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1.
BMC Surg ; 24(1): 177, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38844909

ABSTRACT

OBJECTIVE: The objective of this study is to evaluate and compare the surgical outcomes and complications of Percutaneous Endoscopic Lumbar Decompression (PELD) and traditional revision surgery in treating symptomatic Adjacent Segment Degeneration (ASD). This comparison aims to delineate the advantages and disadvantages of these methods, assisting spine surgeons in making informed surgical decisions. METHODS: 66 patients with symptomatic ASD who failed conservative treatment for more than 1 month and received repeated lumbar surgery were retrospectively collected in the study from January 2015 to November 2018, with the average age of 65.86 ± 11.04 years old. According to the type of surgery they received, all the patients were divided in 2 groups, including 32 patients replaced the prior rod in Group A and 34 patients received PELD at the adjacent level in Group B. Patients were followed up routinely and received clinical and radiological evaluation at 3, 6, 12 months and yearly postoperatively. Complications and hospital costs were recorded through chart reviews. RESULTS: The majority of patients experienced positive surgical outcomes. However, three cases encountered complications. Notably, Group B patients demonstrated superior pain relief and improved postoperative functional scores throughout the follow-up period, alongside reduced hospital costs (P < 0.05). Additionally, significant reductions in average operative time, blood loss, and hospital stay were observed in Group B (P < 0.05). Notwithstanding these benefits, three patients in Group B experienced disc re-herniation and underwent subsequent revision surgeries. CONCLUSIONS: While PELD offers several advantages over traditional revision surgery, such as reduced operative time, blood loss, and hospital stay, it also presents a higher likelihood of requiring subsequent revision surgeries. Future studies involving a larger cohort and extended follow-up periods are essential to fully assess the relative benefits and drawbacks of these surgical approaches for ASD.


Subject(s)
Decompression, Surgical , Endoscopy , Lumbar Vertebrae , Reoperation , Humans , Male , Female , Lumbar Vertebrae/surgery , Decompression, Surgical/methods , Reoperation/statistics & numerical data , Retrospective Studies , Aged , Middle Aged , Endoscopy/methods , Treatment Outcome , Intervertebral Disc Degeneration/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology
2.
RSC Adv ; 14(21): 15106-15111, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38720981

ABSTRACT

Glutathione (GSH) as an antioxidant greatly attenuates the reactive oxygen species (ROS) treatment strategy based on peroxidase-activity nanozymes. Therefore, nanozymes with multiple properties that generate ROS and further GSH-depletion functions would be of great benefit to improve antimicrobial efficacy. Herein, focusing on the green, safe and abundant functional prospects of metal-phenolic networks (MPNs) and the strong prospect of biomedical applications, we have synthesized copper tannic acid (CuTA) nanozymes with dual functional properties similar to peroxidase-like activity and GSH depletion. CuTA can catalyze the decomposition of H2O2 to hydroxyl radicals (˙OH). In addition, CuTA nanozymes can efficiently deplete available GSH, thus enhancing ROS-mediated antimicrobial therapy. The antibacterial results show that CuTA has an excellent antibacterial effect against E. coli.

3.
J Nanobiotechnology ; 22(1): 256, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755613

ABSTRACT

BACKGROUND: Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among cancer patients, coupled with a suboptimal postoperative survival prognosis. Nectin-4, an overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) to treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically for gastric cancer, and conventional immunoglobulin G (IgG)-based ADCs frequently encounter binding site barriers. Based on the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug conjugates (NDCs) for the treatment of gastric cancer. RESULTS: An immunized phage display library was established and employed for the selection of Nectin-4-specific Nbs using phage display technology. Subsequently, these Nbs were engineered into homodimers to enhance Nb affinity. To prolong in vivo half-life and reduce immunogenicity, we fused an Nb targeting human serum albumin (HSA), resulting in the development of trivalent humanized Nbs. Further, we site-specifically conjugated a monomethyl auristatin E (MMAE) at the C-terminus of the trivalent Nbs, creating Nectin-4 NDC (huNb26/Nb26-Nbh-MMAE) with a drug-to-antibody ratio (DAR) of 1. Nectin-4 NDC demonstrated excellent in vitro cell-binding activities and cytotoxic efficacy against cells with high Nectin-4 expression. Subsequent administration of Nectin-4 NDC to mice bearing NCI-N87 human gastric cancer xenografts demonstrated rapid tissue penetration and high tumor uptake through in vivo imaging. Moreover, Nectin-4 NDC exhibited noteworthy dose-dependent anti-tumor efficacy in in vivo studies. CONCLUSION: We have engineered a Nectin-4 NDC with elevated affinity and effective tumor uptake, further establishing its potential as a therapeutic agent for gastric cancer.


