Immunophenotypic, genetic, and clinical characterization of adult T-cell leukemia/lymphoma: A single tertiary care center experience in the United States.

OBJECTIVES: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Its most common immunophenotype is CD4+/CD7-/CD25+, although unusual immunophenotypes can occur and may lead to misdiagnosis. METHODS: The immunophenotypes, cytogenetics, molecular features, clinical presentations, treatment, and prognosis of 131 patients with ATLL were retrospectively studied in a large tertiary medical center in the United States. RESULTS: All cases showed loss of CD7 expression. While 82.4% of cases demonstrated CD4+, 17.6% exhibited unusual phenotypes, including CD4+/CD8+ (6.9%), CD4-/CD8- (2.3%), CD5- (3.1%), CD2-, and CD3-. The most common cytogenetics abnormalities included polysomy 3 (34.6%), translocation 1 (23.1%), and abnormalities found on chromosome 11 (30.8%) and chromosome 14 (26.9%). The common gene mutations identified by the next-generation sequencing study were TP53 (16.7%), TBL1XR1 (16.7%), EP300 (14.3%), and NOTCH1 (14.3%). TBL1XR1 mutation is associated with genetic instabilities. There was no significant difference between the clinical presentations of these 2 groups. CONCLUSIONS: Adult T-cell leukemia/lymphoma exhibits versatile immunophenotypic, cytogenetic, and molecular features. Simultaneous involvement of blood, lymph nodes, and other organs, along with hypercalcemia in a patient from an endemic area, necessitates HTLV-1 testing to avoid underdiagnosis of this dismal disease that might need aggressive chemotherapy followed by bone marrow transplant.

Gold nanoclusters-based fluorescence resonance energy transfer for rapid and sensitive detection of Pb2.

Lead pollution has remained a significant global concern for several decades due to its detrimental effects on the brain, heart, kidneys, lungs, and immune system across all age groups. Addressing the demand for detecting trace amounts of lead in food samples, we have developed a novel biosensor based on fluorescence resonance energy transfer (FRET) from fluorescein R6G to gold nanoclusters (AuNCs-CCY). By utilizing polypeptides as a template, we successfully synthesized AuNCs-CCY with an excitation spectrum that overlaps with the emission spectrum of R6G. Exploiting the fact that Pb2+ induces the aggregation of gold nanoclusters, leading to the separation of R6G from AuNCs-CCY and subsequent fluorescence recovery, we achieved the quantitative detection of Pb2+. Within the concentration range of 0.002-0.20 µM, a linear relationship was observed between the fluorescence enhancement value (F-F0) and Pb2+ concentration, characterized by the linear equation y = 2398.69x + 87.87 (R2 = 0.996). The limit of detection (LOD) for Pb2+ was determined to be 0.00079 µM (3σ/K). The recovery rate ranged from 96 % to 104 %, with a relative standard deviation (RSD) below 10 %. These findings demonstrate the potential application value of our biosensor, which offers a promising approach to address the urgent need for sensitive detection of heavy metal ions, specifically Pb2+, in food samples.

Retrospective analysis of discordant results between histology and other clinical diagnostic tests on helicobacter pylori infection.

