Glycogen accumulation and phase separation drives liver tumor initiation.

Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.

A deep learning method to predict bacterial ADP-ribosyltransferase toxins.

MOTIVATION: ADP-ribosylation is a critical modification involved in regulating diverse cellular processes, including chromatin structure regulation, RNA transcription, and cell death. Bacterial ADP-ribosyltransferase toxins (bARTTs) serve as potent virulence factors that orchestrate the manipulation of host cell functions to facilitate bacterial pathogenesis. Despite their pivotal role, the bioinformatic identification of novel bARTTs poses a formidable challenge due to limited verified data and the inherent sequence diversity among bARTT members. RESULTS: We proposed a deep learning-based model, ARTNet, specifically engineered to predict bARTTs from bacterial genomes. Initially, we introduced an effective data augmentation method to address the issue of data scarcity in training ARTNet. Subsequently, we employed a data optimization strategy by utilizing ART-related domain subsequences instead of the primary full sequences, thereby significantly enhancing the performance of ARTNet. ARTNet achieved a Matthew's correlation coefficient (MCC) of 0.9351 and an F1-score (macro) of 0.9666 on repeated independent test datasets, outperforming three other deep learning models and six traditional machine learning models in terms of time efficiency and accuracy. Furthermore, we empirically demonstrated the ability of ARTNet to predict novel bARTTs across domain superfamilies without sequence similarity. We anticipate that ARTNet will greatly facilitate the screening and identification of novel bARTTs from bacterial genomes. AVAILABILITY AND IMPLEMENTATION: ARTNet is publicly accessible at http://www.mgc.ac.cn/ARTNet/. The source code of ARTNet is freely available at https://github.com/zhengdd0422/ARTNet/.

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.

Casein kinase 1 alpha (CK1α) is a serine/threonine kinase with numerous functions, including regulating the Wnt/ß-catenin and p53 pathways. CK1α has a well-established role in inhibiting the p53 tumor suppressor by binding to MDMX and stimulating MDMX-p53 interaction. MDMX purified from cells contains near-stoichiometric amounts of CK1α, suggesting that MDMX may in turn regulate CK1α function. We present evidence that MDMX is a potent competitive inhibitor of CK1α kinase activity (Ki  = 8 nM). Depletion of MDMX increases CK1α activity and ß-catenin S45 phosphorylation, whereas ectopic MDMX expression inhibits CK1α activity and ß-catenin phosphorylation. The MDMX acidic domain and zinc finger are necessary and sufficient for binding and inhibition of CK1α. P53 binding to MDMX disrupts an intramolecular auto-regulatory interaction and enhances its ability to inhibit CK1α. P53-null mice expressing the MDMXW200S/W201G mutant, defective in CK1α binding, exhibit reduced Wnt/ß-catenin target gene expression and delayed tumor development. Therefore, MDMX is a physiological inhibitor of CK1α and has a role in modulating cellular response to Wnt signaling. The MDMX-CK1α interaction may account for certain p53-independent functions of MDMX.

ZmELF3.1 integrates the RA2-TSH4 module to repress maize tassel branching.

Tassel branch number (TBN) is a key agronomic trait for adapting to high-density planting and grain yield in maize. However, the molecular regulatory mechanisms underlying tassel branching are still largely unknown. Here, we used molecular and genetic studies together to show that ZmELF3.1 plays a critical role in regulating TBN in maize. Previous studies showed that ZmELF3.1 forms the evening complex through interacting with ZmELF4 and ZmLUX to regulate flowering in maize and that RA2 and TSH4 (ZmSBP2) suppresses and promotes TBN in maize, respectively. In this study, we show that loss-of-function mutants of ZmELF3.1 exhibit a significant increase of TBN. We also show that RA2 directly binds to the promoter of TSH4 and represses its expression, thus leading to reduced TBN. We further demonstrate that ZmELF3.1 directly interacts with both RA2 and ZmELF4.2 to form tri-protein complexes that further enhance the binding of RA2 to the promoter of TSH4, leading to suppressed TSH4 expression and consequently decreased TBN. Our combined results establish a novel functional link between the ELF3-ELF4-RA2 complex and miR156-SPL regulatory module in regulating tassel branching and provide a valuable target for genetic improvement of tassel branching in maize.

