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This paper proposed an event-driven clockless level-crossing ADC (LC-ADC) suitable for biomedical applications. Thanks to the LC loop, the sampling rate of the converter automatically adapts to the input activities. Activity-dependent power consumption and data compression can thus be realized, saving system power, especially during time-sparse signal acquisition. Meanwhile, a SAR-assisted loop is exploited to resolve the loop-delay-induced distortion in conventional LC-ADC. Therefore, the resolution and power efficiency of the LC-ADC are improved effectively while maintaining the event-driven feature. Implemented in a 55nm process, the proposed LC-ADC achieves a scalable power consumption and a peak SNDR of 62.2dB for a 20kHz input. It also achieves a Walden FoM of 29.7fJ/conv.-step and a Schreier FoM of 158.6dB, which is best in class, without using off-chip calibration. Sub µW power is realized when the input frequency is below 1.5kHz. The proposed LC-ADC is also verified by simulated electrocardiogram (ECG), neural spike, and electromyogram (EMG) signals. It provides a ~7X data compression for ECG input, providing an attractive solution for time-sparse signal acquisition in biomedical applications.
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Hybrid ferroelastic crystals have emerged as a hot research topic in recent years owing to their prospective applications in piezoelectric sensors, mechanical switches, and optoelectronic devices. Nevertheless, most of the documented materials exhibit one-step or two-step ferroelastic phase transition(s), and those with multistep ferroelastic transitions are extremely scarce. We present a new hexagonal molecular perovskite based on a fluoro-substituted flexible cyclic ammonium cation, (1-fluoromethyl-1-methylpyrrolidine)[CdCl3] (1), undergoing unusual three-step ferroelastic phase transitions from hexagonal paraelastic phase to orthorhombic, monoclinic, and triclinic ferroelastic phases at 388, 376, and 311 K, respectively, with Aizu notation of 6/mmmFmmm, mmmF2/m, and 2/mF-1, featuring spontaneous strain of 0.002, 0.023, and 0.110, respectively. Furthermore, variable-temperature single-crystal diffraction reveals that the phase-transition mechanism in 1 principally originates from intriguing dynamic change of organic cations and synchronous displacement of inorganic chains. This scarce instance of multistep hybrid ferroelastic provides important clues for finding advanced ferroelastic materials.
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Argonaute (Ago) proteins are ubiquitous across all kingdoms of life. Eukaryotic Agos (eAgos) use small RNAs to recognize transcripts for RNA silencing in eukaryotes. In contrast, the functions of prokaryotic counterparts (pAgo) are less well known. Recently, short pAgos in conjunction with the associated TIR or Sir2 (SPARTA or SPARSA) were found to serve as antiviral systems to combat phage infections. Herein, we present the cryo-EM structures of nicotinamide adenine dinucleotide (NAD+)-bound SPARSA with and without nucleic acids at resolutions of 3.1 Å and 3.6 Å, respectively. Our results reveal that the APAZ (Analogue of PAZ) domain and the short pAgo form a featured architecture similar to the long pAgo to accommodate nucleic acids. We further identified the key residues for NAD+ binding and elucidated the structural basis for guide RNA and target DNA recognition. Using structural comparisons, molecular dynamics simulations, and biochemical experiments, we proposed a putative mechanism for NAD+ hydrolysis in which an H186 loop mediates nucleophilic attack by catalytic water molecules. Overall, our study provides mechanistic insight into the antiphage role of the SPARSA system.
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Bacteriófagos , Ácidos Nucleicos , NAD , ARN Guía de Sistemas CRISPR-Cas , Proteínas Argonautas/genética , Bacteriófagos/genéticaRESUMEN
The multiplex and simultaneous determination of blood glucose, creatinine and uric acid is essential for the early screening of chronic diseases or regular disease monitoring. Here, we report for the first time a biosensing array for the multiplex and simultaneous determination of plasma glucose, creatinine and uric acid. The sensing electrodes are fabricated on a PET surface, including three working electrodes, one reference electrode, and one counter electrode. Each specific enzyme is immobilized on its corresponding working electrode. The biosensing array can exhibit high sensitivity and selectivity for the simultaneous determination of blood glucose, creatinine and uric acid in real blood samples, and the measurement results are accurate and consistent with those from the clinical biochemistry analyzer in the hospital. It is expected that this work could provide new avenues for the fundamental study of biosensing device construction, as well as practical applications of the detection of biomarkers in chronic diseases.
