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Celangulin V is a natural

Coniella has a wide distribution as plant pathogens, saprobes and endophytes. Some Coniella species infect leaves, fruits, stems and roots of plants. A coniella-like species was isolated from symptomatic leaves of Castanea mollissima (Fagaceae) from orchard in Tai’an City, Shandong Province, China. Based on multi-locus phylogenetic analyses of ITS, LSU, RPB2 and TEF1-α sequence data and morphology, Coniella castanea sp. nov. is introduced. A detailed description and illustration has been provided and new specieswas compared with related taxa.

Ellisembia appendiculata is described and illustrated as a new species from a specimen collected on dead branches of an unidentified broadleaf tree in Hainan Province. The fungus is characterized by distinct, unbranched conidiophores with monoblastic conidiogenous cells that produce distoseptate, obclavate or ellipsoidal conidia with 1 – 2 filiform, hyaline, aseptate, simple or branched appendages.

Gangliostilbe wuzhishanensis is described and illustrated as a new species from dead branches of an unidentified broadleaf tree in Hainan Province, China. The fungus is characterized by synnematous conidiophores with monoblastic conidiogenous cells producing 3–6-euseptate, 22–30 × 5–7 μm, clavate conidia. A key to Gangliostilbe species is provided.

Kidney transplantation is the ideal treatment for end-stage renal disease (ESRD). Chronic antibody-mediated rejection (CAMR) is the main cause of graft failure. Tfh and B cells are key immune cells that play important roles in CAMR. In this study, the populations of different Tfh cell phenotypes and B cell subsets in CAMR were investigated in a total of 36 patients. Based on Banff-2019, 15 patients were diagnosed with CAMR (CAMR group), 11 recipients were diagnosed with recurrent or de novo IgA nephropathy (IgAN group), and 10 patients displayed stable renal function (stable group). The Tfh and B cell subsets were analyzed by flow cytometry. The percentage and absolute number of PD-1+ICOS+Tfh cells were significantly higher in CAMR ( p < 0.05 ), as was the ratio of CD226+Tfh cells to TIGIT+Tfh cells ( p < 0.05 ). Compared with stable recipients, CAMR patients had lower naïve B cells and higher unswitched memory B cells, which were also significantly related to renal function ( p < 0.05 ). Using the logistic regression model, we concluded that the estimated glomerular filtration rate (eGFR), absolute number of PD-1+ICOS+Tfh cells, and ratio of CD226+Tfh cells to TIGIT+Tfh cells were independent risk factors for CAMR. The combination of eGFR, PD-1+ICOS+Tfh cells, and the ratio of CD226+Tfh cells to TIGIT+Tfh cells showed better diagnostic efficacy for CAMR than each single parameter. The collective findings show that monitoring different Tfh phenotypes and B cell subsets is beneficial to kidney transplant recipients and implicate the combination of eGFR, number of PD-1+ICOS+Tfh cells, and ratio of CD226+Tfh cells to TIGIT+Tfh cells as a biomarker for diagnosing CAMR. The findings may also inform new strategies to identify and treat CAMR.

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Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management.Significance:Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion–positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related video: https://vimeo.com/438254885See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

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Supplementary Figure 6 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Supplementary Figure 7 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Supplementary Figure 5 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Supplementary Figure 1 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Supplementary Figure 8 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Supplementary Figure 3 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Supplementary Figure 2 from Melanocyte-Stimulating Hormone Directly Enhances UV-Induced DNA Repair in Keratinocytes by a Xeroderma Pigmentosum Group A–Dependent Mechanism

Interstitial lung disease (ILD) is one of the most serious lung complications of connective tissue disease (CTD). The application of proteomics in the past decade has revealed that various proteins are involved in the pathogenesis of each subtype of CTD-ILD through different pathways, providing novel ideas to study pathological mechanisms and clinical biomarkers. On this basis, a multidimensional diagnosis or prediction model is established. This paper reviews the results of proteomic detection of different subtypes of CTD-ILD and discusses the role of some differentially expressed proteins in the development of pulmonary fibrosis and their potential clinical applications.

A new anamorphic genus and species,Neoacrodictys elegans, is illustrated and described from dead branches of an unidentified plant in Hainan Province, China. The genus is characterized by darkly pigmented turbinate to obpyriform muriform conidia produced from monoblastic integrated terminal conidiogenous cells on macronematous unbranched conidiophores.