BACKGROUND: A reliable test is essential for diagnosing Helicobacter pylori (H. pylori) infection, and crucial for managing H. pylori-related diseases. Serving as an excellent method for detecting H. pylori infection, histologic examination is a test that clinicians heavily rely on, especially when complemented with immunohistochemistry (IHC). Additionally, other diagnostic tests for H. pylori, such as the rapid urease test (CLO test) and stool antigen test (SA), are also highly sensitive and specific. Typically, the results of histology and other tests align with each other. However, on rare occasions, discrepancy between histopathology and other H. pylori diagnostic tests occurs. AIM: To investigate the discordance between histology and other H. pylori tests, the underlying causes, and the impact on clinical management. METHODS: Pathology reports of gastric biopsies were retrieved spanning August 2013 and July 2018. Reports were included in the study only if there were other H. pylori tests within seven days of the biopsy. These additional tests include CLO test, SA, and H. pylori culture. Concordance between histopathology and other tests was determined based on the consistency of results. In instances where histology results were negative while other tests were positive, the slides were retrieved for re-assessment, and the clinical chart was reviewed. RESULTS: Of 1396 pathology reports were identified, each accompanied by one additional H. pylori test. The concordance rates in detecting H. pylori infection between biopsy and other tests did not exhibit significant differences based on the number of biopsy fragments. 117 discrepant cases were identified. Only 20 cases (9 with CLO test and 11 with SA) had negative biopsy but positive results in other tests. Four cases initially stained with Warthin-Starry turned out to be positive for H. pylori with subsequent IHC staining. Among the remaining 16 true discrepant cases, 10 patients were on proton pump inhibitors before the biopsy and/or other tests. Most patients underwent treatment, except for two who were untreated, and two patients who were lost to follow-up. CONCLUSION: There are rare discrepant cases with negative biopsy but positive in SA or CLO test. Various factors may contribute to this inconsistency. Most patients in such cases had undergone treatment.

Recurrent Primary Peritoneal Psammocarcinoma: A Case Report on a Diagnostic Challenge in Cytology.

Psammocarcinoma (PCa) is a rare variant of low-grade papillary serous carcinoma that can arise from the peritoneal as well as ovarian surfaces. When this tumor involves the extra-ovarian peritoneum significantly and the ovarian surface minimally or not at all, it is considered of peritoneal origin. PCa has a recurrent indolent clinical course. It is challenging to diagnose peritoneal PCa, particularly on cytological smears because of the bland cellular features of neoplastic cells. We report a case of recurrent metastatic primary peritoneal PCa in a 71-year-old female of Ashkenazi Jewish ancestry diagnosed on cytology of ascitic and cystic fluid.

A review on surfactin: molecular regulation of biosynthesis.

Surfactin has many biological activities, such as inhibiting plant diseases, resisting bacteria, fungi, viruses, tumors, mycoplasma, anti-adhesion, etc. It has great application potential in agricultural biological control, clinical medical treatment, environmental treatment and other fields. However, the low yield has been the bottleneck of its popularization and application. It is very important to understand the synthesis route and control strategy of surfactin to improve its yield and purity. In this paper, based on the biosynthetic pathway and regulatory factors of surfactin, its biosynthesis regulation strategy was comprehensively summarized, involving enhancement of endogenous and exogenous precursor supply, modification of the synthesis pathway of lipid chain and peptide chain, improvement of secretion and efflux, and manipulation some global regulatory factors, such as Spo0A, AbrB, ComQXP, phrCSF, etc. to directly or indirectly stimulate surfactin synthesis. And the current production and separation and purification process of surfactin are briefly described. This review also provides a scientific reference for promoting surfactin production and its applications in various fields.

Nitric Oxide Extends the Postharvest Life of Water Bamboo Shoots Partly by Maintaining Mitochondrial Structure and Energy Metabolism.

Harvested water bamboo shoots can be stored for only a few days before they lose weight and become soft. Nitrogen oxide (NO) and modified atmosphere packaging (MAP) have previously been used to prolong horticultural crop storage. In the present study, we analyzed the joint effect of these two methods on extending the postharvest quality of water bamboo shoots. Water bamboo shoots were treated with (1) 30 µL L-1 NO, (2) MAP, and (3) a combination of NO and MAP. The NO treatment delayed the softness and weight loss through maintaining the integrity of the mitochondrial ultrastructure and enhancing the ATP level by activating the expressions and activities of succinic dehydrogenase, malic acid dehydrogenase, and cytochrome oxidase. MAP improved the effect of NO on the mitochondrial energy metabolism. These results indicate that NO and MAP treatments are effective at suppressing the quality deterioration of water bamboo shoots, MAP improves the effect of NO in extending postharvest life, and NO may be the main effective factor in the combination of NO and MAP.

Differences in xylem development between Dutch and Japanese tomato (Solanum lycopersicum) correlate with cytokinin levels in hypocotyls.

