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This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. Methods: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. Results: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. Conclusion: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies. [ABSTRACT FROM AUTHOR]

The joint action-value function (JAVF) plays a key role in the centralized training of multi-agent deep reinforcement learning (MADRL)-based algorithms using the value function decomposition (VFD) and in the generating process of a collaborative policy between agents. However, under the influence of multiple factors such as environmental noise, inadequate exploration and iterative updating mechanism, estimation bias is inevitably introduced, causing its overestimation problem, which in turn prevents agents from obtaining accurate reward signals during the learning process, and fails to correctly approximate the optimal policy. To address this problem, this paper first analyzes the causes of joint action-value function overestimation, gives the corresponding mathematical proofs and theoretical derivations, and obtains the lower bound of the overestimation error; then, a MADRL overestimation reduction method based on the multi-step weighted double estimation named λWD QMIX is proposed. Specifically, the λWD QMIX method effectively achieves more stable and accurate JAVF estimation results using the bias correction estimation mechanisms based on the weighted double estimation and multi-step updating based on eligibility trace backup, without additionally adding or changing any network structure. The results of a series of experiments on the StarCraft II micromanipulation benchmark show that the proposed λWD QMIX algorithm can effectively improve the final performance and learning efficiency of the baseline algorithm, and can be seamlessly integrated with the partially MADRL algorithms based on communication learning. [ABSTRACT FROM AUTHOR]

Direct enantioselective reduction of the C=C bond of β-polyfluoro-alkylated enones is an important but long-pending subject in asymmetric catalysis. Here, we report on the viability of visible light-driven cooperative photoredox and chiral hydrogen-bonding catalysis to effectively address this challenge, as a variety of products are obtained in high yields (up to 85%) with good to excellent enantioselectivities (up to 98% ee). The formation of thermodynamically favorable enol intermediates after double single-electron reduction represents the center of the success. Additionally, the utility of the current method is validated by the convenient regio-specific and -diverse synthesis of various deuterated derivatives for these products using inexpensive D2O as the deuterium source. [ABSTRACT FROM AUTHOR]

An alternative route is offered for the electrodeposition of polymelamine (pMel) by electropolymerization in deep eutectic solvents, which has been proposed previously (Electrocatalysis 12:238–250, 2021) but difficultly synthesizing pMel in (Electrocatalysis 14:131–137, 2023). The introduction of a modest amount of water as an additive into deep eutectic solvents enables the electropolymerzation of melamine to pMel on carbon electrodes. The electrochemical behavior and catalytic activity of active chlorine species in different proportions of water-containing deep eutectic solvents was studied carefully by cyclic voltammetry. Electrochemical quartz crystal microbalance and atomic force microscopy studies confirmed the mass changes and nanostructure formation that occurred during pMel deposition. [ABSTRACT FROM AUTHOR]

This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case–control study was conducted, and high-throughput sequencing of the V4–V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research. [ABSTRACT FROM AUTHOR]

The TiO2/FeOCl composites were prepared by a simple calcination method, and the photo-Fenton performance of the TiO2/FeOCl photo-Fenton catalysts was investigated for the degradation of Rhodamine B (RhB) and Tetracycline (TC) in simulated sunlight under different conditions. The structure, morphology, elemental composition and optical properties of the samples were investigated by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy and ultraviolet–visible absorption spectroscopy (UV–vis). The results showed that the synthesized. TiO2/FeOCl catalysts exhibited enhanced visible light absorption and excellent photo-Fenton performance. Compared with pure FeOCl, TiO2/FeOCl has a stronger degradation ability for both RhB and TC, and within 10 min, the degradation rate of RhB reaches 90.9%, which is about 6 times the degradation efficiency of FeOCl, and the removal rate of TC reaches 86%, which is about 2 times the removal efficiency of FeOCl; within 60 min, the degradation rate of RhB reaches 98% and the degradation rate of TC reaches 94%. The heterojunction formed between TiO2 and FeOCl inhibited the recombination of electron–hole pairs, and at the same time, the presence of e-promoted the cycling of Fe3+ and Fe2+ in FeOCl, which facilitated the generation of hydroxyl radicals (·OH) from H2O2 and improved the photo-Fenton activity to achieve the pollutant degradation effect. Free radical trapping experiments confirmed that hydroxyl radicals were the main active groups, and the possible mechanism of photo-Fenton degradation was analyzed in detail. In this study, the efficient photo-Fenton performance of TiO2/FeOCl provides a new idea for the modification of pure FeOCl. [ABSTRACT FROM AUTHOR]

The transmission characteristics of terahertz waves in inhomogeneous magnetized dusty plasma are studied by using the shift-operator finite-difference-time-domain (SO-FDTD) method. The Epstein distribution model is employed to simulate the electron density distribution in dusty plasmas. The results given by the SO-FDTD method are in good agreement with those gotten by the Wentzel–Kramers–Brillouin method. Both the left-hand and right-hand circularly polarized (LCP and RCP) waves are taken into account. The transmission characteristics of RCP waves are more complicated than LCP waves. The numerical results show that all the physical parameters, such as the electron density, dust particle density, dust particle radius, effective collision frequency, electron relaxation rate and external magnetic field intensity, and so on, can affect the propagation, absorption and reflection of terahertz waves in dusty plasma. These theoretical results may be useful for alleviating the "blackout" problem and improving electromagnetic waves communication. [ABSTRACT FROM AUTHOR]

