Deep metagenomic characterization of the gut virome in pregnant women with preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Prevalence of depressive symptoms in patients with advanced schistosomiasis in China: A systematic review and meta-analysis.

BACKGROUND: Advanced schistosomiasis is the most serious outcome of infection and has a negative impact on both physical fitness and mental health of patients, the latter of which has long been overlooked. Therefore, we performed this systematic review and meta-analysis to estimate the overall prevalence of depressive symptoms, one of the most common mental problems, in patients with advanced schistosomiasis in China. METHODS: Six electronic databases were searched for studies reporting the prevalence of depressive symptoms in the targeted patients. Assessments were pooled using a fixed- or random-effects model based on heterogeneity test. Subgroup analyses were further performed and differences between/among groups were examined using the chi-squared test. The protocol had previously been registered in PROSPERO (CRD42023406708). RESULTS: A total of 11 studies with 1,673 participants were included. The pooled prevalence of depressive symptoms in advanced schistosomiasis in China was 62.01% (95% CI: 51.30% - 72.72%), with a significant heterogeneity among studies. Depressive symptoms were more prevalent in patients with complications and more than half of the patients suffered a mild- or moderate-level of depression. No publication bias was found, and sensitivity analysis showed a stable result. CONCLUSIONS: The overall prevalence of depressive symptoms in advanced schistosomiasis in China was high enough to warrant psychotherapeutic interventions, especially for patients with complications. This would greatly prevent or/and reduce depression and improve their quality of life.

Effects of lavender essential oil inhalation aromatherapy on depression and sleep quality in stroke patients: A single-blind randomized controlled trial.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has major implications for rehabilitation, motor recovery, activities of daily living, social and interpersonal functioning, and mortality. In view of the side effects of antidepressants, aromatherapy, a widely used non-pharmacological therapy, has received growing attention in recent years for its benefits of reduced complications, accessibility, and effectiveness. This study was designed to assess the effects of inhalation aromatherapy with lavender essential oil on depression and sleep quality in patients with PSD. MATERIALS AND METHODS: Forty patients with PSD were enrolled and randomized into experimental and placebo groups. Experimental-group patients inhaled microencapsulated lavender essential oil every night at bedtime over a period of 4 weeks. A nonwoven bag containing 2.3 g of microcapsules with about 1.5 g of lavender essential oil was placed on or under the patient's pillow, depending on the patient's scent sensitivity. Placebo-group patients used the empty nonwoven bags for the same period as the experimental group. The 17-item Hamilton Rating Scale for Depression (HAMD-17), the Zung Self-Rating Depression Scale (SDS), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure outcomes. RESULTS: The HAMD-17 score, SDS score, and PSQI score showed statistically significant differences between both groups before and after intervention (P ≤ 0.01). The improvement in the experimental group was more marked than in the placebo group (P < 0.05). CONCLUSION: Lavender essential oil inhalation aromatherapy may help reduce depression and improve sleep quality in patients with PSD.

Novel Signaling Pathway and NSC689534 as a Potential Drug Candidate for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. METHODS: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. RESULTS: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. CONCLUSIONS: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.

Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study.

Primary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture-based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co-occurred with KIT mutation and amplification. The most common pathways affected were the mitogen-activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression-free survival (hazard ratio [HR] = 5.14, 95% confidence interval [CI] = 1.32-19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22-15.30). Treatment with immune-checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01-0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs.

Comparison of Thyroglobulin and Thyroid Function in Pregnant Women between Counties with a Median Urinary Iodine Concentration of 100-149 µg/L and 150-249 µg/L.

Objective: This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 µg/L maintained through sustainable universal salt iodization. Methods: This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits. Results: The median UIC (mUIC) in pregnant women was 130.8 µg/L (interquartile range = 91.5-198.1 µg/L) in the counties with an mUIC of 100-149 µg/L (Group I), and 172.0 µg/L (interquartile range = 123.5-244.4 µg/L) in the counties with an mUIC of 150-249 µg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (µg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken. Conclusion: Compared with an mUIC of 150-249 µg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 µg/L achieved through sustainable universal salt iodization in Fujian Province, China.

