Electrochemical/fluorescent dual-mode aptasensor based on 3D porous AuNPs/MXene for detection of ultra-trace mercury (Hg2+).

In this work, the dual-mode aptasensor based on 3D porous AuNPs/MXene using "turn-on" electrochemical method and "turn-off" fluorescent strategy was fabricated. Here, 2D MXene was processed into 3D porous MXene by sacrificial polymethylmethacrylate (PMMA) spherical template. And the meteor hammer-like AuNPs which had good electrochemical properties and quenching effect on fluorescence was synthesized by single electrodeposition. Dual-signal labeled Nile Blue (NB) was in situ grafted to the Hg2+ aptamer ends of 3D porous AuNPs/MXene/GCE, and an efficient and sensitive signal interface was constructed to realize the sensitive detection of Hg2+. 3D porous AuNPs/MXene had the advantages of large specific surface area, excellent electron transmission performance and signal amplification. The experimental results indicated that this sensor exhibited high sensitivity to Hg2+ in both electrochemical and fluorescent sensing, with detection limits of 2.69 fM and 1.60 fM, respectively. Further, the dual-mode aptasensor can ensure the detection accuracy and target quantization. The dual-mode aptasensor has been successfully applied to the ultra-trace detection of Hg2+ in actual water samples, which shows the potential of aptamer sensor in detecting heavy metal ions in environmental monitoring.

Preclinical Assessment of the PI3Kα Selective Inhibitor Inavolisib and Prediction of Its Pharmacokinetics and Efficacious Dose in Human.

1. Small molecule inhibitors of the PI3K pathway have been extensively investigated as potential anticancer agents. Among the effectors in this pathway, PI3Kα is the kinase most frequently associated with the development of tumors, through mutations and amplifications of the PIK3CA gene encoding the p110α catalytic subunit.2. Inavolisib (GDC-0077) is a potent and PI3Kα-selective inhibitor that also specifically triggers the degradation of the mutant p110α protein.3. We characterized inavolisib ADME properties in preclinical in vitro and in vivo studies, assessed its efficacy in the PIK3CA mutant KPL-4 breast cancer xenograft model, and predicted its pharmacokinetics and efficacious dose in humans.4. Inavolisib had a moderate permeability (1.9•10-6 cm/s) in MDCK cells and was a P-gp and Bcrp1 substrate. It appeared metabolically stable in hepatocytes incubations from human and preclinical species. The systemic clearance was low in mouse, monkey and dog and high in rat. Oral bioavailability ranged from 57.5% to 100%. Inavolisib was efficacious in the KPL-4 sub-cutaneous xenograft model.5. The PK/PD model parameters estimated from the efficacy study, combined with PBPK model-predicted human PK profiles, projected that a dose of 3 mg could lead to clinical response. Inavolisib is currently being tested in phase 3 trials.

Recent advances on COF-based single-atom and dual-atom sites for oxygen catalysis.

Covalent organic frameworks (COFs) have emerged as promising platforms for the construction of single-atom and dual-atom catalysts (SACs and DACs), owing to their well-defined structures, tunable pore sizes, and abundant active sites. In recent years, the development of COF-based SACs and DACs as highly efficient catalysts has witnessed a remarkable surge. The synergistic interplay between the metal active sites and the COF has established the design and fabrication of COF-based SACs and DACs as a prominent research area in electrocatalysis. These catalytic materials exhibit promising prospects for applications in energy storage and conversion devices. This review summarizes recent advances in the design, synthesis, and applications of COF-based SACs and DACs for oxygen catalysis. The catalytic mechanisms of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are comprehensively explored, providing a comparative analysis to elucidate the correlation between the structure and performance, as well as their functional attributes in battery devices. This review highlights a promising approach for future research, emphasizing the necessity of rational design, breakthroughs, and in-situ characterization to further advance the development of high-performance COF-based SACs and DACs for sustainable energy applications.

The efficacy of patellar denervation on prognosis and kneeling capacity after unicompartmental knee arthroplasty: a randomized clinical trial.

