Dry seeding rice cultivation is increasing in double-cropping paddy fields in northern Kyushu. For effective weed control, it is required to spray herbicide twice in the dry period, soil-applied ...herbicide after seeding, and foliar-applied herbicide before flooding. However, weed control with a single spray is required for more labor savings. In this study, the effects of the tank-mix application of soil-applied herbicides, prometryn + benthiocarb emulsifiable concentrate (PB), and trifluralin emulsifiable concentrate (T), were estimated for 3 years from 2019 to 2021. It rained moderately in 2019 and 2021, but it was extremely dry before and after sowing in 2020. A stable and highly weed control was obtained with tank-mix application of both herbicides between 3 and 10 days after sowing (DAS). It was considered that weeds that emerged in the early DAS could be controlled, so the PB herbicide controls one leaf stage Echinochloa spp., and it was enhanced by tank-mix application with the T herbicide. The control effect became higher when the tank-mix application was delayed. However, it must be applied before rice emerges. If there are few weeds, it is possible to omit the application of foliar-applied herbicides before flooding.
This cross-sectional study aimed to investigate the post-acute consequences of COVID-19. We conducted a self-administered questionnaire survey on sequelae, psychological distress (K6), impairments in ...work performance (WFun), and COVID-19-related experiences of stigma and discrimination in two designated COVID-19 hospitals in Hiroshima Prefecture, Japan, between August 2020 and March 2021. The prevalence of sequelae was calculated by age and COVID-19 severity. Factors independently associated with sequelae or psychological distress were identified using logistic regression analysis. Among 127 patients who had recovered from COVID-19, 52.0% had persistent symptoms at a median of 29 days IQR 23-128 after COVID-19 onset. Among patients with mild COVID-19, 49.5% had sequelae. The most frequent symptoms were olfactory disorders (15.0%), taste disorders (14.2%), and cough (14.2%). Multivariate analysis showed that age was an independent risk factor for sequelae (adjusted odds ratios AOR for ≥ 60 years vs. < 40 years 3.63, p = 0.0165). Possible psychological distress was noted in 30.7% (17.9% of males and 45.0% of females). Female sex and the presence of sequelae were independent risk factors for psychological distress. Of all participants, 29.1% had possible impairments in work performance. Experiences of stigma and discrimination were reported by 43.3% of participants. This study revealed the significant impacts of Long COVID on health in local communities. A large-scale, long-term cohort study is desired.
Background
The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of ...drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish.
Methods
In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments.
Results
We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth.
Conclusions
Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases.
The utility of glypican-3 (GPC3) expression for the detection of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) patients has not been elucidated. The aim of this study was to ...identify associations between the presence of GPC3-positive CTCs and clinicopathological factors of these patients, furthermore, to evaluate whether CTC can predict microscopic portal vein invasion (mPVI). This study was done on 85 patients who underwent hepatectomy as the first-line treatment and whose preoperative imaging showed no evidence of macroscopic PVI and distant metastases. Peripheral blood was collected from all patients immediately before surgery. Cells were purified initially by density gradient centrifugation followed by immunomagnetic positive enrichment based upon the expression of GPC3. The numbers of CTCs contained in the enriched samples were enumerated via flow cytometry. Protocol validation using HepG2 cells spiked into 8.0 mL of blood from a healthy volunteer indicated that we were able to recover 12.1% of the tumor cells. A median number of 3 CTCs (range: 0-27) was detected in the 8.0 mL of peripheral blood of the 85 analyzed HCC patients. Thirty-three patients had CTCs ≥5, and these patients had a higher incidence of mPVI (p < 0.001), a lower disease-free survival (p = 0.015), and a lower overall survival (p = 0.047) than those with CTCs <5. Multivariate analysis identified CTCs ≥5 as an independent predictor of mPVI (p < 0.001). In conclusion, preoperative GPC3-positive CTCs ≥5 was a risk factor of mPVI and poor prognosis, and therefore may be a useful biomarker for HCC patient outcomes.