With increasing complexity of soil contamination and more variety in remediation technologies, remediation alternatives must be assessed thoroughly and urgently. Life cycle assessment (LCA) can be used to analyze the environmental impact of a technical process and avoid the transfer of the environmental impact. LCA has been applied in soil remediation technology from a single method to a combination of multiple methods, focusing on a few environmental impacts to approximately 20 types of environmental impacts. The life-cycle stage contributions and environmental impact characteristics of LCA are also reviewed. The proposed optimization measures cover the life cycle stages, specific energies or substances, and technology process nodes. The LCA methodology framework of remediation technology must be established by including functional unit determination considering the remediation duration and environmental impact selection methods. Primary, secondary, and tertiary impacts should be considered to reflect technical efficiency, process optimization of technology, and land reuse after restoration. LCA application still needs to be improved in terms of technological processes to reveal the relationship between technical parameters and environmental impacts. This study provides an insightful overview of the methodological elements of LCA in soil remediation technology evaluation, such as the functional unit definition, the system boundary determination, and the selection of impact categories, which can support the revolution of LCA methods applied in soil remediation technology. [ABSTRACT FROM AUTHOR]

Reasonable construction of high activity and low cost non-noble metal oxygen reduction reaction (ORR) catalyst is of great importance for the wide application of zinc-air batteries (ZABs). Using bimetallic MOF as a precursor combined with electrospinning, high-temperature carbonization and electrodeposition, we successfully developed a porous carbon nanofiber (Co@Fe-CNFs-1000) with bimetallic active center as an efficient catalyst for ORR. The successful construction of this special core-shell structure directly explores the synergy between different active centers. The results showed that the synthesized Co@Fe-CNFs-1000 catalyst exhibited ORR performance comparable to that of Pt/C in 0.1 mol/L KOH electrolyte, high half-wave potential (E1/2=0.81 V) and limiting current density (JL=5.4 mA-cm−2). In addition, homemade liquid ZABs with Co@Fe-CNFs-1000 as the air cathode showed excellent power density (155.8 mW·cm−2), specific capacity (780.6 mAh·gZn−1) and long-term stability (over 100 h at 2 mA·cm−2), surpassing even Pt/C-based batteries. In addition, the flexible solid-state ZABs assembled based on Co@Fe-CNFs-1000 demonstrates excellent flexibility and durability. This work provides a new idea for constructing ORR catalysts with high activity centers. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is considered the main contributor to acquired heart diseases in developed countries. However, the precise pathogenesis of KD remains unclear. Neutrophils play roles in KD. This study aimed to select hub genes in neutrophils in acute KD. Methods: mRNA microarray of neutrophils from four acute KD patients and three healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). DE-mRNAs were analyzed and predicted by Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction networks. Real time-PCR was finally conducted to confirm the reliability and validity of the expression level of DE-mRNAs from blood samples of healthy controls and KD patients in both acute and convalescent stage. Results: A total of 1950 DE-mRNAs including 1287 upregulated and 663 downregulated mRNAs were identified. GO and KEGG analyses revealed the DE-mRNAs were mainly enriched in the regulation of transcription from RNA polymerase II promoter, apoptotic process, intracellular signal transduction, protein phosphorylation, protein transport, metabolic pathways, carbon metabolism, lysosome, apoptosis, pyrimidine metabolism, alzheimer disease, prion disease, sphingolipid metabolism, huntington disease, glucagon signaling pathway, non-alcoholic fatty liver disease, pyruvate metabolism, sphingolipid signaling pathway, and peroxisome. Twenty hub DE-mRNAs were selected including GAPDH, GNB2L1, PTPRC, GART, HIST2H2AC, ACTG1, H2AFX, CREB1, ATP5A1, ENO1, RAC2, PKM, BCL2L1, ATP5B, MRPL13, SDHA, TLR4, RUVBL2, TXNRD1, and ITGAM. The real-time PCR results showed that BCL2L1 and ITGAM mRNA were upregulated in acute KD and were normalized in the convalescent stage. Conclusions: These findings may improve our understanding of neutrophils in KD. Key Points • Neutrophilic BCL2L1 and ITGAM mRNA were first reported to be correlated with the pathogenic mechanism of KD. [ABSTRACT FROM AUTHOR]

Two structurally different Tb(III)-nitronyl nitroxide (NITR) complexes, [Tb(hfac)3(NITpPh3Py)(H2O)] 1 and [Tb(hfac)3(NITpPh3Py)]22 (NITpPh3Py is 2-[4-methoxyphenyl(3-pyridinyl)]-4,4,5,5-tetramethyl-imidazoline1-oxyl-3-oxide; hfac is hexaflfluoroacetylacetonate) have been synthesized and characterized structurally as well as magnetically. The two complexes can be selectively obtained by controlling the reaction temperature and time of Tb(hfac)3·2H2O and the radical ligand NITpPh3Py. Single crystal X-ray diffraction studies reveal that complex 1 crystallizes in the orthorhombic space group Pbca with Z = 8, while complex 2 is in monoclinic space group P21/n with Z = 2. In complex 1, NITpPh3Py as monodentate ligand links to Tb(III) ion through the oxygen atom of ON group. In 2, it acts as a bridging ligand linking two Tb(III) ions through the N atom of pyridine unit and the oxygen atom of ON group to form a cyclic dimer. The static magnetic measurements on 1 and 2 exhibit antiferromagnetic interaction between Tb(III) ion and the radical ligand. Alternating current (ac) susceptibility measurements for 1 and 2 were carried out at low temperature under a zero-external field with an oscillation of 2.5 Oe, which show frequency dependent out-of-phase signals, indicating likely single-molecule magnet SMM behavior. [ABSTRACT FROM AUTHOR]

