Chromosome stability of synthetic Triticum turgidum-Aegilops umbellulata hybrids.

BACKGROUND: Unreduced gamete formation during meiosis plays a critical role in natural polyploidization. However, the unreduced gamete formation mechanisms in Triticum turgidum-Aegilops umbellulata triploid F1 hybrid crosses and the chromsome numbers and compostions in T. turgidum-Ae. umbellulata F2 still not known. RESULTS: In this study, 11 T.turgidum-Ae. umbellulata triploid F1 hybrid crosses were produced by distant hybridization. All of the triploid F1 hybrids had 21 chromosomes and two basic pathways of meiotic restitution, namely first-division restitution (FDR) and single-division meiosis (SDM). Only FDR was found in six of the 11 crosses, while both FDR and SDM occurred in the remaining five crosses. The chromosome numbers in the 127 selfed F2 seeds from the triploid F1 hybrid plants of 10 crosses (no F2 seeds for STU 16) varied from 35 to 43, and the proportions of euploid and aneuploid F2 plants were 49.61% and 50.39%, respectively. In the aneuploid F2 plants, the frequency of chromosome loss/gain varied among genomes. The chromosome loss of the U genome was the highest (26.77%) among the three genomes, followed by that of the B (22.83%) and A (11.81%) genomes, and the chromosome gain for the A, B, and U genomes was 3.94%, 3.94%, and 1.57%, respectively. Of the 21 chromosomes, 7U (16.54%), 5 A (3.94%), and 1B (9.45%) had the highest loss frequency among the U, A, and B genomes. In addition to chromosome loss, seven chromosomes, namely 1 A, 3 A, 5 A, 6 A, 1B, 1U, and 6U, were gained in the aneuploids. CONCLUSION: In the aneuploid F2 plants, the frequency of chromosome loss/gain varied among genomes, chromsomes, and crosses. In addition to variations in chromosome numbers, three types of chromosome translocations including 3UL·2AS, 6UL·1AL, and 4US·6AL were identified in the F2 plants. Furthermore, polymorphic fluorescence in situ hybridization karyotypes for all the U chromosomes were also identified in the F2 plants when compared with the Ae. umbellulata parents. These results provide useful information for our understanding the naturally occurred T. turgidum-Ae. umbellulata amphidiploids.

Ge-Doped Hematite with FeCoNi-Bi as Cocatalyst for High-Performing Photoelectrochemical Water Splitting.

Hematite is a promising photoanode material for photoelectrochemical water-splitting technology. However, the low current density associated with the low conductivity, low charge carrier mobility, and poor oxygen evolution catalytic activity is a challenging issue for the material. In this study, the challenge is addressed by introducing Germanium (Ge) doping, coupled with the use of FeCoNi-Bi as a co-catalyst. Ge doping not only increases the conductivity and charge carrier concentration of the hematite photoanode, but also induces nanopores, thereby expanding its electrochemical reactive surface area to facilitate the oxygen evolution reaction. In the meantime, the FeCoNi-Bi cocatalyst electrodeposited onto the surface of Ge-doped hematite, improves the oxygen evolution reaction performance. As a result, the obtained photoanode achieves a photocurrent density of 2.31 mA cm-2 at 1.23 VRHE, which is three times higher than that of hematite (0.72 mA cm-2). Moreover, a new analytical method is introduced to scrutinize both the positive and negative effects of Ge doping and FeCoNi-Bi cocatalyst on the photoanode performance by decoupling the photoelectrochemical process steps. Overall, this study not only enhances the performance of hematite photoanodes but also guides their rational design and systematic assessment.

Interfacial Modulation of Spin-Orbit Torques Induced by Two-Dimensional van der Waals Material ZrSe3.

