Performance enhancement, bacterial communities optimization and emerging pollutants elimination by microalgal-bacterial consortium for treating aquaculture pond sediments.

Aquaculture pond sediments have a notable influence on the ecosystem balance and farmed animal health. In this study, microalgal-bacterial immobilization (MBI) was designed to improve aquaculture pond sediments via synergistic interactions. The physicochemical characteristics, bacterial communities, and the removal efficiencies of emerging pollutants were systematically investigated. The consortium containing diatom Navicula seminulum and Alcaligenes faecalis was cultivated and established in the free and immobilized forms for evaluating the treatment performance. The results indicated that the immobilized group exhibited superior performance in controlling nutrient pollutants, shaping and optimizing the bacterial community compositions with the enrichment of functional bacteria. Additionally, it showed a stronger positive correlation between the bacterial community shifts and nutrient pollutants removal compared to free cells. Furthermore, the immobilized system maintained the higher removal performance of emerging pollutants (heavy metals, antibiotics, and pathogenic Vibrios) than free group. These findings confirmed that the employment of immobilized N. seminulum and A. faecalis produced more synergistic benefits and exerted more improvements than free cells in ameliorating aquaculture pond sediments, suggesting the potential for engineering application of functional microalgal-bacterial consortium in aquaculture.

Feasibility and safety of modified en-bloc resection in endoscopic thyroid surgery via bilateral areolar approach - long-term institutional analysis ten years after surgery.

Purpose: This study aimed to introduce a new modified en-bloc resection method and evaluate its feasibility and safety in endoscopic thyroid surgery via bilateral areolar approach (BAA). Methods: Papillary thyroid carcinoma (PTC) patients who underwent lobectomy and ipsilateral central node dissection (CND) via the BAA approach were retrospectively reviewed. Their clinical characteristics and outcomes were evaluated, including operative duration, lymph node yield (LNY), surgical complications, recurrence rate, and metastasis rate, over a ten-year follow-up period. Simultaneous lobectomy and CND were performed in the modified en-bloc group, whereas lobectomy was performed first, followed by CND in the conventional group. Results: The study included 108 patients in the modified en-bloc group and 213 in the conventional group. There were no significant differences in gender, age, tumor locations, tumor dominant nodule size, or the incidence of concomitant Hashimoto thyroiditis when comparing clinicopathologic characteristics. The comparison of operative duration (P = 0.14), blood loss (P = 0.13), postoperative hospital stay (P = 0.58), incidence of transient vocal cord paralysis (P = 0.90) and hypocalcemia (P = 0.60) did not show any differences. The mean LNY achieved in the central compartment of the modified en-bloc group (7.5 ± 4.5) was significantly higher than that in the conventional group (5.6 ± 3.6). Two patients in the modified en-bloc group and two in the conventional group experienced metastasis after surgery during the ten-year follow-up (1.8% vs. 0.9%, P = 0.60). The learning curve analysis showed a significant decrease in operative duration after the 25-35th cases for modified en-bloc resection. Conclusions: The modified en-bloc resection method in endoscopic thyroid surgery via BAA is a technically feasible and safe procedure with excellent cosmetic outcomes for selective PTC patients.

Photodynamic Effect of Vascular-targeted Polyphenol Nanoparticles on Endothelial Cells.

