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Wilson's disease (WD) is an inherited disorder characterized by abnormal copper metabolism with complex pathological features. Currently, the mechanism of copper overload-induced hepatic injury is unclear. Green tea is a natural chelator, and its main ingredients, green tea polyphenol (GTP) and L-theanine (L-TA) are good at binding to heavy metals like iron and copper. There have been no reports on green tea extracts (GTE) for the treatment of Wilson's disease. This study investigated the hepatoprotective effect of GTE on WD model mice. Initially, we examined the impact of green tea extract on copper metabolism, excretion, and hepatoprotective effects in WD model toxic milk mice. Then, Ultra performance liquid chromatography (UPLC-DAD) was established to analyze GTP and L-TA in green tea extract. Further screening of eight active components and copper complex active components in green tea extract was carried out by ion analyzer. Finally, we verified the pharmacodynamic effects of these active ingredients at the animal level. The results showed that GTE improves liver function and attenuates liver injury in TX mice by promoting tissue copper excretion and inhibiting oxidative stress, which provides a theoretical basis for green tea's potential to improve the clinical symptoms of WD.

Circular RNAs (circRNAs) are covalently closed non-coding RNAs formed by back-splicing, lacking a 5' cap and poly-A tail. They could act as important regulatory factors in the host's anti-tuberculosis immune process, but only a few have been identified, and their molecular mechanisms remain largely unclear. Here, we identified a novel circRNA, circ-ZNF277, which responds to Mycobacterium tuberculosis ( Mtb ) infection in THP-1 cells. Circ-ZNF277 binds microRNA-378d (miR-378d) in vivo. The expression level of circ-ZNF277 affects the clearance of the intracellular Mtb in THP-1 cells. Mechanistically, more circ-ZNF277 molecules could absorb more miR-378d, thereby competitively activating the NF-κB signaling pathway, promoting the release of pro-inflammatory cytokines including interleukins IL-1β and IL-6, and tumor necrosis factor-α (TNF-α), and inhibiting the survival of intracellular Mtb . Expressing miR-378d or si-Rab10 targeting the transcription of Rab10 could antagonize the effects of overexpression of circ-ZNF277, resulting in the reduced intracellular survival of Mtb . In summary, circ-ZNF277 inhibits the intracellular survival of Mtb via the miR-378d/Rab10 axis. This finding represents a novel mechanism of circular RNA in regulating host immune responses during Mtb infection.

In this study, we designed a biomimetic artificial visual system (AVS) inspired by biological visual system that can process RGB images. Our approach begins by mimicking the photoreceptor cone cells to simulate the initial input processing followed by a learnable dendritic neuron model to replicate ganglion cells that integrate outputs from bipolar and horizontal cell simulations. To handle multi-channel integration, we utilize a nonlearnable dendritic neuron model to simulate the lateral geniculate nucleus (LGN), which consolidates outputs across color channels, an essential function in biological multi-channel processing. Cross-validation experiments show that AVS demonstrates strong generalization across varied object-background configurations, achieving accuracy where traditional models like EfN-B0, ResNet50, and ConvNeXt typically fall short. Additionally, our results across different training-to-testing data ratios reveal that AVS maintains over 96% test accuracy even with limited training data, underscoring its robustness in low-data scenarios. This demonstrates the practical advantage of the AVS model in applications where large-scale annotated datasets are unavailable or expensive to curate. This AVS model not only advances biologically inspired multi-channel processing but also provides a practical framework for efficient, integrated visual processing in computational models.

Mutations in calcium-dependent papain-like protease CALPAIN3 (CAPN3) cause Limb-Girdle Muscular Dystrophy Recessive Type 1 (LGMDR1), the most common limb-girdle muscular dystrophy in humans. In addition to progressive muscle weakness, persistent inflammatory infiltration is also a feature of LGMDR1. Despite the underlying mechanism remaining poorly understood, we consider that it may relate to the newly defined role of CAPN3/Capn3b in the nucleolus. Here, we report that the loss of function of zebrafish capn3b, the counterpart of human CAPN3, induces an autoimmune response akin to that in LGMDR1 patients. capn3b mutant larvae are more susceptible to Listeria monocytogenes injection, characterized by recruiting more macrophages. Under germ-free conditions, transcriptome analysis of the capn3b mutant muscle reveals a significant upregulation of the chemokine-production-related genes. Coincidently, more neutrophils are recruited to the injury site imposed by either muscle stabbing or tail fin amputation. Nucleolar proteomic analysis and enzymatic assays reveal NKAP, an activating factor of the NF-κB pathway, to be a target of CAPN3. We conclude that the accumulation of Nkap and other factors in the capn3b mutant may be involved in the over-activation of innate immunity. Our studies indicate that the zebrafish capn3b mutant is a powerful model for studying the immunity-related progression of human LGMDR1., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Compared to mechanical ones, liquid crystal (LC) beam deflectors present several advantages, such as non-mechanical control, compactness, and low power consumption, making them a viable alternative. In this work, we demonstrate an LC-based polarization-dependent, electrically tunable beam deflector, which is a composite blazed grating fabricated using a single-step photopolymerization-induced phase separation (PIPS) technique. We investigated the effect of different factors on the performance of the deflector, including the thickness of the upper substrate, the grating period, and the cell gap. The prepared sample demonstrated a diffraction angle of 2°6', and a diffraction efficiency of 40.0%. Unlike previous ones, our proposed fabrication technique for the LC beam deflector provides many benefits, such as simplicity, cost-effectiveness, and large-area production.

Engineering black carbon (e.g. biochar) has been widely found in natural environments due to natural processes and extensive applications in engineering systems, and could influence the geochemical processes of coexisting arsenic (As V ) and Fe II , especially when they are exposed to oxic conditions. Here, we studied time-varying kinetics and efficiencies of As V immobilization by solid-phase Fe II (Fe II solid ) and Fe III (Fe III solid ) in Fe II -As V -biochar systems under both anoxic and oxic conditions at pH 7.0, with focuses on the effects of biochar surface and biochar-derived dissolved organic carbon (DOC). Under anoxic conditions, Fe II could rapidly immobilize As V via co-adsorption onto biochar surfaces, which also serves as the dominant pathway of As V immobilization at the initial stage of reaction (0-5 min) under oxic conditions at high biochar concentrations. Subsequently, with increasing biochar concentrations, Fe III solid precipitation from aqueous Fe II (Fe II aq ) oxidation (5-60 min) starts to play an important role in As V immobilization but in decreased efficiencies of As V immobilization per unit iron. In the following stage (60-300 min), Fe II solid oxidation is suppressed and leads to As V release into solutions at >1.0 g·L -1 biochar. The decreasing efficiency of As V immobilization over time is attributed to the gradual release of DOC into solution from biochar particles, which significantly inhibit As V immobilization when Fe III solid is generated from Fe II solid oxidation in the vicinity of biochar surfaces. Specifically, 4.06 mg·L of biochar-derived DOC can completely inhibit the immobilization of As V in the 100 μM Fe II system under oxic conditions. The findings are crucial to comprehensively understand and predict the behavior of Fe II and As V with coexisting engineering black carbon in natural environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We propose an innovative design for interdigital transducers (IDTs), enabling phase modulation of surface acoustic waves (SAWs) with a dislocated electrode structure. By designing the size and arrangement of these dislocated IDTs, a novel type of Airy SAWs can be generated, exhibiting self-accelerating, self-bending, and self-healing characteristics. The acceleration of the generated Airy SAW is 0.081 cm -1 . Furthermore, particles and bubbles can be precisely manipulated using the generated Airy SAW. The proposed dislocated IDTs could be used for generation of many other types of SAWs, hence holding great promise for applications including SAW shaping, particle manipulation/sorting, and acoustic sensing/detection.

