A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury.

JOURNAL/nrgr/04.03/01300535-202502000-00028/figure1/v/2024-05-28T214302Z/r/image-tiff Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases. However, conventional topical drug delivery often results in a burst release of the drug, leading to transient retention (inefficacy) and undesirable diffusion (toxicity) in vivo. Therefore, a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke. Matrix metalloproteinase-2 (MMP-2) is gradually upregulated after cerebral ischemia. Herein, vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG (TIMP) and customizable peptide amphiphilic (PA) molecules to construct nanofiber hydrogel PA-TIMP-QK. PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro. The results indicated that PA-TIMP-QK promoted neuronal survival, restored local blood circulation, reduced blood-brain barrier permeability, and restored motor function. These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

A comprehensive review of deactivation and modification of selective catalytic reaction catalysts installed in cement kilns.

After the ultralow emission transformation of coal-fired power plants, cement production became China's leading industrial emission source of nitrogen oxides. Flue gas dust contents at the outlet of cement kiln preheaters were as high as 80-100 g/m3, and the calcium oxide content in the dust exceeded 60%. Commercial V2O5(-WO3)/TiO2 catalysts suitable for coal-fired flue gas suffer from alkaline earth metal Ca poisoning of cement kiln flue gas. Recent studies have also identified the poisoning of cement kiln selective catalytic reaction (SCR) catalysts by the heavy metals lead and thallium. Investigation of the poisoning process is the primary basis for analyzing the catalytic lifetime. This review summarizes and analyzes the SCR catalytic mechanism and chronicles the research progress concerning this poisoning mechanism. Based on the catalytic and toxification mechanisms, it can be inferred that improving the anti-poisoning performance of a catalyst enhances its acidity, surface redox performance-active catalytic sites, and shell layer protection. The data provide support in guiding engineering practice and reducing operating costs of SCR plants. Finally, future research directions for SCR denitrification catalysts in the cement industry are discussed. This study provides critical support for the development and optimization of poisoning-resistant SCR denitrification catalysts.

Preparation, characterization, antimicrobial evaluation, and grape preservation applications of polyvinyl alcohol/gelatin composite films containing zinc oxide@quaternized chitosan nanoparticles.

This study employed a precipitation method to synthesize zinc oxide@quaternised chitosan nanoparticles (ZnO@QAC NPs) containing different concentrations of zinc oxide, namely ZnO@QAC-2, ZnO@QAC-4, and ZnO@QAC-6. Subsequently, these nanoparticles were incorporated into matrices consisting of gelatine (Gn) and polyvinyl alcohol (PVA) separately, which were prepared by casting to form a biodegradable film. We assessed the physicochemical properties of ZnO@QAC NPs and physicochemical characteristics, antioxidant properties, antimicrobial activity and grape preservation efficacy of the film. Compared to the control group, the films showed a reduction in water vapor permeability by >9.38 %, an increase in tensile strength by over 51.95 %, over 70 % scavenging of ABTS free radicals, and good biocompatibility. Additionally, the antimicrobial activity of the films containing ZnO@QAC-6 increased by 37.6 %. In the grape preservation experiment, the weight loss of grapes wrapped in ZnO@QAC-2 film was reduced by 40.13 % on day 15 compared to unwrapped grapes. These results demonstrate that ZnO@QAC/PVA/Gn films have considerable potential for food packaging applications.

No-reference Bitstream-based Perceptual Quality Assessment of Octree-Lifting Encoded 3D Point Clouds.

No-reference point cloud quality assessment (PCQA) based on bitstreams uses information extracted from the bitstream for quality monitoring at network nodes. We develop a no-reference PCQA model based on bitstreams for the perceived quality assessment of Octree-Lifting coded point clouds. At first, our research explores the essential correlation between subjective visual quality degradation and the texture quantization parameter (TQP) when using lossless geometric coding. Then, we enhance the proposed model by incorporating texture complexity (TC) while taking into account the dependence of perceptual coding distortion on the texture characteristics of a point cloud. We estimate TC by utilizing TQP and calculating the average standard deviation of the Y-component of the attribute value ( Y_ std), both of which are extracted from the bitstream. Then, a texture distortion assessment model is constructed based on TQP and Y_ std. The integration of the texture distortion model with the position quantization scale (PQS) results in the derivation of an overall no-reference bitstream-based PCQA model, named streamPCQ-OL. The findings from the conducted experiments highlight a significant superiority of the proposed model over existing approaches in terms of performance. The dataset and source code will be publicly released and made available for access at https://github.com/qdushl/Waterloo-Point-Cloud-Database-4.0.

