ABSTRACT
OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.
Subject(s)
Brain , Diabetes, Gestational , Diet, High-Fat , Fatty Acids , Prenatal Exposure Delayed Effects , Animals , Pregnancy , Female , Diabetes, Gestational/metabolism , Mice , Diet, High-Fat/adverse effects , Brain/metabolism , Prenatal Exposure Delayed Effects/metabolism , Male , Fatty Acids/metabolism , Disease Models, Animal , Maternal Nutritional Physiological PhenomenaABSTRACT
To improve the biodistribution of the drug in the tumor, a supramolecular prodrug of SN38 was fabricated in situ between endogenous albumin and SN38 prodrug modified with semaglutide side chain. Firstly, SN38 was conjugated with semaglutide side chain and octadecanedioic acid via glycine linkers to obtain SI-Gly-SN38 and OA-Gly-SN38 prodrugs, respectively. Both SI-Gly-SN38 and OA-Gly-SN38 exhibited excellent stability in PBS for over 24 h. Due to the strong binding affinity of the semaglutide side chain with albumin, the plasma half-life of SI-Gly-SN38 was 2.7 times higher than that of OA-Gly-SN38. Furthermore, with addition of HSA, the fluorescence intensity of SI-Gly-SN38 was 4 times higher than that of OA-Gly-SN38, confirming its strong binding capability with HSA. MTT assay showed that the cytotoxicity of SI-Gly-SN38 and OA-Gly-SN38 was higher than that of Irinotecan. Even incubated with HSA, the SI-Gly-SN38 and OA-Gly-SN38 still maintained high cytotoxicity, indicating minimal influence of HSA on their cytotoxicity. In vivo pharmacokinetic studies demonstrated that the circulation half-life of SI-Gly-SN38 was twice that of OA-Gly-SN38. SI-Gly-SN38 exhibited significantly reduced accumulation in the lungs, being only 0.23 times that of OA-Gly-SN38. The release of free SN38 in the lungs from SI-Gly-SN38 was only 0.4 times that from OA-Gly-SN38 and Irinotecan. The SI-Gly-SN38 showed the highest accumulation in tumors. The tumor inhibition rate of SI-Gly-SN38 was 6.42% higher than that of OA-Gly-SN38, and 8.67% higher than that of Irinotecan, respectively. These results indicate that the supramolecular prodrug delivery system can be constructed between SI-Gly-SN38 and endogenous albumin, which improves drug biodistribution in vivo, enhances tumor accumulation, and plays a crucial role in tumor growth inhibition.
Subject(s)
Irinotecan , Prodrugs , Irinotecan/chemistry , Irinotecan/pharmacology , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/chemical synthesis , Animals , Humans , Mice , Tissue Distribution , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacokinetics , Molecular Structure , Drug Screening Assays, Antitumor , Cell Proliferation/drug effects , Cell Line, Tumor , Mice, Inbred BALB C , Mice, Nude , Albumins/chemistry , Male , Structure-Activity Relationship , Serum Albumin, Human/chemistry , Glucagon-Like PeptidesABSTRACT
The purpose of this study was to explore the mechanism of "simmer pus and grow meat" method based on bFGF regulating WNT / ß-Catenin signaling pathway. Of 100 SPF rats, 25 were randomly selected as blank group, and 75 rats were established chronic infectious wound model and divided into blank group, model group (normal saline treatment, n = 25), experimental group (purple and white ointment treatment, n = 25), and wet burn ointment group (wet burn treatment, n = 25). The wound healing rate of rats was compared. The protein expressions of PCAN, VEGF, bFGF, ß-Catenin, GSK-3ß and C-Myc in granulation tissues were detected. On the 7th day, the wound healing rate of the model group was lower than that of the other 3 groups (P<0.05), and the wound healing rate of the positive control group was higher than that of the experimental group and the control group (P<0.05). The expressions of bFGF, GSK-3ß and C-MyC in model group were higher than those in control group (P<0.05). The ß-catenin protein expression in the model group was lower than that in the control group (P<0.05), and the ß-catenin protein expression in the experimental group and the positive control group was higher than that in the model group (P<0.05). The expressions of PCAN and VEGF in model group were lower than those in model group (P<0.05). We found that Zibai ointment promotes chronic wound healing by modulating the bFGF/Wnt/ß-Catenin signaling pathway.
