Higher oxidative balance score is associated with lower kidney stone disease in US adults: a population-based cross-sectional study.

PURPOSE: Oxidative balance stress (OBS) was an important indicator for assessing exposure to oxidative stress related to diet and lifestyle. The purpose of this study was to explore the relationship between OBS and kidney stone disease (KSD). METHODS: Secondary dataset analysis was performed by the study from six survey cycles (2007-2018) in the National Health and Nutrition Examination Survey (NHANES). OBS was the exposure factor and ever had kidney stone (yes or no) was the outcome. Weighted univariate or multivariate logistic regression models were used to estimate the associations. RESULTS: The prevalence of KSD among participants was 8.6%. OBS showed a significant negative correlation with KSD (OR: 0.98, 95% CI 0.96-0.999), 35% reduction in KSD in the highest OBS quartile compared to the lowest OBS quartile. Dietary OBS was significantly negatively correlated with KSD (OR: 0.98, 95% CI 0.96-0.9998), but not with lifestyle OBS. In addition, OBS had a negative correlation with KSD in females (OR: 0.97, 95% CI 0.94-0.996), non-diabetic participants (OR: 0.98, 95% CI 0.96-0.99), and hypertensive participants (OR: 0.96, 95% CI 0.93-0.99), but OBS was not observed to be associated with KSD in gout participants. Interestingly, this relationship existed in participants aged 30-60 years and a ratio of family income to poverty (PIR) of 1.3-3.5 (all P value < 0.05). CONCLUSION: Our study revealed that OBS was negative associated with KSD, and high OBS might be a protective factor in KSD. Targeting one of the components of OBS might be beneficial.

Genome-Wide Analysis of the Oat (Avena sativa) HSP90 Gene Family Reveals Its Identification, Evolution, and Response to Abiotic Stress.

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.

Antioxidant diet/lifestyle could mitigate the adverse impacts of urinary polycyclic aromatic hydrocarbons on lung function.

BACKGROUND: Extant research has demonstrated a correlation between exposure to polycyclic aromatic hydrocarbons (PAHs) and impaired lung function. The maintenance of an antioxidant-rich diet/lifestyle positively benefits pulmonary health. However, the potential ameliorative impact of an antioxidant-based diet/lifestyle on PAH-induced detrimental effects remains unclear. METHODS: The study drew upon cross-sectional data encompassing 1615 participants derived from the National Health and Nutrition Examination Survey 2007 to 2012. To gauge the maintenance of an antioxidant-rich diet/lifestyle, we employed Oxidative Balance Score (OBS) that incorporates sixteen nutrients and four lifestyle factors. Lung function was evaluated using percent-predicted Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1), FEV1/FVC, and fractional exhaled nitric oxide (FENO). Our analytical approach entailed the utilization of weighted linear models. RESULTS: Our analysis unveiled interaction effects between urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and OBS concerning lung function. A one-unit increase in ∑OH-PAH (sum of eight OH-PAHs) was linked to a -0.75% reduction (95% CI: -1.28, -0.22) in FEV1/FVC. Individuals exhibiting low OBS displayed a marked decrease in FEV1/FVC (mean difference = -1.10%; 95% CI: -1.82, -0.39) for each unit increase in ∑OH-PAH, whereas no significant associations were discerned for those with medium or high OBS. Further stratification by gender yielded consistent results. The correlation between ∑OH-PAH and FENO proved statistically significant among participants with low OBS (P = 0.002) and medium OBS (P = 0.001), but non-significant for those with high OBS. Parallel findings emerged when examining percent-predicted FEV1 and FVC. CONCLUSIONS: In conclusion, our study underscores the existence of statistically significant interactions between OH-PAHs and the maintenance of an antioxidant-rich diet and lifestyle concerning lung function. These findings underscore the pivotal role of maintaining an antioxidant-based diet and lifestyle in mitigating the adverse impacts of PAH exposure on lung function.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

Relationship between urinary tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and lung function: Evidence from NHANES 2007-2012.