In areas affected by arsenicosis, zerovalent iron (ZVI)/sand filters are extensively used by households to treat groundwater, but ZVI surface passivation and filter clogging limit their arsenic (As) removal performance. Here we present a magnetic confinement-enabled column reactor coupled with periodic ultrasonic depassivation (MCCR-PUD), which efficiently and sustainably removes As by reaction with continuously generated iron (oxyhydr)oxides from ZVI oxidative corrosion. In the MCCR, ZVI microparticles self-assemble into stable millimeter-scale wires in forest-like arrays in a parallel magnetic field (0.42-0.48 T, produced by two parallel permanent magnets), forming a highly porous structure (87 % porosity) with twice the accessible reactive surface area of a ZVI/sand mixture. For a feed concentration of 100 μg/L As(III), the MCCR-PUD, with a short empty bed contact time (1.6 min), treated ca. 7340 empty bed volume (EBV) of water at breakthrough (10 μg/L), 9.4 folds higher than that of a ZVI/sand filter. Due to the large interspace between ZVI wires, the MCCR-PUD effectively prevented column clogging that occurred in the ZVI/sand filter. The high water treatment capacity was attributed to the much enhanced ZVI reactivity in the magnetic field, sustained through rejuvenation by PUD. Furthermore, most of As was structurally incorporated into the produced iron (oxyhydr)oxides (mostly ferrihydrite) in the MCCR-PUD, as revealed by Mössbauer spectroscopy, X-ray absorption spectroscopy, and sequential extraction experiments. This finding evinced a different mechanism from the surface adsorption in the ZVI/sand filter. The structural incorporation of As also resulted in much less As remobilization from the produced corrosion products during aging in water, in total ∼1 % in 28 days. Furthermore, the MCCR-PUD exihibted robust performance when treating complex synthetic groundwater containing natural organic matter and common ions (∼3700 EBV at breakthrough). Taken together, our study demonstrates the potential of the magnetic confinement-enabled ZVI reactor as a promising decentralized As treatment platform., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Parkinson's disease (PD) is a common neurodegenerative disease that severely affects patients' daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD., Methods: We divided 78 mice into six equal groups, including five model PD groups (W1-W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression., Results: We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages., Conclusion: Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Dynamic control of circularly polarized photoluminescence has aroused great interest in quantum optics and nanophotonics. Chiral plasmonic metasurfaces enable the manipulation of the polarization state via plasmon-photon coupling. However, current plasmonic light-emitting metasurfaces for effective deterministic modulation of spin-dependent emission at near-infrared wavelengths are underexplored in terms of dissymmetry and tunability. Here, we demonstrate a microfluidic hybrid emitting system of a suspended twisted stacking metasurface coated with PbS quantum dots. The suspended metasurface is fabricated with a single step of electron beam exposure, exhibiting a strong optical chirality of 309° μm -1 with a thickness of less than λ/10 at key spectral locations. With significant chiral-selective interactions, enhanced photoluminescence is achieved with strong dissymmetry in circular polarization. The dissymmetry factor of the induced circularly polarized emission can reach 1.54. More importantly, altering the refractive index of the surrounding medium at the bottom surface of the metasurface can effectively manipulate the chiroptical responses of the hybrid system, hence leading to chirality-reversed emission. This active hybrid emitting system could be a resultful platform for chirality-switchable light emission from achiral quantum emitters, holding great potential for anticounterfeiting, biosensing, light sources, imaging, and displays.

Clay minerals are ubiquitous in subsurface environments and have long been recognized as having a limited or negligible impact on the fate of arsenic (As) due to their negatively charged surfaces. Here, we demonstrate the significant role of kaolinite (Kln), a pervasive clay mineral, in enhancing As(V) immobilization during ferrous iron (Fe(II)) oxidation at near-neutral pH. Our results showed that Fe(II) oxidation alone was not capable of immobilizing As(V) at relatively low Fe/As molar ratios (≤2) due to the generation of Fe(III)-As(V) nanocolloids that could still migrate easily as truly dissolved As did. In the presence of kaolinite, dissolved As(V) was significantly immobilized on the kaolinite surfaces via forming Kln-Fe(III)-As(V) ternary precipitates, which had large sizes (at micrometer levels) to reduce the As mobility. The kaolinite-induced heterogeneous pathways for As(V) immobilization involved Fe(II) adsorption, heterogeneous oxidation of adsorbed Fe(II), and finally heterogeneous nucleation/precipitation of Fe(III)-As(V) phases on the edge surfaces of kaolinite. The surface precipitates were mixtures of amorphous basic Fe(III)-arsenate and As-rich hydrous ferric oxide. Our findings provide new insights into the role of clay minerals in As transformation, which is significant for the fate of As in natural and engineered systems.

Background and Purpose: Until now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, the lung immune prognostic index (LIPI), has shown relatively high prognostic value in patients with solid cancer. Therefore, this study aimed to further identify the association between LIPI and the survival of patients with NSCLC who receive immune checkpoint inhibitors (ICIs)., Methods: Several electronic databases were searched for available publications up to April 23, 2023. Immunotherapy outcomes included overall survival (OS), progression-free survival (PFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis based on the study design and comparison of the LIPI was conducted., Results: In this meta-analysis, 21 studies with 9,010 patients were included in this meta-analysis. The pooled results demonstrated that elevated LIPI was significantly associated with poor OS (HR = 2.50, 95% CI:2.09-2.99, p < 0.001) and PFS (HR = 1.77, 95% CI:1.64-1.91, p < 0.001). Subgroup analyses stratified by study design (retrospective vs. prospective) and comparison of LIPI (1 vs. 0, 2 vs. 0, 1-2 vs. 0, 2 vs. 1 vs. 0, 2 vs. 0-1 and 2 vs. 1) showed similar results., Conclusion: LIPI could serve as a novel and reliable prognostic factor in NSCLC treated with ICIs, and elevated LIPI predicts worse prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Lei, Zheng, Yang, Luo, Li and Xie.)