Subject(s)
Fibroblast Growth Factor 2 , Wnt Signaling Pathway , Wound Healing , beta Catenin , Animals , Wound Healing/drug effects , Wnt Signaling Pathway/drug effects , Fibroblast Growth Factor 2/metabolism , beta Catenin/metabolism , Rats , Male , Glycogen Synthase Kinase 3 beta/metabolism , Vascular Endothelial Growth Factor A/metabolism , Rats, Sprague-Dawley , Burns/metabolism , Burns/drug therapy , Burns/pathology , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Disease Models, Animal , Granulation Tissue/drug effects , Granulation Tissue/metabolism , Granulation Tissue/pathologyABSTRACT
Fungal infection has become a major threat to crop loss and affects food safety. The waste water from agar processing industries extraction has a number of active substances, which could be further transformed by microorganisms to synthesize antifungal active substances. In this study, Bacillus subtilis was used to ferment the waste water from agar processing industries extraction to analyze the antifungal activity of the fermentation broth on Alternaria alternata and Alternaria spp. Results showed that 25% of the fermentation broth was the most effective in inhibited A. alternata and Alternaria spp., with fungal inhibition rates of 99.9% and 96.1%, respectively, and a minimum inhibitory concentration (MIC) was 0.156 µg/mL. Metabolomic analysis showed that flavonoid polyphenols such as coniferyl aldehyde, glycycoumarin, glycitin, and procyanidin A1 may enhance the inhibitory activity against the two pathogenic fungal strains. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that polyphenols involved in the biosynthesis pathways of isoflavonoid and phenylpropanoid were upregulated after fermentation. The laser confocal microscopy analyses and cell conductivity showed that the cytoplasm of fungi treated with fermentation broth was destroyed. This study provides a research basis for the development of new natural antifungal agents and rational use of seaweed agar waste. KEY POINTS: ⢠Bacillus subtilis fermented waste water has antifungal activity ⢠Bacillus subtilis could transform active substances in waste water ⢠Waste water is a potential raw material for producing antifungal agents.
Subject(s)
Antifungal Agents , Bacillus subtilis , Bacillus subtilis/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Agar , Wastewater , Fermentation , AlternariaABSTRACT
BACKGROUND: Ultrasound cycloplasty is a noninvasive surgery used to reduce intraocular pressure in patients with glaucoma, with fewer severe complications. This report presents several cases of iris neovascularization and neurotrophic keratopathy following ultrasound cycloplasty. CASE PRESENTATION: Six patients diagnosed with refractory glaucoma underwent ultrasound cycloplasty at our clinic. Three cases developed iris neovascularization at postoperative day 3, week 2 and week 4 respectively, with intraocular pressure ranging from 12 to 24 mmHg. The other three cases developed neurotrophic keratopathy at postoperative week 3, week 6 and week 8 which completely healed within 60 days. CONCLUSIONS: Iris neovascularization and neurotrophic keratopathy can be triggered after ultrasound cycloplasty, which are uncommon and self-limited but potentially vision-threatening. Preoperative risk assessment and regular postoperative follow-up are recommended to manage complications effectively.
Subject(s)
Glaucoma , Intraocular Pressure , Iris , Adult , Aged , Female , Humans , Male , Middle Aged , Corneal Diseases/surgery , Corneal Diseases/etiology , Glaucoma/surgery , Intraocular Pressure/physiology , Iris/surgery , Iris/blood supply , Iris/diagnostic imaging , Neovascularization, Pathologic , Postoperative ComplicationsABSTRACT
Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.
