miR-130b regulates B cell proliferation via CYLD-mediated NF-κB signaling.

Previous studies have revealed that B cell activation is regulated by various microRNAs(miRNAs). However, the role of microRNA-130b regulating B cell activation and apoptosis is still unclear. In the present study, we first found that the expression of miR-130b was the lowest in Pro/Pre-B cells and the highest in immature B cells. Besides, the expression of miR-130b decreased after activation in B cells. Through the immuno-phenotypic analysis of miR-130b transgenic and knockout mice, we found that miR-130b mainly promoted the proliferation of B cells and inhibited B cell apoptosis. Furthermore, we identified that Cyld, a tumor suppressor gene was the target gene of miR-130b in B cells. Besides, the Cyld-mediated NF-κB signaling was increased in miR-130b overexpressed B cells, which further explains the enhanced proliferation of B cells. In conclusion, we propose that miR-130b promotes B cell proliferation via Cyld-mediated NF-κB signaling, which provides a new theoretical basis for the molecular regulation of B cell activation.

DTX3L Enhances Type I Interferon Antiviral Response by Promoting the Ubiquitination and Phosphorylation of TBK1.

Studies already revealed that some E3 ubiquitin ligases participated in the immune response after viral infection by regulating the type I interferon (IFN) pathway. Here, we demonstrated that type I interferon signaling enhanced the translocation of ETS1 to the nucleus and the promoter activity of E3 ubiquitin ligase DTX3L (deltex E3 ubiquitin ligase 3L) after virus infection and thus increased the expression of DTX3L. Further experiments suggested that DTX3L ubiquitinated TBK1 at K30 and K401 sites on K63-linked ubiquitination pathway. DTX3L was also necessary for mediating the phosphorylation of TBK1 through binding with the tyrosine kinase SRC: both together enhanced the activation of TBK1. Therefore, DTX3L, being an important positive-feedback regulator of type I interferon, exerted a key role in antiviral response. IMPORTANCE Our present study evaluated DTX3L as an antiviral molecule by promoting IFN production and establishing an IFN-ß-ETS1-DTX3L-TBK1 positive-feedback loop as a novel immunomodulatory step to enhance interferon signaling and inhibit respiratory syncytial virus (RSV) infection. Our finding enriches and complements the biological function of DTX3L and provides a new strategy to protect against lung diseases such as bronchiolitis and pneumonia that develop with RSV.

Convolutional neural network-based measurement of crown-implant ratio for implant-supported prostheses.

STATEMENT OF PROBLEM: Research has revealed that the crown-implant ratio (CIR) is a critical variable influencing the long-term stability of implant-supported prostheses in the oral cavity. Nevertheless, inefficient manual measurement and varied measurement methods have caused significant inconvenience in both clinical and scientific work. PURPOSE: This study aimed to develop an automated system for detecting the CIR of implant-supported prostheses from radiographs, with the objective of enhancing the efficiency of radiograph interpretation for dentists. MATERIAL AND METHODS: The method for measuring the CIR of implant-supported prostheses was based on convolutional neural networks (CNNs) and was designed to recognize implant-supported prostheses and identify key points around it. The experiment used the You Only Look Once version 4 (Yolov4) to locate the implant-supported prosthesis using a rectangular frame. Subsequently, two CNNs were used to identify key points. The first CNN determined the general position of the feature points, while the second CNN finetuned the output of the first network to precisely locate the key points. The network underwent testing on a self-built dataset, and the anatomic CIR and clinical CIR were obtained simultaneously through the vertical distance method. Key point accuracy was validated through Normalized Error (NE) values, and a set of data was selected to compare machine and manual measurement results. For statistical analysis, the paired t test was applied (α=.05). RESULTS: A dataset comprising 1106 images was constructed. The integration of multiple networks demonstrated satisfactory recognition of implant-supported prostheses and their surrounding key points. The average NE value for key points indicated a high level of accuracy. Statistical studies confirmed no significant difference in the crown-implant ratio between machine and manual measurement results (P>.05). CONCLUSIONS: Machine learning proved effective in identifying implant-supported prostheses and detecting their crown-implant ratios. If applied as a clinical tool for analyzing radiographs, this research can assist dentists in efficiently and accurately obtaining crown-implant ratio results.

Long-cycling and High-voltage Solid State Lithium Metal Batteries Enabled by Fluorinated and Crosslinked Polyether Electrolytes.

