Case report: Systemic presentation of ALK-positive Histiocytosis.

ALK-positive Histiocytosis (ALK-HSs) is a recently identified rare clinical entity characterized by tissue histiocytic alterations associated with ALK gene rearrangement. Clinical presentations can be solitary, multifocal, or systemic (involving multiple sites and organs). Due to limited reported cases, there is inadequate understanding of this disease. This report presents a case of ALK-HSs in a 71-year-old male patient who presented with hematuria for one week. Imaging studies conducted at an external hospital showed multiple lesions in the penis, bilateral testes, back skin, and the third lumbar vertebra. Histopathological findings included spindle and histiocytic cell proliferation with mild or indistinct cellular atypia, interstitial infiltration of lymphocytes, plasma cells, foamy histiocytes, and fibrous tissue proliferation. Immunohistochemistry of the lesion cells revealed positivity for CD68, CD163, ALK1, ALK (D5F3), and Vimentin. FISH testing indicated ALK gene separation in the lesion cells. NGS testing identified the fusion genes KIF5B(NM_004521) and ALK(NM_004304) in the lesion cells. We combined the characteristics of this case with a review of the literature to enhance our understanding of this rare clinical entity.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Loss of SATB2 and CDX2 expression is associated with DNA mismatch repair protein deficiency and BRAF mutation in colorectal cancer.

The relationship between the expression of the SATB2 and CDX2 proteins and common molecular changes and clinical prognosis in colorectal cancer (CRC) still needs further clarification. We collected 1180 cases of CRC and explored the association between the expression of SATB2 and CDX2 and clinicopathological characteristics, molecular alterations, and overall survival of CRC using whole-slide immunohistochemistry. Our results showed that negative expression of SATB2 and CDX2 was more common in MMR-protein-deficient CRC than in MMR-protein-proficient CRC (15.8% vs. 6.0%, P = 0.001; 14.5% vs. 4.0%, P = 0.000, respectively). Negative expression of SATB2 and CDX2 was more common in BRAF-mutant CRC than in BRAF wild-type CRC (17.2% vs. 6.1%, P = 0.003; 13.8% vs. 4. 2%; P = 0.004, respectively). There was no relationship between SATB2 and/or CDX2 negative expression and KRAS, NRAS, and PIK3CA mutations. The lack of expression of SATB2 and CDX2 was associated with poor histopathological features of CRC. In multivariate analysis, negative expression of SATB2 (P = 0.030), negative expression of CDX2 (P = 0.043) and late clinical stage (P = 0.000) were associated with decreased overall survival of CRC. In conclusion, the lack of SATB2 and CDX2 expression in CRC was associated with MMR protein deficiency and BRAF mutation, but not with KRAS, NRAS and PIK3CA mutation. SATB2 and CDX2 are prognostic biomarkers in patients with CRC.

Co-option of a non-retroviral endogenous viral element in planthoppers.

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.

Horizontally Transferred Salivary Protein Promotes Insect Feeding by Suppressing Ferredoxin-Mediated Plant Defenses.

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.

Transcriptomic Analysis of Tobacco Plants in Response to Whitefly Infection.

The whitefly Bemisia tabaci is one of the most destructive pests worldwide, and causes tremendous economic losses. Tobacco Nicotiana tabacum serves as a model organism for studying fundamental biological processes and is severely damaged by whiteflies. Hitherto, our knowledge of how tobacco perceives and defends itself against whiteflies has been scare. In this study, we analyze the gene expression patterns of tobacco in response to whitefly infestation. A total of 244 and 2417 differentially expressed genes (DEGs) were identified at 12 h and 24 h post whitefly infestation, respectively. Enrichment analysis demonstrates that whitefly infestation activates plant defense at both time points, with genes involved in plant pattern recognition, transcription factors, and hormonal regulation significantly upregulated. Notably, defense genes are more intensely upregulated at 24 h post infestation than at 12 h, indicating an increased immunity induced by whitefly infestation. In contrast, genes associated with energy metabolism, carbohydrate metabolism, ribosomes, and photosynthesis are suppressed, suggesting impaired plant development. Taken together, our study provides comprehensive insights into how plants respond to phloem-feeding insects, and offers a theoretical basis for better research on plant-insect interactions.

