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1.
J Microbiol Biotechnol ; 34(7): 1455-1465, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38973400

RESUMO

Soil extracellular enzyme plays a vital role in changing soil nitrogen (N) mineralization of rice field. However, the effects of soil extracellular enzyme activities (EEA) and microbial community composition response to N mineralization of rice field under short-term tillage treatment needed to be further explored. In this study, we investigated the impact of short-term (8-year) tillage practices on rhizosphere soil N transformation rate, soil enzyme activities, soil microorganism community structure and their N mineralization function genes in double-cropping rice field in southern China. The experiment consisted of four tillage treatments: rotary tillage with crop straw input (RT), conventional tillage with crop straw input (CT), no-tillage with crop straw retention (NT), and rotary tillage with all crop straws removed as a control (RTO). The results indicated that rhizosphere soil N transformation rate in paddy field in NT and RTO treatments were significantly lower than that in RT and CT treatments. Compared with NT and RTO treatments, soil protease, urease, ß-glucosaminidase and arginase activities with CT treatment were significantly improved, as were abundances of soil sub, npr and chiA with CT and RT treatments. Moreover, diversity of overall soil bacterial communities in NT and RTO treatments were significantly lower than that in RT and CT treatments. Soil chitinolytic and bacterial ureolytic communities were also obviously changed combined with tillage and crop straw input practices.

2.
J Pharmacol Toxicol Methods ; 128: 107527, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852685

RESUMO

INTRODUCTION: Cardiovascular safety and the risk of developing the potentially fatal ventricular tachyarrhythmia, Torsades de Pointes (TdP), have long been major concerns of drug development. TdP is associated with a delayed ventricular repolarization represented by QT interval prolongation in the electrocardiogram (ECG), typically due to block of the potassium channel encoded by the human ether-a-go-go related gene (hERG). Importantly however, not all drugs that prolong the QT interval are torsadagenic and not all hERG blockers prolong the QT interval. Recent clinical reports suggest that partitioning the QT interval into early (J to T peak; JTp) and late repolarization (T peak to T end; TpTe) components may be valuable for distinguishing low-risk mixed ion channel blockers (hERG plus calcium and/or late sodium currents) from high-risk pure hERG channel blockers. This strategy, if true for nonclinical animal models, could be used to de-risk QT prolonging compounds earlier in the drug development process. METHODS: To explore this, we investigated JTp and TpTe in ECG data collected from telemetered dogs and/or monkeys administered moxifloxacin or amiodarone at doses targeting relevant clinical exposures. An optimized placement of the Tpeak fiducial mark was utilized, and all intervals were corrected for heart rate (QTc, JTpc, TpTec). RESULTS: Increases in QTc and JTpc intervals with administration of the pure hERG blocker moxifloxacin and an initial QTc and JTpc shortening followed by prolongation with the mixed ion channel blocker amiodarone were detected as expected, aligning with clinical data. However, anticipated increases in TpTec by both standard agents were not detected. DISCUSSION: The inability to detect changes in TpTec reduces the utility of these subintervals for prediction of arrhythmias using continuous single­lead ECGs collected from freely moving dogs and monkeys.

3.
J Cutan Pathol ; 51(8): 604-608, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38711196

RESUMO

Anogenital mammary-like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69-year-old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary-like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well-established breast lesions rather than cutaneous adnexal tumors.


Assuntos
Neoplasias da Mama , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/metabolismo , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Carcinoma Papilar/patologia , Carcinoma Papilar/diagnóstico , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico
4.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2585-2596, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812159

RESUMO

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ciclo-Oxigenase 2 , Fígado , NF-kappa B , Panax , Saponinas , Transdução de Sinais , Animais , Acetaminofen/efeitos adversos , Acetaminofen/toxicidade , Camundongos , Panax/química , Masculino , Saponinas/farmacologia , Saponinas/administração & dosagem , NF-kappa B/genética , NF-kappa B/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia
5.
Am J Clin Pathol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716796