Stimuli-responsive materials have garnered substantial interest in recent years, particularly liquid crystal networks (LCNs) with sophisticatedly designed structures and morphing capabilities. Extensive efforts have been devoted to LCN structural designs spanning from two-dimensional (2D) to three-dimensional (3D) configurations and their intricate morphing behaviors through designed alignment. However, achieving microscale structures and large-area preparation necessitates the development of novel techniques capable of facilely fabricating LCN microstructures with precise control over both overall shape and alignment, enabling a 3D-to-3D shape change. Herein, a simple and cost-effective in-cell soft lithography (ICSL) technique is proposed to create LCN microstructures with customized shapes and predesigned morphing. The ICSL technique involves two sequential steps: fabricating the desired microstructure as the template by using the photopolymerization-induced phase separation (PIPS) method and reproducing the LCN microstructures through templating. Meanwhile, surface anchoring is employed to design and achieve molecular alignment, accommodating different deformation modes. With the proposed ICSL technique, cylindrical and spherical microlens arrays (CMLAs and SMLAs) have been successfully fabricated with stimulus-driven polarization-dependent focusing effects. This technique offers distinct advantages including high customizability, large-area production, and cost-effectiveness, which pave a new avenue for extensive applications in different fields, exemplified by adaptive soft micro-optics and photonics.

Rheumatoid arthritis (RA) is a persistent autoimmune condition with no identified cure currently. Recently, scientists have applied metabolomics to investigate altered metabolic profiles and unique diseases-associated metabolic signatures. Herein, we applied metabolomics approach to analyze serum samples of 41 RA patients and 42 healthy controls (HC) with the aim to characterize RA patients' metabolic profile, investigate related underlying pathological processes, and identify target metabolites. By utilizing ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we found 168 proposed metabolites and 45 vital metabolic pathways. Our analysis revealed that deoxyinosine (DI), a metabolite of the purine metabolic pathway, was the most significant reduced metabolite in RA patients. Furthermore, through targeted detection, we confirmed lower concentration of DI in RA patients' peripheral blood. Moreover, DI inhibited lipopolysaccharide-induced inflammation both in vitro and in vivo . We further assessed DI's therapeutic potential in a collagen-induced arthritis (CIA) murine model. The results revealed that DI attenuated CIA, as evidenced by significantly lowered clinical scores of arthritis, alleviated joint swelling, and mitigated bone destruction. Moreover, we elucidated the underlying mechanism by which DI increased the population of myeloid-derived suppressor cells (MDSCs) and suppressed the proliferation of induced T cells. Collectively, these findings suggested that DI potentially ameliorated RA by inducing immunosuppressive MDSCs. The study provides key observations on RA pathogenesis and may contribute to developing novel therapeutic strategies for this debilitating condition., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Parkinson's disease (PD) is inseparable from metabolic disorders but lacks assessment of specific metabolite alteration. To explore the sequential metabolic changes in PD progression, we evenly divided 78 C57BL/6 mice (10 weeks) into six groups (one control group and five experimental groups) and collected the hippocampus tissue of mice after treating with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and probenecid (twice a week) at five periods (1, 2, 3, 4, and 5 weeks) for metabolome analysis. Our study identified 567 differentially abundant metabolites (DAMs) (total 4348 metabolites). Compared with controls, 145, 146, 171, 208, and 213 DAMs were obtained from the five experimental groups, respectively. Notably, 40 shared DAMs were present in five experimental groups, of which 22 shared DAMs formed a new metabolic network based on amino acid metabolism. Compared with group W3, 84 DAMs were identified in group W5, including 12 unique DAMs. DAMs in different stages of PD were significantly enriched in amino acid metabolism pathway, lipid metabolism pathway, and ferroptosis pathway. l-Glutamine, spermidine, and l-tryptophan were the key hubs in the whole metabolic process of PD. N-Formyl-l-methionine gradually increased in abundance with PD progression, whereas 5-methylcytosine gradually decreased. The study emphasized the sequential changes in DAMs in PD progression, stimulating subsequent studies., (© 2024 John Wiley & Sons Ltd.)

Purpose: To further identify the effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) for pre- and apneic oxygenation during the anesthesia induction by comparison to facemask ventilation (FMV) based on current available evidence., Methods: Medline, EMBASE, Web of Science, Cochrane Library and CNKI databases were searched from inception to December 22, 2023 for available randomized controlled trials (RCTs). Primary outcomes were PaO2 and PaCO2 after intubation and safe apnoea time. Secondary outcomes included the O2 desaturation, end expiratory carbon dioxide (EtCO2) and complications. The effect measures for continuous and categorical outcomes were separately the mean difference (MD) and relative risk (RR) with 95% confidence interval., Results: Twelve RCTs with 403 patients in the THRIVE group and 401 patients in th FMV group were included. Pooled results demonstrated that the PaO2 after intubation was significantly higher (MD = 82.90mmHg, 95% CI: 12.25~153.54mmHg, P = 0.02) and safe apnoea time (MD = 103.81s, 95% CI: 42.07~165.56s, P = 0.001) was longer in the THRIVE group. Besides, the incidence rate of O2 desaturation (RR = 0.28, 95% CI: 0.12-0.66, P = 0.004) and gastric insufflation (RR = 0.26, 95% CI: 0.13-0.49, P<0.001) was significantly lower in the THRIVE group., Conclusion: Based on current evidence, THRIVE manifested better effectiveness representing as improved oxygenation, prolonged safe apnoea time and decreased risk of complications compared to standard FMV in surgical patients. Therefore, THRIVE could be served as a novel and valuable oxygenation technology for patients during anesthesia induction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diffractive optical element is advantageous for miniaturization, arraying and integration of optical systems. They have been widely used in beam shaping, diffractive imaging, generating beam arrays, spectral optimization and other aspects. Currently, the vast majority of diffractive optics are not tunable. This limits the applicability and functionality of these devices. Here we report a tunable diffractive optical element controlled by light in the visible band. The diffractive optical element consists of a square gold microarray deposited on a deformable substrate. The substrate is made of a liquid crystal elastomer. When pumped by a 532 nm laser, the substrate is deformed to change the crystal lattice. This changes the far-field diffraction pattern of the device. The proposed concept establishes a light-controlled soft platform with great potential for tunable/reconfigurable photonic devices, such as filters, couplers, holograms and structural color displays.

Objective: To assess the key factors influencing the effectiveness of nirmatrelvir/ritonavir in treating elderly patients with COVID-19., Methods: This study was conducted on patients aged ≥60 who were admitted to the Second Affiliated Hospital of Soochow University for COVID-19 infection and were treated with nirmatrelvir/ritonavir. Clinical information was collected from patients and steady-state blood concentrations of nirmatrelvir and ritonavir were measured. Factors associated with treatment effects were searched by univariate and multivariate analysis., Results: A total of 68 (51 males and 17 females) patients had a median age of 80 (73.0-84.8) years were enrolled in this study. The blood concentration measurements (trough concentrations) of nirmatrelvir and ritonavir were 5.1 (2.6-7.1) and 0.4 (0.2-0.9) μg/mL, respectively. Adverse drug reaction was reported in 4 (5.9%) patients. Univariate analysis showed that age, clinical classification, APACHE II score, total bilirubin (TBil), aspartate transaminase (AST), lactate dehydrogenase (LDH), and total cholesterol (TC) were significantly associated with the effectiveness of treatment (P value <0.05). Concentration of nirmatrelvir was also associated with treatment outcome (P value <0.1). Based on the results of univariate analysis, the above factors were introduced into the multiple linear regression equation as independent variables, and the results showed that clinical classification was included in the regression equation model and was the most important factor affecting the treatment outcome. By receiver operating characteristic curve analysis, the area under curve of age + biochemical indicators + APACHE II score + clinical classification was 0.968 (95% CI = 0.919-1.000; P <0.0001). Among the 68 patients included in the study, 4 cases experienced adverse drug reactions., Conclusion: Age, clinical classification, APACHE II score, TBil, AST, LDH, and TC were significantly associated with the effectiveness of treatment in elderly patients with COVID-19., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xiang et al.)

