Revealing the impact of autophagy-related genes in rheumatoid arthritis: Insights from bioinformatics.

Background: Rheumatoid arthritis is a systemic inflammatory autoimmune disease that severely impacts physical and mental health. Autophagy is a cellular process involving the degradation of cellular components in lysosomes. However, from a bioinformatics perspective, autophagy-related genes have not been comprehensively elucidated in rheumatoid arthritis. Methods: In this study, we performed differential analysis of autophagy-related genes in rheumatoid arthritis patients using the GSE93272 dataset from the Gene Expression Omnibus database. Marker genes were screened by least absolute shrinkage and selection operator. Based on marker genes, we used unsupervised cluster analysis to elaborate different autophagy clusters, and further identified modules strongly associated with rheumatoid arthritis by weighted gene co-expression network analysis. In addition, we constructed four machine learning models, random forest model, support vector machine model, generalized linear model and extreme gradient boosting based on marker genes, and based on the optimal machine learning model, a nomogram model was constructed for distinguishing between normal individuals and rheumatoid arthritis patients. Finally, five external independent rheumatoid arthritis datasets were used for the validation of our results. Results: The results showed that autophagy-related genes had significant expression differences between normal individuals and osteoarthritis patients. Through least absolute shrinkage and selection operator screening, we identified 31 marker genes and found that they exhibited significant synergistic or antagonistic effects in rheumatoid arthritis, and immune cell infiltration analysis revealed significant changes in immune cell abundance. Subsequently, we elaborated different autophagy clusters (cluster 1 and cluster 2) using unsupervised cluster analysis. Next, further by weighted gene co-expression network analysis, we identified a brown module strongly associated with rheumatoid arthritis. In addition, we constructed a nomogram model for five marker genes (CDKN2A, TP53, ATG16L2, FKBP1A, and GABARAPL1) based on a generalized linear model (area under the curve = 1.000), and the predictive efficiency and accuracy of this nomogram model were demonstrated in the calibration curves, the decision curves and the five external independent datasets were validated. Conclusion: This study identified marker autophagy-related genes in rheumatoid arthritis and analyzed their impact on the disease, providing new perspectives for understanding the role of autophagy-related genes in rheumatoid arthritis and providing new directions for its individualized treatment.

Lactate acid promotes PD-1+ Tregs accumulation in the bone marrow with high tumor burden of Acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) displayed poor response to programmed death-1 (PD-1) blockade therapy. Regulatory T cells (Tregs) was one of major immunosuppressive components in Tumor microenvironment and plays a vital role in the resistance of immunotherapy. Coinhibitory receptors regulate function of regulatory Tregs and are associated with resistance of PD-1 blockade. However, the coinhibitory receptors expression and differentiated status of Tregs in AML patients remain to be unclear. METHODS: Phenotypic determination of Tregs and CD8+ T cells in bone marrow of healthy donors and AML patients was performed by flow cytometry. Coculture experiments of AML and Tregs in vitro were performed and the concentrations of lactate acid (LA) in the supernatant were examined by ELISA. RESULTS: More Tregs differentiated into effector subsets in AML patients. However, PD-1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression on Tregs were comparable in healthy donors and AML patients. Further analysis showed that PD-1+ and PD-1+TIGIT+Tregs are more abundant in the bone marrow of patients with higher leukemic load. Moreover, PD-1+ Tregs accumulation was associated with higher level of senescent CD4+ T cells and increased frequencies of exhausted CD4+ as well as CD8+ T cells. Notably, neither Tregs nor their effector subsets were decreased among patients in complete remission. PD-1 expression was significantly downregulated in Tregs after achieving complete remission. Mechanistically, both AML cell line (KG-1α) and primary AML blasts produced high concentration of LA. Blockade of LA by lactate transporter inhibitor abrogated the upregulation of PD-1 by AML cells. CONCLUSION: PD-1+ Tregs accumulation in bone marrow in higher leukemic burden setting was linked to lactate acid secreted by AML blasts and decreased after disease remission. Our findings provided a novel insight into Tregs in AML and possible mechanism for resistance of PD-1 blockade in AML.