RESUMO

OBJECTIVES: Severe macrovesicular steatosis in donor livers is associated with primary graft dysfunction. The Banff Working Group on Liver Allograft Pathology has proposed recommendations for steatosis assessment of donor liver biopsy specimens with a consensus for defining "large droplet fat" (LDF) and a 3-step algorithmic approach. METHODS: We retrieved slides and initial pathology reports from potential liver donor biopsy specimens from 2010 to 2021. Following the Banff approach, we reevaluated LDF steatosis and employed a computer-assisted manual quantification protocol and artificial intelligence (AI) model for analysis. RESULTS: In a total of 113 slides from 88 donors, no to mild (<33%) macrovesicular steatosis was reported in 88.5% (100/113) of slides; 8.8% (10/113) was reported as at least moderate steatosis (≥33%) initially. Subsequent pathology evaluation, following the Banff recommendation, revealed that all slides had LDF below 33%, a finding confirmed through computer-assisted manual quantification and an AI model. Correlation coefficients between pathologist and computer-assisted manual quantification, between computer-assisted manual quantification and the AI model, and between the AI model and pathologist were 0.94, 0.88, and 0.81, respectively (P < .0001 for all). CONCLUSIONS: The 3-step approach proposed by the Banff Working Group on Liver Allograft Pathology may be followed when evaluating steatosis in donor livers. The AI model can provide a rapid and objective assessment of liver steatosis.

6.
Int J Toxicol ; 43(3): 231-242, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327194

RESUMO

During drug discovery, small molecules are typically assayed in vitro for secondary pharmacology effects, which include ion channels relevant to cardiac electrophysiology. Compound A was an irreversible inhibitor of myeloperoxidase investigated for the treatment of peripheral artery disease. Oral doses in dogs at ≥5 mg/kg resulted in cardiac arrhythmias in a dose-dependent manner (at Cmax, free ≥1.53 µM) that progressed in severity with time. Nevertheless, a panel of 13 different cardiac ion channel (K, Na, and Ca) assays, including hERG, failed to identify pharmacologic risks of the molecule. Compound A and a related Compound B were evaluated for electrophysiological effects in the isolated rabbit ventricular wedge assay. Compounds A and B prolonged QT and Tp-e intervals at ≥1 and ≥.3 µM, respectively, and both prolonged QRS at ≥5 µM. Compound A produced early after depolarizations and premature ventricular complexes at ≥5 µM. These data indicate both compounds may be modulating hERG (Ikr) and Nav1.5 ion channels. In human IPSC cardiomyocytes, Compounds A and B prolonged field potential duration at ≥3 µM and induced cellular dysrhythmia at ≥10 and ≥3 µM, respectively. In a rat toxicology study, heart tissue: plasma concentration ratios for Compound A were ≥19X at 24 hours post-dose, indicating significant tissue distribution. In conclusion, in vitro ion channel assays may not always identify cardiovascular electrophysiological risks observed in vivo, which can be affected by tissue drug distribution. Risk for arrhythmia may increase with a "trappable" ion channel inhibitor, particularly if cardiac tissue drug levels achieve a critical threshold for pharmacologic effects.


Assuntos
Arritmias Cardíacas , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Animais , Miócitos Cardíacos/efeitos dos fármacos , Cães , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Coelhos , Arritmias Cardíacas/induzido quimicamente , Masculino , Ventrículos do Coração/efeitos dos fármacos , Canais Iônicos/metabolismo , Feminino
7.
Lab Invest ; 104(2): 100288, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37977550

RESUMO

Liver transplantation is an effective treatment for end-stage liver disease, acute liver failure, and primary hepatic malignancy. However, the limited availability of donor organs remains a challenge. Severe large-droplet fat (LDF) macrovesicular steatosis, characterized by cytoplasmic replacement with large fat vacuoles, can lead to liver transplant complications. Artificial intelligence models, such as segmentation and detection models, are being developed to detect LDF hepatocytes. The Segment-Anything Model, utilizing the DEtection TRansformer architecture, has the ability to segment objects without prior knowledge of size or shape. We investigated the Segment-Anything Model's potential to detect LDF hepatocytes in liver biopsies. Pathologist-annotated specimens were used to evaluate model performance. The model showed high sensitivity but compromised specificity due to similarities with other structures. Filtering algorithms were developed to improve specificity. Integration of the Segment-Anything Model with rule-based algorithms accurately detected LDF hepatocytes. Improved diagnosis and treatment of liver diseases can be achieved through advancements in artificial intelligence algorithms for liver histology analysis.


