The efficient uptake of uranium by amine-functionalized ß-cyclodextrin supported fly ash composite from polluted water.

A novel polyethyleneimine/polydopamine-functionalized ß-cyclodextrin supported fly ash adsorbent (PEI/PDA/ß-CD/FA) had been synthesized to uptake uranium from polluted water. At pH = 5.0 and T = 298 K, the uranium uptake efficiency and capacity of PEI/PDA/ß-CD/FA reached to 98.7 % and 622.8 mg/g, respectively, which were much higher than those of FA (71.4 % and 206.7 mg/g).The excellent uranium uptake properties of PEI/PDA/ß-CD/FA could be explained by three points: (1) using ß-CD as a supporting material could effectively avoid the aggregation of FA and improve the hydrophily of FA; (2) the unique cavity structure of ß-CD could form chelates with uranyl ions; (3) the formation of PEI/PDA co-deposition coating on FA further enhanced the affinity of FA to UO22+. With the presence of interfering ions, the uptake efficiency of PEI/PDA/ß-CD/FA for uranium was still up to 94.5 % after five cycles, indicating the high selectively and recoverability of PEI/PDA/ß-CD/FA. In terms of the results of characterizations, uranium was captured by PEI/PDA/ß-CD/FA via electrostatic attraction, hydrogen bond, coordination and complexation. To sum up, PEI/PDA/ß-CD/FA was expected to be used for actual sewage treatment owing to its excellent uranium uptake efficiency/capacity, selectivity, cycle stability and feasibility of actual application.

Primary cilia restrict autoinflammation by mediating PD-L1 expression.

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Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking.

BACKGROUND: Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear. METHODS: Male and female C57BL/6 mice (8-12 weeks) and male cynomolgus monkeys (7-10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms. RESULTS: The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200+) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200+ DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates. CONCLUSIONS: Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.

Surface-Enhanced Raman Scattering Based on Sb2S3 Microstructures via Femtosecond Laser Direct Writing.

The noble-metal-free surface-enhanced Raman scattering (SERS) substrates have gained significant attention due to their abundant sources, signal uniformity, biocompatibility, and chemical stability. However, the lack of controllable synthesis and fabrication methods for high-SERS-activity noble-metal-free substrates hinders their practical applications. In this study, we demonstrate the use of a femtosecond laser direct writing technique to precisely manipulate and modify microstructures, resulting in enhanced SERS signals from Sb2S3 nonmetal-oxide semiconductor materials. Compared with unpatterned Sb2S3 samples, the Sb2S3 microstructures exhibited up to a 16-fold increase in Raman scattering intensity. Interestingly, our results indicate that the femtosecond laser can induce a transformation in the crystalline state of Sb2S3 and significantly enhance the Raman spectrum signal within the Sb2S3 microstructures. This enhancement is also highly dependent on the period and depth of the microstructures, possibly due to the cavity effects, resulting in a stronger local field enhancement.

Second-harmonic flat-top beam shaping via a three-dimensional nonlinear photonic crystal.

We experimentally extend the nonlinear Gaussian to flat-top beam shaping from one to two dimensions through a three-dimensional nonlinear photonic crystal. Employing a near-infrared femtosecond laser, we induce a modification inside lithium niobate to achieve a second-order nonlinear optical coefficient modulation in three dimensions. The flat-topped truncation of wavefront has been adjusted in a mutual perpendicular coordinate separately. Among the generated flat-topped beams, the optimal flatness is 97.1%, and the nonlinear conversion efficiency is 10-2 at the peak power of 37 kW with the interaction length of 630 µm. By adding an extra dimension, our work simultaneously enables full-wavefront flat-top distribution and nonlinear frequency conversion.

XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis.

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-ß (TGF-ß), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-ß-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.

ATF4 inhibits TRPV4 function and controls itch perception in rodents and nonhuman primates.

ABSTRACT: Acute and chronic itch are prevalent and incapacitating, yet the neural mechanisms underlying both acute and chronic itch are just starting to be unraveled. Activated transcription factor 4 (ATF4) belongs to the ATF/CREB transcription factor family and primarily participates in the regulation of gene transcription. Our previous study has demonstrated that ATF4 is expressed in sensory neurons. Nevertheless, the role of ATF4 in itch sensation remains poorly understood. Here, we demonstrate that ATF4 plays a significant role in regulating itch sensation. The absence of ATF4 in dorsal root ganglion (DRG) neurons enhances the itch sensitivity of mice. Overexpression of ATF4 in sensory neurons significantly alleviates the acute and chronic pruritus in mice. Furthermore, ATF4 interacts with the transient receptor potential cation channel subfamily V member 4 (TRPV4) and inhibits its function without altering the expression or membrane trafficking of TRPV4 in sensory neurons. In addition, interference with ATF4 increases the itch sensitivity in nonhuman primates and enhances TRPV4 currents in nonhuman primates DRG neurons; ATF4 and TRPV4 also co-expresses in human sensory neurons. Our data demonstrate that ATF4 controls pruritus by regulating TRPV4 signaling through a nontranscriptional mechanism and identifies a potential new strategy for the treatment of pathological pruritus.