Two-dimensional van der Waals (2D vdW) materials are widely used in spin-orbit torque (SOT) devices. Recent studies have demonstrated the low crystal symmetry and large spin Hall conductivity of 2D vdW ZrSe3, indicating its potential applications in low-power SOT devices. Here, we study the interfacial contribution of SOTs and current-induced magnetization switching in the ZrSe3/Py (Ni80Fe20) and ZrSe3/Cu/Py heterostructures. SOT efficiencies of samples are detected by the spin-torque ferromagnetic resonance (ST-FMR), and out-of-plane damping-like torque (τB) is observed. The ratio between τB and the field-like torque (τA) decreases from 0.175 to 0.138 when inserting 1 nm Cu at the interface and then drops to 0.001 when the thickness of Cu intercalation is 2 nm, indicating that Cu intercalation inhibits the τB component of SOT. Moreover, the SOT efficiency is increased from 3.05 to 5.21, which may be attributed to the Cu intercalation being beneficial to improve the interface between Py and ZrSe3. Theoretical calculation has shown that the Cu spacer can change the conductivity of ZrSe3 from semiconductor to conductor, thereby decreasing the Schottky barrier and increasing the transmission efficiency of the spin current. Furthermore, magneto-optical Kerr effect (MOKE) microscopy is employed to verify the current-driven magnetization switching in these structures. In comparison to the ZrSe3/Py bilayer, the critical current density of ZrSe3/Cu/Py is reduced when inserting 1 nm Cu, demonstrating the higher SOT efficiency and lower power consumption in ZrSe3/Cu/Py structures.

Epicardial Adipose Tissue and Major Adverse Cardiovascular Events in Myocardial Infarction Patients with and without Diabetes.

BACKGROUND: Epicardial adipose tissue (EAT) accumulation plays a key role in the progression myocardial infarction (MI) and diabetes. Diabetic patients have elevated risk of major adverse cardiac events (MACEs) compared to non-diabetic patients. We aimed to investigate the prognostic value of EAT volume in MI patients with and without diabetes. METHODS: This study included 458 MI patients who underwent cardiac computed tomography (CT) imaging and received successful stent implantation. EAT volume was quantified with cardiac CT imaging. Sub-study stratification of patients by diabetes status was further analyzed. Cox proportional hazards regression models were applied to evaluate the association between EAT volume and MACEs. RESULTS: Diabetes was identified in 135 of the 458 patients (29.5%). EAT volume was significantly higher in diabetes than non-diabetes. During a median follow-up of 1154 days, MACEs occurred more frequently in patients with versus without diabetes. EAT volume was independent predictor of MACEs in all MI patients after adjustment for risk factors, and showed good predictive value in the evaluation of MACEs. Moreover, EAT volume was also significantly associated with MACEs after adjustment for risk factors in diabetes and non-diabetes in the subgroup analysis. CONCLUSION: MI patients with diabetes had higher EAT volume and experienced higher rate of MACEs compared to non-diabetes. EAT volume is an independent risk of prognosis of MI, regardless of the diabetes status.

Polarized vortex Smith-Purcell radiation with cascaded metasurfaces.

We introduce the concept of polarized vortex Smith-Purcell radiation by the interaction of an electron beam and cascaded metasurfaces. The spin and orbital angular momenta of Smith-Purcell radiation are determined by the cascaded metasurface that consists of a grating and a phase gradient metasurface. The grating converts the electron beam radiation into the desired polarized light, while the phase gradient metasurface generates the vortex light. Furthermore, the vortex Smith-Purcell radiation with linear and circular polarizations can be achieved by the various cascaded metasurfaces. In particular, the conversion of chirality in the Smith-Purcell radiation carrying circular polarization is accompanied by the alteration of positive and negative topological charges. This work paves the way for generating polarized vortex electron radiation and is beneficial to promote the development of free-electron-driven devices.

A Polyzwitterionic@MOF Hydrogel with Exceptionally High Water Vapor Uptake for Efficient Atmospheric Water Harvesting.

Atmospheric water harvesting (AWH) is considered a promising strategy for sustainable freshwater production in landlocked and arid regions. Hygroscopic salt-based composite sorbents have attracted widespread attention for their water harvesting performance, but suffer from aggregation and leakage issues due to the salting-out effect. In this study, we synthesized a PML hydrogel composite by incorporating zwitterionic hydrogel (PDMAPS) and MIL-101(Cr) as a host for LiCl. The PML hydrogel was characterized using various techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and thermogravimetric analysis (TGA). The swelling properties and water vapor adsorption-desorption properties of the PML hydrogel were also assessed. The results demonstrate that the MIL-101(Cr) was uniformly embedded into PDMAP hydrogel, and the PML hydrogel exhibits a swelling ratio of 2.29 due to the salting-in behavior. The PML hydrogel exhibited exceptional water vapor sorption capacity of 0.614 g/g at 298 K, RH = 40% and 1.827 g/g at 298 K, RH = 90%. It reached 80% of its saturated adsorption capacity within 117 and 149 min at 298 K, RH = 30% and 90%, respectively. Additionally, the PML hydrogel showed excellent reversibility in terms of water vapor adsorption after ten consecutive cycles of adsorption-desorption. The remarkable adsorption capacity, favorable adsorption-desorption rate, and regeneration stability make the PML hydrogel a potential candidate for AWH. This polymer-MOF synergistic strategy for immobilization of LiCl in this work offers new insights into designing advanced materials for AWH.