Subject(s)
Hydrocortisone , Sleep Deprivation , Sleep Deprivation/blood , Hydrocortisone/blood , HumansABSTRACT
Objective: Our aim was to analyze the effect of refined specialized nursing intervention in elderly patients with diabetes and concurrent pulmonary infection and the impact on patients' conditions and outcomes. Methods: Clinical data from 87 elderly patients with type 2 diabetes (T2D) complicated by pulmonary infection treated in Lishui Municipal Central Hospital in China from February 2021 to February 2023 were retrospectively analyzed. All patients conformed to complete inclusion and exclusion criteria. Patients were divided into a control group (n=43) and an observation group (n=44) based on the nursing intervention they received. The control group received routine nursing intervention, while the observation group received refined specialized nursing intervention. The nursing intervention effects, hospitalization duration, disease knowledge acquisition, blood glucose indicators (fasting plasma glucose [FPG], 2-hour postprandial glucose [2hPG]), inflammatory marker indicators (C-reactive protein [CRP], heparin-binding protein [HBP]) levels, comfort levels and nursing satisfaction were compared between the 2 groups. Results: (1) Nursing intervention effect and hospitalization duration: The observation group showed significantly higher overall intervention effectiveness and notably shorter hospital stays compared with the control group (P < .05). (2) Disease knowledge acquisition and blood glucose indicator levels: Before the intervention, there were no significant differences in disease knowledge acquisition, FPG or 2hPG levels between the 2 groups (P > .05); after the intervention, the observation group exhibited significantly higher disease knowledge acquisition and lower FPG and 2hPG levels than the control group (P < .05). (3) Inflammatory marker indicator levels: Prior to the intervention, there were no significant differences in CRP or HBP levels between the 2 groups (P > .05); post-intervention, the observation group showed markedly lower CRP and HBP levels compared with the control group (P < .05). (4) Comfort levels: Prior to the intervention, there were no significant differences in physiological, psychological, environmental or social comfort scores between the 2 groups (P > .05); after the intervention, the observation group exhibited significantly higher scores in all comfort aspects compared with the control group (P < .05). (5) Nursing satisfaction: Nursing satisfaction in the control group was 74.42%, while in the observation group it was 90.91%, indicating significantly higher nursing satisfaction in the observation group (P < .05). Conclusion: Refined specialized nursing intervention significantly improved outcomes in elderly patients with diabetes and concurrent pulmonary infection. Compared with routine nursing intervention, refined specialized nursing intervention remarkably enhanced patient comfort during hospitalization, improved disease knowledge acquisition, rapidly adjusted blood glucose levels and reduced systemic inflammatory response, facilitating better patient recovery. Moreover, it moderately enhanced satisfaction for patients and their families, holding significant implications for promoting harmonious doctor-patient relationships, hence advocating for its clinical dissemination.
ABSTRACT
Growing evidences have shown that the decline in honey bee populations is mainly caused by the combination of multiple stressors. However, the impacts of parasitic Nosema ceranae to host fitness during long-term pesticide exposure-induced stress is largely unknown. In this study, the effects of chronic exposure to a sublethal dose of dinotefuran, in the presence or absence of N. ceranae, was examined in terms of survival, food consumption, detoxification enzyme activities and gut microbial community. The interaction between dinotefuran and Nosema ceranae on the survival of honey bee was synergistic. Co-exposure to dinotefuran and N. ceranae led to less food consumption and greater changes of enzyme activities involved in defenses against oxidative stress. Particularly, N. ceranae and dinotefuran-N. ceranae co-exposure significantly impacted the gut microbiota structure and richness in adult honey bees, while dinotefuran alone did not show significant alternation of core gut microbiota compared to the control group. We herein demonstrated that chronical exposure to dinotefuran decreases honey bee's survival but is not steadily associated with the gut microbiota dysbiosis; by contrast, N. ceranae parasitism plays a dominant role in the combination in influencing the gut microbial community of the host honey bee. Our findings provide a comprehensive understanding of combinatorial effects between biotic and abiotic stressors on one of the most important pollinators, honey bees.