As of 31 December 2017, a total of 9242 liver transplants have been carried out in 67 institutions in Japan. There were 447 deceased donor transplants (444 from heart‐beating donors and 3 from ...non‐heart‐beating donors) and 8795 living‐donor transplants. The annual total of liver transplants in 2017 was 416 (69 deceased donor transplants and 347 living‐donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. In terms of hepatocellular disease in 2017, cirrhosis due to hepatitis C and B decreased (13 and 8, respectively), whereas alcoholic cirrhosis markedly increased (32). Patient survival following transplantation from heart‐beating donor (444 transplants: 1 year, 89.1%; 3 years, 85.2%; 5 years, 82.9%; 10 years, 75.4%; 15 years, 70.7%) was similar to that from living‐donor (8794 transplants: 1 year, 85.0%; 3 years, 80.9%; 5 years, 78.5%; 10 years, 73.2%; 15 years, 68.5%; 20 years, 65.7%; 25 years, 64.6%). Graft survival was very much the same as patient survival (heart‐beating donor: 1 year, 88.4%; 3 years, 84.5%; 5 years, 82.2%; 10 years, 74.7%; 15 years, 70.1%; living donor: 1 year, 84.3%; 3 years, 79.9%; 5 years, 77.3%; 10 years, 71.4%; 15 years, 66.3%; 20 years, 63.3%; 25 years, 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO compatibility, and other factors.
Purpose
A retrospective study was performed to clarify the role of conversion therapy (surgery with a prospect of R0 resection performed in initially unresectable metastatic cancer that responded to ...the chemotherapy) in stage IV gastric cancer (GC).
Patients and methods
We treated 259 stage IV GC patients with systemic chemotherapy at Gifu and Hiroshima University Hospitals between 2001–2013. Of these, 84 patients who were subsequently treated by surgery were classified into four categories according to our previously published classification of stage IV GC, and short- and long-term outcomes were analyzed.
Results
Surgery was performed in 84 patients, of which 7 were performed following the neoadjuvant chemotherapy, whereas the other 77 that excluded neoadjuvant chemotherapy cases were considered the conversion therapy. The postoperative mortality and morbidity were comparable with those reported clinical trials. The MSTs of the patients with/without surgery for each category were 28.3/5.8 months for category 1, 30.5/11.0 months for category 2, 31.0/18.5 months for category 3 and 24.7/10.0 months for category 4. The MST of the R0 resected patients (41.3 months) was far better than that of the R1–2 resected patients (21.2 months). The MSTs of the patients with R0/R1–2 resection were 56.2/16.3 months for category 2, 33.3/29.6 months for category 3 and 40.7/17.8 months for category 4.
Conclusion
There were long-term survivors who underwent conversion therapy for stage IV GC. Adequate selection of stage IV GC patients for conversion therapy may be an important role for the surgical oncologist in the new era.
The aim of this study was to use small unmanned aerial vehicles (UAVs) for determining high-resolution normalized difference vegetation index (NDVI) values. Subsequently, these results were used to ...assess their correlations with fertilizer application levels and the yields of rice and wheat crops. For multispectral sensing, we flew two types of small UAVs (DJI Phantom 4 and DJI Phantom 4 Pro)—each equipped with a compact multispectral sensor (Parrot Sequoia). The information collected was composed of numerous RGB orthomosaic images as well as reflectance maps with spatial resolution greater than a ground sampling distance of 10.5 cm. From 223 UAV flight campaigns over 120 fields with a total area coverage of 77.48 ha, we determined that the highest efficiency for the UAV-based remote sensing measurement was approximately 19.8 ha per 10 min while flying 100 m above ground level. During image processing, we developed and used a batch image alignment algorithm—a program written in Python language–to calculate the NDVI values in experimental plots or fields in a batch of NDVI index maps. The color NDVI distribution maps of wide rice fields identified differences in stages of ripening and lodging-injury areas, which accorded with practical crop growth status from aboveground observation. For direct-seeded rice, variation in the grain yield was most closely related to that in the NDVI at the early reproductive and late ripening stages. For wheat, the NDVI values were highly correlated with the yield ( R 2 = 0.601–0.809) from the middle reproductive to the early ripening stages. Furthermore, using the NDVI values, it was possible to differentiate the levels of fertilizer application for both rice and wheat. These results indicate that the small UAV-derived NDVI values are effective for predicting yield and detecting fertilizer application levels during rice and wheat production.