Treatment of bilateral developmental dysplasia of the hip joint with an improved technique: A case report.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common osteoarticular deformity in pediatric orthopedics. A patient with bilateral DDH was diagnosed and treated using our improved technique "(powerful overturning acetabuloplasty)" combined with femoral rotational shortening osteotomy. CASE SUMMARY: A 4-year-old girl who was diagnosed with bilateral DDH could not stand normally, and sought surgical treatment to solve the problem of double hip extension and standing. As this child had high dislocation of the hip joint and the acetabular index was high, we changed the traditional acetabuloplasty to "powerful turnover acetabuloplasty" combined with femoral rotation shortening osteotomy. During the short-term postoperative follow-up (1, 3, 6, 9, 12, and 15 months), the child had no discomfort in her lower limbs. After the braces and internal fixation plates were removed, formal rehabilitation training was actively carried out. CONCLUSION: Our "powerful overturning acetabuloplasty" combined with femoral rotational shortening osteotomy is feasible in the treatment of DDH in children. This technology may be widely used in the clinic.

Zishen Qingre Lishi Huayu recipe promotes proliferation and inhibits apoptosis of GCs of PCOS via KLF4-C/EBPß pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zishen Qingre Lishi Huayu recipe (ZQLHR) is a herbal recipe created on the basis on the theory of traditional Chinese medicine and clinical practice, and is mainly used in the treatment of polycystic ovary syndrome (PCOS). However, the underlying mechanism for this fact has not been clearly elucidated. AIM OF THE STUDY: To verify whether ZQLHR regulates granulosa cells (GCs) proliferation and apoptosis through the Krüppel-like factor 4 (KLF4) - CCATT enhancer-binding proteinß (C/EBPß) pathway, and to provide in vitro molecular mechanism supporting for the effects of ZQLHR to enhance follicular development and treat patients with PCOS. MATERIALS AND METHODS: Based on previous experiments, we performed the following experiments. Firstly, we treated KGN cells (a steroidogenic human granulosa-like tumor cell line) for 48 h using different concentrations of ZQLHR in order to observe apoptosis in each group. Secondly, the mRNA and protein expression levels of KLF4 and C/EBPß in KGN cells after administrated with ZQLHR were examined by quantitative real-time PCR(q-PCR) and Western blot assay. Thirdly, after knocking down KLF4 and C/EBPß using siRNAs, the relationship between KLF4 and C/EBPß in KGN cells was detected. Further, cell counting kit-8 assay, colony formation assay and flow cytometry were used to verify whether ZQLHR promotes proliferation and facilitates apoptosis in KGN cells through the KLF4-C/EBPß pathway. Finally, q-PCR and Western blot were used to test whether ZQLHR mediated proliferation and apoptosis-related factors such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (BAX), proliferating cell nuclear antigen (PCNA) and cleaved caspase-3 to affect the proliferation and apoptosis of KGN cells through the KLF4-C/EBPß pathway. CONCLUSIONS: ZQLHR, containing 0.2% by volume, administered to KGN cells resulted in the lowest rate of apoptosis. The expression levels of KLF4 and C/EBPß were increased in KGN cells following ZQLHR treatment. Additionally, ZQLHR promoted proliferation and inhibited apoptosis of KGN cells by modulating proliferation and apoptosis-related factors via the KLF4-C/EBPß pathway. Furthermore, we confirmed that KLF4 and C/EBPß regulate each other in KGN cells. These findings indicate that ZQLHR enhances the proliferation of GCs and suppresses their apoptosis, which constitutes a therapeutic mechanism for treating patients with PCOS.

Decade Milestone Advancement of Defect-Engineered g-C3N4 for Solar Catalytic Applications.