Global, regional, and national burdens of HIV/AIDS acquired through sexual transmission 1990-2019: an observational study.

Background Sexual transmission accounts for a substantial proportion of HIV infections. Although some countries are experiencing an upward trend in HIV infections, there has been a lack of studies assessing the global burden of HIV/AIDS acquired through sexual transmission. We assessed the global, regional, and national burdens of HIV/AIDS acquired through sexual transmission from 1990 to 2019. Methods Data on deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALY) of HIV/AIDS acquired through sexual transmission in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study (GBD) 2019. The burdens and trends were evaluated using the age-standardised rates (ASR) and estimated annual percentage change (EAPC). Results Globally, HIV/AIDS acquired through sexual transmission accounted for ~695.8 thousand (95% uncertainty interval 628.0-811.3) deaths, 33.0million (28.7-39.9) YLLs, 3.4million (2.4-4.6) YLDs, and 36.4million (32.2-43.1) DALYs in 2019. In 2019, Southern sub-Saharan Africa (11350.94), Eastern sub-Saharan Africa (3530.91), and Western sub-Saharan Africa (2037.74) had the highest ASR of DALYs of HIV/AIDS acquired through sexual transmission per 100,000. In most regions of the world, the burden of HIV/AIDS acquired through sexual transmission has been increasing from 1990 to 2019, mainly in Oceania (EAPC 17.20, 95% confidence interval 12.82-21.75), South Asia (9.00, 3.94-14.30), and Eastern Europe (7.09, 6.35-7.84). Conclusions HIV/AIDS acquired through sexual transmission results in a major burden globally, regionally, and nationally.

Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 µmol/L and 6.37 µmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl 3-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

Recent progress in tyrosine kinase 2 inhibitors for atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by persistent itching. Conventional treatments for AD include topical corticosteroids and calcineurin inhibitors, but there are emerging therapies targeting the JAK-TYK2 pathway that are promising for the treatment of AD. AREAS COVERED: This review comprehensively explores the pathogenesis, triggers, clinical manifestations, and conventional treatment options for AD. In addition, we discuss novel therapeutic agents targeting alternative signaling pathways, with a focus on clinical trials evaluating tyrosine kinase 2 (TYK2) inhibitors, including systemic and topical agents. We also provide a detailed assessment of ICP-332 efficacy, safety, and potential adverse effects in moderate-to-severe AD. EXPERT OPINION: Janus kinase inhibitors that have been recently approved have shown promise for the treatment of AD, especially for patients with severe phenotypes. Preliminary findings from randomized controlled trials suggest that TYK2 inhibitors exhibit rapid efficacy and acceptable safety in the management of AD; however, additional investigations, including long-term trials, are warranted to fully understand their efficacy and safety profile.

Enhanced neural recovery and reduction of secondary damage in spinal cord injury through modulation of oxidative stress and neural response.

Spinal cord injury (SCI) presents a critical medical challenge, marked by substantial neural damage and persistent functional deficits. This study investigates the therapeutic potential of cold atmospheric plasma (CAP) for SCI, utilizing a tailored dielectric barrier discharge (DBD) device to conduct comprehensive in vivo and in vitro analyses. The findings show that CAP treatment significantly improves functional recovery after SCI, reduces neuronal apoptosis, lowers inflammation, and increases axonal regeneration. These findings illustrate the efficacy of CAP in fostering a conducive environment for recovery by modulating inflammatory responses, enhancing neuronal survival, and encouraging regenerative processes. The underlying mechanism involves CAP's reactive oxygen species (ROS) reduction, followed by activating antioxidant enzymes. These findings position CAP as a pioneering approach for spinal cord injury (SCI) treatment, presenting opportunities for improved neural recovery and establishing a new paradigm in SCI therapy.

Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.

The liver possesses a distinctive capacity for regeneration within the human body. Under normal circumstances, liver cells replicate themselves to maintain liver function. Compensatory replication of healthy hepatocytes is sufficient for the regeneration after acute liver injuries. In the late stage of chronic liver damage, a large number of hepatocytes die and hepatocyte replication is blocked. Liver regeneration has more complex mechanisms, such as the transdifferentiation between cell types or hepatic progenitor cells mediated. Dysregulation of liver regeneration causes severe chronic liver disease. Gaining a more comprehensive understanding of liver regeneration mechanisms would facilitate the advancement of efficient therapeutic approaches. This review provides an overview of the signalling pathways linked to different aspects of liver regeneration in various liver diseases. Moreover, new knowledge on cellular interactions during the regenerative process is also presented. Finally, this paper explores the potential applications of new technologies, such as nanotechnology, stem cell transplantation and organoids, in liver regeneration after injury, offering fresh perspectives on treating liver disease.