OBJECTIVE: The aim of this study was to investigate the effect of patellar denervation (PD) on pain, function and ability to kneel after unicompartmental knee arthroplasty (UKA). METHODS: Patients with medial knee osteoarthritis who underwent UKA were prospectively selected. Patients were randomly divided into PD and non-PD groups based on whether patellar denervation was performed. Clinical assessment was performed using the Hospital for Special Surgery (HSS) knee score, Kujiala score, visual analogue scale (VAS) and forgotten joint score (FJS-12), as well as postoperative complications were recorded. The patients' postoperative self-perception and actual ability to perform different kneeling positions were assessed in the two groups. RESULTS: UKA patients treated with PD achieved better Kujiala scores and FJS-12 scores, reduced anterior knee pain and improved kneeling ability postoperatively, validating the effectiveness of PD in UKA. Perception and actual performance of kneeling remained mismatched in PD patients, but performance during different kneeling activities was generally better than in non-PD patients. TRIAL REGISTRATION: Clinical Trial Registration: ChiCTR1900025669. CONCLUSION: Patellar denervation can safely and effectively improve patellofemoral joint function, pain and kneeling ability in the early postoperative period after UKA.

Two different mirror neuron pathways for social and non-social actions? A meta-analysis of fMRI studies.

Mirror neurons (MNs) represent a class of neurons that are activated when performing or observing the same action. Given their role in social cognition and previous research in patients with psychiatric disorders, we proposed that the human MN system (MNS) might display different pathways for social and non-social actions. To examine this hypothesis, we conducted a comprehensive meta-analysis of 174 published human functional magnetic resonance imaging studies. Our findings confirmed the proposed hypothesis. Our results demonstrated that the non-social MN pathway exhibited a more classical pattern of frontoparietal activation, whereas the social MN pathway was activated less in the parietal lobe but more in the frontal lobe, limbic lobe, and sublobar regions. Additionally, our findings revealed a modulatory role of the effector (i.e. face and hands) within this framework: some areas exhibited effector-independent activation, while others did not. This novel subdivision provides valuable theoretical support for further investigations into the neural mechanisms underlying the MNS and its related disorders.

Design, synthesis and biological evaluation of marine naphthoquinone-naphthol derivatives as potential anticancer agents.

1'-Hydroxy-4',8,8'-trimethoxy-[2,2'-binaphthalene]-1,4-dione (compound 5), a secondary metabolite recently discovered in marine fungi, demonstrates promising cytotoxic and anticancer potential. However, knowledge regarding the anticancer activities and biological mechanisms of its derivatives remains limited. Herein, a series of novel naphthoquinone-naphthol derivatives were designed, synthesised, and evaluated for their anticancer activity against cancer cells of different origins. Among these, Compound 13, featuring an oxopropyl group at the ortho-position of quinone group, exhibited the most potent inhibitory effects on HCT116, PC9, and A549 cells, with IC50 values decreasing from 5.27 to 1.18 µM (4.5-fold increase), 6.98 to 0.57 µM (12-fold increase), and 5.88 to 2.25 µM (2.6-fold increase), respectively, compared to compound 5. Further mechanistic studies revealed that compound 13 significantly induced cell apoptosis by increasing the expression levels of cleaved caspase-3 and reducing Bcl-2 proteins through downregulating the EGFR/PI3K/Akt signalling pathway, leading to the inhibition of proliferation in HCT116 and PC9 cells. The present findings suggest this novel naphthoquinone-naphthol derivative may hold potential as an anticancer therapeutic lead.

Negative allosteric modulator of Group â mGluRs: Recent advances and therapeutic perspective for neuropathic pain.

Neuropathic pain (NP) is a widespread public health problem that existing therapeutic treatments cannot manage adequately; therefore, novel treatment strategies are urgently required. G-protein-coupled receptors are important for intracellular signal transduction, and widely participate in physiological and pathological processes, including pain perception. Group I metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, are predominantly implicated in central sensitization, which can lead to hyperalgesia and allodynia. Many orthosteric site antagonists targeting Group I mGluRs have been found to alleviate NP, but their poor efficacy, low selectivity, and numerous side effects limit their development in NP treatment. Here we reviewed the advantages of Group I mGluRs negative allosteric modulators (NAMs) over orthosteric site antagonists based on allosteric modulation mechanism, and the challenges and opportunities of Group I mGluRs NAMs in NP treatment. This article aims to elucidate the advantages and future development potential of Group I mGluRs NAMs in the treatment of NP.

Pandemic scars: long-term impact of COVID-19 on work stress among healthcare workers in China.