Metal-support interaction boosts the stability of Ni-based electrocatalysts for alkaline hydrogen oxidation.

Ni-based hydrogen oxidation reaction (HOR) electrocatalysts are promising anode materials for the anion exchange membrane fuel cells (AEMFCs), but their application is hindered by their inherent instability for practical operations. Here, we report a TiO2 supported Ni4Mo (Ni4Mo/TiO2) catalyst that can effectively catalyze HOR in alkaline electrolyte with a mass activity of 10.1 ± 0.9 A g-1Ni and remain active even up to 1.2 V. The Ni4Mo/TiO2 anode AEMFC delivers a peak power density of 520 mW cm-2 and durability at 400 mA cm-2 for nearly 100 h. The origin for the enhanced activity and stability is attributed to the down-shifted d band center, caused by the efficient charge transfer from TiO2 to Ni. The modulated electronic structure weakens the binding strength of oxygen species, rendering a high stability. The Ni4Mo/TiO2 has achieved greatly improved stability both in half cell and single AEMFC tests, and made a step forward for feasibility of efficient and durable AEMFCs.

A preliminary study on the association of single nucleotide polymorphisms and methylation of dopamine system-related genes with psychotic symptoms in patients with methamphetamine use disorder.

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.

A Two-stage Diagnostic Framework for Post-ablation Treatment Response Assessment in Patients with Hepatocellular Carcinoma.

Contrast-enhanced ultrasound (CEUS) video plays an important role in post-ablation treatment response assessment in patients with hepatocellular carcinoma (HCC). However, the assessment of treatment response using CEUS video is challenging due to issues such as high inter-frame data repeatability, small ablation area and poor imaging quality of CEUS video. To address these issues, we propose a two-stage diagnostic framework for post-ablation treatment response assessment in patients with HCC using CEUS video. The first stage is a location stage, which is used to locate the ablation area. At this stage, we propose a Yolov5-SFT to improve the location results of the ablation area and a similarity comparison module (SCM) to reduce data repeatability. The second stage is an assessment stage, which is used for the evaluation of postoperative efficacy. At this stage, we design an EfficientNet-SK to improve assessment accuracy. The Experimental results on the self-collected data show that the proposed framework outperforms other selected algorithms, and can effectively assist doctors in the assessment of post-ablation treatment response.

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models.

T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.

The influence of biological sex in human skeletal muscle transcriptome during ageing.

Sex is a crucial biological variable, and influence of biological sex on the change of gene expression in ageing skeletal muscle has not yet been fully revealed. In this study, the mRNA expression profiles were obtained from the Gene Expression Omnibus database. Key genes were identified by differential expression analysis and weighted gene co-expression network analysis. The gene set enrichment analysis software and Molecular Signatures Database were used for functional and enrichment analysis. A protein-protein interaction network was constructed using STRING and visualized in Cytoscape. The results were compared between female and male subgroups. Differentially expressed genes and enriched pathways in different sex subgroups shared only limited similarities. The pathways enriched in the female subgroup were more similar to the pathways enriched in the older groups without taking sex difference into consideration. The pathways enriched in the female subgroup were more similar to the pathways enriched in the older groups without taking sex difference into consideration. The muscle myosin filament pathways were downregulated in the both aged female and male samples whereas transforming growth factor beta pathway and extracellular matrix-related pathways were upregulated. With muscle ageing, the metabolism-related pathways, protein synthesis and degradation pathways, results of predicted immune cell infiltration, and gene cluster associated with slow-type myofibers drastically different between the female and male subgroups. This finding may indicate that changes in muscle type with ageing may differ between the sexes in vastus lateralis muscle.

Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells.