The effects of Fc fusion protein glucagon-like peptide-1 and glucagon dual receptor agonist with different receptor selectivity in vivo studies.

BACKGROUND: Glucagon-like peptide-1 (GLP-1)/glucagon (GCG) dual receptor agonists with different receptor selectivity are under investigation and have shown significant improvement in both weight loss and glycemic control, but the optimal potency ratio between the two receptors to balance efficacy and safety remains unclear. EXPERIMENTAL APPROACH: We designed and constructed several dual receptor agonists with different receptor potency ratios using Fc fusion protein technology. The long-term effects of the candidates on body weight and metabolic dysfunction-associated steatotic liver disease (MASLD) were evaluated in diet-induced obese (DIO) model mice, high-fat diet (HFD)-ob/ob mice and AMLN diet-induced MASLD mice. Repeat dose toxicity assays were performed to investigate the safety profile of the candidate (HEC-C070) in Sprague Dawley (SD) rats. KEY RESULTS: The high GCG receptor (GCGR) selectivity of HEC-C046 makes it more prominent than other compounds for weight loss and most MASLD parameters but may lead to safety concerns. The weight change of HEC-C052 with the lowest GCG agonism was inferior to that of selective GLP-1 receptor agonist (GLP-1RA) semaglutide in DIO model mice. The GLP-1R selectivity of HEC-C070 with moderate GCG agonism has a significant effect on weight loss and liver function in obese mice, and its lowest observed adverse effect level (LOAEL) was 30 nmol/kg in the repeat dose toxicity study. CONCLUSION: We compared the potential of the Fc fusion protein GLP-1/GCG dual receptor agonists with different receptor selectivity to provide the setting for future GLP-1/GCG dual receptor agonists to treat obesity and MASLD.

Morphological and Molecular Changes during Limb Regeneration of the Exopalaemon carinicauda.

With the increase in breeding density of Exopalaemon carinicauda, appendage breakage may occur, which seriously affects survival and economic benefits. To study the limb regeneration process of E. carinicauda, we induced autotomy of the pereopods. After a period of time, wound swelling disappeared, the pigment gradually accumulated, and a tawny film subsequently formed in the wound. The healing period of the wound occurred 24 h after autotomy, and the blastema formation stage occurred 48 h after autotomy. After 4 days of cutting, the limb buds began to differentiate, grow, and expand rapidly, and this process lasted approximately 15 days. Microscopic observations revealed significant changes in the type and number of associated cells including outer epithelial cells, granulocytes, embryonic cells, columnar epidermal cells, elongated cells, and blastoma cells, during the process from limb fracture to regeneration. A comparative transcriptome analysis identified 1415 genes differentially expressed between the J0h (0 h post autotomy) and J18h (18 h post autotomy), and 3952 and 4366 differentially expressed genes for J0 and J14d (14 days post autotomy) and J18h and J14d, respectively. Some of these genes may be related to muscle growth or molting, as indicated by the presence of troponin C, chitinase, actin, innexin, and cathepsin L. As a functional gene involved in epidermal formation, the mRNA expression level of the innexin inx2 in the pereopod of E. carinicauda changed significantly in the experimental groups (p < 0.05). The results of this study contribute to existing knowledge of regeneration mechanisms in crustaceans.

Detection of Arsenic(V) by Fluorescence Sensing Based on Chlorin e6-Copper Ion.

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 µM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV-visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M-1 and 2.35 × 1012 M-2, respectively, using B-H (Benesi-Hildebrand) plots. Fluorescence lifetimes, B-H plots, FT-IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule.

Megafossils of Betulaceae from the Oligocene of Qaidam Basin and their paleoenvironmental and phytogeographic implications.

Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau, China relies on discovering new plant fossils. The Qaidam Basin has long been regarded as an ideal 'field laboratory' to investigate the paleoclimate and paleobiological evolution of the northern Tibetan Plateau. However, fossil angiosperms from the Qaidam Basin are rare, and our knowledge of its paleovegetation is poor. Here, we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin (Huatugou area). Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus grandis. These findings, together with other reported fossil plants from the same locality, reveal a close floristic linkage between the Qaidam Basin and Europe during the Oligocene. The northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late Paleogene. This floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies, which transported moisture and provided favorable climatic conditions. Indeed, fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest, which differs from the region's modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.