Multi-rater Prism: Learning self-calibrated medical image segmentation from multiple raters.

In medical image segmentation, it is often necessary to collect opinions from multiple experts to make the final decision. This clinical routine helps to mitigate individual bias. However, when data is annotated by multiple experts, standard deep learning models are often not applicable. In this paper, we propose a novel neural network framework called Multi-rater Prism (MrPrism) to learn medical image segmentation from multiple labels. Inspired by iterative half-quadratic optimization, MrPrism combines the task of assigning multi-rater confidences and calibrated segmentation in a recurrent manner. During this process, MrPrism learns inter-observer variability while taking into account the image's semantic properties and finally converges to a self-calibrated segmentation result reflecting inter-observer agreement. Specifically, we propose Converging Prism (ConP) and Diverging Prism (DivP) to iteratively process the two tasks. ConP learns calibrated segmentation based on multi-rater confidence maps estimated by DivP, and DivP generates multi-rater confidence maps based on segmentation masks estimated by ConP. Experimental results show that the two tasks can mutually improve each other through this recurrent process. The final converged segmentation result of MrPrism outperforms state-of-the-art (SOTA) methods for a wide range of medical image segmentation tasks. The code is available at https://github.com/WuJunde/MrPrism.

Residues of veterinary drugs and heavy metal contamination in livestock and poultry meat from Hunan Province, China.

Livestock and poultry meat consumption play an important role in the dietary structure of Chinese residents. However, the extent of residues of veterinary drugs and heavy metal contamination in livestock and poultry meat and their by-products within Hunan province is not extensively studied. This survey aimed to fill this gap by assessing the presence of 76 veterinary drug residues in Hunan province. Additionally, heavy metals in pork and pig liver were also assessed. The obtained findings suggest that residues of veterinary drugs are still present in livestock and poultry meat, as well as their by-products, within Hunan province. However, the contamination of heavy metals remained within the food safety limits. These results underscore the significance of establishing more refined criteria for assessing human exposure, taking into account factors such as consumption patterns, product varieties and chemical compounds of interest.

Chromatin lysine acylation: On the path to chromatin homeostasis and genome integrity.

The fundamental role of cells in safeguarding the genome's integrity against DNA double-strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and the overall genomic stability. Aberrant responses to DNA damage, known as DNA damage responses (DDRs), can result in genomic instability and contribute significantly to tumorigenesis. Unraveling the intricate mechanisms underlying DDRs following severe damage holds the key to identify therapeutic targets for cancer. Chromatin lysine acylation, encompassing diverse modifications such as acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, and butyrylation, has been extensively studied in the context of DDRs and chromatin homeostasis. Here, we delve into the modifying enzymes and the pivotal roles of lysine acylation and their crosstalk in maintaining chromatin homeostasis and genome integrity in response to DDRs. Moreover, we offer a comprehensive perspective and overview of the latest insights, driven primarily by chromatin acylation modification and associated regulators.

A bacteria-based index of biotic integrity indicates aquatic ecosystem restoration.

Intensive ecological interventions have been carried out in highly polluted shallow lakes to improve their environments and restore their ecosystems. However, certain treatments, such as dredging polluted sediment and stocking fish, can impact the aquatic communities, including benthos and fishes. These impacts can alter the composition and characteristics of aquatic communities, which makes community-based ecological assessments challenging. Here we develop a bacteria-based index of biotic integrity (IBI) that can clearly indicate the restoration of aquatic ecosystems with minimal artificial interventions. We applied this method to a restored shallow lake during 3-year intensive ecological interventions. The interventions reduced nutrients and heavy metals by 27.1% and 16.7% in the sediment, while the total organic carbon (TOC) increased by 8.0% due to the proliferation of macrophytes. Additionally, the abundance of sulfur-related metabolic pathways decreased by 10.5% as the responses to improved ecosystem. The score of bacteria-based IBI, which is calculated based on the diversity, composition, and function of benthic bacterial communities, increased from 0.62 in 2018 to 0.81 in 2021. Our study not only provides an applicable method for aquatic ecological assessment under intensive artificial interventions but also extends the application of IBI to complex application scenarios, such as ecosystems with significantly different aquatic communities and comparisons between different basins.