BACKGROUND: Port wine stains (PWS) are vascular malformations, and photodynamic therapy (PDT) is a promising treatment. Emerging drug delivery method employs nanoparticles (NPs) to enhance drug permeability and retention in diseased blood vessels and improving drug bioavailability. (-) -epigallocatechin-3-gallate glycine (EGCG) has anti-angiogenetic effects and boosts photodynamic therapy. Chlorin e6 (Ce6) is capable of efficiently producing singlet oxygen, rendering it a very promising photosensitizer for utilization in nanomedicine. MATERIAL AND METHODS: EGCG-Ce6-NPs were synthesized and characterized using various techniques. The photodynamic effects of EGCG-Ce6-NPs on endothelial cells were evaluated. The compatibility and toxicity of the nanoparticle was tested using the CCK-8 assay. The intracellular uptake of the nanoparticle was observed using an inverted fluorescence microscope, and the intracellular fluorescence intensity was detected using flow cytometry. The ROS generation and apoptosis induced by EGCG-Ce6-NPs was observed using confocal laser scanning microscope and flow cytometry respectively. RESULTS: EGCG-Ce6-NPs exhibited stability, spherical shape of uniform size while reducing the particle diameter, low polydisperse profile and retaining the ability to effectively generate singlet oxygen. These characteristics suggest promising potential for enhancing drug permeability and retention. Additionally, EGCG-Ce6-NPs demonstrated good compatibility with endothelial cells and enhanced intracellular uptake of Chlorin e6. Furthermore, EGCG-Ce6-NPs increased activation efficiency, induced significant toxicity, more reactive oxygen species, and higher rate of late apoptosis after laser irradiation. CONCLUSION: This in vitro study showed the potentials EGCG-Ce6-NPs for the destruction of endothelial cells in vasculature.

KLRB1 defines an activated phenotype of CD4+ T cells and shows significant upregulation in patients with primary Sjögren's syndrome.

OBJECTIVE: This study aimed to investigate the role of KLRB1 (CD161) in human CD4+ T cells and elucidate its significance in primary Sjögren's syndrome (pSS). METHODS: Peripheral blood samples from 37 healthy controls and 44 pSS patients were collected. The publicly available single-cell RNA-Seq data from pSS patient PBMCs were utilized to analyse KLRB1 expression in T cells. KLRB1-expressing T lymphocyte subset proportions in pSS patients and healthy controls were determined by flow cytometry. CD25, Ki-67, cytokine secretion, and chemokine receptor expression in CD4+ KLRB1+ T cells were detected and compared with those in CD4+ KLRB1- T cells. Correlation analysis was conducted between KLRB1-related T-cell subsets and clinical indicators. ROC curves were generated to explore the diagnostic potential of KLRB1 for pSS. RESULTS: KLRB1 was significantly upregulated following T-cell activation, and Ki-67 and CD25 expression was significantly greater in CD4+ KLRB1+ T cells than in CD4+ KLRB1- T cells. KLRB1+ CD4+ T cells exhibited greater IL-17A, IL-21, IL-22, and IFN-γ secretion upon stimulation, and there were significantly greater proportions of CCR5+, CCR2+, CX3CR1+, CCR6+, and CXCR3+ cells among CD4+ KLRB1+ T cells than among CD4+ KLRB1- T cells. Compared with that in HCs, KLRB1 expression in CD4+ T cells was markedly elevated in pSS patients and significantly correlated with clinical disease indicators. CONCLUSION: KLRB1 is a characteristic molecule of the CD4+ T-cell activation phenotype. The increased expression of KLRB1 in the CD4+ T cells of pSS patients suggests its potential involvement in the pathogenesis of pSS and its utility as an auxiliary diagnostic marker for pSS.

The prevention effect of pulsed electromagnetic fields treatment on senile osteoporosis in vivo via improving the inflammatory bone microenvironment.

This study aimed to assess PEMF in a rat model of senile osteoporosis and its relationship with NLRP3-mediated low-grade inflammation in the bone marrow microenvironment. A total of 24 Sprague Dawley (SD) rats were included in this study. Sixteen of them were 24-month natural-aged male SD rats, which were randomly distributed into the Aged group and the PEMF group (n = 8 per group). The remaining 8 3-month -old rats were used as the Young positive control group (n = 8). Rats in the PEMF group received 12 weeks of PEMF with 40 min/day, five days per week, while the other rats received placebo PEMF intervention. Bone mineral density/microarchitecture, serum levels of CTX-1 and P1CP, and NLRP3-related signaling genes and proteins in rat bone marrow were then analyzed. The 12-week of PEMF showed significant mitigation of aging-induced bone loss and bone microarchitecture deterioration, i.e. PEMF increased the bone mineral density of the proximal femur and L5 vertebral body and improved parameters of the proximal tibia and L4 vertebral body. Further analysis showed that PEMF reversed aging-induced bone turnover, specifically, decreased serum CTX-1 and elevated serum P1CP. Furthermore, PEMF also dramatically inhibited NLRP3-mediated low-grade inflammation in the bone marrow, i.e. PEMF inhibited the levels of NLRP3, proCaspase1, cleaved Caspase1, IL-1ß, and GSDMD-N. The study demonstrated that PEMF could mitigate the aging-induced bone loss and reverses the deterioration of bone microarchitecture probably through inhibiting NLRP3-mediated low-grade chronic inflammation to improve the inflammatory bone microenvironment in aged rats.