Solid-state lithium metal batteries (LMBs), constructed through the in situ fabrication of polymer electrolytes, are considered a critical strategy for the next-generation battery systems with high energy density and enhanced safety. However, the constrained oxidation stability of polymers, such as the extensively utilized polyethers, limits their applications in high-voltage batteries and further energy density improvements. Herein, an in situ fabricated fluorinated and crosslinked polyether-based gel polymer electrolyte, FGPE, is presented, exhibiting a high oxidation potential (5.1 V). The fluorinated polyether significantly improves compatibility with both lithium metal and high-voltage cathode, attributed to the electron-withdrawing -CF3 group and the generated LiF-rich electrolyte/electrode interphase. Consequently, the solid-state Li||LiNi0.6Co0.2Mn0.2O2 batteries employing FGPE demonstrate exceptional cycling performances of 1000 cycles with 78 % retention, representing one of the best results ever reported for polymer electrolytes. Moreover, FGPE enables batteries to operate at 4.7 V, realizing the highest operating voltage of polyether-based batteries to date. Notably, our designed in situ FGPE provides the solid-state batteries with exceptional cycling stability even at practical conditions, including high cathode loading (21 mg cm-2) and industry-level 18650-type cylindrical cells (1.3 Ah, 500 cycles). This work provides critical insights into the development of oxidation-stable polymer electrolytes and the advancement of practical high-voltage LMBs.

In-Situ Cross-linked F- and P-Containing Solid Polymer Electrolyte for Long-Cycling and High-Safety Lithium Metal Batteries with Various Cathode Materials.

The practical application of lithium metal batteries (LMBs) has been hindered by limited cycle-life and safety concerns. To solve these problems, we develop a novel fluorinated phosphate cross-linker for gel polymer electrolyte in high-voltage LMBs, achieving superior electrochemical performance and high safety simultaneously. The fluorinated phosphate cross-linked gel polymer electrolyte (FP-GPE) by in-situ polymerization method not only demonstrates high oxidation stability but also exhibits excellent compatibility with lithium metal anode. LMBs utilizing FP-GPE realize stable cycling even at a high cut-off voltage of 4.6 V (vs Li/Li+) with various high-voltage cathode materials. The LiNi0.6Co0.2Mn0.2O2|FP-GPE|Li battery exhibits an ultralong cycle-life of 1200 cycles with an impressive capacity retention of 80.1 %. Furthermore, the FP-GPE-based batteries display excellent electrochemical performance even at practical conditions, such as high cathode mass loading (20.84 mg cm-2), ultrathin Li (20 µm), and a wide temperature range of -25 to 80 °C. Moreover, the first reported solid-state 18650 cylindrical LMBs have been successfully fabricated and demonstrate exceptional safety under mechanical abuse. Additionally, the industry-level 18650 cylindrical LiMn2O4|FP-GPE|Li4Ti5O12 cells demonstrate a remarkable cycle-life of 1400 cycles. Therefore, the impressive electrochemical performance and high safety in practical batteries demonstrate a substantial potential of well-designed FP-GPE for large-scale industrial applications.

Protective Geometry and Reproductive Anatomy as Candidate Determinants of Clutch Size Variation in Pentatomid Bugs.

AbstractMany animals lay their eggs in clusters. Eggs on the periphery of clusters can be at higher risk of mortality. We asked whether the most commonly occurring clutch sizes in pentatomid bugs could result from geometrical arrangements that maximize the proportion of eggs in the cluster's interior. Although the most common clutch sizes do not correspond with geometric optimality, stink bugs do tend to lay clusters of eggs in shapes that protect increasing proportions of their offspring as clutch sizes increase. We also considered whether ovariole number, an aspect of reproductive anatomy that may be a fixed trait across many pentatomids, could explain observed distributions of clutch sizes. The most common clutch sizes across many species correspond with multiples of ovariole number. However, there are species with the same number of ovarioles that lay clutches of widely varying size, among which multiples of ovariole number are not overrepresented. In pentatomid bugs, reproductive anatomy appears to be more important than egg mass geometry in determining clutch size uniformity. In addition, our analysis demonstrates that groups of animals with little variation in ovariole number may nonetheless lay a broad range of clutch shapes and sizes.

