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The interactions between the carbon skeleton and the metal atoms of a binary transition metal carbide (BTMC) are particular interest for industrial applications with openning physics and chemitry questions, especially in magnetoelectric (ME) functional materials and cemented carbides. Chromium and carbon BTMCs are a series of intermetallic compounds with typical chemical formulas and sharepolycrystalline powder c somehromium special characteristics.and carbon as precursors, In this paper,and synthesized s we usedingle-phase bluk Cr7C3 (orthorhombic, with space group: Pnma) with high density and good crystallinity by means of high-temperature and high-pressure quenching method (HTHPQM). We studied the material properties and electronic structures of Cr7C3studied with both experimental measurements and Density Functional Theory (DFT) ab intio simulations, and found that Cr7C3 is acompaction conductor(97.2 %), with anexcellent electrical conductivitythermostability (oxidation (2.32 10×at 1175 -3K)Ω·m), relative highand a magnetic phase transition from paramagnetism to soft ferromagnetism around 50 K, and the electromagnetic propertities are chiefly due to the abundancy of the 3d electrons of Cr, and the orbital hybridization between C and Cr with their 2p and 3d electrons is the reason for the crystal sturcture and high thermostability. Therefore, the prepared Cr7C3 is multifunctional material with better application prospects, and the HPHTQM is a simple and effective mothed to prepare samples as BTMCs.&#xD., (Creative Commons Attribution license.)

Background: Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, the 5-year survival rate for individuals undergoing curative resection remains between 10% and 15%. Consequently, identifying molecular targets that specifically inhibit the proliferation and metastasis of HCC cells is critical for improving treatment outcomes. Database analysis using Targetscan identified complementary binding sites for the human-specific miRNA hsa-miR-6894-3p (hereafter referred to as miR-6894-3p) on SHROOM2, and Starbase data suggested a potential regulatory interaction between lnc-MAP3K13-3:1 and miR-6894-3p in liver cancer., Objective: This study aimed to investigate the role of lnc-MAP3K13-3:1 in regulating miR-6894-3p, with a focus on its impact on proliferation, apoptosis, migration, and related cellular processes in liver cancer cells via SHROOM2 regulation., Methods: Quantitative PCR (qPCR) was initially employed to measure the expression levels of lnc-MAP3K13-3:1 and miR-6894-3p in three HCC cell lines: HepG2, HuH-7, and Li-7. Based on these initial assessments, two cell lines were selected for further experimentation. Stable cell lines overexpressing lnc-MAP3K13-3:1 were developed, and cells were transfected with miR-6894-3p mimics or a mimic negative control (NC). After 24 h, qPCR was utilized to quantify the relative expression of lnc-MAP3K13-3:1, miR-6894-3p, SHROOM2, and Caspase9 mRNA in each group. Cell proliferation was analyzed using the cell counting Kit-8 assay, while flow cytometry was used to assess cell cycle distribution and apoptosis. Migration capabilities were evaluated through cell scratch assays, and dual-luciferase assays were utilized to verify interactions between miR-6894-3p, lnc-MAP3K13-3:1, and SHROOM2., Results: Overexpression of lnc-MAP3K13-3:1 and miR-6894-3p mimic transfection resulted in increased expression of SHROOM2 and Caspase9 mRNA, as demonstrated by qPCR. The miR-6894-3p mimic regulated the activity of lnc-MAP3K13-3:1. Functional assays showed that lnc-MAP3K13-3:1 overexpression inhibited proliferation in HuH-7 and Li-7 cells, promoted apoptosis, reduced migration in Li-7 cells, but enhanced migration in HuH-7 cells. Additionally, lnc-MAP3K13-3:1 overexpression significantly increased the proportion of HuH-7 cells in the G2/M phase and Li-7 cells in the S phase. The miR-6894-3p mimic modulated the effects of lnc-MAP3K13-3:1 on cell proliferation, apoptosis, and migration. Dual-luciferase assays confirmed direct binding between lnc-MAP3K13-3:1 and miR-6894-3p, as well as between miR-6894-3p and SHROOM2., Conclusion: These findings indicate that overexpression of lnc-MAP3K13-3:1 regulates SHROOM2 expression through targeting miR-6894-3p, thereby influencing cell proliferation, apoptosis, migration, and other cellular processes associated with HCC., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted with approval from the Ethics Committee of Jiangxi Provincial Children’s Hospital. This study was conducted in accordance with the declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Several studies reported that the widespread use of perfluoroalkyl and polyfluoroalkyl substances (PFASs) causes increased environmental pollution, subsequently impacting aquatic organisms. Perfluoroalkyl substances such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) reportedly cause cardiotoxicity, neurotoxicity, and developmental toxicity in different organisms. However, whether perfluorodecanoic acid (PFDA), a widely used perfluoroalkyl substance, induces animal embryos developmental toxicity remain unknown. Here, we explored the immunotoxicity and associated mechanisms of PFDA in zebrafish embryos via RNA sequencing, morphological assessment and behavioral alteration detection following exposure to 0.5, 1 and 2 mg/L of PFDA. Interestingly, We found that with the increase of PFDA to drug concentration, including neutrophils and macrophages, significantly increased the number of inherent cells, immune related genes expression. Furthermore, oxidative stress increased in the PFDA-treated embryos in a dose-dependent manner and inhibition of oxidative stress levels effectively rescued the number of neutrophils. Changes in embryonic behavior were observed after exposure to PFDA. Overall, our results suggest that PFDA may induce innate immune response by accumulation of oxidative stress in zebrafish at early developmental stages, and concern is needed about its environmental exposure risks for animals embryos development. ENVIRONMENTAL IMPLICATION: Perfluorinated and polyfluorinated alkyl substances (PFASs) are a class of synthetic organic compounds containing fluorine widely used as lubricants, surfactants, insecticides, etc. The PFDA, a typical perfluorinated compound, is often used as a wetting agent and flame retardant in industries. Several studies showed that PFASs can cause serious environmental pollution, leading to developmental toxicity to various animals, including reproductive toxicity, liver toxicity, heart toxicity, neurotoxicity, and immunotoxicity. However, there are still limited studies on the effects and mechanisms of PFDA on aquatic organisms. Therefore, there is a need to evaluate the ecological risks of PFDA in animals., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Unnatural chemically modified nucleotide sugars UDP-4-SH-GalNAc was synthesized for the first time from a previously reported Benzyl 2-Amino-glucoypranoside derivative, with a total yield of 18.6%. UDP-4-SH-GalNAc was smaller in size than UDP-GalNAc calculated by Multiwfn, and its binding capability with glycosyltransferase was stronger than that of UDP-GalNAc and glycosyltransferase, which means the unnatural nucleotide sugars is equally well recognized by the enzyme and doped into the sugar chains. These findings support the utilization of glycosyltransferases for labeling of target glycans with sulfhydryl bioorthogonal reaction groups from UDP-4-SH-GalNAc, and synthesizing glycan chains with more stable thioside bonds., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis, and the main objective of this study was to reveal the specific mechanism of action of TN-CAP1-mediated macrophage-fibroblast crossinulation in the progression of PDAC, and to evaluate the function and potential therapeutic value of ITGB5 and ITGB1 recombinant proteins in this process. The expression of TN-CAP1 in tumor tissues of PDAC patients was analyzed by immunohistochemistry and compared with normal pancreatic tissues. The co-culture system of macrophages and fibroblasts was constructed using in vitro cell culture model. The intercellular interactions and their effects on the proliferation, migration and invasion of tumor cells were observed by adding or knocking down ITGB5 and ITGB1 proteins. Western blot and RT-PCR were also used to detect the expression changes of related signaling pathway proteins and mRNA, which verified the effects of ITGB5 and ITGB1 recombinant proteins on tumor growth and metastasis in vivo. In vitro experiments showed that the addition of ITGB5 and ITGB1 recombinant proteins significantly enhanced the interaction between macrophages and fibroblasts, and promoted the proliferation and migration of tumor cells. Specifically, ITGB5 and ITGB1 recombinant proteins promote tumor cell aggressiveness by activating the FAK/PI3K/AKT signaling pathway., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introducing a second phase has been an effective way to solve the brittleness of boron carbide (B 4 C) for its application. Though reduced graphene oxide (rGO) is an ideal candidate for reinforcing the B 4 C duo's two-dimensional structure and excellent mechanical properties, the toughness is less than 6 MPa·m 1/2 , or the hardness is lower than 30 GPa in B 4 C-graphene composites. A barrier to enhancing toughness is the weak interface strength between rGO and B 4 C, which limits the bridging and pull-out toughening effects of rGO. In this work, internal stress was introduced using a high-pressure and high-temperature (HPHT) method with B 4 C-rGO composites. The optimal hardness and toughness values for the B 4 C-2 vol% rGO composite reached 30.1 GPa and 8.6 MPa·m 1/2 , respectively. The improvement in toughness was 4 times higher than that of pure B 4 C. The internal stress in the composite increased gradually from 2.3 GPa to 3.3 GPa with an increase in rGO content from 1 vol% to 3 vol% . Crack deflection, bridging, and rGO pull-out are responsible for the improvement in toughness. Moreover, the high internal stress contributed to the formation of good interface strength by embedding rGO into the B 4 C matrix particles, which further enhanced the dissipation of the crack energy during the pull-out process and led to high toughness. This work provides new insights into synthesizing high-toughness B 4 C matrix composites.