Leucine zipper protein 1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling.

INTRODUCTION: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. OBJECTIVES: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. METHODS: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. RESULTS: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. CONCLUSION: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

Lipidomics reveals the lipid metabolism disorders in Fructus Psoraleae-induced hepatotoxicity in rats with kidney-yin deficiency syndrome.

Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Emergency Complex Higher-risk and Indicated Patients.

OBJECTIVE: There is a large population of patients classified as complex higher-risk and indicated patients (CHIPs) in China with a poor prognosis. The treatment of these patients is complex and challenging, especially when acute cardiac events occur, such as acute coronary syndrome (ACS) or heart failure. Pharmacotherapy and some mechanical circulatory support (MCS) therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention (PCI). LDL-C is an important pathogenic factor in atherosclerosis, and the target of blood lipid control. Recent studies have revealed that lipoprotein(a) [Lp(a)], which is formed when a covalent bond between apolipoprotein(a) and apolipoprotein B-100 is made, produces an LDL-like particle. This particle is an independent risk factor for the development of atherosclerosis, and is closely correlated to stent thrombosis and restenosis. Furthermore, this requires active intervention. PCSK9 inhibitors have been used in lipid-lowering treatment, and preventing atherosclerosis. The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS, and the association between the change in Lp(a) and survival after 2 years of follow-up. METHODS: The present real-world, prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020, and these patients were followed up for 2 years. These patients were divided into two groups: PCSK9 group (n=161) given the combined PCSK9 inhibitor (140 mg of evolocumab every 2 weeks) and statins-based therapy, and SOC group (n=160) treated with statin-based lipid-lowering therapy alone. Then, the change in lipid index was measured, and the cardiovascular (CV) event recurrence rate was evaluated after one month and 2 years. Afterwards, the contribution of serum lipid parameters, especially the Lp(a) alteration, in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed. RESULTS: The LDL-C level was significantly reduced in both groups: 52.3% in the PCSK9 group and 32.3% (P<0.001) in the SOC group. It is noteworthy that the Lp(a) level decreased by 13.2% in the PCSK9 group, but increased by 30.3% in the SOC group (P<0.001). Furthermore, the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period. In the PCSK9 group, the Lp(a) reduction was associated with the baseline Lp(a) levels of the patients (r2 =-0.315, P<0.001). Moreover, the decrease in Lp(a) contributed to the decline in CV events in patients who received ACS CHIPs-PCI, and the decrease in Lp(a) level was independent of the LDL-C level reduction. CONCLUSION: The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a) levels in ACS CHIPs-PCI. However, further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.

Targeted demethylation of the CDO1 promoter based on CRISPR system inhibits the malignant potential of breast cancer cells.

BACKGROUND: Cysteine dioxygenase 1 (CDO1) is frequently methylated, and its expression is decreased in many human cancers including breast cancer (BC). However, the functional and mechanistic aspects of CDO1 inactivation in BC are poorly understood, and the diagnostic significance of serum CDO1 methylation remains unclear. METHODS: We performed bioinformatics analysis of publicly available databases and employed MassARRAY EpiTYPER methylation sequencing technology to identify differentially methylated sites in the CDO1 promoter of BC tissues compared to normal adjacent tissues (NATs). Subsequently, we developed a MethyLight assay using specific primers and probes for these CpG sites to detect the percentage of methylated reference (PMR) of the CDO1 promoter. Furthermore, both LentiCRISPR/dCas9-Tet1CD-based CDO1-targeted demethylation system and CDO1 overexpression strategy were utilized to detect the function and underlying mechanism of CDO1 in BC. Finally, the early diagnostic value of CDO1 as a methylation biomarker in BC serum was evaluated. RESULTS: CDO1 promoter was hypermethylated in BC tissues, which was related to poor prognosis (p < .05). The CRISPR/dCas9-based targeted demethylation system significantly reduced the PMR of CDO1 promotor and increased CDO1 expression in BC cells. Consequently, this leads to suppression of cell proliferation, migration and invasion. Additionally, we found that CDO1 exerted a tumour suppressor effect by inhibiting the cell cycle, promoting cell apoptosis and ferroptosis. Furthermore, we employed the MethyLight to detect CDO1 PMR in BC serum, and we discovered that serum CDO1 methylation was an effective non-invasive biomarker for early diagnosis of BC. CONCLUSIONS: CDO1 is hypermethylated and acts as a tumour suppressor gene in BC. Epigenetic editing of abnormal CDO1 methylation could have a crucial role in the clinical treatment and prognosis of BC. Additionally, serum CDO1 methylation holds promise as a valuable biomarker for the early diagnosis and management of BC.

Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors.

BACKGROUND: To date, data on the efficacy of targeted therapies for mucosal melanoma (MM) are limited. In this study, we analyzed genetic alterations according to the primary site of origin, which could provide clues for targeted therapy for MM. METHODS: We conducted a retrospective cohort study of 112 patients with MM. Targeted sequencing was performed to analyze genetic aberrations. Kaplan-Meier analysis was conducted with the log-rank test to compare the significance among subgroups. RESULTS: In total, 112 patients with MM were included according to the anatomic sites: 38 (33.9%) in the head and neck, 22 (19.6%) in the genitourinary tract, 21 (18.8%) in the anorectum, 19 (17.0%) in the esophagus, 10 (8.9%) in the uvea, and 2 (1.8%) in the small bowel. The most significantly mutated genes included BRAF (17%), KIT (15%), RAS (15%), TP53 (13%), NF1 (12%), SF3B1 (11%), GNA11 (7%), GNAQ (5%), and FBXW7 (4%). A large number of chromosomal structural variants was found. The anatomic sites of esophagus and small bowel were independent risk factors for progression-free survival (PFS, hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.42-9.45, P < 0.0001) and overall survival (OS, HR 5.26, 95% CI 2.51-11.03, P < 0.0001). Casitas B-lineage lymphoma (CBL) mutants showed significantly poorer PFS and OS. In contrast, MM patients who received immune checkpoint inhibitors (ICIs) had a significantly more favorable OS (HR 0.39, 95% CI 0.20-0.75, P = 0.008). CONCLUSIONS: Our findings reveal the genetic features of patients with MM, mainly across six anatomic sites, offering a potential avenue for targeted therapies.

Prognostic modelling of colorectal cancer based on oxidative stress-related genes.

BACKGROUND: Colon cancer is one of the most prevalent cancers of the digestive tract. There is mounting evidence that genes associated with oxidative stress might affect the tumour immune microenvironment during tumour growth, maintenance, and treatment response. However, how oxidative stress-related genes affect prognostic importance, tumour microenvironment features, and treatment outcomes in colon cancer patients has not been fully elucidated. METHODS: The Cancer Genome Atlas (TCGA) dataset was used to construct a signature model and nomogram using step and Cox regression approaches to investigate how gene expression affected immunological responses to colon cancer, including the degree of immune infiltration, MSI, and drug sensitivity. RESULTS AND CONCLUSIONS: The nomogram and the signature model had strong prognostic potential for colon cancer, with gene expression highly correlated with multiple immune cells. The first signature model and nomogram including oxidative stress-related genes were constructed for use in clinical decision-making. In addition, SRD5A1, GSR, TXN, TRAF2 and TRAP1 were identified as potential biomarkers for colon cancer diagnosis and indicators for immunotherapy.

Surgical Treatment for Chest "Lock" Keloid Using Autologous Split-Thickness Skin Grafting and Postoperative Radiotherapy.

