A systematic review and meta-analysis on the effectiveness of bivalent mRNA booster vaccines against Omicron variants.

BACKGROUND: A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking. METHODS: We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses. RESULTS: From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: -22.2-82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5-38.2 %) and 28.4 % (95 % CI: 10.2-42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8-39.8 %), 31.4 % (95 % CI: 27.7-35.0 %), and 30.6 % (95 % CI: -13.2-57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5-82.4 %), 57.6 % (95 % CI: 42.4-68.8 %), and 62.1 % (95 % CI: 54.6-68.3 %) for all ages, and 72.0 % (95 % CI: 51.4-83.9 %), 63.4 % (95 % CI: 41.0-77.3 %), and 60.7 % (95 % CI: 52.4-67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively. CONCLUSIONS: The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation.

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study.

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Magnetic superhydrophobic cellulose nanofibril based aerogel with rope-ladder like structure incorporating both superelasticity and excellent oil absorption.

Achieving an equilibrium between exceptional oil absorption and remarkable elasticity has emerged as a formidable challenge for magnetic porous materials designed for oil absorption. Here, we propose an original, magnetic and superhydrophobic cellulose nanofibril (CNF) based aerogel system with a rope-ladder like skeleton by to greatly improve the issue. Within this system, CNF as the skeleton was combined with multiwalled carbon nanotubes (MWCNT)@Fe3O4 as the magnetic and enhanced component, both methyltrimethoxysilane (MTMS) and acetonitrile-extracted lignin (AEL) as the soft-hard associating constituents. The resultant CNF based aerogel shows a rope-ladder like pore structure to contribute to high elasticity and excellent oil absorption (28.34-61.09 g/g for various oils and organic solvents) under the synergistic effect of Fe3O4@MWCNT, AEL and MTMS, as well as good specific surface area (27.97 m2/g), low density (26.4 mg/cm3). Notably, despite the introduced considerable proportion (0.5 times of mass-CNF) of Fe3O4@MWCNT, the aerogel retained an impressive compression-decompression rate (88%) and the oil absorption efficiency of above 87% for various oils due to the soft-hard associating structure supported by both MTMS and AEL. This study provides a prospective strategy to balance between high elasticity and excellent oil absorption of CNF based aerogel doping inorganic particles.

Extracellular vesicles from Fusobacterium nucleatum: roles in the malignant phenotypes of gastric cancer.

The increase of the Fusobacterium nucleatum level has been previously identified in various cancers including gastric cancer (GC), but how the F. nucleatum exerts its carcinogenic role in GC remains unclear. Several studies revealed that F. nucleatum contributes to cancer progression via its secretion of extracellular vehicles (EVs). Hence, it's designed to reveal the influence of F. nucleatum-derived EVs (Fn-EVs) in GC progression. The tumor and adjacent tissues were collected from 30 GC patients, and the abundance of F. nucleatum was found to be highly expressed in tumor samples. The ultracentrifugation was employed to isolate EVs from F. nucleatum and Escherischia coli (E. coli), which were labeled Fn-EVs and E. coli-EVs, respectively. After treating GC cells with Fn-EVs and E. coli-EVs, cell counting kit 8, colony formation, wound healing as well as transwell assay were performed, which revealed that Fn-EVs effectively enhanced oxaliplatin resistance, and facilitated cell proliferation, migration, invasion, and stemness in GC cells while E. coli-EVs exert no significant effect on GC cells. Besides, the stemness and DNA repair of GC cells were also enhanced by Fn-EVs, as revealed by the sphere-forming assay and the detection of stemness- and DNA repair-associated proteins by western blotting. In vivo analyses demonstrated that Fn-EVs administration not only promoted GC tumor growth and liver metastasis but also conferred GC tumor resistance to oxaliplatin resistance. This study first revealed the contributive role of F. nucleatum in GC development via Fn-EVs, which provided a better perspective for manipulating F. nucleatum in treating GC patients with malignant phenotypes.

Patterned growth of AgBiS2 nanostructures on arbitrary substrates for broadband and eco-friendly optoelectronic sensing.