Decoupling conductivity(σ)and Seebeck coefficient(S)by electronic topological transitions (ETT) under high pressure (2-4 GPa) is a promising method for bismuth telluride (Bi 2 Te 3 ) to optimize thermoelectric (TE) performance. However, theScannot dramatically increase with increasingσwhen ETT occurs in Bi 2 Te 3 , which impedes optimizing TE performance by utilizing ETT in Bi 2 Te 3 . A new strategy of enhanced ETT by combining lattice distortions and high pressure is proposed in this work. The lattice distortions in Bi 2 Te 3 were introduced by high pressure and high temperature (HPHT) treatment to generate surplus dislocations. The in-situ measurements ofσandSat HPHT in Bi 2 Te 3 with lattice distortions show an enhanced ETT effect at 2 GPa, which causes decoupleσandSwith an anomalous increase in its|S|about 22%. The ETT effect causes the figure of merit (ZT) of Bi 2 Te 3 can be improved to 0.275 at 1.50-2.62 GPa, 460 K, it is more than 62% compared with 0.79 GPa, at 450 K. The excellent TE performance of Bi 2 Te 3 arising from the lattice distortions can result in local non-hydrostatic pressure which enhances ETT under high pressure. This work provides a new strategy to enhance ETT to decoupleσandS, and search for better TE materials from the pressure dimension in the future., (© 2024 IOP Publishing Ltd.)

This was the first article reported a fatal case of chlorfenapyr poisoning in a child, and the typical symptoms before death include high fever, severe sweating, coma, and limb stiffness, and elevation of myocardial enzymes and myoglobin; neurological symptoms tend to appear earlier in children than in adults., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Dimethyl fumarate (DMF) is an immunosuppressant commonly used to treat multiple sclerosis and other autoimmune diseases. Despite known side effects such as lymphopenia, the effect of DMF on cardiac development remains unclear. To assess this, we used zebrafish to evaluate the cardiac developmental toxicity of DMF. Our study showed that DMF reduced the survival rate of zebrafish embryos, with those exposed to 1, 1.3, and 1.6 mg/L exhibiting heart rate reduction, shortened body length, delayed yolk sac absorption, pericardial edema, increased distance from sinus venous to bulbus arteriosus, and separation of cardiomyocytes and endocardial cells at 72 hpf. Heart development-related genes showed disorder, apoptosis-related genes were up-regulated, and the oxidative stress response was down-regulated. Treatment with cysteamine ameliorated the heart development defects. Our study demonstrates that DMF induces cardiac developmental toxicity in zebrafish, possibly by down-regulating oxidative stress responses. This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF., Competing Interests: Declaration of Competing Interest The author reports no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier B.V.)

Transparent nano-polycrystalline diamond (t-NPD) possesses superior mechanical properties compared to single and traditional polycrystalline diamonds. However, the harsh synthetic conditions significantly limit its synthesis and applications. In this study, a synthesis routine is presented for t-NPD under low pressure and low temperature conditions, 10 GPa, 1600 °C and 15 GPa, 1350 °C similar with the synthesis condition of organic precursor. Self-catalyzed hydrogenated carbon nano-onions (HCNOs) from the combustion of naphthalene enable synthesis under nearly industrial conditions, which are like organic precursor and much lower than that of graphite and other carbon allotropes. This is made possible thanks to the significant impact of hydrogen on the thermodynamics, as it chemically facilitates phase transition. Ubiquitous nanotwinned structures are observed throughout t-NPD due to the high concentration of puckered layers and stacking faults of HCNOs, which impart a Vickers hardness about 140 GPa. This high hardness and optical transparency can be attributed to the nanocrystalline grain size, thin intergranular films, absence of secondary phase and pore-free features. The facile and industrial-scale synthesis of the HCNOs precursor, and mild synthesis conditions make t-NPD suitable for a wide range of potential applications., (© 2023 Wiley-VCH GmbH.)