The dePARylase NUDT16 promotes radiation resistance of cancer cells by blocking SETD3 for degradation via reversing its ADP-ribosylation.

Poly(ADP-ribosyl)ation (PARylation) is a critical posttranslational modification that plays a vital role in maintaining genomic stability via a variety of molecular mechanisms, including activation of replication stress and the DNA damage response. The nudix hydrolase NUDT16 was recently identified as a phosphodiesterase that is responsible for removing ADP-ribose units and that plays an important role in DNA repair. However, the roles of NUDT16 in coordinating replication stress and cell cycle progression remain elusive. Here, we report that SETD3, which is a member of the SET-domain containing protein (SETD) family, is a novel substrate for NUDT16, that its protein levels fluctuate during cell cycle progression, and that its stability is strictly regulated by NUDT16-mediated dePARylation. Moreover, our data indicated that the E3 ligase CHFR is responsible for the recognition and degradation of endogenous SETD3 in a PARP1-mediated PARylation-dependent manner. Mechanistically, we revealed that SETD3 associates with BRCA2 and promotes its recruitment to stalled replication fork and DNA damage sites upon replication stress or DNA double-strand breaks, respectively. Importantly, depletion of SETD3 in NUDT16-deficient cells did not further exacerbate DNA breaks or enhance the sensitivity of cancer cells to IR exposure, suggesting that the NUDT16-SETD3 pathway may play critical roles in the induction of tolerance to radiotherapy. Collectively, these data showed that NUDT16 functions as a key upstream regulator of SETD3 protein stability by reversing the ADP-ribosylation of SETD3, and NUDT16 participates in the resolution of replication stress and facilitates HR repair.

Pyrroloquinoline Quinone Improves Ram Sperm Quality through Its Antioxidative Ability during Storage at 4 °C.

Sperm motility is an important factor in the migration of sperm from the uterus to the oviduct. During sperm preservation in vitro, sperm generates excessive ROS that damages its function. This study aims to investigate whether the addition of pyrroloquinoline quinone (PQQ) to the diluted medium could improve chilled ram sperm quality, and then elucidates the mechanism. Ram semen was diluted with Tris-citric acid-glucose (TCG) medium containing different doses of PQQ (0 nM, 10 nM, 100 nM, 1000 nM, 10,000 nM), and stored at 4 °C. Sperm motility patterns, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential, reactive oxygen species (ROS) levels, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and ATP levels were measured after preservation. Furthermore, the expressions of NADH dehydrogenase 1 (MT-ND1) and NADH dehydrogenase 6 (MT-ND6) in sperm were also detected by western blotting. In addition, sperm capacitation and the ability of sperm to bind to the zona pellucina were also evaluated. It was observed that the addition of PQQ significantly (p < 0.05) improved ram sperm motility, membrane integrity, and acrosome integrity during preservation. The percentage of sperm with high mitochondrial membrane potential in the PQQ treatment group was much higher than that in the control. In addition, supplementation of PQQ also decreased the sperm MDA and ROS levels, while increasing ATP levels. Interestingly, the levels of MT-ND1 and MT-ND6 protein in sperm treated with PQQ were also higher than that of the control. Furthermore, the addition of 100 nM PQQ to the medium decreased ROS damage in MT-ND1 and MT-ND6 proteins. The addition of 100 nM PQQ significantly (p < 0.05) increased protein tyrosine phosphorylation in ram sperm after induced capacitation. Furthermore, the value of the sperm-zona pellucida binding capacity in the 100 nM PQQ treatment group was also much higher than that of the control. Overall, during chilled ram- sperm preservation, PQQ protected ram sperm quality by quenching the ROS levels to reduce ROS damage and maintain sperm mitochondrial function, and preserved the sperm's high ability of fertilization.

Lactobacillus reuteri inhibits Staphylococcus aureus-induced mastitis by regulating oxytocin releasing and gut microbiota in mice.