Insight into phenotypic plasticity in planthoppers.

Planthoppers possess an impressive ability to exhibit phenotypic plasticity, which allows them to adjust their morphology for migration, overwintering, and adaptation to different environmental conditions. The wing and color polyphenism are the two most outward morphologies. Wing polyphenism serves as a classic illustration of a life history trade-off between reproduction and migration, while color polyphenism is potentially correlated with the insect development and immunity. In this review, we present the important contributions that link environment cues to wing and color polyphenism, and highlight recent advances in insulin/insulin-like growth factor signaling-forkhead transcription factor subgroup O (FoxO) pathway-mediated wing development and tyrosine-melanin pathway-mediated coloration. Further work, particularly in the identification of the genes that FoxO regulates and in the elucidation of the intracellular signals that link the stimuli to the tyrosine-melanin pathway, is required.

Case Report: A tortuous diagnosis and successful multimodal treatment of thyroid follicular carcinoma with pelvic metastasis.

Purpose: To provide reference method for the treatment of thyroid follicular carcinoma by studing the clinical imaging, pathological features and multimodal treatment of a case of thyroid follicular carcinoma with bone metastasis. Methods: By identifying the case's clinical, imaging, pathological features of a case of thyroid follicular carcinoma with bone metastasis, reflecting on the case's diagnosis and treatment process, and referring to literature about the characteristics of thyroid follicular carcinoma, the study aims to provide reference for the treatment of this kind of disease. Result: A 67-year-old male patient was admitted to the hospital with clinical symptoms of left pelvic pain. The biopsy pathology showed well-differentiated thyroid tissue. Considering his medical history, conclusion of thyroid follicular carcinoma metastasis could be made.The patient was stable and no tumor progression was observed after a combination of therapies including 131I and topical and targeted agents. Conclusions: Thyroid follicular carcinoma are prone to bone metastasis, and bone metastasis is the first symptom in some cases. Clinical imaging and pathology are needed for correct diagnosis, and a successful treatment requires a combination of multiple approaches including 131I, which is a Radioactive Iodine Therapy(RAI), local therapy and targeted drug therapy.

A secreted salivary effector from Riptortus pedestris impairs soybean defense through modulating phytohormone signaling pathways.

Riptortus pedestris (Fabricius), one of the major piercing-sucking insects in soybeans, causes delayed plant senescence and abnormal pods, known as staygreen syndrome. Recent research has shown that direct feeding of this insect is the major cause of soybean staygreen syndrome. However, it remains unclear whether R. pedestris salivary proteins play vital roles in insect infestation. Here, we found that 4 secretory salivary proteins can induce cell death in Nicotiana benthamiana by transient heterologous expression. The cell death induced by Rp2155 relies on the nucleotide-binding leucine-rich repeat helper, HSP90. Tissue-specificity assays indicated that Rp2155 is specifically expressed in the salivary gland of R. pedestris and is significantly induced during insect feeding. The expression of salicylic acid (SA)-, jasmonic acid (JA)-related genes was increased in soybean when fed by Rp2155-silenced R. pedestris. More importantly, soybean staygreen symptoms caused by R. pedestris were significantly alleviated when Rp2155 was silenced. Together, these results suggest that the salivary effector Rp2155 is involved in promoting insect infestation by suppressing the JA and SA pathways, and it can be considered as a potential RNA interference target for insect control.