The patterning of functional nanomaterials shows a promising path in the advanced fabrication of electronic and optoelectronic devices. Current micropatterning strategies are indispensable for post-etching/liftoff processes that contaminate/damage functional materials. Herein, we developed an innovative, low-temperature, post-liftoff-free, seed-confined fabricating strategy that can tackle this issue, thus achieving designated patterns of flower-shaped AgBiS2 nanostructures at either micro- or macro-scale on arbitrary substrates that are either rigid or flexible. Made of patterned AgBiS2 nanostructures, the photoconductor shows broadband (320 nm-2200 nm), sensitive (Rpeak = 1.56 A W-1), and fast (less than 100 µs) photoresponses. Furthermore, single-pixel raster-scanning and 28 × 12 focal plane array imaging were performed to demonstrate reliable and resolved electrical responses to optical patterns, showcasing the potential of the photoconductor in practical imaging applications. Notably, the patterning process enables strain-releasing micro-structures, which lead to the fabrication of a flexible photodetector with high durability upon over 1000 bending/recovering testing cycles. This study provides a simple, low-temperature, and eco-friendly strategy to address the current challenges in non-aggressive micro-fabrication and arbitrary patterning of semiconductors, which are promising to meet the development of further emerging technologies in scalable and wearable optoelectronic sensors.

Visible Light-Induced 1,2-Diphenyldisulfane-Mediated Defluoroborylation of Polyfluoroarenes.

A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.

Enhancing biohydrogen production from xylose through natural FeS2 ore: Mechanistic insights.

In this study, we investigated the advantages of utilizing natural FeS2 ore in the context of dark fermentative hydrogen production within a fermentation system employing heat-treated anaerobic granular sludge with xylose as the carbon source. The results demonstrated a significant improvement in both hydrogen production and the maximum rate, with increases of 2.58 and 4.2 times, respectively. Moreover, the presence of FeS2 ore led to a reduction in lag time by more than 2-3 h. The enhanced biohydrogen production performance was attributed to factors such as the intracellular NADH/NAD+ ratio, redox-active components of extracellular polymeric substances, secreted flavins, as well as the presence of hydrogenase and nitrogenase. Furthermore, the FeS2 ore served as a direct electron donor and acceptor during biohydrogen production. This study shed light on the underlying mechanisms contributing to the improved performance of biohydrogen production from xylose during dark fermentation through the supplementation of natural FeS2 ore.

Preparation of highly elastic superhydrophobic CNF/Fe3O4 based materials modified in aqueous phase for oil-water separation.

Magnetic superhydrophobic materials have broad application prospect in oil-water separation. In this study, a magnetic and superhydrophobic aerogel with lamellar structure was successfully prepared using cellulose nanofibrils (CNF) as the skeleton, Fe3O4 as the magnetic ion, 1H, 1H, 2H, 2H trialkylfluorooctane triethoxysilane (FS) and 3-(2-aminoethyl amino)-propyl trimethoxysilane (AS) as the combined modifier. The prepared aerogel shows lower density (38.63 mg/cm3), excellent magnetic (15.13 emu/g), high elasticity and good oil sorption properties (21 g/g). In addition, FS/AS also exhibits excellent mechanical properties and superhydrophobic ability (water contact angle (WCA) of 151.9 ± 1.4°), as it provides sufficient toughness and low surface energy for the layer-branch structure. It should be noted that the entire preparation process is carried out in the aqueous phase, without the use of any organic solvents, providing a green oil-water separation strategy.

Subrelativistic Alternating Phase Focusing Dielectric Laser Accelerators.

We demonstrate a silicon-based electron accelerator that uses laser optical near fields to both accelerate and confine electrons over extended distances. Two dielectric laser accelerator (DLA) designs were tested, each consisting of two arrays of silicon pillars pumped symmetrically by pulse front tilted laser beams, designed for average acceleration gradients 35 and 50 MeV/m, respectively. The DLAs are designed to act as alternating phase focusing (APF) lattices, where electrons, depending on the electron-laser interaction phase, will alternate between opposing longitudinal and transverse focusing and defocusing forces. By incorporating fractional period drift sections that alter the synchronous phase between ±60° off crest, electrons captured in the designed acceleration bucket experience half the peak gradient as average gradient while also experiencing strong confinement forces that enable long interaction lengths. We demonstrate APF accelerators with interaction lengths up to 708 µm and energy gains up to 23.7±1.07 keV FWHM, a 25% increase from starting energy, demonstrating the ability to achieve substantial energy gains with subrelativistic DLA.

Influence of saturation level on the acoustic emission characteristics of gas hydrate-bearing coal.