Assuntos
Fígado Gorduroso , Transplante de Fígado , Humanos , Inteligência Artificial , Doadores Vivos , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Fígado/diagnóstico por imagem , Fígado/patologia
8.
DNA Cell Biol ; 42(12): 720-734, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37943983

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by dysregulated immune responses in the gastrointestinal tract. One intriguing aspect of IBD is the potential involvement of ferroptosis, but the mechanism remains incompletely understood. In this study, 27 ferroptosis-related genes (FRGs) were identified differentially expressed between IBD and non-IBD control samples. We used CIBERSORT to compare alterations in the mucosal immune microenvironment between the above two group samples, and found that M1 macrophages and neutrophil infiltration increased in IBD. Two clusters based on consensus clustering of 27 FRGs led to significant changes in the abundance of CD4 memory resting T cells, M2 macrophages, and resting mast cells. Subsequently, 23 hub genes were identified, which could distinguish IBD samples into two distinct clusters with noticeable differences in immune therapy response. Furthermore, scRNA sequencing data based on these 23 hub genes uncovered the highest ferroptosis scores in CD8+ T effector memory (Tem) cells, and their expression underwent significant changes along the differentiation trajectory of CD8+ Tem cells. The random forest model identified eight decisive genes, out of which ferroptosis-related hub genes (SEMA3E, SLC46A1, AC092652.1, DACT2, IL17C, and KRTAP5.2) were confirmed by RT-qPCR in the IBD mouse model. This study reveals ferroptosis-mediated immune microenvironment in IBD and provides multiple potential targets for IBD treatment.


Assuntos
Ferroptose , Doenças Inflamatórias Intestinais , Animais , Camundongos , Ferroptose/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/terapia , Diferenciação Celular , Modelos Animais de Doenças
9.
Dermatopathology (Basel) ; 10(4): 303-309, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37873805

RESUMO

Programmed cell death protein 1 (PD-1) plays a pivotal role in immune system regulation, with its expression levels linked to malignancy prognosis. However, existing reports on PD-1 staining in mycosis fungoides (MF) present conflicting findings, and little attention has been given to PD-1 staining in different MF variants. To address this, we conducted a retrospective study, employing immunohistochemistry to examine PD-1 expression in cases of folliculotropic MF and non-folliculotropic MF. We analyzed 24 cases of folliculotropic MF and 18 cases of non-folliculotropic MF, and recorded both the percentage of PD-1-labeled tumor cells and the intensity score (negative, weak, medium, or strong). Our results revealed significant disparity in PD-1 labeling between patch/plaque MF and folliculotropic MF (p = 0.028). Non-folliculotropic MF exhibited higher PD-1 labeling in tumor cells (58.3%) compared to folliculotropic MF (40.2%). Notably, there was no significant difference in PD-1 staining between folliculotropic MF and non-folliculotropic MF when both were in the early stage/indolent disease category. However, when considering the tumor stage, folliculotropic MF exhibited PD-1 staining in tumor cells at a rate of 21.1%, while non-folliculotropic MF showed PD-1 staining in tumor cells at a rate of 46.6% (p = 0.005). Additionally, among folliculotropic MF cases, 13 out of 24 cases displayed differing PD-1 expression patterns between epidermal and dermal components, with preserved PD-1 staining in the epidermal component and loss of staining in the dermal component. Furthermore, consistent with the prior literature, tumor cells with large cell transformations exhibited significantly lower PD-1 labeling (p = 0.017). Our findings showcase the unique PD-1 staining patterns in MF.