Despite being a clean and renewable energy source, photovoltaic (PV) power generation faces severe challenges in operation due to its strong intermittency and volatility compared to the traditional fossil fuel power generation. Accurate predictions are therefore crucial for PV's grid connections and the system security. The existing methods often rely heavily on weather forecasts, the accuracy of which is hard to be guaranteed. This paper proposes a novel GBDT-BiLSTM day-ahead PV forecasting model, which leverages the Teacher Forcing mechanism to combine the strong time-series processing capabilities of BiLSTM with an enhanced GBDT model. Given the uncertainty and volatility inherent in solar energy and weather conditions, the gradient boosting method is employed to update the weak learner, while a decision tree is incorporated to update the strong learner. Additionally, to explore the correlation between photovoltaic power output and historical time-series data, the adaptive gradient descent-based Adam algorithm is utilized to train the bidirectional LSTM model, enhancing the accuracy and stability of mid- to long-term time-series predictions. A prediction experiment, conducting with the real data from a PV power station in Sichuan Province, China, was compared with other methods to verify the model's effectiveness and robustness. [ABSTRACT FROM AUTHOR]

Although the interactions between traffic flow and epidemic spread dynamics have been extensively studied, the impact of routing strategies on the susceptible–infected–recovered (SIR) epidemic spread driven by traffic flow have not received enough attention. In this paper, the traffic-driven SIR epidemic spread model under the probability path routing strategy and the efficient path routing strategy are studied. The instantaneous scale I p of the infected nodes’ density and the final scale R e of the ever infected nodes’ density are obtained through simulation, and it is found that there exist optimal values of routing parameters to minimise I p and R e , what is more, I p and R e under the probability path routing strategy are smaller than the values under the efficient path routing strategy. This means that the epidemic spreading can be effectively controlled by adjusting the routing strategy. In addition, when the routing parameter is the optimal value, the influence of packet generation rates, infection rates and cure rates on the epidemic spreading under different routing strategies is further discussed, and it is found that the higher the cure rate, the fewer nodes will be infected. Infected nodes’ density increases as the infection rate and packet generation rate increase, thereby accelerating epidemic spreading. These studies have certain guiding significance for controlling the spread of the epidemic. [ABSTRACT FROM AUTHOR]

Offshore platforms are susceptible to structural damage due to prolonged exposure to random loads, such as wind, waves, and currents. This is particularly true for platforms that have been in service for an extended period. Identifying the modal parameters of offshore platforms is crucial for damage diagnosis, as it serves as a prerequisite and foundation for the process. Therefore, it holds great significance to prioritize the identification of these parameters. Aiming at the shortcomings of the traditional Fast Bayesian Fast Fourier Transform (FBFFT) method, this paper proposes a modal parameter identification method based on Automatic Frequency Domain Decomposition (AFDD) and optimized FBFFT. By introducing the AFDD method and Powell optimization algorithm, this method can automatically identify the initial value of natural frequency and solve the objective function efficiently and simply. In order to verify the feasibility and effectiveness of the proposed method, it is used to identify the modal parameters of the IASC-ASCE benchmark model and the jacket platform structure model, and the Most Probable Value (MPV) of the modal parameters and their respective posterior uncertainties are successfully identified. The identification results of the IASC-ASCE benchmark model are compared with the identification results of the MODE-ID method, which verifies the effectiveness and accuracy of the proposed method for identifying modal parameters. It provides a simple and feasible method for quantifying the influence of uncertain factors such as environmental parameters on the identification results, and also provides a reference for modal parameter identification of other large structures. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Low-temperature processing is important for improving the stability and performance of flexible quantum dot light-emitting diodes (QLEDs). In this study, QLEDs were fabricated using poly[bis(4-phenyl) (2,4,6-trimethylphenyl)amine] (PTAA) as a suitable hole transport layer (HTL) material owing to its low-temperature processability and vanadium oxide as the low-temperature solution-processable hole injection layer material. The maximum luminance and highest current efficiency of the QLEDs on a glass substrate with an optimal PTAA HTL was 8.9 × 104 Cd/m2 and 15.9 Cd/A, respectively, which was comparable to that of conventional devices. The QLEDs on a flexible substrate showed a maximum luminance of 5.4 × 104 Cd/m2 and highest current efficiency of 5.1 Cd/A. X-ray and ultraviolet photoelectron spectroscopies were used to investigate the chemical state and interfacial electronic structure according to the materials and the state changes of the HTL, respectively. The interfacial electronic structure showed that PTAA exhibited a better hole transport ability owing to its low hole injection barrier ( Φ h ). Moreover, QLEDs with a PTAA HTL could operate as photosensors under reverse bias conditions. These results indicate that the low-temperature-processed PTAA HTL is suitable for improving the performance of flexible QLEDs. [ABSTRACT FROM AUTHOR]

