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Solving uncertain differential equations is a critical subject in the field of uncertainty theory, where uncertain differential equations are a sort of differential equations that involve Liu processes. Currently, considerable effort has been put into addressing this issue. Regrettably, analytic solutions to uncertain differential equations are not always accessible. As a result, several numerical methods have been investigated. However, numerical methods have certain limitations in terms of providing a continuous representation of the solution as well as more information about the solution. This paper will propose a novel algorithm based on the variational iteration method (VIM) for solving uncertain differential equations analytically or approximately analytically. The associated numerical experiments show that the proposed method is an efficient tool for solving uncertain differential equations.

During the development of COVID-19 caused by SARS-CoV-2 infection from mild disease to severe disease, it can trigger a series of complications and stimulate a strong cellular and humoral immune response. However, the precise identification of blood immune cell response dynamics and the relevance to disease progression in COVID-19 patients remains unclear. We propose for the first time to use changes in cell numbers to establish new subgroups, which were divided into four groups: first from high to low cell number (H_L_Group), first from low to high (L_H_Group), continuously high (H_Group), and continuously low (L_Group). It was found that in the course of disease development. In the T cell subgroup, the immune response is mainly concentrated in the H_L_Group cell type, and the complications are mainly in the L_H_Group cell type. In the NK cell subgroup, the moderate patients are mainly related to cellular immunity, and the severe patients are mainly caused by the disease, while severe patients are mainly related to complications caused by diseases. Our study provides a dynamic response of immune cells in human blood during SARS-CoV-2 infection and the first subgroup analysis using dynamic changes in cell numbers, providing a new reference for clinical treatment of COVID-19.

The present study investigated patterns of adolescent life changes across multiple life domains and utilized a holistic-interactionistic perspective to examine their individual, familial, and societal correlates with a sample of 2544 Chinese parent-adolescent dyads. Adolescents were aged from 10 to 19 years old (50.16% girls). Latent profile analysis revealed five life change profiles, including three improved profiles at various degrees, one unchanged profile, and one worsened profile. The majority of adolescents had an improved or unchanged life. Multinomial logistic regression analyses found that most of the individual, familial, and societal factors predicted the group memberships. Notably, parent-adolescent conflict was a significant factor that predicted memberships of all patterns. These findings show the resilience of adolescents and indicate the need for policies and interventions that consider the holistic nature of adolescents' person-context system, especially during a global crisis such as the COVID-19 pandemic.

This paper proposes the concepts of uncertain strength, uncertain degree, and uncertain clustering coefficient under uncertain networks, along with the proposes uncertain k -shell decomposition algorithm and uncertain h -index. Susceptible-Infected-Recovered (SIR) epidemic model is used to simulate the propagation process under uncertain networks. When compared to with the propagation process under uncertain k -shell decomposition algorithm and uncertain h -index, it is discovered that there are few differences among these methods. In order to find a better node importance identification algorithm, this paper combines these methods using the information entropy to form a new node importance identification method, which is called uncertain entropy method. SIR epidemic model is used to illustrate the difference among these methods.

Starch from Pueraria lobata (PLS) had polyhedral or spherical granules, displaying a bimodal size distribution within 0.6-30 μm. It showed a trimodal distribution of different molecular weight peaks, with amylose fraction of 18.2 %. PLS had a high crystallinity degree of 37.76 % and consisted of C-type starch, which gelatinized at 64.46-79.61 °C, with a high range of gelatinization (15.15 °C) and high enthalpy (13.98 J/g). A 21-day supplementation of PLS presented a regulative effect on gut microbiota in normal mice, and alleviated DSS-induced murine colitis through attenuating colonic inflammation, maintaining barrier function, preventing gut dysbiosis, increasing the short-chain fatty acids production and inhibiting NF-κB/IL-1β axis. The protective effect of PLS against colitis was in a gut microbiota-dependent manner. Notably, the amylose fraction was responsible for the prebiotic effect of PLS. The results would potentiate new application of PLS and the amylose fraction as functional prebiotics for prevention of colitis.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Increasing studies showed that long non-coding RNAs (lncRNAs), a novel class of RNAs that are greater than 200 nucleotides in length but lack the ability to encode proteins, exert crucial roles in the occurrence and progression of HCC. LncRNAs promote the proliferation, migration, invasion, autophagy, and apoptosis of tumor cells by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can be used as biomarkers to predict the efficacy of HCC treatment strategies, such as surgery, radiotherapy, chemotherapy, and immunotherapy, and as a potential individualized tool for HCC diagnosis and treatment. In this review, we overview up-to-date findings on lncRNAs as potential biomarkers for HCC surgery, radiotherapy, chemotherapy resistance, target therapy, and immunotherapy, and discuss the potential clinical application of lncRNA as tools for HCC diagnosis and treatment.

