Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

Effects of umbilical cord mesenchymal stem cells loaded with graphene oxide granular lubrication on cytokine levels in animal models of knee osteoarthritis.

BACKGROUND: The aim of this study was to use umbilical cord mesenchymal stem cells (UCMSCs) loaded with graphene oxide (GO) granular lubricant to treat knee osteoarthritis (KOA) animal models and to analyze their effect on cytokine levels in the articular cavity. METHODS: Twenty-four New Zealand rabbit models of KOA were established by the modified Hulth and cartilage injury method, and they were assigned to the blank group, the GO group, the UCMSC group, and the GO + UCMSC group, each group containing six animal models. The GO and UCMSC groups were treated by a single intra-articular injection. The treatment was started one month after surgical modeling, and the observation period was eight weeks. The expression levels of nitric oxide (NO), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), glycosaminoglycan (GAG), and collagen-II (COL-II) in serum and articular fluid after treatment were compared to analyze the efficacy. RESULTS: The GO granular lubricant caused no significant improvement in the intra-articular environment of the knee joint, and UCMSCs caused a certain degree of improvement in the inflammatory environment. The improvement results of NO, IL-6, TNF-α, GAG, and COL-II were the best in the GO + UCMSC group, but the improvement results of inflammatory cytokine levels in serum and articular fluid were not consistent, especially the differences in NO, IL-6, and TNF-α were greater. CONCLUSION: UCMSCs loaded with the GO granular lubricant can reduce the inflammatory level and improve the level of biochemical environment in the articular cavity, and thus promote cartilage repair.

Untargeted Metabolomics Combined with Bioassay Reveals the Change in Critical Bioactive Compounds during the Processing of Qingzhuan Tea.

Qingzhuan tea (QZT) is a typical Chinese dark tea that has a long-time manufacturing process. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to study the chemical changes of tea samples during QZT processing. Untargeted metabolomics analysis revealed that the pile-fermentation and turnover (post-fermentation, FT) was the crucial stage in transforming the main compounds of QZT, whose contents of flavan-3-ols and flavonoids glycosides were decreased significantly. The bioactivities, including the antioxidant capacities and inhibitory effects on α-amylase and α-glucosidase, were also reduced after the FT process. It was suggested that although the QZT sensory properties improved following pile-fermentation and aging, the bioactivities remained restrained. Correlation analysis indicated that the main galloylated catechins and flavonoid glycosides were highly related to their antioxidant capacity and inhibitory effects on α-amylase and α-glucosidase.

Fluoride absorption, transportation and tolerance mechanism in Camellia sinensis, and its bioavailability and health risk assessment: a systematic review.

Tea is the one of the most popular non-alcoholic caffeinated beverages in the world. Tea is produced from the tea plant (Camellia sinensis (L.) O. Kuntze), which is known to accumulate fluoride. This article systematically analyzes the literature concerning fluoride absorption, transportation and fluoride tolerance mechanisms in tea plants. Fluoride bioavailability and exposure levels in tea infusions are also reviewed. The circulation of fluoride within the tea plantation ecosystems is in a positive equilibrium, with greater amounts of fluoride introduced to tea orchards than removed. Water extractable fluoride and magnesium chloride (MgCl2 ) extractable fluoride in plantation soil are the main sources of absorption by tea plant root via active trans-membrane transport and anion channels. Most fluoride is readily transported through the xylem as F- /F-Al complexes to leaf cell walls and vacuole. The findings indicate that tea plants employ cell wall accumulation, vacuole compartmentalization, and F-Al complexes to co-detoxify fluoride and aluminum, a possible tolerance mechanism through which tea tolerates higher levels of fluoride than most plants. Furthermore, dietary and endogenous factors influence fluoride bioavailability and should be considered when exposure levels of fluoride in commercially available dried tea leaves are interpreted. The relevant current challenges and future perspectives are also discussed. © 2020 Society of Chemical Industry.

Evaluation of the feasibility of short-term electrodialysis for separating naturally occurring fluoride from instant brick tea infusion.