BACKGROUND AND AIMS: Dutch tomato cultivars tend to have a greater yield than Japanese cultivars even if they are grown under the same conditions. Factors contributing to the increased yield of the Dutch cultivars were a greater light use efficiency and greater leaf photosynthetic rate. On the other hand, the relationship between tomato yields and anatomical traits is still unclear. The aim of this study is to identify the anatomical traits related to the difference in yield between Dutch and Japanese cultivars. METHODS: Anatomical properties were compared during different growth stages of Dutch and Japanese tomatoes. Hormone profiles and related gene expression in hypocotyls of Dutch and Japanese cultivars were compared in the hypocotyls of 3- and 4-week-old plants. KEY RESULTS: Dutch cultivars have a more developed secondary xylem than Japanese cultivars, which would allow for greater transport of water, mineral nutrients and phytohormones to the shoots. The areas and ratios of the xylem in the hypocotyls of 3- to 6-week-old plants were larger in the Dutch cultivars. In reciprocal grafts of the Japanese and Dutch cultivars, xylem development at the scion and rootstock depended on the scion cultivar, suggesting that some factors in the scion are responsible for the difference in xylem development. The cytokinin content, especially the level of N6-(Δ 2-isopentenyl) adenine (iP)-type cytokinin, was higher in the Dutch cultivars. This result was supported by the greater expression of Sl-IPT3 (a cytokinin biosynthesis gene) and Sl-RR16/17 (a cytokinin-responsive gene) in the Dutch cultivars. CONCLUSIONS: These results suggest that iP-type cytokinins, which are locally synthesized in the hypocotyl, contribute to xylem development. The greater xylem development in Dutch cultivars might contribute to the high yield of the tomato.

Waterlogging-induced adventitious root formation in cucumber is regulated by ethylene and auxin through reactive oxygen species signalling.

Development of adventitious roots (ARs) at the base of the shoot is an important adaptation of plants to waterlogging stress; however, its physiological mechanisms remain unclear. Here, we investigated the regulation of AR formation under waterlogged conditions by hormones and reactive oxygen species (ROS) in Cucumis sativus L., an agriculturally and economically important crop in China. We found that ethylene, auxin, and ROS accumulated in the waterlogged cucumber plants. On the other hand, application of the ethylene receptor inhibitor 1-methylcyclopropene (1-MCP), the auxin transport inhibitor 1-naphthylphthalamic acid (NPA), or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the number of ARs induced by waterlogging. Auxin enhanced the expression of ethylene biosynthesis genes, which led to ethylene entrapment in waterlogged plants. Both ethylene and auxin induced the generation of ROS. Auxin-induced AR formation was inhibited by 1-MCP, although ethylene-induced AR formation was not inhibited by NPA. Both ethylene- and auxin-induced AR formation were counteracted by DPI. These results indicate that auxin-induced AR formation is dependent on ethylene, whereas ethylene-induced AR formation is independent of auxin. They also show that ROS signals mediate both ethylene- and auxin-induced AR formation in cucumber plants.

The major-effect quantitative trait locus CsARN6.1 encodes an AAA ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.

In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an AAA ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the AAA ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance.

Fine mapping of a dominantly inherited powdery mildew resistance major-effect QTL, Pm1.1, in cucumber identifies a 41.1 kb region containing two tandemly arrayed cysteine-rich receptor-like protein kinase genes.