PURPOSE: This study mainly focused on the long-term effect of different risk exposure levels and prior anti-epidemic experience of healthcare workers in mitigating COVID-19 on their work stress in the post-COVID era. DESIGN/METHODOLOGY/APPROACH: The study sample included 359 physicians, 619 nurses, 229 technicians and 212 administrators, for a total of 1,419 healthcare workers working in the Lanzhou area during the investigation. Data were analyzed by multivariate regression models. FINDINGS: Our findings indicated that the interaction between pandemic effect mitigation experience and high-risk exposure significantly affected healthcare workers in the post-COVID era by increasing their work stress (p < 0.001) and reducing their rest time (p < 0.001). Healthcare workers may have experienced worse outcomes in the long term if they had higher levels of risk exposure and more experience in fighting epidemics. Furthermore, poor mental health (p < 0.001) and prior experience with SARS (p < 0.001) further amplified these adverse effects. However, surprisingly, we did not observe any effect of prior anti-epidemic experience or high-risk exposure on the mental health of healthcare workers in the post-COVID era (p > 0.1). RESEARCH LIMITATIONS/IMPLICATIONS: The adverse impact of COVID-19 may have left long-lasting effects on Health professionals (HPs), particularly those with high Risk exposure (RE) and more mitigation experience. Poor Mental health (MH) and previous experience in mitigating previous similar outbreaks (such as SARS) are risk factors that should be considered. Support programs must be designed and promoted to help HPs respond and improve their performance. ORIGINALITY/VALUE: Our study presents compelling evidence that the COVID-19 pandemic will have long-term detrimental effects on the work stress of healthcare workers.

Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.

Neuropathic pain, a multifaceted and incapacitating disorder, impacts a significant number of individuals globally. Despite thorough investigation, the development of efficacious remedies for neuropathic pain continues to be a formidable task. Recent research has revealed the potential of metabotropic glutamate receptor 5 (mGlu5) as a target for managing neuropathic pain. mGlu5 is a receptor present in the central nervous system that has a vital function in regulating synaptic transmission and the excitability of neurons. This article seeks to investigate the importance of mGlu5 in neuropathic pain pathways, analyze the pharmacological approach of targeting mGlu5 for neuropathic pain treatment, and review the negative allosteric mGlu5 modulators used to target mGlu5. By comprehending the role of mGlu5 in neuropathic pain, we can discover innovative treatment approaches to ease the distress endured by persons afflicted with this incapacitating ailment.

Copper aggravated synaptic damage after traumatic brain injury by downregulating BNIP3-mediated mitophagy.

Synaptic damage is a crucial pathological process in traumatic brain injury. However, the mechanisms driving this process remain poorly understood. In this report, we demonstrate that the accumulation of damaged mitochondria, resulting from impaired mitphagy, plays a significant role in causing synaptic damage. Moreover, copper induced downregulation of BNIP3 is a key player in regulating mitophagy. DMSA alleviates synaptic damage and mitochondrial dysfunction by promoting urinary excretion of copper. Mechanistically, we find that copper downregulate BNIP3 by increasing the nuclear translocation of NFKB, which is triggered by TRIM25-mediated ubiquitination-dependent degradation of NFKBIA. Our study underscores the importance of copper accumulation in the regulation of BNIP3-mediated mitophagy and suggests that therapeutic targeting of the copper-TRIM25-NFKB-BNIP3 axis holds promise to attenuate synaptic damage after traumatic brain injury.

How does family resilience develop among stroke survivors and their caregivers? A mixed-method study using a chain mediating model.

Background: Walsh's family resilience theory indicated that families could foster resilient outcomes among their members when they are facing changes or crises. However, little is known about family resilience among Chinese stroke survivors and their caregivers. Objectives: To explore the direct and indirect relationships between the family resilience of stroke survivors, perceived social support, self-perceived burden, self-efficacy, and the burden on their principal caregivers, and to examine the journey of adapting to family resilience among stroke survivors. Design: An explanatory sequential mixed-method study. Methods: A quantitative assessment of perceived social support, self-perceived burden, self-efficacy, and family resilience was conducted among a cohort of stroke survivors. For a deeper understanding of the family resilience formation process, semi-structured, in-depth interviews were undertaken with a purposefully selected subset of participants, consisting of 15 stroke survivors and their principal caregivers who met the study criteria. Data analysis encompassed descriptive statistics, mediation models, and content analysis to integrate and interpret both quantitative and qualitative data. Results: In a comprehensive hospital in Guangdong Province, China, 379 participants-229 men (60.4%) and 150 women (39.6%)-completed a cross-sectional questionnaire survey. The quantitative phase revealed significant statistical differences (p < 0.05) in total family resilience scores among stroke survivors related to various factors, such as age, marital status, educational level, occupational status, average monthly income per capita, first-time onset, and types of stroke. Self-perceived burden and self-efficacy partially mediate the relationship between perceived social support and family resilience, contributing to a sequential chain-mediated effect. During the qualitative phase, in-depth interviews revealed a progressive trajectory from the initial shock of diagnosis through the ongoing presence of stress and challenges to the ultimate development of family resilience and an adaptive perspective toward the future. Conclusions: Exploring the factors influencing family resilience in stroke survivors could assist healthcare professionals developing interventions to enhance family resilience and lessen the burden on principal caregivers from individual, family, and social perspectives.