Mastitis is the most frequent disease of cows and has well-recognized detrimental effects on animal wellbeing and dairy farm profitability. With the advent of the postantibiotic era, alternative antibiotic agents, especially probiotics, have received increasing attention in the treatment of mastitis. Based on research showing that Lactobacillus reuteri (L. reuteri) has anti-inflammatory effects, this study explored the protective effects and mechanisms of L. reuteri against mastitis induced by Staphylococcus aureus (S. aureus) in mice. First, mice with S. aureus-induced mastitis were orally administered L. reuteri, and the inflammatory response in the mammary gland was observed. The results showed that L. reuteri significantly inhibited S. aureus-induced mastitis. Moreover, the concentration of oxytocin (OT) and protein expression of oxytocin receptor (OTR) were measured, and inhibition of OTR or vagotomy reversed the protective effect of L. reuteri or its culture supernatant (LCS) on S. aureus-induced mastitis. In addition, in mouse mammary epithelial cells (MMECs), OT inhibited the inflammation induced by S. aureus by inhibiting the protein expression of OTR. It was suggested that L. reuteri protected against S. aureus-induced mastitis by releasing OT. Furthermore, microbiological analysis showed that the composition of the microbiota was altered, and the relative abundance of Lactobacillus was significantly increased in gut and mammary gland after treatment with L. reuteri or LCS. In conclusion, our study found the L. reuteri inhibited the mastitis-induced by S. aureus via promoting the release of OT, and treatment with L. reuteri increased the abundance of Lactobacillus in both gut and mammary gland.

Enhancing propellant performance through intermolecular interactions: cyclodextrin-based MOF loading in nitrocellulose.

Metal-organic frameworks (MOFs) offer promising opportunities for modifying energetic materials due to their micro-porous structure and high performance. In this study, we present a novel green MOF named cyclodextrin-MOF (CD-MOF), which incorporates potassium ions, synthesized using a simple methanol vapor diffusion approach. The CD-MOF incorporates potassium ions and enhances propellant performance through intermolecular force optimization with nitrocellulose (NC). Molecular dynamics simulations reveal stronger interactions between the CD-MOF and NC. The loading of the CD-MOF within NC forms a stable structure with resistance to migration and defense against crystalline precipitation and water absorption. Notably, in static combustion and pyrolysis tests, the CD-MOF exhibits efficient flame and flash inhibition. The thermal degradation and cauterization of the CD-MOF resulted in the formation of a complex microporous material capable of absorbing flammable and harmful gases such as CO, NO, NO2, and N2O. These findings shed light on the superior performance of the CD-MOF compared to conventional inorganic salts, and the comprehensive characterization and molecular simulations provide insights into the unique properties and applications of the CD-MOF, emphasizing its significant contribution to the field of green propellants.

Diverse ranking metamaterial inverse design based on contrastive and transfer learning.

Metamaterials, thoughtfully designed, have demonstrated remarkable success in the manipulation of electromagnetic waves. More recently, deep learning can advance the performance in the field of metamaterial inverse design. However, existing inverse design methods based on deep learning often overlook potential trade-offs of optimal design and outcome diversity. To address this issue, in this work we introduce contrastive learning to implement a simple but effective global ranking inverse design framework. Viewing inverse design as spectrum-guided ranking of the candidate structures, our method creates a resemblance relationship of the optical response and metamaterials, enabling the prediction of diverse structures of metamaterials based on the global ranking. Furthermore, we have combined transfer learning to enrich our framework, not limited in prediction of single metamaterial representation. Our work can offer inverse design evaluation and diverse outcomes. The proposed method may shrink the gap between flexibility and accuracy of on-demand design.

Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) in healthy subjects.

Aims: To verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference. Methods: This was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022. Results: After administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR10%max≈11 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated. Conclusions: The PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile. Clinical trial registration: Clinicaltrials.gov, identifier NCT04975022.

Quantitative 1H NMR with global spectral deconvolution approach for quality assessment of natural and cultured Cordyceps sinensis.

Cordyceps sinensis is a precious medicinal food which has been successfully cultivated indoors. It remains to be investigated for a simultaneous comparison on aqueous components of natural and cultivated samples. Herein, an approach of quantitative nuclear magnetic resonance (qNMR) analysis combined with global spectral deconvolution (GSD) was established for simultaneous quantification of 26 aqueous components in C. sinensis. Processed by GSD, the distorted baselines of 1H NMR spectra were greatly improved, and overlapped signals were also well separated so as to achieve accurate identification and quantitation of components in C. sinensis. Method validation by UHPLC-QTOF-MS and TOF-SIMS analysis revealed that qNMR combined with GSD is a reliable approach for simultaneous quantification of multiple components including characteristic markers of glutamine, GABA and trehalose in authentic and fake C. sinensis. The well-established qNMR approach can be used for quality assessment of natural and cultivated C. sinensis as well as differentiation from fake ones.

