A facile and intelligent detection method for diclazuril based on a stable dual emissive Eu3+-dopped metal-organic framework.

Diclazuril (DIC) is a broad-spectrum anti-coccidiosis drug of the triazine class, widely used in poultry farming. The overuse of DIC may lead to its accumulation in animal bodies, which may enter the food chain and threaten human health. In this work, we fabricated a stable Eu3+-doped UiO-66 fluorescence sensor (EuUHIPA-30) for the sensitive detection of DIC. Among 20 veterinary drugs, the fluorescence of EuUHIPA-30 selectively responds to DIC, with a low detection limit (0.19 µM) and fast response (10 s). EuUHIPA-30 is recyclable and can detect DIC in chicken and eggs with good recoveries. Moreover, a smartphone-integrated paper-based sensor enables the instrument-free, rapid, visual, and intelligent detection of DIC in chickens and eggs. This work provides a promising candidate for practical fluorescent DIC sensing in animal-derived food to promote food safety.

NR2F6 is essential for brown adipocyte differentiation and systemic metabolic homeostasis.

OBJECTIVE: Brown adipose tissue (BAT) development and function are essential for maintaining energy balance. However, the key factors that specifically regulate brown adipogenesis require further identification. Here, we demonstrated that the nuclear receptor subfamily 2 group F member 6 (NR2F6) played a pivotal role in brown adipogenesis and energy homeostasis. METHODS: We examined the differentiation of immortalized brown adipocytes and primary brown adipocytes when NR2F6 were deleted, and explored the mechanism through which NR2F6 regulated adipogenesis using ChIP-qPCR in vitro. Male wild type (WT) and Pdgfra-Cre-mediated deletion of Nr2f6 in preadipocytes (NR2F6-PKO) mice were fed with high fat diet (HFD) for 12 weeks, and adiposity, glucose intolerance, insulin resistance and inflammation were assessed. RESULTS: NR2F6 exhibited abundant expression in BAT, while its expression was minimal in white adipose tissue (WAT). Within BAT, NR2F6 was highly expressed in preadipocytes, experienced a transient increase in the early stage of brown adipocyte differentiation, and significantly decreased in the mature adipocytes. Depletion of NR2F6 in preadipocytes inhibited brown adipogenesis, caused hypertrophy of brown adipocytes, and impaired thermogenic function of BAT, but without affecting WAT development. NR2F6 transcriptionally regulated PPARγ expression to promote adipogenic process in brown adipocytes. Loss of NR2F6 in preadipocytes led to increased susceptibility to diet-induced metabolic disorders. CONCLUSIONS: Our findings unveiled NR2F6 as a novel key regulator of brown adipogenesis, potentially opening up new avenues for maintaining metabolic homeostasis by targeting NR2F6.

Dual-emissive Eu(III)-functionalized metal-organic frameworks for visual, rapid, and intelligent sensing of albendazole and albendazole sulfoxide in animal-origin food.

Albendazole (ABZ), a benzimidazole-based anthelmintic, is widely used to treat helminth infections. The extensive and improper use of ABZ may cause drug residues in animal-origin food and anthelmintics resistance, which potentially threaten human health. Meanwhile, albendazole sulfoxide (ABZSO), a metabolite of ABZ, also exhibits toxic effects. Therefore, the detection of ABZ and ABZSO in animal-derived food is significantly necessary. Herein, a dual-emission europium fluorescent sensor (EuUHC-30) was rationally designed and constructed. EuUHC-30 exhibits high selectivity and sensitivity towards ABZ and ABZSO with a detection limit of 0.10 and 0.13 µM, respectively. Furthermore, EuUHC-30 was successfully applied for quantification of ABZ and ABZSO in milk and pig kidney, which were verified by HPLC analysis. Moreover, a smartphone-assisted EuUHC-30 fluorescent paper sensor was fabricated for the practical determination of ABZ and ABZSO in real food. Overall, this work provides a visual, rapid, and intelligent method for the detection of ABZ and ABZSO in animal-origin food.

A recyclable Eu3+-functionalized dual-emissive metal-organic framework for portable, rapid detection and efficient removal of malachite green.

A europium-functionalized, dual-emissive, metal-organic framework-based fluorescence sensor (EuUCNDA) was constructed via post-synthetic modification of an UiO-66-type precursor through coordination interactions. EuUCNDA exhibited extremely high selectivity and sensitivity for malachite green (MG) with a low detection limit of 13.01 nM, a wide linear concentration range (0.05-50 µM), excellent anti-interference properties, a rapid response (<1 min), and the possibility of recycling. The good sensing performance of EuUCNDA enables the practical detection of MG in fish pond water and grass carp with good recoveries. Moreover, EuUCNDA can be reused for sensing MG and over 90% of fluorescence intensity can be restored after 7 cycles. Furthermore, EuUCNDA-embedded paper-based sensors combined with smartphone imaging afford portable and visual monitoring of MG in real samples. Notably, besides good sensing performance, EuUCNDA could efficiently remove MG from water. Hence, this work provides a recyclable and sensitive fluorescence sensor for portable, visual, rapid detection and efficient removal of MG.