PLC1 mediated Cycloastragenol-induced stomatal movement by regulating the production of NO in Arabidopsis thaliana.

BACKGROUND: Astragalus grows mainly in drought areas. Cycloastragenol (CAG) is a tetracyclic triterpenoid allelochemical extracted from traditional Chinese medicine Astragalus root. Phospholipase C (PLC) and Gα-submit of the heterotrimeric G-protein (GPA1) are involved in many biotic or abiotic stresses. Nitric oxide (NO) is a crucial gas signal molecule in plants. RESULTS: In this study, using the seedlings of Arabidopsis thaliana (A. thaliana), the results showed that low concentrations of CAG induced stomatal closure, and high concentrations inhibited stomatal closure. 30 µmol·L-1 CAG significantly increased the relative expression levels of PLC1 and GPA1 and the activities of PLC and GTP hydrolysis. The stomatal aperture of plc1, gpa1, and plc1/gpa1 was higher than that of WT under CAG treatment. CAG increased the fluorescence intensity of NO in guard cells. Exogenous application of c-PTIO to WT significantly induced stomatal aperture under CAG treatment. CAG significantly increased the relative expression levels of NIA1 and NOA1. Mutants of noa1, nia1, and nia2 showed that NO production was mainly from NOA1 and NIA1 by CAG treatment. The fluorescence intensity of NO in guard cells of plc1, gpa1, and plc1/gpa1 was lower than WT, indicating that PLC1 and GPA1 were involved in the NO production in guard cells. There was no significant difference in the gene expression of PLC1 in WT, nia1, and noa1 under CAG treatment. The gene expression levels of NIA1 and NOA1 in plc1, gpa1, and plc1/gpa1 were significantly lower than WT, indicating that PLC1 and GPA1 were positively regulating NO production by regulating the expression of NIA1 and NOA1 under CAG treatment. CONCLUSIONS: These results suggested that the NO accumulation was essential to induce stomatal closure under CAG treatment, and GPA1 and PLC1 acted upstream of NO.

Influence of Cirrhosis on 68Ga-FAPI PET/CT in Intrahepatic Tumors.

Background Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) is of great diagnostic value for intrahepatic tumors. However, cirrhosis may lead to increased 68Ga-FAPI uptake in background liver, affecting the diagnostic ability of 68Ga-FAPI. Purpose To assess the effect of cirrhosis on liver parenchyma and intrahepatic tumor uptake of 68Ga-FAPI and to compare the ability of 68Ga-FAPI and fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT to depict intrahepatic tumors in patients with cirrhosis. Materials and Methods In this secondary analysis of a prospective trial, patients who underwent both 68Ga-FAPI and 18F-FDG PET/CT and those who underwent only 68Ga-FAPI PET/CT between August 2020 and May 2022 were considered for inclusion in the cirrhotic or noncirrhotic group, respectively. Patients with cirrhosis were chosen via a comprehensive assessment of imaging and clinical data, and patients without cirrhosis were randomly selected. 68Ga-FAPI and 18F-FDG PET/CT data were measured by two radiologists. Between-groups and within-group data were tested with the Mann-Whitney U test and the Wilcoxon signed-rank test, respectively. Results A total of 39 patients with cirrhosis (median age, 58 years [IQR, 50-68]; 29 male; 24 intrahepatic tumors) and 48 patients without cirrhosis (median age, 59 years [IQR, 51-67]; 30 male; 23 intrahepatic tumors) were evaluated. In patients without intrahepatic tumors, the liver 68Ga-FAPI average standardized uptake value (SUVavg) was higher in the cirrhotic group than in the noncirrhotic group (median SUVavg, 1.42 [IQR, 0.55-2.85] vs 0.45 [IQR, 0.41-0.72]; P = .002). However, no difference was observed in the diagnosis of intrahepatic tumor sensitivity (98% vs 93%, respectively). When compared with 18F-FDG, the sensitivity of 68Ga-FAPI PET/CT in the detection of intrahepatic tumors in patients with cirrhosis (41% vs 98%, respectively) and maximum standardized uptake value of tumors (median SUVmax, 2.60 [IQR, 2.14-4.49] vs 6.68 [IQR, 4.65-10.08]; P < .001) were higher. Conclusion The sensitivity of 68Ga-FAPI in the diagnosis of intrahepatic tumors was not affected by cirrhosis, and diagnostic accuracy of 68Ga-FAPI was higher than that of 18F-FDG in patients with cirrhosis. © RSNA, 2023 Supplemental material is available for this article.