In December 2021, the U.S. Food and Drug Administration (FDA) granted emergency authorization for Paxlovid® as an antiviral treatment for COVID-19. Paxlovid® is composed of two tablets, nirmatrelvir and ritonavir. Dose adjustment is necessary in cases of renal insufficiency. The aim of present study is to establish a LC-HRMS method for simultaneous determination of nirmatrelvir/ritonavir in human serum for therapeutic drug monitoring. Internal standard saquinavir was added in 25 μL human serum samples, and then the samples were precipitated with methanol. The analytes were separated by gradient elution on a C18 column, using a mobile phase of 0.1 % formic acid-water and methanol, at a flow rate of 0.4 mL/min. The injection volume was 2 μL, and the analysis time was 5 min. The determination of the analytes was performed by electrospray ionization in positive mode by full mass monitoring. The detected ions of nirmatrelvir, ritonavir and saquinavir were m/z 500.24792, 721.32004 and 671.39155, respectively. The linear concentration range for nirmatrelvir was 78.13-20000 ng mL -1 , for ritonavir was 15.63-4000 ng mL -1 (r 2 ＞0.9900). The accuracy ranged from 87.45 %∼104.63 %, and the intra-day and inter-day precision RSD was <15 %. The recovery of nirmatrelvir ranged from 98.72 %∼109.83 %, and that of ritonavir was 95.41∼112.36 %. The matrix effect of nirmatrelvir was 88.31∼97.73 %, and that of ritonavir was 85.17∼103.05 %. This method was used to measure the trough concentrations of nirmatrelvir/ritonavir in 17 patients. The trough concentration of nirmatrelvir was 1331.7-8352.5 ng/mL, and that of ritonavir was 53.4-1325.5 ng mL -1 , with large individual differences. The method is simple, sensitive, specific, and reproducible, and can be used for monitoring the blood concentration and pharmacokinetic study of nirmatrelvir/ritonavir in COVID-19 patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Introduction: The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to provide a basis for clinical prevention of recurrence of NMIBC., Methods: From January 2012 to December 2020, 592 patients with NMIBC who underwent TURBT attending the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively included in this study. Patients were divided into relapse and relapse-free groups according to whether relapse occurred within 2 years. Ultimately, 72 patients were included in the relapse group and 350 patients were included in the relapse-free group. Observation indicators included age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, tumor size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion in initial pathology, tumor base (sessile, pedunculated), use of intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine)., Results: In this study, the 2-year recurrence rate of NMIBC patients after TURBT was 17.06%. There were significant differences in comparison of pirarubicin, BCG, and mitomycin treatment between the two groups (p &lt; 0.05). To avoid missing risk factors for recurrence, factors with p &lt; 0.1 were analyzed. The results of univariate logistic regression analysis showed that NMIBC patients with BCG treatment (OR = 5.088, 95% CI = 1.444-17.73, p = 0.012), high pathology grading (OR = 0.415, 95% CI = 0.197-0.880, p = 0.023), T1 stage (OR = 2.097, 95% CI = 0.996-4.618, p = 0.059), mitomycin treatment (OR = 5.029, 95% CI = 1.149-21.77, p = 0.031), and pirarubicin treatment (OR = 1.794, 95% CI = 1.079-3.030, p = 0.024) had significantly higher risk of recurrence within 2 years after TURBT. The results of multivariate logistic regression analysis showed that NMIBC patients with high pathology grading (OR = 0.4030, 95% CI = 0.1702-0.8426, p = 0.0241), pirarubicin treatment (OR = 1.961, 95% CI = 1.159-3.348, p = 0.0125), and BCG treatment (OR = 6.201, 95% CI = 1.275-29.73, p = 0.0190) had significantly higher risk of recurrence within 2 years after TURBT., Conclusion: Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of mitomycin and BCG on recurrence rates., (© 2023 S. Karger AG, Basel.)

Conventionally, the fabrication of liquid crystal lenticular microlens arrays (LCLMLAs) is complicated and costly. Here, we demonstrate a one-step fabrication technique for LCLMLAs, which is prepared through the photopolymerization-induced phase separation in the LC/polymer composite. The LCLMLAs possess both polarization-dependent and electrically tunable focusing properties. Furthermore, we construct a 14-view 2D/3D switchable autostereoscopic display prototype based on a 2D LCD panel and the prepared LCLMLA, which has a viewing angle of 14° and a crosstalk of 46.2% at the optimal viewing zone. The proposed LCLMLAs have the merits of simple fabrication, large-scale production, and low cost.

In recent years, ozone has become one of the key pollutants affecting the urban air quality. Direct catalytic decomposition of ozone emerges as an effective method for ozone removal. Field experiments were conducted to evaluate the effectiveness of exterior wall coatings with ozone decomposition catalysts for ozone removal in practical applications. ANSYS 2020R1 software was first used for simulation and analysis of ozone concentration and flow fields to investigate the decomposition boundary of these wall coatings. The results show that the exterior wall coatings with manganese-based catalysts can effectively reduce the ozone concentration near the wall coating. The ozone decomposition efficiency is negatively correlated with the distance from the coating and the decomposition boundary range is around 18 m. The decomposition boundary will increase with the increase of temperature, and decrease with the increase of the wind speed and the relative humidity. These results underscore the viability of using exterior wall coatings with catalysts for controlling ozone pollution in atmospheric environments. This approach presents a promising avenue for addressing ozone pollution through self-purifying materials on building external wall., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Circular RNAs (circRNAs) are noncoding RNAs with diverse functions. However, most Mycobacterium tuberculosis ( M.tb )-related circRNAs remain undiscovered. In this study, we infected THP-1 cells with virulent and avirulent M.tb strains and then sequenced the cellular circRNAs. Bioinformatic analysis predicted 58,009 circRNAs in all the cells. In total, 2035 differentially expressed circRNAs were identified between the M.tb -infected and uninfected THP-1 cells and 1258 circRNAs were identified in the virulent and avirulent M.tb strains. Further, the top 10 circRNAs were confirmed by Sanger sequencing, among which four circRNAs, namely circSOD2 , circCHSY1 , circTNFRSF21 , and circDHTKD1 , which were highly differentially expressed in infected cells compared with those in uninfected cells, were further confirmed by ring formation, specific primers, and RNase R digestion. Next, circRNA-miRNA-mRNA subnetworks were constructed, such as circDHTKD1 / miR-660-3p / IL-12B axis. Some of the individual downstream genes, such as miR-660-3p and IL-12B , were previously reported to be associated with cellular defense against pathological processes induced by M.tb infection. Because macrophages are important immune cells and the major host cells of M.tb, these findings provide novel ideas for exploring the M.tb pathogenesis and host defense by focusing on the regulation of circRNAs during M.tb infection.

