: From March 2003 to March 2009, a total of 152 consecutive patients younger than 2 years old who had undergone IHP were enrolled. In the balloon plasty group (n = 72), transventricular pulmonary valvuloplasty, or transaortic balloon dilatation were performed for pulmonary atresia, pulmonary stenosis, or coactation of the aorta. In the device group (n = 43), transventricular device closure was performed for ventricular septal defect (VSD), or transatrial device closure for atrial septal defect (ASD). In the collateral arteries occlusion group (n = 37), the major aortopulmonary collateral arteries (MPCAs) were occluded with coils for tetralogy of Fallot or other cyanotic CHDs. All procedures were image guided and performed in a specially designed hybrid operation room. All surviving patients were followed up, and the major adverse cardiovascular events that occurred were recorded., Results: In the balloon plasty group, all patients received successful transventricular valvuloplasty or transaortic balloon angioplasty. However, severe right ventricle outflow obstruction was observed in 2 cases. One patient was transferred to regular open-heart surgery immediately, and another underwent regular open-heart procedure after discharge. Furthermore, 1 neonate with pulmonary atresia with intact ventricular septum died from liver failure 6 months after IHP. In the device closure group, the device closure failed to be performed in 3 cases (2 with ASD and 1 with VSD). One young child with VSD died from pneumonia, even after successful device closure. No device malposition was observed in the device closure group during follow-up. All patients who received MPCA occlusion and associated open-heart correction were eventually discharged., Conclusion: IHP could avoid or shorten the application of cardiopulmonary bypass and reduce surgical trauma for selected young children with CHD. Although IHP is feasible and safe, the image outfits, image-guided technology, and IHP-related devices should be developed and improved.

Venomous animals possess an arsenal of toxins for predation and defense. These toxins have great diversity in function and structure as well as evolution and therefore are of value in both basic and applied research. Recently, toxinomics researches using cDNA library sequencing and proteomics profiling have revealed a large number of new toxins. Although several previous groups have attempted to manage these data, most of them are restricted to certain taxonomic groups and/or lack effective systems for data query and access. In addition, the description of the function and the classification of toxins is rather inconsistent resulting in a barrier against exchanging and comparing the data. Here, we report the ATDB database and website which contains more than 3235 animal toxins from UniProtKB/Swiss-Prot and TrEMBL and related toxin databases as well as published literature. A new ontology (Toxin Ontology) was constructed to standardize the toxin annotations, which includes 745 distinct terms within four term spaces. Furthermore, more than 8423 TO terms have been manually assigned to 2132 toxins by trained biologists. Queries to the database can be conducted via a user-friendly web interface at http://protchem.hunnu.edu.cn/toxin.

Aim: To compare the efficacy of a combined chemotherapy regimen of 5-fluouracil (5-FU) and adriamycin (ADM) with nimustine hydrochloride (ACNU; brand name Nidran), a new nitrosourea agent, or with methyl-CCNU for advanced gastric cancer., Methods: One-hundred-and-three cases of advanced gastric cancer were randomly allocated into Group A (Me-CCNU, 5-FU and ADM combination) and Group B (ACNU, 5-FU and ADM combination). The quality of life (QOL) questionnaire, composed of 11 ordinal categorical items, was used to collect data from these patients., Results: Group A had no case of complete remission (CR) or partial remission (PR), while Group B had no CR but 8 PR (8/46 cases), for a response rate of 0% in Group A and 17.4% in Group B. The median survival time in Group A was 108 d and in Group B was 112 d. Both groups tolerated the treatment well and there were no serious adverse effects. QOL evaluations showed better psychological and physical feelings of tiredness for Group B than for Group A, and scores based on facial scaling showed a more pleasant inclination for the former., Conclusion: ACNU combination is superior to the Me-CCNU combination for advanced gastric cancer patients.