Subject(s)
Gastrointestinal Microbiome , Guanidines , Nitro Compounds , Nosema , Bees , Animals , Neonicotinoids/toxicity , Nitro Compounds/toxicityABSTRACT
Electrolyte modulation and electrode structure design are two common strategies to suppress dendrites growth on Li metal anode. In this work, a self-adaptive electrode construction method to suppress Li dendrites growth is reported, which merges the merits of electrolyte modulation and electrode structure design strategies. In detail, negatively charged titania nanosheets with densely packed nanopores on them are prepared. These holey nanosheets in the electrolyte move spontaneously onto the anode under electrical field, building a mesoporous structure on the electrode surface. The as-formed porous electrode has large surface area with good lithiophilicity, which can efficiently transfer lithium ion (Li+ ) inside the electrode, and induce the genuine lithium plating/stripping. Moreover, the negative charges and nanopores on the sheets can also regulate the lithium-ion flux to promote uniform deposition of Li metal. As a result, the symmetric and full cells using the holey titania nanosheets containing electrolyte, show much better performance than the ones using electrolyte without holey nanosheets inside. This work points out a new route for the practical applications of Li-metal batteries.
ABSTRACT
Optical anisotropy, which is quantified by birefringence (Δn) and linear dichroism (Δk), can significantly modulate the angle-resolved polarized Raman spectroscopy (ARPRS) response of anisotropic layered materials (ALMs) by external interference. This work studies the separate modulation of birefringence on the ARPRS response and the intrinsic response by selecting transparent birefringent crystal α-MoO3 as an excellent platform. It is found that there are several anomalous ARPRS responses in α-MoO3 that cannot be reproduced by the real Raman tensor widely used in non-absorbing materials; however, they can be well explained by considering the birefringence-induced Raman selection rules. Moreover, the systematic thickness-dependent study indicates that birefringence modulates the ARPRS response to render an interference pattern; however, the amplitude of modulation is considerably lower than that by linear dichroism as occurred in black phosphorous. This weak modulation brings convenience to the crystal orientation determination of transparent ALMs. Combining the atomic vibrational pattern and bond polarizability model, the intrinsic ARPRS response of α-MoO3 is analyzed, giving the physical origins of the Raman anisotropy. This study employs α-MoO3 as an example, although it is generally applicable to all transparent birefringent ALMs.
ABSTRACT
BACKGROUND: Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted. METHODS: We systematically searched four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs. RESULTS: Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated. CONCLUSION: This study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs.
Subject(s)
Anti-Infective Agents , Intraabdominal Infections , Adult , Humans , Metronidazole/adverse effects , Meropenem/therapeutic use , Network Meta-Analysis , Tigecycline/therapeutic use , Cefepime/therapeutic use , Anti-Bacterial Agents/adverse effects , Intraabdominal Infections/drug therapy , Intraabdominal Infections/microbiology , Tazobactam/therapeutic use , Anti-Infective Agents/adverse effectsABSTRACT
Titanium dioxide (TiO2) is a common additive in foods, medicines, and personal care products. In recent years, nano-scale particles in TiO2 additives have been an increasing concern due to their potential adverse effects on human health, especially gut health. The objective of this study was to determine the impact of titanium dioxide nanoparticles (TiO2 NPs, 30 nm) on beneficial gut bacteria and host response from a metabolomics perspective. In the in vitro study, four bacterial strains, including Lactobacillus reuteri, Lactobacillus gasseri, Bifidobacterium animalis, and Bifidobacterium longum were subjected to the treatment of TiO2 NPs. The growth kinetics, cell viability, cell membrane permeability, and metabolomics response were determined. TiO2 NPs at the concentration of 200 µg/mL showed inhibitory effects on the growth of all four strains. The confocal microscope results indicated that the growth inhibitory effects could be associated with cell membrane damage caused by TiO2 NPs to the bacterial strains. Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health. In the in vivo study, mice were fed with TiO2 NPs (0.1 wt% in diet) for 8 weeks. Mouse urine was collected for metabolomics analysis and the tryptophan metabolism pathway was also significantly affected in TiO2 NPs-fed mice. Moreover, four neuroprotective metabolites were significantly reduced in both in vitro bacteria and in vivo urine samples. Overall, this study provides insights into the potential adverse effects of TiO2 NPs on gut bacteria and the metabolic responses of both bacteria and host. Further research is needed to understand the causality between gut bacteria composition and the metabolism pathway, which is critical to monitor the gut-microbiome mediated metabolome changes in toxicological assessment of food components.
