A sensitive and versatile electrochemical sensor based on hybridization chain reaction and CRISPR/Cas12a system for antibiotic detection.

A sensitive electrochemical platform was constructed with NH2-Cu-MOF as electrochemical probe to detect antibiotics using CRISPR/Cas12a system triggered by hybridization chain reaction (HCR). The sensing system consists of two HCR systems. HCR1 occurred on the electrode surface independent of the target, generating long dsDNA to connect signal probes and producing a strong electrochemical signal. HCR2 was triggered by target, and the resulting dsDNA products activated the CRISPR/Cas12a, thereby resulting in effective and rapid cleavage of the trigger of HCR1, hindering the occurrence of HCR1, and reducing the number of NH2-Cu-MOF on the electrode surface. Eventually, significant signal change depended on the target was obtained. On this basis and with the help of the programmability of DNA, kanamycin and ampicillin were sensitively detected with detection limits of 60 fM and 10 fM (S/N = 3), respectively. Furthermore, the sensing platform showed good detection performance in milk and livestock wastewater samples, demonstrating its great application prospects in the detection of antibiotics in food and environmental water samples.

Label-free electrochemical sensing platform for sensitive detection of ampicillin by combining nucleic acid isothermal enzyme-free amplification circuits with CRISPR/Cas12a.

The residue of ampicillin (AMP) in food and ecological environment poses a potential harm to human health. Therefore, a reliable system for detecting AMP is in great demand. Herein, a label-free and sensitive electrochemical sensor utilizing NH2-Co-MOF as an electrocatalytic active material for methylene blue (MB) was developed for rapid and facile AMP detection by combining hybridization chain reaction (HCR), catalytic hairpin assembly (CHA) with CRISPR/Cas12a. The surface of glassy carbon electrode modified with NH2-Co-MOF was able to undergo HCR independent of the AMP, forming long dsDNA complexes to load MB, resulting in strong original electrochemical signal. The presence of AMP could trigger upstream CHA circuit to activate the CRISPR/Cas12a system, thereby achieving rapid non-specific cleavage of the trigger ssDNA of HCR on the electrode surface, hindering the occurrence of HCR and reducing the load of MB. Significant signal change triggered by the target was ultimately obtained, thus achieving sensitive detection of the AMP with a detection limit as low as 1.60 pM (S/N = 3). The proposed sensor exhibited good stability, selectivity, and stability, and achieved reliable detection of AMP in milk and livestock wastewater samples, demonstrating its promising application prospects in food safety and environmental monitoring.

In situ fast self-assembled preparation of dandelion-like Cu(OH)2@Cu3(HHTP)2 with core-shell heterostructure arrays for electrochemical sensing of formaldehyde in food samples.

Formaldehyde is known to harm the respiratory, nervous, and digestive systems of people. In this paper, a novel dandelion-like electrocatalyst with core-shell heterostructure arrays were fast self-assembled prepared in situ using copper foam (CF) as support substrate and 2,3,6,7,10,11 hexahydroxy-triphenyl (HHTP) as ligand (Cu(OH)2@Cu3(HHTP)2/CF) by a simple two-step hydrothermal reaction. The 1D Cu(OH)2 nanorods "core" and the 2D π-conjugated conducting metal-organic frameworks (Cu3(HHTP)2cMOF) "shell" with remote delocalized electrons give the dandelion-like heterogeneous catalysts excellent electrochemical activity such as a large specific surface area, high conductivity and a fast electron transfer rate. The Cu(OH)2@Cu3(HHTP)2/CF exhibited excellent electrocatalytic performance for formaldehyde under alkaline conditions with a linear range of 0.2 µmol/L - 125 µmol/L and 125 µmol/L - 8 mmol/L, a detection limit as low as 15.9 nmol/L (S/N = 3), as well as good accuracy, consistency, and durability, and it effectively identified FA in food.

Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in Mycobacterium tuberculosis.