Oral Metal-Free Melanin Nanozymes for Natural and Durable Targeted Treatment of Inflammatory Bowel Disease (IBD).

Oral antioxidant nanozymes bring great promise for inflammatory bowel disease (IBD) treatment. To efficiently eliminate reactive oxygen species (ROS), various metal-based nanozymes have been developed for the treatment of IBD but their practical applications are seriously impaired by unstable ROS-eliminating properties and potential metal ion leakage in the digestive tract. Here, the authors for the first time propose metal-free melanin nanozymes (MeNPs) with excellent gastrointestinal stability and biocompatibility as a favorable therapy strategy for IBD. Moreover, MeNPs have extremely excellent natural and long-lasting characteristics of targeting IBD lesions. In view of the dominant role of ROS in IBD, the authors further reveal that oral administration of MeNPs can greatly alleviate the six major pathological features of IBD: oxidative stress, endoplasmic reticulum stress, apoptosis, inflammation, gut barrier disruption, and gut dysbiosis. Overall, this strategy highlights the great clinical application prospects of metal-free MeNPs via harnessing ROS scavenging at IBD lesions, offering a paradigm for antioxidant nanozyme in IBD or other inflammatory diseases.

The emerging roles of MAPK-AMPK in ferroptosis regulatory network.

Ferroptosis, a newform of programmed cell death, driven by peroxidative damages of polyunsaturated-fatty-acid-containing phospholipids in cellular membranes and is extremely dependent on iron ions, which is differs characteristics from traditional cell death has attracted greater attention. Based on the curiosity of this new form of regulated cell death, there has a tremendous progress in the field of mechanistic understanding of ferroptosis recent years. Ferroptosis is closely associated with the development of many diseases and involved in many diseases related signaling pathways. Not only a variety of oncoproteins and tumor suppressors can regulate ferroptosis, but multiple oncogenic signaling pathways can also have a regulatory effect on ferroptosis. Ferroptosis results in the accumulation of large amounts of lipid peroxides thus involving the onset of oxidative stress and energy stress responses. The MAPK pathway plays a critical role in oxidative stress and AMPK acts as a sensor of cellular energy and is involved in the regulation of the energy stress response. Moreover, activation of AMPK can induce the occurrence of autophagy-dependent ferroptosis and p53-activated ferroptosis. In recent years, there have been new advances in the study of molecular mechanisms related to the regulation of ferroptosis by both pathways. In this review, we will summarize the molecular mechanisms by which the MAPK-AMPK signaling pathway regulates ferroptosis. Meanwhile, we sorted out the mysterious relationship between MAPK and AMPK, described the crosstalk among ferroptosis and MAPK-AMPK signaling pathways, and summarized the relevant ferroptosis inducers targeting this regulatory network. This will provide a new field for future research on ferroptosis mechanisms and provide a new vision for cancer treatment strategies. Video Abstract.

Associations between visceral adipose index and stress urinary incontinence among US adult women: a cross-sectional study.

OBJECTIVE: Visceral adipose index (VAI) is a novel parameter for the evaluation of visceral obesity. The present study aimed to investigate the association between VAI levels and stress urinary incontinence (SUI) in a nationally representative population. MATERIALS AND METHODS: The National Health and Nutrition Examination Survey (NHANES) women population aged > 20 years were analyzed from 2001 to 2018. SUI was determined by self-reported questions. VAI was calculated using physical examination data and laboratory tests. Survey-weighted logistic regression models were used to analyze the correlation between SUI and VAI. RESULTS: The final analysis included 9709 women. Among them, 4032 (41.53%) were any SUI, 1130 (11.64%) were at least weekly SUI, and 506 (5.21%) were at least daily SUI. In multivariate analysis, the odds ratio (OR) for overall SUI increased slightly after full adjustment (OR 1.06, 95% CI 1.03-1.10, P = 0.001). Similar results were observed in weekly (OR 1.04, 95% CI 1.00-1.08, P = 0.0327) and daily (OR 1.04, 95% CI 1.00-1.09, P = 0.0702) SUI. The analysis of VAI categorized showed an increased OR of any, weekly, and daily SUI in the highest compared to the lowest tertile (OR 1.44, 95% CI 1.26-1.65, P < 0.0001 for trend, OR 1.38, 95% CI 1.07-1.78, P = 0.0153 for trend, OR 1.33, 95% CI 0.94-1.87, P = 0.094 for trend). CONCLUSION: This study revealed a significant association between SUI and VAI among US adult women. VAI is an easily applicable index for the evaluation of visceral fat dysfunction, which might be useful for the calculation of SUI risk.

