ι-Carrageenan catabolism is initiated by key sulfatases in the marine bacterium Pseudoalteromonas haloplanktis LL1.

Marine bacteria contribute substantially to cycle macroalgae polysaccharides in marine environments. Carrageenans are the primary cell wall polysaccharides of red macroalgae. The carrageenan catabolism mechanism and pathways are still largely unclear. Pseudoalteromonas is a representative bacterial genus that can utilize carrageenan. We previously isolated the strain Pseudoalteromonas haloplanktis LL1 that could grow on ι-carrageenan but produce no ι-carrageenase. Here, through a combination of bioinformatic, biochemical, and genetic analyses, we determined that P. haloplanktis LL1 processed a desulfurization-depolymerization sequential pathway for ι-carrageenan utilization, which was initiated by key sulfatases PhSulf1 and PhSulf2. PhSulf2 acted as an endo/exo-G4S (4-O-sulfation-ß-D-galactopyranose) sulfatase, while PhSulf1 was identified as a novel endo-DA2S sulfatase that could function extracellularly. Because of the unique activity of PhSulf1 toward ι-carrageenan rather than oligosaccharides, P. haloplanktis LL1 was considered to have a distinct ι-carrageenan catabolic pathway compared to other known ι-carrageenan-degrading bacteria, which mainly employ multifunctional G4S sulfatases and exo-DA2S (2-O-sulfation-3,6-anhydro-α-D-galactopyranose) sulfatase for sulfate removal. Furthermore, we detected widespread occurrence of PhSulf1-encoding gene homologs in the global ocean, indicating the prevalence of such endo-acting DA2S sulfatases as well as the related ι-carrageenan catabolism pathway. This research provides valuable insights into the enzymatic processes involved in carrageenan catabolism within marine ecological systems.IMPORTANCECarrageenan is a type of linear sulfated polysaccharide that plays a significant role in forming cell walls of marine algae and is found extensively distributed throughout the world's oceans. To the best of our current knowledge, the ι-carrageenan catabolism in marine bacteria either follows the depolymerization-desulfurization sequential process initiated by ι-carrageenase or starts from the desulfurization step catalyzed by exo-acting sulfatases. In this study, we found that the marine bacterium Pseudoalteromonas haloplanktis LL1 processes a distinct pathway for ι-carrageenan catabolism employing a specific endo-acting DA2S-sulfatase PhSulf1 and a multifunctional G4S sulfatase PhSulf2. The unique PhSulf1 homologs appear to be widely present on a global scale, indicating the indispensable contribution of the marine bacteria containing the distinct ι-carrageenan catabolism pathway. Therefore, this study would significantly enrich our understanding of the molecular mechanisms underlying carrageenan utilization, providing valuable insights into the intricate roles of marine bacteria in polysaccharide cycling in marine environments.

Haplotype-resolved gapless genome and chromosome segment substitution lines facilitate gene identification in wild rice.

The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.

Genome-Wide Identification and Expression Analysis of the Starch Synthase Gene Family in Sweet Potato and Two of Its Closely Related Species.

The starch synthase (SS) plays important roles in regulating plant growth and development and responding to adversity stresses. Although the SS family has been studied in many crops, it has not been fully identified in sweet potato and its two related species. In the present study, eight SSs were identified from Ipomoea batatas (I. batata), Ipomoea trifida (I. trifida), and Ipomoea trlioba (I. trlioba), respectively. According to the phylogenetic relationships, they were divided into five subgroups. The protein properties, chromosomal location, phylogenetic relationships, gene structure, cis-elements in the promoter, and interaction network of these proteins were also analyzed; stress expression patterns were systematically analyzed; and real-time polymerase chain reaction (qRT-PCR) analysis was performed. Ipomoea batatas starch synthase (IbSSs) were highly expressed in tuber roots, especially Ipomoea batatas starch synthase 1 (IbSS1) and Ipomoea batatas starch synthase 6 (IbSS6), which may play an important role in root development and starch biosynthesis. At the same time, the SS genes respond to potassium deficiency, hormones, cold, heat, salt, and drought stress. This study offers fresh perspectives for enhancing knowledge about the roles of SSs and potential genes to enhance productivity, starch levels, and resistance to environmental stresses in sweet potatoes.