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo. It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of TrpE, which is the first enzyme in the Trp synthesis pathway of M. tuberculosis. However, other Trp structural analogs, such as indolmycin, also target tryptophanyl-tRNA synthetase (TrpRS), which has two functions in bacteria: synthesis of tryptophanyl-AMP by catalyzing ATP + Trp and producing Trp-tRNATrp by transferring Trp to tRNATrp. So, we speculate that IPA may also target TrpRS. In this study, we found that IPA can dock into the Trp binding pocket of M. tuberculosis TrpRS (TrpRSMtb), which was further confirmed by isothermal titration calorimetry (ITC) assay. The biochemical analysis proved that TrpRS can catalyze the reaction between IPA and ATP to generate pyrophosphate (PPi) without Trp as a substrate. Overexpression of wild-type trpS in M. tuberculosis increased the MIC of IPA to 32-fold, and knock-down trpS in Mycolicibacterium smegmatis made it more sensitive to IPA. The supplementation of Trp in the medium abrogated the inhibition of M. tuberculosis by IPA. We demonstrated that IPA can interfere with the function of TrpRS by mimicking Trp, thereby impeding protein synthesis and exerting its anti-TB effect.

Preclinical evaluation of the SARS-CoV-2 Mpro inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir.

Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.4 nM and suggests that it dissociates about 12 times slower from Mpro compared with nirmatrelvir. The crystal structure of the SARS-CoV-2 Mpro:RAY1216 complex shows that RAY1216 covalently binds to the catalytic Cys145 through the α-ketoamide group. In vitro and using human ACE2 transgenic mouse models, RAY1216 shows antiviral activities against SARS-CoV-2 variants comparable to those of nirmatrelvir. It also shows improved pharmacokinetics in mice and rats, suggesting that RAY1216 could be used without ritonavir, which is co-administered with nirmatrelvir. RAY1216 has been approved as a single-component drug named 'leritrelvir' for COVID-19 treatment in China.

NiCo-LDH coupled with 2D ZIF-derived Co nitrogen doped carbon nanosheet arrays as a self-supporting electrocatalyst for detection of formaldehyde.

Formaldehyde is susceptible to illegal addition to foodstuffs to extend their shelf life due to its antimicrobial, preservative and bleaching properties. In this study, a self-supporting "nanosheet on nanosheet" arrays electrocatalyst with core-shell heterostructure was prepared in situ by coupling NiCo layer double hydroxide with 2D ZIF derived Co-nitrogen-doped porous carbon on carbon cloth (Co-N/C@NiCo-LDH NSAs/CC). Co-N/C nanosheet arrays act as a scaffold core with good electrical conductivity, providing more NiCo-LDH nucleation sites to avoid NiCo-LDH agglomeration, thus having fast mass/charge transfer performance. While the NiCo-LDH nanosheet arrays shell with high specific surface area provide more active sites for electrochemical reactions. As an electrocatalytic sensing electrode, Co-N/C@NiCo-LDH NSAs/CC has a wide linear range of 1 µM to 13 mM for formaldehyde detection, and the detection limit is 82 nM. Besides, the sensor has been applied to the detection of formaldehyde in food samples with satisfactory results.

Construction of Co-ZIF-derived CoS2@Cu hollow heterogeneous nanotube array for the detection of hydrazine in environmental water samples.

As a neurotoxin, it is necessary to establish a low cost, stable and sensitive method for the quantitative detection of hydrazine. Using Co-ZIF (zeolite imidazole framework) nanorods as precursor, CoS2 hollow nanotube array heterogeneous structure loaded with Cu nanoparticles were prepared on carbon cloth (CC) by etching, calcination and plasma magnetron sputtering (CoS2@Cu HNTA/CC). As a self-supporting electrode, its hollow heterogeneous structure provides a large area of electron transfer channel for the oxidation of the food pollutant hydrazine. In addition, bimetallic synergies and in situ N doping regulated the electronic structure of CoS2@Cu HNTA/CC, and thus significantly improved the electrical conductivity and catalytic activity. As an efficient hydrazine sensor with a wide linear range of 1 µM L-1-10 mM (1 µM-1 mM and 1 mM-10 mM), its sensitivity and the limit of detection are 7996 µA mM-1 cm-2, 3772 µA mM-1 cm-2 and 0.276 µM (S/N = 3), respectively. This study provides a new strategy for the construction of MOFs (Metal Organic Framework)-derived bimetallic composites and their application in electrochemical sensing.

Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

A sensitive "off-on" electrochemiluminescence DNA sensor based on signal cascade amplification circuit and distance-dependent energy transfer.

A sensitive "off-on" electrochemiluminescence (ECL) DNA sensor was constructed based on Exo III-assisted cascade amplification system. In the cascade amplification circuit, target DNA and Exo III cutting substrate were designed into an inverted T-shaped binding mode to form a stable DNA junction, thus effectively triggering Exo III digestion cycle. During the biosensor assembly process, ferrocene (Fc) and distance-dependent ECL resonance energy transfer (ECL-RET) and surface plasmon resonance (SPR) effects were introduced to regulate the ECL of semiconductor quantum dots (QDs). Carboxylated ZnCdSe/ZnS QDs were used as ECL signal probes and K2S2O8 was coreactant, and the initial cathodic ECL signal of QDs was efficiently quenched through electron and energy transfer with Fc and ECL-RET with Au NPs, leaving the system in "off" state. After the products of cascade amplification were introduced into the electrode surface, the single-stranded DNA modified with Fc was displaced, and the distance between Au NPs and QDs became farther, resulting in a transition from ECL-RET to SPR, and then a significant ECL signal boost was achieved, turning the system into "on" state. The combination of efficient cascade amplification system and sensitive "off-on" ECL signal change mode enabled the biosensing platform to detect target DNA with high selectivity (able to distinguish single-base mutated DNA) and ultra-high sensitivity (limit of detection was 31.67 aM, S/N = 3), providing a new perspective for designing highly sensitive and programmable ECL biosensors.

A novel hollow CuMn-PBA@NiCo-LDH nanobox for efficient detection of glucose in food.

Designing a rapid and sensitive glucose detection method is of great significance to public health. Herein, hollow CuMn-PBA@NiCo-LDH nanoboxes (CuMn-PBA@NiCo-LDH NBs) were prepared using acid etching, cation exchange, and reflux method. The modified electrode exhibited outstanding electrocatalytic performance for glucose oxidation due to the unique hollow nanostructure and synergistic effects. The CuMn-PBA@NiCo-LDH NBs electrode displayed excellent electrocatalytic oxidation activity for glucose in an alkaline solution. Under optimal conditions, the electrode achieved a wide linear range (0.0005-1 mmol L-1, and 1-7 mmol L-1) and high sensitivity (10,300 µA L/mmol cm-2 and 5310 µA L/mmol cm-2), with a limit of detection (LOD) of 19 nmol L-1. The feasibility of the sensor applied to the detection of glucose was verified in real food samples through spiked recovery experiments. This electrode material offers an alternative method for the non-enzymatic glucose sensors.

NR1 Splicing Variant NR1a in Cerebellar Granule Neurons Constitutes a Better Motor Learning in the Mouse.

As an excitatory neuron in the cerebellum, the granule cells play a crucial role in motor learning. The assembly of NMDAR in these neurons varies in developmental stages, while the significance of this variety is still not clear. In this study, we found that motor training could specially upregulate the expression level of NR1a, a splicing form of NR1 subunit. Interestingly, overexpression of this splicing variant in a cerebellar granule cell-specific manner dramatically elevated the NMDAR binding activity. Furthermore, the NR1a transgenic mice did not only show an enhanced motor learning, but also exhibit a higher efficacy for motor training in motor learning. Our results suggested that as a "junior" receptor, NR1a facilitates NMDAR activity as well as motor skill learning.

Analysis of risk factors for non-alcoholic fatty liver disease in hospitalized children with obesity before the late puberty stage.