Over the past decade, graphitic carbon nitride (g-C3N4) has emerged as a universal photocatalyst toward various sustainable carbo-neutral technologies. Despite solar applications discrepancy, g-C3N4 is still confronted with a general fatal issue of insufficient supply of thermodynamically active photocarriers due to its inferior solar harvesting ability and sluggish charge transfer dynamics. Fortunately, this could be significantly alleviated by the "all-in-one" defect engineering strategy, which enables a simultaneous amelioration of both textural uniqueness and intrinsic electronic band structures. To this end, we have summarized an unprecedently comprehensive discussion on defect controls including the vacancy/non-metallic dopant creation with optimized electronic band structure and electronic density, metallic doping with ultra-active coordinated environment (M-Nx, M-C2N2, M-O bonding), functional group grafting with optimized band structure, and promoted crystallinity with extended conjugation π system with weakened interlayered van der Waals interaction. Among them, the defect states induced by various defect types such as N vacancy, P/S/halogen dopants, and cyano group in boosting solar harvesting and accelerating photocarrier transfer have also been emphasized. More importantly, the shallow defect traps identified by femtosecond transient absorption spectra (fs-TAS) have also been highlighted. It is believed that this review would pave the way for future readers with a unique insight into a more precise defective g-C3N4 "customization", motivating more profound thinking and flourishing research outputs on g-C3N4-based photocatalysis.

Hematological and biochemical markers influencing breast cancer risk and mortality: Prospective cohort study in the UK Biobank by multi-state models.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer-related death among women. However, evidence concerning hematological and biochemical markers influencing the natural history of breast cancer from in situ breast cancer to mortality is limited. METHODS: In the UK Biobank cohort, 260,079 women were enrolled during 2006-2010 and were followed up until 2019 to test the 59 hematological and biochemical markers associated with breast cancer risk and mortality. The strengths of these associations were evaluated using the multivariable Cox regression models. To understand the natural history of breast cancer, multi-state survival models were further applied to examine the effects of biomarkers on transitions between different states of breast cancer. RESULTS: Eleven biomarkers were found to be significantly associated with the risk of invasive breast cancer, including mainly inflammatory-related biomarkers and endogenous hormones, while serum testosterone was also associated with the risk of in-situ breast cancer. Among them, C-reactive protein (CRP) was more likely to be associated with invasive breast cancer and its transition to death from breast cancer (HR for the highest quartile = 1.46, 95 % CI = 1.07-1.97), while testosterone and insulin-like growth factor-1 (IGF-1) were more likely to impact the early state of breast cancer development (Testosterone: HR for the highest quartile = 1.31, 95 % CI = 1.12-1.53; IGF-1: HR for the highest quartile = 1.17, 95 % CI = 1.00-1.38). CONCLUSION: Serum CRP, testosterone, and IGF-1 have different impacts on the transitions of different breast cancer states, confirming the role of chronic inflammation and endogenous hormones in breast cancer progression. This study further highlights the need of closer surveillance for these biomarkers during the breast cancer development course.

Identifying Crucial Biomarkers in Osteoporosis and Ulcerative Colitis Through Bioinformatics Analysis of Co-expressed Genes.

Osteoporosis (OP) and ulcerative colitis (UC), prevalent immune diseases, exert a substantial socioeconomic impact globally. This study identifies biomarkers for these diseases, paving the way for in-depth research. Initially, the Gene Expression Omnibus (GEO) database was employed to analyze datasets GSE35958 and GSE87466. This analysis aimed to pinpoint co-expression differential genes (DEGs) between OP and UC. Subsequently, the Metascape database facilitated the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these DEGs' co-expression. For network construction and visualization, the STRING11.5 database along with Cytoscape 3.7.2 (Cytoscape Team, USA) were utilized to create a protein-protein interaction (PPI) network. Moreover, Cytoscape's cytoHubba plugin was instrumental in identifying the central genes, known as hub genes. In the datasets GSE35958 and GSE87466, 156 co-expressed DEGs were discovered. The PPI network, constructed using STRING11.5 and Cytoscape 3.7.2, comprises 96 nodes and 222 connections. Notably, seven hub genes were identified, namely COL6A1, COL6A2, BGN, NID1, PLAU, TGFB1, and PLAUR. These DEGs were predominantly enriched in pathways such as extracellular matrix organization and collagen-containing extracellular matrix, as per GO analysis. For diagnostic model construction and hub gene validation, datasets GSE56815 and GSE107499 from the GEO database were employed. The top five hub genes were validated. In conclusion, the hub genes identified in this study played a significant role in the early diagnosis, prevention, and treatment of OP and UC. Furthermore, they provide fresh insights into the underlying mechanisms of these diseases' development and progression.