Intestinal stem cells (ISCs) play an important role in maintaining intestinal homeostasis via promoting a healthy gut barrier. Within the stem cell niche, gut microbiota linking the crosstalk of dietary influence and host response has been identified as a key regulator of ISCs. Emerging insights from recent research reveal that ISC and gut microbiota interplay regulates epithelial self-renewal. This article reviews the recent knowledge on the key role of ISC in their local environment (stem cell niche) associating with gut microbiota and their metabolites as well as the signaling pathways. The current progress of intestinal organoid culture is further summarized. Subsequently, the key challenges and future directions are discussed.

The unique gate failure mode of SiC MOSFETs is often identified but has not been fully understood yet. In this letter, post-failure cell inspections demonstrate that its main cause is the crack at the SiO2 dielectric layer with melted source aluminum inside. An electro-thermal-mechanical simulation is performed to reproduce the failure transition, and it reveals that the crack forms at an early stage. This new failure mechanism further enlightens on the vulnerability of the vertical power MOSFET structure in extremely high-temperature operation.

Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.

To improve the quality of grapes and wine in warm viticulture regions, the effects of pearl, red and black photoselective nets on the quality of grapes and wine were systematically investigated. Compared with the CK (open field), three nets improved the microclimate conditions and reduced grape sugar and wine alcohol levels. However, the nets differentially affected other quality profiles of the grapes and wine. The pearl net reduced the total flavanol contents in grapes and total aromatic volatiles in wine. The red net increased the total flavanol, tannin and total aromatic volatile contents in wine by approximately 40%, 95% and 10%, respectively, and the percentages for the black net were 30%, 45% and 3%, respectively. The red and pearl nets were more inclined to improve the taste and aroma sensory qualities of wine than the black net did. The red net had the highest comprehensive scores via principal component analysis.

Background: Within China's hierarchical medical system, many patients seek medical care in different hospitals independently without integrated management. As a result, multi-hospital visiting is associated with fragmented service utilization and increased incidence of polypharmacy behaviors, especially for patients with chronic disease. It has been confirmed that factors from the perspective of patients may cause polypharmacy behaviors in Chinese community patients; whether having a usual primary care provider for chronic disease patients could reduce the polypharmacy behaviors and the effect size remains unanswered, and that is what our study aimed to answer.Methods: Our study adopted a cluster sampling method to select 1,196 patients with hypertension or diabetes and measured some information about them. The propensity score weighting method was adopted to eliminate the influence of confounding bias, and then a multivariate logistic regression model was conducted to test the relationship between having a usual primary care provider and polypharmacy behaviors.Results: Patients without usual primary care providers were significantly correlated with polypharmacy behaviors (OR = 2.40, 95%CI: 1.74–3.32, p p p p = 0.008), who communicate frequently with doctors (OR = 3.14, 95%CI: 1.62–6.19, p p = 0.027), who used to have meat-based food (OR = 1.42, 95%CI: 1.00–2.00, p = 0.049), and have vegetarian-based diet (OR = 1.42, 95%CI: 1.00–2.00, p = 0.049) are more likely to have polypharmacy behaviors, while patients aged between 65 and 75 years (OR = 0.50, 95%CI: 0.33–0.77, p = 0.020), used to be brain workers (OR = 0.67, 95%CI: 0.45–0.99, p = 0.048), with disease history between 10 and 20 years (OR = 0.56, 95%CI: 0.37–0.83, p = 0.005), have had adverse drug reactions (OR = 0.64, 95%CI: 0.45–0.93, p = 0.019), and participated in medical insurance for urban and rural residents (OR = 0.35, 95%CI: 0.21–0.58, p Conclusion: The results suggest that having a usual primary care provider may reduce the incidence of having polypharmacy behaviors; we can take intervention measures to promote establishing a long-term relationship between patients and primary care providers.