The JAK-STAT pathway promotes persistent viral infection by activating apoptosis in insect vectors.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved signaling pathway that can regulate various biological processes. However, the role of JAK-STAT pathway in the persistent viral infection in insect vectors has rarely been investigated. Here, using a system that comprised two different plant viruses, Rice stripe virus (RSV) and Rice black-streaked dwarf virus (RBSDV), as well as their insect vector small brown planthopper, we elucidated the regulatory mechanism of JAK-STAT pathway in persistent viral infection. Both RSV and RBSDV infection activated the JAK-STAT pathway and promoted the accumulation of suppressor of cytokine signaling 5 (SOCS5), an E3 ubiquitin ligase regulated by the transcription factor STAT5B. Interestingly, the virus-induced SOCS5 directly interacted with the anti-apoptotic B-cell lymphoma-2 (BCL2) to accelerate the BCL2 degradation through the 26S proteasome pathway. As a result, the activation of apoptosis facilitated persistent viral infection in their vector. Furthermore, STAT5B activation promoted virus amplification, whereas STAT5B suppression inhibited apoptosis and reduced virus accumulation. In summary, our results reveal that virus-induced JAK-STAT pathway regulates apoptosis to promote viral infection, and uncover a new regulatory mechanism of the JAK-STAT pathway in the persistent plant virus transmission by arthropod vectors.

Primary Langerhans cell sarcoma in the urinary bladder: Case report and literature review.

Langerhans cell sarcoma (LCS) is a rare malignancy of dendritic cells and usually results in a poor oncological outcome. Thus, LCS is usually given a positive administration. Herein, we presented the first case of primary LCS in the urinary bladder staged T1N0M0 and treated by TURBT and short-term local chemotherapy. Our experience in this unique case may suggest that LCS in the urinary bladder with a non-muscle-invasive stage may be managed according to the treatment model of non-muscle-invasive urothelial carcinoma of the urinary bladder.

Complete genome analysis of a novel iflavirus from the spotted lanternfly Lycorma delicatula.

The spotted lanternfly (Lycorma delicatula) is an invasive pest that causes serious economic losses in fruit and wood production. Here, we identified a novel iflavirus named "Lycorma delicatula iflavirus 1" (LDIV1), in a spotted lanternfly. The full genome sequence of LDIV1 is 10,222 nt in length and encodes a polyprotein containing a picornavirus capsid-protein-domain-like domain, a cricket paralysis virus capsid superfamily domain, an RNA helicase domain, a peptidase C3 superfamily domain, and an RNA-dependent RNA polymerase (RdRp) domain. LDIV1 replicates in the host insect and activates small interfering RNA (siRNA)-based host antiviral immunity. Phylogenetic analysis demonstrated that LDIV1 is most closely related to an unspecified member of the order Picornavirales, with 61.7% sequence identity in the RdRp region and 57.6% sequence identity in the coat protein region, and thus meets the demarcation criteria for new species in the genus Iflavirus. To the best of our knowledge, LDIV1 is the first virus discovered in L. delicatula.

UBC Mediated by SEPT6 Inhibited the Progression of Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most common malignancies in men. Protein ubiquitination is an important mechanism for regulating protein activity and level in vivo. We aimed to study the mechanism of SEPT6 and UBC action in prostate cancer to identify new targets. METHODS: The ubiquitin-protein and the ubiquitin coding gene UBA52, UBA80, UBB, and UBC expressions were detected in clinical tissues and cells. Overexpression and knockdown of UBC were performed in prostate cancer DU145 cells. Cell Counting Kit 8 (CCK-8) assay was performed to detect cell proliferation. Cell cycle at 24 h was detected by flow cytometry. Clonal formation assay was used to measure cell clone number. Immunofluorescence (IF) was performed to detect the colocalization of SEPT6 and UBC in prostate cancer cells. Next, we overexpressed or knocked down SEPT6 expression in DU145 cells. Pearson correlation coefficient was applied to analyze the relationship between SEPT6 and UBC in prostate cancer tissue. oe-SEPT6+oe-UBC coexpressing cells were constructed to detect the upstream and downstream relationship between SEPT6 and UBC on prostate cancer cells. The tumor formation experiment was performed to explore SEPT6/UBC effect on prostate cancer. RESULTS: UBC was upregulated in prostate cancer tissues and cells. Overexpression of UBC promoted cell survival and proliferation. IF revealed the colocalization of SEPT6 and UBC in prostate cancer cells. UBC expression decreased after oe-SEPT6, while increased after sh-SEPT6, indicating that UBC was downstream of SEPT6. Pearson correlation coefficient analysis showed that SEPT6 was negatively correlated with UBC in prostate cancer tissues. SEPT6 as an upstream gene of UBC regulated prostate cancer cell behavior through UBC. The tumor formation experiment showed that SEPT6 could inhibit tumor growth. CONCLUSION: In general, SEPT6 inhibited UBC expression, thereby reducing the overall ubiquitination level, affecting the expression level of downstream cell proliferation-related genes, and then affecting the progression of prostate cancer.