Due to the unique self-acceleration, self-healing, and non-diffraction properties, Airy beams have been explored extensively and found applications in various fields. It has been proven as an essential aspect to tune the trajectory of Airy beams for extensive applications. In this paper, we propose a method based on liquid crystal (LC) alignment with metasurfaces, which enables dynamic tuning of the trajectory of Airy beams. Benefiting from both the tunable property of LCs and the compact alignment of metasurfaces, we achieve a sizeable linear potential in a short distance, which leads to the effective tuning of the trajectory of Airy beams dynamically. The introduction of metasurfaces into the alignment of LCs provides a promising method to manipulate the planar optical field., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Urethral stricture is a common disorder of the lower urinary tract in men. A complex network of pathways and interactions are involved in the pathogenesis of urethral fibrosis. However, the mechanisms underlying urethral fibrosis remain poorly understood. Objectives: To investigate the critical role of the canonical Wnt pathway in development of urethral fibrosis and explore DKK1, the endogenous inhibitor of Wnt pathway, as a potential target to prevent urethral fibrosis in vitro and in vivo . Methods: Urethral fibrosis tissue derived from patients and rat models were harvested to assess the activation of the canonical Wnt pathway by using western blot, qRT-PCR and immunohistochemistryWe performed histological staining, western blot, qRT-PCR and immunohistochemistry to examine the effects of DKK1 treatment on in vivo rat urethral fibrosis models. In vitro , human urethral fibroblasts (HUFs) were cultured to examine the effects of DKK1 in TGFβ1-induced HUFs by CCK-8 assay, hydroxyproline assay, flow cytometry, cell migration assay, western blot, qRT-PCR and immunofluorescence. Results: The key components of Wnt signaling were upregulated in urethral fibrosis tissue derived from patients and rat models while DKK 1 was downregulated. DKK1 ameliorated TGFβ1-induced urethral fibrosis in rats. TGFβ1 induced myofibroblast differentiation by upregulating collagen I, collagen III, α-SMA, β-catenin and p-GSK-3β, while DKK1 was decreased. DKK1 significantly inhibited cell proliferation, collagen content, cell migration and promoted cell apoptosis in TGFβ1-induced HUFs. DKK1 significantly suppressed myofibroblast differentiation of TGFβ1-induced HUFs by downregulating collagen I, collagen III, α-SMA, β-catenin and p-GSK-3β with a mechanism independent of Smad2/3. Conclusions: Our study demonstrated that canonical Wnt pathway may be an essential mechanism underlying the pathogenesis of urethral fibrosis and explored the potential role of DKK1 participation in the development of urethral fibrosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Circular RNAs (circRNAs) take on regulatory roles in renal cell carcinoma (RCC). The research's goal was to figure out circ-CSPP1's role and molecular mechanism in RCC. The results clarified that circ-CSPP1 expression was enhanced in RCC. Down-regulating circ-CSPP1 refrained the proliferation, migration, invasion, and Warburg effect (aerobic glycolysis), but accelerated apoptosis of RCC cells. The luciferase activity assay exhibited that circ-CSPP1 could perform as an endogenous sponge for miR-493-5p. Elevating miR-493-5p repressed RCC progression. The bioinformatics website starBase confirmed that ras-related C3 botulinum toxin substrate 1 (RAC1) was a target gene of miR-493-5p. Circ-CSPP1 up-regulated RAC1 by sponging miR-493-5p, and elevating RAC1 could turn around the effect of down-regulating circ-CSPP1 on RCC cells. Taken together, circ-CSPP1 is identified as a novel RCC-promoting RNA that could serve as a latent therapeutic target for RCC therapy.

Objective: To investigate the value of gemcitabine and pirarubicin in patients with non-muscle-invasive bladder cancer (NMIBC)., Methods: 405 patients with non-muscle invasive bladder cancer admitted to our hospital from January 2012 to December 2020 who underwent transurethral bladder tumor electronic resection were studied. 177 patients were treated with gemcitabine (Gemcitabine group) and 228 patients were treated with pirarubicin (Pirarubicin group) after surgery. The efficacy and adverse effects of the two groups were observed and the patients were followed up., Results: No differences were found when comparing age, gender, smoking, bladder mass, number of masses, hypertension, diabetes, coronary artery disease, hematuria and tumor diameter between the 2 groups (P > 0.05). In the Gemcitabine group, bladder irritation signs, meatus hematuria, fever, nausea and vomiting were lower than those in the Pirarubicin group (P < 0.05). The recurrence rates were 6.21% and 12.28% at 1 year, 11.86% and 23.68% at 2 years, 15.82% and 25.88% at 3 years in the Gemcitabine and Pirarubicin groups respectively, with the Gemcitabine group having a significantly lower recurrence rate than the Pirarubicin group (P < 0.05). The tumor recurrence-free survival rate for 5 years of gemcitabine was significantly higher than that of the Pirarubicin group (P < 0.05)., Conclusion: Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We demonstrated a low-cost, highly sensitive hybrid Ag-Cu substrate with enhanced absorption for the excitation laser beam via the nanosphere lithography technique. The hybrid Ag-Cu surface-enhanced Raman spectroscopy (SERS) substrate consists of a Cu nanoarray covered with Ag nanoparticles. The geometry of the deposited Cu nanoarray is precisely determined through a self-assembly nanosphere etching process, resulting in optimized absorption for the excitation laser beam. Further Raman enhancement is achieved by incorporating plasmonic hotspots formed by dense Ag nanoparticles, grown by immersing the prepared Cu nanoarray in a silver nitrate solution. The structural design enables analytical enhancement factor of hybrid Ag-Cu SERS substrates of 1.13 × 10 5 . The Ag-Cu SERS substrates exhibit a highly sensitive and reproducible SERS activity, with a low detection limit of 10 -13 M for Rhodamine 6G detection and 10 -9 M for 4,4'-Bipyridine. Our strategy could pave an effective and promising approach for SERS-based rapid detection in biosensors, environmental monitoring and food safety.