This study investigated the metabolic differences of ‘Zicui’ raisins produced at different drying temperatures (30 °C, 40 °C and 50 °C). Glucose, fructose, malic acid, shikimic acid and succinic acid contents were the highest in raisins dried at 50 °C. Compared with others, the drying temperature of 40 °C was more conducive to the accumulation of chalcones, dihydroflavones, dihydroflavonols, flavanols, flavonoid carbonosides, proanthocyanidins, and other phenols, while the drying temperature of 30 °C was more conducive to the accumulation of anthocyanins, flavonoid, and flavonols. Most volatile ketones and acids accumulated more in raisins produced at 30 °C, of which the content of 2,6-dimethyl-4-heptanone with sweet odour reached 70.34 μg/L, significantly higher than that in other raisins. Overall, the appropriate drying temperature should be selected according to the demand for specific nutritional or aromatic metabolites during raisins production.

ERECTA family (ERf) genes are found in many dicots and monocots, and play important roles in plant developmental processes and stress responses. However, there is little known on ERf genes in grape (Vitis vinifera L.). The primary objective of this study was to identify the ERf genes in grape, and to analyze their expression profiles in different organs, during development, and in response to hormone treatments and abiotic/biotic stresses. ERf protein sequences of dicots were aligned in the grape genome (V. vinifera cv. Pinot Noir, PN40024, 12X) with Blast server. The locus tags obtained were inputted in NCBI to retrieve corresponding nucleotide and protein accession numbers. The subcellular localization experiment was performed by the transient expression of VvERECTA-GFP and VvERL2-GFP in mesophyll protoplasts of Arabidopsis. The expression levels of ERf genes in grape leaves were detected by qRT-PCR after hormone treatments and abiotic/biotic stresses. We first identified the ERf genes in the grape genome, including VvERECTA and VvERL2. Their cDNA full-length sequences were obtained with the accession numbers MG601756 and MG601757. The result of subcellular localization indicated that the fusion proteins of VvERECTA and VvERL2 were localized in the plasma membrane. There were four conserved domains identified in VvERECTA and VvERL2, including a LRRNT-2, a LRR, a transmembrane and a protein kinase domain. The grape ERf genes expressed highly in young aboveground organs. As grape leaves or berries becoming mature, VvERECTA expressed in a declining trend. The transcript abundance of VvERL2 decreased during leaves development, but showed no significant differences during berries development. The hormone treatments of ABA, SA, MeJA and BR could induce the expression of VvERECTA and VvERL2. The treatments of heat, drought, downy and powdery mildew significantly increased the expression levels of the grape ERf genes. The grape ERECTA gene family might play crucial roles in response to abiotic and biotic stresses. We provide the first description of the grape ERf genes and the most comprehensive analysis of their expressions in different biological processes.

The frequency of convergence insufficiency was determined in a sample of Chinese high school students. The associations between the frequency of convergence insufficiency, gender, refractive error and accommodative insufficiency were investigated.This was a single-site, prospective cross-sectional study. In total, 928 eligible teenagers (mean age 15.9 ± 0.8) from a local high school in Guangzhou, Guangdong Province, China participated in this study. Refraction and binocular vision tests were performed on all eligible participants. The following three signs were used to classify participants: sign 1, exophoria at near at least 4The number and frequency of individuals with 3-Sign, 2-Sign, and 1-Sign convergence insufficiency as well as no convergence insufficiency group were 25 (2.7 per cent), 119 (12.8 per cent), 303 (32.6 per cent) and 481 (51.8 per cent), respectively. Gender (χCompared to the data from school- and clinic-based populations in the USA and South Africa, the data from this sample of Chinese high school students showed a lower frequency of 3-Sign convergence insufficiency (2.7 per cent). Convergence insufficiency was associated with refractive error, gender and accommodative insufficiency.

Developing economic, effective and stable bifunctional electrocatalysts to achieve sustainable hydrogen production is highly desired. Herein, C-coated CoP hollow microporous nanocages (C-CoP-1/12) are synthesized by calcination of a Prussian blue analog precursor and subsequent phosphorization treatment. Under alkaline condition, the C-CoP-1/12 exhibit splendid electrocatalytic performance with a low overpotential of 173 mV for hydrogen evolution reaction (HER) and 333 mV for oxygen evolution reaction (OER) at a current density of 10 mA cm-2. The C-CoP-1/12 show high electrocatalytic performance for overall water splitting at a low potential of only 1.650 V for the driving current density of 10 mA cm-2, and they exhibit remarkable stability for at least 24 h. The engineering of phosphating is the critical step for the synthesis of pure-phase CoP with hollow nanoarchitecture. Compared with Co2P, CoP possesses lower water dissociation barrier and favorable ΔGH* value according to theoretical calculations, resulting in superior electrocatalytic performance. Such impressive water splitting performance is mainly attributed to the collective effects of metal phosphide with unique electronic structure, the shortened electron transport paths, and the conductive C coating. This strategy is believed to provide a basis for the development of electrode materials with highly efficient electrocatalytic water-splitting capability.