Regulated synthesis of an Au NB-DT@Ag bimetallic core-molecule-shell nanostructure for reliable SERS detection.

In recent research, anisotropic plasmonic core-shell nanomaterials have gained a lot of attention in surface-enhanced Raman scattering (SERS) due to their brilliant uniformity and optical properties. Herein, a bimetallic core-molecule-shell (CMS) composite nanorod SERS substrate nanomaterial (Au NB-DT@Ag NRs) was designed and synthesized under precise regulation. The inner core is gold nanobipyramids (Au NBs), which possess superior plasmonic properties. Uniform Au NBs of five different sizes were fabricated via a penta-twinned gold seed mediated growth method. The length varied from 160 to 62 nm and the corresponding diameter varied from 60 to 23 nm while the longitudinal surface plasmonic resonance (SPR) changed from 908 to 715 nm. The SERS activity of five Au NBs were compared and the optimally sized one with a length of 78 nm and width of 28 nm was set as the inner core. After modification with the Raman reporter (DT), different amounts of silver were deposited on the surface of Au NB-DTs to form an Au NB-DT@Ag nanocomposite. The shape of the nanostructure gradually became a rod and lengthened while the longitudinal SPR wavelength varied from 733 nm to 664 nm with an increase in the amount of silver nitrate added. The Au NB-DT@Ag NRs with the best SERS activity (b-3) could realize the quantitative detection of the toxic dyes malachite green (MG) and crystal violet (CV) of concentrations as low as 5 × 10-9 M, showing good reproducibility and stability. This work offers a new design strategy for a SERS substrate for reliable quantitative SERS detection applications.

Precise Defect Engineering on Graphitic Carbon Nitrides for Boosted Solar H2 Production.

Defect engineering has been regarded as an "all-in-one strategy" to alleviate the insufficient solar utilization in g-C3 N4 . However, without appropriate modification, the defect benefits will be partly offset due to the formation of deep localized defect states and deteriorated surface states, lowering the photocarrier separation efficiency. To this end, the defective g-C3 N4 is designed with both S dopants and N vacancies via a dual-solvent-assisted synthetic approach. The precise defect control is realized by the addition of ethylene glycol (EG) into precursor formation and molten sulfur into the pyrolysis process, which simultaneously induced g-C3N4. with shallow defect states. These shallow defect energy levels can act as a temporary electron reservoir, which are critical to evoke the migrated electrons from CB with a moderate trapping ability, thus suppressing the bulky photocarrier recombination. Additionally, the optimized surface states of DCN-ES are also demonstrated by the highest electron-trapping resistance (Rtrapping ) of 9.56 × 103 Ω cm2 and the slowest decay kinetics of surface carriers (0.057 s-1 ), which guaranteed the smooth surface charge transfer rather than being the recombination sites. As a result, DCN-ES exhibited a superior H2 evolution rate of 4219.9 µmol g-1 h-1 , which is 29.1-fold higher than unmodified g-C3 N4 .

Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection.

Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules; stronger cytotoxicity against HCMV-infected fibroblasts; and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32-0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18-0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.

High-Throughput Drug Screen for Potential Combinations With Venetoclax Guides the Treatment of Transformed Follicular Lymphoma.