During a survey of saprophytic microfungi on dead leaves from Futian Mangrove Nature Reserve in Guangdong Province, China, a new species of asexual ascomycota, Beltrania shenzhenica, was identified based on morphology and phylogenetic analyses of partial gene sequences of ITS and LSU. The detailed morphological description, phylogenetic tree, and photographs are provided.

In our previous study, serum soluble T-cell immunoglobulin and mucin structure-3 (sTim-3) and galactosin-9 (sGal-9) were found to be associated with renal function after kidney transplantation. However, it is unclear whether these two indicators can predict adverse outcomes after transplantation.Ninety-one recipients of kidney transplantation were enrolled and divided into a stable group and an adverse outcome group (consisting of biopsy-proven rejection, graft loss, death and clinically diagnosed rejection). The expression levels of sTim-3 and sGal-9 before (pre-Tim-3 and pre-Gal-9) and one month after transplantation (post-Tim-3 and post-Gal-9) were measured by ELISA.The level of pre-Tim-3 was significantly higher in the stable group than in the adverse outcome group [median (range), 2275 (840-4236) pg/mL vs. 1589 (353-3094) pg/mL, P = 0.002]. The level of post-Gal-9 was significantly lower in the stable group than in the adverse outcome group [median (range), 4869 (1418-13080) pg/mL vs. 6852: (4128-10760) pg/mL, P = 0.003]. The areas under the curve (AUCs) for pre-Tim-3 and post-Gal-9 were 0.737 (P = 0.002) and 0.751 (P = 0.003), respectively, better than AUC of post-eGFR (0.633) (P = 0.071), according to the receiver operating characteristic (ROC) curve. Through Cox regression analysis, including pre-Tim-3, post-Gal-9, post-eGFR, sex, age, BMI of recipients and donors, pre-Tim-3 and post-Gal-9 were independent risk factors for adverse outcomes after kidney transplantation (P = 0.016, P = 0.033, respectively).Serum sTim-3 and sGal-9 can predict adverse outcomes within two years after kidney transplantation.

CDK4/6 inhibitors such as palbociclib in combination with endocrine therapy (ET) have remarkablyimproved the outcome of patients with ER+/HER2- metastatic breast cancer (MBC). However, manypatients are intrinsically resistant to CDK4/6i therapy, and those who respond eventually acquireresistance. Although high baseline CCNE1 expression and rare alterations in RB1 and FAT1 geneshave been shown to be associated with CDK4/6i resistance, the molecular mechanisms of CDK4/6iresistance are complex and remain poorly understood. To better understand and overcome CDK4/6iresistance, we performed multi-omics profiling of paired tumor biopsies from ER+/HER2- MBCpatients treated with palbociclib combined with ET. Tumor biopsies taken at pre-treatment, on-treatment, and progressive disease (PD) from 71 patients were profiled using whole-exomesequencing (WES), whole-transcriptome sequencing (RNA-Seq) and IHC analysis. Ourcomprehensive analysis identified several tumor intrinsic molecular markers associated with worsePFS, including the Luminal B subtype (p=0.012, HR=2.593), BRCA1/2 pathogenic mutation (p=0.012,HR=2.67) and mutation signatures linked to APOBEC enzymatic activity (p=0.002, HR=3.19).Conversely, the estrogen response signature (p=0.006, HR=0.43) was associated with favorableprognosis. Unsupervised analysis revealed a cluster of tumors enriched in homologousrecombination deficiency (HRD) linked genomic scars that was associated with poor prognosis(p=0.005, HR=2.49). Of note, these HRD-high tumors responded even more poorly to treatment whenco-occurring with TP53 somatic mutations. Integrative analysis further identified three poorprognosis clusters (IC2-4) enriched in Luminal B, proliferative and HRD features when compared tothe favorable prognosis cluster (IC1).Comparing baseline vs. PD samples, we observed a pattern of post-treatment enrichment for the poorprognosis markers. In addition, breast cancer-associated genes such as BRCA1/2, TP53 and PTENharbored a higher prevalence of genomic alterations including somatic mutation, amplification,. deletion and gene fusion at PD. Cell cycle gene expression and signatures also markedly increased atPD compared to baseline whereas estrogen response signatures decreased. Upon diseaseprogression, tumors had frequently switched to molecular subtypes with aggressive and estrogenindependent characteristics, demonstrating high plasticity in response to CDK4/6i and ET treatment.These patterns of acquired resistance were validated by IHC analysis of cyclins E1 and E2, Ki67 andpRb. To investigate the genomic alterations responsible for acquired resistance, we compared 21paired baseline and PD samples. We observed that PD-specific RB1 loss-of-function events occurredwith higher prevalence than previously reported, underscoring a major role of cell cycle de-regulation in conferring resistance to CDK4/6 inhibition. In this prospective longitudinal multi-omicsstudy, we identified novel candidate biomarkers that can be used to improve prediction of responseto CDK4/6i. In addition, we derived new insights into the molecular mechanisms of drug resistanceto palbociclib plus ET that will help guide therapeutic strategies and drug development inHR+/HER2− MBC. Citation Format: Zhengyan Kan, Seock-Ah Im, Kyunghee Park, Ji Wen, Kyung-Hun Lee, Yoon-La Choi, Won-Chul Lee, Ahrum Min, Vinicius Bonato, Seri Park, Sripad Ram, Dae-Won Lee, Ji-Yeon Kim, Su Kyeong Lee, Won-Woo Lee, Jisook Lee, Miso Kim, Scott L. Weinrich, Han Suk Ryu, Tae Yong Kim, Stephen Dann, Diane Fernandez, Jiwon Koh, Song Yi Park, Shibing Deng, Eric Powell, Rupesh Kanchi Ravi, Jadwiga Bienkowska, Paul A. Rejto, Woong-Yang Park, Yeon Hee Park. Serial genomic profiling reveals molecular mechanisms of breast cancer resistance to palbociclib [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD2-08.