Subject(s)
Antineoplastic Agents , Cell Adhesion Molecules , Immunoconjugates , Mice, Nude , Single-Domain Antibodies , Stomach Neoplasms , Stomach Neoplasms/drug therapy , Humans , Animals , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/pharmacology , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Mice , Immunoconjugates/chemistry , Immunoconjugates/pharmacology , Immunoconjugates/pharmacokinetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Mice, Inbred BALB C , Female , Xenograft Model Antitumor Assays , Oligopeptides/chemistry , Oligopeptides/pharmacology , Nectins
4.
IEEE Trans Med Imaging ; PP2024 May 23.
Article in English | MEDLINE | ID: mdl-38781069

ABSTRACT

Open-sided magnetic particle imaging (OS-MPI) has garnered significant interest due to its potential for interventional applications. However, the system matrix calibration in OS-MPI using sequential scans is a time-consuming task and susceptible to the low signal-to-noise ratio (SNR) resulting from the small calibration sample size. These challenges have hindered the practical implementation of system matrix-based reconstruction for sequentially scanned OS-MPI. To address these issues, we propose a novel calibration method, named sequential scan-based single-dimension multi-voxel calibration (SS-SDMVC), to efficiently obtain a high-SNR system matrix. This method was implemented in a cylindrical field of view (FOV), where a bar calibration sample parallel to the field-free line (FFL) was shifted along a fixed radial direction. A standard image reconstruction process was also introduced to verify the feasibility of SS-SDMVC. Through simulations, we analyzed the effects of noise levels and scanner imperfections on the SS-SDMVC-based reconstruction and demonstrated its robustness. In experiments, we compared the imaging performance of SS-SDMVC and the sequential scan-based traditional cubic-FOV SMC. The results showed that SS-SDMVC reduced the number of measurements by a factor of 210.94 and achieved higher reconstruction quality. Therefore, SS-SDMVC is expected to improve the reconstruction quality of human-scale or high-gradient FFL MPI scanners.

5.
IEEE Trans Biomed Eng ; PP2024 May 13.
Article in English | MEDLINE | ID: mdl-38739521

ABSTRACT

OBJECTIVE: Magnetic Particle Imaging (MPI) is a radiation-free tracer-based imaging technology that visualizes the spatial distribution of superparamagnetic iron oxide nanoparticles. Conventional spatial encoding methods in MPI rely on a gradient magnetic field with a constant gradient strength to generate a field-free point or line for spatial scanning. However, increasing the gradient strength can enhance theoretical spatial resolution but also lead to a decrease in the Signal-to-Noise Ratio (SNR) and sensitivity of the imaging system. This poses a technical challenge in balancing spatial resolution and sensitivity, necessitating intricate hardware design. METHODS: To address this, we present a Space-Specific Mixing Excitation (SSME) technique for achieving high-SNR spatial encoding in MPI. By utilizing a dual-frequency excitation magnetic field with a non-homogeneous field strength, magnetic particles at each position generate unique intermodulation responses. By performing multi-channel acquisitions across the entire field of view, high SNR MPI signals can be acquired. When combined with reconstruction techniques based on system matrix, multi-dimensional SSME-MPI can be achieved. RESULTS: The effectiveness of the proposed method was validated through phantom and in vivo imaging experiments. The results demonstrate significant improvements in sensitivity (3.6-fold improvement) and spatial resolution (better than 1 mm) without any hardware modifications. CONCLUSION: These findings demonstrate the capability of SSME to enhance both the spatial resolution and sensitivity of MPI. SIGNIFICANCE: This method provides a solution to the ongoing challenge of balancing spatial resolution and sensitivity in MPI, potentially facilitating the implementation of MPI in a wider range of medical applications.