BACKGROUND: Removing excessive naturally occurring fluoride from tea and/or infusions is difficult because the process has low efficiency and causes secondary pollution. In this study, a novel electrodialysis (ED) technology was developed. We examined the effect of crucial parameters (electrolyte concentration, operation voltage, ED duration and initial concentration of the tea infusion) on defluoridation performance using a highly efficient ion-exchange membrane with five-compartment cells. RESULTS: The most effective ED system results were obtained at an electrolyte concentration of 10 g kg-1 and operating voltage of 20 V. Moreover, the fluoride removal capacity (10.70-66.93%) was highly dependent on the ED duration (1-15 min) and initial concentration of the tea infusion (0.5-10 g kg-1 ). The longer the ED duration and the lower the initial concentration, the higher was the defluoridation performance. During ED, limited loss of the main inclusions (total polyphenols, catechins, caffeine and selected ions) was observed. Furthermore, the D201 anion resin-filled ED stack (0.5-5 g) and improvement of concentrate compartment electrolyte (≥5 times the dilute compartment electrolyte) in the ED system enhanced the defluoridation rate significantly. CONCLUSION: ED is a potentially effective method that can be used for defluoridation in the deep processing of tea products. © 2019 Society of Chemical Industry.

Positron-emitting tracer imaging of fluoride transport and distribution in tea plant.

BACKGROUND: Tea (Camellia sinensis (L.) O. Kuntze) is a hyper-accumulator of fluoride (F). To understand F uptake and distribution in living plants, we visually evaluated the real-time transport of F absorbed by roots and leaves using a positron-emitting (18 F) fluoride tracer and a positron-emitting tracer imaging system. RESULTS: F arrived at an aerial plant part about 1.5 h after absorption by roots, suggesting that tea roots had a retention effect on F, and then was transported upward mainly via the xylem and little via the phloem along the tea stem, but no F was observed in the leaves within the initial 8 h. F absorbed via a cut petiole (leaf 4) was mainly transported downward along the stem within the initial 2 h. Although F was first detected in the top and ipsilateral leaves, it was not detected in tea roots by the end of the monitoring. During the monitoring time, F principally accumulated in the node. CONCLUSION: F uptake by the petiole of excised leaf and root system was realized in different ways. The nodes indicated that they may play pivotal roles in the transport of F in tea plants. © 2020 Society of Chemical Industry.

Tea Plant Information Archive: a comprehensive genomics and bioinformatics platform for tea plant.

Tea is the world's widely consumed nonalcohol beverage with essential economic and health benefits. Confronted with the increasing large-scale omics-data set particularly the genome sequence released in tea plant, the construction of a comprehensive knowledgebase is urgently needed to facilitate the utilization of these data sets towards molecular breeding. We hereby present the first integrative and specially designed web-accessible database, Tea Plant Information Archive (TPIA; http://tpia.teaplant.org). The current release of TPIA employs the comprehensively annotated tea plant genome as framework and incorporates with abundant well-organized transcriptomes, gene expressions (across species, tissues and stresses), orthologs and characteristic metabolites determining tea quality. It also hosts massive transcription factors, polymorphic simple sequence repeats, single nucleotide polymorphisms, correlations, manually curated functional genes and globally collected germplasm information. A variety of versatile analytic tools (e.g. JBrowse, blast, enrichment analysis, etc.) are established helping users to perform further comparative, evolutionary and functional analysis. We show a case application of TPIA that provides novel and interesting insights into the phytochemical content variation of section Thea of genus Camellia under a well-resolved phylogenetic framework. The constructed knowledgebase of tea plant will serve as a central gateway for global tea community to better understand the tea plant biology that largely benefits the whole tea industry.

Using stable isotope signatures to delineate the geographic point-of-origin of Keemun black tea.

BACKGROUND: Confirmation of food labeling that claims production in a small geographic region is critical to traceability, quality control and brand protection. In the current study, isotope ratio mass spectrometry (IRMS) was used to generate profiles of δ13 C and δ15 N to determine if the stable isotope signatures of Keemun black tea differ within the three counties that claim production. Other factors (cultivar type, leaf maturity and manufacturing process) were considered for their potential effects. RESULTS: Both cultivar type and leaf maturity have remarkable impact on the δ15 N values of tea leaves, and that the cultivar influenced the δ13 C values. Keemun black tea from Qimen county could be easily discriminated from samples from Dongzhi and Guichi counties based on δ15 N signatures. The k-NN model was cross-validated with an accuracy of 91.6%. Environmental factors and/or genotype seem to be the major reasons for δ15 N differences in Keemun black tea from the selected regions. CONCLUSION: This article provides a potential effective method to delineate the geographic point-of-origin of Keemun black tea based on δ15 N signatures. © 2018 Society of Chemical Industry.