Ir Nanoparticles Supported on Oxygen-Deficient Vanadium Oxides Prepared by a Polyoxovanadate Precursor for Enhanced Electrocatalytic Hydrogen Evolution.

Developing highly active electrocatalysts is crucial for the application of electrocatalytic water splitting. In this study, we prepared vanadium oxide-graphene carbon nanocomposites (VxOy/C) with abundant defects using a carbon- and oxygen-rich hexavanadate derivative Na2[V6O7{(OCH2)3CCH3}4] as a precursor without the addition of an extra carbon source. Subsequently, the VxOy/C was used as a catalyst support to load a small amount of Ir, forming the Ir/VxOy/C nanoelectrocatalyst. This catalyst exhibited low hydrogen evolution overpotentials of only 18.90 and 13.46 mV at a working current density of 10 mA cm-2 in 1.0 M KOH and 0.5 M H2SO4 electrolyte systems, outperforming the commercial Pt/C catalysts. Additionally, the catalyst showed excellent chemical stability and long-term durability. This work provides a new strategy for the design and synthesis of highly active electrocatalysts for water splitting.

CoS2-MoS2 Nanoflower Arrays for Efficient Hydrogen Evolution Reaction in the Universal pH Range.

To explore, highly active electrocatalysts are essential for water splitting materials. Polyoxometalates (POMs) have drawn interesting attention in recent years due to their abundant structure and unique electrocatalytic properties. In this study, by using a POM-based precursor Co2Mo10, novel bimetallic sulfide (CoS2-MoS2) nanocomposites are rationally designed and synthesized under hydrothermal conditions. The incorporation of Co2+ to the host electrocatalyst could effectively increase the exposure of active sites of MoS2. Compared to pure MoS2, the CoS2-MoS2 nanocomposite exhibited a perfect hydrogen evolution reaction (HER) ability, for it merely requires overpotentials of 120 and 153 mV for 10 mA cm-2 working current density toward the HER in 1 M KOH and 0.5 M H2SO4 electrolyte systems, respectively. Additionally, the nanocomposite exhibited outstanding chemical stability and long-term durability. This study presents a novel strategy that utilizes POMs to enrich the exposed edge sites of MoS2, resulting in the preparation of efficient electrocatalysts.

Efficient Hydrogen Production over Molybdenum Tungsten Bimetallic Oxide NF/PMonW12-n Catalyst on Nickel Foam.

Developing inexpensive, efficient, and stable catalysts is crucial for reducing the cost of electrolytic hydrogen production. Recently, polyoxometalates (POMs) have gained attention and widespread use due to their excellent electrocatalytic properties. This study designed and synthesized three composite materials, NF/PMonW12-n, by using phosphomolybdic-tungstic heteropolyacids as precursors to grow in situ on nickel foam via the hydrothermal process and subsequent calcination. Then, their catalytic performances are systematically investigated. This work demonstrates that the NF/PMonW12-n catalysts generate more low valent oxides under the synergistic effect of Mo and W, further enhancing activity for hydrogen evolution reaction (HER). Among these electrocatalysts, NF/PMo6W6 exhibits the perfect HER performance, η10 is only 74 mV. It also shows great stability during long-term electrolysis. The current study introduces a fresh approach for producing electrocatalysts that are both cost-effective and highly efficient.

Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice.

Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA-seq analysis revealed significant immune and metabolic disorder in the LDDL-conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL-challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of ß-NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both ß-NMN and melatonin administration could significantly rescue the light-disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. ß-NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light-disruption associated CKD.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Prediction of injury localization in preoperative patients with gastrointestinal perforation: a multiomics model analysis.