Transformed follicular lymphoma (t-FL) is an aggressive malignancy that is refractory and rapidly progressing with poor prognosis. There is currently no effective treatment. High-throughput screening (HTS) platforms are used to profile the sensitivity or toxicity of hundreds of drug molecules, and this approach is applied to identify potential effective treatments for t-FL. We randomly selected a compound panel from the School of Pharmaceutical Sciences Xiamen University, tested the effects of the panel on the activity of t-FL cell lines using HTS and the CCK-8 assay, and identified compounds showing synergistic anti-proliferative activity with the Bcl-2 inhibitor venetoclax (ABT-199). Bioinformatics tools were used to analyze the potential synergistic mechanisms. The single-concentration compound library demonstrated varying degrees of activity across the t-FL cell lines evaluated, of which the Karpas422 cells were the most sensitive, but it was the cell line with the least synergy with ABT-199. We computationally identified 30 drugs with synergistic effects in all cell lines. Molecularly, we found that the targets of these 30 drugs didn't directly regulate Bcl-2 and identified 13 medications with high evidence value above .9 of coordination with ABT-199, further confirming TP53 may play the largest role in the synergistic effect. Collectively, these findings identified the combined regimens of ABT-199 and further suggested that the mechanism is far from directly targeting Bcl-2, but rather through the regulation and synergistic action of p53 and Bcl-2. This study intended to reveal the best synergistic scheme of ABT-199 through HTS to more quickly inform the treatment of t-FL.

Genetic and lifestyle factors for breast cancer risk assessment in Southeast China.

BACKGROUND: Despite the rising incidence and mortality of breast cancer among women in China, there are currently few predictive models for breast cancer in the Chinese population and with low accuracy. This study aimed to identify major genetic and life-style risk factors in a Chinese population for potential application in risk assessment models. METHODS: A case-control study in southeast China was conducted including 1321 breast cancer patients and 2045 controls during 2013-2016, in which the data were randomly divided into a training set and a test set on a 7:3 scale. The association between genetic and life-style factors and breast cancer was examined using logistic regression models. Using AUC curves, we also compared the performance of the logistic model to machine learning models, namely LASSO regression model and support vector machine (SVM), and the scores calculated from CKB, Gail and Tyrer-Cuzick models in the test set. RESULTS: Among all factors considered, the best model was achieved when polygenetic risk score, lifestyle, and reproductive factors were considered jointly in the logistic regression model (AUC = 0.73; 95% CI: 0.70-0.77). The models created in this study performed better than those using scores calculated from the CKB, Gail, and Tyrer-Cuzick models. However, the logistic model and machine learning models did not significantly differ from one another. CONCLUSION: In summary, we have found genetic and lifestyle risk predictors for breast cancer with moderate discrimination, which might provide reference for breast cancer screening in southeast China. Further population-based studies are needed to validate the model for future applications in personalized breast cancer screening programs.

The temporal trend of women's cancer in Changle, China and a migrant epidemiological study.

Background: Although the etiology of women's cancer has been extensively studied in the last few decades, there is still little evidence comparing the temporal pattern of these cancers among different populations. Methods: Cancer incidence and mortality data from 1988 to 2015 were extracted from the Changle Cancer Register in China, and cancer incidence data for Los Angeles were extracted from Cancer Incidence in Five Continents plus database. A Joinpoint regression model was used to analyze the temporal trends of incidence and mortality for breast, cervical, corpus uteri and ovarian cancers. The standardized incidence ratios were applied to compare the cancer risk across populations. Results: An increasing trend of incidence rate for breast, cervical, corpus uteri and ovarian cancer was observed in Changle, although the rate leveled off for breast and cervical cancer after 2010, although not statistically significant. The mortality rate of breast and ovarian cancer was slightly increased during this period, while we found a decreased mortality of cervical cancer from 2010. The mortality of corpus uteri cancer showed a decreasing and then increasing trend. The incidence of breast, corpus uteri and ovarian cancer in Chinese American immigrants in Los Angeles was significantly higher than indigenous Changle Chinese and lower than Los Angeles whites. However, the incidence of cervical cancer in Chinese American immigrants shifted from significantly exceeding to lower than Changle Chinese. Conclusion: The incidence and mortality of women's cancers in Changle were generally on the rise, and this study concluded that environmental changes were important factors affecting the occurrence of these cancers. Appropriate preventive measures should be taken to control the occurrence of women's cancers by addressing different influencing factors.

