Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm²), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.
Humans ; Male ; Esophagogastric Junction/pathology* ; Aged ; Carcinoma, Neuroendocrine/pathology* ; Vacuoles/pathology* ; Esophageal Neoplasms/pathology* ; Cell Nucleus/pathology* ; Adenocarcinoma, Papillary/pathology* ; Stomach Neoplasms/pathology*

As a generally-recognized-as-safe microorganism, Saccharomyces cerevisiae is a widely studied chassis cell for the production of high-value or bulk chemicals in the field of synthetic biology. In recent years, a large number of synthesis pathways of chemicals have been established and optimized in S. cerevisiae by various metabolic engineering strategies, and the production of some chemicals have shown the potential of commercialization. As a eukaryote, S. cerevisiae has a complete inner membrane system and complex organelle compartments, and these compartments generally have higher concentrations of the precursor substrates (such as acetyl-CoA in mitochondria), or have sufficient enzymes, cofactors and energy which are required for the synthesis of some chemicals. These features may provide a more suitable physical and chemical environment for the biosynthesis of the targeted chemicals. However, the structural features of different organelles hinder the synthesis of specific chemicals. In order to ameliorate the efficiency of product biosynthesis, researchers have carried out a number of targeted modifications to the organelles grounded on an in-depth analysis of the characteristics of different organelles and the suitability of the production of target chemicals biosynthesis pathway to the organelles. In this review, the reconstruction and optimization of the biosynthesis pathways for production of chemicals by organelle mitochondria, peroxisome, golgi apparatus, endoplasmic reticulum, lipid droplets and vacuole compartmentalization in S. cerevisiae are reviewed in-depth. Current difficulties, challenges and future perspectives are highlighted.
Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism* ; Golgi Apparatus/metabolism* ; Metabolic Engineering ; Vacuoles/metabolism*

The World Health Organization 2016 edition assigned anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) as an emerging renal tumor entity. Identifying ALK-RCC is important because ALK inhibitors have been shown to be effective in treatment. Here, we report the case of a 14-year-old young man with ALK-RCC. Computed tomography revealed a well-demarcated 5.3-cm enhancing mass at the upper pole of the left kidney. There was no further history or symptoms of the sickle-cell trait. The patient underwent left radical nephrectomy. Pathologically, the mass was diagnosed as an unclassified RCC. Targeted next-generation sequencing identified a TPM3-ALK fusion gene. The present report and literature review demonstrate that TPM3-ALK RCC may be associated with distinct clinicopathological features. Microscopically, the tumors showed diffuse growth and tubulocystic changes with inflammatory cell infiltration. Tumor cells were dis-cohesive and epithelioid with abundant eosinophilic cytoplasm and cytoplasmic vacuoles. If morphological features and TFE3 expression are present in adolescent and young patients, molecular tests for ALK translocation should be performed. This awareness is critically important, because ALK rearrangement confers sensitivity to ALK inhibitors.
Adolescent ; Carcinoma, Renal Cell ; Cytoplasm ; Eosinophils ; Gene Rearrangement ; Humans ; Kidney ; Lymphoma ; Nephrectomy ; Phosphotransferases ; Vacuoles ; World Health Organization

Important progress has been made in the interpretation of subcellular location, ion transport characteristics and biological functions of endosomal Na⁺,K⁺/H⁺ antiporter in Arabidopsis thaliana. The endosomal Na⁺,K⁺/H⁺ antiporter contain two members, AtNHX5 and AtNHX6, whose amino acid sequence similarity is 78.7%. Studies have shown that AtNHX5 and AtNHX6 are functionally redundant, and they are all located in Golgi, trans-Golgi network (TGN), endoplasmic reticulum (ER) and prevacuolar compartment (PVC). AtNHX5 and AtNHX6 are critical for salt tolerance stress and the homeostasis of pH and K⁺. It has been reported that there are conservative acidic amino acid residues that can regulate their ion activity in the endosomal NHXs transmembrane domain, which plays a decisive role in their own functions. The results of the latest research indicate that endosomal NHXs affect vacuolar transport and protein storage, and participate in the growth of auxin-mediated development in A. thaliana. In this paper, the progress of subcellular localization, ion transport, function and application of endosomal NHXs in A. thaliana was summarized.
Arabidopsis ; Arabidopsis Proteins ; Endosomes ; Sodium-Hydrogen Exchangers ; Vacuoles

Secretory carcinoma of the salivary gland (SC) is a newly introduced rare salivary gland tumor that shares histological, immunohistochemical, and genetic characteristics with secretory carcinoma of the breast. Here, we report the cytologic features of two cases of SC confirmed by surgical resection. In these two cases, SC was incidentally detected in a 64-year-old female and a 56-yearold male. Fine needle aspiration cytology revealed nests of tumor cells with a papillary or glandular structure floating in mucinous secretions. The tumor cells demonstrated uniform, round, smooth nuclear contours and distinct nucleoli. Multiple characteristic cytoplasmic vacuoles were revealed. Singly scattered tumor cells frequently showed variable sized cytoplasmic vacuoles. The cytopathologic diagnosis of SC should be considered when characteristic cytological findings are revealed. Further immunohistochemistry and gene analyses are helpful to diagnose SC.
Biopsy, Fine-Needle ; Breast ; Clothing ; Cytoplasm ; Diagnosis ; Female ; Humans ; Immunohistochemistry ; Male ; Mammary Analogue Secretory Carcinoma ; Middle Aged ; Mucins ; Salivary Glands ; Vacuoles