Electric field-enabled aptasensing interfacial engineering to simultaneously enhance specific preconcentration and electrochemical detection of mercury and lead ions.

Aptamers with strong affinity to heavy metal ions (HMIs) allow fabrication of electrochemical sensors with high selectivity and sensitivity, while controllable regulation of aptamer-HMI recognition at the sensing interface, which is vital for better analytical performance, remains challenging. Here, an electric field-based strategy for engineering an aptasensing interface was proposed to realize the specific preconcentration and accurate detection of mercury (Hg2+) and lead (Pb2+) ions with a ratiometric electrochemical sensor. The working principle is to apply an electric field to drive HMIs to approach the aptamer and retain the orientation of the DNA structure. Anthraquinone-2-carboxylic acid (AQ)-labeled complementary DNA was designed to simultaneously bind a ferrocene (Fc)-labeled aptamer for Hg2+ and a methylene blue (MB)-labeled aptamer for Pb2+, and the sensing interface was fabricated with this presynthesized DNA structure. For preconcentration, an electric field of 3.0 V pushed HMIs to approach the aptamer and retained the orientation of DNA to favor the following recognition; for detection, the oriented DNA in 2.5 V electric field offered a stable current of AQ as a reference. In this way, currents of AQ, Fc and MB were used to produce ratiometric signals of IAQ/IFc and IAQ/IMB for Hg2+ and Pb2+, respectively. Such a strategy allowed the simultaneous detection of Hg2+ and Pb2+ within 30 min with detection limits of 0.69 pM and 0.093 pM, respectively. The aptasensor was applied for soil, water, and crayfish analysis in paddy fields. The electric field-enabled strategy offers a new way to fabricate high-performance electrochemical aptasensor for HMIs detection.

Development of a novel Fc fusion protein dual glucagon-like peptide-1 and gastric inhibitory polypeptide receptor agonists.

AIM: To develop and investigate an imbalanced dual gastric inhibitory polypeptide receptor (GIPR)/glucagon-like peptide-1 receptor (GLP-1 R) agonist with Fc fusion protein structure. METHODS: We designed and constructed an Fc fusion protein that is a dual agonist (HEC-CG115) with an empirically optimized potency ratio for GLP-1R and GIPR. The long-term effects of HEC-CG115 on body weight and glycaemic control were evaluated in diet-induced obese mice and diabetic db/db mice. Repeat dose toxicity assays were performed to investigate the safety profile of HEC-CG115 in Sprague-Dawley rats. RESULTS: HEC-CG115 displayed high potency for GIPR and relatively low potency for GLP-1R, and we labelled it 'imbalanced'. In animal models, HEC-CG115 (3 nmol/kg) led to more weight loss than semaglutide at a higher dose (10 nmol/kg) in diet-induced obese model mice. HEC-CG115 (one dose every 3 days) reduced fasting blood glucose and glycated haemoglobin levels similar to those after semaglutide (once daily) at the same dose. In a 4-week subcutaneous toxicity study conducted to assess the biosafety of HEC-CG115, the no observed adverse effect level was determined to be 3 mg/kg. CONCLUSION: HEC-CG115 is a novel Fc fusion protein with imbalanced dual agonism that shows superior weight loss, glycaemic control and metabolic improvement in animal models, and has an optimal safety profile according to a repeat-dose toxicity study. Therefore, the use of HEC-CG115 appears to be safe and effective for the treatment of obesity and type 2 diabetes.

Three-dimensional molecular architecture of mouse organogenesis.

Mammalian embryos exhibit sophisticated cellular patterning that is intricately orchestrated at both molecular and cellular level. It has recently become apparent that cells within the animal body display significant heterogeneity, both in terms of their cellular properties and spatial distributions. However, current spatial transcriptomic profiling either lacks three-dimensional representation or is limited in its ability to capture the complexity of embryonic tissues and organs. Here, we present a spatial transcriptomic atlas of all major organs at embryonic day 13.5 in the mouse embryo, and provide a three-dimensional rendering of molecular regulation for embryonic patterning with stacked sections. By integrating the spatial atlas with corresponding single-cell transcriptomic data, we offer a detailed molecular annotation of the dynamic nature of organ development, spatial cellular interactions, embryonic axes, and divergence of cell fates that underlie mammalian development, which would pave the way for precise organ engineering and stem cell-based regenerative medicine.