KEY MESSAGE: A dominantly inherited major-effect QTL for powdery mildew resistance in cucumber was fine mapped. Two tandemly arrayed cysteine-rich receptor-like protein kinase genes were identified as the most possible candidates. Powdery mildew (PM) is one of the most severe fungal diseases of cucumber (Cucumis sativus L.) and other cucurbit crops, but the molecular genetic mechanisms of powdery mildew resistance in cucurbits are still poorly understood. In this study, through marker-assisted backcrossing with an elite cucumber inbred line, D8 (PM susceptible), we developed a single-segment substitution line, SSSL0.7, carrying 95 kb fragment from PM resistance donor, Jin5-508, that was defined by two microsatellite markers, SSR16472 and SSR16881. A segregating population with 3600 F2 plants was developed from the SSSL0.7 × D8 mating; segregation analysis confirmed a dominantly inherited major-effect QTL, Pm1.1 in cucumber chromosome 1 underlying PM resistance in SSSL0.7. New molecular markers were developed through exploring the next generation resequenced genomes of Jin5-508 and D8. Linkage analysis and QTL mapping in a subset of the F2 plants delimited the Pm1.1 locus into a 41.1 kb region, in which eight genes were predicted. Comparative gene expression analysis revealed that two concatenated genes, Csa1M064780 and Csa1M064790 encoding the same function of a cysteine-rich receptor-like protein kinase, were the most likely candidate genes. GFP fusion protein-aided subcellular localization indicated that both candidate genes were located in the plasma membrane, but Csa1M064780 was also found in the nucleus. This is the first report of dominantly inherited PM resistance in cucumber. Results of this study will provide new insights into understanding the phenotypic and genetic mechanisms of PM resistance in cucumber. This work should also facilitate marker-assisted selection in cucumber breeding for PM resistance.

Molecular progress in research on fruit astringency.

Astringency is one of the most important components of fruit oral sensory quality. Astringency mainly comes from tannins and other polyphenolic compounds and causes the drying, roughening and puckering of the mouth epithelia attributed to the interaction between tannins and salivary proteins. There is growing interest in the study of fruit astringency because of the healthy properties of astringent substances found in fruit, including antibacterial, antiviral, anti-inflammatory, antioxidant, anticarcinogenic, antiallergenic, hepatoprotective, vasodilating and antithrombotic activities. This review will focus mainly on the relationship between tannin structure and the astringency sensation as well as the biosynthetic pathways of astringent substances in fruit and their regulatory mechanisms.

Genome survey sequencing provides clues into glucosinolate biosynthesis and flowering pathway evolution in allotetrapolyploid Brassica juncea.

BACKGROUND: Brassica juncea is an economically important vegetable crop in China, oil crop in India, condiment crop in Europe and selected for canola quality recently in Canada and Australia. B. juncea (2n = 36, AABB) is an allotetraploid derived from interspecific hybridization between B. rapa (2n = 20, AA) and B. nigra (2n = 16, BB), followed by spontaneous chromosome doubling. RESULTS: Comparative genome analysis by genome survey sequence (GSS) of allopolyploid B. juncea with B. rapa was carried out based on high-throughput sequencing approaches. Over 28.35 Gb of GSS data were used for comparative analysis of B. juncea and B. rapa, producing 45.93% reads mapping to the B. rapa genome with a high ratio of single-end reads. Mapping data suggested more structure variation (SV) in the B. juncea genome than in B. rapa. We detected 2,921,310 single nucleotide polymorphisms (SNPs) with high heterozygosity and 113,368 SVs, including 1-3 bp Indels, between B. juncea and B. rapa. Non-synonymous polymorphisms in glucosinolate biosynthesis genes may account for differences in glucosinolate biosynthesis and glucosinolate components between B. juncea and B. rapa. Furthermore, we identified distinctive vernalization-dependent and photoperiod-dependent flowering pathways coexisting in allopolyploid B. juncea, suggesting contribution of these pathways to adaptation for survival during polyploidization. CONCLUSIONS: Taken together, we proposed that polyploidization has allowed for accelerated evolution of the glucosinolate biosynthesis and flowering pathways in B. juncea that likely permit the phenotypic variation observed in the crop.

Follicular dendritic cells activate HIV-1 replication in monocytes/macrophages through a juxtacrine mechanism mediated by P-selectin glycoprotein ligand 1.