pH-Responsive Carrier-Free Polyphenol Nanoparticles Assembled by Oxidative Polymerization with Enhanced Stability and Antioxidant Activity for Improved Bioaccessibility.

Encapsulation of plant polyphenols with micro-/nano-carriers for enhanced bioavailability has been well documented, but the preparation of these carriers and subsequent loading of polyphenols is a multiple process, which is generally complicated with potentially unexpected negative effects on the bioactivity of the polyphenols. Here, we reported a convenient method to assemble carrier-free polyphenol nanoparticles (NPs) based on oxidative coupling polymerization. The effectiveness was assessed with five different polyphenols including pyrocatechol (PY), catechin (CA), epigallocatechin gallate (EGCG), tannic acid (TA), and proanthocyanidin (PC). The structural characteristics of these assembled nanoparticles (PY NPs, CA NPs, EG NPs, TA NPs, and PC NPs) were systematically analyzed with dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR). All NPs were colloidally stable with varying NaCl concentrations from 0 to 300 mM, were acid-resistant and alkali-intolerant, and were suitable for oral administration. An array of antioxidant assays further confirmed the superior antioxidant capabilities of NPs over Trolox and polyphenol monomers, indicating that the oxidative polymerization of polyphenols did not compromise the polyphenol activity of NPs. The in vitro simulated digestion studies validated that these responsive NPs were actually gastrointestinal pH-responsive and applicable to the gastrointestinal physiological environment. The bioaccessibility assessments by using a static in vitro digestion model revealed that better results were achieved with NPs than polyphenol monomers, with TA NPs showing about 1.5-fold higher bioaccessibility than other polyphenol nanoparticles. The present study with five polyphenols demonstrated that the oxidative polymerization of polyphenols provides an effective platform to assemble various carrier-free NPs with enhanced antioxidant activity, favorable stability, and improved bioaccessibility, which could be used promisingly as a functional food ingredient in food matrices or as oral drug delivery candidates for helping to manage human health or treating various gastrointestinal disorders in both the pharmaceutical and nutritional fields.

Ultrastable and highly active Co-vacancies-enriched IrCo bifunctional nanoalloys for proton exchange membrane water electrolysis.

Exploring the electrocatalysts with high intrinsic activity and stability for both anode and cathode to tolerate the extremely acidic condition in proton exchange membrane water electrolyzer (PEMWE) is crucial for widespread industrial application. Herein, we constructed the bifunctional IrCox nanoalloys with abundant metal vacancies via the combination of chemical reduction and electrochemical treatment for overall water splitting. The developed IrCo0.13 exhibits ultra-low overpotentials of 238 mV for OER and 18.6 mV for HER at 10 mA cm-2 in 0.1 M HClO4, and achieves the exceptional stability of 1000 h for OER and 100 h for HER at 10 mA cm-2. Further, the cell voltage is only 1.68 V to reach a high current density of 1 A cm-2 in PEMWE with IrCo0.13 as the both cathode and anode catalytic layer, and it shows excellent corrosion resistance in acidic environment, evidenced by 415 h stable operation at 1 A cm-2. The strong electronic interactions in the Ir-Co atomic heterostructure and the in-situ generation of Co vacancies by electrochemical oxidation synergistically contribute to the enhanced activity and stability via optimizing the electronic structure of adjacent Ir active sites, enhancing the conductivity and electrochemical active surface area of the catalyst, accelerating charge transfer and kinetics. This work provides a new perspective for designing bifunctional catalysts for practical application in PEMWE.