Implementation of CsLIS/NES in linalool biosynthesis involves transcript splicing regulation in Camellia sinensis.

Volatile terpenoids produced in tea plants (Camellia sinensis) are airborne signals interacting against other ecosystem members, but also pleasant odorants of tea products. Transcription regulation (including transcript processing) is pivotal for plant volatile terpenoid production. In this study, a terpene synthase gene CsLIS/NES was recovered from tea plants (C. sinensis cv. "Long-Men Xiang"). CsLIS/NES transcription regulation resulted in 2 splicing forms: CsLIS/NES-1 and CsLIS/NES-2 lacking a 305 bp-fragment at N-terminus, both producing (E)-nerolidol and linalool in vitro. Transgenic tobacco studies and a gene-specific antisense oligo-deoxynucleotide suppression applied in tea leaves indicated that CsLIS/NES-1, localized in chloroplasts, acted as linalool synthase, whereas CsLIS/NES-2 localized in cytosol, functioned as a potential nerolidol synthase, but not linalool synthase. Expression patterns of the 2 transcript isoforms in tea were distinctly different and responded differentially to the application of stress signal molecule methyl jasmonate. Leaf expression of CsLIS/NES-1, but not CsLIS/NES-2, was significantly induced by methyl jasmonate. Our data indicated that distinct transcript splicing regulation patterns, together with subcellular compartmentation of CsLIS/NE-1 and CsLIS/NE-2 implemented the linalool biosynthesis regulation in tea plants in responding to endogenous and exogenous regulatory factors.

Comparative effects of green and black tea extracts on lowering serum uric acid in hyperuricemic mice.

CONTEXT: Tea (Camellia sinensis (L.) Kuntze [Theaceae]) is used to induce urination and inducing nervous excitation. Green and black teas have multifarious physiological functions. The different effects of green and black tea aqueous extracts (GTEs and BTEs) on hyperuricemia are not definitely reported. OBJECTIVE: The different effects of GTEs and BTEs on lowering serum uric acid (UA) in hyperuricemic mice were determined. MATERIALS AND METHODS: Kunming mice were divided into nine groups (n = 6/each group). GTEs and BTEs at the doses of 0.5, 1 and 2 g/kg were orally administrated to mice for seven days, respectively. Hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) activities as mechanisms of actions were assessed. RESULTS: Research indicated that the LD50 of tea extract is greater than 2 g/kg in mice. UA levels were suppressed significantly with dose-dependent treatment of 0.5, 1 and 2 g/kg BTEs (up to 25.5%, 28.7% and 29.8%, respectively); the serum UA levels were decreased by GTEs but not significant. The activities of XOD and ADA in high dose (2 g/kg) groups of both GTEs and BTEs were notably lower than those of the model group. DISCUSSION AND CONCLUSIONS: The results suggested that both GTEs and BTEs have hypouricaemic and renal protective effects on hyperuricemic mice and the latter one was better. Our study sheds light on the research and development of anti-hyperuricemic functional foods and drugs from tea.

Effect of Medium Supplements on Agrobacterium rhizogenes Mediated Hairy Root Induction from the Callus Tissues of Camellia sinensis var. sinensis.