In a recent paper titled "Electrochemical characterisation of polymelamine electropolymerised in deep eutectic solvents for selective detection of dopamine" by Chang et al. (Electrocatalysis 12:238–250, 2021), the authors reported that synthesis of polymelamine (pMel) was achieved in deep eutectic solvents (DES) and the pMel (ethaline) composite was further selected for application in dopamine sensing. In terms of first try, to electrosynthesize pMel in DES system was a worthy contribution in their paper. However, there are some missing points that may lead to incorrect analysis of cyclic voltammetry in DES and eventually difficult to synthesis pMel under the conditions described in the paper. This work shows how the related conclusions are challenged by detailed characterization of electropolymerization process by cyclic voltammetry, electrochemical quartz crystal microbalance (EQCM) and atomic force microscopy (AFM). [ABSTRACT FROM AUTHOR]

Due to the excellent properties of titanium alloys, they are widely used in various fields. However, the poor tribological performance limits the further development of titanium alloys. In this paper, TC4 with microporous channels was manufactured by laser additive manufacturing technology. On this basis, TC4-Sn-Ag-Cu (TSAC) and TC4-Sn-Ag-Cu-Nb2C (TSACN) self-lubricating materials were prepared. The friction and wear tests were carried out under dry friction conditions, and tribological behaviors and friction-induced noise were analyzed. The results show that TSACN self-lubricating composite has outstanding tribological properties and noise suppression performance. Compared with TC4, the friction coefficient and equivalent sound pressure level of TSACN are reduced by 20.1 and 6.7%, respectively. The excellent tribological properties are mainly attributed to the synergistic effect of microporous channel and Sn-Ag-Cu-Nb2C. Microporous channel can promote the diffusing of lubricants and accelerate the formation rate of lubricating film; Nb2C can enhance soft metal lubricant Sn-Ag-Cu to make the lubricating film more dense. The lubricating film can repair wear pits, furrows and other defects on the worn surface and avoid the direct contact between the counterpart ball and the sample, thereby improving the tribological properties of TC4 and reducing the friction-induced vibration and noise. [ABSTRACT FROM AUTHOR]

Inspired by rhombic textures on shark skin surface, this paper designs bionic micro-textures filled by solid lubricants SnAgCu and Ti3C2TX to improve the tribological properties of 42CrMo steel. Compared with 42CrMo steel, the average friction coefficient and wear depth of 42CrMo-SnAgCu-Ti3C2TX with bionic micro-textures at 25 N were separately decreased by 41.52 and 79.07%, and decreased by 50.77 and 80% at 35 N, respectively. Two-dimensional material Ti3C2TX can be well combined with SnAgCu to promote the formation of a smooth and continuous lubricating film on the worn surface, which plays an excellent antifriction and wear resistance role under the specific working conditions. [ABSTRACT FROM AUTHOR]

To construct a protein arginine methyltransferase 1 (PRMT1) knockout human embryonic kidney cell line 293T (HEK293T/293T) and elucidate the effect on the proliferation of 293T cells, we generated a PRMT1 protein knockout 293T cell line with the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing and performed flow cytometry. Single edited 293T cells were screened by DNA sequencing and protein immunoblotting. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were performed to detect the effect of PRMT1 knockout on the proliferation of 293T cells, and the effects on 293T cell cycle distribution and apoptosis after PRMT1 knockout were analyzed by flow cytometry. The expression levels of c-Myc, a proliferation-related protein, and caspase-8, which classically triggers the extrinsic apoptotic pathway, in the wild-type (WT) 293T cell line and PRMT1 knockout cell lines were detected via western blotting. The cellular experimental results showed that knockout of PRMT1 inhibited the growth rate and clonal formation ability of 293T cells. In addition, 293T cells were arrested at the G2/M phase, and the proportion of apoptotic cells was increased as a result of PRMT1 depletion. Moreover, the expression levels of c-Myc and caspase-8 in the PRMT1 knockout cells were decreased compared with those in the WT 293T cells. Conclusion: Knockout of PRMT1 repressed the proliferation of 293T cells, more specifically, altering the distribution of cell cycle phases in 293T cells and promoting cell apoptosis of 293T cells. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Microplastics can act as carriers of heavy metals and may enter humans through ingestion and threaten human health. However, the bioaccessibility of heavy metals associated with microplastics and its implications for human health risk assessments are poorly understood. Therefore, in this study, four typical heavy metals (As(V), Cr(VI), Cd(II), and Pb(II)) and one typical microplastic (polyvinyl chloride, PVC) were chosen to estimate the human health risk of microplastic-associated heavy metals by incorporating bioaccessibility. Significant adsorption of heavy metals was observed with the following order for adsorption capacity: Pb(II) > Cr(VI) > Cd(II) > As(V); the efficiencies for desorption of these four heavy metals from PVC microplastics were all below 10%. The Fourier transform infrared spectroscopy results indicated that the functional groups on the surface of the virgin PVC microplastics did not play an important role in the capture process. Heavy metals in both gastric and small intestinal phases were prone to release from PVC microplastics when bioaccessibility was evaluated with the in vitro SBRC (Soluble Bioavailability Research Consortium) digestion model. In addition, Pb(II) bioaccessibility in the gastric phase was significantly higher than those in the other phases, while As(V), Cr(VI), and Cd(II) bioaccessibilities showed the opposite trend. After incorporating bioaccessibility adjustments, the noncarcinogenic hazards and carcinogenic risks determined were lower than those based on total metal contents. The individual hazard quotients (HQ) and carcinogenic risks (CR) for ingestion of these four heavy metals from PVC microplastics were all lower than the threshold values for adults and children. In summary, this study will provide a new view of the human health risks of heavy metals associated with microplastics. [ABSTRACT FROM AUTHOR]