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Técnicas Biosensibles , Glucosa , Humanos , Ácido Úrico , Creatinina , Glucemia , Técnicas Biosensibles/métodos , Electrodos , Enfermedad CrónicaRESUMEN
Hybrid ferroelastics have attracted increasing attention for their potential application as mechanical switches. The sporadically documented anomalous ferroelastic phase transitions, i.e., ferroelasticity that appears at a high-temperature phase rather than a low-temperature phase, are of particular interest but are not well understood at the molecular level. By judiciously choosing a polar and flexible organic cation (Me2NH(CH2)2Br+) with cis-/anti- conformations as an A-site component, we obtained two new polar hybrid ferroelastics, A2[MBr6] (M = Te for 1 and Sn for 2). These materials undergo distinct thermal-induced ferroelastic phase transitions. The larger [TeBr6]2- anions anchor the adjacent organic cations well and essentially endow 1 with a conventional ferroelastic transition (P21 â Pm21n) arising from a common order-disorder transition of organic cations without conformational changes. Moreover, the smaller [SnBr6]2- anions can interact with the adjacent organic cations in energetically similar sets of intermolecular interactions, enabling 2 to undergo an anomalous ferroelastic phase transition (P212121 â P21) arising from an unusual cis-/anti-conformational reversal of organic cations. These two instances demonstrate the importance of the delicate balance of intermolecular interactions for inducing anomalous ferroelastic phase transitions. The findings here provide important insights for seeking new multifunctional ferroelastic materials.
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Diabetes is a chronic disease affecting 10% of the population globally, and can lead to serious damage in the heart, kidneys, eyes, blood vessels or nerves. Commercial artificial closed-loop feedback systems can significantly improve diabetes management and save lives. However, they are large and expensive for users. Here, we demonstrate for the first time a wearable, minimally-invasive, fully electrochemically-controlled feedback minisystem for diabetes management. Both the working principles of the sensor and pump in the feedback system are based on electrochemical reactions. The smart minisystem was constructed based on integrating the thermoplastic polyurethane hollow microneedles with an electrochemical biosensing device on its outer layer and an electrochemical micropump facing the inner layer of the microneedles. The sensing device was constructed based on sputtering thin metal films through a shadow mask and electroplating Prussian blue on the surface of the microneedles, followed by the immobilization of glucose oxidase on the working electrode. The electrochemical micropump was constructed by sputtering the interdigital electrodes, followed by sealing with a thin elastic film, which was further integrated with the inner channels of the microneedles. Both the sensor and the pump were electrically powered. Via being controlled by a printed circuit board, the biosensing device monitored the levels of interstitial glucose continuously to drive the electrochemical pump to deliver insulin intelligently, in order to control blood glucose within the normal range. The closed-loop feedback system was studied for its capability in maintaining the blood glucose levels of diabetic rats under various physiological conditions. The utility of the intelligent feedback system was successfully demonstrated on diabetic rats for controlling the blood glucose levels within the normal range. The minisystem is wearable, small, cost-effective, precise, stable and painless. It is anticipated that this approach opens a new paradigm for the development of closed-loop diabetes minisystems and may lead to a compelling future for diabetes management.
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Técnicas Biosensibles , Diabetes Mellitus Experimental , Dispositivos Electrónicos Vestibles , Ratas , Animales , Glucemia , Retroalimentación , Diabetes Mellitus Experimental/terapia , GlucosaRESUMEN
Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment, and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.