To study the effects of gas hydrates on the prevention and control of coal and gas protrusions, this paper reports the results of acoustic emission experiments on coal bodies containing gas hydrates with different saturation levels. The results showed that few acoustic emission events were generated in the elasticity stages of coal bodies containing gas hydrates, and the first sudden increase in the number of ringing counts generally occurred before and after the yielding point. Additionally, the acoustic emission events in the yielding stage were more active, and the cumulative number of ringing counts increased faster. The peak ringing counts appeared around the damage point, and a small number of acoustic emission events were still generated after destruction of the coal samples. The cumulative ringing counts decreased linearly with increasing saturation. The effect of saturation on the cumulative ringing counts in the elasticity stage of the gas hydrate-containing coal samples was small, but the difference between the cumulative ringing counts in the yielding stage and those in the destruction stage was larger. The total cumulative ringing counts and the cumulative ringing counts during each stage for the gas hydrate-containing coal samples decreased with increasing enclosure pressure. The energy and amplitude of the loading process were consistent with the trend for the ringing counts. The acoustic emission ringing counts of gas-containing coals were greater than those of gas hydrate-containing coals in the yielding and destructing stages.

Deep learning methods for fully automated dental age estimation on orthopantomograms.

OBJECTIVES: This study aimed to use all permanent teeth as the target and establish an automated dental age estimation method across all developmental stages of permanent teeth, accomplishing all the essential steps of tooth determination, tooth development staging, and dental age assessment. METHODS: A three-step framework for automatically estimating dental age was developed for children aged 3 to 15. First, a YOLOv3 network was employed to complete the tasks of tooth localization and numbering on a digital orthopantomogram. Second, a novel network named SOS-Net was established for accurate tooth development staging based on a modified Demirjian method. Finally, the dental age assessment procedure was carried out through a single-group meta-analysis utilizing the statistical data derived from our reference dataset. RESULTS: The performance tests showed that the one-stage YOLOv3 detection network attained an overall mean average precision 50 of 97.50 for tooth determination. The proposed SOS-Net method achieved an average tooth development staging accuracy of 82.97% for a full dentition. The dental age assessment validation test yielded an MAE of 0.72 years with a full dentition (excluding the third molars) as its input. CONCLUSIONS: The proposed automated framework enhances the dental age estimation process in a fast and standard manner, enabling the reference of any accessible population. CLINICAL RELEVANCE: The tooth development staging network can facilitate the precise identification of permanent teeth with abnormal growth, improving the effectiveness and comprehensiveness of dental diagnoses using pediatric orthopantomograms.

Vascular Aging and Atherosclerosis: A Perspective on Aging.

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological and clinical research has demonstrated an intimate connection between aging and AS, the candidate mechanisms still require thorough examination. This review adopts an aging-centric perspective to deepen the comprehension of the intricate relationship between biological aging, vascular cell senescence, and AS. Various aging-related physiological factors influence the physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, and insulin resistance. These factors cause endothelial dysfunction, barrier damage, sclerosis, and inflammation for VA and promote AS via distinct or shared pathways. Furthermore, the increase of senescent cells inside the vascular tissues, caused by genetic damage, dysregulation, secretome changes, and epigenetic modifications, might be the primary cause of VA.

Knocking Down HN1 Blocks Helicobacter pylori-Induced Malignant Phenotypes in Gastric Mucosal Cells and Inhibits Gastric Cancer Cell Proliferation, Cytoskeleton Remodeling, and Migration.

Helicobacter pylori (H. pylori) is implicated in the aberrant proliferation and malignant transformation of gastric mucosal cells, heightening the risk of gastric cancer (GC). HN1 is involved in the development of various tumors. However, precise mechanistic underpinnings of HN1 promoting GC progression in H. pylori remain elusive. The study collected 79 tissue samples of GC patients, including 47 with H. pylori-positive GC and 32 H. pylori-negative controls. Using human gastric epithelial cells (GES-1) and human gastric adenocarcinoma cells (HGC-27), the effect of overexpression / knocking down of HN1 and H. pylori infection was evaluated on cell function (proliferation, migration, apoptosis), cytoskeleton, and expression of cell malignant phenotype factors that promote the malignant biological behavior of cancer cells. The expression of HN1 in GC tissues is higher than that in paracancerous tissue and is closely related to infiltration, lymphatic metastasis, distant metastasis, survival, and H. pylori infection. Downregulation of HN1 effectively hinders the ability of H. pylori strains 26695 and SS1 to promote migration of GES-1 and HGC-27 cells, while lowering the expression of key indicators associated with malignant phenotype. Downregulated GSK3B, ß-catenin, and Vimentin after knockdown Integrinß1, but HN1 expression remained largely unchanged, when HN1 and Integrinß1 were knocked down, GSK3B, ß-catenin, and Vimentin expression were considerably reduced. Our research demonstrated the crucial role of HN1 in H. pylori-induced acquisition of a malignant phenotype in GES-1 cells. Knockdown of HN1 blocked the pathogenic mechanism of H. pylori-induced GC and downregulated the expression of GSK3Β, ß-catenin and Vimentin via Integrin ß1.