Modeling blood metabolite homeostatic levels reduces sample heterogeneity across cohorts.

Blood metabolite levels are affected by numerous factors, including preanalytical factors such as collection methods and geographical sites. These perturbations have caused deleterious consequences for many metabolomics studies and represent a major challenge in the metabolomics field. It is important to understand these factors and develop models to reduce their perturbations. However, to date, the lack of suitable mathematical models for blood metabolite levels under homeostasis has hindered progress. In this study, we develop quantitative models of blood metabolite levels in healthy adults based on multisite sample cohorts that mimic the current challenge. Five cohorts of samples obtained across four geographically distinct sites were investigated, focusing on approximately 50 metabolites that were quantified using 1H NMR spectroscopy. More than one-third of the variation in these metabolite profiles is due to cross-cohort variation. A dramatic reduction in the variation of metabolite levels (90%), especially their site-to-site variation (95%), was achieved by modeling each metabolite using demographic and clinical factors and especially other metabolites, as observed in the top principal components. The results also reveal that several metabolites contribute disproportionately to such variation, which could be explained by their association with biological pathways including biosynthesis and degradation. The study demonstrates an intriguing network effect of metabolites that can be utilized to better define homeostatic metabolite levels, which may have implications for improved health monitoring. As an example of the potential utility of the approach, we show that modeling gender-related metabolic differences retains the interesting variance while reducing unwanted (site-related) variance.

Foam Cell Targeted Liposomes Co-Encapsulating Superoxide Dismutase and Catalase to Attenuate Atherosclerosis by Inhibiting Oxidative Stress.

BACKGROUND: Oxidative stress, propelled by reactive oxygen species (ROS), serves as a significant catalyst for atherosclerosis (AS), a primary contributor to vascular diseases on a global scale. Antioxidant therapy via nanomedicine has emerged as a pivotal approach in AS treatment. Nonetheless, challenges such as inadequate targeting, subpar biocompatibility, and limited antioxidant effectiveness have restrained the widespread utilization of nanomedicines in AS treatment. This study aimed to synthesize a specialized peptide-modified liposome capable of encapsulating two antioxidant enzymes, intending to enhance targeted antioxidant therapy for AS. METHODS: The film dispersion method was employed for liposome preparation. Fluorescence quantification was conducted to assess the drug encapsulation rate. Characterization of liposome particle size was performed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Laser confocal microscopy and flow cytometry were utilized to analyze liposome cell uptake and target foam cells. Antioxidant analysis was conducted using 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, while pro-lipid efflux analysis utilized Oil Red O (ORO) staining. Safety evaluation was performed using Hematoxylin and Eosin (H&E) staining. The level of inflammatory factors was determined through enzyme-linked immunosorbent assay (ELISA). The degree of lipid oxidation at the cellular level was assessed using the malonaldehyde (MDA) assay. In vivo targeting analysis was conducted using small animal live imaging. RESULTS: Our in vitro and in vivo findings substantiated that the modification of Lyp-1 led to increased delivery of antioxidant enzymes into foam cells (p < 0.05), the primary pathological cells within AS plaques. Upon accumulation in foam cells, liposomes loaded with superoxide dismutase (SOD) and catalase (CAT) (LyP-lip@SOD/CAT) effectively mitigated excess ROS and shielded macrophages from ROS-induced damage (p < 0.01). Furthermore, the reduction in ROS levels notably hindered the endocytosis of oxidized low-density lipoprotein (Ox-LDL) by activated macrophages, subsequently alleviating lipid accumulation at atherosclerotic lesion sites, evident from both in vitro and in vivo ORO staining results (p < 0.01). LyP-lip@SOD/CAT significantly curbed the secretion of inflammatory factors at the plaque site (p < 0.001). Additionally, LyP-lip@SOD/CAT demonstrated commendable biological safety. CONCLUSIONS: In this study, we effectively synthesized LyP-lip@SOD/CAT and established its efficacy as a straightforward and promising nano-agent for antioxidant therapy targeting atherosclerosis.

Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity of < 20/40.

PURPOSE: To identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network protocol AC. DESIGN: Post hoc analysis of data from a randomized clinical trial. PARTICIPANTS: Two hundred seventy participants with one or both eyes harboring CI-DME with visual acuity (VA) letter score of 69 to 24 (Snellen equivalent, 20/50-20/320). METHODS: Eligible eyes were assigned to receive intravitreal aflibercept monotherapy (n = 158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (n = 154). MAIN OUTCOME MEASURES: Meeting switching criteria: (1) at any time, (2) at 12 weeks, and (3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models. RESULTS: In the group receiving bevacizumab first, older participants showed a higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age of 1.32 (95% confidence interval [CI], 1.11-1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (for male vs. female: odds ratio [OR], 4.84 [95% CI, 1.32-17.81]; 5-letter lower baseline VA: OR, 1.30 [95% CI, 1.03-1.63]). Worse 12-week central subfield thickness (CST; 10-µm greater: HR, 1.06 [95% CI, 1.04-1.07]) was associated with increased risk of switching after 12 weeks. The mean ± standard deviation improvement in visual acuity after completing the switch to aflibercept was 3.7 ± 4.9 letters compared with the day of switching. CONCLUSIONS: The identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At 12 weeks, thicker CST was predictive of eyes most likely to be switched in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Collagen Scaffolds Functionalized by Cu2+-Chelated EGCG Nanoparticles with Anti-Inflammatory, Anti-Oxidation, Vascularization, and Anti-Bacterial Activities for Accelerating Wound Healing.

Skin injury is a common health problem worldwide, and the highly complex healing process poses critical challenges for its management. Therefore, wound dressings with salutary effects are urgently needed for wound care. However, traditional wound dressing with a single function often fails to meet the needs of wound repair, and the integration of multiple functions has been required for wound repair. Herein, Cu2+-chelated epigallocatechin gallate nanoparticles (EAC NPs), with radical scavenging, inflammation relieving, bacteria restraining, and vascularization accelerating capacities, are adopted to functionalize collagen scaffold, aiming to promote wound healing. Radical scavenging experiments verify that EAC NPs could efficiently scavenge radicals. Additionally, EAC NPs could effectively remove Escherichia coli and Staphylococcus aureus. H2O2 stimuli-responsive EAC NPs show slow and sustained release properties of Cu2+. Furthermore, EAC NPs exhibit protective effects against H2O2-induced oxidative-stress damage and anti-inflammatory activity in vivo. Physicochemical characterizations show that the introduction of EAC NPs does not disrupt the gelation behavior of collagen, and the composite scaffolds (CS) remain porous structure similar to collagen scaffold. Animal experiments demonstrate that CS could promote wound healing through improving the thickness of renascent epidermis and number of new vessels. CS with multiple salutary functions is a promising dressing for wound care.

Influences of carboxymethyl chitosan upon stabilization and gelation of O/W Pickering emulsions in the presence of inorganic salts.

The objective of this study was to investigate the effects of carboxymethyl chitosan (CMCS) on the stabilization and gelation of oil-in-water (O/W) Pickering emulsions (PEs) with polyphenol-amino acid particles in the presence of inorganic salts. The results revealed that the CMCS-induced depletion interactions contributed to improving the emulsification ability and interfacial adsorption efficiency of polyphenol-amino acid particles as well as constructing the network structures in the continuous phase. These relevant changes collectively resulted in elevating stability, viscosity and moduli of PEs. The additional effects of different inorganic salts with varying additions were further investigated, and the addition-dependent phenomena were observed. At low additions of inorganic salts, the occurrence of the chelation of inorganic salts with CMCS consolidated the constructed network structure, favorable to the gelation of PEs. With increasing additions, this chelation effect became stronger which compromised the CMCS-induced depletion, gradually leading to destabilization of PEs. In terms of ion species, the more pronounced effect on emulsion stability was achieved with calcium ions than with potassium and iron ions. This study expects to provide a new perspective on the extending application of cationic CMCS for improving the stability of O/W PEs in the food industry.

