TSPO-induced degradation of the ethylene receptor RhETR3 promotes salt tolerance in rose (Rosa hybrida).

The gaseous plant hormone ethylene regulates plant development, growth, and responses to stress. In particular, ethylene affects tolerance to salinity; however, the underlying mechanisms of ethylene signaling and salt tolerance are not fully understood. Here, we demonstrate that salt stress induces the degradation of the ethylene receptor ETHYLENE RESPONSE 3 (RhETR3) in rose (Rosa hybrid). Furthermore, the TspO/MBR (Tryptophan-rich sensory protein/mitochondrial benzodiazepine receptor) domain-containing membrane protein RhTSPO interacted with RhETR3 to promote its degradation in response to salt stress. Salt tolerance is enhanced in RhETR3-silenced rose plants but decreased in RhTSPO-silenced plants. The improved salt tolerance of RhETR3-silenced rose plants is partly due to the increased expression of ACC SYNTHASE1 (ACS1) and ACS2, which results in an increase in ethylene production, leading to the activation of ETHYLENE RESPONSE FACTOR98 (RhERF98) expression and, ultimately accelerating H2O2 scavenging under salinity conditions. Additionally, overexpression of RhETR3 increased the salt sensitivity of rose plants. Co-overexpression with RhTSPO alleviated this sensitivity. Together, our findings suggest that RhETR3 degradation is a key intersection hub for the ethylene signalling-mediated regulation of salt stress.

Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Characteristics of the oral and gastric microbiome in patients with early-stage intramucosal esophageal squamous cell carcinoma.

BACKGROUND: Oral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC). METHOD: A total of 104 samples were collected from 31 patients with EIESC and 21 healthy controls. The compositions of oral and gastric microbiota were analyzed using 16 S rRNA V3-V4 amplicon sequencing. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. The correlation between oral microbiota and clinicopathological factors was evaluated using Spearman correlation analysis. Additionally, co-occurrence networks were established and random forest models were utilized to identify significant microbial biomarkers for distinguishing between the EIESC and control groups. RESULTS: A total of 292 oral genera and 223 species were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar. CONCLUSION: Our study potentially indicates that the dysbacteriosis of both the oral and gastric microbiome was associated with EIESC. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of EIESC. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563).

Influence of annealing pretreatment in different atmospheres on crystallization quality and UV photosensitivity of gallium oxide films.

Due to their high wavelength selectivity and strong anti-interference capability, solar-blind UV photodetectors hold broad and important application prospects in fields like flame detection, missile warnings, and secure communication. Research on solar-blind UV detectors for amorphous Ga2O3 is still in its early stages. The presence of intrinsic defects related to oxygen vacancies significantly affects the photodetection performance of amorphous Ga2O3 materials. This paper focuses on growing high quality amorphous Ga2O3 films on silicon substrates through atomic layer deposition. The study investigates the impact of annealing atmospheres on Ga2O3 films and designs a blind UV detector for Ga2O3. Characterization techniques including atomic force microscopy (AFM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) are used for Ga2O3 film analysis. Ga2O3 films exhibit a clear transition from amorphous to polycrystalline after annealing, accompanied by a decrease in oxygen vacancy concentration from 21.26% to 6.54%. As a result, the response time of the annealed detector reduces from 9.32 s to 0.47 s at an external bias of 10 V. This work demonstrates that an appropriate annealing process can yield high-quality Ga2O3 films, and holds potential for advancing high-performance solar blind photodetector (SBPD) development.

Causal effects of lipid-lowering therapies on aging-related outcomes and risk of cancers: a drug-target Mendelian randomization study.