Hepatocellular carcinoma (HCC) is defined as a universal malignancy while radiation therapy is the effective treatment for it. This study validated the mechanism of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed gene (CRNDE) in radiation resistance in HCC. LncRNA CRNDE upregulation was detected in HCC cells. The radiation-resistant cell strains Huh7R and SNU-387R were established. After silencing lncRNA CRNDE, the cell colony formation ability, cell activity, apoptosis, cell cycles, and γ-H2AX positive rate in Huh7R and SNU-387R were detected. Silencing lncRNA CRNDE decreased the cell activity, colony formation ability, and cell number in the G2 phase and facilitated DNA damage and apoptosis. The binding relations of specificity protein 1 (SP1) with lncRNA CRNDE and 3-phosphoinositide dependent protein kinase 1 (PDK1) were verified. LncRNA CRNDE regulated PDK1 transcription by binding to transcription factor SP1. PDK1 overexpression partially reversed the inhibition of silencing lncRNA CRNDE on radiation resistance in HCC cells. The transplanted tumor mouse model was established and showed that silencing lncRNA CRNDE decreased tumor volume and weight and Ki67-positive cells in HCC mice in vivo. Collectively, lncRNA CRNDE was upregulated in HCC cells and promoted PDK1 transcription by binding to SP1, thus enhancing radiation resistance in HCC cells.

BACKGROUND Online mindfulness-based programs (MBPs) for parents and families, especially in clinical populations, are limited. Low engagement and substantial dropout are major issues in MBP implementation. OBJECTIVE In this pilot study, we examined the effects of an online MBP on parents of children with attention deficit/hyperactivity disorder (ADHD). METHODS A mixed methods study was applied to evaluate the effects of the online MBP. Forty-three parents were recruited and randomly assigned to the intervention group and waitlist control group. The MBP lasted for 28 days and consisted of 20 psychoeducation videos, with homework guidance audios, and 4 instructor-led online group meetings. Purposive sampling was then used to recruit parents who had completed the program to share their experiences and suggestions for improving the program in semi-structured online interviews. RESULTS The quantitative data showed that the participants of the online MBP perceived a medium to large effect on the reduction of child ADHD symptoms. The participants of the semi-structured interviews reported positive experiences regarding their help-seeking intention and regarding personal changes, such as in emotion regulation and paying quality attention to their children. The interview participants further made suggestions for the improvement of the MBP. CONCLUSIONS The online MBP had promising effects. A large-scale randomized controlled trial should be conducted to investigate the effects of the MBP in clinical populations. CLINICALTRIAL ClinicalTrials.gov NCT05480423