6.
Diabetes Metab Res Rev ; 40(4): e3814, 2024 May.
Article in English | MEDLINE | ID: mdl-38769695

ABSTRACT

AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.


Subject(s)
Diabetes, Gestational , Folic Acid , Methylenetetrahydrofolate Reductase (NADPH2) , Humans , Female , Diabetes, Gestational/blood , Diabetes, Gestational/metabolism , Pregnancy , Folic Acid/blood , Prospective Studies , Adult , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Biomarkers/blood , Follow-Up Studies , Ferredoxin-NADP Reductase/genetics , Genotype , China/epidemiology , Prognosis , Pregnancy Trimester, Second/blood , Homocysteine/blood , Homocysteine/metabolism
7.
J Exp Clin Cancer Res ; 43(1): 106, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589927

ABSTRACT

INTRODUCTION: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Recently, targeted therapies including PD1 (programmed cell death 1) antibodies have been used in advanced GC patients. However, identifying new biomarker for immunotherapy is still urgently needed. The objective of this study is to unveil the immune evasion mechanism of GC cells and identify new biomarkers for immune checkpoint blockade therapy in patients with GC. METHODS: Coimmunoprecipitation and meRIP were performed to investigate the mechanism of immune evasion of GC cells. Cocuture system was established to evaluate the cytotoxicity of cocultured CD8+ T cells. The clinical significance of HSPA4 upregulation was analyzed by multiplex fluorescent immunohistochemistry staining in GC tumor tissues. RESULTS: Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. The cytotoxicity of CD8+ T cells are impaired and PD1/PDL1 axis is activated when CD8+ T cells are cocultured with HSPA4 overexpressed GC cells. HSPA4 upregulation is associated with worse 5-year overall survival of GC patients receiving only surgery. It is an independent prognosis factor for worse survival of GC patients. In GC patients receiving the combined chemotherapy with anti-PD1 immunotherapy, HSPA4 upregulation is observed in responders compared with non-responders. CONCLUSION: HSPA4 upregulation causes the decrease of CD58 in GC cells via HSPA4/ALKBH5/CD58 axis, followed by PD1/PDL1 activation and impairment of CD8+ T cell's cytotoxicity, finally induces immune evasion of GC cells. HSPA4 upregulation is associated with worse overall survival of GC patients with only surgery. Meanwhile, HSPA4 upregulation predicts for better response in GC patients receiving the combined immunotherapy.


Subject(s)
CD8-Positive T-Lymphocytes , Stomach Neoplasms , Humans , CD8-Positive T-Lymphocytes/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Up-Regulation , Immune Evasion , Drug Therapy, Combination , HSP110 Heat-Shock Proteins/metabolism , AlkB Homolog 5, RNA Demethylase/metabolism
8.
BMC Pregnancy Childbirth ; 24(1): 297, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649888

ABSTRACT

BACKGROUND: Maternal overweight/obesity and excessive gestational weight gain (GWG) are frequently reported to be risk factors for obesity and other metabolic disorders in offspring. Cord blood metabolites provide information on fetal nutritional and metabolic health and could provide an early window of detection of potential health issues among newborns. The aim of the study was to explore the impact of maternal prepregnancy overweight/obesity and excessive GWG on cord blood metabolic profiles. METHODS: A case control study including 33 pairs of mothers with prepregnancy overweight/obesity and their neonates, 30 pairs of mothers with excessive GWG and their neonates, and 32 control mother-neonate pairs. Untargeted metabolomic profiling of umbilical cord blood samples were performed using UHPLC‒MS/MS. RESULTS: Forty-six metabolites exhibited a significant increase and 60 metabolites exhibited a significant reduction in umbilical cord blood from overweight and obese mothers compared with mothers with normal body weight. Steroid hormone biosynthesis and neuroactive ligand‒receptor interactions were the two top-ranking pathways enriched with these metabolites (P = 0.01 and 0.03, respectively). Compared with mothers with normal GWG, in mothers with excessive GWG, the levels of 63 metabolites were increased and those of 46 metabolites were decreased in umbilical cord blood. Biosynthesis of unsaturated fatty acids was the most altered pathway enriched with these metabolites (P < 0.01). CONCLUSIONS: Prepregnancy overweight and obesity affected the fetal steroid hormone biosynthesis pathway, while excessive GWG affected fetal fatty acid metabolism. This emphasizes the importance of preconception weight loss and maintaining an appropriate GWG, which are beneficial for the long-term metabolic health of offspring.