BACKGROUND: Despite the widespread use of statins, newer lipid-lowering drugs have been emerging. It remains unclear how the long-term use of novel lipid-lowering drugs affects the occurrence of cancers and age-related diseases. METHODS: A drug-target Mendelian randomization study was performed. Genetic variants of nine lipid-lowering drug-target genes (HMGCR, PCKS9, NPC1L1, LDLR, APOB, CETP, LPL, APOC3, and ANGPTL3) were extracted as exposures from the summary data of Global Lipids Genetics Consortium Genome-Wide Association Studies (GWAS). GWAS summary data of cancers and noncancerous diseases were used as outcomes. The inverse-variance weighted method was applied as the main statistical approach. Sensitivity tests were conducted to evaluate the robustness, pleiotropy, and heterogeneity of the results. RESULTS: In addition to marked effects on decreased risks of atherosclerotic cardiovascular diseases, genetically proxied lipid-lowering variants of PCKS9, CETP, LPL, LDLR, and APOC3 were associated with longer human lifespans (q<0.05). Lipid-lowering variants of ANGPTL3 and LDLR were associated with reduced risks of colorectal cancer, and ANGPTL3 was also associated with lower risks of gastric cancer (q<0.05). Lipid-lowering LPL variants were associated with decreased risks of hypertension, type 2 diabetes, nonalcoholic fatty liver disease, and bladder cancer (q<0.05). Lipid-lowering variants of PCKS9 and HMGCR were associated with decreased risks of osteoporosis (q<0.05). Lipid-lowering APOB variants were associated with a decreased risk of thyroid cancer (q<0.05). CONCLUSIONS: Our study provides genetic evidence that newer nonstatin lipid-lowering agents have causal effects on decreased risks of several common cancers and cardiometabolic diseases. These data provide genetic insights into the potential benefits of newer nonstatin therapies.

A day-to-day management model improves patient compliance to treatment for Helicobacter pylori infection: a prospective, randomized controlled study.

BACKGROUND: The day-to-day (DTD) management model encourages patients to actively participate in their healthcare by setting goals. We determined the effectiveness of the DTD model in the treatment of Helicobacter pylori (H. pylori) infection, as compared with conventional outpatient education (OE). METHODS: We randomized 254 H. pylori-positive patients into a DTD group (127 patients) and an OE group (127 patients) prior to primary treatment with 14-day bismuth-containing quadruple therapy, including esomeprazole, amoxicillin, and clarithromycin. Both groups received consistent medication instructions. Patients in the DTD group recorded daily attendance after completing their daily medication plan from day 1 to day 14. The medication compliance, follow-up compliance, H. pylori eradication rates, and adverse events (AEs) were evaluated. RESULTS: In the modified intention-to-treat (MITT) and per-protocol (PP) analyses, the DTD group showed significantly higher medication compliance than the OE group (P = 0.001 and P = 0.031, respectively). Both the MITT and PP analyses showed significant differences in follow-up compliance (P < 0.001 and P = 0.003, respectively) and timing of the review urea breath test (P < 0.001 and P = 0.001, respectively) between the two groups. However, no significant differences were observed in the H. pylori eradication rates (95.8% vs. 93.8%, P = 0.529) in the PP analysis, or AEs incidence (25.4% vs. 28.3%, P = 0.603) between the two groups. CONCLUSION: This study demonstrated the novel application of the DTD model in the treatment of H. pylori infection, which enabled patients to develop habitual medication-taking behaviors without physician intervention.

Alternation of the gut microbiota in irritable bowel syndrome: an integrated analysis based on multicenter amplicon sequencing data.

BACKGROUND: Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive. METHOD: A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes. RESULTS: A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae, Moraxellaceae and Sphingobacteriaceae; the genera Streptococcus, Bacillus, Enterocloster, Sphingobacterium, Holdemania and Acinetobacter. IBS-depleted: the phyla Firmicutes, Euryarchaeota, Cyanobacteria, Acidobacteria and Lentisphaerae; the families Bifidobacteriaceae, Ruminococcaceae, Methanobacteriaceae and the other 25 families; the genera Faecalibacterium, Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community. CONCLUSION: This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.

Metagenomic analysis of the interaction between the gut microbiota and colorectal cancer: a paired-sample study based on the GMrepo database.