BACKGROUND: The location of gastrointestinal perforation is essential for severity evaluation and optimizing the treatment approach. We aimed to retrospectively analyze the clinical characteristics, laboratory parameters, and imaging features of patients with gastrointestinal perforation and construct a predictive model to distinguish the location of upper and lower gastrointestinal perforation. METHODS: A total of 367 patients with gastrointestinal perforation admitted to the department of emergency surgery in Fujian Medical University Union Hospital between March 2014 and December 2020 were collected. Patients were randomly divided into training set and test set in a ratio of 7:3 to establish and verify the prediction model by logistic regression. The receiver operating characteristic curve, calibration map, and clinical decision curve were used to evaluate the discrimination, calibration, and clinical applicability of the prediction model, respectively. The multiomics model was validated by stratification analysis in the prediction of severity and prognosis of patients with gastrointestinal perforation. RESULTS: The following variables were identified as independent predictors in lower gastrointestinal perforation: monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, free air in peritoneal cavity by univariate logistic regression analysis and stepwise regression analysis. The area under the receiver operating characteristic curve of the prediction model was 0.886 (95% confidence interval, 0.840-0.933). The calibration curve shows that the prediction accuracy and the calibration ability of the prediction model are effective. Meanwhile, the decision curve results show that the net benefits of the training and test sets are greater than those of the two extreme models as the threshold probability is 20-100%. The multiomics model score can be calculated via nomogram. The higher the stratification of risk score array, the higher the number of transferred patients who were admitted to the intensive care unit (P < 0.001). CONCLUSION: The developed multiomics model including monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, and free air in the peritoneal cavity has good discrimination and calibration. This model can assist surgeons in distinguishing between upper and lower gastrointestinal perforation and to assess the severity of the condition.

Rapid and large-scale synthesis of MoS2via ultraviolet laser-assisted technology for photodetector applications.

Two-dimensional transition metal dichalcogenide (TMDC) thin films have been extensively employed in microelectronics research. Molybdenum disulfide (MoS2), as one of prominent candidates of this class, has been applied in photodetectors, integrated electronic devices, gas sensing, and electrochemical catalysis, owing to its extraordinary optoelectronic, chemical, and mechanical properties. Synthesis of MoS2crystal film is the key to its application. However, the reported technology revealed several drawbacks, containing limited surface area, prolonged high-temperature environment, and unsatisfying crystallinity. In order to enhance the convenience of MoS2applications, there is a pressing need for optimized fabrication technology, which could be quicker, with a large area, with adequate crystallinity and heat-saving. In this work, we presented an ultraviolet laser-assisted synthesis technology, accomplishing rapid growth (with the growth rate of about 40µm s-1) of centimeter-scale MoS2films at room temperature. To achieve this, we self-assembled a displaceable reaction chamber system, coupled with krypton fluoride ultraviolet pulse laser. The laser motion speed and trajectory could be customized in the software, allowing the maskless patterning of crystal films. As application, we exhibited a photodetector with the integration of synthesized MoS2and lead sulfide colloidal quantum dots (PbS CQDs), displaying broadband photodetection from ultraviolet, visible to near-infrared spectrum (365-1550 nm), with the detectivity of 109-1010Jones, and the rising time of 0.2-0.3 s. This work not only demonstrated a high-process-efficiency synthesis of TMDC materials, but also has opened up new opportunities for ultraviolet laser used in optoelectronics.

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects.