INTRODUCTION: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a tobacco-specific carcinogen. Spirometry values (FEV1%, PEF%, etc.) are commonly used as clinical indicators to assess the condition of lung function and the results can be used to diagnose respiratory diseases. However, the relationship between urinary NNAL levels and lung function is unclear. METHODS: We performed a secondary dataset analysis of the three cycles of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. The association of urinary NNAL with spirometry values was assessed using weighted linear models. In addition, subgroup analyses by gender were also tested. RESULTS: One unit increased in urinary NNAL could result in a 28% decrease of FEV1/FVC% (mean difference, MD= -0.28; 95% CI: -0.39 - -0.17), 44% decrease of FEV1% (MD= -0.44; 95% CI: -0.69 - -0.18), and FEV1/FEV6% and FEV3/FEV6% decreased by 20% and 8%, respectively. Increased urinary NNAL was associated with lower PEF% (MD= -0.85; 95% CI: -1.19 - -0.51), FEF25-75% (MD= -1.40; 95% CI: -1.94 - -0.87), and FENO (MD= -0.67; 95% CI: -0.92 - -0.42). But forced expiratory time (FET) showed an increment (MD=0.10; 95% CI: 0.03-0.16). The FEV1/FEV6% and FEV3/FEV6% showed decreasing trend from the lowest urinary NNAL quartiles to the highest urinary NNAL quartiles, while FET showed an increased trend. PEF%, FEF 25-75%, and FENO showed the same decreasing trend (all p<0.05). In addition, urinary NNAL seemed to affect spirometry values more in males. CONCLUSIONS: Urinary NNAL was negatively correlated with FEV1/FVC%, FEV1%, FEV1/FEV6%, FEV3/FEV6%, PEF%, FEF25-75%, and FENO, which was closely related to lung function.

Adjuvant Radiotherapy Is Not Necessary for Stage III Mucinous Rectal Cancer: Evidence Based on Long Survival Analysis from SEER Data.

BACKGROUND: Although rectal mucinous adenocarcinoma (RMC) is less sensitive to radiotherapy, adjuvant radiotherapy is still recommended for RMC patients. This study aimed to explore whether adjuvant radiotherapy is necessary for stage III RMC. METHODS: Data of patients with stage III RMC were obtained from the National Cancer Institute's SEER database (2004-2015). The survival rates were calculated by Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were used to assess the impact of clinicopathological parameters on overall survival (OS) and cancer-specific survival (CSS). RESULTS: RMC has a worse T and N stage at diagnosis than rectal adenomatous carcinoma (RAC) (all p < 0.001). Multivariate Cox regression analyses revealed that histopathological type MC was an independent poor prognostic factor for OS (HR 1.27; 95%CI 1.14-1.41; p < 0.001) and CSS (HR 1.34; 95%CI 1.18-1.51; p < 0.001). Subgroup analysis based on different treatment regimens showed no significant difference between chemotherapy group and chemotherapy plus radiotherapy group. After the propensity score matching, no significant difference was also found in OS and CSS between chemotherapy group and chemotherapy plus radiotherapy group. CONCLUSIONS: RMC is an independent poor prognostic factor for OS and CSS. Adjuvant radiotherapy for RMC was not beneficial in improving survival outcomes.

Promotion of uterine reconstruction by a tissue-engineered uterus with biomimetic structure and extracellular matrix microenvironment.

The recurrence rate for severe intrauterine adhesions is as high as 60%, and there is still lack of effective prevention and treatment. Inspired by the nature of uterus, we have developed a bilayer scaffold (ECM-SPS) with biomimetic heterogeneous features and extracellular matrix (ECM) microenvironment of the uterus. As proved by subtotal uterine reconstruction experiments, the mechanical and antiadhesion properties of the bilayer scaffold could meet the requirement for uterine repair. With the modification with tissue-specific cell-derived ECM, the ECM-SPS had the ECM microenvironment signatures of both the endometrium and myometrium and exhibited the property of inducing stem cell-directed differentiation. Furthermore, the ECM-SPS has recruited more endogenous stem cells to promote endometrial regeneration at the initial stage of repair, which was accompanied by more smooth muscle regeneration and a higher pregnancy rate. The reconstructed uterus could also sustain normal pregnancy and live birth. The ECM-SPS may thereby provide a potential treatment for women with severe intrauterine adhesions.

