DNA Self-Assembly Optimization by Betaine and Its Analogs.

The self-assembly yield of DNA nanostructures can be exponentially lower with increasing structural complexity. Few optimizing strategies are available in the DNA nanotechnology field for the assembly yield improvement. Here, betaine and its analogs are applied as supplementary ingredients in DNA self-assembly. Such a simple implementation results in effective yield improvement. Through a comprehensive investigation, a reliable yield improvement of two- to threefold is achieved for a number of DNA nanostructures with considerable complexity.

Recent advances in neuroinflammation prevention and therapy: the role of natural products and underlying mechanisms based on molecular targets.

Neuroinflammation is initiated in response to a variety of endogenous and exogenous sources. As the resident macrophages of the central nervous system, the polarization of microglia into either the M1 pro-inflammatory phenotype or the M2 anti-inflammatory phenotype holds great promise as a therapeutic strategy for neuroinflammation. Natural products, comprising a vital chemical library with distinctive structures and diverse functions, have been extensively employed to modulate microglial polarization for the treatment of neuroinflammation. In this review, we present up-to-date and extensive insights into the therapeutic effects and underlying mechanisms of natural products in the context of neuroinflammation. Furthermore, the review aims to present a new perspective by focusing on the targets of natural compounds, elucidating the molecular mechanisms and guiding the transition from natural-derived lead compounds to potential anti-neuroinflammatory drugs. Additionally, we provide a comprehensive overview of the challenges and limitations associated with the utilization of natural products for neuroinflammation therapy.

Walnut-Derived Peptides Ameliorate Scopolamine-Induced Memory Impairments in a Mouse Model via Activation of Peroxisome Proliferator-Activated Receptor γ-Mediated Excitotoxicity.

We investigated the protective effect of walnut peptides and YVPFPLP (YP-7) on scopolamine-induced memory impairment in mice and ß-amyloid (Aß)-induced excitotoxic injury in primary hippocampal neurons, respectively. Additionally, the protective mechanism of YP-7 on neuronal excitotoxicity was explored. Mouse behavioral and hippocampal slice morphology experiments indicate that YP-7 improves the learning and memory abilities of cognitively impaired mice and protects synaptic integrity. Immunofluorescence, western blotting, and electrophysiological experiments on primary hippocampal neurons indicate that YP-7 inhibits neuronal damage caused by excessive excitation of neurons induced by Aß. HT-22 cell treatment with peroxisome proliferator-activated receptor γ (PPARγ) activators and inhibitors showed that YP-7 activates PPARγ expression and maintains normal neuronal function by forming stable complexes with PPARγ to inhibit the extracellular regulated protein kinase pathway. Therefore, YP-7 can ameliorate glutamate-induced excitotoxicity and maintain neuronal signaling. This provides a theoretical basis for active peptides to ameliorate excitotoxicity and the development of functional foods.

Application of nanoparticles as novel adsorbents in blood purification strategies.

BACKGROUND: Blood purification therapy for patients overloaded with metabolic toxins or drugs still needs improvement. Blood purification therapies, such as in hemodialysis or peritoneal dialysis can profit from a combined application with nanoparticles. SUMMARY: In this review, the published literature is analyzed with respect to nanomaterials that have been customized and functionalized as nano-adsorbents during blood purification therapy. Liposomes possess a distinct combined structure composed of a hydrophobic lipid bilayer and a hydrophilic core. The liposomes which have enzymes in their aqueous core or obtain specific surface modifications of the lipid bilayer can offer appreciated advantages. Preclinical and clinical experiments with such modified liposomes show that they are highly efficient and generally safe. They may serve as indirect and direct adsorption materials both in hemodialysis and peritoneal dialysis treatment for patients with renal or hepatic failure. Apart from dialysis, nanoparticles made of specially designed metal and activated carbon have also been utilized to enhance the removal of solutes during hemoadsorption. Results are a superior adsorption capacity and a good hemocompatibility shown during treatment of patients with toxication or end-stage renal disease. In summary, nanomaterials are promising tools for improving the treatment efficacy of organ failure or toxication. KEY MESSAGES The pH-transmembrane liposomes and enzyme-loaded liposomes are two representatives of liposomes with modified aqueous inner core which have been put into practice in dialysis. Unmodified or physiochemically modified liposomal bilayers are ideal binders for lipophilic protein-bound uremic toxins or cholestatic solutes, thus liposome-supported dialysis could become the next-generation hemodialysis treatment of artificial liver support system. Novel nano-based sorbents featuring large surface area, high adsorption capacity and decent biocompatibility have shown promise in treatment of uremia, hyperbilirubinemia, intoxication, and sepsis. A major challenge of production lies in avoiding changes in physical and chemical properties induced by manufacturing and sterilizing procedures.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