Follicular dendritic cells (FDCs) are located in the lymphoid follicles of secondary lymphoid tissues and play a pivotal role in the selection of memory B lymphocytes within the germinal center, a major site for HIV-1 infection. Germinal centers are composed of highly activated B cells, macrophages, CD4(+)T cells, and FDCs. However, the physiological role of FDCs in HIV-1 replication remains largely unknown. We demonstrate in our current study that FDCs can efficiently activate HIV-1 replication in latently infected monocytic cells via an intercellular communication network mediated by the P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction. Upon coculture with FDCs, HIV-1 replication was significantly induced in infected monocytic cell lines, primary monocytes, or macrophages. These cocultures were found to synergistically induce the expression of P-selectin in FDCs via NF-kappaB activation and its cognate receptor PSGL-1 in HIV-1-infected cells. Consistent with this observation, we find that this response is significantly blocked by antagonistic Abs against PSGL-1 and almost completely inhibited by PSGL-1 small interfering RNA. Moreover, a selective inhibitor for Syk, which is a downstream effector of PSGL-1, blocked HIV-1 replication in our cultures. We have thus elucidated a novel regulatory mechanism in which FDCs are a potent positive bystander that facilitates HIV-1 replication in adjacent infected monocytic cells via a juxtacrine signaling mechanism.

Rapid authentication of olive oil adulteration by Raman spectrometry.

The authentication of olive oil and its adulteration with lower priced oils are still serious problems in the olive oil industry. In this study, a method based on the intensity ratio of the Raman spectroscopy vibration bands, especially on the intensity ratio of the cis ( ==C-H) and cis (C=C) bonds normalized by the band at 1441 cm(-1) (CH(2)), was established to authenticate genuine/fake olive oil. These intensity ratios of the vibration bands given in the form of a two-dimensional chart allow first the discrimination between the various grades of olive oil and the seed oils and then the detection of olive oil fraud by the line of y = 0.7, which is observed under most experiments and dot charts. This method can reliably distinguish the genuine olive oils from the olive oils containing 5% (volume percentage) or more of other edible oils, such as soybean oil, rapeseed oil, sunflower seed oil, or corn oil. Compared to the traditional principal component analysis method, this method is more intuitive, more precise, and easier to use. Moreover, this method also has the advantages of simplicity efficiency and has no need for sample preprocessing, being especially suitable for on-site testing in field applications.

Statin-induced inhibition of HIV-1 release from latently infected U1 cells reveals a critical role for protein prenylation in HIV-1 replication.

Latent infection of human immunodeficiency virus type 1 (HIV-1) represents a major hurdle in the treatment of acquired immunodeficiency syndrome (AIDS) patients. Statins were recently reported to suppress acute HIV-1 infection and reduce infectious virion production, but the precise mechanism of inhibition has remained elusive. Here we demonstrate that lypophilic statins suppress HIV-1 virion release from tumor necrosis factor alpha-stimulated latently infected U1 cells through inhibition of protein geranylgeranylation, but not by cholesterol depletion. Indeed, this suppression was reversed by the addition of geranylgeranylpyrophosphate, and a geranylgeranyltransferase-1 inhibitor reduced HIV-1 production. Notably, silencing of the endogenous Rab11a GTPase expression in U1 cells by RNA interference destabilized Gag and reduced virion production both in vitro and in NOD/SCID/gammac null mice. Our findings thus suggest that small GTPase proteins play an important role in HIV-1 replication, and therefore could be attractive molecular targets for anti-HIV-1 therapy.

Overexpressed NF-kappaB-inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells.

The nuclear factor-kappaB (NF-kappaB) transcription factors play important roles in cancer development by preventing apoptosis and facilitating the tumor cell growth. However, the precise mechanisms by which NF-kappaB is constitutively activated in specific cancer cells remain largely unknown. In our current study, we now report that NF-kappaB-inducing kinase (NIK) is overexpressed at the pretranslational level in adult T-cell leukemia (ATL) and Hodgkin Reed-Sternberg cells (H-RS) that do not express viral regulatory proteins. The overexpression of NIK causes cell transformation in rat fibroblasts, which is abolished by a super-repressor form of IkappaBalpha. Notably, depletion of NIK in ATL cells by RNA interference reduces the DNA-binding activity of NF-kappaB and NF-kappaB-dependent transcriptional activity, and efficiently suppresses tumor growth in NOD/SCID/gammac(null) mice. These results indicate that the deregulated expression of NIK plays a critical role in constitutive NF-kappaB activation in ATL and H-RS cells, and suggest also that NIK is an attractive molecular target for cancer therapy.