Identification and Validation of Reference Genes for RT-qPCR Analysis in Reed Canary Grass during Abiotic Stress.

Reed canary grass (Phalaris arundinacea L.) is known for its tolerance to drought, heavy metals, and waterlogging, making it a popular choice for forage production and wetland restoration in the Qinghai-Tibet Plateau (QTP). To accurately assess gene expression in reed canary grass under different abiotic stresses, suitable reference genes need to be identified and validated. Thirteen candidate reference gene sequences were selected and screened using RT-qPCR to detect their expression levels in reed canary grass leaves under drought, salt, cadmium, and waterlogging stresses. Four algorithms were used to assess the stability of the expression levels of the candidate reference genes. The most stably expressed genes were UBC and H3 under drought Cd, ETF and CYT under salt stress, and ETF and TUB under waterlogging stress. GAPDH was found to be less stable under abiotic stresses. PIP-1, PAL, NAC 90, and WRKY 72A were selected as response genes for quantitative expression assessment under drought, salt, Cd, and waterlogging stresses to confirm the accuracy of the selected stable reference genes. These results provide a theoretical reference for assessing gene expression in reed canary grass under abiotic stresses.

Complete chloroplast genomes of three wild perennial Hordeum species from Central Asia: genome structure, mutation hotspot, phylogenetic relationships, and comparative analysis.

Hordeum L. is widely distributed in mountain or plateau of subtropical and warm temperate regions around the world. Three wild perennial Hordeum species, including H. bogdanii, H. brevisubulatum, and H. violaceum, have been used as forage and for grassland ecological restoration in high-altitude areas in recent years. To date, the degree of interspecies sequence variation in the three Hordeum species within existing gene pools is still not well-defined. Herein, we sequenced and assembled chloroplast (cp) genomes of the three species. The results revealed that the cp genome of H. bogdanii showed certain sequence variations compared with the cp genomes of the other two species (H. brevisubulatum and H. violaceum), and the latter two were characterized by a higher relative affinity. Parity rule 2 plot (PR2) analysis illuminated that most genes of all ten Hordeum species were concentrated in nucleotide T and G. Numerous single nucleotide polymorphism (SNP) and insertion/deletion (In/Del) events were detected in the three Hordeum species. A series of hotspots regions (tRNA-GGU ~ tRNA-GCA, tRNA-UGU ~ ndhJ, psbE ~ rps18, ndhF ~ tRNA-UAG, etc.) were identified by mVISTA procedures, and the five highly polymorphic genes (tRNA-UGC, tRNA-UAA, tRNA-UUU, tRNA-UAC, and ndhA) were proved by the nucleotide diversity (Pi). Although the distribution and existence of cp simple sequence repeats (cpSSRs) were predicted in the three Hordeum cp genomes, no rearrangement was found between them. A similar phenomenon has been found in the cp genome of the other seven Hordeum species, which has been published so far. In addition, evolutionary relationships were reappraised based on the currently reported cp genome of Hordeum L. This study offers a framework for gaining a better understanding of the evolutionary history of Hordeum species through the re-examination of their cp genomes, and by identifying highly polymorphic genes and hotspot regions that could provide important insights into the genetic diversity and differentiation of these species.

Hepatocellular carcinoma cells remodel the pro-metastatic tumour microenvironment through recruitment and activation of fibroblasts via paracrine Egfl7 signaling.

