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The post-encapsulation method (such as single-layered encapsulation) is a promising strategy to synthesize yolk-shell structures that protect functional nanoparticles by the molecular sieving effect. However, this method exhibited limited loading capacity and nonuniform encapsulation during the co-encapsulation of various nanoparticles owing to the insufficient surface area for nanoparticle attachment. To address these limitations, we proposed a double-layered encapsulation method comprising an increased number of silica template layers and separate attachment of multifarious nanoparticles to different layers. Compared with conventional methods, this strategy can precisely adjust the ratio of encapsulated nanoparticles and increase the loading amount, which improves the functionality of yolk-shell structures, such as the photothermal properties of gold nanoparticle-encapsulated yolk-shell structures (â¼69%). We describe, for the first time, the precise control of the ratio of encapsulated nanoparticles and the loading of numerous nanoparticles. Consequently, this strategy has significant potential for various applications of yolk-shell structures.
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Purpose: This study aimed to investigate the potential role of copine-1 (CPNE1), a calcium-dependent membrane-binding protein encoded by the CPNE1 gene, in colorectal cancer (CRC). Despite previous research on the involvement of copine family members in various solid tumors, the specific role of CPNE1 in CRC remains poorly understood. Methods: We conducted clinicopathological analysis and functional studies to explore the impact of CPNE1 in human CRC. We examined the expression levels of CPNE1 in CRC patients and correlated it with invasive depth, lymph node metastasis, distant metastasis, lymphatic invasion, and TNM stage. Additionally, we performed experiments to assess the functional consequences of CPNE1 knockdown in CRC cells, including proliferation, colony formation, migration, invasion, and the expression of key regulators involved in the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, we evaluated the effects of CPNE1 knockdown on tumor growth using a xenograft mouse model. Results: High expression of CPNE1 was significantly associated with advanced tumor features in CRC patients. CPNE1 knockdown in CRC cells led to impaired abilities in proliferation, colony formation, migration, and invasion. Furthermore, CPNE1 silencing resulted in the suppression of protein expression related to the cell cycle and EMT. In the xenograft mouse model, CPNE1 knockdown inhibited tumor growth. Conclusion: CPNE1 plays a crucial role in promoting tumorigenesis and metastasis in human CRC. By regulating the cell cycle and EMT, CPNE1 influences critical cellular processes at the membrane-cytoplasm interface. These results provide valuable insights into the potential development of novel therapeutic strategies for CRC targeting CPNE1.
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Host adaptation plays a crucial role in virus evolution and is a consequence of long-term interactions between virus and host in a complex arms race between host RNA silencing and viral RNA silencing suppressor (RSS) as counterdefense. Leek yellow stripe virus (LYSV), a potyvirus causing yield loss of garlic, infects several species of Allium plants. The unexpected discovery of an interspecific hybrid of garlic, leek, and great-headed (GH) garlic motivated us to explore the host-adaptive evolution of LYSV. Here, using Bayesian phylogenetic comparative methods and a functional assay of viral RSS activity, we show that the evolutionary context of LYSV has been shaped by the host adaptation of the virus during its coevolution with Allium plants. Our phylogenetic analysis revealed that LYSV isolates from leek and their taxonomic relatives (Allium ampeloprasum complex; AAC) formed a distinct monophyletic clade separate from garlic isolates and are likely to be uniquely adapted to AAC. Our comparative studies on viral accumulation indicated that LYSV accumulated at a low level in leek, whereas LYSVs were abundant in other Allium species such as garlic and its relatives. When RSS activity of the viral P1 and HC-Pro of leek LYSV isolate was analyzed, significant synergism in RSS activity between the two proteins was observed in leek but not in other species, suggesting that viral RSS activity may be important for the viral host-specific adaptation. We thus consider that LYSV may have undergone host-specific evolution at least in leek, which must be driven by speciation of its Allium hosts. IMPORTANCE Potyviruses are the most abundant plant RNA viruses and are extremely diversified in terms of their wide host range. Due to frequent host switching during their evolution, host-specific adaptation of potyviruses may have been shaped by numerous host factors. However, any critical determinants for viral host range remain largely unknown, possibly because of the repeated gain and loss of virus infectivity of plants. Leek yellow stripe virus (LYSV) is a species of the genus Potyvirus, which has a relatively narrow host range, generally limited to hosts in the genus Allium. Our investigations on leek and leek relatives (Allium ampeloprasum complex), which must have been generated through interspecies hybridization, revealed that LYSV accumulation remained low in leek as a result of viral host adaptation in competition with host resistance such as RNA silencing. This study presents LYSV as an ideal model to study the process of host-adaptive evolution and virus-host coevolution.