A wild rice CSSL population facilitated identification of salt tolerance genes and rice germplasm innovation.

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.

Potential causal associations between leisure sedentary behaviors, physical activity, sleep traits, and myopia: a Mendelian randomization study.

BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.

Analysis of Bifidobacterium animalis subsp. lactis BB-12 ® and Lactobacillus rhamnosus GG on underweight and malabsorption in premature infants.

OBJECTIVE: This study aimed to explore and analyze the therapeutic effect of the combination of Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG on underweight and malabsorption in premature infants. METHODS: This is a retrospective study. The clinical data of 68 premature infants admitted to Beijing United Family Hospital (Private Secondary Comprehensive Hospital, Chaoyang District, Beijing, China) from January 2016 to January 2022 were analyzed retrospectively. Preterm infants less than 37 weeks of gestational age admitted to the neonatal intensive care unit were included in the study. Patients with intestinal malformations, necrotizing enterocolitis, etc., who require long-term fasting were excluded. A telephone follow-up was performed 3-6 months after discharge. They were classified as treatment groups A and B according to the treatment plan. The treatment group A included parenteral nutrition, enteral nutrition, etc. In treatment group B, based on treatment group A, the premature infants were treated with Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG. The time to regain birthweight and the weight on day 30 were compared between the two groups, as was the duration of transition from parenteral nutrition to total enteral nutrition. RESULTS: The time of weight regain birthweight in group B was shorter than that in group A (t=-2.560; t=-4.287; p<0.05). The increase of weight on day 30 in group B was significantly higher than that in group A (t=2.591; t=2.651; p<0.05). The time from parenteral nutrition to total enteral nutrition in group B was shorter than that in group A (z=-2.145; z=-2.236; p<0.05). CONCLUSION: In the treatment of premature infants, the combination of Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG can have a better therapeutic effect on the underweight and malabsorption of premature infants, and this treatment method can be popularized in clinics.

Clinical analysis of PAFAH1B1 gene variants in pediatric patients with epilepsy.

PURPOSE: PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. Our objective was to characterize the genotypes and phenotypes of PAFAH1B1-related epilepsy. METHODS: We conducted a comprehensive analysis of the medical histories, magnetic resonance imaging findings, and video-electroencephalogram recordings of 11 patients with PAFAH1B1 variants at the Neurology Department of Beijing Children's Hospital from June 2017 to November 2022. RESULTS: The age of onset of epilepsy ranged from 2 months to 4 years, with a median onset age of 5 months. Among these 11 patients (comprising 6 boys and 5 girls), all were diagnosed with lissencephaly type 1. Predominantly, generalized tonic-clonic and spasm seizures characterized PAFAH1B1-related epilepsy. Additionally, 10 out of the 11 patients exhibited severe developmental disorders. All patients exhibited de novo variants, with three individuals displaying 17p13.3 deletions linked to haploinsufficiency of PAFAH1B1. Four variants were previously unreported. Notably, three patients with 17p13.3 deletions displayed developmental delay and drug resistant epilepsy, whereas the single patient with mild developmental delay, Intelligence Quotient (IQ) 57 and well-controlled seizures had a splicing-site variant. CONCLUSION: The severity of the phenotype in patients with PAFAH1B1 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. These observations underscore the clinical heterogeneity of PAFAH1B1-related disorders, with most patients exhibiting developmental disorders. Moreover, the severity of epilepsy appears to be linked to genetic variations.