The comorbidity of chronic pain and mental dysfunctions such as anxiety disorders has long been recognized, but the underlying mechanisms remained poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated that the thalamic paraventricular nucleus (PVT) played a critical role in chronic pain-induced anxiety-like behavioral abnormalities. Fiber photometry and electrophysiology demonstrated that chronic pain increased the activities in PVT glutamatergic neurons. Chemogenetic manipulation revealed that suppression of PVT glutamatergic neurons relieved pain-like behavior and anxiety-like behaviors. Conversely, selective activation of PVT glutamatergic neurons showed algesic and anxiogenic effects. Furthermore, the elevated excitability of PVT glutamatergic neurons resulted in increased excitatory inputs to the basolateral complex (BLA) neurons. Optogenetic manipulation of the PVT-BLA pathway bilaterally modulates both the pain-like behavior and anxiety-like phenotypes. These findings shed light on how the PVT-BLA pathway contributed to the processing of pain-like behavior and maladaptive anxiety, and targeting this pathway might be a straightforward therapeutic strategy to both alleviate nociceptive hypersensitivity and rescue anxiety behaviors in chronic pain conditions., (© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Vascular fibrosis is a widespread pathologic condition that arises during vascular remodeling in cardiovascular dysfunctions. According to previous studies, vascular fibrosis is characterized by endothelial matrix deposition and vascular wall thickening. The RAAS and TGF-β/Smad signaling pathways have been frequently highlighted. It is, however, far from explicit in terms of understanding the cause and progression of vascular fibrosis. In this review, we collected and categorized a large number of molecules which influence the fibrosing process, in order to acquire a better understanding of vascular fibrosis, particularly of pathologic dysfunction. Furthermore, several mediators that prevent vascular fibrosis are discussed in depth in this review, with the aim that this will contribute to the future prevention and treatment of related conditions., Competing Interests: The author(s) declare financial support was received for the research, authorship, and/or publication of this article., (© 2023 Hua, Gao, He, Xin, Wang, Zhang, Gao, Tao, Wu, Sun and Xu.)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80-85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.

Two-dimensional (2D) van der Waals heterostructures (VDWHs) containing a charge-density wave (CDW) and superconductivity (SC) have revealed rich tunability in their properties, which provide a new route for optimizing their novel exotic states. The interaction between SC and CDW is critical to its properties; however, understanding this interaction within VDWHs is very limited. A comprehensive in situ study and theoretical calculation on bulk 4 Hb -TaSe 2 VDWHs consisting of alternately stacking 1 T -TaSe 2 and 1 H -TaSe 2 monolayers are investigated under high pressure. Surprisingly, the superconductivity competes with the intralayer and adjacent-layer CDW order in 4 Hb -TaSe 2 , which results in substantially and continually boosted superconductivity under compression. Upon total suppression of the CDW, the superconductivity in the individual layers responds differently to the charge transfer. Our results provide an excellent method to efficiently tune the interplay between SC and CDW in VDWHs and a new avenue for designing materials with tailored properties.

This study aimed to investigate the impact of caloric restriction (CR) on cognitive function in aged C57BL/6 mice after surgery, as well as the underlying mechanisms. Forty 14-month-old male C57BL/6 mice were randomly assigned to the ad libitum (AL, n = 20) group and the CR (n = 20) group. After feeding for 12 weeks, they were subdivided into four groups: AL control (ALC, n = 10), AL with surgery (ALS, n = 10), CR control (CRC, n = 10), and CR with surgery (CRS, n = 10). The Morris Water Maze (MWM) test was used to assess learning and memory capacity. By using western blot and immunofluorescence, the expression of Sirt1, MeCP2, and BDNF in the hippocampus and hippocampal CA1 region was quantified. According to the behavioral test, the CRC and CRS groups had significantly better learning and memory abilities than the ALC and ALS groups, respectively. Sirt1, MeCP2, and BDNF expression in the hippocampus and CA1 region in the hippocampus of the ALC and CRC groups of mice were correlated with cognitive improvement. In conclusion, CR could enhance the postoperative cognitive function in aged mice, most likely by increasing the expression of Sirt1, MeCP2, and BDNF in the CA1 region of the hippocampus.

Nickel borides are promising multifunctional materials for high hardness and excellent properties in catalysis and magnetism. However, it is still a blank of intrinsic properties in Ni-B compounds, because crystallization of the single phases of Ni-B compounds with micro-size is a challenge. In this work, single phases of Ni 2 B ( I 4 /mcm ), α-Ni 4 B 3 ( Pnma ), β-Ni 4 B 3 ( C 2 /c ), and NiB ( Cmcm ) are synthesized by high pressure and high temperature (HPHT). The results indicate that synthesizing α-Ni 4 B 3 and β-Ni 4 B 3 requires more energy than Ni 2 B and NiB. The growth process of Ni-B compounds is that Ni covers B to form Ni-B compounds under HPHT, which also makes the slight excess of B necessary. So, generating homogeneous distribution of starting materials and increasing the interdiffusion between Ni and B are two keys to synthesize well crystallized and purer samples by HPHT. This work uncovers the growth process of Ni-B compounds, which is significant to guide the synthesis of highly crystalline transition metal borides (TMBs) in the future., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

High boron content transition metal (TM) borides (HB-TMBs) have recently been regarded as the promising candidate for superhard multifunctional materials. High hardness stems from the covalent bond skeleton formed by high content of boron (B) atoms to resist deformation. High valence electron density of TM and special electronic structure from p-d hybridization of B and TM are the sources of multifunction. However, the reason of hardness variation in different HB-TMBs is still a puzzle because hardness is a complex property mainly associated with structures, chemical bonds, and mechanical anisotropy. Rich types of hybridization in B atoms ( sp, sp 2 , sp 3 ) generate abundant structures in HB-TMBs. Studying the intrinsic interaction of structures and hardness or multifunction is significant to search new functional superhard materials. In this review, the stable structure, hardness, and multifunctionality of HB-TMBs are summarized. It is concluded that the structures of HB-TMBs are mainly composed by sandwiched stacking of B and TM layers. The hardness of HB-TMBs shows a increasing tendency with the decreasing atom radius. The polyhedron in strong B skeleton provides hardness support for HB-TMBs, among which C2/ m is the most possible structure to meet the superhard standard. The shear modulus ( G 0 ) generates a positive effect for hardness of HB-TMBs, but the effect from bulk modulus ( G 0 ) is complex. Importantly, materials with a value of B 0 / G 0 less than 1.1 are more possible to achieve the superhard standard. As for the electronic properties, almost all TMB 3 and TMB 4 structures exhibit metallic properties, and their density of states near the Fermi level are derived from the d electrons of TM. The excellent electrical property of HB-TMBs with higher B ratio such as ZrB 12 comes from the channels between B-B π -bond and TM-d orbitals. Some HB-TMBs also indicate superconductivity from special structures, most of them have stronger hybridization of d electrons from TM atoms than p electrons from B atoms near the Fermi level. This work is meaningful to further understand and uncover new functional superhard materials in HB-TMBs., (© 2023 IOP Publishing Ltd.)

Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study, we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL, while cells with MDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Xu, Li, Ji, Jin, Chen, Gan, Tao and Chai.)