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Y-satellite RNA (Y-sat) of cucumber mosaic virus upregulates the expression of the aphid ABCG4 gene, which promotes aphid wing formation. We used ABCG4 virus-induced gene silencing (VIGS) to prevent the wing-induction mechanism of Y-sat and thus inhibited aphid wing formation. Of the aphids on plants with VIGS of ABCG4, only about 30% had wings, and 60-70% of the winged aphids were small and likely impaired in flying ability. In addition, we showed that double-stranded RNAs (dsRNAs) and small RNAs were transferred from the plant to the aphid to adequately silence aphid genes. Supplying ABCG4 dsRNA by VIGS to aphids is thus a potential strategy to inhibit aphid wing formation.
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Áfidos , Cucumovirus , Animales , Satélite de ARN/metabolismo , Áfidos/genética , Cucumovirus/genética , ARN Bicatenario/genética , ARN Bicatenario/metabolismoRESUMEN
The genus Allexivirus currently includes eight virus species that infect allium plants. Previously, we showed that there are two distinct groups of allexiviruses (deletion [D]-type and insertion [I]-type) based on the presence or absence of a 10- to 20-base insert (IS) between the coat protein (CP) and cysteine rich protein (CRP) genes. In the present study of CRPs to analyze their functions, we postulated that evolution of allexiviruses may have been largely directed by CRPs and thus proposed two evolutionary scenarios for allexiviruses based mainly on the presence or absence of IS and determined by how the allexiviruses challenge host resistance mechanisms (RNA silencing and autophagy). We found that both CP and CRP are RNA silencing suppressors (RSS), that they can inhibit each other's RSS activity in the cytoplasm, and that CRP becomes a target of host autophagy in the cytoplasm but not CP. To mitigate CRP interference with CP, and to increase the CP's RSS activity, allexiviruses developed two strategies: confinement of D-type CRP in the nucleus and degradation of I-type CRP by autophagy in the cytoplasm. Here, we demonstrate that viruses of the same genus achieve two completely different evolutionary scenarios by controlling expression and subcellular localization of CRP.
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Flexiviridae , Virus , Flexiviridae/genética , Flexiviridae/metabolismo , Interferencia de ARN , Virus/genética , Plantas/metabolismo , Autofagia/genética , ARN Viral/genética , Nicotiana , Enfermedades de las Plantas/genéticaRESUMEN
Breast malignancy remains one of the most common causes of cancer-associated mortalities among women. MicroRNA (miR)-221 and miR-222 are homologous miRs and have a substantial impact on cancer progression. In the present study, the regulatory mechanisms of miR-221/222 and its target annexin A3 (ANXA3) in breast cancer cells were investigated. Breast tissue samples were collected to evaluate the expression patterns of miR-221/222 levels in breast cancer cell lines and cancer tissues according to clinical characteristics. The levels of miR-221/222 were increased or decreased in cancer cell lines compared with normal breast cell lines according to cell line subtype. Subsequently, the changes in the progression and invasion of breast cancer cells were investigated using cell proliferation, invasion assay, gap closure and colony formation assays. Western blotting of cell cycle proteins and flow cytometry were performed to evaluate the possible pathway of miR-221/222 and ANXA3 axis. Chemosensitivity tests were performed to explore the suitability of the miR-221/222 and ANXA3 axis as a therapeutic target in breast cancer. The expression levels of miR-221/222 were associated with aggressive characteristics of breast cancer subtypes. Cell transfection assay demonstrated the regulation of breast cancer proliferation and invasiveness by miR-221/222. MiR-221/222 directly targeted the 3'-untranslated region of ANXA3 and suppressed the expression of ANXA3 at the mRNA and protein levels. In addition, miR-221/222 negatively regulated cell proliferation and the cell cycle pathway in breast cancer cells by targeting ANXA3. In combination with adriamycin, downregulation of ANXA3 may sensitize adriamycin-induced cell death to induction of persistent G2/M and G0/G1 arrest. Decreased expression of ANXA3 through increased expression of miR-221/222 reduced breast cancer progression and increased the effectiveness of the chemotherapy drug. The present results indicated the miR-221/222 and ANXA3 axis to be a possible novel therapeutic target for the treatment of breast cancer.