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Mpox , Humanos , Niño , Mpox/diagnóstico , Mpox/epidemiología , Mpox/prevención & control , Salud Pública , Diagnóstico Diferencial , Vacunación , China/epidemiologíaRESUMEN
Diabetes is a chronic metabolic disease with a high blood glucose level, leading to both seriously acute and chronic complications. The closed-loop system is an ideal system for diabetes management. However, the large size and high cost of the commercial systems restrict their widespread uses. Here, we present for the first time a microtube-based wearable closed-loop minisystem for diabetes management. The closed-loop minisystem includes a biosensing device, an electroosmotic micropump, and a printed circuit board (PCB) with an algorithm. The microtube-based sensing device coated on the outer surface of the microtube is inserted into subcutaneous tissue for detecting interstitial glucose; the current signal for sensing glucose is processed by the PCB to power the electroosmotic micropump intelligently for the delivery of insulin into the subcutaneous tissue via the microtube channel. The closed-loop minisystem worn on a diabetic SD rat can successfully maintain its blood glucose level within a safe level. It is expected that this new closed-loop paradigm could open up new prospects for clinical diabetes management.
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Legionella pneumophila, a bacterial pathogen that causes a severe pneumonia known as Legionnaires' disease, extensively exploits the ubiquitin (Ub) pathway in the infected host cells through certain virulence effectors excreted by the Dot/Icm system. To date, several Dot/Icm effectors have been found to act as Ub ligases, and four effectors, including LotA, LotB, LotC, and Ceg7, have been identified as deubiquitinases (DUBs) from the ovarian tumor (OTU) domain family. LotA is unique among other OTU DUBs because it possesses two distinct DUB domains and exclusively exhibits catalytic activity against K6-linked diUb and polyUb chains. However, the structure of LotA and the molecular mechanism for the dual DUB activity remains elusive. In this study, we solved the structure of LotA in complex with proximally bound Ub and distal covalently bound Ub. Both Ub molecules are bound to the DUB1 domain and mimic a K6-linked diUb. Structural analysis reveals that the DUB1 domain utilizes a distinct mechanism for recognition of the K6-linked diUb within a large S1' binding site that is uncommon to OTU DUBs. Structural fold of the LotA DUB2 domain closely resembles LotB and LotC, similarly containing an extra α-helix lobe that has been demonstrated to play an important role in Ub binding. Collectively, our study uncovers the structural basis for the dual catalytic activity of the unique OTU family DUB LotA.
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Proteínas Bacterianas , Enzimas Desubicuitinizantes , Legionella pneumophila , Proteínas Bacterianas/química , Enzimas Desubicuitinizantes/química , Legionella pneumophila/enzimología , Ubiquitina/metabolismo , Catálisis , Dominios Proteicos , Conformación Proteica en Hélice alfaRESUMEN
Chirality, an intrinsic property of nature, has received increased attention in chemistry, biology, and materials science because it can induce optical rotation, ferroelectricity, nonlinear optical response, and other unique properties. Here, by introducing chirality into hybrid rare-earth double perovskites (HREDPs), we successfully designed and synthesized a pair of enantiomeric three-dimensional (3D) HREDPs, [(R)-N-methyl-3-hydroxylquinuclidinium]2RbEu(NO3)6 (R1) and [(S)-N-methyl-3-hydroxylquinuclidinium]2RbEu(NO3)6 (S1), which possess ferroelasticity, multiaxial ferroelectricity, high quantum yields (84.71% and 83.55%, respectively), and long fluorescence lifetimes (5.404 and 5.256 ms, respectively). Notably, the introduction of chirality induces the coupling of multiaxial ferroelectricity and ferroelasticity, which brings about a satisfactory large piezoelectric response (103 and 101 pC N-1 for R1 and S1, respectively). Moreover, in combination with the chirality and outstanding photoluminescence properties, circularly polarized luminescence (CPL) was first realized in HREDPs. This work sheds light on the design strategy of molecule-based materials with a large piezoelectric response and excellent CPL activity, and will inspire researchers to further explore the role of chirality in the construction of novel multifunctional materials.