A survey on the current status of Helicobacter pylori infection in households in Hainan Province, China.

OBJECTIVE: This study aims to assess the prevalence of Helicobacter pylori (Hp) infection at the household level in Hainan Province in China and identify the factors that contribute to its spread. The findings of this study have significant implications for public health prevention strategies in the Hainan region. METHODS: A total of 421 families, comprising 1355 individuals, were tested for Hp infection across five cities in Hainan Province between July 2021 and April 2022. The study utilized questionnaires that included questions about personal characteristics, household shared lifestyle and dietary habits, and potential pathways of Hp infection in children to identify potential factors linked to household Hp infection and transmission patterns. RESULTS: The prevalence of Hp infection on an individual basis was 46.72% (629/1355), with age ≥ 20 years, being married and having junior secondary education and above as risk factors for Hp infection. The prevalence of Hp infection in households was 80.29% (338/421), household size of 5, 6 and above were risk factors for Hp infection with Odds Ratios (ORs) of 4.09 (1.17-14.33) and 15.19 (2.01-114.73), respectively, household income ≥ 100,000 yuan and drinking boiled water from a tap source were protective factors for Hp infection with ORs of 0.52 (0.31-0.89) and 0.51 (0.28-0.95), respectively. The prevalence of Hp infection among minors in the household was 24.89% (58/233), with paternal infection and maternal infection as risk factors for child infection, with ORs of 2.93 (1.29-6.62) and 2.51 (1.07-5.89), respectively. CONCLUSION: Hp infection was prevalent among Hainan families, and interaction with infected family members may be the primary cause of transmission.

A Breeding Plumage in the Making: The Unique Process of Plumage Coloration in the Crested Ibis in Terms of Chemical Composition and Sex Hormones.

The Crested Ibis (Nipponia nippon) has long fascinated ornithologists with its enigmatic plumage color change. After more than a century of curiosity, the mystery was finally unraveled in the 1970s, unveiling the mechanism behind this remarkable transformation. Unlike other bird species, the Crested Ibis achieves its nuptial plumage coloration through a unique daubing behavior. After a water-bathing, it applies a sticky black substance secreted by a patch of skin in the neck and throat region. However, the chemical components of this black substance have not been studied in detail until now. To address this issue, we conducted a study to detect the components of the black substance and explore the relationship between sex hormone levels and the secretion of the black substance. We used enzyme-linked immunosorbent assay (ELISA) to measure the monthly changes in steroid hormone levels (estradiol E2, testosterone T, and progesterone PROG) levels in feces. We also analyzed the correlation between sex hormone levels and daubing behavior. The results showed that the sex hormone levels are closely related to the secretion and application of the black substance. In addition, we qualitatively analyzed the chemical components of the black substance using gas chromatography-mass spectrometry (GC-MS), uncovering the presence of 117 distinct chemical components. We assume that the black coloration results from the polymerization of selected chemical constituents among these components. These findings provide a groundwork for further exploration into the biological significance of the black substance. Overall, our study detected components in the black substance and studied how sex hormone levels relate to its secretion. Understanding the hormone effects on coloration helps in precise habitat management, like wetland preservation, crucial for Crested Ibis survival. Implementing hormone-boosting measures during breeding seasons enhances reproduction and health, vital for their conservation.

Multifunctional liposomes Co-encapsulating epigallocatechin-3-gallate (EGCG) and miRNA for atherosclerosis lesion elimination.