BACKGROUND: Previous evidence has shown that the gut microbiota plays a role in the development and progression of colorectal cancer (CRC). This study aimed to provide quantitative analysis and visualization of the interaction between the gut microbiota and CRC in order to establish a more precise microbiota panel for CRC diagnosis. METHOD: A paired-sample study was designed by retrieving original metagenomic data from the GMrepo database. The differences in the distribution of the gut microbiota between CRCs and controls were analysed at the species level. A co-occurrence network was established, and the microbial interactions with environmental factors were assessed. Random forest models were used to determine significant biomarkers for differentiating CRC and control samples. RESULTS: A total of 709 metagenomic samples from 6 projects were identified. After matching, 86 CRC patients and 86 matched healthy controls from six countries were enrolled. A total of 484 microbial species and 166 related genera were analysed. In addition to previously recognized associations between Fusobacterium nucleatum and species belonging to the genera Peptostreptococcus, Porphyromonas, and Prevotella and CRC, we found new associations with the novel species of Parvimonas micra and Collinsella tanakaei. In CRC patients, Bacteroides uniformis and Collinsella tanakaei were positively correlated with age, whereas Dorea longicatena, Adlercreutzia equolifaciens, and Eubacterium hallii had positive associations with body mass index (BMI). Finally, a random forest model was established by integrating different numbers of species with the highest model-building importance and lowest inner subcategory bias. The median value of the area under the receiver operating characteristic curve (AUC) was 0.812 in the training cohort and 0.790 in the validation set. CONCLUSIONS: Our study provides a novel bioinformatics approach for investigating the interaction between the gut microbiota and CRC using an online free database. The identification of key species and their associated genes should be further emphasized to determine the relative causality of microbial organisms in the development of CRC.

The Long-Term Outcomes of Surgery Versus Endoscopic Treatment in Patients With Siewert Type II T1M0N0 Adenocarcinoma of the Esophagogastric Junction.

OBJECTIVE: We compared the long-term prognosis of surgery and endoscopic treatment (ET) in patients diagnosed with Siewert Type II pT1N0M0 adenocarcinoma of the esophagogastric junction (AEG). METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a real-world retrospective cohort study and enrolled patients with Siewert Type II pT1N0M0 AEG who underwent surgery or endoscopic treatment (ET) from 2010 to 2018. Matched cohorts were generated using propensity score matching Competing-risk analysis was applied. The cumulative incidence function was used to calculate cancer-specific death and other causes of death (OCD) at different time points. Univariate and multivariate analyses were performed to identify significant prognostic factors by using the subdistribution hazard ratio. RESULTS: We enrolled 725 patients: 462 underwent surgery and 263 received ET. The 5 year cumulative CSD incidence significantly differed between surgery and ET cohorts (16.87% vs 11.08%, P = .01). Following PSM, 2 balanced groups (n = 219 patients each) were analyzed. No significant difference in the 5 year cumulative incidences of CSD was noted between cohorts (17.61% vs. 12.16%, P = .14). In multivariable analysis, the CSD incidence was high among patients with aged ≥65 (SHR 2.29, 95%CI 0.99-5.33, P = .05) and T1b-stage (SHR 1.92, 95%CI 1.03-3.57, P = .04); treatment (surgery or ET) was not significantly associated with cancer survival (SHR 1.51, 95% CI 0.81-2.81, P = .20). CONCLUSION: Long-term survival did not significantly differ among patients with Siewert Type II pT1N0M0 AEG adenocarcinoma undergoing surgery or ET. ET may be considered in patients >65 years old or those with submucosal (T1b-stage) cancer of AEG.

Alternation of the gut microbiota in metabolically healthy obesity: An integrated multiomics analysis.