Multifunctional Eu3+-MOF for simultaneous quantification of malachite green and leuco-malachite green and efficient adsorption of malachite green.

Multi-target detection combined with in-situ removal of contaminants is a challenging issue difficult to overcome. Herein, a dual-emissive Eu3+-metal organic framework (Eu3+-MOF) was constructed by pre-functionalization with a blue-emissive ligand and post-functionalization with red-emissive Eu3+ ions using a UiO-66 precursor. The fluorescence of the synthesized Eu3+-MOF is highly selective and sensitive toward malachite green (MG) and its metabolite leuco-malachite green (LMG), which are environmentally persistent and highly toxic to humans. The limit of detection of MG and LMG are 34.20 and 1.98 nM, respectively. Interestingly, the fluorescence of this Eu3+-MOF showed ratiometric but different responsive modes toward MG and LMG, which enabled the simultaneous quantification of MG and LMG. Furthermore, a paper-based sensor combined with the smartphone was fabricated, which facilitated not only the dual-channel detection of MG, but also its portable, visual, rapid, and intelligent determination. Furthermore, the high surface area of MOFs, together with the coordinate bonding interaction, π-π stacking, and electrostatic interaction sites, endows Eu3+-MOF with the efficient ability toward MG removal. This multifunctional Eu3+-MOF can be successfully used for trace detection, simultaneous determination of MG and LMG, as well as efficient removal of MG. Thus, it exhibits bright prospects for widespread applications in the field of food and environmental analysis.

CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.

Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.

A highly water-stable dual-emission fluorescent probe based on Eu3+-loaded MOF for the simultaneous detection and quantification of Fe3+ and Al3+ in swine wastewater.

A novel dual-emissive Eu3+-loaded metal-organic framework (MOF) is designed and successfully fabricated by introducing 2-hydroxyterephthalic acid (H2BDC-OH) and Eu3+ ions into an UiO-66-type MOF material. The obtained MOF, here referred to as EuUCH, exhibits dual emission at 450 and 614 nm, and both emissions are quite stable in aqueous media in the pH range of 4-11. EuUCH is characterized by a high selectivity and sensitivity toward Fe3+ and Al3+, which yield different responsive modes. The two emissions of EuUCH are quenched by Fe3+; by contrast, only the emission at 450 nm is quenched by Al3+ showing a ratiometric fluorescence signal. More importantly, as there is no clear interference between the signals of Fe3+ and Al3+, EuUCH is successfully utilized for the simultaneous detection of Fe3+ and Al3+ in their mixtures. In addition, the simultaneous quantification of Fe3+ and Al3+ is achieved in more complicated swine wastewater with good recoveries. This work provides a water-stable dual-emissive probe and the possibility to achieve the simultaneous quantification of Fe3+ and Al3+ in complicated environment wastewater.

A dual-channel "on-off-on" fluorescent probe for the detection and discrimination of Fe3+ and Hg2+ in piggery feed and swine wastewater.

Blue-fluorescent blood-CDs were synthesized through a one-pot hydrothermal method using a mixture of chicken blood and trisodium citrate and then explored as a fluorescent probe for detecting Fe3+ and Hg2+. The probe showed excellent selectivity and sensitivity towards Fe3+ and Hg2+ with a dramatic "on-off" fluorescence response. F- recovered the fluorescence quenching by Fe3+, and Al3+ recovered the fluorescence quenching by Hg2+, showing an "off-on" fluorescence response. The blood-CDs were used as an "on-off-on" dual-channel fluorescent sensor for the detection and discrimination of Fe3+ and Hg2+ ions. The probe showed wide linear ranges for determination of Fe3+ (0-100 µM) and Hg2+ (0-120 µM) with low detection limits of 0.23 µM for Fe3+ and 0.17 µM for Hg2+. This probe was practically applied for the determination of Fe3+ and Hg2+ in piggery feed and wastewater with good recoveries. This work provides a fluorescent probe for the quantification of Fe3+ and Hg2+ in livestock feed and environmental water samples.

Study on Factors Associated with High Myopia CNV in Aqueous Humor and Serum.