Atherosclerosis (AS) is a chronic inflammatory disease, characterized by a lipid accumulated plaque. Anti-oxidative and anti-inflammation and lipid metabolism promoting therapeutic strategies have been applied for atherosclerosis treatment. However, the therapeutic effect of a single therapeutic method is limited. It is suggested that a combination of these two strategies could help prevent lipid accumulation caused by inflammation and oxidative stress, and also promote lipid efflux from atherosclerotic plaque, to normalize arteries to the maximum extent. Hence, a strategy involving a multifunctional liposome co-encapsulating an antioxidant and anti-inflammatory drug epigallocatechin-3-gallate (EGCG) and a lipid-efflux-promoting gene miR-223 was established. The system (lip@EGCG/miR-223) could encapsulate miR-223 in core areas of the liposomes to provide a protective effect for gene drugs. Moreover, lip@EGCG/miR-223 was smaller in size (91.28 ± 2.28 nm characterized by DLS), making it easier to target AS lesions, which have smaller vascular endothelial spaces. After being efficiently internalized into the cells, lip@EGCG/miR-223 exhibited excellent antioxidant and anti-inflammatory effects in vitro by eliminating overproduced ROS and decreasing the level of inflammatory cytokines (TNF-α, IL-1ß, and MCP-1), which was due to the effect of EGCG. Besides, the lipid-efflux-promoting protein ABCA1 was upregulated when treated with lip@EGCG/miR-223. Through the two therapies mentioned, lip@EGCG/miR-223 could effectively inhibit the formation of foam cells, which are a main component of atherosclerotic plaques. In AS model mice, after intravenous (i.v.) administration, lip@EGCG/miR-223 was effectively accumulated in atherosclerotic plaques, and the distribution of drugs in the heart and aorta compared to that in the kidney was significantly increased when compared with free drugs (the ratio was 6.27% for the free miR-223-treated group, which increased to 66.10% for the lip@EGCG/miR-223-treated group). By decreasing the inflammation level and lipid accumulation, the arterial vessels in AS were normalized, with less macrophages and micro-angiogenesis, when treated with lip@EGCG/miR-223. Overall, this study demonstrated that lip@EGCG/miR-223 could be developed as a potential system for atherosclerosis treatment by a combined treatment of antioxidant, anti-inflammatory, and lipid-efflux-promoting effects, which provides a novel strategy for the safe and efficient management of atherosclerosis.

Biomimetic mineralization by confined diffusion with viscous hyaluronan network: Assembly of hierarchical flower-like supraparticles.

Biomolecules-mediated biomimetic mineralization has been extensively investigated and applied to fabricate nano-assemblies with unique hierarchical architectures and salient properties. The confined-source ion diffusion plays a key role in the biomineralization process, but little investigative efforts have focused on it. Here, we developed a simple method to mimic the in vivo condition by a confined diffusion method, and hydroxyapatite nanoflower assemblies (HNAs) with exquisite hierarchical architectures were obtained. The HNAs were assembled from needle-like hybrid nanocrystals of hydroxyapatite and hyaluronan. The results revealed that the strong interactions between ions and hyaluronan led to the nucleation of hydroxyapatite and the following aggregation. The combination of the external diffusion field and the internal multiple interactions induced the self-assembling processes. Additionally, HNAs with colloid stability and excellent biocompatibility were proved to be a promising cargo carrier for intranuclear delivery. This work presents a novel biomimetic mineralization strategy based on confined diffusion system for fabricating delicate hydroxyapatite, which offers a new perspective for the development of biomimetic strategies.

Association Between Sleep Duration and Stroke in Different Status of Metabolic Syndrome: A Cross-Sectional Study in Shanghai Adult Residents.