Synthetic Genomics: Repurposing Biological Systems for Applications in Engineering Biology.

Substantial improvements in DNA sequencing and synthesis technologies and increased understanding of genome biology have empowered the development of synthetic genomics. The ability to design and construct engineered living cells boosted up by synthetic chromosomes provides opportunities to tackle enormous current and future challenges faced by humanity and the planet. Here we review the progresses, considerations, challenges, and future direction of the "design-build-test-learn" cycle used in synthetic genomics. We also discuss future applications enabled by synthetic genomics as this emerging field shapes and revolutionizes biomanufacturing and biomedicine.

Metabolome-wide Mendelian randomization reveals causal effects of betaine and N-acetylornithine on impairment of renal function.

Background: Chronic kidney disease (CKD) is a common public health problem, which is characterized as impairment of renal function. The associations between blood metabolites and renal function remained unclear. This study aimed to assess the causal effect of various circulation metabolites on renal function based on metabolomics. Methods: We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of genetically determined metabolites on renal function. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, while summary-level data for creatinine-based estimated glomerular filtration rate (eGFR) or CKD occurrence were set the outcomes. Inverse variance weighted (IVW) was used for primary causality analysis and other methods including weight median, MR-egger, and MR-PRESSO were applied as complementary analysis. Cochran Q test, MR-Egger intercept test, MR-PRESSO global test and leave-one-out analysis were used for sensitivity analysis. For the identified metabolites, reverse MR analysis, linkage disequilibrium score (LDSC) regression and multivariable MR (MVMR) analysis were performed for further evaluation. The causality of the identified metabolites on renal function was further validated using GWAS data for cystatin-C-based eGFR. All statistical analyses were performed in R software. Results: In this MR analysis, a total of 44 suggestive associations corresponding to 34 known metabolites were observed. After complementary analysis and sensitivity analysis, robust causative associations between two metabolites (betaine and N-acetylornithine) and renal function were identified. Reverse MR analysis showed no causal effects of renal function on betaine and N-acetylornithine. MVMR analysis revealed that genetically predicted betaine and N-acetylornithine could directly influence independently of each other. The causal effects of betaine and N-acetylornithine were also found on cystatin-C-based eGFR. Conclusion: Our study provided evidence to support the causal effects of betaine and N-acetylornithine on renal function. These findings required further investigations to conduct mechanism exploration and drug target selection of these identified metabolites.

Comparative genomic and transcriptome analyses of two Pectobacterium brasiliense strains revealed distinct virulence determinants and phenotypic features.

Potato soft rot caused by Pectobacterium spp. are devastating diseases of potato which cause severe economic losses worldwide. Pectobacterium brasiliense is considered as one of the most virulent species. However, the virulence mechanisms and pathogenicity factors of this strain have not been fully elucidated. Here, through pathogenicity screening, we identified two Pectobacterium brasiliense isolates, SM and DQ, with distinct pathogenicity levels. SM exhibits higher virulence compared to DQ in inducing aerial stem rot, blackleg and tuber soft rot. Our genomic and transcriptomic analyses revealed that SM encodes strain specific genes with regard to plant cell wall degradation and express higher level of genes associated with bacterial motility and secretion systems. Our plate assays verified higher pectinase, cellulase, and protease activities, as well as fast swimming and swarming motility in SM. Importantly, a unique endoglucanase S specific to SM was identified. Expression of this cellulase in DQ greatly enhances its virulence compared to wild type strain. Our study sheds light on possible determinants causing different pathogenicity of Pectobacterium brasiliense species with close evolutionary distance and provides new insight into the direction of genome evolution in response to host variation and environmental stimuli.