Rich nutrition decreases the concentration of metals in Chaeturichthys stigmatias.

Metals play a vital role in living organisms, serving as cofactors for enzymes, structural components of proteins, and participants in signaling pathways. However, the relationship between metal content and nutrient levels in organisms has not been thoroughly elucidated, which is the major barrier to regulate metal levels in organisms. In this study, we investigated the association between muscle metal concentration and external nutritional conditions, as well as intrinsic nutrient requirements in Chaeturichthys stigmatias. The results demonstrated a negative correlation between muscle metal levels and body mass index (BMI). Furthermore, our investigation unveiled a negative correlation between metal levels and zooplankter abundance, as well as a positive correlation with the abundance of underlying phytoplankton and chlorophyll. Moreover, metal levels gradually increased during the development of gonads, particularly in female individuals. As the gonads matured and ovulated, metal levels gradually decreased. The same trends were observed in Mouse erythroleukemia cells (MEL) when different concentrations of FBS were added. Collectively, these findings highlight the inherent connection between metal levels and nutrition, and offer potential guidance for regulating metal homeostasis in organisms, as well as reducing the exposure of organisms to toxic heavy metals in the environment. SYNOPSIS: With an increase in the level of external nutrients and a decrease in intrinsic nutrient requirements, the level of metals in the organism gradually decreases.

Research Progress on NMDA Receptor Enhancement Drugs for the Treatment of Depressive Disorder.

Major depressive disorder (MDD) is a severe mental illness with a complex etiology. Currently, many medications employed in clinical treatment exhibit limitations such as delayed onset of action and a high incidence of adverse reactions. Therefore, there is a pressing need to develop antidepressants that exhibit enhanced efficacy and safety. The N-methyl-D-aspartate receptor (NMDAR), a distinctive glutamate-gated ion channel receptor, has been implicated in the onset and progression of depressive disorder, as evidenced by both preclinical and clinical research. The NMDAR antagonist, ketamine, exhibits rapid and sustained antidepressant effects, holding promise as a novel therapeutic approach for depressive disorder. However, its psychotomimetic impact and potential for addiction have restricted its widespread clinical application. Notably, over the past decade, studies have suggested that enhancing NMDAR functionality can produce antidepressant effects with improved safety, especially with the emergence of NMDAR-positive allosteric modulators (PAMs). We view this as a potential novel strategy for treating depression, forming the basis for the narrative review that follows.

UKF-Based Optimal Tracking Control for Uncertain Dynamic Systems With Asymmetric Input Constraints.

To enhance system robustness in the face of uncertainty and achieve adaptive optimization of control strategies, a novel algorithm based on the unscented Kalman filter (UKF) is developed. This algorithm addresses the finite-horizon optimal tracking control problem (FHOTCP) for nonlinear discrete-time (DT) systems with uncertainty and asymmetric input constraints. An augmented system is constructed with asymmetric control constraints being considered. The augmented problem is addressed with a DT Hamilton-Jacobi-Bellman equation (DTHJBE). By analyzing convergence with regard to the cost function and control law, the UKF-based iterative adaptive dynamic programming (ADP) algorithm is proposed. This algorithm approximates the solution of the DTHJBE, ensuring that the cost function converges to its optimal value within a bounded range. To execute the UKF-based iterative ADP algorithm, the actor-estimator-critic framework is built, in which the estimator refers to system state estimation through the application of UKF. Ultimately, simulation examples are presented to show the performance of the proposed method.

Summary Analysis of National Surveillance on Kashin-Beck Disease from 1990 to 2023.

Objective: To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China, and provide the basis for formulating prevention and control measures. Methods: Fixed-point monitoring, moving-point monitoring, and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria, clinical and X-ray assessments were used to confirm the diagnosis. Results: In 1990, the national KBD detectable rate was 21.01%. X-ray detection decreased to below 10% in 2003 and below 5% in 2007. Between 2010 and 2018, the prevalence of KBD in children was less than 0.4%, which fluctuated at a low level, and has decreased to 0% since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion: The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.