Analysis of carotid vulnerable plaque MRI high-risk features and clinical risk factors associated with concomitant acute cerebral infarction.

BACKGROUND: This study aimed to investigate the correlation between the high-risk characteristics of high-resolution MRI carotid vulnerable plaques and the clinical risk factors and concomitant acute cerebral infarction (ACI). METHODS: Forty-five patients diagnosed with a single vulnerable carotid plaque by MRI were divided into two groups based on whether they had ipsilateral ACI. The clinical risk factors and the observation values or frequency of occurrence of high-risk MRI phenotypes of plaque volume, LRNC, IPH and ulcer were statistically compared between the two groups. RESULTS: A total of 45 vulnerable carotid artery plaques were found in 45 patients, 23 patients with ACI and 22 patients without ACI. There were no significant differences in age, sex, smoking, serum TC, TG and LDL between the two groups (all P > 0.05), but the ACI group had significantly more patients with hypertension (P < 0.05) and the without ACI group coronary heart disease (P < 0.05). The volume of vulnerable carotid plaque in the group with ACI (1004.19 ± 663.57 mm3) was significantly larger than that in the group without ACI (487.21 ± 238.64 mm3) (P < 0.05). The phenotype of vulnerable carotid artery plaque was 13 cases of LRNC, 8 cases of LRNC + IPH, 5 cases of LRNC + Ulcer, and 19 cases of LRNC + IPH + Ulcer. There was no significant difference in this distribution between the two groups (all P > 0.05) with the exception of LRNC + IPH + Ulcer. The 14 cases of LRNC + IPH + LRNC + IPH + Ulcer (60.87%) in the group with ACI and was significantly greater than the 5 (22.73%) in patients without ACI (P < 0.05). CONCLUSION: It is preliminarily thought that hypertension is the main clinical risk factor for vulnerable carotid plaques with ACI and the combination of plaque volume with vulnerable carotid plaque and LRNC + IPH + Ulcer is a high-risk factor for complicated ACI. It has high clinical therapeutic value due to the accurate diagnosis of responsible vessels and plaques with high-resolution MRI.

Research Progress on Extraction, Isolation, Structural Analysis and Biological Activity of Polysaccharides from Panax Genus.

The panax genus is a widely used medicinal plant with good biological activity. As one of the main active components of the Panax genus, polysaccharides have various pharmacological effects. This review summarizes the latest research reports on ginseng, American ginseng, and Panax notoginseng polysaccharides and compares the differences in extraction, isolation and purification, structural characteristics, and biological activities. The current research mainly focuses on ginseng polysaccharides, and the process of extraction, isolation, and structure analysis of each polysaccharide is roughly the same. Modern pharmacological studies have shown that these polysaccharides have antioxidants, antitumor, immunomodulatory, antidiabetic, intestinal protection, skin repair, and other biological activities. This review provides new insights into the differences between the three kinds of ginseng polysaccharides which will help to further study the medicinal value of ginseng in traditional Chinese medicine.

Evaluation of the effects of reservoir construction on the relationship between runoff and sediment load in the upper reaches of the Yellow River.

In order to evaluate the impact of the Longyangxia Reservoir construction on the relationship between runoff and sediment load (RRSL) in the upper reaches of the Yellow River, the runoff and sediment load monitoring data are used to identify variation point by sliding correlation coefficient method. Then with Copula function, the various countering situations of runoff and sediment load before and after variation are proposed to innovatively reveal their changing relations. The results demonstrate that (1) the reservoir construction exerts a great impact on the RRSL in the upper reaches of the Yellow River with the occurring variation point in 1987. The correlation of runoff and sediment load is presented better before variation but tends to worse decrease after variation. (2) Either before or after variation, runoff follows the generalized extreme value distribution, while sediment load before variation obeys the normal distribution, but the lognormal distribution after variation. Meanwhile, Frank Copula function accurately simulates the RRSL before variation, whereas Clayton Copula function is selected after variation. (3) The probability of synchronous rich and poor runoff and sediment load is higher before variation. After variation, the RRSL decreases significantly; their synchronous probability decreases by 45.67%. Meanwhile, the asynchronous probability of their extreme events evidently increases. The joint recurrence and co-recurrence intervals before variation are smaller than those after variation, along with the decreasing of their volume peak. This study provides new knowledge of runoff and sediment load influenced by reservoir construction, and also offers guidance for flood control and sediment load-discharge schemes of reservoir.