BACKGROUND: The tumour microenvironment consists of a complex and dynamic milieu of cancer cells, including tumour-associated stromal cells (leukocytes, fibroblasts, vascular cells, etc.) and their extracellular products. During invasion and metastasis, cancer cells actively remodel the tumour microenvironment and alterations of microenvironment, particularly cancer-associated fibroblasts (CAFs), can promote tumour progression. However, the underlying mechanisms of the CAF formation and their metastasis-promoting functions remain unclear. METHODS: Primary liver fibroblasts and CAFs were isolated and characterized. CAFs in clinical samples were identified by immunohistochemical staining and the clinical significance of CAFs was also analysed in two independent cohorts. A transwell coculture system was used to confirm the role of HCC cells in CAF recruitment and activation. qRT-PCR, western blotting and ELISA were used to screen paracrine cytokines. The role and mechanism of Egfl7 in CAFs were explored via an in vitro coculture system and an in vivo mouse orthotopic transplantation model. RESULTS: We showed that CAFs in hepatocellular carcinoma (HCC) are characterized by the expression of α-SMA and that HCC cells can recruit liver fibroblasts (LFs) and activate them to promote their transformation into CAFs. High α-SMA expression, indicating high CAF infiltration, was correlated with malignant characteristics. It was also an independent risk factor for HCC survival and could predict a poor prognosis in HCC patients. Then, we demonstrated that EGF-like domain multiple 7 (Egfl7) was preferentially secreted by HCC cells, and exhibited high potential to recruit and activate LFs into the CAF phenotype. The ability of Egfl7 to modulate LFs relies upon increased phosphorylation of FAK and AKT via the receptor ανß3 integrin. Strikingly, CAFs activated by paracrine Egfl7 could further remodel the tumour microenvironment by depositing fibrils and collagen and in turn facilitate HCC cell proliferation, invasion and metastasis. CONCLUSION: Our data highlighted a novel role of Egfl7 in remodelling the tumour microenvironment: it recruits LFs and activates them to promote their transformation into CAFs via the ανß3 integrin signaling pathway, which further promotes HCC progression and contributes to poor clinical outcomes in HCC patients. Video Abstract.

Association of oxidative balance score with sleep quality: NHANES 2007-2014.

BACKGROUND: Oxidative stress is correlated with sleep quality. A common tool for evaluating dietary and lifestyle exposures to oxidative stress is the Oxidative Balance Score (OBS), with higher OBS suggesting more substantial antioxidant exposures. The relationship between OBS and sleep quality is unclear. Investigating the association between OBS and sleep quality was the purpose of this study. METHODS: To figure out the relationship between OBS and sleep quality, we utilized weighted linear models and weighted logistic regression. Adjusted models were also examined. RESULTS: 6300 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014 were recruited. OBS was negatively associated with sleep disorder (OR: 0.97; 95 % CI: 0.94-0.99), and positively associated with sleep duration (MD: 0.02; 95%CI: 0.01-0.03). Within the range of OBS > 24, each unit increase in OBS will result in a 40 % reduction in sleep disorder, and a 26 % increasement in sleep duration after adjustment (all P for trend <0.05). Dietary and lifestyle components were closely related to sleep quality independently. The relationship between OBS and sleep quality was prominent in the female population under 50 years of age. After stratification by education level, this relationship persisted. LIMITATION: This research was cross-sectional design, and it was not possible to deduce causality. CONCLUSION: Diet and lifestyle might influence sleep quality by modulating oxidative balance. Antioxidant diets and lifestyles were important in reducing sleep problems and our study also provided new ideas for improving sleep quality.

Integrating Full-Length Transcriptome and RNA Sequencing of Siberian Wildrye (Elymus sibiricus) to Reveal Molecular Mechanisms in Response to Drought Stress.