Analysis of Bifidobacterium animalis subsp. lactis BB-12 ® and Lactobacillus rhamnosus GG on underweight and malabsorption in premature infants

SUMMARY OBJECTIVE: This study aimed to explore and analyze the therapeutic effect of the combination of Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG on underweight and malabsorption in premature infants. METHODS: This is a retrospective study. The clinical data of 68 premature infants admitted to Beijing United Family Hospital (Private Secondary Comprehensive Hospital, Chaoyang District, Beijing, China) from January 2016 to January 2022 were analyzed retrospectively. Preterm infants less than 37 weeks of gestational age admitted to the neonatal intensive care unit were included in the study. Patients with intestinal malformations, necrotizing enterocolitis, etc., who require long-term fasting were excluded. A telephone follow-up was performed 3-6 months after discharge. They were classified as treatment groups A and B according to the treatment plan. The treatment group A included parenteral nutrition, enteral nutrition, etc. In treatment group B, based on treatment group A, the premature infants were treated with Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG. The time to regain birthweight and the weight on day 30 were compared between the two groups, as was the duration of transition from parenteral nutrition to total enteral nutrition. RESULTS: The time of weight regain birthweight in group B was shorter than that in group A (t=-2.560; t=-4.287; p<0.05). The increase of weight on day 30 in group B was significantly higher than that in group A (t=2.591; t=2.651; p<0.05). The time from parenteral nutrition to total enteral nutrition in group B was shorter than that in group A (z=-2.145; z=-2.236; p<0.05). CONCLUSION: In the treatment of premature infants, the combination of Bifidobacterium animalis subsp. lactis BB-12® and Lactobacillus rhamnosus GG can have a better therapeutic effect on the underweight and malabsorption of premature infants, and this treatment method can be popularized in clinics.

Independent risk factors for depression in older adult patients receiving peritoneal dialysis for chronic kidney disease.

BACKGROUND: According to the trend of global population aging, the proportion of elderly patients with chronic kidney disease (CKD) is expected to increase. However, there are more than 20 million people in China with decompensated kidney function, of which 19.25% are elderly people. Therefore, special attention should be paid to the education years, sleep quality, anxiety status, comorbidities with diabetes, cardiovascular disease (CVD), and anemia as independent risk factors for depression in elderly CKD patients. This study explores the clinical mana-gement of elderly CKD patients that should address these risk factors to prevent depression and improve their prognosis. AIM: To investigate depression risk factors in older patients receiving peritoneal dialysis, aiding future prevention of depression in these patients. METHODS: This retrospective study included a primary study population of 170 patients with CKD who received peritoneal dialysis from January 2020 to December 2022. We assessed the patients' mental status using the Beck Depression Inventory Score-II (BDI-II), Self-Rating Anxiety Scale (SAS), Anxiety Inventory Score, and the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was employed to identify depression independent risk factors among these patients. RESULTS: The non-depressed group had a significantly longer education period than the depressed group (P < 0.05). The depressed group exhibited significantly higher mental status scores than the non-depressed group (P < 0.001). Patients with diabetes mellitus (DM) or CVD had a higher probability of developing dep-ression. Patients with depression had significantly lower hemoglobin and albumin levels than patients without depression (P < 0.05). Spearman correlation analysis of BDI-II scale scores, measuring depression, indicated positive correlations with BDI-II and SAS scores as risk factors for depression in patients with CKD. In contrast, years of education, hemoglobin levels, and peritoneal Kt/V were negatively correlated, serving as protective factors against depression. An analysis of variance for influences with significant differences in the univariate analysis revealed that years of schooling, BDI-II, SAS, PSQI, DM, CVD, and hemoglobin levels independently influenced depression in older patients with CKD. CONCLUSION: Education, BDI-II, SAS, PSQI, DM, and CVD are independent risk factors for depression in older patients with CKD; therefore, post-treatment psychological monitoring of high-risk patients is crucial to prevent depression.

Genome-Wide Identification and Expression Analysis of Malate Dehydrogenase Gene Family in Sweet Potato and Its Two Diploid Relatives.

Malate dehydrogenase (MDH; EC 1.1.1.37) plays a vital role in plant growth and development as well as abiotic stress responses, and it is widely present in plants. However, the MDH family genes have not been explored in sweet potato. In this study, nine, ten, and ten MDH genes in sweet potato (Ipomoea batatas) and its two diploid wild relatives, Ipomoea trifida and Ipomoea triloba, respectively, were identified. These MDH genes were unevenly distributed on seven different chromosomes among the three species. The gene duplications and nucleotide substitution analysis (Ka/Ks) revealed that the MDH genes went through segmental duplications during their evolution under purifying selection. A phylogenetic and conserved structure divided these MDH genes into five subgroups. An expression analysis indicated that the MDH genes were omni-presently expressed in distinct tissues and responded to various abiotic stresses. A transcription factor prediction analysis proved that Dof, MADS-box, and MYB were the main transcription factors of sweet potato MDH genes. These findings provide molecular features of the MDH family in sweet potato and its two diploid wild relatives, which further supports functional characterizations.