BACKGROUND: The treatment of chest "lock" keloids is challenging due to skin defects and a high recurrence rate. OBJECTIVE: Evaluation of the effectiveness of autologous split-thickness skin graft with local radiotherapy for treating chest "lock" keloids. METHODSAND MATERIALS: Fifty-seven patients with chest "lock" keloids were treated from July 2018 to September 2020. The skin defects were closed with an autologous split-thickness skin graft (STSG) and vacuum sealing drainage. The donor and the recipient sites received the first session of radiotherapy 72 hours postoperation for 3 consecutive days. Patients underwent follow-up examinations 12 months after surgery. The Patient and Observer Scar Assessment Scale (POSAS) was used to assess the treatment outcome. RESULTS: Except for the complaints of pain, which did not improve in the patients' assessments (p = .368), POSAS improved significantly after treatment (p < .0001). The cure rate (including cured and partially cured scars) was 100%. No keloid recurrence was observed during the follow-up period. CONCLUSION: The procedure of treating chest "lock" keloid by keloid debulking and autologous STSG followed by postoperational radiotherapy is a novel combined methodology for treating keloids.

Surgical Core Excision With Tongue Flap Closure in Combination With Electron Beam Radiotherapy in the Treatment of Ear Keloids.

BACKGROUND: Ear keloids are disfiguring disorders resistant to various treatments. OBJECTIVE: The authors aimed to assess the efficacy of surgical treatment of ear keloids in a Chinese population using a tongue flap with electron beam radiotherapy. METHODS: The authors conducted a retrospective analysis of 41 patients treated at the Affiliated Hospital of Nantong University between January 2018 and May 2021. Core excision with a tongue flap was performed, followed by 3 days of electron beam radiotherapy and 3 to 6 months of pressure clip application. The Vancouver Scar Scale (VSS) and the Visual Analog Scale (VAS) were used to assess the results. RESULTS: The mean age of the patients was 28.10 years (9-61 years). Postoperative follow-up ranged from 5 to 32 months (mean:12.07). The patients underwent 3 days of postoperative radiotherapy followed by pressure clips for 2 to 6 months. Thirty-seven patients had no recurrence, whereas 4 had a mild recurrence (<3 mm in height) with redness and itchiness. The VSS and VASscores significantly decreased. (p < .05). CONCLUSION: Excision with a tongue flap and radiotherapy can be used as the primary treatment for ear keloids considering the good outcome and long-term management.

Engineered Sucrose Metabolism Improves the Smut Disease Suppression Potency of Pseudomonas sp. ST4.

Sporisorium scitamineum and Ustilago maydis are two fungal pathogens causing severe sugarcane and maize diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases. We showed recently that in the presence of exogenous glucose, the Pseudomonas sp. strain ST4 could block the fungal mating and display a strong disease suppression potency on S. scitamineum. With the aim of conferring strain ST4 the ability to metabolize sucrose in plants for glucose production, we identified a strong native promoter pSsrA in strain ST4 and additional promoter elements to facilitate translation and peptide translocation for the construction of a fusion gene encoding sucrose metabolism. The cscA gene encoding sucrose hydrolase from Pseudomonas protegens Pf-5 was fused to the promoter pSsrA, a translational coupler bicistronic design and a Tat signal peptide, which was then cloned into mini-Tn7 transposon. This synthetic gene cassette was integrated into the chromosome of strain ST4, and the resultant engineered strain ST4E was able to hydrolyze sucrose with high efficiency and displayed elevated inhibitory activity on the mating and virulence of S. scitamineum and U. maydis. The findings from this study provide a valuable device and useful clues for the engineering of sucrose metabolism in non- or weak-sucrose-utilizing bacterial strains and present an improved biocontrol agent against plant smut pathogens. IMPORTANCE Sporisorium scitamineum and Ustilago maydis are typical dimorphic fungi causing severe sugarcane and maize smut diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases. We previously demonstrated that the biocontrol strain Pseudomonas sp. ST4 could block the fungal mating and displays a strong suppression potency on smut diseases, while it was unable to utilize the host-sourced sucrose for glucose production critical for antifungus efficiency. In this study, we constructed a high-expression gene cassette for minitransposon-mediated genome integration and sucrose hydrolysis in the bacterial periplasmic space. The resultant engineered strain ST4E was able to hydrolyze sucrose and inhibit the mating and hyphal growth of S. scitamineum and U. maydis. These findings provide a valuable tool and useful clues for the engineering of sucrose metabolism in non- or weak-sucrose-utilizing bacterial strains and present an improved biocontrol agent against plant smut pathogens.