Drought is one of the most significant limiting factors affecting plant growth and development on the Qinghai-Tibet Plateau (QTP). Mining the drought-tolerant genes of the endemic perennial grass of the QTP, Siberian wildrye (Elymus sibiricus), is of great significance to creating new drought-resistant varieties which can be used in the development of grassland livestock and restoring natural grassland projects in the QTP. To investigate the transcriptomic responsiveness of E. sibiricus to drought stress, PEG-induced short- and long-term drought stress was applied to two Siberian wildrye genotypes (drought-tolerant and drought-sensitive accessions), followed by third- and second-generation transcriptome sequencing analysis. A total of 40,708 isoforms were detected, of which 10,659 differentially expressed genes (DEGs) were common to both genotypes. There were 2107 and 2498 unique DEGs in the drought-tolerant and drought-sensitive genotypes, respectively. Additionally, 2798 and 1850 DEGs were identified in the drought-tolerant genotype only under short- and long-term conditions, respectively. DEGs numbering 1641 and 1330 were identified in the drought-sensitive genotype only under short- and long-term conditions, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that all the DEGs responding to drought stress in E. sibiricus were mainly associated with the mitogen-activated protein kinase (MAKP) signaling pathway, plant hormone signal transduction, the linoleic acid metabolism pathway, the ribosome pathway, and plant circadian rhythms. In addition, Nitrate transporter 1/Peptide transporter family protein 3.1 (NPF3.1) and Auxin/Indole-3-Acetic Acid (Aux/IAA) family protein 31(IAA31) also played an important role in helping E. sibiricus resist drought. This study used transcriptomics to investigate how E. sibiricus responds to drought stress, and may provide genetic resources and references for research into the molecular mechanisms of drought resistance in native perennial grasses and for breeding drought-tolerant varieties.

Fibroblast growth factor 10 alleviates acute lung injury by inhibiting excessive autophagy via Nrf2.

Acute lung injury (ALI) is associated with an increased incidence of respiratory diseases, which are devastating clinical disorders with high global mortality and morbidity. Evidence confirms that fibroblast growth factors (FGFs) play key roles in mediating ALI. Mice were treated with LPS (lipopolysaccharide: 5 mg/kg, intratracheally) to establish an in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were used to mimic the ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) which improved LPS-induced ALI, including histopathological changes, and reduced pulmonary edema. At the cellular level, FGF10 pretreatment (10 ng/mL) alleviated LPS-induced ALI accompanied by reduced reactive oxygen species (ROS) accumulation and inflammatory responses, such as IL-1ß, IL-6, and IL-10, as well as suppressed excessive autophagy. Additionally, immunoblotting and co-immunoprecipitation showed that FGF10 activated nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway via Nrf2 nuclear translocation by promoting the interaction between p62 and keap1, thereby preventing LPS-induced ALI. Nrf2 knockout significantly reversed these protective effects of FGF10. Together, FGF10 protects against LPS-induced ALI by restraining autophagy via p62-Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway, implying that FGF10 could be a novel therapy for ALI.

Development and validation of a clinical survival model for young-onset colorectal cancer with synchronous liver-only metastases: a SEER population-based study and external validation.

Background: The morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM. Methods: The YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly (1488 and 639 patients, respectively). Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model's predictive accuracy. The calibration plots were used to determine the Nomogram's discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram's net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software. Results: The Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score<234) had significantly better survival outcomes than middle-risk (234-318) and high-risk (>318) patients (P < 0.001). Conclusion: A nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment.

Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Analysis of Complete Chloroplast Genome: Structure, Phylogenetic Relationships of Galega orientalis and Evolutionary Inference of Galegeae.