Objective: The objective is to investigate the relationship and correlation between PEDF and TGF-ß in aqueous humor and serum and high myopia CNV lesions. Methods: For each group of patients (namely, group A: patients with high myopia CNV (mCNV); group B: patients with high myopia without CNV; group C: patients with CNV caused by other eye diseases; and group D (control group): patients with simple cataract (without CNV and high myopia)), 20 patients were collected. A total of 40 patients have been collected since the beginning of the study in December 2020, including 7 patients in group A, 13 patients in group B, 10 patients in group C, and 10 patients in group D. Serum and aqueous humor samples were collected, and PEDF and TGF-ß levels in serum and aqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). SPSS 26.0 statistical software was used to process the data. Independent sample t-test was used to compare the data of the same factor in the same group between serum and aqueous humor. Comparisons of the same factors between different groups were performed using a one-way analysis of variance (ANOVA). Correlation analysis was conducted by the Pearson correlation coefficient test. P < 0.05 indicated that the difference was statistically significant. Results: There were no significant differences in age, gender, and course of disease among all groups (P > 0.05). The concentration of PEDF in aqueous humor in group A and group C was higher than that in group B and group D. There was no significant correlation between serum PEDF content and the above-mentioned diseases. The concentration of TGF-ß in aqueous humor in groups A, B, and C was significantly higher than that in group D. However, there was no significant correlation between TGF-ß content in serum and the above-mentioned diseases. There was no significant correlation between aqueous humor and serum PEDF. There was no significant correlation between the content of TGF-ß in aqueous humor and serum. Conclusion: TGF-ß in aqueous humor may be involved in the development of high myopia and intraocular CNV disease. However, PEDF in aqueous humor may be involved in the development of intraocular CNV disease and has no significant correlation with high myopia. At the same time, TGF-ß and PEDF in serum had no significant correlation with high myopia and intraocular CNV disease. There was no significant correlation between the concentrations of TGF-ß and PEDF in aqueous humor and serum.

A luminescent Eu3+-functionalized MOF for sensitive and rapid detection of tetracycline antibiotics in swine wastewater and pig kidney.

Tetracyclines (TCs), a type of antibiotics, are widely used in human therapy and animal husbandry. Public concerns about tetracyclines residues have been raised due to their negative impact on the environment and food, causing bacterias drug resistance and human health concerns. In this work, a luminescent europium MOF (EuUCBA) is constructed via post-synthetic attachment of Eu3+ into a UiO-66 type MOF. The luminescent of EuUCBA exhibits high stability in aqueous media in the pH range of 4-11. Among 36 common veterinary drugs, the synthesized probe is highly selective and sensitive to six tetracyclines with low detection limits of 0.118 µM, 0.228 µM, 0.102 µM, 0.138 µM, 0.206 µM, and 0.078 µM for oxytetracycline (OTC), chlortetracycline (CTC), methylenetetracycline (MTC), minocycline (MOC), tetracycline (TC), and doxycycline (DOXY), respectively. Furthermore, the probe shows good anti-interference ability and fast response. Finally, EuUCBA was successfully to detect DOXY in swine wastewater and pig kidney with good recoveries. This work provides an excellent fluorescent sensor for highly selective and rapid detection of TCs residues in wastewater and complex biological samples.

Recyclable europium functionalized metal-organic fluorescent probe for detection of tryptophan in biological fluids and food products.

An europium functionalized metal-organic fluorescent probe, Eu3+@UiO-66-FDC was constructed by post-synthetic modification through coordination interactions. Eu3+@UiO-66-FDC displayed high selectivity and sensitivity toward Tryptophan (Trp) among all the 20 natural amino acids and other general compounds in food and biological samples, with a wide linear concentration range (0-1000 µM), low detection limit (0.29 µM), and a rapid response (<1 min). Besides, this probe was utilized to detect Trp in rabbit blood serum and milk samples with good recoveries, which were verified by high-performance liquid chromatography (HPLC). Notably, this fluorescent probe proved to be a recyclable material. Hence, this work provides a reliable and recyclable fluorescent probe applicable toward the detection of Trp in biological fluids and/or food products.

Highly sensitive and rapid detection of thiabendazole residues in oranges based on a luminescent Tb3+-functionalized MOF.

Thiabendazole (TBZ), has been extensively employed as a pesticide and/or a fungicide in agriculture, while its residues would threaten to public health and safety. Simple, rapid and sensitive probes for detection of TBZ in real food samples is significantly desirable. In present work, a highly selective and sensitive luminescent sensor for monitoring TBZ in oranges has been constructed based on a Tb3+-functionalized Zr-MOF (Tb3+@1). Tb3+@1 exhibited many attractive sensing properties toward TBZ, including broad linear range (0-80 µM), high selectivity, low LOD (0.271 µM) and rapid response time (less than1 min). Moreover, the probe was employed to determine TBZ in real orange samples, in which good recoveries from 98.41 to 104.48% were obtained. It only takes 35 min for the whole process of detection TBZ in real orange samples combined with QuEChERS method. Therefore, this work provided a reliable and rapid method for monitoring the TBZ in real orange samples.

Predicting disease risks by matching quantiles estimation for censored data.

In time to event data analysis, it is often of interest to predict quantities such as t-year survival rate or the survival function over a continuum of time. A commonly used approach is to relate the survival time to the covariates by a semiparametric regression model and then use the fitted model for prediction, which usually results in direct estimation of the conditional hazard function or the conditional estimating equation. Its prediction accuracy, however, relies on the correct specification of the covariate-survival association which is often difficult in practice, especially when patient populations are heterogeneous or the underlying model is complex. In this paper, from a prediction perspective, we propose a disease-risk prediction approach by matching an optimal combination of covariates with the survival time in terms of distribution quantiles. The proposed method is easy to implement and works flexibly without assuming a priori model. The redistribution-of-mass technique is adopted to accommodate censoring. We establish theoretical properties of the proposed method. Simulation studies and a real data example are also provided to further illustrate its practical utilities.