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We report a case about successful surgical treatment of a granular cell tumor in the ascending colon. A 36-year-old man underwent screening colonoscopy. An endoscopic examination revealed a 10-mm yellowish and hemispheric mass in the ascending colon, and lower endoscopic ultrasonography revealed a hypoechoic-to-isoechoic mass invaded the submucosal layer. The mass was suspected to be a colonic carcinoid tumor. Based on the preoperative evaluation, endoscopic complete resection was considered difficult. Therefore, the lesion was removed via laparoscopic right hemicolectomy. Histological examination revealed that the tumor consisted of nests of polygonal cells with abundant granular eosinophilic cytoplasm. Immunohistochemical staining revealed diffuse positivity for S100 and CD68. Therefore, the tumor was diagnosed as a granular cell tumor. We suggest that surgical resection should be considered if it is located in the thin-walled ascending colon prone to perforation, difficult to rule out malignant tumor due to submucosal invasion, or to remove endoscopically.
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It has previously been found that turnip mosaic virus (TuMV) greatly suppresses anthocyanin accumulation (AA) in Brassica rapa leaves, and that such leaves become infected whilst anthocyanin-enriched leaves on the same plants are rarely infected. To clarify whether AA is a defense against TuMV, in this study we examined tissue-level patterns of spontaneous AA in relation to the cellular localization of a TuMV strain that expresses a yellow fluorescent protein. We found that TuMV infection was significantly blocked by AA, suggesting that it functions as a chemical barrier against TuMV. We next analysed changes in expression of genes related to anthocyanin biosynthesis in TuMV-infected leaves of Arabidopsis. TuMV also suppressed AA that is induced by high light in Arabidopsis, and this this suppression was mainly due to inhibited expression of anthocyanin late-biosynthesis genes (LBGs). Most positive transcription factors of LBGs were also down-regulated, while the negative regulator SPL15 was highly up-regulated. Cucumber mosaic virus (CMV) also moderately suppressed AA in Arabidopsis, but in a different manner. Since it appeared that anthocyanin-enriched leaves of Arabidopsis were resistant to TuMV but not CMV, our results suggested that the anthocyanin-associated resistance that we observed was specific to TuMV.
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Arabidopsis , Brassicaceae , Potyvirus , Arabidopsis/genética , Brassicaceae/genética , Antocianinas , Potyvirus/genética , Enfermedades de las Plantas/genéticaRESUMEN
PURPOSE: Several studies demonstrated that obesity and underweight were negatively associated with outcomes of breast cancer. However, the results are still controversial, and the impact of body mass index (BMI) on distant metastasis-free survival (MFS), which might directly affect mortality, was less well evaluated. Our study aimed to verify the prognostic effect of BMI in breast cancer. METHODS: A retrospective analysis of 504 patients with stage I-III breast cancer who underwent surgery from January 2005 to December 2013 was performed. The patients were divided into three groups according to preoperative BMI: underweight <18.5 kg/m2, normal weight 18.5-24.9 kg/m2, and overweight ≥25 kg/m2. The association between body weight status and breast cancer recurrence was analyzed. Subgroup analysis by tumor subtype according to receptor status was also performed. RESULTS: The median follow-up period was 88 months. For disease recurrence, histologic grade and human epidermal growth factor receptor 2 (HER2)-positivity were independent prognostic factors in multivariate analysis. Stage, histologic grade, HER2-positivity, and BMI status were independent prognostic factors for distant metastasis. In survival analysis, overweight and underweight were significant predisposing factors for MFS, but not for disease-free survival (DFS). In the estrogen receptor (ER)-positive group, overweight and underweight patients had significantly worse DFS and MFS than normal weight patients. In the ER-negative or HER2-positive group, BMI status had no significant association with DFS and MFS. CONCLUSION: The prognostic role of BMI on the survival outcomes of patients with breast cancer was different by tumor subtype. In ER-positive patients, overweight and underweight statuses had a negative prognostic effect on DFS and MFS, respectively.