Transition metal diborides (TMdBs, P6/mmm , AlB 2 -type) have attracted much attention for decades, due to TMdBs can be conductors, superconductors, magnetism materials, and catalysts. The layered structure caused by the borophene subunit is the source of functions and also makes TMdBs a potential bank of Mbene. However, TMdBs also exhibit high hardness which is not supposed to have in the layered structure. The high hardness of TMdBs arises from covalent bonds of boron-boron (B-B) and strong p - d orbit hybridization of B and TM. While strong B-TM bonds will eliminate the layered structure which may damage the functional properties. Understanding the basic mechanism of hardness and function is significant to achieve optimal TMdBs. This work summarizes the basic properties of TMdBs including hardness, superconductor, and catalytic properties. It can be found that Young's modulus ( E ) and Shear modulus ( G ) are beneficial for the hardness of TMdBs and the Poisson's ratio is the opposite. Increasing the atomic radius of TM brings an improvement in the hardness of TMdBs before it reaches the highest value of 1.47 Å, beyond which hardness decreases. Besides, TMdBs also have excellent activity comparable with some noble metals for hydrogen evolution reaction, which is closely related to the d-band center. More importantly, higher valence electron concentrations were found to be adverse to the hardness and superconductivity of TMdBs and greatly affect their catalytic properties. This review is of guiding significance for further exploring the relationship between structures and properties of TMdBs., (© 2022 IOP Publishing Ltd.)

Purpose: To compare the efficacy and safety of immunotherapy plus regorafenib versus regorafenib only in patients with pretreated hepatocellular carcinoma (HCC)., Methods: Immunotherapy plus regorafenib or regorafenib alone was analyzed in patients with advanced HCC with documented tumor progression on front-line therapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs) were assessed., Results: Of the 125 patients enrolled in this study, 50 patients received combination (pCOM) treatment as front-line treatment, and 60 patients received monotherapy (pMONO) as front-line treatment. In the pCOM cohort, median OS was significantly longer with for patients regorafenib plus immunotherapy than regorafenib alone treatment (15.0 vs. 2.0 months; P = 0.035). The DCR numerically increased in the regorafenib plus immunotherapy treatment in both cohorts (40.6 % vs. 22.2 %, 72.7 % vs. 54.7 %, respectively). There were no differences in PFS with regorafenib according to whether or not regorafenib was combined with immunotherapy in the pCOM and pMONO cohorts (PFS, P = 0.17, P = 0.91, respectively). Regarding the number of TRAEs occurred, regorafenib plus immunotherapy group was comparable to regorafenib group in the pCOM cohort (65.6 % vs. 72.2 %). In the pMONO cohort, TRAEs occurred in fewer patients receiving regorafenib than regorafenib plus immunotherapy (69.8 % vs. 95.5 %)., Conclusions: Immunotherapy plus regorafenib may significantly improve clinical outcomes and have a manageable safety profile compared with regorafenib monotherapy in advanced HCC after front-line therapy failure. The efficacy of combination therapy needs to be validated in prospective studies with large samples., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although thoracoscopic surgery has become the routine surgical method for esophageal atresia/tracheoesophageal fistula (EA/TEF), thoracoscopic treatment for recurrent tracheoesophageal fistula (rTEF) is far from popularized., Objectives: We aimed to explore the safety and efficacy of thoracoscopic treatment for rTEF with a large-cohort study., Methods: We retrospectively analyzed the clinical characteristics and outcomes of 103 consecutive patients who underwent thoracoscopic surgery for rTEF by one surgeon after EA/TEF repair at two different institutions in China from 2014 to 2021., Results: One hundred and three pediatric patients (67 boys) were enrolled and the primary operations were performed via thoracoscopic (n = 75, 72.82%) or open surgery (n = 28, 27.18%). The median age at rTEF diagnosis was 5 (3, 10) months after the primary repair. Patients were diagnosed with recurrent fistula to the trachea (n = 97, 94.17%), bronchi (n = 4, 3.88%), and lung parenchyma (n = 2, 1.94%), and all of them underwent thoracoscopic surgery at a median age of 7 (5, 14) months with a median weight of 6200 (4870, 7650) g. After the repair of rTEF, the incidence of esophageal leakage, esophageal stricture, and TEF recurrence were 12.8%, 33.4%, and 10.8%, respectively. After the follow-up, 87 patients survived, 6 died, and 10 were lost to follow-up., Conclusions: The results of thoracoscopic surgery for rTEF were comparable with previously reported thoracotomy surgery. Owing to the clear field during the operation, rapid patient recovery and esthetic results, the thoracoscopic approach could be a better choice for experienced pediatric surgeons., Level of Evidence: LEVEL IV., (Copyright © 2022. Published by Elsevier Inc.)

High-quality P 6 3 22 Mn 2 N 0.86 samples were synthesised using a high-pressure metathesis reaction, and the properties of the material were investigated. The measurements revealed that the Vickers hardness was 7.47 GPa, which is less than that predicted by commonly used theoretical models. At low air pressure, Mn 2 N 0.86 and MnO coexist at 500 to 600 °C, and by excluding air, we succeeded in producing Mn 4 N by heating Mn 2 N 0.86 in nitrogen atmosphere; we carefully studied this process with thermogravimetry and differential scanning calorimetry (TG-DSC). This gives a hint that to control temperature, air pressure and gas concentration might be an effective way to prepare fine Mn-N-O catalysis. Magnetic measurements indicated that ferromagnetism and antiferromagnetism coexist within Mn 2 N 0.86 at room temperature and that these magnetic properties are induced by nitrogen vacancies. Ab intio simulation was used to probe the nature of the magnetism in greater detail. The research contributes to the available data and the understanding of Mn 2 N 0.86 and suggests ways to control the formation of materials based on Mn 2 N 0.86 .

Regulating electron structure and electron-phonon coupling by means of pressure and temperature is an effective way to optimize thermoelectric properties. However, in situ testing of thermoelectric transport performance under pressure and temperature is hindered by technical constraints that obscure the intrinsic effects of pressure and temperature on thermoelectric properties. In the present study, a new reliable assembly was developed for testing the in situ thermoelectric transport performance of materials at high pressure and high temperature (HPHT). This reduces the influence of thermal effects on the test results and improves the success rate of in situ experiments at HPHT. The Seebeck coefficient and electrical resistivity of α-Cu 2 Se were measured under HPHT, and the former was found to increase with increasing pressure and temperature; for the latter, although an increase in the pressure acted to lower the electrical resistivity, an increase in the temperature acted to increase it. On increasing pressure from 0.8 to 3 GPa at 333 K, the optimal power factor of α-Cu 2 Se was increased by ∼76% from 2.36 × 10 -4 -4.15 × 10 -4  W m -1  K -2 , and the higher pressure meant that α-Cu 2 Se had its maximum power factor at lower temperature. The present work is particularly important for understanding the thermoelectric mechanism under HPHT.

Novel transition-metal borides have attracted considerable attention because they exhibit high stability under extreme conditions. Compared with binary borides, ternary transition-metal borides (TTMBs) exhibit novel boron substructures and diverse properties, which result in excellent designability. In this study, we synthesized the MAB-like (where M = iron, A = molybdenum, and B = boron) phase Fe(MoB) 2 using a high-pressure and high-temperature method. Fe(MoB) 2 exhibited ferromagnetic metastable characteristics with a saturation magnetization of 8.35 emu/g at room temperature. Microhardness measurement revealed an indentation hardness of 10.72 GPa, which was higher than those of conventional magnetic materials. First-principles calculations revealed excellent mechanical properties, which mainly originated from the strong covalent short B 2 chains. Furthermore, magnetism was attributed to the Fe 3 d electrons. Numerous d - d hybridizations existed between the Fe 3 d e g and Mo 4 d orbitals, and the antibonding/nonbonding state difference for up/down-spin electrons in the hybridization orbitals led to the local magnetic moment of Fe(MoB) 2 . The magnetic anisotropy energy analyses reveal that Fe(MoB) 2 prefers the easy magnetization axis along the z direction, and Mo atom acts as a medium to realize the exchange action between two Fe atoms. The B-B and Fe-B bonds were considerably stronger than the Fe-Mo and Mo-B bonds, and Fe(MoB) 2 exhibited a class of atomically laminate composed of FeB 2 and Mo layers. These results may provide guidance for the design of novel multifunctional TTMBs by adjusting the interactions between binary metal components.