Loss of CD28 expression associates with severe T-cell exhaustion in acute myeloid leukemia.

Introduction: Despite accumulated evidence in T-cell exhaustion in acute myeloid leukemia (AML), the immunotherapeutic targeting exhausted T cells such as programmed cell death protein 1 (PD-1) blockade in AML failed to achieve satisfying efficacy. Characteristics of exhausted T cells in AML remained to be explored. Methods: Phenotypic analysis of T cells in bone marrow (BM) using flow cytometry combining senescent and exhausted markers was performed in de novo AML patients and healthy donors as well as AML patients with complete remission (CR). Functional analysis of T-cell subsets was also performed in de novo AML patients using flow cytometry. Results: T cells experienced a phenotypic shift to terminal differentiation characterized by increased loss of CD28 expression and decrease of naïve T cells. Additionally, lack of CD28 expression could help define a severely exhausted subset from generally exhausted T cells (PD-1+TIGIT+). Moreover, CD28- subsets rather than CD28+ subsets predominantly contributed to the significant accumulation of PD-1+TIGIT+ T cells in AML patients. Further comparison of de novo and CR AML patients showed that T-cell exhaustion status was improved after disease remission, especially in CD28+ subsets. Notably, higher frequency of CD28-TIGIT-CD4+ T cells correlated with the presence of minimal residual disease in AML-CR group. However, the correlation between CD28- exhausted T cells and cytogenetic risk or white blood cell count was not observed, except for that CD28- exhausted CD4+ T cells correlated with lymphocyte counts. Intriguingly, larger amount of CD28-TGITI+CD8+ T cells at diagnosis was associated with poor treatment response and shorter leukemia free survival. Discussion: In summary, lack of CD28 expression defined a severely exhausted status from exhausted T cells. Accumulation of CD28- exhausted T cells was linked to occurrence of AML, and correlated to poor clinical outcome. Our data might facilitate the development of combinatory strategies to improve the efficacy of PD-1 blockade in AML.

Time-Domain Numerical Simulation and Experimental Study on Pulsed Eddy Current Inspection of Tubing and Casing.

Fundamental theory and methods are investigated of inspecting tubing and casing simultaneously using pulsed eddy current testing by numerical simulations and experiments. The distribution and variation of eddy current field are given in the finite element simulation for the inspection of undamaged and corroded casing and tubing combinations, with tubing outer diameter 73.8 mm, wall thickness 5.7 mm, corrosion depth 1.25 mm, 2.5 mm, 3.75 mm, and casing outer diameter 141.5 mm, wall thickness 7.7 mm, corrosion depth 1.25 mm, 2.5 mm, and 3.75 mm, respectively. The results show that eddy current field propagates around and to the depth after the direct section of the exciting current is cut off and the intensity center of eddy current field shifts gradually from the inner side of the tubing to the casing, which forms the basis of analyzing inspection mechanism. Corrosion at a particular depth is related to a particular optimum time slice of the induced voltage (namely with deepest concave) and a highest sensitivity is obtained at this slice. The time associated with this slice is in accordance with the time when the intensity center of eddy current reaches the corrosion. Corrosion at different depths has different voltage time slices starting to show signal of defect, which can be used to estimate the depth of the defect in order to judge the defect coming from tubing or casing. Furthermore, sinking degree of the time slice reflects the size of the defect. All machined defects can be recognized in the experiments and the optimum time slice appears at 0.01 s and 0.008 s after the excitation current is cut off for the tubing corrosion of 1.25 mm and 2.5 mm, respectively. The optimum time slice appears at the last moment of cut-off period, 0.625, for the casing corrosion. Experimental results agree well with the simulations and show the existence of the optimum correspondence between depth of corrosion and starting time of the defect signal of time slice, relations between sinking degree of the time slice, and corrosion size.