Identification of Riptortus pedestris Salivary Proteins and Their Roles in Inducing Plant Defenses.

The bean bug, Riptortus pedestris (Fabricius), is one of the most important soybean pests. It damages soybean leaves and pods with its piercing-sucking mouthparts, causing staygreen-like syndromes in the infested crops. During the feeding process, R. pedestris secretes a mixture of salivary proteins, which play critical roles in the insect-plant interactions and may be responsible for staygreen-like syndromes. The present study aimed to identify the major salivary proteins in R. pedestris saliva by transcriptomic and proteomic approaches, and to screen the proteins that potentially induced plant defense responses. Altogether, 136 salivary proteins were identified, and a majority of them were involved in hydrolase and binding. Additionally, R. pedestris saliva contained abundant bug-specific proteins with unknown function. Transient expression of salivary proteins in Nicotiana benthamiana leaves identified that RpSP10.3, RpSP13.4, RpSP13.8, RpSP17.8, and RpSP10.2 were capable of inducing cell death, reactive oxygen species (ROS) burst, and hormone signal changes, indicating the potential roles of these proteins in eliciting plant defenses. Our results will shed more light on the molecular mechanisms underlying the plant-insect interactions and are useful for pest management.

Dioscin Promotes Prostate Cancer Cell Apoptosis and Inhibits Cell Invasion by Increasing SHP1 Phosphorylation and Suppressing the Subsequent MAPK Signaling Pathway.

Dioscin possesses antioxidant effects and has anticancer ability in many solid tumors including prostate cancer (PCa). Nevertheless, its effect and mechanism of anti-PCa action remain unclear. The tyrosine protein phosphatase SHP1, which contains an oxidation-sensitive domain, has been confirmed as a target for multicancer treatment. Further studies are needed to determine whether dioscin inhibits PCa through SHP1. We performed in vitro studies using androgen-sensitive (LNCaP) and androgen-independent (LNCaP -C81) cells to investigate the anticancer effects and possible mechanisms of dioscin after administering interleukin-6 (IL-6) and dihydrotestosterone (DHT). Our results show that dioscin inhibited cell growth and invasion by increasing SHP1 phosphorylation [p-SHP1 (Y536)] and inhibiting the subsequent P38 mitogen-activated protein kinase signaling pathway. Further in vivo studies confirmed that dioscin promoted caspase-3 and Bad-related cell apoptosis in these two cell lines. Our research suggests that the anticancer effects of dioscin on PCa may occur through SHP1. Dioscin may be useful to treat androgen-sensitive and independent PCa in the future.

miR-223-5p targeting ERG inhibits prostate cancer cell proliferation and migration.