Natural biodegradable polymers generally include polysaccharides (starch, alginate, chitin/chitosan, hyaluronic acid derivatives, etc.) and proteins (collagen, gelatin, fibrin, etc.). In transdermal drug delivery systems (TDDS), these polymers play a vital role in controlling the device's drug release. It is possible that natural polymers can be used for TDDS to attain predetermined drug delivery rates due to their physicochemical properties. These polymers can be employed to market products and scale production because they are readily available and inexpensive. As a result of these polymers, new pharmaceutical delivery systems can be developed that is both regulated and targeted. The focus of this article is the application of a biodegradable polymeric platform based on natural polymers for TDDS. Due to their biocompatibility and biodegradability, natural biodegradable polymers are frequently used in biomedical applications. Additionally, these natural biodegradable polymers are being studied for their characteristics and behaviors. [ABSTRACT FROM AUTHOR]

Histone demethylases containing the JmjC domain play an extremely important role in maintaining the homeostasis of histone methylation and are closely related to plant growth and development. Currently, the JmjC domain–containing proteins have been reported in many species; however, they have not been systematically studied in grapes. In this paper, 21 VviJMJ gene family members were identified from the whole grape genome, and the VviJMJ genes were classified into five subfamilies: KDM3, KDM4, KDM5, JMJD6, and JMJ-only based on the phylogenetic relationship and structural features of Arabidopsis and grape. After that, the conserved sites of VviJMJ genes were revealed by protein sequence analysis. In addition, chromosomal localization and gene structure analysis revealed the heterogeneous distribution of VviJMJ genes on grape chromosomes and the structural features of VviJMJ genes, respectively. Analysis of promoter cis-acting elements demonstrated numerous hormone, light, and stress response elements in the promoter region of the VviJMJ genes. Subsequently, the grape fruit was treated with MTA (an H3K4 methylation inhibitor), which significantly resulted in the early ripening of grape fruits. The qRT-PCR analysis showed that VviJMJ genes (except VviJMJ13c) had different expression patterns during grape fruit development. The expression of VviJMJ genes in the treatment group was significantly higher than that in the control group. The results indicate that VviJMJ genes are closely related to grape fruit ripening. [ABSTRACT FROM AUTHOR]

A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. To achieve this, quantitative trait locus (QTL) mapping of genetic variants with intermediate molecular phenotypes such as gene expression and splicing have been widely adopted1,2. However, despite successes, the molecular basis for a considerable fraction of trait-associated and disease-associated variants remains unclear3,4. Here we show that ADAR-mediated adenosine-to-inosine RNA editing, a post-transcriptional event vital for suppressing cellular double-stranded RNA (dsRNA)-mediated innate immune interferon responses5–11, is an important potential mechanism underlying genetic variants associated with common inflammatory diseases. We identified and characterized 30,319 cis-RNA editing QTLs (edQTLs) across 49 human tissues. These edQTLs were significantly enriched in genome-wide association study signals for autoimmune and immune-mediated diseases. Colocalization analysis of edQTLs with disease risk loci further pinpointed key, putatively immunogenic dsRNAs formed by expected inverted repeat Alu elements as well as unexpected, highly over-represented cis-natural antisense transcripts. Furthermore, inflammatory disease risk variants, in aggregate, were associated with reduced editing of nearby dsRNAs and induced interferon responses in inflammatory diseases. This unique directional effect agrees with the established mechanism that lack of RNA editing by ADAR1 leads to the specific activation of the dsRNA sensor MDA5 and subsequent interferon responses and inflammation7–9. Our findings implicate cellular dsRNA editing and sensing as a previously underappreciated mechanism of common inflammatory diseases.cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. Methods: A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. Results: The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13–13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05–11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. Conclusions: APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION. [ABSTRACT FROM AUTHOR]

Quantitative real-time polymerase chain reaction (qRT-PCR) is a sensitive and widely used technique for quantifying gene expression levels, and its accuracy depends on the reference genes used for data normalization. To date, no reference gene has been reported in the nutritious and functional vegetable okra (Abelmoschus esculentus L.). Herein, 11 candidates of reference genes were selected and evaluated for their expression stability in okra in different tissues at different developmental stages by using three software algorithms (geNorm, NormFinder, BestKeeper) and a web-based tool (RefFinder). Among them, eukaryotic initiation factor 4 alpha (eIF4A) and protein phosphatase 2A (PP2A) showed the highest stability, while TUA5 had the lowest stability. The combined usage of these two most stable reference genes was sufficient to normalize gene expression in okra. Then, the above results were further validated by normalizing the expression of the cellulose synthase gene CesA4. This work provides appropriate reference genes for transcript normalization in okra, which will facilitate subsequent functional gene research on this vegetable crop. [ABSTRACT FROM AUTHOR]