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In Japan, the P1 protein (S-type) encoded by leek yellow stripe virus (LYSV) isolates detected in Honshu and southward is shorter than the P1 (N-type) of LYSV isolates from garlic grown in Hokkaido due to a large deletion in the N-terminal half. In garlic fields in Hokkaido, two types of LYSV isolate with N- and S-type P1s are sometimes found in mixed infections. In this study, we confirmed that N- and S-type P1 sequences were present in the same plant and that they belong to different evolutionary phylogenetic groups. To investigate how LYSV with S-type P1 (LYSV-S) could have invaded LYSV with N-type P1 (LYSV-N)-infected garlic, we examined wild Allium spp. plants in Hokkaido and found that LYSV was almost undetectable. On the other hand, in Honshu, LYSV-S was detected at a high frequency in Allium spp. other than garlic, suggesting that the LYSV-S can infect a wider host range of Allium spp. compared to LYSV-N. Because P1 proteins of potyviruses have been reported to promote RNA silencing suppressor (RSS) activity of HC-Pro proteins, we analyzed whether the same was true for P1 of LYSV. In onion, contrary to expectation, the P1 protein itself had RSS activity. Moreover, the RSS activity of S-type P1 was considerably stronger than that of N-type P1, suggesting that LYSV P1 may be able to enhance its RSS activity when the deletion is in the N-terminal half and that acquiring S-type P1 may have enabled LYSV to expand its host range.
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Although laparoscopic treatment for T1 gallbladder cancer (GBC) has been described previously, the differences in oncologic outcomes between laparoscopic and conventional open surgery for T2 GBC have not been investigated. We aimed to assess the role of laparoscopic surgery using retrospectively collected data for 81 patients with T2 GBC who underwent surgical resection between January 2010 and December 2017. Eligible patients were classified into "laparoscopic" and "open" groups. Propensity-score matching was performed in a 1:1 ratio. The effects of surgery type on surgical and oncological outcomes were investigated. After propensity-score matching, 19 patients were included in the open and laparoscopic surgery groups. The median follow-up durations were 70 and 26 months in the open and laparoscopic groups, respectively. The operative time (316.8 ± 80.3 vs. 218.9 ± 145.0 min, p = 0.016) and length of postoperative hospital stay (14.4 ± 6.0 vs. 8.4 ± 5.9 days, p = 0.004) were significantly shorter in the laparoscopic group. The three-year overall (86.3% vs. 88.9%, p = 0.660) and disease-free (76.4% vs. 60.2%, p = 0.448) survival rates were similar between the groups. Propensity-score matching showed that laparoscopic surgery for T2 GBC yielded similar long-term oncological outcomes and favorable short-term outcomes in comparison with open surgery. Laparoscopic treatment should be considered in patients with T2 GBC.
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Orchid seeds depend on colonization by orchid mycorrhizal (OM) fungi for their germination; therefore, the orchids and OM fungi have long maintained a close relationship (e.g., formation of the hyphal mass structure, peloton) during their evolution. In the present study, we isolated new partitiviruses from OM fungi; partitivirus were separately found in different subcultures from the same fungi. Partitiviruses have been believed to lack an RNA silencing suppressor (RSS), which is generally associated with viral pathogenicity, because most partitiviruses isolated so far are latent in both plants and fungi. However, we found that the coat protein (CP) of our partitiviruses indeed had RSS activity, which differed among the virus isolates from OM fungi; one CP showed RSS activity in both plants and fungi, while another CP showed no activity. The family Partitiviridae include viruses isolated from plants and fungi, and it has been suggested that these viruses may occasionally be transmitted between plant and fungal hosts. Given that there are several reports showing that viruses can adapt to nonhost using strong RSS, we here discussed the idea that partitiviruses may be better able to migrate between the orchid and fungus probably through the pelotons formed in the orchid cells, if host RNA silencing is suppressed by partitivirus RSS.