Objective: To study and develop a predictive model for the differential diagnosis of acute appendicitis (AA) and Henoch-Schonlein purpura (HSP) in children and to validate the model internally and externally. Methods: The complete data of AA and HSP cases were retrospectively analyzed and divided into internal and external verification groups. SPSS software was used for single-factor analysis and screening of independent variables, and R software was used for the development and verification of the diagnostic model. Lasso regression analysis was used to screen predictors and Lasso-logistic regression model was constructed, and K-fold cross-validation was used for the internal verification. In addition, nonfever patients were selected for model development and validation in the same way. Receiver operating characteristic (ROC) curves and calibration curves were drawn, respectively, to evaluate the 2 models. Results: Internal development and validation of the model showed that fever, neutrophil ratio (NEUT%), albumin (ALB), direct bilirubin (DBIL), C-reactive protein (CRP), and K were predictive factors for the diagnosis of HSP. The model was presented in the form of a nomogram, and the area under ROC curve of the development group and verification group was 0.9462 (95% confidence interval [CI] = 0.9402-0.9522) and 0.8931 (95% CI = 0.8724-0.9139), respectively. In the model of patients without fever, NEUT%, platelets (PLT), ALB, DBIL, alkaline phosphatase (ALP), CRP, and K were predictive factors for the diagnosis of HSP, and the area under ROC curve of the development group and verification group was 0.9186 (95% CI = 0.908-0.9293) and 0.8591 (95% CI = 0.8284-0.8897), respectively. Conclusion: In this study, 2 diagnostic models were constructed for fever or not, both of which had good discrimination and calibration, and were helpful to distinguish AA and HSP in children.

Background: Endoscopic ultrasound (EUS) is widely used as a cost-effective method for detecting pancreatic neuroendocrine tumors (PNTs), but its diagnostic value is variable among published studies. This meta-analysis aimed to determine the diagnostic value of EUS for PNTs., Methods: Three electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for studies published up to July 2018. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve were calculated to evaluate the diagnostic value of EUS using the random-effects model., Results: Thirteen studies involving 609 patients were included in this meta-analysis. The summary sensitivity and specificity of EUS for detecting PNTs were 0.86 and 0.89, respectively. The PLR and NLR of EUS were 7.81 and 0.15, respectively. The DOR of EUS for diagnosing PNTs was 24.20. The area under the ROC was 0.90. Finally, the subgroup analyses indicated that publication year and percentage of males could introduce potential biases for the DOR of EUS., Conclusions: This meta-analysis suggests that EUS has a relatively high diagnostic value for diagnosing PNTs., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Total pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations., Methods: The study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis., Results: For all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 vs. 20 months, P=0.0058; median CSS: 24 vs. 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 vs. 19 months, P=0.0016; median CSS: 22 vs. 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05)., Conclusions: Compared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2217/coif).The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Chemotherapy is the first-line treatment for human retinoblastoma (RB), but the occurrence of drug resistance greatly limited its efficacy in practice. RING-finger protein 6 (RNF6) is an E3 ubiquitin ligase that is aberrantly upregulated in a range of cancers and plays important roles in cancer progression. However, the role of RNF6 in RB is largely unknown. In this study, we investigated the role of RNF6 in RB drug resistance. Two carboplatin-resistant RB cells, Y-79/CR and SO-Rb50/CR, were generated based on Y-79 and SO-Rb50 cells. RT-PCR and western blot analyses showed that RNF6 expression on both mRNA and protein levels was significantly increased in Y-79/CR and SO-Rb50/CR cells comparing to their parental cells. Knockdown of RNF6 using siRNA in Y-79/CR and SO-Rb50/CR cells resulted in cells sensitive to carboplatin on a RNF6 siRNA dose dependent manner. Similarly, RNF6 overexpression in parental Y-79 and SO-Rb50 cells could help cells gain resistance to carboplatin on a RNF6 expression dependent manner. Signaling pathway analyses revealed that JAK2/STAT3 pathway was involved in the RNF6-induced carboplatin resistance in RB cells. We further revealed that RNF6 expression in both Y-79 and SO-Rb50 cells could render cells resistant to multiple anti-cancer drugs including carboplatin, vincristine and etoposide, an implication of RNF6 as a biomarker for RB drug resistance. Taken together, our study has revealed that RNF6 is upregulated in drug-resistant RB cells and RNF6 promotes drug resistance through JAK2/STAT3 signaling pathway. The importance of RNF6 in RB cells drug resistance may represent this protein as a potential biomarker and treatment target for drug resistance in RB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chai, Jiao, Peng, Gan, Chen, Hu, Hao, Zhang and Tao.)

Wurtzite CuInS 2 exhibits great potential for optoelectronic applications because of its excellent optical properties and good stability. However, exploring effective strategies to simultaneously optimize its optical and photoelectrical properties remains a challenge. In this study, the bandgap of wurtzite CuInS 2 nanocrystals is successfully extended and the photocurrent is enhanced synchronously using external pressure. The bandgap of wurtzite CuInS 2 increases with pressure and reaches an optimal value (1.5 eV) for photovoltaic solar energy conversion at about 5.9 GPa. Surprisingly, the photocurrent simultaneously increases nearly 3-fold and reaches the maximum value at this critical pressure. Theoretical calculation indicates that the pressure-induced bandgap extention in wurtzite CuInS 2 may be attributed to an increased charge density and ionic polarization between the In-S atoms. The photocurrent preserves a relatively high photoresponse even at 8.8 GPa, but almost disappears above 10.3 GPa. The structural evolution demonstrates that CuInS 2 undergoes a phase transformation from the wurtzite phase ( P 6 3 mc ) to the rock salt phase ( Fm 3̄ m ) at about 10.3 GPa, which resulted in a direct to indirect bandgap transition and fianlly caused a dramatic reduction in photocurrent. These results not only map a new route toward further increase in the photoelectrical performance of wurtzite CuInS 2 , but also advance the current research of A I - B III - C VI2 materials.