Studies have indicated that RIG-I may act as a tumor suppressor and participate in the tumorigenesis of some malignant diseases. However, RIG-I induces distinct cellular responses via different downstream signaling pathways depending on the cell type. To investigate the biological function and underlying molecular mechanism of RIG-I in the tumorigenesis of melanoma, we constructed RIG-I knockout, RIG-I-overexpressing B16-F10 and RIG-I knockdown A375 melanoma cell lines, and analyzed the RIG-I-mediated change in the biological behavior of tumor cells in spontaneous and poly (I:C)-induced RIG-I activation. Cell proliferation, cell cycling, apoptosis and migration were detected by CCK-8 assay, BrdU incorporation assay, Annexin V–PI staining assay and Transwell assay, respectively. In vivo tumorigenicity was evaluated by tumor xenograft growth in nude mice and subsequently by Ki67 staining and TUNEL assays. Furthermore, Western blotting was utilized to explore the underlying mechanism of RIG-I in melanoma cells. Our data showed that RIG-I promotes apoptosis and inhibits proliferation by G1 phase cell cycle arrest in the melanoma cell lines. Mechanistically, RIG-I induced the phosphorylation of p38 MAPK and MAPK kinases MKK3 and MKK4. In conclusion, the current study demonstrated that RIG-I suppressed the development of melanoma by regulating the activity of the MKK/p38 MAPK signaling pathway, which is relevant to research on novel therapeutic targets for this malignant disease. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is the most serious infectious disease pandemic in the world in a century, and has had a serious impact on the health, safety, and social and economic development of all mankind. Since the earth entered the "Anthropocene", human activities have become the most important driving force of the evolution of the earth system. At the same time, the epidemic frequency of major human infectious diseases worldwide has been increasing, with more than 70% of novel diseases having zoonotic origins. The review of several major epidemics in human history shows that there is a common rule, i.e., changes in the natural environment have an important and profound impact on the occurrence and development of epidemics. Therefore, the impact of the natural environment on the current COVID-19 pandemic and its mechanisms have become scientific issues that need to be resolved urgently. From the perspective of the natural environment, this study systematically investigated several major issues concerning the environmental transmission and risk prevention of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). From a macroscopic temporal and spatial scale, the research focus on understand the impact of the destruction of the natural environment and global changes on the outbreak of infectious diseases; the threat of zoonotic diseases to human health; the regularity for virus diffusion, migration and mutation in environmental media; the mechanisms of virus transmission from animals and environmental media to humans; and environmental safety, secondary risk prevention and control of major epidemics. Suggestions were made for future key research directions and issues that need attention, with a view to providing a reference for the prevention and control of the global coronavirus disease 2019, and to improving the ability of response to major public health emergencies. [ABSTRACT FROM AUTHOR]

Purpose: To summary the clinical features of premenopausal women with functioning gonadotroph adenomas (FGAs) and preliminarily explore their molecular characterization. Methods: 12 premenopausal females with FGAs in our center were retrospectively analyzed. Previously reported cases were also summarized. The patients were clinically divided into FSH- or LH-predominant types according to their preoperative serum FSH/LH ratio. The expressions of related genes in the tumor tissues of female FGAs, non-functioning gonadotroph adenomas (NFGAs), and silent corticotropin adenomas were evaluated by RT-qPCR. Results: Of all the 12 patients with FGAs from our center, 11 (91.7%) were diagnosed as FSH-predominant type, and they all had menstrual disorders, including 9 with spontaneous ovarian hyperstimulation syndrome (sOHSS). Their hormonal profiles showed non-suppressed FSH (12.45 ± 7.34 IU/L) with hyperestrogenemia [median estradiol level 1353.0 pg/mL (636.0, 3535.0)]. The other patient (8.3%) with LH-predominant type mainly manifested with infertility and sustained elevated serum LH without FSH or estradiol increasing. 65 premenopausal FGAs patients were systematic reviewed. 60 patients (92.3%) were FSH-predominant type, including 86.7% presented with menstrual disorders, 16.7% reported infertility, and 98.2% (55/56) showed sOHSS. No sOHSS or hyperestrogenemia were found in the 5 patients (7.7%) with LH-predominant type. Pituitary imaging data revealed macroadenomas and microadenomas accounted for 89.2% and 10.8%, respectively. Of 63 patients (96.9%) who underwent pituitary adenoma resection, 77.8% had complete tumor resection and no recurrence at the last follow-up. The relative expressions of KISS1 mRNA were significantly higher in FGA group than in NFGA group (p = 0.018), and significantly positively correlated with the preoperative serum estradiol levels (p = 0.004). Conclusions: Different clinical features were observed in premenopausal women with FGAs of FSH- or LH-predominant types. The elevated KISS1 expression in tumor tissues might involve in the secretion function of FGAs. [ABSTRACT FROM AUTHOR]