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Micorrizas , Orchidaceae , Virus ARN , Hongos , Micorrizas/genética , Orchidaceae/microbiología , Filogenia , Plantas , Interferencia de ARN , Virus ARN/genética , SimbiosisRESUMEN
The 2b protein (2b) of cucumber mosaic virus (CMV), an RNA-silencing suppressor (RSS), is a major pathogenicity determinant of CMV. 2b is localized in the nucleus and cytoplasm, and its nuclear import is determined by two nuclear localization signals (NLSs); a carrier protein (importin [IMPα]) is predicted to be involved in 2b's nuclear transport. Cytoplasmic 2bs play a role in suppression of RNA silencing by binding to small RNAs and AGO proteins. A putative nuclear export signal (NES) motif was also found in 2b, but has not been proved to function. Here, we identified a leucine-rich motif in 2b's C-terminal half as an NES. We then showed that NES-deficient 2b accumulated abundantly in the nucleus and lost its RSS activity, suggesting that 2b exported from the nucleus can play a role as an RSS. Although two serine residues (S40 and S42) were previously found to be phosphorylated, we also found that an additional phosphorylation site (S28) alone can affect 2b's nuclear localization and RSS activity. Alanine substitution at S28 impaired the IMPα-mediated nuclear/nucleolar localization of 2b, and RSS activity was even stronger compared to wild-type 2b. In a subcellular fractionation assay, phosphorylated 2bs were detected in the nucleus, and comparison of the accumulation levels of nuclear phospho-2b between wild-type 2b and the NES mutant showed a greatly reduced level of the phosphorylated NES mutant in the nucleus, suggesting that 2bs are dephosphorylated in the nucleus and may be translocated to the cytoplasm in a nonphosphorylated form. These results suggest that 2b manipulates its nucleocytoplasmic transport as if it tracks down its targets, small RNAs and AGOs, in the RNA silencing pathway. We infer that 2b's efficient RSS activity is maintained by a balance of phosphorylation and dephosphorylation, which are coupled to importin/exportin-mediated shuttling between the nucleus and cytoplasm.
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Transporte Activo de Núcleo Celular/fisiología , Cucumovirus/fisiología , Inmunidad de la Planta/fisiología , Interferencia de ARN/fisiología , Proteínas Virales/metabolismo , Carioferinas/metabolismoRESUMEN
PURPOSE: Fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) affects the management of patients with breast cancer. Our study aimed to determine the predictive ability of characteristics such as lymph node involvement or subtype and the prognostic value of pretreatment FDG-PET/CT in breast cancer. METHOD: A total of 270 patients who were confirmed with breast cancer histopathologically and underwent pretreatment FDG-PET/CT were enrolled in the study. Nuclear medicine specialists obtained the readings and measured the maximum standardized uptake value (SUVmax) of the images. Tumor and lymph node SUVmax were evaluated according to lymph node metastasis and subtype status. Survival outcomes were analyzed by the Kaplan-Meier method. RESULTS: The lymph node SUVmax and the lymph node/tumor SUVmax ratio were significantly higher in the subgroup of patients with lymph node metastasis than in those without lymph node metastasis. High cutoff lymph node SUVmax value and lymph node/tumor SUVmax ratio were confirmed as significant predictive factors in multivariate analysis. In a comparison of the tumor SUVmax values, the more biological aggressive subtype showed higher tumor SUVmax values. In survival analysis, tumor SUVmax and lymph node SUVmax were significant predisposing factors for disease-free survival in breast cancer. In subgroup analysis, tumor SUVmax was a more significant prognostic factor in patients who had breast cancer with tumor sizes of ≤2 cm. The lymph node SUVmax was more a significant prognostic factor in patients who had breast cancer with lymph node metastasis. CONCLUSION: In this study, we showed that the SUVmax of FDG-PET/CT was a useful predictor of lymph node metastasis and breast cancer prognosis.