Purpose: This study aimed to investigate the relationship between sleep duration (SD) and stroke, and examine the effects of SD on stroke with or without metabolic syndrome (Mets) and its components among the adult residents in Shanghai, China. Participants and Methods: A total of 20,245 participants (51.72% male, mean age 44.66 years) were included from Shanghai Chronic Disease and Risk Factors Surveillance (SCDRFS) in 2017. The weighted logistic regressions were performed to examine the associations between SD and stroke in different status of Mets and its components. Results: The mean SD was 7.51±0.03 h/d. After adjusting for all the potential factors, SD<6 h/d (OR=1.73, 95% CI: 1.35-2.20) or ≥10 h/d (OR=1.66, 95% CI: 1.08-2.57) was significantly positively associated with stoke in the total participants; moreover, in the non-Mets group, only SD<6 h/d (OR=1.77, 95% CI: 1.19, 2.64) significantly increased the risk of stroke; while, in the Mets group, SD<6 h/d (OR=1.80, 95% CI:1.17-2.76) and ≥10 h/d (OR=1.97, 95% CI: 1.00-3.88) both had a positive significantly association with stoke. In addition, the effects of SD<6 h/d on stroke were more pronounced among those with high WC (OR=2.24, 95% CI: 1.40-3.58) and high TG (OR=2.60, 95% CI: 1.86-3.62), and the effects of SD≥10 h/d on stroke were more evident among those with high TG (OR=2.28, 95% CI: 1.02-5.08) and high FBG (OR=2.58, 95% CI: 1.30-5.10). Conclusion: Both short and long SD were significantly positively associated with stroke in the total participants, and the associations were stronger in the Mets group; conversely, in the non-Mets group, only short SD was significantly positively associated with stroke, and no significant association was observed between long SD and stroke. Therefore, more precise sleep measures may be needed to prevent stroke according to the different status of Mets.

A high-resolution genotype-phenotype map identifies the TaSPL17 controlling grain number and size in wheat.

BACKGROUND: Large-scale genotype-phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments. RESULTS: We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection. CONCLUSION: Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.

The mechanism of nanozyme activity of ZnO-Co3O4-v: Oxygen vacancy dynamic change and bilayer electron transfer pathway for wound healing and virtual reality revealing.

Since the catalyst's surface was the major active location, the inner structure's contribution to catalytic activity was typically overlooked. Here, ZnO-Co3O4-v nanozymes with several surfaces and bulk oxygen vacancies were created. The O atoms of H2O2 moved inward to preferentially fill the oxygen vacancies in the interior and form new "lattice oxygen" by the X-ray photoelectron spectroscopy depth analysis and X-ray absorption fine structure. The internal Co2+ continually transferred electrons to the surface for a continuous catalytic reaction, which generated a significant amount of reactive oxygen species. Inner and outer double-layer electron cycles accompanied this process. A three-dimensional model of ZnO-Co3O4-v was constructed using virtual reality interactive modelling technology to illustrate nanozyme catalysis. Moreover, the bactericidal rate of ZnO-Co3O4-v for Methionine-resistant Staphylococcus aureus and Multiple drug resistant Escherichia coli was as high as 99%. ZnO-Co3O4-v was biocompatible and might be utilized to heal wounds following Methionine-resistant Staphylococcus aureus infection. This work offered a new idea for nanozymes to replace of conventional antibacterial medications.

New pattern of individualized management of chronic diseases: focusing on inflammatory bowel diseases and looking to the future.

Non-infectious chronic diseases, especially inflammatory bowel diseases (IBDs), hypertension, and diabetes mellitus, are characterized by a prolonged and multisystemic course, and their incidence increases annually, usually causing serious economic burden and psychological stress for patients. Therefore, these diseases deserve scientific and consistent disease management. In addition, the lack of a comprehensive "early disease clues tracking-personalized treatment system-follow-up" model in hospitals also exacerbates this dilemma. Based on these facts, we propose an individualized prediction management system for IBDs based on chronic diseases, focusing on the established IBDs-related prediction models and summarizing their advantages and disadvantages. We call on researchers to pay attention to the integration of models with clinical practice and the continuous correction of models to achieve truly individualized medical treatment for chronic diseases, thus providing substantial value for the rapid diagnosis and adequate treatment of chronic diseases such as IBDs, which follow the "relapse-remission" disease model, and realizing long-term drug use and precise disease management for patients. The goal is to achieve a new level of chronic disease management by scientifically improving long-term medication, precise disease management, and individualized medical treatment, effectively prolonging the remission period and reducing morbidity and disability rates.