Tea (Camellia sinensis L.) is recalcitrant to Agrobacterium-mediated genetic transformation largely due to the bactericidal effects of tea polyphenols and phenolics oxidation induced by necrosis of explant tissue over the process of transformation. In this study, different antioxidants/adsorbents were added as supplements to the co-cultivation and post co-cultivation media to overcome these problems for the transformation improvement. Tea-cotyledon-derived calli were used as explants and Agrobacterium rhizognes strain ATCC 15834 was used as a mediator. Results showed that Agrobacterium growth, virulence (vir) gene expression and browning of explant tissue were greatly influenced by different supplements. Murashige and Skoog (MS) basal salts medium supplemented with 30 g·L(-1) sucrose, 0.1 g·L(-1) l-glutamine and 5 g·L(-1) polyvinylpolypyrrolidone (PVPP) as co-cultivation and post co-cultivation media could maintain these parameters better that ultimately led to significant improvement of hairy root generation efficiency compared to that in the control (MS + 30 g·L(-1) sucrose). Additionally, the reporter genes ß-glucuronidase (gusA) and cyan fluorescent protein (cfp) were also stably expressed in the transgenic hairy roots. Our study would be helpful in establishing a feasible approach for tea biological studies and genetic improvement of tea varieties.

Anion Channel Inhibitor NPPB-Inhibited Fluoride Accumulation in Tea Plant (Camellia sinensis) Is Related to the Regulation of Ca²âº, CaM and Depolarization of Plasma Membrane Potential.

Tea plant is known to be a hyper-accumulator of fluoride (F). Over-intake of F has been shown to have adverse effects on human health, e.g., dental fluorosis. Thus, understanding the mechanisms fluoride accumulation and developing potential approaches to decrease F uptake in tea plants might be beneficial for human health. In the present study, we found that pretreatment with the anion channel inhibitor NPPB reduced F accumulation in tea plants. Simultaneously, we observed that NPPB triggered Ca(2+) efflux from mature zone of tea root and significantly increased relative CaM in tea roots. Besides, pretreatment with the Ca(2+) chelator (EGTA) and CaM antagonists (CPZ and TFP) suppressed NPPB-elevated cytosolic Ca(2+) fluorescence intensity and CaM concentration in tea roots, respectively. Interestingly, NPPB-inhibited F accumulation was found to be significantly alleviated in tea plants pretreated with either Ca(2+) chelator (EGTA) or CaM antagonists (CPZ and TFP). In addition, NPPB significantly depolarized membrane potential transiently and we argue that the net Ca(2+) and H⁺ efflux across the plasma membrane contributed to the restoration of membrane potential. Overall, our results suggest that regulation of Ca(2+)-CaM and plasma membrane potential depolarization are involved in NPPB-inhibited F accumulation in tea plants.

Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake.

Two new oleanane-type saponins, named oleiferasaponins C4 (1) and C5 (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3ß-O-[ß-d-galacto-pyranosyl-(1→2)]-[ß-d-glucopyranosyl-(1→2)-ß-d-galactopyranosy-(1→3)]-ß-d-glucopyranosid-uronic acid methyl ester (1) and 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxy-methylene-olean-12-ene-3ß-O-[ß-d-galactopyranosyl-(1→2)]-[ß-d-galactopyranosyl-(1→3)]-ß-d-glucopyranosiduronic acid methyl ester (2) through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB).

Al(3+) -promoted fluoride accumulation in tea plants (Camellia sinensis) was inhibited by an anion channel inhibitor DIDS.

BACKGROUND: Generally, tea plants are grown in acid soil which is rich in aluminum (Al) and fluoride (F). A recent publication showed that pretreatment with Al(3+) promoted F accumulation in tea plants by increasing endogenous Ca(2+) and calmodulin (CaM). A high level of F in tea leaves not only impairs tea quality but also might pose a health risk for people drinking tea regularly. Therefore it is important to try to find some clues which might be beneficial in controlling F accumulation in tea plants grown in acid soil (Al(3+) ). RESULTS: It was found that diisothiocyanostilbene-2,2-disulfonic acid (DIDS) significantly reduced Al(3+) -promoted F accumulation in tea plants. Additionally, Al(3+) plus DIDS treatment stimulated significantly higher Ca(2+) efflux and decreased the CaM level in tea roots compared with Al(3+) treatment. Besides, significantly higher depolarization of membrane potential was shown in tea roots treated with Al(3+) plus DIDS than in those treated with Al(3+) , as well as higher net total H(+) efflux and plasma membrane H(+) -ATPase activity. CONCLUSION: Al(3+) -promoted F accumulation in tea plants was inhibited by an anion channel inhibitor DIDS. Ca(2+) /CaM and membrane potential depolarization may be the components involved in this process. © 2016 Society of Chemical Industry.