Psychosocial treatment options for adolescents and young adults with alcohol use disorder: systematic review and meta-analysis.

Introduction: Psychosocial intervention is imperative for treating alcohol use disorder (AUD), but there is no comprehensive evidence regarding its effectiveness. Therefore, this study aimed to determine the effectiveness of psychosocial interventions in treating AUD amongadolescents and young adults. Methods: In this systematic review and meta-analysis, articles were searched from EMBASE, PubMed, Medline, CINAHL, Web of Science, PsycINFO, and Scopus. Also, articles were retrieved from gray literature. The quality of articles has been assessed using the Cochrane risk of bias assessment. Results: A total of 12 randomized controlled trials were included. Integrated family and CBT, CBT, guided self-change, and ecologically based family therapy had a mild effect in reducing alcohol use frequency. On the other hand, integrated motivational enhancement therapy and CBT (-0.71 [95% CI: -0.97, -0.45]) and common elements treatment approaches (4.5 [95% CI: 6.9, 2.2]) had the highest effect size for reducing alcohol use frequency and amount, respectively. In conclusion, most of the interventions had no significant effect on different drinking outcomes. Nonetheless, the effectiveness of combined interventions surpassed that of the single interventions. The effect of psychosocial interventions on abstinence was inconclusive. Therefore, future studies will explore alternative, newly emerged third-wave therapeutic approaches. Systematic review registration: PROSPERO, CRD42023435011, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=435011.

SnF2-Catalyzed Lithiophilic-Lithiophobic Gradient Interface for High-Rate PEO-based All-Solid-State Batteries.

Polyethylene oxide (PEO)-based all solid-state lithium metal batteries (ASSLMBs) are strongly hindered by the fast dendrite growth at the Li metal/electrolyte interface, especially under large rates. The above issue stems from the suboptimal interfacial chemistry and poor Li+ transport kinetics during cycling. Herein, a SnF2-catalyzed lithiophilic-lithiophobic gradient solid electrolyte interphase (SCG-SEI) of LixSny/LiF-Li2O is in-situ formed. The superior ionic LiF-Li2O rich upper layer (17.1 nm) possesses high interfacial energy and fast Li+ diffusion channels, wherein lithiophilic LixSny alloy layer (8.4 nm) could highly reduce the nucleation overpotential with lower diffusion barrier and promote rapid electron transportation for reversible Li+ plating/stripping. Simultaneously, the insoluble SnF2-coordinated PEO promotes the rapid Li+ ion transport in the bulk phase. As a result, an over 46.7 and 3.5 times improvements for lifespan and critical current density of symmetrical cells are achieved, respectively. Furthermore, LiFePO4-based ASSLMBs deliver a recorded cycling performance at 5 C (over 1000 cycles with a capacity retention of 80.0%). More importantly, impressive electrochemical performances and safety tests with LiNi0.8Mn0.1Co0.1O2 and pouch cell with LiFePO4, even under extreme conditions (i.e., 100 ℃), are also demonstrated, reconfirmed the importance of lithiophilic-lithiophobic gradient interfacial chemistry in the design of high-rate ASSLMBs for safety applications.

Cellulose nanofibers-based composite film with broadening MXene layer spacing and rapid moisture separation for humidity sensing and humidity actuators.

Based on the basic idea of expanding the interlayer spacing of MXene, utilizing the effect of gallic acid-modified cellulose nanofibers for rapid moisture separation, the flexible sensing and driving composite film with a perfect balance among humidity signal response and mechanical properties was prepared. Inspired by the stacking of autumn fallen leaves, the cellulose nanofibers-based composite films were formed by self-assembly under vacuum filtration of blending gallic acid-modified cellulose nanofibers with MXene. The enhanced mechanical properties (tensile strength 131.1 MPa, puncture load 0.88 N, tearing strength 165.55 N/mm, and elongation at break 16.14 %), humidity sensing (the stable induced voltage 63.7 mV and response/recovery time 3.2/5.1 s), and humidity driving (154.7° bending angle) properties were observed. The synergistic effect of hydrogen bonds, the "pinning effect" arising from the side chains, and the hierarchical layered microstructure contributed to the enhanced performance. This work exemplifies the application of green natural product for preparing intelligent sensing, wearable devices, and biomimetic robots.