10.
Breast ; 72: 103586, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37812963

RESUMO

BACKGROUND: Retesting for Human epidermal growth factor receptor-2 (HER2) in post-neoadjuvant therapy resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. METHODS: We identified 104 patients with localized HER2 IHC 3+ breast cancer who received neoadjuvant trastuzumab(T)/pertuzumab(P) containing chemotherapy at Yale Cancer Center between 2012 and 2022. Patients were divided into 3 cohorts by response and HER2 IHC in the residual disease: Cohort 1 pathologic complete response (pCR), Cohort 2 pre-treatment IHC 3+/post treatment IHC 1+/2+, and Cohort 3 pre-treatment IHC 3+/post-treatment IHC 3+. Kaplan-Meier survival analysis was performed to assess recurrence free survival at 36 months. RESULTS: The overall pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had residual disease (RD). Among patients with RD, 58.9% (23/39) remained IHC 3+ and 41.1% (16/39) had reduced HER2 expression IHC1+ or 2+. In patients with HER2 IHC 3+ RD, 26% (6/23) developed local recurrence or distant metastasis while none of patients with post NAT HER2 IHC 1+ or 2+ RD had relapse (p = 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis revealed superior disease-free survival in patients with reduced HER2 IHC expression compared to those with remained IHC 3+ (log rank p = 0.004). CONCLUSION: We conclude that reduced HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates in HER2 IHC 3+ breast cancer. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to stratify patients in adjuvant trials and identify patients who may benefit from more intensive adjuvant therapy and post therapy surveillance.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Prognóstico , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/etiologia , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico
11.
Clin Lymphoma Myeloma Leuk ; 23(11): e405-e410, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37659965

RESUMO

BACKGROUND: In advanced stages, Cutaneous T-cell lymphomas (CTCL) can metastasize to extracutaneous regions. CTCL with metastasis exhibits unique clinicopathologic characteristics. PATIENTS AND METHODS: This study collected 35 cases of primary CTCL with extracutaneous metastasis from a single institution over a period of 20 years. Clinicopathologic features including demographics, CD30 expression, large cell transformation, metastatic sites, T-cell receptor clonality studies and survival data were analyzed. RESULTS: The study identified various CTCL entities including mycosis fungoides (MF), Sezary syndrome (SS), cutaneous anaplastic large cell lymphoma (C-ALCL), and primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS). Limited data showed that metastasis can be independent of large cell transformation and/or CD30 expression. Lymph nodes were the most common site of metastasis, followed by the bone marrow. Oropharyngeal metastasis is likely to accompany visceral organ or brain metastasis (P = .049). MF had a longer interval to metastasis than SS (P = .038). Patients with lymph node only metastasis have better survival than patients with metastasis to other sites (P = .012). CONCLUSION: To the best of our knowledge, there are limited studies analyzing the clinicopathologic features of different CTCL entities with metastasis as a single population. This research provides valuable insights into the unique characteristics of metastatic CTCL.


Assuntos
Linfoma Anaplásico de Células Grandes , Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Micose Fungoide/patologia , Síndrome de Sézary/patologia , Pele/patologia , Medula Óssea/patologia , Linfoma Cutâneo de Células T/patologia
12.
J Cutan Pathol ; 50(11): 1001-1005, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37565491