TMDB: a literature-curated database for small molecular compounds found from tea.

BACKGROUND: Tea is one of the most consumed beverages worldwide. The healthy effects of tea are attributed to a wealthy of different chemical components from tea. Thousands of studies on the chemical constituents of tea had been reported. However, data from these individual reports have not been collected into a single database. The lack of a curated database of related information limits research in this field, and thus a cohesive database system should necessarily be constructed for data deposit and further application. DESCRIPTION: The Tea Metabolome database (TMDB), a manually curated and web-accessible database, was developed to provide detailed, searchable descriptions of small molecular compounds found in Camellia spp. esp. in the plant Camellia sinensis and compounds in its manufactured products (different kinds of tea infusion). TMDB is currently the most complete and comprehensive curated collection of tea compounds data in the world. It contains records for more than 1393 constituents found in tea with information gathered from 364 published books, journal articles, and electronic databases. It also contains experimental 1H NMR and 13C NMR data collected from the purified reference compounds or collected from other database resources such as HMDB. TMDB interface allows users to retrieve tea compounds entries by keyword search using compound name, formula, occurrence, and CAS register number. Each entry in the TMDB contains an average of 24 separate data fields including its original plant species, compound structure, formula, molecular weight, name, CAS registry number, compound types, compound uses including healthy benefits, reference literatures, NMR, MS data, and the corresponding ID from databases such as HMDB and Pubmed. Users can also contribute novel regulatory entries by using a web-based submission page. The TMDB database is freely accessible from the URL of http://pcsb.ahau.edu.cn:8080/TCDB/index.jsp. The TMDB is designed to address the broad needs of tea biochemists, natural products chemists, nutritionists, and members of tea related research community. CONCLUSION: The TMDB database provides a solid platform for collection, standardization, and searching of compounds information found in tea. As such this database will be a comprehensive repository for tea biochemistry and tea health research community.

(Z, Z, Z)-3,6,9-Nonadecadiene, a potential inhibitor of sex pheromone of Grey Tea Geometrid (Lepidoptera: Geometridae): electroantennogram test, wind tunnel, and in silico study.

Sex pheromone analogs have high structural similarity to sex pheromone components. They also play a role in studying many agricultural pests. In our study, (Z, Z, Z)-3,6,9-nonadecadiene (Z3Z6Z9-19:Hy) was successfully synthesized, which is an analogue to 1 of 2 sex pheromone components of Ectropis grisescens Warren (Z, Z, Z)-3,6,9-octadecatriene (Z3Z6Z9-18:Hy), and it showed potential inhibition in experiments. In the electroantennogram test, Z3Z6Z9-19:Hy showed a dose-dependent response, and only measured half the response of Z3Z9-6,7-epo-18:Hy. However, the compound significantly reduced positive response of E. grisescens males by up to 70% in the Y-tube olfactometer. Furthermore, in the wind tunnel, it significantly inhibited all types of behavioral responses. The percentage of moths contacting the pheromone odor source was reduced even at the lowest dose tested. In silico study afterward, molecular docking results showed affinity between Z3Z6Z9-19:Hy and sensory neuron membrane protein 1. Our study revealed the potential of Z3Z6Z9-19:Hy as a sex pheromone inhibitor, which would provide new tools for monitoring and mating disruption of E. grisescens.

EGCG inhibit chemical reactivity of iron through forming an Ngal-EGCG-iron complex.

Accumulated evidence indicates that the interconversion of iron between ferric (Fe(3+)) and ferrous (Fe(2+)) can be realized through interaction with reactive oxygen species in the Fenton and Haber-Weiss reactions and thereby physiologically effects redox cycling. The imbalance of iron and ROS may eventually cause tissue damage such as renal proximal tubule injury and necrosis. Many approaches were exploited to ameliorate the oxidative stress caused by the imbalance. (-)-Epigallocatechin-3-gallate, the most active and most abundant catechin in tea, was found to be involved in the protection of a spectrum of renal injuries caused by oxidative stress. Most of studies suggested that EGCG works as an antioxidant. In this paper, Multivariate analysis of the LC-MS data of tea extracts and binding assays showed that the tea polyphenol EGCG can form stable complex with iron through the protein Ngal, a biomarker of acute kidney injury. UV-Vis and Luminescence spectrum methods showed that Ngal can inhibit the chemical reactivity of iron and EGCG through forming an Ngal-EGCG-iron complex. In thinking of the interaction of iron and ROS, we proposed that EGCG may work as both antioxidant and Ngal binding siderphore in protection of kidney from injuries.