From DNMT1 degrader to ferroptosis promoter: Drug repositioning of 6-Thioguanine as a ferroptosis inducer in gastric cancer.

Though various therapeutic strategies have been developed to overcome gastric cancer, the overall prognosis and therapeutic effect are still not optimistic. As a novel identified type of cell death, ferroptosis has been considered as a promising tumor suppression mechanism with therapeutic potential against gastric cancer. In this work, we screened a collection of 4890 bioactivity compounds and committed to find novel agents that can induce apoptosis in gastric cancer. Among these compounds, 6-TG was identified as a potential ferroptosis inducer in gastric cancer cells for the first time. It could inactivate system xc-, block the generation of GSH, down-regulate the expression of GPX4, increase the level of lipid ROS, and finally trigger the Fe2+-mediated ferroptosis in MGC-803 and AGS cell lines. The date in vivo also suggested that compound 6-TG performed anti-tumor activity via inducing ferroptosis. These findings gave a support for 6-TG may play as a novel leading compound for gastric cancer treatment as a ferroptosis inducer.

CD38-Directed Vincristine Nanotherapy for Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although intensive chemotherapy greatly improved the survival rate, it is often accompanied by severe and lifelong side effects as a result of weak ALL selectivity. The intensive and poorly selective chemotherapy is also detrimental to patients' immune system. There is an urgent need to develop more selective and less toxic chemotherapy for ALL. Here, we report daratumumab-polymersome-vincristine (DP-VCR) as a CD38-directed nanotherapy for ALL. DP-VCR showed selective uptake in CD38-positive 697 and Nalm-6-Luc ALL cells and potent anti-ALL activity with an IC50 as low as 0.06 nM VCR, which was 13.7-fold more potent than free VCR. In contrast, no toxicity to human peripheral blood mononuclear cells was detected for DP-VCR even at 108.3 nM VCR. The apoptotic assays confirmed a high selectivity of DP-VCR to CD38-positive ALL cells. DP-VCR exhibited superior treatment of both 697 and Nalm-6-Luc orthotopic ALL models to all controls, as revealed by significant survival benefit and marked reduction of leukemia burden in bone marrow, blood, spleen, and liver. Importantly, DP-VCR induced few side effects. DP-VCR emerges as a safe and potent nanotherapy for CD38-positive ALL.

Synergetic Effects of Zn Alloying and Defect Engineering on Improving the CdS Buffer Layer of Cu2ZnSnS4 Solar Cells.

The inferior electrical properties at the interface of the Cu2ZnSnS4/CdS (CZTS/CdS) heterojunction resulting in the severe loss of open-circuit voltage (Voc) highly restrict the photovoltaic efficiency of CZTS solar cell devices. Here, first-principles calculations show that the Zn-alloyed CdS buffer layer reverses the unfavorable cliff-like conduction band offset (CBO) of CZTS/CdS to the desirable spike-like CBO of CZTS/Zn0.25Cd0.75S, which suppresses carrier nonradiative recombination and blocks electron backflow. In addition, the weakened n-type conductivity of Zn0.25Cd0.75S can be enhanced by In, Ga, and Cl doping without the introduction of detrimental deep-level defects and severe band-tail states, which improves the Voc of CZTS solar cells by promoting strong band bending and large quasi-Fermi-level splitting at the absorber side of the CZTS/Zn0.25Cd0.75S heterojunction. This study finds that the synergetic effects of Zn alloying and defect engineering on the CdS buffer layer are promising for overcoming the long-standing issue of the Voc deficit in CZTS solar cells, and understanding the optimized interfacial electrical properties provides theoretical guidance for improving the efficiency of semiconductor devices.

ATF2 accelerates the invasion and metastasis of hepatocellular carcinoma through targeting the miR-548p/TUFT1 axis.