Polar Aromatic Two-dimensional Dion-Jacobson Halide Perovskites for Efficient Photocatalytic H2 Evolution.

Polar materials with spontaneous polarization (Ps) have emerged as highly promising photocatalysts for efficient photocatalytic H2 evolution owing to the Ps-enhanced photogenerated carrier separation. However, traditional inorganic polar materials often suffer from limitations such as wide band gaps and poor carrier transport, which hinders their photocatalytic H2 evolution efficiency. Here, we rationally synthesized a series of isostructural two-dimensional (2D) aromatic Dion-Jacobson (DJ) perovskites, namely (2-(2-Aminoethyl)pyridinium)PbI4 (2-APDPI), (3-(2-Aminoethyl)pyridinium)PbI4 (3-APDPI), and (4-(2-Aminoethyl)pyridinium)PbI4 (4-APDPI), where 2-APDPI and 4-APDPI crystalize in polar space groups with piezoelectric constants (d33) of approximately 40 pm V-1 and 3-APDPI adopts a centrosymmetric structure. Strikingly, owing to the Ps-facilitated separation of photogenerated carriers, polar 2-APDPI and 4-APDPI exhibit a 3.9- and 2.8-fold increase, respectively, in photocatalytic H2 evolution compared to the centrosymmetric 3-APDPI. As a pioneering study, this work provides an efficient approach for exploring new polar photocatalysts and highlights their potential in promoting photocatalytic H2 evolution.

Identification of YCH2823 as a novel USP7 inhibitor for cancer therapy.

Inhibition of the human ubiquitin-specific protease 7 (USP7), the key deubiquitylating enzyme in regulating p53 protein levels, has been considered an attractive anticancer strategy. In order to enhance the cellular activity of FT671, scaffold hopping strategy was employed. This endeavor resulted in the discovery of YCH2823, a novel and potent USP7 inhibitor.YCH2823 demonstrated remarkable efficacy in inhibiting the growth of a specific subset of TP53 wild-type, -mutant, and MYCN-amplified cell lines, surpassing the potency of FT671 by approximately 5-fold. The mechanism of action of YCH2823 involves direct interaction with the catalytic domain of USP7, thereby impeding the cleavage of ubiquitinated substrates. An increase in the expression of p53 and p21, accompanied by G1 phase arrest and apoptosis, was observed upon treatment with YCH2823. Subsequently, the knockdown of p53 or p21 in CHP-212 cells exhibited a substantial reduction in sensitivity to YCH2823, as evidenced by a considerable increase in IC50 values up to 690-fold. Furthermore, YCH2823 treatment specifically enhanced the transcriptional and protein levels of BCL6 in sensitive cells. Moreover, a synergistic effect between USP7 inhibitors and mTOR inhibitors was observed, suggesting the possibility of novel therapeutic strategies for cancer treatment. In conclusion, YCH2823 exhibits potential as an anticancer agent for the treatment of both TP53 wild-type and -mutant tumors.

CAR-T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives.

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR-T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR-T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR-T cell therapy, and considers future outlooks for research development.

Effectiveness of abdominal sandbag training in enhancing diaphragm muscle function and exercise tolerance in patients with chronic respiratory failure.