BACKGROUND AND PURPOSE: GNE myopathy is a rare progressive myopathy caused by biallelic mutations in the GNE gene, and frequently accompanied by rimmed vacuoles in muscle pathology. The initial symptom of foot drop or hip-girdle weakness eventually spreads to all limbs over a period of decades. Recent advances in pathophysiologic research have facilitated therapeutic trials aimed at resolving the core biochemical defect. However, there remains unsettled heterogeneity in its natural course, which confounds the analysis of therapeutic outcomes. We performed the first large-scale study of Korean patients with GNE myopathy. METHODS: We gathered the genetic and clinical profiles of 44 Korean patients with genetically confirmed GNE myopathy. The clinical progression was estimated retrospectively based on a patient-reported questionnaire on the status of the functional joint sets and daily activities. RESULTS: The wrist and neck were the last joints to lose antigravity functionality irrespective of whether the weakness started from the ankle or hip. Two-thirds of the patients could walk either independently or with an aid. The order of losing daily activities could be sorted from standing to eating. Patients with limb-girdle phenotype showed an earlier age at onset than those with foot-drop onset. Patients with biallelic kinase domain mutations tended to progress more rapidly than those with epimerase and kinase domain mutations. CONCLUSIONS: The reported data can guide the clinical management of GNE myopathy, as well as provide perspective to help the development of clinical trials.
Age of Onset ; Ankle ; Disease Progression ; Eating ; Extremities ; Foot ; Hip ; Humans ; Joints ; Muscular Diseases ; Muscular Dystrophies, Limb-Girdle ; Neck ; Pathology ; Phenotype ; Phosphotransferases ; Population Characteristics ; Retrospective Studies ; Surveys and Questionnaires ; Vacuoles ; Wrist

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.
Autophagy ; Cell Wall ; Cryptococcus neoformans* ; Cryptococcus* ; Endoplasmic Reticulum Stress ; Fluconazole ; GTP Phosphohydrolases ; Guanine Nucleotide Exchange Factors ; Humans ; Hypersensitivity ; Inhalation ; Insects ; Saccharomyces cerevisiae ; Vacuoles ; Virulence*

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2–8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.
Animals ; Cricetinae* ; Cricetulus ; Cyclophosphamide ; Fertility ; Gonadotropins ; Growth Hormone-Releasing Hormone ; Humans ; In Situ Nick-End Labeling ; Infertility ; Infertility, Male* ; Male ; Male* ; Pregnancy Rate ; Reproduction ; Testis ; Testosterone ; Vacuoles

Limb-girdle muscular dystrophies (LGMD) are heterogeneous disorders with autosomal inheritance. Autosomal dominant LGMD mapped to 7q36.3 has been classified as LGMD type 1D (LGMD1D) in the Human Gene Nomenclature Committee Database. LGMD1D is characterized predominantly by limb-girdle weakness and may also show a bulbar symptom in some cases. In the past, the frequency of this disease was uncommon, and this disorder was mainly found in Europe and the United States. However, recently, this disorder has been reported in Asia, including Japan, Korea, and Taiwan. Here, we report on three LGMD1D patients, including one with a novel mutation in DNAJB6, c.298T>A. While two patients complained of limb-girdle weakness, as would be expected, one patient had distal weakness. They had various serum creatine kinase levels. Radiologic findings in one patient showed fatty degeneration and atrophy in the posterior part of distal muscles. Pathologic findings in one of the patients showed rimmed vacuoles. Although LGMD1D is still uncommon in Korea, we discovered three Korean patients with LGMD1D, including one novel mutation in DNAJB6, p.Phe100Ile (c.298T>A).
Asia ; Atrophy ; Creatine Kinase ; Europe ; Humans ; Japan ; Korea ; Muscles ; Muscular Diseases ; Muscular Dystrophies, Limb-Girdle* ; Taiwan ; United States ; Vacuoles ; Wills

This study was carried out to determine the pathogen-causing diarrhoea in sheep Ovis aries in the Qinghai Tibetan Plateau Area, China. A trophozoite was identified as species of ciliate alveolates infecting the sheep based on morphological characteristics examined by microscope. It was mostly spherical, colourless and transparent, with many vesicles. Macronucleus and contractile vacuoles could not be distinguished. Size of the trophozoite was 80–180×70–150 μm and its surface was covered with cilia. Molecular analysis based on sequences of 18S rRNA and ITS genes confirmed the ciliate species as Balantidium coli. According to the literature, there have been many epidemiological investigations of B. coli infection in pigs, monkeys and humans. To our knowledge, this was the first report of B. coli infections in sheep in the Qinghai Tibetan Plateau Area of China, or eleswhere around the world. Importantly, the sheep case was rare but raised our concern that B. coli may spread across species and expand its host range.
Balantidium ; China ; Cilia ; Haplorhini ; Host Specificity ; Humans ; Macronucleus ; Sheep ; Sheep, Domestic ; Swine ; Trophozoites ; Vacuoles