A new norisoprenoid and other compounds from Fuzhuan brick tea.

Fuzhuan brick tea, a kind of dark tea consumed mainly in the border regions of Southwestern and Northwestern China since the 1860s, is produced from the leaves of Camellia sinensis var. sinensis by microbial fermentation. From this special fermented tea, a new norisoprenoid, 3R,9R-oxido-5-megastigmene, was isolated, together with α-linolenic acid, strictin, isovitexin, astragalin, (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, (+)-gallocatechin, (-)-epigallocatechin, (-)-epigallocatechin gallate and gallic acid. The structures of the compounds were identified by spectroscopic means. The new compound didn't show any inhibition activity against the tested enteric pathogenic microorganisms at a concentration of 800 µg/mL by the hole plate diffusion method.

Preferentially expressed antigen in melanoma immunohistochemistry as an adjunct for differential diagnosis in acral lentiginous melanoma and acral nevi.

Preferentially expressed antigen in melanoma (PRAME) has shown promising utility in distinguishing benign melanocytic lesions from melanomas, but knowledge of its expression pattern in acral lentiginous melanoma (ALM) and acral nevi (ANs) is limited. Immunohistochemical expression of PRAME was examined in 75 ALMs and 34 ANs. The clinical and histopathologic characteristics of patients with ALM were collected. PRAME was immunoreactive in 89.3% (67/75) of ALMs, but entirely negative in 94.1% (32/34) of ANs. When staining at least 50% of lesional melanocytes was determined as positivity, the sensitivity and specificity of PRAME for distinguishing ALM from ANs were 69.3% and 100%, respectively. Seventy-one cases of ALMs had tumor cells in the epidermis; 71.8% (51/71) of them showed positive for PRAME. By contrast, 61 ALMs had tumor cells in the dermis; 65.6% (40/61) exhibited positive expression. Twenty-nine of 39 (74.4%) epithelioid cell ALMs were observed to be positive for PRAME. By comparison, 63.8% (23/36) of ALMs with spindle tumor cells were positive for PRAME. However, PRAME positive expression was not associated with any clinical and histopathologic characteristics of patients with ALM, including Breslow thickness, ulcer, cytomorphology, lymph node metastasis, or tumor-infiltrated lymphocytes (TILs). Nevertheless, we observed that 82.6% (19/23) of ALMs with lymph node involvement at diagnosis expressed PRAME, compared with 57.6% (20/35) of those without. In summary, PRAME immunohistochemistry can serve as a helpful adjunct in the differential diagnosis of ALMs and ANs with good sensitivity and high specificity. Additionally, PRAME tends to have a higher positive rate in epidermal melanocytes than in the dermis and is inclined to express in epithelioid cells than in spindle cells of ALMs.

Microbial and Nonvolatile Chemical Diversities of Chinese Dark Teas Are Differed by Latitude and Pile Fermentation.

Understanding the microbial and chemical diversities, as well as what affects these diversities, is important for modern manufacturing of traditional fermented foods. In this work, Chinese dark teas (CDTs) that are traditional microbial fermented beverages with relatively high sample diversity were collected. Microbial DNA amplicon sequencing and mass spectrometry-based untargeted metabolomics show that the CDT microbial ß diversity, as well as the nonvolatile chemical α and ß diversities, is determined by the primary impact factors of geography and manufacturing procedures, in particular, latitude and pile fermentation after blending. A large number of metabolites sharing between CDTs and fungi were discovered by Feature-based Molecular Networking (FBMN) on the Global Natural Products Social Molecular Networking (GNPS) web platform. These molecules, such as prenylated cyclic dipeptides and B-vitamins, are functionally important for nutrition, biofunctions, and flavor. Molecular networking has revealed patterns in metabolite profiles on a chemical family level in addition to individual structures.