RESUMO

BACKGROUND: Some dysplastic nevi, termed sclerosing nevi with pseudomelanomatous features, may have florid fibroplasia associated with features that cause melanoma to be a prominent consideration in the differential diagnosis. PRAME (PReferentially expressed Antigen in MElanoma) immunohistochemistry (IHC) has been shown to be a useful marker in the distinction of melanoma and nevus. PRAME expression in such sclerosing nevi with pseudomelanomatous features has not been evaluated to our knowledge. METHODS: Thirty-two sclerosing nevi with pseudomelanomatous features were stained with PRAME IHC, with positive labeling defined as staining of >75% of the cytomorphologically atypical lesional cells. RESULTS: All 32 cases had variable cytologic atypia, bridging of elongated rete, fibroplasia, and a vertically oriented trizonal appearance. Some cases (23/32) had centrally located flattening of the rete ridge pattern bilaterally flanked by fibroplasia associated with elongated rete. PRAME labeling was negative (<1% labeling) in 28/32 cases. Four cases, also interpreted as having negative labeling with PRAME, showed only weak nuclear positivity of <50% of the melanocytes within the pseudomelanomatous foci. p16 staining was positive in 28/28 lesions. CONCLUSIONS: Rare sclerosing nevi with pseudomelanomatous features (4/32; ~13%) had weak PRAME labeling of 25%-50% of atypical foci. Twenty-eight of 32 lesions had virtually no labeling with PRAME. PRAME results support classifying sclerosing nevi with pseudomelanomatous features as indolent lesions.

13.
J Cutan Pathol ; 50(7): 595-600, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37082914

RESUMO

We highlight the utility of interferon regulatory factor 8 (IRF8), a novel marker of monocytic and dendritic cell lineages, in the diagnosis of a case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) presenting initially in the skin. A 60-year-old male with a previous history of myelodysplastic syndrome presented with cutaneous nodules on chest and scalp. A punch biopsy specimen of a skin nodule showed a diffuse dermal infiltrate of atypical mononuclear cells. The neoplastic cells expressed CD4, CD56, CD43, and TdT but showed minimal reaction for TCL-1 and CD123, and were negative for CD34, CD117, and MPO, confounding the diagnosis. IRF8 performed in retrospect was strongly positive. A new punch biopsy specimen of a chest nodule showed the blastoid tumor cells were positive for TCL-1, CD4, and CD56, but dim CD123. Subsequent bone marrow involvement showed blastoid tumor cells with intense positivity for CD123, CD4, and CD56, which was supportive of the BPDCN diagnosis. BPDCN cases with weak or variable CD123 and TCL-1 expression represent a potential diagnostic pitfall. In a recent study, 15 cases of BPDCN showed uniformly strong staining for IRF8, while CD123 was dim or negative in 4 of these 15 cases. We suggest IRF8 may be a useful marker for BPDCN, especially in cases with weak or variable expression of CD123 and TCL1.


Assuntos
Neoplasias Hematológicas , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Células Dendríticas/patologia , Neoplasias Cutâneas/patologia , Fatores Reguladores de Interferon , Neoplasias Hematológicas/patologia
14.
Hum Pathol ; 140: 32-38, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37001739

RESUMO

Squamous carcinogenesis is incompletely understood, but more recent genetic studies support that the order of acquired mutations is important. This paper will review more recent genetic studies with an emphasis on the potential truncal mutations, mutations critical to the trunk of the cancer evolutionary tree, in actinic keratosis, squamous cell carcinoma in situ, cutaneous squamous cell carcinoma, keratoacanthoma, and keratoacanthoma-like squamous proliferation.

15.
J Pharmacol Toxicol Methods ; 121: 107266, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36963703

RESUMO

INTRODUCTION: Characterization of the incidence of spontaneous arrhythmias to identify possible drug-related effects is often an important part of the analysis in safety pharmacology studies using telemetry. METHODS: A retrospective analysis in non-clinical species with and without telemetry transmitters was conducted. Electrocardiograms (24 h) from male and female beagle dogs (n = 131), Göttingen minipigs (n = 108) and cynomolgus non-human primates (NHP; n = 78) were analyzed. RESULTS: Ventricular tachycardia (VT) was observed in 3% of the dogs but was absent in minipigs and NHPs. Ventricular fibrillation (VF) was not observed in the 3 species. Ventricular premature beats (VPBs) were more frequent during daytime and atrioventricular blocks (AVBs) were more frequent at night in all species. A limited number of animals exhibited a high arrhythmia frequency and there was no correlation between animals with higher frequency of an arrhythmia type and the frequency of other arrythmias in the same animals. Clinical chemistry or hematology parameters were not different with or without telemetry devices. NHP with a transmural left ventricular pressure (LVP) catheter exhibited a greater incidence of VPBs and PJCs compared to telemetry animals without LVP. DISCUSSION: All species were similar with regards to the frequency of ventricular ectopic beats (26-46%) while the dog seemed to have more frequent junctional complexes and AVB compared to NHP and minipigs. Arrhythmia screening may be considered during pre-study evaluations, to exclude animals with abnormally high arrhythmia incidence.