TaBZR1 enhances wheat salt tolerance via promoting ABA biosynthesis and ROS scavenging.

Brassinosteroids (BRs) are vital plant steroid hormones involved in numerous aspects of plant life including growth, development, and responses to various stresses. However, the underlying mechanisms of how BR regulates abiotic stress responses in wheat (Triticum aestivum L.) remain to be elucidated. Here, we find that BR signal core transcription factor BRASSINAZOLE-RESISTANT1 (TaBZR1) is significantly up-regulated by salt treatment. Overexpression of Tabzr1-1D (a gain-of-function TaBZR1 mutant protein) improves wheat salt tolerance. Furthermore, we show that TaBZR1 binds directly to the G-box motif in the promoter of ABA biosynthesis gene TaNCED3 to activate its expression and promotes ABA accumulation. Moreover, TaBZR1 associates with the promoters of ROS-scavenging genes TaGPX2 and TaGPX3 to activate their expression. Taken together, our results elucidate that TaBZR1 improves salt-stress tolerance by activating some genes involved in the biosynthesis of ABA and ROS scavenging in wheat, which gives us a new strategy to improve the salt tolerance of wheat.

Effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with diabetic nephropathy and chronic renal failure.

BACKGROUND: Diabetic nephropathy (DN) is frequently seen in the development of diabetes mellitus, and its pathogenic factors are complicated. Its current treatment is controversial, and there is a lack of a relevant efficacy prediction model. AIM: To determine the effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with DN and chronic renal failure (CRF), and to construct an efficacy prediction model. METHODS: We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022. We selected 94 patients who met the inclusion and exclusion criteria. Patients were assigned to a dialysis group (n = 45) and a joint group (n = 49) in relation to therapeutic regimen. The clinical efficacy of the two groups was compared after treatment. The changes in laboratory indexes after treatment were evaluated, and the two groups were compared for the incidence of adverse reactions. The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed. RESULTS: The dialysis group showed a notably worse improvement in clinical efficacy than the joint group (P = 0.017). After treatment, the joint group showed notably lower serum levels of serum creatinine, uric acid (UA) and blood urea nitrogen (BUN) than the dialysis group (P < 0.05). After treatment, the joint group had lower serum levels of phosphorus, procollagen type I amino-terminal propeptide (PINP) and intact parathyroid hormone than the dialysis group, but a higher calcium level (P < 0.001). Both groups had a similar incidence of adverse reactions (P > 0.05). According to least absolute shrinkage and selection operator regression analysis, UA, BUN, phosphorus and PINP were related to treatment efficacy. According to further comparison, the non-improvement group had higher risk scores than the improvement group (P < 0.0001), and the area under the curve of the risk score in efficacy prediction was 0.945. CONCLUSION: For treatment of CRF and DN, combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients, with good safety.

Irisin inhibits neutrophil extracellular traps formation and protects against acute pancreatitis in mice.

INTRODUCTION: Irisin is a newly discovered myokine which links exercise to inflammation and inflammation-related diseases through macrophage regulation. However, the effect of irisin on the activity of inflammation related immune cells (such as neutrophils) has not been clearly described. OBJECTIVES: The objective of our study was to explore the effect of irisin on the neutrophil extracellular traps (NETs) formation. METHODS: Phorbol-12-myristate-13-acetate (PMA) was used to construct a classic neutrophil inflammation model that was used to observe the formation of NETs in vitro. We studied the effect of irisin on NETs formation and its regulation mechanism. Subsequently, acute pancreatitis (AP) was used to verify the protective effect of irisin in vivo, which was an acute aseptic inflammatory response disease model closely related to NETs. RESULTS: Our study found that addition of irisin significantly reduced the formation of NETs via regulation of the P38/MAPK pathway through integrin αVß5, which might be the one of key pathways in NETs formation, and which could theoretically offset the immunoregulatory effect of irisin. Systemic treatment with irisin reduced the severity of tissue damage common in the disease and inhibited the formation of NETs in pancreatic necrotic tissue of two classical AP mouse models. CONCLUSION: The findings confirmed for the first time that irisin could inhibit NETs formation and protect mice from pancreatic injury, which further elucidated the protective effect of exercise on acute inflammatory injury.