Ectopic expression of miR-223-5p, the lagging strand of miR-223 duplex, has been reported acting as anti-tumor miRNA in many cancers. How miR-223-5p influencing prostate cancer (PCa) remains obscure and worth of experimental investigation. In this study, the expressions of miR-223-5p and ERG in common PCa cell lines were detected and compared to RWPE-1, respectively. Then luciferase reporter assay was performed to verify whether miR-223-5p could specifically target and regulate ERG. Further discovery ERG's role in the PCa oncogenesis was also conducted by up or down regulating miR-223-3p expression. We found miR-223-5p was significantly down-regulated in DU145, while it was only up-regulated in LNCaP. Similarly, ERG expression remarkably decreased in both PC-3 and DU145 than that in RWPE-1, but significantly increasing in LNCaP. Luciferase assay demonstrated slightly decreased ERG expression after miR-223-5p-mimics but significantly increased ERG expression after miR-223-5p-inhibtor. Using gene interference, we further confirmed that both ERG mRNA and protein expressions were decreased in all PCa lines transfected ERG siRNA, but increasing in both DU145 and LNCaP cells with miR-223-5p antisense oligonucleotides. MTT assay, Transwell invasion and migration assay supported the function of ERG in PCa oncogenesis. We revealed tumor suppressive abilities of miR-223-5p in PCa by negatively targeting ERG gene. It could serve as a fundamental supplement and extension of our previous study about miR-223-3p in PCa, revealing the coordinative regulation between miR-223-5p and miR-223-3p in PCa cell biological behaviors. Exploration of miR-233-duplex orientated pathway networks may help us develop novel potential therapeutic options for PCa.

Salivary DNase II from Laodelphax striatellus acts as an effector that suppresses plant defence.

Extracellular DNA, released by damaged plant cells, acts as a damage-associated molecular pattern (DAMP). We demonstrated previously that the small brown planthopper (Laodelphax striatellus, SBPH) secreted DNase II when feeding on artificial diets. However, the function of DNase II in insect feeding remained elusive. The influences of DNase II on SBPHs and rice plants were investigated by suppressing expression of DNase II or by application of heterogeneously expressed DNase II. We demonstrated that DNase II is mainly expressed in the salivary gland and is responsible for DNA-degrading activity of saliva. Knocking down the expression of DNase II resulted in decreased performance of SBPH reared on rice plants. The dsDNase II-treated SBPH did not influenced jasmonic acid (JA), salicylic acid (SA), ethylene (ET) pathways, but elicited a higher level of H2 O2 and callose accumulation. Application of heterogeneously expressed DNase II in DNase II-deficient saliva slightly reduced the wound-induced defence response. We propose a DNase II-based invading model for SBPH feeding on host plants, and provide a potential target for pest management.

A mitochondrial membrane protein is a target for rice ragged stunt virus in its insect vector.

Rice ragged stunt virus (RRSV; Reoviridae) is exclusively transmitted by the brown planthopper Nilaparvata lugens in a persistent-propagative manner. It is understood that RNA viral proliferation is associated with the intracellular membranes of the insect host cells. However, the molecular mechanisms of the interaction between the RRSV proliferation and the intracellular membranes remain essentially unknown. It will be of great interest to determine whether RRSV protein(s) directly interact with intracellular membrane components of its host cells. In this study, we identified a RRSV nonstructural protein Pns10 interacting with a host oligomycin-sensitivity conferral protein (OSCP) using yeast two-hybrid system. The interaction between RRSV Pns10 and N. lugens OSCP was verified by a glutathione S-transferase pull-down assay. Confocal miscopy revealed colocalization of these two proteins in the cytoplasm of the salivary gland cells during the viral infection. The virions were further detected in the mitochondria under confocal miscopy and transmission electron microscopy combined with western blotting assay. This is the first observation that RRSV protein has a direct link with mitochondria. Suppressing OSCP gene expression by RNA interference notably decreased the viral loads in RRSV-infected insects. These findings revealed novel aspects of a viral protein in targeting the host mitochondrial membrane and provide insights concerning the mitochondrial membrane protein-based virus proliferation mode in the insect vector.