Assuntos
Arritmias Cardíacas , Telemetria , Animais , Cães , Suínos , Masculino , Feminino , Porco Miniatura , Incidência , Estudos Retrospectivos , Eletrocardiografia
16.
Environ Sci Pollut Res Int ; 30(17): 50759-50771, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36800093

RESUMO

Cropland conversion has been cited as one of the most effective measures for increasing soil nitrogen pool in karst degraded regions. However, it is still unclear how N associated with aggregate patterns and their contribution to net soil N accumulation after cropland conversion. The experiment included four treatments with one control and three restoration strategies, that is, maize-soybean rotation cultivation (the control), sugarcane, mulberry, and forage grass cultivation. Soil samples were selected to determine the soil aggregate amount and its associated N content and stock across 0-30 cm soil layer. Macro-aggregate (> 2 mm) was the predominant aggregate fraction in all cropland use types and had the largest N stock. Forage grass cultivation substantially increased N stocks in bulk soil and aggregate fractions. The N contents and stocks associated with aggregate were shown to be positively correlated with bulk soil N stocks. Furthermore, the increase in N stock in forage grass soil was largely caused by an increase in N stock within macro-aggregates (> 2 mm), which is further attributed to the increased N content within macro-aggregates. Overall, forage grass cultivation replaced maize-soybean cultivation which was proposed as an ecological restoration model to improve soil N sequestration capacity due to its function in increasing the N stock of aggregate in the karst degraded region of Southwest China.


Assuntos
Carbono , Solo , Carbono/análise , Poaceae , China , Zea mays , Nitrogênio/análise , Grão Comestível/química
17.
Sci Rep ; 13(1): 1773, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36720912

RESUMO

Cropland conversion has a major impact on soil C sequestration. However, it remains unclear about the changes in soil aggregate and their contribution to C accumulation following cropland conversion in a karst region, southwest China. In this study, three different cropland use types (sugarcane, mulberry and forage grass cultivation) were selected to replace maize-soybean cultivation. The soil was collected at a depth of 0 to 30 cm for analysis of soil aggregates and their OC content. Results showed that macro-aggregate was the predominant component underlying four cropland use types. Forage grass cultivation remarkably increased the OC stock and aggregate stability (MWD and GMD). OC content and stock associated with aggregate varied with cropland use types and soil depth, but were typically highest in forage grass fields. Macro-aggregates contained higher OC content and stock than other aggregate fractions, along with soil depth underlying four cropland use types. The increases in OC stock in forage grass field was mainly due to increased OC stocks within macro-aggregates, which is further attributed to the increase in OC content within macro-aggregates. Overall, forage grass cultivation replaced maize-soybean cultivation was suggested as an ecological restoration model to enhance soil C sequestration potential, owing to its role in increasing OC stock of aggregation and aggregate stability, in the karst region of southwest China.

18.
J Autism Dev Disord ; 53(2): 746-758, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34105046

RESUMO

Few eye tracking studies have examined how people with autism spectrum disorder (ASD) visually attend during live interpersonal interaction, and none with the Chinese population. This study used an eye tracker to record the gaze behavior in 20 Chinese children with ASD and 23 children with typical development (TD) when they were engaged in a structured conversation. Results demonstrated that children with ASD looked significantly less at the interlocutor's mouth and whole-face, and more at background. Additionally, gaze behavior was found to vary with the conversational topic. Given the great variability in eye tracking findings in existing literature, future explorations might consider investigating how fundamental factors (i.e., participant's characteristics, tasks, and context) influence the gaze behavior in people with ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Criança , População do Leste Asiático , Atenção , Fixação Ocular
19.
Clin Breast Cancer ; 23(2): 199-210, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36577560