Discussion on the need for correction during isotopic analysis of nitrogen by the denitrifier method.

The nitrogen and oxygen isotopes of NO3 - are effectively used to trace the main nitrogen sources and migration processes in the atmosphere, water and soil. NO3 - can be converted into N2O by the bacterial denitrification method, which is an advanced method with high sensitivity. However, due to the existence of a small but inevitable blank during the whole experimental process, the N isotopic signal of N2O produced by denitrification superimposes on that of the N blank. Currently, the standard curve correction method is used to correct measured nitrogen isotope results to mitigate blank interference. It has been reported that high variability of the nitrogen isotope results have been produced by the denitrifier method by conducting an interlaboratory comparison of denitrifier methods and other methods on standards and environmental samples, and to reduce this problem, the nitrogen isotope calibration process with a standard curve is examined in depth in this paper, which uses PreCon-GC-IRMS to determine the nitrogen isotopes in N2O. We demonstrate for the first time that reliable results can be obtained without correction for samples with nitrogen isotope composition ranging from -9.9 to 19.5‰, which covers the natural sample range. This study establishes the double test approach for the bacterial denitrification method, ensuring the accuracy and long-term stability of different batches of nitrogen isotope results.

Association between handgrip strength and heart failure in adults aged 45 years and older from NHANES 2011-2014.

Growing evidence indicates that handgrip strength (HGS) is a conspicuous marker for assessing some diseases affecting middle-aged and elderly individuals. However, research regarding HGS and heart failure (HF) is sparse and controversial. Hence, we aimed to investigate the association between HGS and HF among adults aged 45 years and older in the United States. In this cross-sectional study, we included 4524 adults older than 45 years who were part of the National Health and Nutrition Examination Survey. A generalized additive model was used to estimate the association between HGS and HF. Age, gender, race, income, education, body mass index, smoking status, drinking status, diabetes, hypertension, stroke, vigorous physical activity, total energy intake, total protein intake, total sugars intake, and total fat intake covariates were adjusted using multiple regression models. And further subgroup analysis was conducted. We documented 189 cases of HF, including 106 men and 83 women. HGS was negatively associated with HF after adjusting for all the covariates (odds ratio = 0.97, 95% confidence interval = 0.96-0.99; P < 0.001). Compared with the lowest quintile, the highest quintile was associated with an 82% lower incidence of HF (odds ratio = 0.18, 95% confidence interval = 0.08-0.43; P < 0.001). Subgroup analysis showed that the results remained stable. In US adults older than 45, HGS was negatively associated with HF after adjusting for covariates. This finding had the potential to draw attention to the physiological and pathological effects of decreased muscle function on HF and may influence further prospective studies with intervention trials.

Banzhilian formula alleviates psoriasis-like lesions via the LCN2/MMP-9 axis based on transcriptome analysis.

Introduction: Oral Banzhilian formula (BZLF) is effective in the clinical treatment of psoriasis. However, the effectiveness and mechanism of different drug delivery routes deserve further study. Methods: First, we established the mouse model of psoriasis using imiquimod (IMQ), and high-performance liquid chromatography (HPLC) was used for the quality control of BZLF. Secondly, Total RNA Sequencing and bioinformatics analysis were used to explore the regulatory mechanism of BZLF in improving psoriatic lesions. Finally, further verification was based on animal experiments. Results: we externally applied BZLF for skin lesions in an imiquimod-induced psoriasis mouse model and found that BZLF alleviated psoriasis-like skin lesions while inhibiting the expression of Ki67 and inflammatory factors (Il17a, Tnf-α, S100a7 and Cxcl1) in skin lesions. Transcriptome sequencing results suggested that BZLF inhibited signalling pathways closely related to psoriatic inflammation, such as the IL-17 signalling pathway, chemokine signalling pathway, TNF signalling pathway, and NF-kappa B signalling pathway, and the protein-protein interaction (PPI) network identified LCN2 as one of the core target genes and screened out its regulated downstream gene MMP9. Discussion: Our findings suggest that the anti-psoriatic mechanism of BZLF involved in downregulating the LCN2/MMP-9 axis.