Subject(s)
Fetal Blood , Gestational Weight Gain , Metabolome , Humans , Female , Fetal Blood/chemistry , Fetal Blood/metabolism , Case-Control Studies , Pregnancy , Adult , Infant, Newborn , Metabolome/physiology , Overweight/blood , Obesity/blood , Pregnancy Complications/blood , Metabolomics/methods , Obesity, Maternal/blood
9.
Food Sci Nutr ; 12(4): 2908-2916, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38628221

ABSTRACT

Asparagus, a vital economic contributor, is a well-liked vegetable grown around the globe, and some secondary metabolites in its spear are beneficial to human health. Asparagus spears possess a significant quantity of nutrients and phytochemicals; however, the difference in these chemical compositions among various varieties has not been sufficiently studied. This work aimed to detect the chemical compositions of 30 varieties of asparagus and to assess them by principal component analysis (PCA). The results showed that the contents of these chemical compositions varied in varieties. Selenium (Se, 1.12-2.9 µg/100 g dry-weight [DW]) was abundant in asparagus, with an average dry matter content of 8.25%. Free amino acids (5.60-9.98 g/100 g DW) and polyphenols (6.34-8.67 mg/g DW) were both present in high amounts, along with flavonoids (4.218-8.22 mg/g DW) and protodioscin (0.44-1.96 mg/g DW). Correlation analysis, PCA, and hierarchical cluster analysis were used to conduct a comprehensive evaluation of asparagus. Atlas, Appolo, Jinggang 111, Jingke 2, and WS-1 were the top five varieties with comprehensive scores. This study provided valuable data for the breeding, quality improvement, processing, and utilization of asparagus varieties in the future.

10.
Front Endocrinol (Lausanne) ; 15: 1348382, 2024.
Article in English | MEDLINE | ID: mdl-38628589

ABSTRACT

Objective: To examine the effects of gestational weight gain on pregnancy outcomes and determine the optimal range of weight gain during pregnancy for Chinese women with type 2 diabetes mellitus. Methods: This retrospective cohort study included 691 Chinese women with type 2 diabetes mellitus from 2012 to 2020. The study utilized a statistical-based approach to determine the optimal range of gestational weight gain. Additionally, multivariate logistic regression analysis was conducted to assess the impact of gestational weight gain on pregnancy outcomes. Results: (1) In the obese subgroup, gestational weight gain below the recommendations was associated with decreased risks of large for gestational age (adjusted odds ratio [aOR] 0.19; 95% confidence interval [CI] 0.06-0.60) and macrosomia (aOR 0.18; 95% CI 0.05-0.69). In the normal weight subgroup, gestational weight gain below the recommendations of the Institute of Medicine was associated with decreased risks of preeclampsia (aOR 0.18; 95% CI 0.04-0.82) and neonatal hypoglycemia (aOR 0.38; 95% CI 0.15-0.97). (2) In the normal weight subgroup, gestational weight gain above the recommendations of the Institute of Medicine was associated with an increased risk of large for gestational age (aOR 4.56; 95% CI 1.54-13.46). In the obese subgroup, gestational weight gain above the recommendations was associated with an increased risk of preeclampsia (aOR 2.74; 95% CI 1.02, 7.38). (3) The optimal ranges of gestational weight gain, based on our study, were 9-16 kg for underweight women, 9.5-14 kg for normal weight women, 6.5-12 kg for overweight women, and 3-10 kg for obese women. (4) Using the optimal range of gestational weight gain identified in our study seemed to provide better prediction of adverse pregnancy outcomes. Conclusion: For Chinese women with type 2 diabetes, inappropriate gestational weight gain is associated with adverse pregnancy outcomes, and the optimal range of gestational weight gain may differ from the Institute of Medicine recommendations.