Subject(s)
Gastrointestinal Microbiome , Metal Nanoparticles , Animals , Humans , Mice , Bacteria , Nanoparticles/toxicity , Titanium/toxicity , Tryptophan/pharmacology , Gastrointestinal Microbiome/drug effectsABSTRACT
BACKGROUND: This study aimed to compare the predictive value of two diagnostic criteria for bronchopulmonary dysplasia (BPD) in preterm infants with gestational age (GA) < 32 weeks for death or severe respiratory morbidity at corrected age of 18-24 months. METHODS: In this retrospective cohort study, clinical data from July 2019 to September 2021 were classified by 2018 National Institute of Child Health and Human Development (NICHD) and 2019 Jensen definitions of BPD. Based on the follow-up results, the enrolled population was divided into adverse outcome group and normal outcome group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to explore the risk factors of adverse outcomes and evaluate the predictive value of both diagnostic criteria. RESULTS: Of 451 infants, 141 (31.3%) had adverse outcomes, which increased with increasing severity of BPD. Logistic regression analysis showed only BPD was an independent risk factor for adverse outcomes in preterm infants. ROC analysis revealed that both diagnostic criteria showed similar predictive values (2018 NICHD definition AUC = 0.771 vs. 2019 Jensen definition AUC = 0.770), with specificities of 93.5% and 96.8%, respectively; however, combining them separately with GA or birth weight did not improve their predictive values. CONCLUSIONS: The two novel definitions of BPD demonstrate similar predictive values in predicting death or severe respiratory morbidity at corrected age of 18-24 months, with higher specificity observed in both.
Subject(s)
Bronchopulmonary Dysplasia , Infant, Premature , Infant, Newborn , Child , Infant , Humans , Child, Preschool , Bronchopulmonary Dysplasia/diagnosis , Retrospective Studies , Gestational Age , Birth WeightABSTRACT
Recent discoveries from large-scale genome-wide association studies (GWASs) explain a larger proportion of the genetic variability to BMI and obesity. The genetic risk associated with BMI and obesity can be assessed by an obesity-specific genetic risk score (GRS) constructed from genome-wide significant genetic variants. The aim of our study is to examine whether the duration and exclusivity of breastfeeding can attenuate BMI increase during childhood and adolescence due to genetic risks. A total sample of 5,266 children (2,690 boys and 2,576 girls) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was used for the analysis. We evaluated the role of breastfeeding (exclusivity and duration) in modulating BMI increase attributed to the GRS from birth to 18 years of age. The GRS was composed of 69 variants associated with adult BMI and 25 non-overlapping SNPs associated with pediatric BMI. In the high genetic susceptible group (upper GRS quartile), exclusive breastfeeding (EBF) to 5 months reduces BMI by 1.14 kg/m2 (95% CI, 0.37 to 1.91, p = 0.0037) in 18-year-old boys, which compensates a 3.9-decile GRS increase. In 18-year-old girls, EBF to 5 months decreases BMI by 1.53 kg/m2 (95% CI, 0.76 to 2.29, p<0.0001), which compensates a 7.0-decile GRS increase. EBF acts early in life by delaying the age at adiposity peak and at adiposity rebound. EBF to 3 months or non-exclusive breastfeeding was associated with a significantly diminished impact on reducing BMI growth during childhood. EBF influences early life growth and development and thus may play a critical role in preventing overweight and obesity among children at high-risk due to genetic factors.
Subject(s)
Body Mass Index , Breast Feeding/statistics & numerical data , Obesity/genetics , Adiposity/genetics , Adolescent , Breast Feeding/methods , Female , Genetic Predisposition to Disease , Humans , Infant , Male , Obesity/epidemiology , Obesity/prevention & control , Polymorphism, Single Nucleotide , Young AdultABSTRACT
Pesticide pollution is one of the most important factors for global bee declines. Despite many studies have revealed that the most important Chinese indigenous speciesï¼Apis cerana, is presenting a high risk on exposure to neonicotinoids, the toxicology information on Apis cerana remain limited. This study was aimed to determine the acute and chronic toxic effects of thiacloprid (IUPAC name: {(2Z)-3-[(6-Chloro-3-pyridinyl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide) on behavioral and physiological performance as well as genome-wide transcriptome in A. cerana. We found the 1/5 LC50 of thiacloprid significantly impaired learning and memory abilities after both acute and chronic exposure, nevertheless, has no effects on the sucrose responsiveness and phototaxis climbing ability of A. cerana. Moreover, activities of detoxification enzyme P450 monooxygenases and CarE were increased by short-term exposure to thiacloprid, while prolonged exposure caused suppression of CarE activity. Neither acute nor chronic exposure to thiacloprid altered honey bee AChE activities. To further study the potential defense molecular mechanisms in Asian honey bee under pesticide stress, we analyzed the transcriptomes of honeybees in response to thiacloprid stress. The transcriptomic profiles revealed consistent upregulation of immune- and stress-related genes by both acute or chronic treatments. Our results suggest that the chronic exposure to thiacloprid produced greater toxic effects than a single administration to A. cerana. Altogether, our study deepens the understanding of the toxicological characteristic of A. cerana against thiacloprid, and could be used to further investigate the complex molecular mechanisms in Asian honey bee under pesticide stress.