AIM: Due to high invasion and metastasis, hepatocellular carcinoma (HCC) is known as one of the most fatal carcinomas. We aim to further investigate regulatory mechanisms of invasion and metastasis to elucidate HCC pathogenesis and develop novel medications. METHODS: Patient specimens were collected for assessing gene expression and correlation between gene expressions. The expression of Ki67 and E-cadherin in subcutaneous xenograft tumor were examined by immunohistochemistry staining. The expression of activating transcription factor 2 (ATF2), miR-548p and TUFT1 were determined using Real-time quantitative reverse transcription polymerase chain reaction. Epithelial-mesenchymal transition and PI3K/AKT signaling-associated markers were examined with western blot. The proliferation, migration and invasion were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, colony formation and transwell assays, respectively. Cell apoptosis was assessed via Annexin V and propidium iodide staining. Gene interaction was confirmed using chromatin immunoprecipitation and luciferase activity assays. Subcutaneous and intravenous xenograft mouse models were established for analyzing HCC growth and metastasis in vivo. RESULTS: ATF2 was up-regulated in HCC patients and cells. ATF2 promoted HCC cell proliferation, migration and invasion and inhibited cell apoptosis through directly targeting miR-548p and controlling its expression. miR-548p suppressed HCC cell proliferation, migration and invasion and enhanced cell apoptosis. miR-548p directly bound to the 3'UTR of TUFT1 to restrain its expression and subsequently suppress the PI3K/AKT signaling. ATF2 knock-down significantly suppressed the growth and metastasis of HCC. CONCLUSION: ATF2 accelerates HCC progression by promoting cell proliferation, migration, invasion and metastasis, which is dependent on regulating the miR-548p/TUFT1 axis.

Response and regulatory mechanisms of heat resistance in pathogenic fungi.

Both the increasing environmental temperature in nature and the defensive body temperature response to pathogenic fungi during mammalian infection cause heat stress during the fungal existence, reproduction, and pathogenic infection. To adapt and respond to the changing environment, fungi initiate a series of actions through a perfect thermal response system, conservative signaling pathways, corresponding transcriptional regulatory system, corresponding physiological and biochemical processes, and phenotypic changes. However, until now, accurate response and regulatory mechanisms have remained a challenge. Additionally, at present, the latest research progress on the heat resistance mechanism of pathogenic fungi has not been summarized. In this review, recent research investigating temperature sensing, transcriptional regulation, and physiological, biochemical, and morphological responses of fungi in response to heat stress is discussed. Moreover, the specificity thermal adaptation mechanism of pathogenic fungi in vivo is highlighted. These data will provide valuable knowledge to further understand the fungal heat adaptation and response mechanism, especially in pathogenic heat-resistant fungi. KEY POINTS: • Mechanisms of fungal perception of heat pressure are reviewed. • The regulatory mechanism of fungal resistance to heat stress is discussed. • The thermal adaptation mechanism of pathogenic fungi in the human body is highlighted.

The function and mechanism of dopamine in the activation of CD4+ T cell.

CONTEXT: It has been demonstrated that dopamine (DA) plays an important role in numerous cellular processes of T cell. Accumulating evidence suggests that the outcomes of T cell treatment with DA is depended on DA concentrations, T cell subtypes and activation states. However, the detail mechanism of DA function on T cell activation or regulatory T cells is largely unclear. OBJECTIVE: This study aims to explore the mechanisms by which DA regulates the activation of CD4+ T cells and the function of Tregs. MATERIALS AND METHODS: T cell proliferation was detected using CCK-8, BrdU incorporation assay or eFluor 450 cell labeling assay, and Western blot were used to detect phosphorylation of p65 and Erk. Nuclear translocation of transcription factors including p65, FOXO1 and NFAT1 were observed under laser confocal microscopy. RESULTS: Our present study demonstrated that DA (17 µM) can directly promote CD4+ T cells activation through D2-like receptors by enhancing the phosphorylation of p65, also can impair regulatory CD4+ T cells (Tregs) stability and suppressive function through D1- and D2-like receptors by inhibiting the expression of FOXO1 and NFAT1, which are the transcriptional factors of FOXP3, and by suppressing the expression of IL-10 in Tregs. Injection of DA can inhibit tumor growth in vivo. CONCLUSIONS: These data indicate a critical role for DA in promotion of CD4+ T helper response, this may applicable in tumor treatment in the future.