Over the past decade, immunotherapy, especially cell-based immunotherapy, has provided new strategies for cancer therapy. Recent clinical studies demonstrated that adopting cell transfer of tumor-infiltrating lymphocytes (TILs) for advanced solid tumors showed good efficacy. TIL therapy is a type of cell-based immunotherapy using the patient’s own immune cells from the microenvironment of the solid tumor to kill tumor cells. In this review, we provide a comprehensive summary of the current strategies and challenges in TIL isolation and generation. Moreover, the current clinical experience of TIL therapy is summarized and discussed, with an emphasis on lymphodepletion regimen, the use of interleukin-2, and related toxicity. Furthermore, we highlight the clinical trials where TIL therapy is used independently and in combination with other types of therapy for solid cancers. Finally, the limitations, future potential, and directions of TIL therapy for solid tumor treatment are also discussed.

The dried roots of Pueraria lobata (Willd.) Ohwi as an edible medicinal herb are enriched with starch. However, the structure, physiology, and biological bioactivity of P. lobata starch (PLS) has not yet been fully investigated. This study showed that PLS consisted of mixed population of granules with polyhedral or spherical surface. The apparent content of resistant starch was 23.14%, and the molecular weight was 1.93 × 10

Raisins are a popular and nutritious snack that is produced through the dehydration of postharvest grape berries under high temperature (HT). However, the response of the endogenous metabolism of white grape varieties to postharvest dehydration under different temperature have not been fully elucidated to date. In this study, the white grape cultivar ‘Xiangfei’ was chosen to investigate the effect of dehydration at 50 °C, 40 °C, and 30 °C on the transcriptomic programme and metabolite profiles of grape berries. Postharvest dehydration promoted the accumulation of soluble sugar components and organic acids in berries. The content of gallic acid and its derivatives increased during the dehydration process and the temperature of 40 °C was the optimal for flavonoids and proanthocyanidins accumulation. High-temperature dehydration stress might promote the accumulation of gallic acid by increasing the expression levels of their biosynthesis related genes and regulating the production of NADP+ and NADPH. Compared with that at 30 °C, dehydration at 40 °C accelerated the transcription programme of 7654 genes and induced the continuous upregulation of genes related to the heat stress response and redox homeostasis in each stage. The results of this study indicate that an appropriate dehydration temperature should be selected and applied when producing polyphenols-rich raisins.

In this study, ultraviolet-C (UV-C) was utilized to improve the quality of post-harvest grape berries, and the transcriptomic and metabolomic basis of this improvement was elucidated. Berries of the red grape variety ‘Zicui’ and the white variety ‘Xiangfei’ were chosen to evaluate the effect of short- and long-term UV-C irradiation. Post-harvest UV-C application promoted malondialdehyde (MDA) and proline accumulation, and reduced the soluble solid content in berries. Both the variety and duration of irradiation could modulate the transcriptomic and metabolomic responses of berries to UV-C. Compared with the control, the differentially expressed genes (DEGs) identified under UV-C treatment were enriched in pathways related to metabolite accumulation, hormone biosynthesis and signal transduction, and reactive oxygen species (ROS) homeostasis. Flavonoid biosynthesis and biosynthesis of other secondary metabolites were the shared pathways enriched with differential metabolites. After long-term UV-C irradiation, cis-resveratrol accumulated in the berries of the two varieties, while the differential chalcone, dihydroflavone, flavonoid, flavanol, and tannin components primarily accumulated in ‘Xiangfei’, and some flavonols and anthocyanins primarily accumulated in ‘Zicui’. Based on an exhaustive survey, we made a summary for the effect of UV-C in regulating the quality development of post-harvest grape berries. The results of this study may help to elucidate the mechanism by which UV-C functions and support its efficient application.