Aim: The gutmicrobiotaplays an important role in human health. In this study, we aimedto investigate whether and whereby the gut microbiota communities are alteredin patients with immuno-mediated necrotizing myopathy (IMNM) and to provide new ideas for further exploring the pathogenesis of IMNM or screening its clinical therapeutic targets in the future. Methods: The gut microbiota in 42 fecal samples collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta diversity analyseswere applied to examine the bacterial diversity and community structure between the IMNM and HC groups. Welch’s t test was performed to identify the significantly abundant taxa (phylum and genera) of bacteria between the two groups. Linear discriminant analysis (LDA) effect size (LefSe) analysis was applied to detect the most discriminatory taxa between the two groups. Spearman correlation analysis was performed to analyze the correlation between the gut microbiota and clinical indicators and the correlation network between the genera. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P Results: The diversity of the gut microbiota of IMNM patients differed from that of healthy people and decreased obviously based on principal coordinate analysis (PCoA)and Chao1, Shannon and Simpson indexes (pBacteroides, Roseburiaand Coprococcus were decreased compared to thosein the HC group, while the relative abundancesof Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, the relative abundance of Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies and anti-Ro52 antibodies and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, we constructed a prediction model using thetop five differential genera to distinguish IMNM patients from healthy individuals, which was verified using an ROC curve (area under curve: 87%, 95% confidence interval: 73–100%). Conclusion: We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and iscorrelated with systemic autoimmune features.

BackgroundThe incidence of kidney, bladder, and prostate cancer ranked ninth, sixth, and third in male cancers respectively, meanwhile, the incidence of testicular cancer also increased gradually in the past 30 years.ObjectiveTo study and present estimates of the incidence, mortality, and disability of kidney, bladder, prostate, and testicular cancer by location and age from 1990 to 2019 and reveal the mortality risk factors of them.MaterialsThe Global Burden of Diseases Study 2019 was used to obtain data for this research. The prediction of cancer mortality and incidence was based on mortality-to-incidence ratios (MIRs). The MIR data was processed by logistic regression and adjusted by Gaussian process regression. The association between the socio-demographic index and the incidence or disease burden was determined by Spearman's rank order correlation.ResultsGlobally in 2019, there were 371,700 kidney cancer cases with an age-standardized incidence rate (ASIR) of 4.6 per 100,000, 524,300 bladder cancer cases, with an ASIR of 6.5 per 100,000, 1,410,500 prostate cancer cases with an ASIR of 4.6 per 100,000 and 109,300 testicular cancer incident cases with an ASIR of 1.4 per 100,000, the ASIR of these four cancers increased by 29.1, 4, 22, and 45.5% respectively. The incidence rate of the four cancers and the burden of kidney cancer were positively correlated with the socio-demographic index (SDI), regions with a higher SDI faced more of a burden attributable to these four cancers. High body-mass index has surpassed smoking to be the leading risk factor in the past thirty years for kidney cancer mortality. Smoking remained the leading risk factor for cancer-related mortality for bladder cancer and prostate cancer and the only risk factor for prostate cancer. However, the contribution of high fasting plasma glucose to bladder cancer mortality has been increasing.ConclusionThe incidence of bladder, kidney, prostate, and testicular cancer is ever-increasing. High-income regions face a greater burden attributable to the four cancers. In addition to smoking, metabolic risk factors may need more attention.

The formation of neutrophil extracellular traps (NETs) is a process releasing into the extracellular space networks of chromatin fibers decorated with granular proteins. It is implicated in infection-related as well as sterile inflammation. Monosodium urate (MSU) crystals serve as damage-associated molecular pattern (DAMP) in various conditions of disease. Formation of NETs or aggregated NETs (aggNETs) orchestrates initiation and resolution of MSU crystals-triggered inflammation, respectively. Elevated intracellular calcium levels and the generation of reactive oxygen species (ROS) are crucial for the formation of MSU crystal-induced NETs. However, the exact signaling pathways involved are still elusive. Herein, we demonstrate that the ROS-sensing, non-selective calcium-permeable channel transient receptor potential cation channel subfamily M member 2 (TRPM2) is required for a full-blown MSU crystal-induced NET formation. Primary neutrophils from TRPM2−/− mice showed reduced calcium influx and ROS production and, consequently a reduced formation of MSU crystal-induced NETs and aggNETs. Furthermore, in TRPM2−/− mice the infiltration of inflammatory cells into infected tissues and their production of inflammatory mediators was suppressed. Taken together these results describe an inflammatory role of TRPM2 for neutrophil-driven inflammation and identify TRPM2 as potential target for therapeutic intervention.