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Toxin-antitoxin (TA) systems are ubiquitous genetic modules in bacteria and archaea. Here, we perform structural and biochemical characterization of the Legionella pneumophila effector Lpg2370, demonstrating that it is a Ser/Thr kinase. Together with two upstream genes, lpg2370 constitutes the tripartite HipBST TA. Notably, the toxin Lpg2370 (HipTLp) and the antitoxin Lpg2369 (HipSLp) correspond to the C-terminus and N-terminus of HipA from HipBA TA, respectively. By determining crystal structures of autophosphorylated HipTLp, its complex with AMP-PNP, and the structure of HipTLp-HipSLp complex, we identify residues in HipTLp critical for ATP binding and those contributing to its interactions with HipSLp. Structural analysis reveals that HipSLp binding induces a loop-to-helix shift in the P-loop of HipTLp, leading to the blockage of ATP binding and inhibition of the kinase activity. These findings establish the L. pneumophila effector Lpg2370 as the HipBST TA toxin and elucidate the molecular basis for HipT neutralization in HipBST TA.
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Antitoxinas , Toxinas Bacterianas , Legionella pneumophila , Sistemas Toxina-Antitoxina , Adenosina Trifosfato , Antitoxinas/genética , Antitoxinas/metabolismo , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Legionella pneumophila/genética , Legionella pneumophila/metabolismo , Sistemas Toxina-Antitoxina/genéticaRESUMEN
The hybrid rare-earth double perovskite (HREDP) system provides great convenience for the construction of multifunctional materials. However, suffering from the high symmetry of their intrinsic structure, HREDPs face the challenges in the realization and optimization of ferroelectric and piezoelectric properties. For the first time, after a systematic investigation of the chirality transformation principle, it is found that the introduction of chirality is an efficient strategy for the targeted construction of multifunctionality, which simultaneously increases the possibility of obtaining multiaxial ferroelectricity and ferroelasticity, and effectively realizes a large piezoelectric response. Moreover, chirality induced ferroelasticity will also achieve excellent magnetic or optical response driven by pressure-sensitive. To verify the feasibility of the above ideas, by using rare-earth ions (Ce3+ ) and suitable chiral organic cations, a new HREDP, (R-N-methyl-3-hydroxylquinuclidinium)2 RbCe(NO3 )6 (R1) is successfully designed, in which ferroelasticity, multiaxial ferroelectricity, satisfactory piezoelectric response, and the pressure-driven single-ion magnetics switch are simultaneously achieved for the first time. This work shows that the induction of chirality and the HREDP system provide an effective strategy and ideal platform for the expansion and optimization of the functions in perovskite ferroelectrics.
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Cellular senescence is associated with tumorigenesis, and the subtype and prognostic signatures of senescence-related genes (SRGs) in the tumor microenvironment (TME) and gut microbiota have not been fully determined. Analysis of 91 SRGs obtained from the GSEA and MSigDB, and mRNA sequencing of genes in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases enabled the identification of two distinct molecular types of colorectal cancer (CRC). Patient samples were clustered into two subtypes, with Kaplan-Meier survival analyses showing significant differences in patient survival between the two subtypes. Cluster C2 was associated with patient clinicopathological features, high immune score, high abundance of immune infiltrating cells and somewhat high abundance of bacteria. A risk model based on eight SRGs showed that a low risk score was characterized by inhibition of immune activity and was indicative of better prognosis in patients with CRC. In combination with clinical characteristics, risk score was found to be an independent prognostic predictor of survival in patients with CRC. In conclusion, the present study showed that senescence-related subtypes and a signature consisting of eight SRGs were associated with CRC patient prognosis, as well as with immune cell infiltration and gut microbiota. These findings may enable better prediction of CRC patient prognosis and facilitate individualized treatments.
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Developing a miniaturized, low-cost, and smart closed-loop system for diabetes could significantly improve life quality and benefit millions of people. Conventional closed-loop devices are large in size and exorbitant. Here, we unprecedentedly demonstrate an electrically controlled flexible closed-loop patch for continuous diabetes management by integrating hollow biodegradable microneedles with a biosensing device and an electroosmotic pump. The hollow microneedles were fabricated using a combination of soft lithography and micromachining. The outer layer of the microneedles was functionalized to serve as a biosensing device for the in situ sensitive and accurate monitoring of interstitial glucose. The inner layer of the microneedles was integrated with a flexible electroosmotic pump to deliver insulin, and the delivery rate was electrically controlled by the glucose level from the biosensing device. The closed-loop system successfully stabilized the blood glucose levels of diabetic rats in a normal and safe range. The system is painless, miniaturized, cost-effective, and flexible. It is anticipated that it could open up exciting new avenues for fundamental studies of new closed-loop devices as well as practical applications for diabetes management.