Galega orientalis, a leguminous herb in the Fabaceae family, is an ecologically and economically important species widely cultivated for its strong stress resistance and high protein content. However, genomic information of Galega orientalis has not been reported, which limiting its evolutionary analysis. The small genome size makes chloroplast relatively easy to obtain genomic sequence for phylogenetic studies and molecular marker development. Here, the chloroplast genome of Galega orientalis was sequenced and annotated. The results showed that the chloroplast genome of G. orientalis is 125,280 bp in length with GC content of 34.11%. A total of 107 genes were identified, including 74 protein-coding genes, 29 tRNAs and four rRNAs. One inverted repeat (IR) region was lost in the chloroplast genome of G. orientalis. In addition, five genes (rpl22, ycf2, rps16, trnE-UUC and pbf1) were lost compared with the chloroplast genome of its related species G. officinalis. A total of 84 long repeats and 68 simple sequence repeats were detected, which could be used as potential markers in the genetic studies of G. orientalis and related species. We found that the Ka/Ks values of three genes petL, rpl20, and ycf4 were higher than one in the pairwise comparation of G. officinalis and other three Galegeae species (Calophaca sinica, Caragana jubata, Caragana korshinskii), which indicated those three genes were under positive selection. A comparative genomic analysis of 15 Galegeae species showed that most conserved non-coding sequence regions and two genic regions (ycf1 and clpP) were highly divergent, which could be used as DNA barcodes for rapid and accurate species identification. Phylogenetic trees constructed based on the ycf1 and clpP genes confirmed the evolutionary relationships among Galegeae species. In addition, among the 15 Galegeae species analyzed, Galega orientalis had a unique 30-bp intron in the ycf1 gene and Tibetia liangshanensis lacked two introns in the clpP gene, which is contrary to existing conclusion that only Glycyrrhiza species in the IR lacking clade (IRLC) lack two introns. In conclusion, for the first time, the complete chloroplast genome of G. orientalis was determined and annotated, which could provide insights into the unsolved evolutionary relationships within the genus Galegeae.

Application of metabolomics in urolithiasis: the discovery and usage of succinate.

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.

A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability, extracellular matrix-inducing bioactivity and function preservation.

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency. However, the inadequate durability, deficient pro-secretion of extracellular matrix (ECM) and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect. Herein, a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism (photo-triggered and dynamic covalent bonds). Owing to its characteristic networks, the synergistic effect of the hydrogel for vocal folds (VFs) vibration and phonation is adequately demonstrated. Notably, owing to its inherent bioactivity of polysaccharides, the hydrogel could significantly enhance the secretion of major components (type I/III collagen and elastin) in the lamina propria of the VFs both in vivo and in vitro. In a rabbit model for glottic insufficiency, the optimized hydrogel (C1A1) has demonstrated a durability far superior to that of the commercially made hyaluronic acid (HA) Gel. More importantly, owing to the ECM-inducing bioactivity, the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel, and were similar to those of the normal VFs. Taken together, through a simple-yet-effective strategy, the novel hydrogel has demonstrated outstanding durability, ECM-inducing bioactivity and physiological function preservation, therefore has an appealing clinical value for treating glottic insufficiency.

An Acquired Anterior Glottic Web Model by Heat Injury with a Laryngoscopic Approach in a Rabbit.

Acquired anterior glottic webs (AGW) can lead to abnormally elevated phonatory pitch, dysphonia, and airway obstruction requiring urgent intervention. In this study, we construct a novel AGW rabbit model using heat injury by a laryngoscopic way. A primary study was conducted to identify the injury depth in rabbits' vocal folds (VFs) by graded heat energy, and the heat energy for the incurrence of epithelial layer, lamina propria, and muscular layer (ML) injury was 25, 30 and 35 W, respectively. Then, four different models were designed based on the depth and degree of the injury to determine the optimal procedure for AGW formation. Morphological features, vibratory capacity, and histopathologic features of the AGW were correspondingly evaluated. The procedure for conferring the heat injury to the depth of ML and the extent of anterior commissure and middle part of bilateral VFs showed the highest success rate of AGW formation (95%, 19/20). For its low cost, effectiveness, and stability for AGW formation, the heat injury rabbit model with a laryngoscopic approach may provide a new platform for testing novel anti-adhesion materials and bioengineered therapies. Impact Statement Tissue engineering based on biomaterials has been a very hot research field and may be introduced to prevent the acquired anterior glottic web (AGW) formation. However, lacking a widely recognized animal model for AGW has limited the trial of anti-adhesion materials in the larynx. In this study, we have developed a novel rabbit model for AGW formation by conferring a heat injury under a laryngoscope; this model is cheap, effective, and stable for the anti-adhesion materials and bioengineered therapies. Thus, this research would arouse crucial interest and be widely employed.