Attention monitoring system is important for various tasks such as driving by alarming the person when he or she is not attending to the task at hand. Past research has not explored a usable attention monitoring system. In the current study, we used eye trackers, depth camera, and infrared cameras to assess the attention of the participants as they read texts. We extracted features from eye tracking and camera data, and then used convolutional neural network to predict the attention state of the participants. We found the eye tracker data yielded a 90% accuracy in predicting attentional state of the subjects. The camera data yielded over 70% accuracy in prediction.

Due to habitat destruction and illegal hunting and trade, the number of pangolins has been sharply reduced. To protect pangolins from extinction, relevant departments are combined and active action have been taken. A total of 21 confiscated Malayan pangolins were rescued in 2019, but died continuously for unknown reasons. This study aimed to investigate the reasons for the death of these pangolin and rescue them. 19 of the 21 confiscated pangolins had ticks on their body integument. A total of 303 ticks were collected and identified as Amblyomma javanense (A. javanense) according to their morphology and the sequences of 16S rRNA and internal transcribed spacer 2 (ITS2). There were multi-organ damages in the dead pangolins, especially congestion and hemorrhage in lung, heart and kidney and inflammation of which were observed using HE staining. Pathogens' nucleic acid detection showed ticks were only positive for Ehrlichia spp, with 56.7% positive rate of collected ticks (127/224), which was further confirmed in tissues from dead pangolins. Our findings confirm that ehrlichiosis caused by Ehrlichia spp. from A. javanense might accelerate the confiscated pangolin's death. More attention should be payed to tick-elimination work and the diagnoses and treatment of tick-borne diseases in the follow-up rescue operation., Graphical abstract Image 1, Highlights • Identification of Amblyomma javanense tick in confiscated Malayan Pangolins. • Internal transcribed spacer 2 (ITS2) regions of Amblyomma javanense were newly sequenced and uploaded in public database. • Ehrlichiosis caused by Ehrlichia spp. from A. javanense might accelerate the death of the confiscated Malayan pangolins. • This research provides an important reference for the diagnosis and prevention of pangolin-related diseases in the future.

This study investigated the effects of foliar nitrogen application from veraison to preharvest (FNVH) on flavonoids, fatty acids and aliphatic volatiles in Cabernet Sauvignon grapes and wines. Solutions with 69 and 138 mg N/plant phenylalanine (P1 and P2, respectively), 69 and 138 mg N/plant urea (U1 and U2, respectively), as well as an aqueous solution without nitrogen (CK), were sprayed three times from veraison to preharvest. U1, P1 had the highest anthocyanins and acylated anthocyanins contents in grapes, respectively. U1 and P2 showed great potential to promote the accumulation of flavonols and flavanols in grapes and wines. U2 increased the contents of almost all free aliphatic volatiles in grapes, while it didn’t affect the undesirable smell, and increased the concentrations of fruity esters in wines instead. The study showed FNVH was a useful fertilization way for improving contents of flavonoids and fruity aroma in grapes and wines in deficit-nitrogen vineyards.

γδT cells, a subgroup of T cells based on theγδTCR, when compared with conventional T cells (αβT cells), make up a very small proportion of T cells. However, its various subgroups are widely distributed in different parts of the human body and are attractive effectors for infectious disease immunity.γδT cells are activated and expanded by nonpeptidic antigens (P-Ags), major histocompatibility complex (MHC) molecules, and lipids which are associated with different kinds of pathogen infections. Activation and proliferation ofγδT cells play a significant role in diverse infectious diseases induced by viruses, bacteria, and parasites and exert their potential effector function to effectively eliminate infection. It is well known that many types of infectious diseases are detrimental to human life and health and give rise to high incidence of illnesses and death rate all over the world. To date, there is no comprehensive understanding of the correlation betweenγδT cells and infectious diseases. In this review, we will focus on the various subgroups ofγδT cells (mainly Vδ1 T cells and Vδ2 T cells) which can induce multiple immune responses or effective functions to fight against common pathogen infections, such asMycobacterium tuberculosis,Listeria monocytogenes, influenza viruses, HIV, EBV, and HBV. Hopefully, the gamma-delta T cell study will provide a novel effective way to treat infectious diseases.