Inadequate invasion and excessive apoptosis of trophoblast cells are associated with the development of preeclampsia. Vitamin D deficiency in pregnant women may lead to an increased risk of preeclampsia. However, the underlying mechanisms by which vitamin D is effective in preventing preeclampsia are not fully understood. The objectives of this study were to investigate the role of lysosome-associated membrane glycoprotein 3 (LAMP3) in the pathogenesis of preeclampsia and to evaluate whether vitamin D supplementation would protect against the development of preeclampsia by regulating LAMP3 expression. Firstly, the mRNA and protein levels of LAMP3 were significantly upregulated in the placentas of preeclampsia patients compared to normal placentas, especially in trophoblast cells (a key component of the human placenta). In the hypoxia/reoxygenation (H/R)-exposed HTR-8/Svneo trophoblast cells, LAMP3 expression was also upregulated. H/R exposure repressed cell viability and invasion and increased apoptosis of trophoblast cells. siRNA-mediated knockdown of LAMP3 increased cell viability and invasion and suppressed apoptosis of H/R-exposed trophoblast cells. We further found that 1,25(OH)2D3 (the hormonally active form of vitamin D) treatment reduced LAMP3 expression in H/R exposed trophoblast cells. In addition, 1,25(OH)2D3 treatment promoted cell viability and invasion and inhibited apoptosis of H/R-exposed trophoblast cells. Notably, overexpression of LAMP3 abrogated the protective effect of 1,25(OH)2D3 on H/R-exposed trophoblast cells. Collectively, we demonstrated trophoblast cytoprotection by vitamin D, a process mediated via LAMP3.

Sulfite Poses a Risk of Hexavalent Chromium Rebound in Vadose Zone: A Challenge of the Stability of CrxFe1-x(OH)3.

Cr(VI) rebound is the primary risk associated with the reduction remediation of Cr(VI)-contaminated soil. The potential impact of sulfites, which can be produced by microbial activities or originate from sulfur-containing remediation agents, on the Cr(VI) rebound in the vadose zone has been overlooked. When sulfites are present, the stability of CrxFe1-x(OH)3 is compromised and significantly inferior to that of Cr(OH)3, as demonstrated in this paper. First, Fe acts as a catalyst for the conversion of adsorbed sulfite to SO4·-, which subsequently triggers the oxidation of Cr(III) and results in the rebound of Cr(VI). The heterogeneous catalysis by Fe on the surface of CrxFe1-x(OH)3 plays a predominant role, contributing to 78% of the actual oxidation of Cr(III) among all employed catalytic processes. The presence of ambient Cl- can exacerbate the rebound effect of Cr(VI) by promoting the generation of HOCl. Furthermore, a portion of released Cr(VI) was reduced to Cr(III) by dissolved sulfite in the presence of dissolved Fe as a catalyst, thereby increasing the dissolution and migration risk associated with CrxFe1-x(OH)3. Hence, the presence of sulfites results in a significant increase in the Cr(VI) rebound and Cr(III) release from CrxFe1-x(OH)3. This challenges the conventional understanding of the stability of CrxFe1-x(OH)3.

Primary cilium-mediated signaling cascade suppresses age-related biliary fibrosis.

The primary cilium is increasingly recognized as a crucial player in the physiology of biliary epithelial cells (BECs). However, the precise role of primary cilia in the development of age-related biliary fibrosis remains unclear. Herein, using cilium-deficient mice, we demonstrate that disruption of ciliary homeostasis in BECs in aged mice leads to significant bile duct proliferation, augmented biliary fibrosis, and heightened indicators of liver injury. Our RNA-sequencing data revealed a dysregulation in genes associated with various biological processes such as bile secretion, fatty acid metabolism, and inflammation. Loss of primary cilia also significantly enhanced signaling pathways driving the development of biliary fibrosis. Our findings collectively suggest that loss of primary cilia in the BECs of aged mice initiates a cascade of signaling events that contribute to biliary fibrosis, highlighting the primary cilium as a potential therapeutic target in the treatment of fibrosing cholangiopathies.

Hydrophobicity-driven self-assembly of nanoplastics and silver nanoparticles for the detection of polystyrene microspheres using surface enhanced Raman spectroscopy.

Microplastics (MPs) and Nanoplastics (NPs) accumulated in the environment have been identified as a major global issue due to their potential harm to wildlife. Current research in the detection of MPs is well established. However, the detection of NPs remains challenging. The aim of this paper is to investigate the detection of polystyrene (PS) NPs on a super-hydrophobic substrate using surface-enhanced Raman spectroscopy (SERS) technology after high-speed centrifugation of PS NPs and AgNPs. The hydrophobic substrate reduces the contact area of droplet, concentrating PS NPs and AgNPs on a small spot, which eliminates the random distribution of nano particles. The condensed PS NPs and AgNPs improve the SERS intensity, reproductivity and detection sensitivity. The results show that SERS measurement on a hydrophobic substrate could significantly improve the detection sensitivity of PS NPs, with the detection limits of PS NPs as low as 0.5 mg/L (500 nm PS NPs) and 1 mg/L (100 nm PS NPs). The study provides an effective and rapid method for the detection of NPs at trace concentration, demonstrating more possibility for the future detection of trace NPs in the aquatic environment.