Cardiovascular morbidity risk attributable to thermal stress: analysis of emergency ambulance dispatch data from Shenzhen, China.

BACKGROUND: Climate change has raised scientific interest in examining the associations of weather conditions with adverse health effects, while most studies determined human thermal stress using ambient air temperature rather than the thermophysiological index. OBJECTIVES: To evaluate the association between emergency ambulance dispatches (EADs) related to cardiovascular causes and heat/cold stress in Shenzhen, a city in southern China, with the aim of providing new insights for local policymakers. METHODS: A time series analysis using ambulance dispatch data of cardiovascular diseases in Shenzhen, China (2013-2019) was conducted. A quasi-Poisson nonlinear distributed lag model was applied to explore the relationship between emergency ambulance dispatches (EADs) due to cardiovascular causes and thermal stress (determined by Universal Thermal Climate Index, UTCI). Attributable fractions were estimated to identify which UTCI ranges have a greater health impact. RESULTS: The relationship between UTCI and EADs due to cardiovascular diseases exhibits a reverse J-shaped curve. The effects of cold stress were immediate and long-lasting, whereas the effects of heat stress were non-significant. Compared with the optimal equivalent temperature (71st percentile of UTCI, 29.22 °C), the relative risks for cumulative (0-21 days) exposures to cold stress (1st percentile, - 0.13 °C; 5th percentile, 7.68 °C) were 1.55 (95%CI:1.28,1.88) and 1.44 (95%CI:1.22,1.69), respectively. Thermal (cold and heat) stress was responsible for 10.81% (95%eCI: 5.67%,15.43%) of EADs for cardiovascular diseases, with 9.46% (95%eCI: 3.98%,14.40%) attributed to moderate cold stress (2.5th ~ 71st percentile). Greater susceptibility to cold stress was observed for males and the elderly. Heat stress showed harmful effects in the warm season. CONCLUSIONS: Our results demonstrated that cold exposure elevates the risk of EADs for cardiovascular causes in Shenzhen, and moderate cold stress cause the highest burden of ambulance dispatches. Health authorities should consider effective adaptation strategies and interventions responding to cold stress to reduce the morbidity of cardiovascular diseases.

Exogenous hydrogen sulfide enhances myogenic differentiation of C2C12 myoblasts under high palmitate stress.

Skeletal muscle atrophy was one of main complications of type 2 diabetes mellitus. Hydrogen sulfide (H2S) is involved in various physiological functions, such as anti-hypertension and anti-oxidant. Skeletal muscle atrophy caused by type 2 diabetes could lead to the regeneration of muscle fibers. Wnt signaling pathway plays a crucial important role in this process. H2S maybe regulate the Wnt signaling pathway to alleviate skeletal muscle atrophy, however, this role has not been clarified. The aim of this study is to investigate the potential regulatory role of H2S in the Wnt signaling pathway. C2C12 myoblasts treated with 500 µmol palmitate as an in vitro model. Western blot was used to detect the levels of CSE, PKM1, ß-catenin, MuRF1, MYOG, MYF6 and MYOD1. In addition, MuRF1 was mutated at Cys44 and MuRF1 S-sulfhydration was detected by biotin switch assay. The interaction between PKM1 and MuRF1 was assessed via Co-immunoprecipitation. Differentiation of C2C12 myoblasts was evaluated using LAMININ staining. These data showed the levels of CSE, ß-catenin, PKM1, MYOG, MYF6 and MYOD1 were decreased in pal group, compared with control and pal + NaHS groups. MuRF1 Cys44 mutants increased the protein levels of ß-catenin, MYOG, MYF6 and MYOD1 in pal group. Our results suggest that H2S regulates the S-sulfhydration levels of MuRF1 at Cys44, influencing the ubiquitination levels of PKM1 and ultimately promoting myoblast differentiation.

Interactions between arbuscular mycorrhizal fungi and phosphate-soluble bacteria affect ginsenoside compositions by modulating the C:N:P stoichiometry in Panax ginseng.