Subject(s)
Diabetes Mellitus, Type 2 , Gestational Weight Gain , Pre-Eclampsia , Pregnancy Complications , Pregnancy , Infant, Newborn , Female , Humans , Pregnancy Outcome/epidemiology , Retrospective Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Tertiary Care Centers , Pregnancy Complications/epidemiology , Pregnancy Complications/etiology , Weight Gain , Obesity/complications , China/epidemiology
11.
BMC Pregnancy Childbirth ; 24(1): 260, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605330

ABSTRACT

OBJECTIVE: The objective was to assess the efficacy and safety of low-dose aspirin for the prevention of preterm birth in nulliparous women. DATA SOURCES: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to June 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared aspirin to placebo in nulliparous women were eligible. METHODS: This study was reported in accordance with the PRISMA 2020 checklist. The primary outcomes of this study were the rates of preterm birth at less than 37 weeks and less than 34 weeks of gestation. The secondary outcomes included postpartum hemorrhage, placental abruption, cesarean section, any hypertensive disorder of pregnancy and small for gestational age. Relative risks with their 95% confidence intervals were calculated for analysis. Heterogeneity was assessed by Cochran's Q test and Higgins's I2. A random-effects model was used when I2 was > 50% to generate the RR and 95% CI; otherwise, a fixed-effects model was used. The risk of publication bias was assessed by funnel plots. We performed sensitivity analysis by sequentially omitting each included study to confirm the robustness of the analysis. RESULTS: Seven studies with a total of 29,029 participants were included in this review. Six studies were assessed as having a low risk of bias or an unclear risk of bias, and one study was judged as having a high risk of bias. In nulliparous women, low-dose aspirin was associated with a significant reduction in the rate of preterm birth at less than 34 weeks of gestational age (RR 0.84,95% CI: 0.71-0.99; I2 = 0%; P = 0.04), but we did not observe a significant difference in the rate of preterm birth at less than 37 weeks of gestation (RR 0.96,95% CI: 0.90-1.02; I2 = 31%; P = 0.18). Low-dose aspirin was associated with a significant increase in the rates of postpartum hemorrhage (RR 1.32,95% CI: 1.14-1.54; I2 = 0%; P = 0.0003), placental abruption (RR 2.18,95% CI: 1.10-4.32; I2 = 16%; P = 0.02) and cesarean section (RR 1.053, 95% CI: 1.001-1.108; I2 = 0%; P = 0.05) in nulliparous women. We also did not observe a significant effect of low-dose aspirin on the rates of any hypertensive disorder of pregnancy (RR 1.05, 95% CI: 0.96-1.14; I2 = 9%; P = 0.28) or small for gestational age (RR 0.96, 95% CI: 0.91-1.02; I2 = 0%; P = 0.16) in nulliparous women. Funnel plots indicated that no significant publication bias existed in this meta-analysis. Except for preterm birth at less than 34 weeks of gestation, placental abruption and cesarean section, the sensitivity analysis showed similar results, which confirmed the robustness of this meta-analysis. CONCLUSIONS: Low-dose aspirin might reduce the risk of preterm birth at less than 34 weeks of gestation in nulliparous women. The use of low-dose aspirin in nulliparous women increased the risk of postpartum hemorrhage and might increase the risk of placental abruption and cesarean section.