Background: Our study seeks to obtain data to assess the impact of circPUM1 on pancreatic cancer (PC) and its mechanism., Methods: The expression of circPUM1 and miR-200c-3p in PC and normal tissues and PC cell lines was collected and detected, and subsequently dual-luciferase assay-based verification of the binding site of the two was carried out. After interfering with circPUM1 expression in MIAPaCa-2 and PANC-1 cells, cell proliferation, viability, apoptosis rate, invasion ability, glucose consumption, and lactate production were measured by MTT, colony formation, flow cytometry, Transwell assays, and glucose and lactate assay kits. Additionally, western blot was utilized for assessing PI3K/AKT signaling pathway-related proteins. From the results, highly expressed circPUM1 and miR-200c-3p in PC tissues and cells were proved., Results: Down-regulation of circPUM1 expression significantly inhibited cell proliferation, cell viability, invasion and glycolysis, while increasing the apoptosis rate. Down-regulated circPUM1 led to the inhibition of the PI3K/AKT signaling pathway activity in PC cells; while up-regulated circPUM1 increased its activity. Further experiments revealed that down-regulation of miR-200c-3p expression reversed the inhibitory effect of lowly expressed circPUM1 on PC cells., Conclusion: In summary, circPUM1 activates PI3K/AKT signaling pathway by sponging miR-200c-3p and promotes PC progression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: As a common postoperative complication to elderly patients, postoperative cognitive dysfunction (POCD) is a central nervous system complication, often taking place after anesthesia and surgery. (Su(var)3-9, enhancer-of-zeste, and trithorax) domain-containing protein 7 (SETD7) plays important roles in metabolic-related diseases, viral infections, tumor formation, and some inflammatory reactions. However, the role and mechanism of SETD7 in POCD have not been previously studied., Methods: RT-PCR and Western blot were performed to evaluate the efficiency of knockdown of SETD7. The pathological changes of hippocampal neurons in isoflurane-anesthetized mice were detected by HE staining, and the Morris water maze experiment was performed to evaluate the learning and memory abilities of mice. The effect of SETD7 on the hippocampus in isoflurane-induced aged mice was examined by Western blot and TUNEL assay. Then ELISA assay was applied to determine the expression of some inflammatory cytokines, followed by the detection of expression of NOD-like receptor protein 3 (NLRP3) inflammasome through Western blot., Results: The data of this research revealed that SETD7 knockdown improved cognitive impairment in isoflurane-anesthetized mice, ameliorated cell pyroptosis, inhibited the release of inflammatory cytokines, and suppressed the activation of NLRP3 inflammasome in the hippocampus in isoflurane-induced aged mice., Conclusion: Collectively, these results provided evidence that the inhibition of SETD7 could alleviate neuroinflammation, pyroptosis, and cognitive impairment by suppressing the activation of the NLRP3 inflammasome in isoflurane-induced aged mice.

Exploring the hydrophobicity of robust conductors is significant for electronic devices to simultaneously be used in a wet environment and extreme conditions. However, a combination of conductivity, strong mechanical properties, and hydrophobicity in one material is hindered by the inherent features of the materials. A new kind of robust hydrophobic conductor is designed in transition-metal diborides (TMdBs: TiB 2 , ZrB 2 , and HfB 2 ) to break through this challenge. The results calculated by density functional theory indicate that high hardness comes from high shear and bulk modulus, which is consistent with experimental results (TiB 2 , 25.0 GPa; ZrB 2 , 17.5 GPa; HfB 2 , 21.5 GPa). The theoretical calculated results reveal that edge sides have a lower surface energy than basal plane (001) in TMdBs. Hence, the edge sides are exposed with a needle-like morphology in TMdBs. Moreover, needle-like surfaces exhibiting hydrophobicity have water contact angles of 132.0° (TiB 2 ), 116.8° (ZrB 2 ), and 114.0° (HfB 2 ). The hydrophobicity arises from a lower surface free energy of edge sides in TMdBs and a rough surface that reduces the contact area of water and a solid. This work develops a new kind of robust functional material in TMdBs.

The combination of various desired physical properties greatly extends the applicability of materials. Magnetic materials are generally mechanically soft, yet the combination of high mechanical hardness and ferromagnetic properties is highly sought after. Here, we report the synthesis and characterization of nanocrystalline manganese boride, CrB-type MnB, using the high-pressure and high-temperature method in a large volume press. CrB-type MnB shares the specificity of large numbers of unpaired electrons of manganese ions and strong covalent boron zigzag chains. Thus, manganese mono-boride exhibits "strong" ferromagnetic, magnetocaloric behavior, and possesses high Vickers hardness. We demonstrate that zigzag boron chains in this structure not only play a pivotal role in strengthening mechanical properties but also tuning the exchange correlations between manganese atoms. Nontoxic and Earth-abundant CrB-type MnB is much more incompressible and tougher than traditional ferromagnetic materials. The unique combination of high mechanical hardness, magnetism, and electrical conductivity properties makes it a particularly promising candidate for a wide range of applications.

Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of 5 mg/L, 10 mg/L, and 15 mg/L from 12 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered, and the apoptotic genes were up-regulated. Oxidative stress level was up-regulated and accumulated in pericardium in a dose-dependent manner. Astaxanthin (ATX) treatment could significantly alleviate zebrafish heart defects. CsA induced up-regulation of Wnt signaling in zebrafish, and IWR-1, an inhibitor of Wnt signaling pathway, could effectively rescue the heart defects induced by CsA. Together, our study indicated that CsA induced cardiac developmental toxicity in zebrafish larvae through up-regulating oxidative stress and Wnt signaling, contributing to a more comprehensive evaluation of the safety of the drug., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wan, Huang, Liu, Liu, Chen, Ni, Xiong, Liao, Lu, Xiao, Tao and Cao.)

Transcatheter arterial chemoembolization (TACE) has been widely used in clinical practice as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the current therapeuticeffect of TACE is far from satisfactory and thus requires further improvement. TACE combined with multifunctional magnetic particles may be a promising approach for the treatment of HCC. In this study, we designed a new magnetic drug carrier system consisting of micron-sized iron powder, barium ferrite (BaFe 12 O 19 ), and carbon-coated iron nanocrystals (CCINs). CCINs possess properties, such as high drug loading and sustained release. BaFe 12 O 19 could attract both CCINs and iron powder to form larger clusters after magnetization. Altogether, the triple therapeutic effects of chemotherapeutic enhancement, embolization, and thermal ablation could be realized herein. Further experiments indicate that the system has a high drug-loading capacity, good controlled-release effect, and no significant cytotoxicity. Under the action of a medium-frequency magnetic induction device, the magnetic induction temperature could reach 43 °C in one min while the maximum temperature of 70.8 °C could be reached in 2.5 h. Overall, this new carrier system displayed excellent antitumor effects in a mouse model. Our findings demonstrate the great application prospects of this system in TACE for HCC., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The lattice compressibility and deformation in superhard tungsten tetraboride (WB 4 ) solid solution with chromium (Cr) are investigated by high-pressure x-ray diffraction and x-ray absorption fine structure (XAFS) spectroscopy up to 54 GPa. In contrast to pure WB 4 , the c -axis softening is effectively suppressed in W 0.9 Cr 0.1 B 4 , and less compressibility is shown for the a - and c -axes in the entire pressure range. Meanwhile, the white-line peak of W L 3 -edge XAFS in W 0.9 Cr 0.1 B 4 shows an absence of the sudden intensity drop as previously observed in WB 4 at ∼21 GPa, suggesting a strong inhibition of W 5 d electron depletion. This phenomenon is followed by an initial increase and then decrease for the W-B bond disorder, with the magnitude greatly lower than that of WB 4 . Besides the apparent atomic size mismatch effect, these results imply that addition of Cr, which has the same number of valence electrons as W, can introduce an unexpected electronic structure change to strengthen the W-B bond via a modification of W vacancies and B trimers distribution in WB 4 lattice. Our findings point out the great significance to precise manipulation of the intrinsic W vacancies and B trimers through different solute atoms to rational optimization of WB 4 hardness., (© 2021 IOP Publishing Ltd.)