Liming acidic paddy soils to near-neutral pH is the most cost-effective strategy to minimize cadmium (Cd) accumulation by rice. However, the liming-induced effect on arsenic (As) (im)mobilization remains controversial and is called upon for further investigation, particularly for the safe utilization of paddy soils co-contaminated with As and Cd. Here, we explored As and Cd dissolution along pH gradients in flooded paddy soils and extracted key factors accounting for their release discrepancy with liming. The minimum As and Cd dissolution occurred concurrently at pH 6.5-7.0 in an acidic paddy soil (LY). In contrast, As release was minimized at pH < 6 in the other two acidic soils (CZ and XX), while the minimum Cd release still appeared at pH 6.5-7.0. Such a discrepancy was determined largely by the relative availability of Fe under overwhelming competition from dissolved organic carbon (DOC). A mole ratio of porewater Fe/DOC at pH 6.5-7.0 is suggested as a key indicator of whether co-immobilization of As and Cd can occur in flooded paddy soils with liming. In general, a high mole ratio of porewater Fe/DOC (≥ 0.23 in LY) at pH 6.5-7.0 can endow co-immobilization of As and Cd, regardless of Fe supplement, whereas such a case is not in the other two soils with lower Fe/DOC mole ratios (0.01-0.03 in CZ and XX). Taking the example of LY, the introduction of ferrihydrite promoted the transformation of metastable As and Cd fractions to more stable ones in the soil during 35 days of flooded incubation, thus meeting a class I soil for safe rice production. This study demonstrates that the porewater Fe/DOC mole ratio can indicate a liming-induced effect on co-(im)mobilization of As and Cd in typical acidic paddy soils, providing new insights into the applicability of liming practice for the paddy soils., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury., Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay., Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury., Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wang et al.)

Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications., (© 2023. The Author(s).)

The unique triple helix structure of collagen plays an important role in its biological properties, and the triple helix integrity is closely correlated with its molecular behavior and biological functions. Nevertheless, there is still a lack of convenient, accurate and practical methods for quantitatively determining collagen triple helix integrity. Herein, we first prepared bovine skin collagen peptide (BSCP)-protected Au/Ag nanoclusters (Au/AgNCs@BSCP) with excellent optical properties, high stability and good biocompatibility, which could adsorb on WS 2 surface leading to fluorescence quenching. Upon the addition of collagen, the interaction of collagen and Au/AgNCs@BSCP led to the detachment of Au/AgNCs@BSCP from the WS 2 surface, causing an increase in the fluorescence signal. Using the difference in the fluorescence recovery of the different samples, we achieved the quantitative determination of collagen triple helix integrity. This developed strategy exhibited excellent accuracy, selectivity, and practicality, thus showing promising potentials in biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Membrane chemical reactors (MCRs) have demonstrated a great potential for simultaneous removal of wide-spectrum pollutants in advanced water treatment. However, current catalyst (re)loading and catalytic reactivity limitations obstruct their practical applications. Herein, as a proof-of-concept, we report a hollow fiber membrane chemical reactor (HF-MCR) with high and sustainable catalytic reactivity, enabled by novel magnetic confinement engineering of the catalysts. Namely, the zerovalent iron (ZVI) nanocatalysts were spatially dispersed and confined to nearly parallel magnetic induction lines, forming forest-like microwire arrays in the membrane lumen. Such arrays exhibited ultrahigh hydrodynamic stability. The HF-MCR integrated sequential membrane separation and Fenton-like catalysis, thus being capable of high and synergistic wide-spectrum decontamination. The membrane separation process completely removed large nanoplastics (NPs) via size exclusion, and thus the subsequent Fenton-like catalysis process enhanced removal efficiency of otherwise permeated bisphenol A (BPA) and phosphate (P) by in situ generated reactive oxygen species (primarily 1 O 2 ) and iron (oxyhydr)oxides, respectively. Furthermore, highly dispersed ZVI arrays and their continuous surface depassivation driven by magnetic gradient and hydrodynamic forces conferred abundant accessible catalytic sites (i.e., Fe 0 and Fe II ) to stimulate Fenton-like catalysis. The consequent enhancement of BPA and P removal kinetics was 3-765 and 49-492 folds those in conventional (flow-through or batch) systems, respectively. Periodic ZVI reloading ensured sustained decontamination performance of the HF-MCR. This is the first demonstration of the magnetic confinement engineering that enables efficient and unlimited catalyst (re)loading and sustainable catalytic reactivity in the MCR for water treatment, which is beyond the reach of current approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Metasurfaces can enable polarization multiplexing of light so as to carry more information. Specific polarized light necessitates bulk polarizers and waveplates, which significantly increases the form size of metasurface devices. We propose an electrically programmable metasurface enabled by dual-frequency cholesteric liquid crystals (DF-CLCs) for simultaneous near- and far-field displays. Moreover, the integrated device can be electrically programmed to demonstrate 6 different optical images by engineering the DF-CLCs with frequency-modulated voltage pulses. Such programmable metasurfaces are potentially useful for many applications including information storage, displays, anti-counterfeiting, and so on.

Cadmium (Cd) removal from paddy soil to reduce Cd accumulation in brown rice is essential for agroecology, food safety, and human health. In this study, we demonstrate that ferric chloride (FeCl 3 ) washing combined with biochar treatment efficiently remediates Cd-contaminated paddy soil in field trials. Our results showed that 30.9 % of total Cd and 41.6 % of bioavailable Cd were removed by the addition of 0.03 M FeCl 3 at a liquid/soil ratio of 1.5:1. The subsequent addition of 1 % biochar further reduced bioavailable Cd by 36.5 and 41.5 %, compared with FeCl 3 washing or biochar treatment alone. The principal component regression analysis showed that the Cd content in brown rice was primarily affected by the bioavailable Cd in soil. The combined remediation contributed to the decreased Cd contents in brown rice by 45.5-62.5 %, as well as a 2.7-11.8 % increase in rice yield. The Cd contents in brown rice decreased to 0.12 and 0.04 mg kg -1 in two cultivars of rice (Zhuliangyou189 and Zhuliangyou929), lower than the national food safety standard limit value of China (0.2 mg kg -1 ). Meanwhile, the combined remediation promoted the restoration of soil pH and organic matter as well as the improvement of available nutrients. This finding suggests that the combination of FeCl 3 washing and biochar is an effective remediation strategy to minimize Cd bioavailability in paddy soil, and improves soil quality, thus contributing to food safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chirality induction, transfer, and manipulation have aroused great interest in achiral nanomaterials. Here, we demonstrate strong upconverted circularly polarized luminescence from achiral core-shell upconversion nanoparticles (UCNPs) via a plasmonic chiral metasurface-induced optical chirality transfer. The Yb 3+ -sensitized core-shell UCNPs with good dispersity exhibit intense upconversion luminescence of Tm 3+ and Nd 3+ through the energy transfer process. By spin-coating the core-shell UCNPs on this chiral metasurface, strong enhancement and circular polarization modulation of upconversion luminescence can be achieved due to resonant coupling between surface plasmons and upconversion nanoparticles. In the UCNPs-on-metasurface composite, a significant upconversion luminescence enhancement can be achieved with a maximum enhancement factor of 32.63 at 878 nm and an overall enhancement factor of 11.61. The luminescence dissymmetry factor of the induced upconverted circularly polarized luminescence can reach 0.95 at the emission wavelength of 895 nm. The UCNPs-on-metasurface composite yields efficient modulation for the emission intensity and polarization of UCNPs, paving new pathways to many potential applications in imaging, sensing, and anticounterfeiting fields.