Subject(s)
Bees , Insecticides , Neonicotinoids , Thiazines , Animals , Bees/genetics , Bees/metabolism , Bees/physiology , Insecticides/toxicity , Neonicotinoids/toxicity , Thiazines/toxicity , Toxicity Tests, Subacute , Toxicity Tests, Chronic , China , Acetylcholinesterase/genetics , Acetylcholinesterase/metabolism , Stress, Physiological/geneticsABSTRACT
Resistance training is employed for pursuing muscle strength characterized by activation of mammalian target of rapamycin (mTOR)-mediated hypertrophic signaling for protein production. Endurance training elevates peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling of mitochondrial adaptations for oxidative phosphorylation. Now, emerging evidence suggests that, like endurance training, resistance training also elicits profound effects on mitochondrial adaptations in skeletal muscle, which means that resistance training yields both strength and endurance phenotypes in myofibers, which has treatment value for the muscle loss and poor aerobic capacity in humans. Our review outlines a brief overview of muscle hypertrophic signals with resistance training, and focuses on the effects of resistance training on mitochondrial biogenesis and respiration in skeletal muscle. This study provides novel insights into the therapeutic strategy of resistance training for the metabolically dysfunctional individuals with declined mitochondrial function.
Subject(s)
Resistance Training , Transcription Factors , Humans , Transcription Factors/genetics , Mitochondria/metabolism , Signal Transduction/physiology , Muscle, Skeletal/physiology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolismABSTRACT
As a worldwide major ornamental flower and a edible plant, lotus (Nelumbo nucifera) is also used as medicine and tea beverage. Here, transcriptome and metabolites of yellow (MLQS) and white (YGB) lotus cultivars during five key flower coloration stages were profiled. 2014 differentially expressed genes were detected with 11 carotenoids in lotus were identified for the first time. Then, regulatory networks between and within functional modules was reconstructed, and the correlation between module-metabolites and gene-metabolites was conducted within 3 core modules. 18 candidate genes related to the formation of yellow flower were screened out and a gene regulatory model for the flower color difference between MLQS and YGB were speculated as follows: The substrate competition between F3'H and F3'5'H and substrate specificity of FLS, together with differential expression of CCD4a and CCD4b were contribute to the differences in flavonoids and carotenoids. Besides, UGT73C2, UGT91C1-2 and SGTase, and regulation of UGTs by transcription factors PLATZ, MADS, NAC031, and MYB308 may also play a role in the upstream regulation. The following verification results indicated that functional differences existed in the coding sequences of NnCCD4b and promoters of NnCCD4a of MLQS and YGB. In all, this study preliminarily reveals the mechanism of yellow flower coloration in lotus and provides new ideas for the study of complex ornamental characters of other plants.