BACKGROUND: Liver transplantation (LT) is the only effective therapy for end-stage liver diseases, but some patients usually present with serious infection and immune rejection. Those with immune rejection require long-term administration of immunosuppressants, leading to serious adverse effects. Mesenchymal stem cells (MSCs) have various advantages in immune regulation and are promising drugs most likely to replace immunosuppressants. SUMMARY: This study summarized the application of MSCs monotherapy, its combination with immunosuppressants, MSCs genetic modification, and MSCs derivative therapy (cell-free therapy) in LT. This may deepen the understanding of immunomodulatory role of MSCs and promote the application of MSCs in immune rejection treatment after LT. KEY MESSAGES: MSCs could attenuate ischemia-reperfusion injury and immune rejection. There is no consensus on the effects of types and concentrations of immunosuppressants on MSCs. Although genetically modified MSCs have contributed to better outcomes to some extent, the best modification is still unclear. Besides, multiple clinical complications developed frequently after LT. Unfortunately, there are still few studies on the polygenic modification of MSCs for the simultaneous treatment of these complications. Therefore, more studies should be performed to investigate the potency of multi-gene modified MSCs in treating complications after LT. Additionally, MSC derivatives mainly include exosomes, extracellular vesicles, and conditioned medium. Despite therapeutic effects, these three therapies still have some limitations such as heterogeneity between generations and that they cannot be quantified accurately.

Ixekizumab-induced urticaria is associated with the short duration of remission in psoriasis by activation of mast cells.

BACKGROUND: Mast cell degranulation plays a pivotal role in urticaria and is also an early histologic characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of interleukin (IL)-17A blockers remains unclear. OBJECTIVE: To investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. METHODS: A retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathologic features were assessed. Patterns were compared between patients with ITAUR and nonurticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. RESULTS: Patients with ITAUR experienced early relapse compared with NUR group after treatment withdrawal. Transcriptomic and histopathologic analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A+ mast cells was inversely correlated with the duration of remission. LIMITATIONS: The mechanism of mast cell activation in ITAUR has not been precisely elucidated. CONCLUSION: Ixekizumab treatment increases IL-17A+ mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal.

Estimation of linezolid exposure in patients with hepatic impairment using machine learning based on a population pharmacokinetic model.

PURPOSE: To investigate the pharmacokinetic changes of linezolid in patients with hepatic impairment and to explore a method to predict linezolid exposure. METHODS: Patients with hepatic impairment who received linezolid were recruited. A population pharmacokinetic model (PPK) was then built using NONMEM software. And based on the final model, virtual patients with rich concentration values was constructed through Monte Carlo simulations (MCS), which were used to build machine learning (ML) models to predict linezolid exposure levels. Finally, we investigated the risk factors for thrombocytopenia in patients included. RESULTS: A PPK model with population typical values of 3.83 L/h and 34.1 L for clearance and volume of distribution was established, and the severe hepatic impairment was identified as a significant covariate of clearance. Then, we built a series of ML models to predict the area under 0 -24 h concentration-time curve (AUC0-24) of linezolid based on virtual patients from MCS. The results showed that the Xgboost models showed the best predictive performance and were superior to the methods for estimating linezolid AUC0-24 based on though concentration or daily dose. Finally, we found that baseline platelet count, linezolid AUC0-24, and combination with fluoroquinolones were independent risk factors for thrombocytopenia, and based on this, we proposed a method for calculating the toxicity threshold of linezolid. CONCLUSION: In this study, we successfully constructed a PPK model for patients with hepatic impairment and used ML algorithm to estimate linezolid AUC0-24 based on limited data. Finally, we provided a method to determine the toxicity threshold of linezolid.

Intrinsic excitability of human right parietal cortex shapes the experienced visual size illusions.

Converging evidence has found that the perceived visual size illusions are heritable, raising the possibility that visual size illusions might be predicted by intrinsic brain activity without external stimuli. Here we measured resting-state brain activity and 2 classic visual size illusions (i.e. the Ebbinghaus and the Ponzo illusions) in succession, and conducted spectral dynamic causal modeling analysis among relevant cortical regions. Results revealed that forward connection from right V1 to superior parietal lobule (SPL) was predictive of the Ebbinghaus illusion, and self-connection in the right SPL predicted the Ponzo illusion. Moreover, disruption of intrinsic activity in the right SPL by repetitive transcranial magnetic stimulation (TMS) temporally increased the Ebbinghaus rather than the Ponzo illusion. These findings provide a better mechanistic understanding of visual size illusions by showing the causal and distinct contributions of right parietal cortex to them, and suggest that spontaneous fluctuations in intrinsic brain activity are relevant to individual difference in behavior.