RESUMO

BACKGROUND: Carcinoma with apocrine differentiation (AC) is a subtype of breast carcinoma with apocrine features in >90% of the tumor. Molecular studies demonstrate AC has high expression of androgen receptor (AR) mRNA. Pure AC lack estrogen receptor (ER), progesterone receptor (PR), and express AR, with variable human epidermal growth factor 2 (HER2) status. Currently, in triple negative AC, no targetable therapies or specific diagnostic markers exist. MATERIALS AND METHODS: α-Methylacyl CoA racemase (AMACR) expression was investigated as a marker of apocrine differentiation using a single-plex immunoperoxidase stain, and a novel AMACR/p63 dual stain in a subset of cases, across 1) benign apocrine lesions (apocrine metaplasia, adenosis) 2) apocrine DCIS (ADCIS), 3) AC/ invasive ductal carcinoma (IDC) with apocrine features, 4) non-apocrine triple negative breast cancer (TNBC) and 5) IDC, no special type. A sub-set of cases were evaluated by tissue microarray. RESULTS: AMACR expression was increased in both AC and ADCIS, with minimal expression in benign breast tissue, TNBC and IDC, NST cases. In invasive cases, those with positive AMACR (>5% positivity) were significantly associated with higher histologic grade (P = .006), initial N stage (chi squared 0.044), and lack of ER or PR expression (both P < .001), with no correlation with overall survival. Analysis of TCGA breast cancer datasets revealed AMACR expression was significantly higher in molecularly defined apocrine carcinomas relative to basal and luminal subtypes. Moreover, high AMACR expression predicted worse relapse-free and distant-metastasis free survival, among both ER-/PR-/Her2- and ER-/PR-/Her2+ breast cancer cohorts (log-rank P = .081 and .00011, respectively). CONCLUSION: AMACR represents a promising diagnostic and prognostic marker in apocrine breast lesions. Further study is needed to determine the biologic and clinical significance of this protein in AC.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico , Metástase Linfática , Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Racemases e Epimerases
20.
Environ Sci Pollut Res Int ; 30(1): 1502-1519, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35918580

RESUMO

The soil microbial community is a key indicator used to evaluate the effectiveness of land use changes in degraded ecosystems. However, there is currently limited information on the vertical variations of soil microbial communities under different cropland types in the karst region of southwest China. In this study, three different cropland types (sugarcane, mulberry, and forage grass) were selected to replace maize-soybean cultivation in a karst area of southwest China. Secondary forest was included for comparison. Soil was collected at soil depths of 0-10 cm, 10-20 cm, 20-30 cm, and 30-50 cm to conduct a phospholipid fatty acid (PLFA) analysis of the soil microbial communities. The results showed that the abundances of total PLFAs and PLFAs of bacteria, fungi, actinomycetes, and arbuscular mycorrhizal fungi were significantly higher in forage grass cultivation and secondary forest areas than those in other three cropland types. The abundance of total PLFA and its functional groups significantly decreased with increasing soil depth. Bacteria was the predominant community (> 52%) across all land use types and soil depths. A principal component analysis indicated that soil microbial PLFA composition in forage grass field and secondary forest areas differed significantly from that in mulberry, sugarcane, and maize-soybean fields across 0-50-cm soil layer. Soil organic carbon was identified as the primary factor affecting the abundance and structure of soil microbial communities in the four soil layers. These results suggest that greater improvements in soil quality and fertility could be made by replacing the maize-soybean rotation system with forage grass cultivation than by replacing it with mulberry or sugarcane cultivation in the karst region of southwest China.


Assuntos
Microbiota , Micorrizas , Solo/química , Ecossistema , Ácidos Graxos , Fosfolipídeos , Carbono , Microbiologia do Solo , China , Poaceae , Bactérias , Grão Comestível
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