It remains impossible to accurately assess the prognosis after thermal ablation in patients with hepatocellular carcinoma (HCC). Our aim was to build a nomogram to predict the survival rate of HCC patients after thermal ablation. We developed and validated a nomogram using data of 959 HCC patients after thermal ablation from two centers. Harrell's concordance index (C-index), calibration plot and Decision curve analysis (DCA) were used to measure the performance of the nomogram, and we compared it with the Barcelona Clinic Liver Cancer (BCLC) staging system and a previous nomogram. Six variables including age, serum albumin, operation method, risk area, tumor number and early recurrence were selected to construct the nomogram. In the training cohort, internal validation cohort, and external validation cohort, the nomogram all had a higher C-index to predict survival rate than both the BCLC staging system and the previous nomogram (0.736, 0.558 and 0.698, respectively; 0.763, 0.621 and 0.740, respectively; and 0.825, 0.551 and 0.737, respectively). Calibration plots showed a high degree of consistency between prediction and actual observation. Decision curve analysis (DCA) presented that compared with BCLC system and the previous nomogram, our nomogram had the highest net benefit. In all three cohorts, the nomogram could accurately divide patients into three subgroups according to predicted survival risk. A nomogram was developed and validated to predict survival of HCC patients who underwent thermal ablation, which is helpful for prognostic prediction and individual surveillance in clinical practice., Competing Interests: None., (AJCR Copyright © 2021.)

Objective: To find risk markers and develop new clinical predictive models for the differential diagnosis of hand-foot-and-mouth disease (HFMD) with varying degrees of disease., Methods: 19766 children with HFMD and 64 clinical indexes were included in this study. The patients included in this study were divided into the mild patients' group (mild) with 12292 cases, severe patients' group (severe) with 6508 cases, and severe patients with respiratory failure group (severe-RF) with 966 cases. Single-factor analysis was carried out on 64 indexes collected from patients when they were admitted to the hospital, and the indexes with statistical differences were selected as the prediction factors. Binary multivariate logistic regression analysis was used to construct the prediction models and calculate the adjusted odds ratio (OR)., Results: SP, DP, NEUT#, NEUT%, RDW-SD, RDW-CV, GGT, CK/CK-MB, and Glu were risk markers in mild/severe, mild/severe-RF, and severe/severe-RF. Glu was a diagnostic marker for mild/severe-RF (AUROC = 0.80, 95% CI: 0.78-0.82); the predictive model constructed by temperature, SP, MOMO%, EO%, RDW-SD, GLB, CRP, Glu, BUN, and Cl could be used for the differential diagnosis of mild/severe (AUROC > 0.84); the predictive model constructed by SP, age, NEUT#, PCT, TBIL, GGT, Mb, β 2MG, Glu, and Ca could be used for the differential diagnosis of severe/severe-RF (AUROC > 0.76)., Conclusion: By analyzing clinical indicators, we have found the risk markers of HFMD and established suitable predictive models., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Feng Zhuo et al.)

Improving the poor electrical conductivity of hard materials is important, as it will benefit their application. High-hardness metallic Mo 2 B was synthesized by high-pressure and high-temperature methods. Temperature-dependent resistivity measurements suggested that Mo 2 B has excellent metallic conductivity properties and is a weakly coupled superconductor with a T c of 6.0 K. The Vickers hardness of the metal-rich molybdenum semiboride reaches 16.5 GPa, exceeding the hardness of MoB and MoB 2 . The results showed that a proper boron concentration can improve the mechanical properties, not necessarily a high boron concentration. First-principles calculations revealed that the pinning effect of light elements is related to hardness. The high hardness of boron-pinned layered Mo 2 B demonstrated that the design of high-hardness conductive materials should be based on the structure formed by light elements rather than high-concentration light elements., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Can the active kernels in ultrasmall metal nanoparticles (nanoclusters, NCs) react with one another, or can the internanocluster reaction occur when they are in close enough proximity? To resolve this fundamental issue, we investigated the solid-state internanocluster reaction of the most studied gold NC Au 25 (SR) 18 (SR: thiolate). A novel NC was produced by increasing the pressure to 5 GPa, whose composition was determined to be Au 32 (SC 2 H 4 Ph) 24 by mass spectrometry and thermogravimetric analysis. As revealed by single-crystal X-ray crystallography, the structure, a bicuboid Au 14 kernel and three pairs of interlocked trimetric staples, has not been reported and endows the NC with obvious photoluminescence. DFT calculations indicate that the staples contribute substantially to the absorption properties. Further experiments reveal the pressure (internanocluster distance) can tune the internanocluster reaction, and the resulting product is not necessarily the thermodynamic product., (© 2021 Wiley-VCH GmbH.)

Background: The members of the cell division cycle-associated ( CDCA ) gene family are significant regulators of cell proliferation known to play key roles in various cancers. However, the function of CDCA genes in hepatocellular carcinoma (HCC) is unclear. The aim of this research was to clarify the roles of CDCA family members in HCC using bioinformatics analysis tools., Methods: We studied data on the mRNA and protein expression of CDCA genes and survival in patients with HCC using the Oncomine, UALCAN, HPA, CCLE, LinkedOmics, cBioPortal, and Metascape databases., Results: Significant overexpression of all CDCA members was found in HCC tissues. The expression levels of CDCA s were related to the tumor stage, and high expression levels were correlated with a low survival rate in patients with HCC. Also, we observed a high mutation rate (45%) of CDCA s in the HCC samples, which manifested as deep deletion, amplification, or increased mRNA expression. In the correlation analysis, we found that any 2 CDCA members were significantly positively correlated with each other. Cycle-related genes including AHCTF1 , AKT1 , BIRC5 , CENPF , CENPL , and CENPQ were closely associated with CDCA gene alterations., Conclusions: The findings of this study indicate that CDCA s may be potential therapeutic targets and prognostic indicators for patients with HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-21-110). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: The structural changes of gastric mucosa are considered as an important window of early gastric lesions. This article shows an imaging method of the stomach that does not use imaging agents. X-ray phase-contrast images of different stages of gastric development were taken using micrometer level X-ray in-line phase-contrast imaging (XILPCI) technique on synchrotron radiation facility. The aim of the study was to demonstrate that the imaging technique is an appropriate method for micron imaging of the gastric structures., Methods: The stomachs of 4-, 6- and 12-week-old rats were removed and cleaned. XILPCI has 1000 times greater soft tissue contrast than that of X-ray traditional absorption radiography. The projection images of the rats stomachs were recorded by an XILPCI charge coupled device (CCD) at 9-μm image resolution., Results: The X-ray in-line phase-contrast images of the different stages of rats' gastric specimens clearly showed the gastric architectures and the details of the gastro-duodenal region. 3-dimensional (3D) stomach anatomical structure images were reconstruction., Conclusion: The reconstructed gastric 3D images can clearly display the internal structure of the stomach. XILPCI may be a useful method for medical research in the future.