Subject(s)
Abruptio Placentae , Hypertension , Postpartum Hemorrhage , Premature Birth , Female , Pregnancy , Infant, Newborn , Humans , Premature Birth/epidemiology , Premature Birth/prevention & control , Premature Birth/drug therapy , Abruptio Placentae/epidemiology , Abruptio Placentae/prevention & control , Cesarean Section , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/prevention & control , Postpartum Hemorrhage/drug therapy , Placenta , Aspirin , Hypertension/drug therapy , Randomized Controlled Trials as Topic
12.
Mol Pharm ; 21(5): 2272-2283, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38607681

ABSTRACT

Over the years, there has been significant interest in PEGylated lipid-based nanocarriers within the drug delivery field. The inevitable interplay between the nanocarriers and plasma protein plays a pivotal role in their in vivo biological fate. Understanding the factors influencing lipid-based nanocarrier and protein corona interactions is of paramount importance in the design and clinical translation of these nanocarriers. Herein, discoid-shaped lipid nanodiscs (sNDs) composed of different phospholipids with varied lipid tails and head groups were fabricated. We investigated the impact of phospholipid components on the interaction between sNDs and serum proteins, particle stability, and biodistribution. The results showed that all of these lipid nanodiscs remained stable over a 15 day storage period, while their stability in the blood serum demonstrated significant differences. The sND composed of POPG exhibited the least stability due to its potent complement activation capability, resulting in rapid blood clearance. Furthermore, a negative correlation between the complement activation capability and serum stability was identified. Pharmacokinetic and biodistribution experiments indicated that phospholipid composition did not influence the capability of sNDs to evade the accelerated blood clearance phenomenon. Complement deposition on the sND was inversely associated with the area under the curve. Additionally, all lipid nanodiscs exhibited dominant adsorption of apolipoprotein. Remarkably, the POPC-based lipid nanodisc displayed a significantly higher deposition of apolipoprotein E, contributing to an obvious brain distribution, which provides a promising tool for brain-targeted drug delivery.


Subject(s)
Nanoparticles , Phospholipids , Protein Corona , Protein Corona/chemistry , Animals , Phospholipids/chemistry , Tissue Distribution , Mice , Nanoparticles/chemistry , Drug Carriers/chemistry , Nanostructures/chemistry , Male , Complement Activation/drug effects , Lipids/chemistry , Drug Delivery Systems/methods , Blood Proteins/metabolism , Blood Proteins/chemistry
13.
China CDC Wkly ; 6(13): 261-266, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38633198

ABSTRACT

What is already known about this topic?: The level of molybdenum (Mo) in a mother's urine has been linked to the growth rate of the fetus and the blood pressure levels in children. What is added by this report?: We evaluated the variations in maternal plasma Mo concentrations throughout pregnancy and their potential association with the risk of spontaneous preterm birth (SPB). What are the implications for public health practice?: Future research must determine the Mo levels in pregnant women across various regions in China. Moreover, particular attention needs to be given to the potential increase in Mo concentration throughout pregnancy and its possible adverse impacts on the health of both the mother and the fetus.

14.
Nutr Diabetes ; 14(1): 24, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38658555

ABSTRACT

BACKGROUND: Dietary imbalance, such as a lower proportion of complex carbohydrates and a higher protein diet, may contribute to gestational diabetes mellitus (GDM) risks through their metabolisms. However, there is a lack of knowledge regarding the association between butyrate, iso-butyrate, and GDM, which are metabolisms of the two primary nutrients above. This study aimed to clarify the association of butyrate and iso-butyrate with GDM. METHODS: A nested case-control study was conducted based on the Beijing Birth Cohort Study (BBCS) from 2017 to 2018. Totally, 99 singleton women were involved (GDM: n = 49, control: n = 50). All participants provided blood samples twice (in their first and second trimesters). Gas chromatography-mass spectrometry (GC-MS) was used for butyrate and iso-butyrate detection. Unconditional logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. RESULTS: The results showed that butyrate in the first trimester was negatively correlated with GDM (odds ratio (OR): 0.00, 95% confidential interval (CI): 0.00-0.21, P = 0.008), and iso-butyrate in the second trimester was positively related to GDM (OR: 627.68, 95% CI: 40.51-9724.56, P < 0.001). The ratio (butyrate/iso-butyrate) was negatively associated with GDM, both in the first trimester (OR: 0.00, 95%CI: 0.00-0.05, P < 0.001) and in the second trimester (OR: 0.52, 95% CI: 0.34-0.80, P = 0.003). The area under the curve (AUC) using the ratio in the first trimester combined with clinical risk factors achieved 0.89 (95% CI: 0.83-0.95). Iso-butyrate in the second trimester combined with clinical risk factors achieved an AUC of 0.97 (95% CI: 0.92-1.00). CONCLUSIONS: High iso-butyrate and low butyrate levels may be associated with an increased risk of GDM. As they are produced through dietary nutrient formation by gut microbiota, further studies on the association of dietary intake and butyrate or iso-butyrate concentration in plasma may help find a novel approach to nutritional intervention for GDM.