Isolation and characterization of pure cultures for metabolizing 1,4-dioxane in oligotrophic environments.

1,4-Dioxane concentration in most contaminated water is much less than 1 mg/L, which cannot sustain the growth of most reported 1,4-dioxane-metabolizing pure cultures. These pure cultures were isolated following enrichment of mixed cultures at high concentrations (20 to 1,000 mg/L). This study is based on a different strategy: 1,4-dioxane-metabolizing mixed cultures were enriched by periodically spiking 1,4-dioxane at low concentrations (≤1 mg/L). Five 1,4-dioxane-metabolizing pure strains LCD6B, LCD6D, WC10G, WCD6H, and WD4H were isolated and characterized. The partial 16S rRNA gene sequencing showed that the five bacterial strains were related to Dokdonella sp. (98.3%), Acinetobacter sp. (99.0%), Afipia sp. (99.2%), Nitrobacter sp. (97.9%), and Pseudonocardia sp. (99.4%), respectively. Nitrobacter sp. WCD6H is the first reported 1,4-dioxane-metabolizing bacterium in the genus of Nitrobacter. The net specific growth rates of these five cultures are consistently higher than those reported in the literature at 1,4-dioxane concentrations <0.5 mg/L. Compared to the literature, our newly discovered strains have lower half-maximum-rate concentrations (1.8 to 8.2 mg-dioxane/L), lower maximum specific 1,4-dioxane utilization rates (0.24 to 0.47 mg-dioxane/(mg-protein ⋅ d)), higher biomass yields (0.29 to 0.38 mg-protein/mg-dioxane), and lower decay coefficients (0.01 to 0.02 d-1). These are characteristics of microorganisms living in oligotrophic environments.

High Energy Density in All-Organic Polyimide-Based Composite Film by Doping of Polyvinylidene Fluoride-Based Relaxor Ferroelectrics.

Recently, due to the advantages of superior compatibility, fewer interface defects, and a high electric breakdown field, all-organic dielectric composites have attracted significant research interest. In this investigation, we produced all-organic P(VDF-TrFE-CFE) terpolymer/PI (terp/PI) composite films by incorporating a small amount of terpolymer into PI substrates for high energy density capacitor applications. The resulting terp/PI-5 (5% terpolymer) composite films exhibit a permittivity of 3.81 at 1 kHz, which is 18.7% greater than that of pristine PI (3.21). Furthermore, the terp/PI-5 film exhibited the highest energy density (9.67 J/cm3) and a relatively high charge-discharge efficiency (84.7%) among the terp/PI composite films. The energy density of the terp/PI-5 film was increased by 59.8% compared to that of the pristine PI film. The TSDC results and band structure analysis revealed the presence of deeper traps in the terp/PI composites, contributing to the suppression of leakage current and improved charge-discharge efficiency. Furthermore, durability tests confirm the stability of the composite films under extended high-temperature exposure and cycling, establishing their viability for practical applications.

Associations of dichlorophenols, trichlorophenols, and ortho-phenylphenol with the risk and prognosis of diabetes and prediabetes: A population-based study.