Interfacial Engineering of Ni/V2 O3 Heterostructure Catalyst for Boosting Hydrogen Oxidation Reaction in Alkaline Electrolytes.

Alkaline fuel cells can permit the adoption of platinum group metal-free (PGM-free) catalysts and cheap bipolar plates, thus further lowering the cost. With the exploration of PGM-free hydrogen oxidation reaction (HOR) catalysts, nickel-based compounds have been considered as the most promising HOR catalysts in alkali. Here we report an interfacial engineering through the formation of nickel-vanadium oxide (Ni/V2 O3 ) heterostructures to activate Ni for efficient HOR catalysis in alkali. The strong electron transfer from Ni to V2 O3 could modulate the electronic structure of Ni sites. The optimal Ni/V2 O3 catalyst exhibits a high intrinsic activity of 0.038 mA cm-2 and outstanding stability. Experimental and theoretical studies reveal that Ni/V2 O3 interface as the active sites can enable to optimize the hydrogen and hydroxyl bindings, as well as protect metallic Ni from extensive oxidation, thus achieving the notable activity and durability.

Orelabrutinib and venetoclax synergistically induce cell death in double-hit lymphoma by interfering with the crosstalk between the PI3K/AKT and p38/MAPK signaling.

PURPOSE: Double-hit lymphoma (DHL) is a rare and aggressive mature B-cell malignancy with concurrent MYC and BCL2 rearrangements. When DHL becomes relapsed or refractory, it becomes resistant to the majority of therapeutic approaches and has subpar clinical results. Therefore, innovative therapeutics for this particular patient population are urgently needed. METHODS: Orelabrutinib, a new oral BTK inhibitor, combined with the Bcl-2 inhibitor venetoclax, was used to confirm the antitumor effect of DHL. Cell counting kit-8 and Annexin V-FITC/PI assays were used to examine the interaction of this combined regimen on DHL cell lines and primary lymphoma cells. RNA sequencing, EdU incorporation assay, mitochondrial membrane potential assay, and western blotting were employed to explore the molecule mechanism for the cytotoxicity of orelabrutinib with or without venetoclax against DHL cell lines. RESULTS: In this study, orelabrutinib combined with venetoclax synergistically induced DHL cell death, as evidenced by the inhibition of cell proliferation, the induct of cell cycle arrest, and the promotion of cell apoptosis via the mitochondrial pathway. Orelabrutinib treatment alters genome-wide gene expression in DHL cells. The combined regimen decreases the expression of BTK and Mcl-1, potentially interfering with the activity and crosstalk of PI3K/AKT signaling and p38/MAPK signaling. In addition, the combination of orelabrutinib and venetoclax shows cytotoxic activity in primary B-lymphoma cells. CONCLUSION: In summary, these findings reveal a novel therapy targeting BCR signaling and the Bcl-2 family for DHL patients with a poor prognosis.

[Bryophyte diversity and microhabitat characteristics of bryophyte-dominated biological soil crusts development in water-wind erosion crisscross region of the northern Loess Plateau, China]. / é»„åœŸé«˜åŽŸåŒ—éƒ¨æ°´èš€é£Žèš€äº¤é”™åŒºè‹”è—“å¤šæ ·æ€§åŠè‹”è—“ç»“çš®å‘è‚²çš„å¾®ç”Ÿå¢ƒç‰¹å¾.