Evaluating and diagnosing ecosystem health of the "three-lake" watershed in Yuxi, Yunnan, China from 2010 to 2020 by PSR-KDE.

To carry out the diagnosis and evaluation of the ecosystem health in Yuxi three-lake watershed, this paper presents the changing trend of its health state, and predicts the future development. This also provides ideas for maintaining the regional ecosystem health, and then gradually improves the ecological environment quality. Taking Fuxian Lake, Qilu Lake and Xingyun Lake (the three-lake watershed) in Yuxi City, Yunnan Province, Southwest China as the research object, a model combining pressure-state-response and kernel density estimation (PSR-KDE) adopts to diagnose and evaluate the ecosystem health of the "three lake" watershed from 2010 to 2020, and the distribution map of ecosystem health index has obtained by the evaluation indexes integration based on GIS spatial analysis. Hence, the evaluation results have visualized on the map. The results show that: The distribution of ecosystem health index in the study area was 0.1530-0.7045 in 2010, 0.2056-0.7512 in 2015, and 0.2248-0.7662 in 2020. 0.12% was in the pathological area in 2010. After 2015, the pathological condition of ecosystem health has completely solved, and the proportion of unhealthy ecosystems was 11.95% in 2010, 7.38% in 2015, and 5.97% in 2020. The ecosystem health index of the study region was 0.5523 in 2010, 0.5807 in 2015, and 0.5815 in 2020, it indicates that the ecosystem was in a sub-health state. From 2010 to 2020, the ecosystem health around Qilu Lake was the most worrying, followed by the northwest of Fuxian Lake and the northern and southern regions of Xingyun Lake. The ecosystem health of the three-lake watershed showed significant improvement from 2010 to 2020. The study ecosystem health assessment and early warning in the three-lake watershed is significant to the ecological environment protection and management of the plateau lake basin, the restoration of the territorial space ecology and the economic development of the surrounding area.

Application of Indian ink markers for locating gastric varices under endoscopic ultrasonography.

OBJECTIVE: The present study aimed to investigate the accuracy of endoscopic ultrasonography (EUS) combined with Indian ink in locating target vessels of gastric varices (GVs) compared with conventional endoscopic techniques. Additionally, the characteristics of GVs under conventional endoscopy were also explored. METHODS: All 50 cirrhotic patients with GVs between August 2021 and December 2022 were included in the study. Firstly, conventional endoscopy was employed to identify GVs and to record the expected injection sites. Subsequently, EUS was used to locate the perforated vessel and the injection site was them marked with India ink followed by injection with cyanoacrylate (CYA). Finally, conventional endoscopy was used to examine GVs, to identify the marker points of Indian ink and to compare whether the injection points under conventional endoscopy were consistent with those marked with Indian ink. Furthermore, patients with consistent and inconsistent distribution of endoscopic markers and injection sites were divided into two groups. RESULTS: EUS could detect the perforating vessels in real time and intuitively. The distribution of markers using EUS was significantly different compared with the injection points obtained by conventional endoscopy (P < 0.001). Therefore, 20 cases were allocated to the consistent group and 30 cases to the non-consistent group. 16 patients who showed red wale signs were obtained in the consistent group and 11 patients in the non-consistent group (P = 0.048). The diameter of the largest GVs was 13.5 (10-15) mm in the consistent group compared with 10 (7.5-10) mm in the non-consistent group (P = 0.006). CONCLUSION: EUS could provide the exact location of GVs, thus more accurately describing the endoscopic characteristics of the GVs. Furthermore, the red wale signs and diameter of the largest GVs obtained using conventional endoscopy were helpful in determining the location of target GVs.