2,4-dichlorophenol (2,4-DCP), 2,5-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP, and ortho-phenylphenol (OPP) are widely present in the environment. However, their associations with risk and prognosis of diabetes and prediabetes remains unclear. We investigated the associations of these five phenols with the risk of diabetes and prediabetes, and with all-cause and cardiovascular disease (CVD) mortality, in adults with diabetes or prediabetes (n=6419). Information on diabetes and prediabetes indicators, and mortality data was collected from the National Health and Nutrition Examination Survey. Logistic and Cox regression models were used to explore the associations of the five phenols with risk and prognosis of diabetes and prediabetes. Participants in the highest urinary 2,4-DCP and 2,5-DCP tertiles had higher odds of diabetes [adjusted odds ratio (aOR), 1.34, 95 % confidence interval (CI): 1.10, 1.62; aOR, 1.29, 95 % CI: 1.07, 1.56, respectively] than those in the lowest tertiles. Participants with urinary OPP concentrations above the limit of detection (LOD), but below median had an aOR of 1.25 (95 % CI: 1.08, 1.46) for prediabetes compared to those with concentrations below the LOD. In adults with diabetes, the highest 2,4-DCP and 2,5-DCP tertiles were associated with all-cause mortality [adjusted hazard ratio (aHR), 1.49; 95 % CI: 1.08, 2.06; aHR, 1.49; 95 % CI: 1.08, 2.05, respectively] and CVD mortality (aHR, 2.58; 95 % CI: 1.33, 4.97; aHR, 1.96; 95 % CI: 1.06, 3.60, respectively) compared with the lowest tertiles. Compared with 2,4,5-TCP concentrations below the LOD, those above median were associated with all-cause mortality (aHR: 1.75; 95 % CI: 1.24, 2.48) and CVD mortality (aHR: 2.34; 95 % CI: 1.19, 4.63) in adults with prediabetes. Furthermore, the associations between these phenols and mortality were strengthened in some subgroups. Environmental exposure to 2,4-DCP, 2,5-DCP, 2,4,5-TCP, and OPP increases the risk or adverse prognosis of diabetes or prediabetes in adults in the US. Further studies are required to confirm these findings.

Correction: Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice.

Correction for 'Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice' by Yanru Li et al., Food Funct., 2024, 15, 2295-2313, https://doi.org/10.1039/D3FO05076A.

Advancements in acne detection: application of the CenterNet network in smart dermatology.

Introduction: Acne detection is critical in dermatology, focusing on quality control of acne imagery, precise segmentation, and grading. Traditional research has been limited, typically concentrating on singular aspects of acne detection. Methods: We propose a multi-task acne detection method, employing a CenterNet-based training paradigm to develop an advanced detection system. This system collects acne images via smartphones and features multi-task capabilities for detecting image quality and identifying various acne types. It differentiates between noninflammatory acne, papules, pustules, nodules, and provides detailed delineation for cysts and post-acne scars. Results: The implementation of this multi-task learning-based framework in clinical diagnostics demonstrated an 83% accuracy in lesion categorization, surpassing ResNet18 models by 12%. Furthermore, it achieved a 76% precision in lesion stratification, outperforming dermatologists by 16%. Discussion: Our framework represents a advancement in acne detection, offering a comprehensive tool for classification, localization, counting, and precise segmentation. It not only enhances the accuracy of remote acne lesion identification by doctors but also clarifies grading logic and criteria, facilitating easier grading judgments.

[Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis]. / å›Šæ€§çº¤ç»´åŒ–å„¿ç«¥è¥å »çŠ¶å†µä¸Žä¸´åºŠç‰¹å¾å’Œè‚ºåŠŸèƒ½çš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function. METHODS: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed. RESULTS: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin (P<0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group (P<0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters (P<0.05). CONCLUSIONS: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Toward High-Performance Hydrogenation at Room Temperature Through Tailoring Nickel Catalysts Stable in Aqueous Solution.

The development of highly active, reusable catalysts for aqueous-phase reactions is challenging. Herein, metallic nickel is encapsulated in a nitrogen-doped carbon-silica composite (SiO2@Ni@NC) as a catalyst for the selective hydrogenation of vanillin in aqueous media. The constructed catalyst achieved 99.8% vanillin conversion and 100% 4-hydroxymethyl-2-methoxyphenol selectivity at room temperature. Based on combined scanning transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman analyses, the satisfactory catalytic performance is attributed to the composite structure consisting of an active metal, carbon, and silica. The hydrophilic silica core promoted dispersion of the catalyst in aqueous media. Moreover, the external hydrophobic NC layer has multiple functions, including preventing oxidation or leaching of the internal metal, acting as a reducing agent to reduce the internal metal, regulating the active-site microenvironment by enriching the concentrations of H2 and organic reactants, and modifying the electronic structure of the active metal via metal-support interactions. Density functional theory calculations indicated that NC facilitates vanillin adsorption and hydrogen dissociation to promote aqueous-phase hydrogenation. This study provides an efficient strategy for constructing encapsulated Ni-based amphiphilic catalysts to upgrade biomass-derived compounds.