Subject(s)
Butyrates , Diabetes, Gestational , Humans , Female , Diabetes, Gestational/blood , Diabetes, Gestational/prevention & control , Pregnancy , Adult , Case-Control Studies , Butyrates/blood , Pregnancy Trimester, First/blood , Pregnancy Trimester, Second/blood , Cohort Studies
15.
Front Plant Sci ; 15: 1368260, 2024.
Article in English | MEDLINE | ID: mdl-38529061

ABSTRACT

Anthocyanin is an important pigment that prevents oxidative stress and mediates adaptation of plants to salt stress. Peanuts with dark red and black testa are rich in anthocyanin. However, correlation between salt tolerance and anthocyanin content in black and dark red testa peanuts is unknown. In this study, three peanut cultivars namely YZ9102 (pink testa), JHR1 (red testa) and JHB1 (black testa) were subjected to sodium chloride (NaCl) stress. The plant growth, ion uptake, anthocyanin accumulation, oxidation resistance and photosynthetic traits were comparatively analyzed. We observed that the plant height, leaf area and biomass under salt stress was highly inhibited in pink color testa (YZ9102) as compare to black color testa (JHB1). JHB1, a black testa colored peanut was identified as the most salt-tolerance cultivar, followed by red (JHR1) and pink(YZ9102). During salt stress, JHB1 exhibited significantly higher levels of anthocyanin and flavonoid accumulation compared to JHR1 and YZ9102, along with increased relative activities of antioxidant protection and photosynthetic efficiency. However, the K+/Na+ and Ca2+/Na+ were consistently decreased among three cultivars under salt stress, suggesting that the salt tolerance of black testa peanut may not be related to ion absorption. Therefore, we predicted that salt tolerance of JHB1 may be attributed to the accumulation of the anthocyanin and flavonoids, which activated antioxidant protection against the oxidative damage to maintain the higher photosynthetic efficiency and plant growth. These findings will be useful for improving salt tolerance of peanuts.

18.
Comput Biol Med ; 171: 108127, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38350397

ABSTRACT

Identifying drug-protein interactions (DPIs) is crucial in drug discovery and repurposing. Computational methods for precise DPI identification can expedite development timelines and reduce expenses compared with conventional experimental methods. Lately, deep learning techniques have been employed for predicting DPIs, enhancing these processes. Nevertheless, the limitations observed in prior studies, where many extract features from complete drug and protein entities, overlooking the crucial theoretical foundation that pharmacological responses are often correlated with specific substructures, can lead to poor predictive performance. Furthermore, certain substructure-focused research confines its exploration to a solitary fragment category, such as a functional group. In this study, addressing these constraints, we present an end-to-end framework termed BCMMDA for predicting DPIs. The framework considers various substructure types, including branch chains, common substructures, and specific fragments. We designed a specific feature learning module by combining our proposed multi-dimensional attention mechanism with convolutional neural networks (CNNs). Deep CNNs assist in capturing the synergistic effects among these fragment sets, enabling the extraction of relevant features of drugs and proteins. Meanwhile, the multi-dimensional attention mechanism refines the relationship between drug and protein features by assigning attention vectors to each drug compound and amino acid. This mechanism empowers the model to further concentrate on pivotal substructures and elements, thereby improving its ability to identify essential interactions in DPI prediction. We evaluated the performance of BCMMDA on four well-known benchmark datasets. The results indicated that BCMMDA outperformed state-of-the-art baseline models, demonstrating significant improvement in performance.