Background: The impact of activating transcription factor 4 (ATF4), differentially expressed in colorectal cancer (CRC), on 5-Fluorouracil (5-FU) chemoresistance has not been fully explained. The purpose of this study is to evaluate the clinical significance of ATF4-mediated microRNA-145 (miR-145)/histone deacetylase 4 (HDAC4)/p53 axis in CRC. Methods: Initially, the expression of ATF4, miR-145, HDAC4, and p53 in CRC tissues and cells was quantified by RT-qPCR and immunoblotting. Next, luciferase activity and chromatin immunoprecipitation assays were performed to verify the binding affinity among miR-145, ATF4, and HDAC4. Moreover, proliferation, clone formation, and apoptosis in CRC cells treated with 5-FU were assessed after gain- or loss-of-function of ATF4, miR-145, and/or HDAC4. Furthermore, the tumorigenicity and chemoresistance of CRC cells in mice were assayed for validating the in vitro findings. Results: ATF4 and HDAC4 were highly expressed, while miR-145 and p53 were poorly expressed in CRC tissues and cells. miR-145 targeted and negatively regulated HDAC4 to activate p53, and miR-145 expression was suppressed by ATF4. Of note, ATF4 facilitated cell proliferation and clone formation ability and repressed apoptosis to promote autophagy and chemoresistance of CRC cells by regulating the miR-145/HDAC4/p53 axis. In vivo experiment elucidated that ATF4-mediated miR-145/HDAC4/p53 axis enhanced tumorigenesis and resistance of CRC cells to 5-FU. Conclusion: In conclusion, ATF4-mediated miR-145 inhibition accelerated autophagy of CRC cells and boosted their resistance to 5-FU via the HDAC4/p53 axis. [ABSTRACT FROM AUTHOR]

Children (n = 240) between the ages of 2 and 17 years were randomly selected from three cities in China. The total amount of soil and dust (SD) on their hands was measured and ranged from 3.50–187.39 mg (median = 19.49 mg). We screened for seven elements (Ce, V, Y, Al, Ba, Sc, and Mn), and Ce levels were used to calculate hand SD by variability and soil elements. The main factors affecting SD amount were location and age group, as identified using a conditional inference tree. Hand SD and the hand SD intake rate were highest in Gansu Province, followed by Guangdong and Hubei provinces, respectively. Hand SD and the hand SD intake rate were highest among children in primary school, followed by kindergarten and secondary school, respectively. The hand SD intake rate of the three typical areas was 11.9 mg/d, which was about 26.6% of the children's soil intake rate (44.8 mg/d), indicating that hand-to-mouth contact is not the main route for children's soil intake in the three areas of China. [ABSTRACT FROM AUTHOR]

LRK10L-2 is known to be related to the plant disease response, little information is available about the relationship of LRK10L-2 and fruit ripening. The protein physicochemical properties, conserved domains, gene structures, subcellular localization, expression patterns during grape fruit development and promoter activity of the members of grape LRK10L-2 gene family were explored in this study. A total of 109 LRK10L-2 family gene members were identified, and mainly distributed on chromosome 16. Almost all of them were located in the plasma membrane. Most of the LRK10L-2 genes contain four or five motifs, ranging from 0 to 5 introns and have the cis-acting elements related to hormones in their promoter regions. There were 20 pairs of tandem duplicates and 293 pairs of segmental duplication in LRK10L-2 family genes. It was proved that the expression of LRK10L-2 gene varied at the different fruit development stages of 'Kyoho' and its early-ripening bud mutant, 'Fengzao'. The subcellular localization of VIT_16s0098g00160 and VIT_16s0098g00400 were in the plasma membrane, and had a significant enrichment of the GUS signal in N.benthamiana leaves for the promoter. The results lay a solid basis for the further functional researches of the LRK10L-2 genes for grape fruit ripening. [ABSTRACT FROM AUTHOR]

The heteroepitaxial δ-Ta2O5 films were deposited on α-Al2O3 (0001) by MOCVD. As the growth temperature increases from 650 °C to 800 °C, the structure of δ-Ta2O5 films changes from amorphous to single crystal, and finally to mixed phase structure. The film deposited at 750 °C exhibited the highest crystallinity and the corresponding epitaxial relationship were determined as δ-Ta2O5 ( 10 1 ¯ 1 ) ‖ α-Al2O3 (0001) with δ-Ta2O5 ⟨ 1 ¯ 2 1 ¯ 0 ⟩ ‖ α-Al2O3 ⟨ 10 1 ¯ 0 ⟩ . A simplified diagram was proposed to illustrate the growth mechanism. The optical bandgap of the prepared films was within 4.20–4.22 eV. The refractive index of the amorphous and heteroepitaxial films was within 2.1–2.5. [ABSTRACT FROM AUTHOR]

Mg-doped p-GaN, which cannot be etched and porosified by wet etching, is annealed in a N2 environment to fabricate porous p-GaN for the first time. In the annealing temperature range of 900–1150 °C, the pore size and pore density increase with the annealing temperature rising. The porous p-GaN with a V-shape pore structure obtained at 1050 °C presents the best crystal quality. We demonstrate that the formation of porous structures is largely due to the decomposition of GaN molecules located at the defects in the p-GaN epitaxial film. Porous p-GaN epitaxial wafers can be used to prepare violet light photodetectors. Compared with the as-grown sample, the porous GaN obtained at 1050 °C exhibits faster carrier mobility, higher light response speed, lower surface state density and similar visible light transmittance. Our work will promote the development of porous p-type GaN materials. [ABSTRACT FROM AUTHOR]