The biomass production as well as the accumulation of secondary metabolites of plant is highly determined by the absorption of nutritional elements, in particular nitrogen (N) and phosphorus (P). Arbuscular mycorrhizal fungi (AMF) can absorb soluble P and transport it to plants, while phosphate solubilizing bacteria (PSB) can increase the content of solubilizing P in soil. Previous studies have identified the effects of either AMF or PSB inoculation on altering plant C:N:P stoichiometry, whether AMF interact with PSB in promoting plant growth and changing elemental concentration and composition of secondary metabolites by altering plant C:N:P stoichiometry remains ambiguous. In this study, we investigated the effects of inoculation of AMF, PSB, and their co-inoculation AMP (AMF and PSB) on the biomass growth, the C:N:P stoichiometry, the core microorganisms of rhizosphere soil, and the ginsenoside compositions of ginseng (Panax ginseng). The results showed that compared to control or single inoculation of AMF or PSB, co-inoculation of AMF and PSB significantly increased the AMF colonization rate on ginseng roots, increased the biomass of both above and under-ground parts of ginseng. Similarly, co-inoculation of AMF and PSB substantially increased the concentrations of N and P, reduced the ratios of C:P and N:P in the above-ground part of ginseng. The co-inoculation of AMF and PSB also increased concentrations of total ginsenosides and altered the compositions of ginsenosides in both the above and under-ground parts of ginseng. Analysis the rhizosphere microorganism showed that the co-inoculation of AMF and PSB recruited distinct core microorganisms that differ from the control and treatments with single inoculation of AMF or PSB. Our results suggested that PSB inoculation enhanced the positive effect of AMF in improving the absorption of nutrimental elements, altered the C:N:P stoichiometry and, ginsenosides concentration and composition of ginseng, influenced the plant rhizosphere microbial community. These findings offer valuable insights into enhancing plant biomass production and promoting secondary metabolites by improving the plant-fungi-bacterial relationships.

New insights into uranium biomineralization mediated by Pseudomonas sp. WG2-6 in the presence of organic phosphorus: Promoting effect of extracellular polymeric substance and formation of U-P nanominerals.

Microbial biomineralization significantly affects the uranium (U) behavior in the environment. However, the mechanism of microbial biomineralization of U is still not fully understood. In this study, a dominant bacterium (Pseudomonas sp. WG2-6) was isolated from U tail mining area. Abiotic precipitation tests demonstrated that U biomineralization was entirely attributed to the mediation of Pseudomonas sp. WG2-6 when the concentration ratio of exogenous ß-glycerophosphate (SGP) to U was 10:1. Pseudomonas sp. WG2-6 exhibited strong immobilization ability towards U (97.59 %) according to batch experiments, and acylamide, carbonyls, and phosphate groups were the main functional groups that interacted with U. Besides, U mainly existed in the form of amorphous U-P complexes after biomineralization by Pseudomonas WG2-6, which could be converted into crystalline nano-minerals H2(UO2)2(PO4)2·8H2O in the presence of SGP. In particular, the formation and structural composition changes of extracellular polymeric substance (EPS) as well as the decrease in U4f binding energy were observed during the U biomineralization process of Pseudomonas sp. WG2-6 in the presence of SGP, indicating that EPS provided the nucleation site for the formation of stable biomineralized products. This work provides new insight into the mechanism of U microbial biomineralization and a theoretical basis for the remediation of U contaminated environments through microbial biomineralization.

211At radiolabeled APBA-FAPI for enhanced targeted-alpha therapy of glioma.

Fibroblast activation protein-α (FAPα) is highly expressed in tumor-associated cells and has become one of the most attractive targeting sites in cancer diagnosis and therapy. To ameliorate the rapid metabolism of FAPα inhibitor (FAPI), here, a multifunctional binding agent was introduced to simultaneously achieve 211At radiolabeling and tumor retention prolongation of corresponding radiolabeled drug. 211At-APBA-FAPI was successfully synthesized by conjugating 211At with the designed FAPI carrier in satisfactory radiochemical yield (>60 %). 211At-APBA-FAPI exhibited excellent in vitro stability, significant tumor affinity and specific killing effect on FAPα-positive U87MG cells. Molecular docking reveals that FAPI decorated with albumin binder can bind with FAPα protein via multiple intermolecular interactions with a considerable binding energy of -9.66 kcal/mol 211At-APBA-FAPI exhibits good targeting in murine xenograft models, showing obviously longer tumor retention than previously-reported radioastatinated compound. As a result, 211At-APBA-FAPI presents pronounced therapeutic effect with ignorable normal organs/tissues biotoxicity. All these indicate that introducing a multifunctional binding agent can effectively enhance the availability of FAPI for 211At conjugation and tumoricidal effect, providing vital hints for the translation of targeted-alpha therapy based on radiolabeled FAPI derivatives.