Subject(s)
Nelumbo , Nelumbo/genetics , Gene Expression ProfilingABSTRACT
'Huangguan' pear (Pyrus bretschneideri Rehd) fruit is susceptible to cold, characterized by developing peel browning spots (PBS) during cold storage. Additionally, ethylene pretreatment reduces chilling injury (CI) and inhibits PBS occurrence, but the mechanism of CI remains unclear. Here, we deciphered the dynamic transcriptional changes during the PBS occurrence with and without ethylene pretreatment via time-series transcriptome. We found that ethylene suppressed the cold-signaling gene expression, thereby decreasing the cold sensitivity of the 'Huangguan' fruit. Moreover, the "Yellow" module closely correlated with PBS occurrence was identified via weighted gene co-expression network analysis (WGCNA), and this module was related to plant defense via Gene Ontology (GO) enrichment analysis. Local motif enrichment analysis suggested that the "Yellow" module genes were regulated by ERF and WRKY transcription factors. Functional studies demonstrated that PbWRKY31 has a conserved WRKY domain, lacks transactivation activity, and localizes in the nucleus. PbWRKY31-overexpressed Arabidopsis were hypersensitive to cold, with higher expression levels of cold signaling and defense genes, suggesting that PbWRKY31 participates in regulating plant cold sensitivity. Collectively, our findings provide a comprehensive transcriptional overview of PBS occurrence and elucidate the molecular mechanism by which ethylene reduces the cold sensitivity of 'Huangguan' fruit as well as the potential role of PbWRKY31 in this process.
Subject(s)
Pyrus , Transcriptome , Pyrus/genetics , Pyrus/metabolism , Ethylenes/pharmacology , Ethylenes/metabolism , Gene Expression Profiling , Fruit/genetics , Fruit/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Cold TemperatureABSTRACT
Regular consumption of fish promotes sustainable health while reducing negative environmental impacts. Fermentation has long been used for preserving perishable foods, including fish. Fermented fish products are popular consumer foods of historical and cultural significance owing to their abundant essential nutrients and distinct flavor. This review discusses the recent scientific progress on fermented fish, especially the involved flavor formation processes, microbial metabolic activities, and interconnected biochemical pathways (e.g., enzymatic/non-enzymatic reactions associated with lipids, proteins, and their interactions). The multiple roles of fermentation in preservation of fish, development of desirable flavors, and production of health-promoting nutrients and bioactive substances are also discussed. Finally, prospects for further studies on fermented fish are proposed, including the need of monitoring microorganisms, along with the precise control of a fermentation process to transform the traditional fermented fish to novel, flavorful, healthy, and affordable products for modern consumers. Microbial-enabled innovative fermented fish products that consider both flavor and health benefits are expected to become a significant segment in global food markets. The integration of multi-omics technologies, biotechnology-based approaches (including synthetic biology and metabolic engineering) and sensory and consumer sciences, is crucial for technological innovations related to fermented fish. The findings of this review will provide guidance on future development of new or improved fermented fish products through regulating microbial metabolic processes and enzymatic activities.
Subject(s)
Food , Microbiota , AnimalsABSTRACT
BACKGROUND AND AIMS: difficulty of cecal intubation should be a main indicator for the need of sedated colonoscopy and skilled endoscopists. The present study aimed to explore the factors associated with easy and difficult cecal intubation in unsedated colonoscopy. METHODS: all consecutive patients who underwent unsedated colonoscopy at our department by the same endoscopist from December 3, 2020 to August 30, 2022 were retrospectively collected. Age, gender, body mass index (BMI), reasons for colonoscopy, position change, Boston Bowel Preparation Scale score, cecal intubation time (CIT) and major colonoscopic findings were analyzed. CIT < 5 min, CIT 5-10 min and CIT > 10 min or failed cecal intubation were defined as easy, moderate and difficult cecal intubation, respectively. Logistic regression analyses were performed to identify independent factors associated with easy and difficult cecal intubation. RESULTS: overall, 1,281 patients were included. The proportions of easy and difficult cecal intubation were 29.2 % (374/1,281) and 27.2 % (349/1,281), respectively. Multivariate logistic regression analysis found that age ≤ 50 years, male, BMI > 23.0 kg/m2 and the absence of position change were independently associated with easy cecal intubation, and that age > 50 years, female, BMI ≤ 23.0 kg/m2, position change, and insufficient bowel preparation were independently associated with difficult cecal intubation. CONCLUSIONS: some convenient factors independently associated with easy and difficult cecal intubation have been identified, which will be potentially helpful to determine whether a colonoscopy should be sedated and a skilled endoscopist should be selected. The current findings should be further validated in large-scale prospective studies.