Correction: Study on mechanism of elemene reversing tumor multidrug resistance based on luminescence pharmacokinetics in tumor cells in vitro and in vivo.

[This corrects the article DOI: 10.1039/D0RA00184H.].

aKNNO: single-cell and spatial transcriptomics clustering with an optimized adaptive k-nearest neighbor graph.

Typical clustering methods for single-cell and spatial transcriptomics struggle to identify rare cell types, while approaches tailored to detect rare cell types gain this ability at the cost of poorer performance for grouping abundant ones. Here, we develop aKNNO to simultaneously identify abundant and rare cell types based on an adaptive k-nearest neighbor graph with optimization. Benchmarking on 38 simulated and 20 single-cell and spatial transcriptomics datasets demonstrates that aKNNO identifies both abundant and rare cell types more accurately than general and specialized methods. Using only gene expression aKNNO maps abundant and rare cells more precisely compared to integrative approaches.

Study on the Fracture Extension Pattern of Shale Reservoir Fracturing under the Influence of Mineral Content.

This study aimed to investigate the effect of the microstructure of shale on fracture initiation and extension during hydraulic fracturing. The Longmaxi Formation shale reservoir in the Sichuan Basin was considered as the research object; its structure was modeled from a microscopic perspective, and a zero-thickness cohesive unit was embedded within the solid unit. Numerical simulations were performed to study the effect of mineral content on the microextension of the hydraulic fracture, extension behavior, and evolution law of shale. The results showed that changes in the mineral content resulted in changes in the forces between molecules within the minerals, which, in turn, affected the shale's brittleness. The percentages of brittle mineral content in the Long I, II, and III reservoir sections are 60.37, 47.60, and 53.56%, respectively. The fracture initiation pressures of the three reservoirs were 29.22, 31.42, and 30.22 MPa, respectively, and a linear correlation was found between the fracture initiation pressures and the brittle mineral contents of the reservoir sections. An increase in the reservoirs' percentage of brittle mineral content facilitated the fracture initiation, with a corresponding gradual decrease in the resistance to fracture initiation. The pore pressures of the fractures in the three reservoirs after fracture initiation were 0.90, 1.18, and 1.00 MPa, respectively. The larger the percentage of brittle minerals was, the lower was the fracture pore pressure. The greater the length, number, area, and width of the cracks were, the more likely they were to form longer and wider cracks. Hence, reservoirs with a high percentage of brittle minerals should be prioritized as the target formations for hydraulic fracturing operations. The results of this study reveal how the mineral content affects the extension of microscopic hydraulic fractures in shale reservoirs. As such, this work can provide a theoretical basis for rationally selecting a hydraulic fracturing operation layer in shale gas reservoirs.

Uncovering the Nonequilibrium Evolution Mechanism between Na2+2 δFe2- δ(SO4)3 Cathode and Impurities in the Na2SO4-FeSO4·7H2O Binary System for High-Voltage Sodium-Ion Batteries.

Sodium-ion batteries are increasingly recognized as ideal for large-scale energy storage applications. Alluaudite Na2+2 δFe2- δ(SO4)3 has become one of the focused cathode materials in this field. However, previous studies employing aqueous-solution synthesis often overlooked the formation mechanism of the impurity phase. In this study, the nonequilibrium evolution mechanism between Na2+2 δFe2- δ(SO4)3 and impurities by adjusting ratios of the Na2SO4/FeSO4·7H2O in the binary system is investigated. Then an optimal ratio of 0.765 with reduced impurity content is confirmed. Compared to the poor electrochemical performance of the Na2.6Fe1.7(SO4)3 (0.765) cathode, the optimized Na2.6Fe1.7(SO4)3@CNTs (0.765@CNTs) cathode, with improved electronic and ionic conductivity, demonstrates an impressive discharge specific capacity of 93.8 mAh g-1 at 0.1 C and a high-rate capacity of 67.84 mAh g-1 at 20 C, maintaining capacity retention of 71.1% after 3000 cycles at 10 C. The Na2.6Fe1.7(SO4)3@CNTs//HC full cell reaches an unprecedented working potential of 3.71 V at 0.1 C, and a remarkable mass-energy density exceeding 320 Wh kg-1. This work not only provides comprehensive guidance for synthesizing high-voltage Na2+2 δFe2- δ(SO4)3 cathode materials with controllable impurity content but also lays the groundwork of sodium-ion batteries for large-scale energy storage applications.