Background: Although the gut microbiota may be involved in obesity onset and progression, the exact association of the gut microbiota in metabolically healthy obesity (MHO) remains largely unknown. Methods: An integrated paired-sample metagenomic analysis was conducted to investigate the gut microbial network and biomarkers of microbial species from the MHO and healthy non-obese subjects in the GMrepo database. Further explorations were performed in the MHO mice model using a multiomics analysis to detect changes in the composition and function of the intestinal microbiome and associated metabolites. Results: In the human study, 314 matched metagenomic data were qualified for the final analysis. We identified seven significantly changed species possibly involved in MHO pathogenesis (MHO-enriched: Bacteroides vulgatus, Megamonas sp; MHO-depleted: Butyrivibrio crossotus, Faecalibacterium prausnitzii, Bacteroides cellulosilyticus; Eubacterium siraeum; Bacteroides massiliensis). In the murine study, we found 79 significantly-changed species which may have possible associations with the MHO phenotype. The depletion of Bacteroides cellulosilyticus was commonly recognized in the human and murine MHO phenotype. Consistent with the metagenomic data, liquid chromatography-mass spectrometry (LC/MS) revealed significantly changed gut metabolites, which may promote MHO pathogenesis by altering the amino acids and lipid metabolic pathways. In the microbe-metabolites interaction analysis, we identified certain fatty acids (Dodecanedioic acid, Arachidic Acid, Mevalonic acid, etc.) that were significantly correlated with the MHO-enriched or depleted species. Conclusion: This study provides insights into identifying specific microbes and metabolites that may involve in the development of obesity without metabolic disorders. Future modalities for MHO intervention may be further validated by targeting these bacteria and metabolites.

Establishment of a Preoperative Laboratory Panel to identify Lymph Node Metastasis in Superficial Esophageal Cancer.

Background and Aims: In superficial esophageal squamous cell carcinoma (SESCC), the lymph node status is considered as one of the essential factors to determine the primary treatment strategy. Nevertheless, current noninvasive staging methods before surgical intervention have limited accuracy. This study aimed to establish a simple and noninvasive serum-testing panel that facilitates the preoperative prediction of pathological nodal status in SESCC patients. Methods: Data for preoperative hematological parameters were retrospectively collected from 256 SESCC patients who underwent esophagectomy from December 2017 to May 2020. The random forest classification and decision tree algorithms were applied to identify the optimal combination of serum parameters for accurately identifying positive nodal metastasis. Results: Twelve candidate parameters were identified for statistical significance in predicting positive nodal metastasis. A multi-analyte panel was established by using a random forest classification method, incorporating four optimal parameters: Hematocrit (HCT), Activated Partial Thromboplastin Time (APTT), Retinol-Binding Proteins (RBP), and Mean Platelet Volume (MPV). A schematic decision tree was yielded from the above panel with an 89.1% accuracy of classification capability. Conclusions: This study established a simple laboratory panel in discerning the preoperative lymph nodal status of SESCC patients. With further validation, this panel may serve as a simple tool for clinicians to choose appropriate intervention (surgery versus endoscopic resection) for SESCC patients.

RhRab5ip, a new interactor of RhPIP1;1, was involved in flower opening of cut rose during water deficit.

Flower opening is a process primarily caused by water uptake-driven petal cell expansion. while which is easily affected by water deficit during transportation of cut flowers, resulting in abnormal flower opening. The knowledge of important players during this process remains limited. We previously reported that the aquaporin RhPIP1;1 plays an important role in ethylene-regulated petal cell expansion in rose flower. Here, we identified RhRab5ip as a new interactor of RhPIP1;1. RhRab5ip belongs to the Rab5-interacting protein (Rab5ip) family and may function in vesicle trafficking pathway. By using split ubiquitin yeast two-hybrid (SUY2H) system, bimolecular fluorescence complementation (BiFC) and subcellular colocalization we confirmed the existence of physical interaction between RhPIP1;1 and RhRab5ip in yeast and plant cell. The interaction of these two proteins happened at the small punctate structures in the cytoplasm. Expression of RhRab5ip in petals increased substantially at the initial stage of flower opening and maintained at high level until flower wilting. The transcripts of both RhRab5ip and RhPIP1;1 were greatly up-regulated by ABA and GA3 treatments, while only RhPIP1;1 was down-regulated by ethylene. Moreover, both RhRab5ip and RhPIP1;1 were significantly induced by water deficit treatment after 12 h-treatment, when flowers started to wilt and showed neck bending. Taken together, these findings suggested that RhRab5ip might functionally coordinate with RhPIP1;1 in response to water deficit stress in rose flower, expanding our understanding of the possible involvement of Rab5ip protein in the regulatory network of flower opening during water deficit.

[Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network].

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.

TRV-GFP: a modified Tobacco rattle virus vector for efficient and visualizable analysis of gene function.

Virus-induced gene silencing (VIGS) is a useful tool for functional characterization of genes in plants. Unfortunately, the efficiency of infection by Tobacco rattle virus (TRV) is relatively low for some non-Solanaceae plants, which are economically important, such as rose (Rosa sp.). Here, to generate an easy traceable TRV vector, a green fluorescent protein (GFP) gene was tagged to the 3' terminus of the coat protein gene in the original TRV2 vector, and the silencing efficiency of the modified TRV-GFP vector was tested in several plants, including Nicotiana benthamiana, Arabidopsis thaliana, rose, strawberry (Fragaria ananassa), and chrysanthemum (Dendranthema grandiflorum). The results showed that the efficiency of infection by TRV-GFP was equal to that of the original TRV vector in each tested plant. Spread of the modified TRV virus was easy to monitor by using fluorescent microscopy and a hand-held UV lamp. When TRV-GFP was used to silence the endogenous phytoene desaturase (PDS) gene in rose cuttings and seedlings, the typical photobleached phenotype was observed in 75-80% plants which were identified as GFP positive by UV lamp. In addition, the abundance of GFP protein, which represented the concentration of TRV virus, was proved to correlate negatively with the level of the PDS gene, suggesting that GFP could be used as an indicator of the degree of silencing of a target gene. Taken together, this work provides a visualizable and efficient tool to predict positive gene silencing plants, which is valuable for research into gene function in plants, especially for non-Solanaceae plants.

Involvement of rose aquaporin RhPIP1;1 in ethylene-regulated petal expansion through interaction with RhPIP2;1.

Aquaporins (AQPs) are multifunctional membrane channels and facilitate the transport of water across plant cell membranes. Among the plant AQPs, plasma membrane intrinsic proteins (PIPs), which cluster in two phylogenetic groups (PIP1 and PIP2), play a key role in plant growth. Our previous work has indicated that RhPIP2;1, a member of PIP2, is involved in ethylene-regulated cell expansion of rose petals. However, whether PIP1s also play a role in petal expansion is still unclear. Here, we identified RhPIP1;1, a PIP1 subfamily member, from 18 PIPs assemble transcripts in rose microarray database responsive to ethylene. RhPIP1;1 was rapidly and significantly down-regulated by ethylene treatment. RhETRs-silencing also clearly decreased the expression of RhPIP1;1 in rose petals. The activity of the RhPIP1;1 promoter was repressed by ethylene in rosettes and roots of Arabidopsis. RhPIP1;1 is mainly localized on endoplasmic reticulum and plasma membrane. We demonstrated that RhPIP1;1-silencing significantly inhibited the expansion of petals with decreased petal size and cell area, as well as reduced fresh weight when compared to controls. Expression of RhPIP1;1 in Xenopus oocytes indicated that RhPIP1;1 was inactive in terms of water transport, while coexpression of RhPIP1;1 with the functional RhPIP2;1 led to a significant increase in plasma membrane permeability. Yeast growth, ß-Galactosidase activity, bimolecular fluorescence complementation, and colocalization assay proved existence of the interaction between RhPIP1;1 and RhPIP2;1. We argue that RhPIP1;1 plays an important role in ethylene-regulated petal cell expansion, at least partially through the interaction with RhPIP2;1.