Application of Hyperspectral Imaging as a Nondestructive Technology for Identifying Tomato Maturity and Quantitatively Predicting Lycopene Content.

Maturity is a crucial indicator in assessing the quality of tomatoes, and it is closely related to lycopene content. Using hyperspectral imaging, this study aimed to monitor tomato maturity and predict its lycopene content at different maturity stages. Standard normal variable (SNV) transformation was applied to preprocess the hyperspectral data. Then, using competitive adaptive reweighted sampling (CARS), the characteristic wavelengths were selected to simplify the calibration models. Based on the full and characteristic wavelengths, a support vector classifier (SVC) model was developed to determine tomato maturity qualitatively. The results demonstrated that the classification accuracy using the characteristic wavelength led to the obtention of better results with an accuracy of 95.83%. In addition, the support vector regression (SVR) and partial least squares regression (PLSR) models were utilized to predict lycopene content. With a coefficient of determination for prediction (R2P) of 0.9652 and a root mean square error for prediction (RMSEP) of 0.0166 mg/kg, the SVR model exhibited the best quantitative prediction capacity based on the characteristic wavelengths. Following this, a visual distribution map was created to evaluate the lycopene content in tomato fruit intuitively. The results demonstrated the viability of hyperspectral imaging for detecting tomato maturity and quantitatively predicting the lycopene content during storage.

Sex difference and risk factors in burden of urogenital congenital anomalies from 1990 to 2019.

Urogenital congenital anomalies (UCAs) is defined as "any live-birth with a urinary or genital condition" and affects millions of men and women worldwide. However, sex differences and related environmental risk factors in UCAs burden on a global scale have not been assessed. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated prevalence, incidence, mortality and disability-adjusted life years (DALYs) of UCAs from 1990 to 2019 by sex, region, and socio-demographic Index (SDI) in 204 countries and territories. The disease burden of UCAs was also estimated attributable to each risk factor were estimated according to risk exposure. In 2019, UCAs caused 10,200 all-ages deaths (95% UI 7550-13,400). The combined global incidence rate was 8.38 per 1000 (95% UI 5.88-12.0) live births. The ASIR increased slightly, while the ASDR decreased from 1990 to 2019.The UCAs burden varies greatly depending on the development level and geographical location. The UCAs burden was significantly higher in men than in women, and the sex differences showed an enlarging trend. Health risks and issues, including pollution, child and maternal malnutrition, diet habits, unsafe sanitation and water source, were detected to be positively related to UCAs burden. Albeit the age-standardised prevalence, mortality, incidence, and DALYs of UCAs have decreased, they still cause a public health challenge worldwide. The high deaths and DALYs rates in low and low-middle SDI countries highlight the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for enhancing water safety, reducing pollution, and healthy diets are crucial steps in reducing the burden of UCAs.

An advanced ratiometric molecularly imprinted sensor based on metal ion reoxidation for indirect and ultrasensitive glyphosate detection in fruit.

An indirect and ultrasensitive ratiometric molecularly imprinted (MIP) sensor, based on metal ion reoxidation, is introduced for glyphosate (GLY) determination in fruit. As high-performance signal amplification substrates, carbon nanotubes (MWCNTs) and gold nanoparticles (AuNPs) are conveniently modified on GCE. The artificial antibody-MIP membrane, presents typical three-dimensional structure to GLY template. Built-in reference methylene blue (MB) is directly electropolymerized on MWCNTs-Au/GCE. Particularly, Cu2+ and GLY interestingly form chelate complex, and the Cu2+ (ICu) in Cu(Ⅱ)-GLY-complex can be reoxidized, and indirectly quantizes GLY. The reference signal (IMB) presents noteworthy stability with different GLY levels, and the ratiometric readout (ICu/IMB) is recognized as a more trustworthy indicator to quantize GLY. Proposed sensor presents broad range as 1.73 âˆ¼ 400 ng/mL, and limit of detection is well found as 0.24 ng/mL (S/N = 3). Finally, as-fabricated method is verified with standard HPLC in real-fruit-sample, and the errors and recovery rates are calculated as 3.4% âˆ¼ 6.7% and 94.4% âˆ¼ 104.6%, respectively.