Effect of Vaginal Microecological Alterations on Female Pelvic Organ Prolapse.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the correlation between endogenous vaginal microecological alterations and female pelvic organ prolapse (POP). METHODS: Patients who underwent vaginal hysterectomy were retrospectively analyzed as the POP group (n = 30) and the non-POP group (n = 30). The vaginal microbial metabolites and enzyme levels were tested using the dry chemoenzymatic method. The mRNA and protein expression were tested using real-time quantitative PCR and immunohistochemistry. SPSS version 25.0 and GraphPad Prism 8.0 were performed for statistical analysis. RESULTS: Compared with the non-POP group, the vaginal pH, H2O2 positivity and leukocyte esterase positivity were higher in patients with POP (all p < 0.05). Further analysis showed that patients with pelvic organ prolapse quantification (POP-Q) stage IV had higher rates of vaginal pH, H2O2 positivity and leukocyte esterase positivity than those with POP-Q stage III. Additionally, the mRNA expression of decorin (DCN), transforming growth factor beta 1 (TGF-ß1), and matrix metalloproteinase-3 (MMP-3) in uterosacral ligament tissues were higher, whereas collagen I and III were lower. Similarly, the positive expression of MMP-3 in uterosacral ligament tissue was significantly upregulated in the POP group compared with the non-POP group (p = 0.035), whereas collagen I (p = 0.004) and collagen III (p = 0.019) in uterosacral ligament tissue were significantly downregulated in the POP group. Correlation analysis revealed that there was a significant correlation between vaginal microecology and collagen metabolism. In addition, MMP-3 correlated negatively with collagen I and collagen III (p = 0.002, r = -0.533; p = 0.002, r = -0.534 respectively), whereas collagen I correlated positively with collagen III (p = 0.001, r = 0.578). CONCLUSIONS: Vaginal microecological dysbiosis affects the occurrence of female POP, which could be considered a novel therapeutic option.

The Brachypodium distachyon DREB transcription factor BdDREB-39 confers oxidative stress tolerance in transgenic tobacco.

Key message BdDREB-39 is a DREB/CBF transcription factor, localized in the nucleus with transactivation activity, and BdDREB-39-overexpressing transgenic yeasts and tobacco enhanced the tolerance to oxidative stress.Abstract The DREB/CBF transcription factors are generally recognized to play an important factor in plant growth, development and response to various abiotic stresses. However, the mechanism of DREB/CBFs in oxidative stress response is largely unknown. This study isolated a DREB/CBF gene BdDREB-39 from Brachypodium distachyon (B. distachyon). Multiple sequence alignment and phylogenetic analysis showed that BdDREB-39 was closely related to the DREB proteins of oats, barley, wheat and rye and therefore its study can provide a reference for the excavation and genetic improvement of BdDREB-39 or its homologs in its closely related species. The transcript levels of BdDREB-39 were significantly up-regulated under H2O2 stress. BdDREB-39 was localised in the nucleus and functioned as a transcriptional activator. Overexpression of BdDREB-39 enhanced H2O2 tolerance in yeast. Transgenic tobaccos with BdDREB-39 had higher germination rates, longer root, better growth status, lesser reactive oxygen species (ROS) and malondialdehyde (MDA), and higher superoxide dismutase (SOD) and peroxidase (POD) activities than wild type (WT). The expression levels of ROS-related and stress-related genes were improved by BdDREB-39. In summary, these results revealed that BdDREB-39 can improve the viability of tobacco by regulating the expression of ROS and stress-related genes, allowing transgenic tobacco to accumulate lower levels of ROS and reducing the damage caused by ROS to cells. The BdDREB-39 gene has the potential for developing plant varieties tolerant to stress.