Objective: This study aimed to determine the clinical characteristics of obese pediatric non-alcoholic fatty liver disease (NAFLD) in central China and verify the applicability of some known risk factors for pediatric NAFLD before late puberty. Methods: This was a retrospective case-control study. A total of 1,029 inpatients at Wuhan Children's Hospital before the late puberty stage were enrolled in the study, including 815 children with obesity (non-NAFLD group) and 214 children with obesity and NAFLD (NAFLD group) diagnosed by liver ultrasound. Subgroup analyses were performed according to sex and puberty. The anthropometric indices and laboratory test data of these 1,029 children were sorted. After intergroup comparison, a logistic regression model was used to determine the risk factors for pediatric NAFLD. Significant risk factors for NAFLD were further tested using receiver operating characteristic (ROC) curves to evaluate their ability to predict an early diagnosis of NAFLD. Results: The NAFLD group had a mean age of 11.03 ± 1.66, with 11.18 ± 1.66 and 10.27 ± 1.45 years for male and female children, respectively (p < 0.05 and p < 0.01, respectively). Even subdivided by both sex and puberty, raised body mass index (BMI), homeostatic model-insulin resistance, triglycerides, alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γ-GT) were still found in the non-NAFLD and NAFLD groups (p < 0.05 and p < 0.01, respectively). The results of logistic regression analysis showed that BMI (odds ratio [OR], 1.468;95% confidence interval [CI], 1.356-1.590; p<0.001) and ALT (OR, 1.073;95%CI, 1.060-1.087; P<0.001) were two most independent risk factors for NAFLD. The maximal OR for BMI was 1.721 (95% CI, 1.336-2.217). In the female group, the maximal OR of ALT was found to be 1.104 (95% CI, 1.061-1.148). Age and thyroid-stimulating hormone (TSH) and γ-GT levels were also risk factors, but they appeared only in some groups. The results of the ROC analysis showed that ALT was a better predictor of pediatric NAFLD than BMI. The maximum area under the ROC curve in six of the nine groups belongs to ALT. Conclusions: BMI, ALT, and age are risk factors for NAFLD in children with obesity before late puberty. BMI had the greatest exposure risk for NAFLD, and ALT had the highest predictive value for the diagnosis of NAFLD. At the stratified level, for exposure risk, age was specific to the male sex, TSH was specific to the early puberty stage, and γ-GT was specific to the female sex plus the prepuberty stage. On a stratified level, for the female sex, even with age stratification, BMI rather than ALT has a better ability for the diagnosis of NAFLD.

Programmable electrochemical biosensing platform based on catalytic hairpin assembly and entropy-driven catalytic cascade amplification circuit.

Herein, powerful DNA strand displacement reaction and sensitive electrochemical analysis method were ingeniously integrated to develop a programmable biosensing platform. Using DNA as the detection model, a cascade amplification system based on catalytic hairpin assembly and entropy-driven catalytic was constructed, and the reaction rate and signal amplification effect were significantly improved. The product of the cascade amplification circuit could undergo strand displacement reaction with the signal probe on the electrode surface to obtain sensitive electrochemical signal changes and realize highly sensitive detection of the target. In addition, without redesigning the DNA sequences in the cascade amplification circuit, the by-product strand typically wasted in traditional entropy-driven catalytic reactions can be fully utilized to construct a single-signal output biosensing system and even a dual-signal output ratiometric biosensing platform, improving the detection repeatability and reliability of the system, and expanding the application of DNA strand displacement reaction in electrochemical biosensing. Furthermore, benefiting from the design flexibility of the DNA molecules, the constructed biosensing platform realized the sensitive detection of aptamer substrate (kanamycin as an example) and certain metal ion (mercury as an example) by simply recoding the corresponding recognition sequence, demonstrating the good versatility of the biosensing platform.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

The efficacy and safety in radioactive iodine refractory thyroid cancer patients treated with sorafenib.