Diketopyrrolopyrroles (DPP) have been recognized as a promising acceptor unit for construction of semiconducting donor-acceptor (D-A) polymers, which are typically flanked by spacers such as thiophene rings via a carbon-carbon single bond formation. It may suffer from a decrease in the coplanarity of the molecules especially when bulky side chains are installed. In this work, the two N atoms in the DPP unit are further fused with C-3 of the two flanking thiophene rings, yielding a π-expanded, very planar fused-ring building block (DPPFu). A novel DPPFu-based D-A copolymer (PBDTT-DPPFu) was successfully synthesized, consisting of a benzo[1,2- b :4,5- b ']dithiophene (BDTT) unit as a donor and a DPPFu unit as an acceptor. For comparison, the unfused DPP-based counterpart PBDTT-DPP was also synthesized. Two dodecyl alkyl chains were attached to thiophene rings of DPP moieties to ensure good solubility of the DPPFu-based polymer. The influence of the ring-fusion effect on their structure, photophysical properties, electronic properties, molecular packing, and charge transport properties is investigated. Ring-fusion enhances the intermolecular interactions of PBDTT-DPPFu polymer chains as indicated by density functional theory calculation and analysis of electrostatic potential and van der Waals potential and results in significantly improved molecular packing for both the in-plane and out-of-plane directions as suggested by X-ray measurements. Finally, we correlate the molecular packing to the device performance by fabricating field-effect transistors based on these two polymers. The charge carrier mobility of the ring-fused polymer PBDTT-DPPFu is significantly higher as compared to the PBDTT-DPP polymer without ring-fusion, although PBDTT-DPPFu exhibited a much lower number-average molecular weight of 17 kDa as compared to PBDTT-DPP with a molecular weight of 108 kDa. The results from our comparative study provide a robust way to increase the interchain interaction by ring-fusion-promoted coplanarity., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Magnetic materials attract great attention due to their fundamental importance and practical application. However, the relatively inferior mechanical properties of traditional magnetic materials limit their application in a harsh environment. In this work, we report an outstanding magnetic material that exhibits both fantastic mechanical and excellent magnetic properties, CuAl2-type Fe2B, synthesized by the high pressure and high temperature method. The magnetic saturation of Fe2B is 156.9 emu g-1 at room temperature and its Vickers hardness is 12.4 GPa which outclasses those of traditional magnetic materials. It exhibits good conductivity with a resistivity of 5.6 × 10-7 Ω m. Fe2B is a promising strong ferromagnetic material with high hardness, which makes it a good candidate for multifunction applications in a harsh environment. The high hardness of Fe2B originates from the Fe-B bond framework, and the strong ferromagnetism is mainly attributed to the large number of unpaired Fe 3d electrons. The competition of Fe 3d electrons to fall into Fe-B bonds or Fe-Fe bonds is the main factor for its magnetism and hardness. This work bridges the chasm between strong ferromagnetism and high hardness communities.

Tungsten tetraboride (WB 4 )-based solid solutions represent one of the most promising superhard metal candidates; however, their underlying hardening mechanisms have not yet been fully understood. Here, we explore the lattice compressibility of WB 4 binary solid solutions with different manganese (Mn) concentrations using high-pressure x-ray diffraction (XRD) up to 52 GPa. Under initial compression, the lattices of low and high Mn-doped WB 4 alloys (i.e. W 0.96 Mn 0.04 B 4 and W 0.84 Mn 0.16 B 4 ) are shown to be more and less compressible than pure WB 4 , respectively. Then, a c-axis softening is found to occur above 39 GPa in WB 4 , consistent with previous results. However, an anomalous sudden a-axis stiffening is revealed at ~36 GPa in W 0.96 Mn 0.04 B 4 , along with suppression of c-axis softening observed in WB 4 . Furthermore, upon Mn addition, a simultaneous stiffening of a- and c-axes is demonstrated in W 0.84 Mn 0.16 B 4 at ~37 GPa. Speculation on the possible relationship between this anomalous stiffening and the combined effects of valence-electron concentration (VEC) and atomic size mismatch is also included to understand the origin of the nearly identical hardness enhancement in those two solid solutions compared to WB 4 . Our findings emphasize the importance of accurate bonding and structure manipulation via solute atoms to best optimize the hardness of WB 4 solid solutions.

Background: The hepatocellular carcinoma (HCC) belongs to a common malignancy especially in China. Recent data have clarified important roles of long non-coding RNAs (lncRNAs) in HCC. However, the role of a novel intergenic lncRNA termed TGLC15 is still elusive., Methods: We screened for novel lncRNAs using lncRNA profiling. TGLC15 expression was quantified by qRT-PCR. In vitro experiments such as migration and viability assays were performed. In vivo implantation experiments were conducted to investigate tumorigenic functions of TGLC15. Combined RNA immunoprecipitation (RIP) and mass spectrometry (MS) were utilized to uncover Sox4 as TGLC15 binding protein., Results: TGLC15 is significantly overexpressed in tumor tissues and HCC cell lines. Higher TGLC15 levels correlated with advanced malignant characteristics such as TNM stages, tumor size, and metastasis. TGLC15 advanced HCC migration and viability. The in vivo experiments supported that xenograft tumor growth and proliferation were facilitated by TGLC15 overexpression. Mechanistic studies showed that TGLC15 interacted with Sox4 and interaction between TGLC15 and Sox4 could stabilize Sox4 via reduction in proteasome-mediated degradation., Conclusions: Collectively, our data have identified a novel lncRNA TGLC15 during HCC development. The TGLC15-Sox4 signaling might be a potential target for pharmaceutical intervention., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Recent reports exposed an astonishing factor of high hardness that the connection between transition-metal (TM) atoms could enhance hardness, which is in contrast to the usual understanding that TM-TM will weaken hardness as the source of metallicity. It is surprising that there are two opposite mechanical characteristics in the one TM-TM bond. To uncover the intrinsic reason, we studied two appropriate mononitrides, CrN and WN, with the same light-element (LE) content and valence electron concentration. The two high-quality compounds were synthesized by a new metathesis under high pressure, and the Vickers hardness is 13.0 GPa for CrN and 20.0 GPa for WN. Combined with theoretical calculations, we found that the strong correlation of d electrons in TM-TM could seriously affect hardness. Thus, we make the complementary suggestions of the previous hardness factors that the antibonding d-electron state in TM-TM near the Fermi level should be avoided and a strong d covalent coupling in TM-TM is very beneficial for high hardness. Our results are very important for the further design of high-hardness and multifunctional TM and LE compounds.

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Yang Chen et al.)