DFSNet: A 3D Point Cloud Segmentation Network toward Trees Detection in an Orchard Scene.

In order to guide orchard management robots to realize some tasks in orchard production such as autonomic navigation and precision spraying, this research proposed a deep-learning network called dynamic fusion segmentation network (DFSNet). The network contains a local feature aggregation (LFA) layer and a dynamic fusion segmentation architecture. The LFA layer uses the positional encoders for initial transforming embedding, and progressively aggregates local patterns via the multi-stage hierarchy. The fusion segmentation module (Fus-Seg) can format point tags by learning a multi-embedding space, and the generated tags can further mine the point cloud features. At the experimental stage, significant segmentation results of the DFSNet were demonstrated on the dataset of orchard fields, achieving an accuracy rate of 89.43% and an mIoU rate of 74.05%. DFSNet outperforms other semantic segmentation networks, such as PointNet, PointNet++, D-PointNet++, DGCNN, and Point-NN, with improved accuracies over them by 11.73%, 3.76%, 2.36%, and 2.74%, respectively, and improved mIoUs over the these networks by 28.19%, 9.89%, 6.33%, 9.89, and 24.69%, respectively, on the all-scale dataset (simple-scale dataset + complex-scale dataset). The proposed DFSNet can capture more information from orchard scene point clouds and provide more accurate point cloud segmentation results, which are beneficial to the management of orchards.

A Synthesis of α-Alkyl Cycloenones by Pd-Catalyzed Suzuki-Miyaura Coupling with Cyclic Morita-Baylis-Hillman Adducts.

We herein disclose a Pd-catalyzed Suzuki-Miyaura coupling of cyclic Morita-Baylis-Hillman adducts with organoboronic acids under mild conditions, which allows for a rapid access to diverse α-alkyl substituted cycloenones. The advantage of this method resides in the employment of functionalized allyl alcohols as the unprecedented electrophilic partners in the absence of external activators.

Single-cluster Functionalized TiO2 Nanotube Array for Boosting Water Oxidation and CO2 Photoreduction to CH3OH.

Solar-driven CO2 reduction and water oxidation to liquid fuels represents a promising solution to alleviate energy crisis and climate issue, but it remains a great challenge for generating CH3OH and CH3CH2OH dominated by multi-electron transfer. Single-cluster catalysts with super electron acceptance, accurate molecular structure, customizable electronic structure and multiple adsorption sites, have led to greater potential in catalyzing various challenging reactions. However, accurately controlling the number and arrangement of clusters on functional supports still faces great challenge. Herein, we develop a facile electrosynthesis method to uniformly disperse Wells-Dawson- and Keggin-type polyoxometalates on TiO2 nanotube arrays, resulting in a series of single-cluster functionalized catalysts P2M18O62@TiO2 and PM12O40@TiO2 (M = Mo or W). The single polyoxometalate cluster can be distinctly identified and serves as electronic sponge to accept electrons from excited TiO2 for enhancing surface-hole concentration and promote water oxidation. Among these samples, P2Mo18O62@TiO2-1 exhibits the highest electron consumption rate of 1260 µmol g-1 for CO2-to-CH3OH conversion with H2O as the electron source, which is 11 times higher than that of isolated TiO2 nanotube arrays. This work supplied a simple synthesis method to realize the single-dispersion of molecular cluster to enrich surface-reaching holes on TiO2, thereby facilitating water oxidation and CO2 reduction.

Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.