Background: Sorafenib included in Chinese medical insurance is the earliest targeted drug for radioactive iodine refractory differentiated thyroid cancer (RR-DTC). This study is to further demonstrate the clinical efficacy and safety of sorafenib used in Zhujiang Hospital of Southern Medical University. Methods: RR-DTC patients treated at our Department of Nuclear Medicine in Zhujiang Hospital of Southern Medical University (October 2017-May 2020) were retrospectively analyzed. Treatment effects, progression-free survival (PFS), and adverse effects (AEs) during medication were evaluated. Results: Of the 31 patients included, 26 patients were evaluated for efficacy with a median follow-up time of 17.5 months (4.0-51.0 months). The disease control rate (DCR) was 57.7% (n = 15) and the objective response rate (ORR) was 26.9% (n = 7). Most patients with disease control had thyroglobulin decreases of more than 60% (p = 0.004), ORRs were favorable in patients with lung metastasis and lung-only metastasis (p = 0.010 and 0.001, respectively). The PFS of the 26 patients analyzed was 16.5 months (95%CI: 14.41 -23.90 months). In the subgroup analysis, female, patients with lung-only metastasis, hand-foot skin syndrome (HFS), and thyroglobulin response ≥ 60% observed longer PFS (p = 0.038, 0.045, 0.035, and 0.000, respectively), while patients with bone metastasis had lower PFS (p = 0.035). The most common toxicity profile was HFS (93.5%), followed by diarrhea (83.9%), alopecia (74.2%). All the side effects were mainly grade 1-2. Grade 3-4 adverse reactions were more common in diarrhea and HFS. Conclusions: Sorafenib has promising efficacy in RR-DTC, especially in patients with lung metastasis and lung-only metastasis. The AEs of sorafenib were generally mild, and the main AE was HFS.

Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China.

Objective: This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC). Methods: This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups. Results: In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P < 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P < 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221). Conclusion: Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.

Construction of rose flower-like NiCo-LDH electrode derived from bimetallic MOF for highly sensitive electrochemical sensing of hydrazine in food samples.

It is necessary to efficient detection hydrazine in food. Exploring highly sensitive, low-cost and fast response electrochemical hydrazine sensing methods has been a challenge in this field. In this paper, a conformal transformation method is used to prepare rose flower-like NiCo-LDH derivating from the bimetallic NiCo-MOFs, and the N2H4 sensing platform with a large electrocatalytic area, high conductivity and good stability was constructed. Based on the synergy between Ni and Co and the remarkable catalytic activity of the rough 3D flower-like structure, the N2H4 sensor has a linear response in the concentration range of 0.001-1 mmol/L and 1-7 mmol/L, with a sensitivity of 5342 µA L mmol-1 cm-2 and 2965 µA L mmol-1 cm-2 (S/N = 3), respectively, and low limit of detection of 0.043 µmol/L. This study opens a new door for the successful application of electrochemical sensors to detect N2H4 in real food samples.

Ag-containing metal organic framework reacted with AsH3: Mechanism and application for inorganic arsenic detection by hydride generation-smartphone RGB readout colorimetric system.

The reaction mechanism of Ag-containing metal organic framework (Ag-BTC) and hydrogen arsenide (AsH3) was discussed in detail in this work. Silver ions in Ag-BTC were reacted with AsH3, and silver nanoparticles were generated on the surface of Ag-BTC, causing its color changed. This property was further applied to a hydride generation-colorimetric analytical system. As(III) was converted to AsH3via hydride generation and then reacted with the Ag-BTC (immobilized on test paper), leading to the test paper changed from white to black. Visual colorimetric and smartphone RGB readout mode were used for this analytical system. The results could be readout by naked-eye in visual colorimetric mode and a smartphone in RGB readout mode. Under the optimized conditions, As(III) concentration as low as 10 µg/L and 50 µg/L could be readout by smartphone and naked-eye, respectively. This method was further successful applied to As(III) determination in real samples (drinking water samples and scented tea samples), with recoveries of 91-113%.

Corrigendum: Incorporation size of lymph node metastasis focus and pre-ablation stimulated Tg could more effectively predict clinical outcomes in differentiated thyroid cancer patients without distant metastases.

[This corrects the article DOI: 10.3389/fendo.2023.1094339.].

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.