Milk vetch (MV, Astragalus sinicus L.) is used in agricultural production as a green manure; however, its impact on accumulation levels of heavy metals (e.g., Cd) in rice remains poorly understood. This study investigated the effects of MV on Cd accumulation in rice, iron plaque formation, soil properties, and the soil microbial community structure through field experiments. The results showed that MV reduced Cd concentration in the roots, stem, leaves, and grains by 33%, 60%, 71%, and 49%, respectively. Chemical fertilizer and MV treatment promoted iron plaque formation, and MV considerably increased the Fe/Mn ratio in the iron plaque. More importantly, MV inhibited Cd transportation from the root iron plaque to the root by 74%. The concentrations of CaCl 2 -extractable Cd, available phosphorus, and available potassium, as well as the cation exchange capacity and urease activity, were significantly reduced in the MV treatment. Furthermore, 16 S rDNA high-throughput sequencing results of the soil microbial community structure showed that compared with the control, MV increased the soil microbial richness, increased the relative abundance of anaerobic microorganisms, and significantly increased the relative abundance of Thermodesulfovibrio and Geobacter at the genus level. The increase in anaerobic microbial abundance was closely related to the decrease in CaCl 2 -extractable Cd concentration. The application of MV promoted the formation of iron plaque, inhibited the transport of Cd, increased the abundance of anaerobic microorganisms, decreased the CaCl 2 -extractable Cd concentration, and reduced the Cd concentration in rice grain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Red coloration is a salient feature of the natural world. Many vertebrates produce red color by converting dietary yellow carotenoids into red ketocarotenoids via an unknown mechanism. Here, we show that two enzymes, cytochrome P450 2J19 (CYP2J19) and 3-hydroxybutyrate dehydrogenase 1-like (BDH1L), are sufficient to catalyze this conversion. In birds, both enzymes are expressed at the sites of ketocarotenoid biosynthesis (feather follicles and red cone photoreceptors), and genetic evidence implicates these enzymes in yellow/red color variation in feathers. In fish, the homologs of CYP2J19 and BDH1L are required for ketocarotenoid production, and we show that these enzymes are sufficient to produce ketocarotenoids in cell culture and when ectopically expressed in fish skin. Finally, we demonstrate that the red-cone-enriched tetratricopeptide repeat protein 39B (TTC39B) enhances ketocarotenoid production when co-expressed with CYP2J19 and BDH1L. The discovery of this mechanism of ketocarotenoid biosynthesis has major implications for understanding the evolution of color diversity in vertebrates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Digestive-organ expansion factor (Def) is a nucleolar protein that recruits cysteine proteinase Calpain3 (CAPN3) into the nucleolus to form the Def-CAPN3 complex in both human and zebrafish. This complex mediates the degradation of the tumor suppressor p53 and ribosome biogenesis factor mitotic phosphorylated protein 10 (Mpp10) in nucleolus, demonstrating the importance of this complex in regulating cell cycle and ribosome biogenesis. However, the Def and CAPN3 interacting motifs have yet been identified. In this report, by using a series of truncated or internally deleted human CAPN3 (hCAPN3) derivatives we identify that an essential motif of 86 amino acids (86-aa) (430-515aa) in hCAPN3 for its interaction with human Def (hDef), and this 86-aa motif is highly conserved in zebrafish Capn3b (zCapn3b) and is also required for the interaction between zebrafish Def (zDef) and zCapn3b. We further identify the 2/3 C-terminus of hDef is responsible for mediating the hDef-hCAPN3 interaction, and the corresponding region is conserved for the zDef and zCapn3b interaction. Our results lay the ground to resolve the structure of the Def-CAPN3 complex in the future., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Solid-state lithium batteries (SSLBs) based on Ta-doped Li 6.5 La 3 Zr 1.5 Ta 0.5 O 12 (LLZTO) suffer from lithium dendrite growth, which hinders their practical application. Herein, first principles simulations indicate that the Ta element prefers to segregate along grain boundaries in the form of Ta 2 O 5 precipitates due to a high energy difference induced by Ta doping. Grain boundary engineering is employed to regulate the distribution of the Ta element and enhance the density of LLZTO by introducing the La 2 O 3 additive. The sufficient La 2 O 3 additive reacts with the Ta 2 O 5 precipitates, while the residual La 2 O 3 nanoparticles fill up void defects, promoting the homogeneous distribution of the Ta element and improving the relative density to ∼98%. Critical current density of the symmetric Li battery reaches 2.12 mA·cm -2 at room temperature with the solid-state electrolyte (LLZTO + 5 wt % La 2 O 3 ), which increases by 41% compared to pure LLZTO. SSLBs with the LiFePO 4 cathode achieve a stable cycling performance with a discharge capacity of 138.6 mA·h·g -1 after 400 cycles at 0.2 C. This work provides theoretical insights into the distribution of Ta-doped LLZTO and inhibits lithium dendrite growth through grain boundary engineering.

Tilletia laevis causes common bunt disease in wheat, with severe losses of production yield and seed quality. Metabolomics studies provide detailed information about the biochemical changes at the cell and tissue level of the plants. Ultrahigh-performance liquid chromatography-Q-exactive mass spectrometry (UPLC-QE-MS) was used to examine the changes in wheat grains after T. laevis infection. PCA analysis suggested that T. laevis -infected and non-infected samples were scattered separately during the interaction. In total, 224 organic acids and their derivatives, 170 organoheterocyclic compounds, 128 lipids and lipid-like molecules, 85 organic nitrogen compounds, 64 benzenoids, 31 phenylpropanoids and polyketides, 21 nucleosides, nucleotides, their analogues, and 10 alkaloids and derivatives were altered in hyphal-infected grains. According to The Kyoto Encyclopedia of Genes and genomes analysis, the protein digestion and absorption, biosynthesis of amino acids, arginine and proline metabolism, vitamin digestion and absorption, and glycine, serine, and threonine metabolism pathways were activated in wheat crops after T. laevis infection.

Cardiovascular disease is a global problem that seriously endangers human health and life. At present, hypertension is considered to be a polygenic disease caused by the interaction of environmental factors and genetic factors. Various environmental factors have been proved to promote the occurrence and development of cardiovascular disease. MicroRNA (miR), as an essential gene regulatory factor in vivo, has been confirmed to participate in the regulation of many cell pathways, and its abnormal expression is closely related to a variety of human diseases. MiR-485-5p is located at 7q22.1, which has been proved to play an essential role in the tumor and cardiovascular system. Therefore, this paper discussed the mechanism of miR-485-5p on the morphology and function of the cardiovascular system. It is believed that miR-485-5p will impact the morphology and function of the cardiovascular system. Therefore, in the current study, 1655 unrelated patients with cardiovascular system diseases were simulated and analyzed based on the above background. A double luciferase reporter gene detection system verified the combination of miRNAs target recognition. The results showed that miR-485-5p significantly inhibited the luciferase activity of pGL-miR-wt but had no effect on pGL6-miR-mut. The lack of miR-485-5p can promote the activation of cardiac fibroblasts. The findings of this study can provide a new understanding and direction for the study of cardiovascular system morphology and function.