Formyl peptide receptor 2 as a potential therapeutic target for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a global health burden whose existing treatment is largely dependent on anti-inflammatory agents. Despite showing some therapeutic actions, their clinical efficacy and adverse events are unacceptable. Resolution as an active and orchestrated phase of inflammation involves improper inflammatory response with three key triggers, specialized pro-resolving mediators (SPMs), neutrophils and phagocyte efferocytosis. The formyl peptide receptor 2 (FPR2/ALX) is a human G protein-coupled receptor capable of binding SPMs and participates in the resolution process. This receptor has been implicated in several inflammatory diseases and its association with mouse model of IBD was established in some resolution-related studies. Here, we give an overview of three reported FPR2/ALX agonists highlighting their respective roles in pro-resolving strategies.

Integrated analysis from multi-center studies identities m7G-derived modification pattern and risk stratification system in skin cutaneous melanoma.

The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.

[Construction of Nursing Quality Index System in Assisted Reproduction Hospitals Based on the Model of "Three-Dimensional Quality Structure"].

Objective To construct a nursing quality index system for the assisted reproduction hospitals integrating outpatient department,wards,and operating rooms and provide a reference for the application of the system in the quality control of clinical reproductive care. Method On the basis of Donabedian's health care quality model of structure-process-outcome,we established a nursing quality index system for assisted reproduction hospitals via literature retrieval,semi-structured interviews,Delphi method,and analytic hierarchy process. Results The two rounds of expert's questionnaire survey demonstrated the response rates of 100% and 92%,the expert authority coefficients of 0.911 and 0.919,and the Kendall coefficients of concordance of 0.228 and 0.253,respectively (all P<0.001).The nursing quality index system for assisted reproduction hospitals was established,which consisted of 3 first-level indicators,13 second-level indicators,and 39 third-level indicators. Conclusion The nursing quality index system of assisted reproduction hospitals is comprehensive,systematic and reasonable,which can be used as quality management standard and provide a reference for clinical application.

Paraoxonase 1 Ameliorates Renal Lipotoxicity by Activating Lipophagy and Inhibiting Pyroptosis.

Several studies in recent years have shown that lipid overload causes lipotoxic damage to the kidney, and oxidative stress, inflammation, and autophagic arrest are all important mechanisms of renal lipotoxicity. However, effective measures with therapeutic effects on renal lipotoxicity are limited. The present study indicated the protective effect of the paraoxonase 1 (PON1) against renal lipotoxicity in high-fat diet-fed scavenger receptor class B type I-deficient (SR-BI-/-) mice. The results showed that SR-BI-/- mice exhibited significant renal pathologic characteristics, such as oxidative stress, inflammation, and fibrosis, under a normal chow diet, and were accompanied by dyslipidemia and reduced plasma PON1 activity and renal PON1 levels. PON1 overexpression significantly attenuated the above pathologic changes in the kidneys of SR-BI-/- mice fed with a high-fat diet. Mechanistically, PON1 may ameliorate renal oxidative stress by reducing reactive oxygen species production, reduce renal lipid accumulation by inhibiting AKT/mechanistic target of rapamycin kinase pathway to activate lipophagy, and reduce the occurrence of inflammation and cell death by inhibiting Nod-like receptor family protein 3 inflammasome-mediated pyroptosis. The present study is the first to show that PON1 overexpression can effectively alleviate renal lipotoxicity injury, and PON1 may be a promising therapeutic strategy for the treatment of renal lipotoxicity-related diseases.