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Neoplasias de la MamaRESUMEN
BACKGROUND: Although the safety and feasibility of conventional laparoscopic surgery (CLS) for appendiceal mucocele (AM) has been reported, studies on single-incision laparoscopic surgery (SILS) for AM have not been reported. Here, we aimed to compare the perioperative and short-term outcomes between SILS and CLS for AM and to evaluate the oncological safety of SILS. METHODS: We retrospectively analyzed the medical records of patients, diagnosed based on computed tomography findings, who underwent laparoscopic surgery for AM between 2010 and 2018 at one institution. We excluded patients strongly suspected of having malignant lesions and those with preoperative appendiceal perforation. Patients were divided into two groups-CLS and SILS. Pathological outcomes and long-term results were investigated. The median follow-up period was 43.7 (range: 12.3-118.5) months. RESULTS: Ultimately, 116 patients (CLS = 68, SILS = 48) were enrolled. Patient demographic characteristics did not differ between the groups. The preoperative mucocele diameter was greater in the CLS than in the SILS group (3.2 ± 2.9 cm vs. 2.3 ± 1.4 cm, P = 0.029). More extensive surgery (right hemicolectomies and ileocecectomies) was performed in the CLS than in the SILS group (P = 0.014). Intraoperative perforation developed in only one patient per group. For appendectomies and cecectomies, the CLS group exhibited a longer operation time than the SILS group (63.3 ± 24.5 min vs. 52.4 ± 17.3 min, P = 0.014); the same was noted for length of postoperative hospital stay (2.9 ± 1.8 days vs. 1.7 ± 0.6 days, P < 0.001). The most common AM etiology was low-grade appendiceal mucinous neoplasm (71/116 [61.2%] patients); none of the patients exhibited mucinous cystadenocarcinoma. Among these 71 patients, there were 8 patients with microscopic appendiceal perforation or positive resection margins. No recurrence was detected. CONCLUSIONS: SILS for AM is feasible and safe perioperatively and in the short-term and yields favorable oncological outcomes. Despite the retrospective nature of the study, SILS may be suitable after careful selection of AM patients.
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Laparoscopía , Mucocele , Colectomía/métodos , Humanos , Laparoscopía/métodos , Tiempo de Internación , Mucocele/diagnóstico por imagen , Mucocele/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Small intestinal malignant tumor accounts for about 3% of all malignant tumors in the gastrointestinal tract, among which 13% are leiomyosarcoma (LMS). In addition, epithelioid LMS is of very rare occurrence. As small intestinal malignant tumors are initially asymptomatic and nonspecific, diagnosis is often delayed, and this can lead to large tumor at the time of detection and lead to intussusception. We observed ileocolonic intussusception in an 80-year-old male patient who was admitted to the hospital with a complaint of abdominal pain and palpable mass on right lower quadrant. The laparoscopic ileocecectomy was performed by the emergency operation because of obstruction. The pathologic examination revealed that the epithelioid LMS developed in the terminal ileum was the leading point of intussusception. To the best of our knowledge, laparoscopic surgery for ileocolonic intussusception with epithelioid LMS has not yet been reported.
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We report considerations related with surgery through 2 cases of acute appendicitis (AA) with coronavirus disease 2019 (COVID-19) infection. In November and December 2020, AA occurred in 2 patients with COVID-19, who underwent emergency surgery. In case 1, an 84-year-old woman was asymptomatic and diagnosed with AA on the 20th day of infection. She was discharged after surgery without complication. In contrast, case 2 was that a 69-year-old man with pneumonia was treated with antibiotics, steroids, and remdesivir. After surgery, he was hospitalized for a long duration due to persistent pneumonia and wound complications. We should perform in well-established negative pressure operating rooms, personal protective equipment, and protocols. Since the physical examination and blood tests were limited, image examination like computed tomography scan should be considered if AA is suspected. If pneumonia is accompanied before surgery, pneumonia may worsen after surgery, or complications such as wound infection may occur.
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Cucumber mosaic virus (CMV) often accompanies a short RNA molecule called a satellite RNA (satRNA). When infected with CMV in the presence of Y-satellite RNA (Y-sat), tobacco leaves develop a green mosaic, then turn yellow. Y-sat has been identified in the fields in Japan. Here, we show that the yellow leaf colour preferentially attracts aphids, and that the aphids fed on yellow plants, which harbour Y-sat-derived small RNAs (sRNAs), turn red and subsequently develop wings. In addition, we found that leaf yellowing did not necessarily reduce photosynthesis, and that viral transmission was not greatly affected despite the low viral titer in the Y-sat-infected plants. Y-sat-infected plants can therefore support a sufficient number of aphids to allow for efficient virus transmission. Our results demonstrate that Y-sat directly alters aphid physiology via Y-sat sRNAs to promote wing formation, an unprecedented survival strategy that enables outward spread via the winged insect vector.