Background: Flexible ureteroscopy (FURS) and holmium laser lithotripsy is considered one of the most minimally invasive and safe surgical methods for the treatment of renal calculi. Renal pseudoaneurysm is a rare complication after FURS holmium laser lithotripsy. We report a case of renal pseudoaneurysm after FURS and holmium laser lithotripsy and review the relevant literature to analyze the possible etiology and summarize the treatment., Case Presentation: A 29-year-old male with a 2-year history of diabetes was admitted to the hospital because of right back pain for 5 days. A doppler ultrasound demonstrated bilateral renal calculi with bilateral mild hydronephrosis. The patient underwent one-stage right FURS and holmium laser lithotripsy and bilateral ureteral stent implantation. The urine was clear on the second day after the operation, and he was discharged from the hospital. Due to severe gross hematuria, he had to be hospitalized 28 days after the operation. A CT scan showed multiple blood clots in the right renal pelvis and bladder. An emergency blood transfusion and removal of the bladder blood clots and bilateral double J tubes were performed. His urine was clear for one week, and he was discharged from the hospital. He was hospitalized again 47 days after the operation because of fever and hematuria. A CT scan demonstrated blood clots in the bladder and right renal pelvis. Angiography showed a pseudoaneurysm in a small branch of the right renal artery, and hematuria stopped after selective renal artery embolization with microcoils., Conclusion: FURS and holmium laser lithotripsy is safe, but we should be aware of the possibility of renal artery pseudoaneurysms (RAP). Through careful operation during the surgery, avoiding kidney injury, reducing intrarenal pressure and controlling the time of operation may prevent the occurrence of this complication. Vascular embolization is the first choice for the treatment of pseudoaneurysms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deng, Zhang, Fu and Fu.)

Plants often face incompatible growing environments like drought, salinity, cold, frost, and elevated temperatures that affect plant growth and development leading to low yield and, in worse circumstances, plant death. The arsenal of versatile compounds for plant consumption and structure is called metabolites, which allows them to develop strategies to stop enemies, fight pathogens, replace their competitors and go beyond environmental restraints. These elements are formed under particular abiotic stresses like flooding, heat, drought, cold, etc., and biotic stress such as a pathogenic attack, thus associated with survival strategy of plants. Stress responses of plants are vigorous and include multifaceted crosstalk between different levels of regulation, including regulation of metabolism and expression of genes for morphological and physiological adaptation. To date, many of these compounds and their biosynthetic pathways have been found in the plant kingdom. Metabolites like amino acids, phenolics, hormones, polyamines, compatible solutes, antioxidants, pathogen related proteins (PR proteins), etc. are crucial for growth, stress tolerance, and plant defense. This review focuses on promising metabolites involved in stress tolerance under severe conditions and events signaling the mediation of stress-induced metabolic changes are presented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Mubeen, Hasnain, Rizwan, Adrees, Naqvi, Iqbal, Kamran, El-Sabrout, Elansary, Mahmoud, Alaklabi, Sathish and Din.)

This study assessed the ability of XP-endo Finisher R (FKG, La Chaux-de-Fonds, Switzerland) to remove filling remnants from curved mesiobuccal canals of maxillary molars, using the passive ultrasonic irrigation (PUI) technique as a comparison. Twenty-four curved main mesiobuccal canals (MB1) of maxillary molars were instrumented with Wave One (#25/07) and filled with gutta-percha points and AH Plus Sealer. Samples were then re-treated with a standardized protocol with Wave One (#35/06) as the master apical file. Micro-CT scans measured baseline volume of remaining filling material (in mm3). Samples were divided into two groups (n = 12) according to the supplementary cleaning approach: (PUI) or XP-endo Finisher R. Statistics compared baseline and final volume of filling material (within-group); and the percentage of filling material reduction (between-group). Mean baseline volumes, final volumes, and percentages of reduction (%) of filling material for XP-endo Finisher R and PUI were respectively: 0.060 mm3, 0.042 mm3, and 31.28%; and 0.064 mm3, 0.054 mm3, and 16.57%. Both tested protocols reduced the amount of filling material (p < 0.05). XP-endo Finisher R had higher percentage of reduction as compared to PUI (p < 0.05). XP-endo Finisher R and PUI used as supplementary cleaning protocols during re-treatment improved the removal of root filling material in curved canals; but XP-endo Finisher R was approximately twice more efficient. The complete filling material removal during re-treatment procedures is still a challenge. Supplementary cleaning protocols may help to remove the remaining material after the complete mechanical preparation of curved canals. XP-endo Finisher R was approximately twice more efficient than PUI.

Alpha-1 antitrypsin deficiency (AATD) is a rare autosomal codominant disease caused by mutations within the SERPINA1 gene. The most prevalent variant in patients is PiZ SERPINA1, containing a single G > A transition mutation. PiZ alpha-1 antitrypsin (AAT) is prone to misfolding, leading to the accumulation of toxic aggregates within hepatocytes. In addition, the abnormally low level of AAT secreted into circulation provides insufficient inhibition of neutrophil elastase within the lungs, eventually causing emphysema. Cytosine and adenine base editors enable the programmable conversion of C⋅G to T⋅A and A⋅T to G⋅C base pairs, respectively. In this study, two different base editing approaches were developed: use of a cytosine base editor to install a compensatory mutation (p.Met374Ile) and use of an adenine base editor to mediate the correction of the pathogenic PiZ mutation. After treatment with lipid nanoparticles formulated with base editing reagents, PiZ-transgenic mice exhibited durable editing of SERPINA1 in the liver, increased serum AAT, and improved liver histology. These results indicate that base editing has the potential to address both lung and liver disease in AATD., Competing Interests: Declaration of interests M.S.P., G.L., L.C., Y.A.S., D.L., S.S., A.S., D.C., B.J.C., B.Y., G.C., and F.M.G. are employees of and shareholders in Beam Therapeutics. This work was funded in part by Beam Therapeutics, which develops base editing therapeutics., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Surface-enhanced Raman spectroscopy (SERS) has long been an ultrasensitive technique for trace molecule detection. However, the development of a sensitive, stable, and reproducible SERS substrate is still a challenge for practical applications. Here, we demonstrate a cost-effective, centimeter-sized, and highly reproducible SERS substrate using the nanosphere lithography technique. It consists of a hexagonally packed Ag metasurface on a SiO 2 /Au/Si substrate. A seconds-lasting etching process of a self-assembled nanosphere mask manipulates the geometry of the deposited Ag metasurface on the SiO 2 /Au/Si substrate, which attains the wavelength matching between the optical absorbance of the Ag/SiO 2 /Au/Si substrate and the excitation laser wavelength as well as the enhancement of Raman signals. By spin-coating a thin layer of graphene oxide on the substrate, a SERS performance with 1.1 × 10 5 analytical enhancement factor and a limit of detection of 10 -9 M for melamine is achieved. Experimental results reveal that our proposed strategy could provide a promising platform for SERS-based rapid trace detection in food safety control and environmental monitoring.