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Técnicas Biosensibles , Diabetes Mellitus Experimental , Animales , Electroósmosis , Glucosa , Humanos , Insulina , RatasRESUMEN
Intra-articular injection of mesenchymal stem cells is a potential therapeutic strategy for cartilage protection and symptom relief for osteoarthritis (OA). However, controlling chondrogenesis of the implanted cells in the articular cavity remains a challenge. In this study, hydrogels containing different concentrations of icariin were prepared by in situ crosslinking of hyaluronic acid and Poloxamer 407. This injectable and thermoresponsive hydrogel, as a 3D cell culture system, showed good biocompatibility with chondrocytes and bone marrow mesenchymal stem cells (BMSCs), as well as promoted proliferation and chondrogenesis of BMSCs through the Wnt/ß-catenin signaling pathway. Intra-articular injection of this kind of BMSC-loaded composite hydrogel can significantly prevent cartilage destruction by inducing chondrogenic differentiation of BMSCs, and relieve pain through regulating the expression of inflammatory cytokines (e.g., IL-10 and MMP-13) in the OA model. Incorporating BMSCs into this novel icariin-loaded hydrogel indicates a more superior efficacy than the single BMSC injection, which suggests a great potential for its application in OA.
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Invited for the cover of this issue are Le-Pingâ Miao, Chaoâ Shi, Yiâ Zhang and co-workers at Jiangxi University of Science and Technology. The image depicts the structure diagrams of the 3D hybrid rare-earth double perovskite compounds. The phase transition temperatures of the two compounds were indicated by the "ice and fire", respectively. It implies the increase of the phase transition temperature of the compounds. Read the full text of the article at 10.1002/chem.202103913.
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Increasing attention has been devoted to studying perovskite-type multifunctional stimuli-responsive materials with multiple channel physical characteristics. However, it remains challenging to simultaneously achieve multifunction and regulate structural phase transition temperature in hybrid perovskites. Here, we report two three-dimensional organic-inorganic hybrid rare-earth double perovskite compounds, (HQ)2 RbEu(NO3 )6 (1, HQ=quinuclidium) and (4FHQ)2 RbEu(NO3 )6 (2, 4FHQ=4-fluoro-quinuclidium), which exhibit ferroelasticity, dielectric switch, and excellent photoluminescence response. The phase transition temperature of 2 increases 169â K compared with 1 through H/F substitution. This result is attributed to the H/F substitution inducing the generation of the Rb-F coordination bond between cations and anions. Meanwhile, the photoluminescence emission intensity of 2 shows no quench with the increase of temperature, in particular, the emission spectrum achieves fine regulation at high temperatures. This work provides a new solution for the realization of multi-functions and regulations of the properties based on hybrid perovskite materials with high critical temperatures.
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GC-SAW was used to carry out online sampling analysis of the main business sources, residential sources, and roads in Rizhao City from August 22 to 29 in 2020. The spatial distribution characteristics of various volatile organic compounds (VOCs) in the atmosphere were obtained, and the chemical reactivity of the main components was studied. The results showed that the VOCs with carbon atoms greater than 5 (VOCC>5) were mainly toluene propylbenzene and n-octane, and the spatial distribution was significant; the average ρ(TVOCC>5) in the port area, downtown area, and industrial area were 80.5, 115.3, and 118.1 µg·m-3, respectively. Combined with road traffic impact and industrial production emissions, the maximum ρ(TVOCC>5) on the main roads in Rizhao City appeared near the Yingbin Road; the concentration value was 164.37 µg·m-3; the ρ(BTEX) in adhesive processing, painting, and glass factories reached 432.34, 1010.84, and 1989.85 µg·m-3, respectively. The chemical reactivity analysis of the main components of VOCC>5 showed that BTEX and n-octane were the important active components of ozone formation in Rizhao City.