Background: Ocular hypertension is a major risk factor for glaucoma, which is characterized by the presence of ganglion cells, ganglion disease, and an irreversible reduction in the number of ganglion cells and axons. Although the anti-inflammatory and detoxifying effects of the maple tree (Acer palmatum Thunb.) leave extract are well known, it is unclear whether the extract can protect the eyes from ocular hypertension. Objective: This study was conducted to investigate whether the alcohol extract from A. palmatum Thunb. leaves (KIOM-2015E) had a protective effect on eyes in an animal model of steroid-induced ocular hypertension. We investigated whether KIOM-2015E had a therapeutic effect on ocular diseases induced by elevated intraocular pressure (IOP) by reducing IOP. Results: Ocular hypertension was induced in 9-week-old female C57BL/6 mice weighing 23–27 g with 4 weeks of steroid injection. After 4 weeks, 1 or 2 mg/mL of KIOM-2015E was instilled in the mice three times a day for 5 weeks. IOP was measured weekly, and the eyes were lysed after drug administration to investigate the changes in the histological parameters and the levels of anti-apoptotic proteins. IOP was elevated, OPN1SW levels were decreased in the retinal tissue, and GFAP levels were increased in the mice with induced ocular hypertension. IOP was lowered in a concentration-dependent manner in the mice treated with KIOM-2015E. KIOM-2015E was confirmed to have an inhibitory effect on the histological changes on the retina, activity of glial and astrocytic cells, and cell death. Conclusions: Treatment with KIOM-2015E improved steroid-induced ocular hypertension. KIOM-2015E prevented retinal degeneration caused by increased ocular pressure by regulating protein levels and histological parameter expression in retina. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT) and coronary artery lesions (CALs) among patients with Kawasaki disease (KD). Methods: Medical records of KD patients presenting to a single center between January 2019 and December 2020 were retrospectively collected and analyzed. Univariate, multivariable-adjusted analyses, subgroup analyses, restricted cubic spline test, and fitted curves were used to evaluate the associations between AST/ALT and CALs. Results: A total of 831 patients were enrolled, of which 201 (24.2%) had CALs on admission and 21 (2.5%) developed CALs de novo after intravenous immunoglobulin (IVIG). Multivariable-adjusted analyses models revealed that a lower AST/ALT was associated with an increased risk of CALs on admission when AST/ALT was a continuous variable (P = 0.007) and when it was a categorical variable (P for trend = 0.004). Each unit increase in AST/ALT was associated with a 22% lower risk of CALs on admission (odds ratio = 0.78, 95% confidence interval 0.65–0.94). A negative linear relationship was noted between AST/ALT and the risk of CALs on admission in both observed and fitted models. However, such associations were not observed in AST/ALT and CALs de novo after IVIG. None of the variables significantly modified the association between AST/ALT and CALs on admission and CALs de novo after IVIG (P > 0.05). Conclusion: Our findings suggested that AST/ALT was a risk factor of CALs, but was not associated with progressive CALs. [ABSTRACT FROM AUTHOR]

Litter decomposition is a key process controlling carbon (C) sequestration in Sphagnum dominated peatlands. Peatland drainage lowers the water table, increases vascular plant richness, and alters species evenness. We hypothesized that abiotic and biotic changes following peatland drainage would greatly accelerate litter decomposition. This hypothesis was tested by a litter decomposition experiment in an undrained and a drained area of a peatland which was partially drained 30 years ago. Litter bags filled with shoots of the peat moss Sphagnum magellanicum and leaves of the dwarf shrub Potentilla fruticosa as single species and species mixtures with three evenness treatments were placed at the surface of the peatland. After 6 months (from August onwards) of decomposition, the single species litter of Potentilla fruticosa, with low initial C/N ratio, decomposed much faster than S. magellanicum litter, with high initial C/N ratio in both undrained and drained areas. Overall, mixed litter produced antagonistic effects (observed values less than expected) on decomposition and C/N ratio. Litter mixtures dominated by S. magellanicum showed lower mass loss than other mixtures. Contrary to our expectation, the undrained area showed higher decomposition than the drained area. Our study suggests that drainage-induced alteration in plant diversity slows down litter decomposition in a short term. However, in drained peatlands, lower C/N ratio of mixed litter may enhance decomposition and reduce C sequestration over time. [ABSTRACT FROM AUTHOR]

The bionic rhombic textures with SnAgCu and Nb2C were used to improve tribological properties of M50. Compared with M50, friction coefficient and wear depth of M50-SnAgCu-Nb2C with 45° textures at 15 N were separately decreased by 42.67 and 70.37%, and those of M50-SnAgCu-Nb2C with 60° textures at 25 N were, respectively, decreased by 42.04 and 65.03%. Nb2C can promote the combination and spread of composite lubricants in bionic textures, and a uniform and dense lubrication layer was formed at the interface. The synergistic effect of SnAgCu-Nb2C and bionic textures can play an excellent antifriction and wear resistance role under specific working conditions. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are environmental chemicals that are formed due to incomplete combustion of the organic matters, or during heat treatment of the food. The objectives of the present study were first to estimate levels of the 15-priority PAHs in the edible vegetable oil (corn oil, sunflower oil, olive oil, and canola oil) collected from Egypt. Furthermore, the effect of heat treatment on the formation of PAHs in the canola oil was further examined. In addition, dietary intakes and cancer risk among Egyptian consumers were additionally calculated. The achieved results indicated presence of 15-priority PAHs in all examined oil samples. Canola oil had the highest residual concentrations of PAHs compared with the other tested oil species. Heat treatment of canola oil led to a drastic increase in the formed B[a]P (316.55%), total 2-PAHs (322.47%), total 4-PAHs (297.42%), total 8-PAHs (285.26%), and total 15-PAHs (443.32%), respectively. The incremental lifetime cancer risk among the Egyptian population is considered safe when was calculated for all examined oil samples. [ABSTRACT FROM AUTHOR]