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Áfidos/genética , Cucumovirus/genética , Proteínas de Insectos/genética , Insectos Vectores/genética , Satélite de ARN/genética , ARN Viral/genética , Animales , Áfidos/fisiología , Áfidos/virología , Cucumovirus/fisiología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Proteínas de Insectos/metabolismo , Insectos Vectores/fisiología , Insectos Vectores/virología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/virología , Hojas de la Planta/genética , Hojas de la Planta/parasitología , Hojas de la Planta/virología , Plantas Modificadas Genéticamente , Satélite de ARN/fisiología , ARN Viral/fisiología , Nicotiana/genética , Nicotiana/parasitología , Nicotiana/virología , Virión/genética , Virión/fisiología , Replicación Viral/genética , Replicación Viral/fisiologíaRESUMEN
Lots of cell death initiator and effector molecules, signalling pathways and subcellular sites have been identified as key mediators in both cell death processes in cancer. The XDeathDB visualization platform provides a comprehensive cell death and their crosstalk resource for deciphering the signaling network organization of interactions among different cell death modes associated with 1461 cancer types and COVID-19, with an aim to understand the molecular mechanisms of physiological cell death in disease and facilitate systems-oriented novel drug discovery in inducing cell deaths properly. Apoptosis, autosis, efferocytosis, ferroptosis, immunogenic cell death, intrinsic apoptosis, lysosomal cell death, mitotic cell death, mitochondrial permeability transition, necroptosis, parthanatos, and pyroptosis related to 12 cell deaths and their crosstalk can be observed systematically by the platform. Big data for cell death gene-disease associations, gene-cell death pathway associations, pathway-cell death mode associations, and cell death-cell death associations is collected by literature review articles and public database from iRefIndex, STRING, BioGRID, Reactom, Pathway's commons, DisGeNET, DrugBank, and Therapeutic Target Database (TTD). An interactive webtool, XDeathDB, is built by web applications with R-Shiny, JavaScript (JS) and Shiny Server Iso. With this platform, users can search specific interactions from vast interdependent networks that occur in the realm of cell death. A multilayer spectral graph clustering method that performs convex layer aggregation to identify crosstalk function among cell death modes for a specific cancer. 147 hallmark genes of cell death could be observed in detail in these networks. These potential druggable targets are displayed systematically and tailoring networks to visualize specified relations is available to fulfil user-specific needs. Users can access XDeathDB for free at https://pcm2019.shinyapps.io/XDeathDB/ .
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Muerte Celular/fisiología , Muerte Celular Regulada/fisiología , Transducción de Señal/fisiología , Animales , COVID-19/metabolismo , COVID-19/fisiopatología , Análisis por Conglomerados , Bases de Datos Factuales , Humanos , Necroptosis , Neoplasias/metabolismo , Neoplasias/fisiopatología , Fagocitosis , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiología , Transducción de Señal/efectos de los fármacos , Programas InformáticosRESUMEN
BACKGROUND: The purpose is to investigate prognosis according to serum CEA levels before and after surgery in patients with stage IIA colon cancer who do not show high-risk features. METHODS: Among the patients diagnosed with colon adenocarcinoma between April 2011 and December 2017, 462 patients were confirmed as low-risk stage IIA after surgery and enrolled. The ROC curve was used to determine cut-off values of pre- and postoperative CEA. Patients were classified into three groups using these new cut-off values. RESULTS: All recurrence occurred in 52 of 463 patients (11.2%). However, recurrence in group H was 15.9%, which was slightly higher than the other two groups (P = 0.04). Group L and M showed 10.5% and 12.8% overall survival, group H was higher at 21.0% (P = 0.005). Recurrence was the only risk factor in group H was significantly higher in group L (HR 2.008, 95% CI, 1.123-3.589, P = 0.019). Mortality was similar to recurrence (HR 1.975, 95% CI 1.091-3.523, P = 0.044). CONCLUSION: Among patients with low-risk stage IIA colon cancer, recurrence and mortality rates were higher when perioperative serum CEA levels were above a certain level. Therefore, high CEA level should be considered a high-risk feature and adjuvant chemotherapy should be performed.