BACKGROUND: Chronic respiratory failure is a common cause of ventilator dependence in the intensive care unit (ICU). The causes of chronic respiratory failure include primary disease or complications, such as ICU-acquired weakness. Traditional practice requires patients to remain immobile and bedridden; however, recent evidence suggests that early adequate exercise promotes recovery without increasing risks. In this study, we explored the efficacy of planned progressive abdominal sandbag training in promoting the successful withdrawal of patients with chronic respiratory failure from mechanical ventilation. METHODS: This study was conducted between April 2019 and November 2020. Patients were recruited and divided into two groups: abdominal sandbag training group and control group (no training). The training group participated in a 3-month daily pulmonary rehabilitation program, which involved a 30-min session of progressive sandbag loading on the upper abdomen as a form of diaphragmatic resistant exercise. The pressure support level of the ventilator was adjusted to maintain a tidal volume of 8 mL/kg. To investigate the effect of abdominal sandbag training on patients with chronic respiratory failure, we compared tidal volume, shallow breathing index, maximum respiratory pressure, and diaphragm characteristics between the training and control groups. RESULTS: This study included 31 patients; of them, 17 (54.8 %) received abdominal sandbag training and 14 (45.2 %) did not. No significant between-group difference was found in baseline characteristics. Compared with the control group, the training group exhibited considerable improvements in ventilation-related parameters (p < 0.001): the tidal volume markedly increased (p = 0.012), rapid shallow breathing index declined (p = 0.016), and maximum respiratory pressure increased (p < 0.001) in the training group. The diaphragm motion value (p = 0.048) and diaphragm thickness (p = 0.041) were greater in the training group than in the control group. Nine patients (52.9 %) in the training group were removed from the ventilator compared with 1 (7.1 %) in the control group (p = 0.008). CONCLUSIONS: Abdominal sandbag training may be beneficial for patients dependent on a ventilator. The training improves the function of the diaphragm muscle, thereby increasing tidal volume and reducing the respiratory rate and rapid shallow breathing index, thus facilitating withdrawal from ventilation. This training approach may also improve the thickness and motion of the diaphragm and the rate of ventilator detachment.

MS-TCNet: An effective Transformer-CNN combined network using multi-scale feature learning for 3D medical image segmentation.

Medical image segmentation is a fundamental research problem in the field of medical image processing. Recently, the Transformer have achieved highly competitive performance in computer vision. Therefore, many methods combining Transformer with convolutional neural networks (CNNs) have emerged for segmenting medical images. However, these methods cannot effectively capture the multi-scale features in medical images, even though texture and contextual information embedded in the multi-scale features are extremely beneficial for segmentation. To alleviate this limitation, we propose a novel Transformer-CNN combined network using multi-scale feature learning for three-dimensional (3D) medical image segmentation, which is called MS-TCNet. The proposed model utilizes a shunted Transformer and CNN to construct an encoder and pyramid decoder, allowing six different scale levels of feature learning. It captures multi-scale features with refinement at each scale level. Additionally, we propose a novel lightweight multi-scale feature fusion (MSFF) module that can fully fuse the different-scale semantic features generated by the pyramid decoder for each segmentation class, resulting in a more accurate segmentation output. We conducted experiments on three widely used 3D medical image segmentation datasets. The experimental results indicated that our method outperformed state-of-the-art medical image segmentation methods, suggesting its effectiveness, robustness, and superiority. Meanwhile, our model has a smaller number of parameters and lower computational complexity than conventional 3D segmentation networks. The results confirmed that the model is capable of effective multi-scale feature learning and that the learned multi-scale features are useful for improving segmentation performance. We open-sourced our code, which can be found at https://github.com/AustinYuAo/MS-TCNet.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Strength and leaching behavior of tailing-based paste backfill at high water content amended with lime activated ground granulated blast furnace slag and flocculant.

Flocculent is commonly used in mining activities to improve the concentration of tailing slurry by enhancing the sedimentation process of small tailings particles. The presence of flocculent in thickened tailings is unavoidable, and it affects the heavy metal leaching performances and mechanical and rheological characteristics of tailing-based cemented paste backfill (CPB). This study is carried out to investigate the physicochemical and leachability of CPB amended with flocculants and lime-activated ground granulated blast-furnace slag (GGBS). The stabilized samples were subjected to a series of model tests, including toxicity characteristics leaching procedure (TCLP) and pH, unconfined compressive strength (UCS), scanning electron microscopy (SEM), and X-ray diffraction. Moreover, the CPB amended with anionic polyacrylamide (APAM) demonstrated better performance in terms of a decrease in heavy metal leachability besides higher mechanical strength than poly aluminum chloride (PAC) and poly ferric chloride (PFC) samples. Furthermore, the UCS results showed that increasing binder content up to 15% negatively influences strength improvement of all stabilized samples because of weak connections between soil particles and cementitious material, resulting in high leachability of heavy metals. The analysis of XRD and SEM showed that anionic polyacrylamide (APAM) cases exhibited more voluminous hydration products, resulting in a compact stabilized matrix and substantially reduced heavy metal leachability.