Fu-Huang ointment ameliorates impaired wound healing associated with diabetes through PI3K-AKT signalling pathway activation.

A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.

Heat Shock Protein B7 Inhibits the Progression of Endometrial Carcinoma by Inhibiting PI3K/AKT/mTOR Pathway.

PURPOSE: To investigate the role and mechanism of action of Heat shock protein B7 (HSPB7) in endometrial carcinoma (EC). METHODS: GEPIA (Gene Expression Profiling Interactive Analysis) was used to analyze the expression and prognostic value of HSPB7 in TCGA data. HSPB7 mRNA and protein expression levels were detected by qRT-PCR and Western blot, respectively. EC cell proliferation, apoptosis, migration, and invasion were determined by colony formation, EdU, flow cytometry, and transwell assays. Mitochondrial membrane potential was determined using JC-1 probe. In addition, apoptosis-related and metastasis-related proteins were quantitatively evaluated. A gene set enrichment analysis of the signaling pathways by which HSPB7 influences EC was performed and the levels of enriched pathway-related proteins were evaluated. RESULTS: We first proved that HSPB7 was downregulated in EC tissues and HSPB7 levels were positively related to survival rates. In functional assays, HSPB7 overexpression suppressed the proliferation, migration, and invasion of EC cells and conversely promoted apoptosis. Moreover, HSPB7 overexpression decreased the mitochondrial membrane potential of EC cells significantly. Bioinformatics analyses revealed that the PI3K/AKT/mTOR pathway was significantly enriched in EC. HSPB7 inhibited the phosphorylation of the PI3K/AKT/mTOR pathway to reduce proliferation, migration and invasion, and increased apoptosis in EC cells. CONCLUSION: HSPB7 was downregulated in EC and influenced EC cell proliferation, invasion, migration, and apoptosis via the PI3K/AKT/mTOR signaling pathway. These findings provide a novel perspective for the development of EC treatment strategies.

Evaluation of the report quality of Chinese and English randomized controlled trials of acupuncture based on CONSORT statement and STRICTA checklist / 中国针灸

OBJECTIVE@#To evaluate the report quality of Chinese and English randomized controlled trials (RCTs) of acupuncture based on the CONSORT statement and STRICTA checklist.@*METHODS@#The Chinese and English RCTs of acupuncture published from January 1, 2015 to December 31, 2019 were searched in 7 databases including PubMed. The report quality of the included RCTs was evaluated with the CONSORT 2010 statement and STRICTA checklist.@*RESULTS@#A total of 506 Chinese RCTs and 76 English RCTs were included. According to the CONSORT statement, in Chinese RCTs, the items with report rate less than 50% accounted for 78.38% of all items, and the report rate of 25 items, such as background and reason, study design, outcome index, and sample size, was less than 10%. In English RCTs, the items with report rate less than 50% accounted for 35.14% of all items, and 5 items had a report rate of less than 10%. The difference of the report rate of 15 items, such as background, reason and study design, was more than 50% between Chinese and English RCTs. The report rate of all items of STRICTA checklist was relatively high in both Chinese and English RCTs. In Chinese RCTs, the items with report rate less than 50% accounted for 29.41% of all items, which included acupuncture rationale and depth of insertion. In English RCTs, only two items had a report rate less than 50%, which were acupuncture rationale, setting and context of treatment. The report rate of five items, including needle retention time, frequency and duration of treatment sessions, details of other interventions administered to the acupuncture group, setting and context of treatment, and precise description of the control or comparator in Chinese RCTs, were higher than in English RCTs.@*CONCLUSION@#The report quality of Chinese acupuncture RCT needs to be improved urgently, and corresponding measures should be taken to further standardize the writing and reporting of acupuncture clinical research.