Refractory B cell responses to T cell–independent (TI) carbohydrate antigens (Ags) are critical drivers of rejection reactions to ABO‐incompatible allogeneic grafts and xenogeneic grafts from other ...species. To explore the biological significance of crosstalk between Toll‐like receptors (TLRs) and B cell receptors (BCRs) in the TI B cell immunity, we here used MyD88‐, TRIF‐, and α‐galactosyltransferase‐deficient mice to study B cell phenotypes and functional properties during TI transplant–related glycan Ag exposure. BCR stimulation alone induced differentiation into CD5high (B‐1a) cells, which were highly sensitive to a calcineurin inhibitor (CNI), while co‐stimulation of TLRs and BCRs induced differentiation into CD5dim (B‐1b) cells in MyD88‐dependent and CNI‐resistant manner. MyD88‐dependent TLR stimulation in B‐1b cells enhanced downstream factors in the BCR‐calcineurin pathway, including a nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). TLR inhibitor together with CNI abrogated refractory B‐1b cell immune responses against the ABO‐blood group Ags, while blocking both BCRs and TLR‐MyD88 by using Bruton's tyrosine kinase inhibitor and histone deacetylase inhibitor abrogated refractory B‐1b cell immune responses against Gal‐glycan Ags. Thus, this study provides a rationale for a novel therapeutic approach to overcome refractory transplant‐related anti‐glycan Ab production by blocking both BCR and TLR‐MyD88 signals.
Blocking both B cell receptors and toll‐like receptor–MyD88 signals by using Bruton’s tyrosine kinase inhibitor and histone deacetylase inhibitor abrogates refractory B‐1b cell immune responses against T cell–independent carbohydrate antigens.
The activation of natural killer (NK) cells in the liver inhibits engraftment of intraportally transplanted islets. We attempted to modulate the activity of NK cells by cotransplanting mesenchymal ...stem cells (MSCs) with islets in mice. We first investigated the ability of MSCs to secrete prostaglandin E2 , a predominant inhibitor of NK cell function, in various combinations of inflammatory cytokines. Notably, we found that prostaglandin E2 production was partially delayed in MSCs activated by inflammatory cytokines in vitro, whereas liver NK cells were activated early after islet transplant in vivo. Accordingly, preactivated MSCs, but not naive MSCs, substantially suppressed the expression of activation markers in liver NK cells after cotransplant with islets. Similarly, cotransplant with preactivated MSCs, but not naive MSCs, markedly improved the survival of islet grafts. These results highlight MSC cotransplant as an effective and clinically feasible method for enhancing engraftment efficiency.
The authors show that in a syngeneic intraportal islet transplantation mouse model, high prostaglandin E2 production from mesenchymal stem cells preactivated by pro‐inflammatory cytokines suppresses NK cells after cotransplantation with islets, and subsequently improves islet graft survival.
Mutations in TGFBR2, a component of the transforming growth factor (TGF)-β signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, ...Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-β-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-β-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium. In this study, we generated CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice, with simultaneous loss of Apc and Tgfbr2. These mice developed tumors, including adenocarcinoma in the proximal colon. We compared gene expression profiles between tumors of the two types of mice using microarray analysis. Our results showed that the expression of the murine homolog of GSDMC was significantly upregulated by 9.25-fold in tumors of CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice compared with those of CDX2P-G19Cre;Apcflox/flox mice. We then investigated the role of GSDMC in regulating CRC tumorigenesis. The silencing of GSDMC led to a significant reduction in the proliferation and tumorigenesis of CRC cell lines, whereas the overexpression of GSDMC enhanced cell proliferation. These results suggested that GSDMC functioned as an oncogene, promoting cell proliferation in colorectal carcinogenesis. In conclusion, combined inactivation of both Apc and Tgfbr2 in the colon epithelium of a CRC mouse model promoted development of adenocarcinoma in the proximal colon. Moreover, GSDMC was upregulated by TGFBR2 mutation in CRC and promoted tumor cell proliferation in CRC carcinogenesis, suggesting that GSDMC may be a promising therapeutic target.
PDF