Microhabitat factors play an important role in regulating bryophyte species distribution and the development of bryophyte-dominated biological soil crusts (hereafter bryophyte crusts). We investigated the distribution and development of bryophytes in eight microhabitats in the water-wind erosion crisscross region of the Loess Pla-teau. We used the line intercept transects to explore and quantify the influencing pathways of microhabitat factors on bryophyte diversity and analyzed the influencing pathways of plant cover, slope aspect, and slope gradient by using structural equation model to quantify influencing coefficients. Our results showed that: 1) The Patrick, Shannon, Pielou, and Simpson indcies of bryophytes under plant canopy were 63.4%, 66.6%, 91.0%, and 68.3% lower than that without plant canopy, respectively, while the thickness, biomass, and chlorophyll content of bryophyte crusts were 0.5, 0.2, and 1.3 times higher than that without plant canopy, respectively. 2) The Patrick, Shannon, Pielou, and Simpson indexes of bryophytes on the north slope were 0.6, 0.9, 5.6, and 0.9 times higher than those on the south slope, while the thickness, biomass, and chlorophyll content of bryophyte crusts were 0.3, 0.3, and 0.6 times higher than those on the south slope, respectively. 3) As the slope increasing from 14° to 34°, the Patrick, Shannon, Pielou, and Simpson indexes of bryophyte were decreased by 59.8%, 84.1%, 57.3% and 68.0%, and the thickness, biomass, and chlorophyll content of bryophyte crusts were decreased by 15.2%, 25.0%, and 16.5%, respectively. 4) The importance of the three microhabitat factors on bryophyte diversity and the development of bryophyte crusts followed an order of plant canopy cover > slope aspect > slope gradient. The primary influencing pathway varied among the microhabitat factors. In conclusion, plant cover, slope aspect, and slope gradient significantly affected the distribution of bryophytes species and developmental level of bryophyte crusts through direct and indirect pathways. Therefore, full consideration should be given to microhabitat conditions when using bryophyte crusts to control desertification.

[Responses of moss biocrusts respiration to simulated grazing and trampling disturbance with different intensities on the fenced forestland of Loess Plateau, China]. / 黄土高原封禁林地藓结皮呼吸速率对放牧踩踏干扰强度的响应.

The changes in soil properties caused by grazing and trampling are important reasons for the changes in soil respiration rates, carbon fixation, and emission. However, the effects of different intensities of grazing and trampling on biocrusts respiration rate are unclear. In this study, we simulated grazing and trampling disturbances of 10%, 30%, 50%, and 70% intensity on moss biocrusts developed in aeolian sandy soil on Loess Plateau, with undisturbed moss biocrusts serving as a control. The changes in respiration rate of moss biocrusts were monitored continuously, and its responses to different disturbance intensities were analyzed. The results showed that: 1) moderate disturbance stimulated moss biocrusts respiration, while heavy disturbance inhibited that. The respiration rate of moss biocrusts was increased by 41.1% and 22.2% at disturbance intensities of 10% and 30%, but was decreased by 8.9% and 15.3% at disturbance intensities of 50% and 70%, respectively. 2) The trampling disturbance significantly changed soil temperature but did not affect soil water content. In comparison to the control, soil temperature of biocrusts was decreased by 0.4 and 1.2 ℃ at disturbance intensities of 10% and 30%, but it was increased by 1.1 and 1.0 ℃ at disturbance intensities of 50% and 70%, respectively. 3) The respiration rate of moss biocrusts showed a significant exponential relationship with soil temperature and a linear positive relationship with soil water content under different disturbance intensities. However, the correlation between respiration rate of moss biocrust and the characteristics of moss biocrust was not significant. Soil temperature and water content could explain 70.6%-96.3% and 49.1%-70.0% of the total variation of respiration rate of moss biocrusts, respectively. In conclusion, grazing and trampling affected the respiration rate of moss biocrusts, with short-term moderate grazing and trampling would have positive effects. On the other hand, excessive grazing and trampling would reduce the rate of moss biocrust respiration. As a result, future studies on soil carbon balance of the Loess Plateau should consider the effects of grazing and trampling on biocrust respiration.

Corrigendum: TEOA inhibits proliferation and induces DNA damage of diffuse large B-cell lymphoma cells through activation of the ROS-dependent p38 MAPK signaling pathway.

[This corrects the article DOI: 10.3389/fphar.2020.554736.].