Subject(s)
Benchmarking , Drug Discovery , Drug Compounding , Neural Networks, Computer
19.
Natl Sci Rev ; 11(3): nwad311, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38312386

ABSTRACT

Optical communication is a particularly compelling technology for tackling the speed and capacity bottlenecks in data communication in modern society. Currently, the silicon photodetector plays a dominant role in high-speed optical communication across the visible-near-infrared spectrum. However, its intrinsic rigid structure, high working bias and low responsivity essentially limit its application in next-generation flexible optoelectronic devices. Herein, we report a narrow-bandgap non-fullerene acceptor (NFA) with a remarkable π-extension in the direction of both central and end units (CH17) with respect to the Y6 series, which demonstrates a more effective and compact 3D molecular packing, leading to lower trap states and energetic disorders in the photoactive film. Consequently, the optimized solution-processed organic photodetector (OPD) with CH17 exhibits a remarkable response time of 91 ns (λ = 880 nm) due to the high charge mobility and low parasitic capacitance, exceeding the values of most commercial Si photodiodes and all NFA-based OPDs operating in self-powered mode. More significantly, the flexible OPD exhibits negligible performance attenuation (<1%) after bending for 500 cycles, and maintains 96% of its initial performance even after 550 h of indoor exposure. Furthermore, the high-speed OPD demonstrates a high data transmission rate of 80 MHz with a bit error rate of 3.5 [Formula: see text] 10-4, meaning it has great potential in next-generation high-speed flexible optical communication systems.

20.
Front Nutr ; 11: 1336361, 2024.
Article in English | MEDLINE | ID: mdl-38362103

ABSTRACT

Introduction: Spontaneous preterm birth (SPB) is a significant cause of neonatal mortality, yet its etiology remains unclear. Cobalt, an essential trace element, might be a risk factor for SPB. This study aims to investigate the relationship between maternal serum cobalt concentration and SPB, and to clarify the role of blood lipids and fasting blood glucose (FBG) in this relationship. Methods: We conducted a nested case-control study within the Beijing Birth Cohort Study. Serum samples were obtained from 222 pregnant women with SPB and 224 controls during the first (7-13 weeks of pregnancy) and third trimesters (32-42 weeks of pregnancy). Serum cobalt concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Fasting blood glucose and lipids levels were detected using a fully automated biochemical immunoassay instrument. Logistic regression models and linear regression models were established to explore the association between serum cobalt concentration and the risk of SPB in pregnant women, and to test the mediating effect of fasting blood glucose (FBG) and lipids. Results: We found that the serum cobalt concentration in mothers with SPB and controls was similar in the first trimester, with values of 0.79 (0.58-1.10) ng/mL and 0.75 (0.51-1.07) ng/mL, respectively. However, in the third trimester, the cobalt concentration increased to 0.88 (0.59-1.14) ng/mL and 0.84 (0.52-1.19) ng/mL, respectively. In the logistic regression model, when considering the third trimester of pregnancy, after adjusting for ethnicity, pre-pregnancy body mass index (BMI), maternal age, education, income, and parity, it was observed that the medium level of cobalt concentration (0.63-1.07 ng/ml) had a negative correlation with the risk of SPB. The odds ratio (OR) was 0.56, with a 95% confidence interval of 0.34-0.90 ng/mL and a p-value of 0.02. This suggests that cobalt in this concentration range played a protective role against SPB. Additionally, it was found that FBG in the third trimester of pregnancy had a partial intermediary role, accounting for 9.12% of the association. However, no relationship between cobalt and SPB risk was found in the first trimester. Conclusion: During the third trimester, intermediate levels of maternal cobalt appear to offer protection against SPB, with FBG playing a partial mediating role. To further clarify the optimal cobalt concentrations during pregnancy for different populations, a multi-center study with a larger sample size is necessary. Additionally, exploring the specific mechanism of FBG's mediating role could provide valuable insights for improving the prevention of SPB.

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