Manganese oxide octahedral molecular sieves (OMS-2) is a kind of excellent redox catalysts, a key challenge still remains to further increase their catalytic performance. Herein, we report a facile reduction method to enhance the catalytic activity of OMS-2 by producing more oxygen vacancy and creating an active interface between the main phase MnO 2 and the minor phase Mn 3 O 4 . Compared to the pristine OMS-2, the OMS-2 catalyst reduced in a relatively short time exhibits superior performance for dimethyl ether combustion with a starting-off temperature of 163 °C and a complete combustion temperature of 230 °C. Such enhanced activity can be ascribed to the higher reducibility, the more oxygen vacancy, and the active heterogeneous interface. These findings open up a new way to design highly efficient catalysts, especially the metal oxides-based catalysts, for redox reactions.

This study investigated the effects of foliar application of fulvic acid antitranspirant (FA-AT) on Cabernet Sauvignon (CS) and Riesling grapes and wines in a warm viticulture region of China. FA-AT controlled the contents of total soluble solids, fructose and glucose in mature grapes and alcohol in wines. FA-AT improved total phenols and flavonoids in Riesling grapes, and total tannin and individual flavanols in CS grapes and wine, while reducing total individual phenolic acids and flavonols in CS wine. Increased volatiles in CS grapes (hexyl acetate, linalool) and wine (isoamyl alcohol, 1-hexanol, 2-phenylethanol) detected by SPME-GC-MS can contribute to the fruity and floral aroma. FA-AT reduced the accumulation of anthocyanins in CS grapes and wine without an eventual reduction in the tonality of wine by sensory analysis, and improved the taste and balance of Riesling wine. Overall, FA-AT can improve the quality of grapes and wines produced in warm viticulture regions.

Hierarchical pine tree-like α-MnO2 architectures are prepared by a facile one-step method without any template. The hierarchical α-MnO2 is composed of branched α-MnO2 short nanorods assembled onto the backbone of an α-MnO2 long nanowire. Time-dependent experiment shows that the growth process of the branched α-MnO2 nanostructures is the formation of β-MnOOH and then the transformation to a α-MnO2 branched structure in a step by step manner. Owing to its specific structure features, the hierarchical pine tree-like α-MnO2 exhibits superior catalytic performance in the catalytic combustion of dimethyl ether with a light-off temperature (T10) at 169 °C and a complete conversion temperature (T90) of 235 °C, which is far better than commercial MnO2.

In the reproduction of SiC MOSFET short-circuit behavior, one major issue that remains is the absence of a proper gate current model, which in tests strongly depends on device temperature. This paper discusses potential mechanisms and determines its origin as thermionic emission effect. By introducing the thermionic current to the classic semiconductor drift-diffusion framework that is coupled with lattice self-heating effect, dynamic gate leakage current development can be mirrored in simulation. Results also shed light on the possible failure physics by revealing the hotspot location, and practical concerns between two unmatched cells. In essence, this modeling method can also be applied to other similar high-temperature operations of SiC MOSFETs.

Methotrexate (MTX), the most commonly used anti-rheumatic drug against RA, enters the cell via the action of the reduced folate carrier 1(RFC1). A major polymorphism of the RFC1 gene, 80G/A, has been reported to influence the activity of RFC1, resulting in variable intracellular MTX-polyglutamate (MTX-PG) levels. However, the association studies addressing the RFC1 80G/A polymorphism and MTX efficacy or toxicity in Rheumatoid arthritis (RA) has yielded conflicting results. In the present meta-analysis, we aimed to evaluate the association between the RFC1 80G/A polymorphism and MTX efficacy or toxicity in RA patients. A total 17 studies met our inclusion criteria. Among them, 12 studies with 2049 subjects reported the association between the RFC1 80G/A and MTX response, and 12 studies involving 2627 subjects were on MTX-related toxicity. Meta-analysis revealed significant association between RFC1 80G/A polymorphism and MTX efficacy (odds ratio (OR) for the A allele=1.29, 95% confidence interval (CI) 1.05-1.67, P=0.02; for AA genotype: OR=1.49, 95%CI 1.17-1.907, P=0.001). However, no association could be detected in the analysis of MTX-related toxicity. Stratification by ethnic population also indicated an association between this polymorphism and MTX efficacy in Asian group (P=0.002 for A allele; P=0.003 for AA genotype), but not in the Caucasian group (P=0.15 for A allele; P=0.05 for AA genotype). In both Asian and Caucasian sub-groups, no influence of the RFC1 80G/A polymorphism on MTX toxicity can be detected. In conclusion, the RFC1 G80A polymorphism is associated with responsiveness to MTX therapy, but may not be associated with MTX toxicity in RA patients.