A novel red-to-near-infrared AIE fluorescent probe for detection of Hg2+ with large Stokes shift in plant and living cells.

Due to the highly toxic nature of mercury ions to living organisms, accurately detecting Hg2+ in water samples and biological systems is of great significance. In this study, we designed and synthesized a novel red-to-near-infrared Aggregation-Induced Emission (AIE) fluorescent probe (named as DS) based Fluorene derivatives on specifically for Hg2+ detection. Probe DS can visually identify Hg2+ through an red-to-near-infrared fluorescence enhancement change, characterized by a large Stokes shift (130 nm) and AIE feature. This probe offers a fast response, high selectivity and sensitivity. The Hg2+-induced deprotection reaction of the thioketal mechanism was thoroughly investigated using nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) calculation. Additionly, dynamic light scattering (DLS) results indicated that the aggregation states changes of the molecular play a crucial role in the AIE fluorescence response of probe DS toward Hg2+. The red-to-near-infrared response with AIE feature not only avoids the interference of auto-fluorescence signals in complex environments, but also reduces the fluorescence quenching caused by probe molecular aggregation. This makes probe DS highly suitable for high-quality imaging detection of Hg2+ in aqueous environments. Furthermore, probe DS demonstrates the capability for visual fluorescence detection of Hg2+ concentrations in water sample, plant roots and living cells.

Efficient Dienyl End-Capping of Ruthenium Catalyzed Ring Opening Metathesis Polymerization with Allyl Compounds through Base-Promoted Metallacyclobutane Decomposition.

Herein we demonstrate an effective and facile end-capping technique for ring-opening metathesis polymerization (ROMP) using readily available allyl compounds as a new type of terminating agents. This new type of end-capping reactions, which are based on the basepromoted decomposition of ruthenocyclobutane intermediates, introduce diene moiety onto the chain end of ROMP polymers while simultaneously deactivating the ruthenium complex. These termination reactions are highly efficient, typically completing within 1 minute at 0 oC with >95% end-capping fidelity.

Modulating the Structure and Optoelectronic Properties of Solution-Processed Bismuth-Based Nanocrystals.

Bismuth-based chalcogenides have emerged as promising candidates for next-generation, solution-processable semiconductors, mainly benefiting from their facile fabrication, low cost, excellent stability, and tunable optoelectronic properties. Particularly, the recently developed AgBiS2 solar cells have shown striking power conversion efficiencies. High performance bismuth-based photodetectors have also been extensively studied in the past few years. However, the fundamental properties of these Bi-based semiconductors have not been sufficiently investigated, which is crucial for further improving the device performance. Here, we introduce multiple time-resolved and steady-state techniques to fully characterize the charge carrier dynamics and charge transport of solution-processed Bi-based nanocrystals. It was found that the Ag-Bi ratio plays a critical role in charge transport. For Ag-deficient samples, silver bismuth sulfide thin films behave as localized state induced hopping charge transport, and the Ag-excess samples present band-like charge transport. This finding is crucial for developing more efficient Bi-based semiconductors and optoelectronic devices.

Characteristics of duplicated gene expression and DNA methylation regulation in different tissues of allopolyploid Brassica napus.

Plant polyploidization increases the complexity of epigenomes and transcriptional regulation, resulting in genome evolution and enhanced adaptability. However, few studies have been conducted on the relationship between gene expression and epigenetic modification in different plant tissues after allopolyploidization. In this study, we studied gene expression and DNA methylation modification patterns in four tissues (stems, leaves, flowers and siliques) of Brassica napusand its diploid progenitors. On this basis, the alternative splicing patterns and cis-trans regulation patterns of four tissues in B. napus and its diploid progenitors were also analyzed. It can be seen that the number of alternative splicing occurs in the B. napus is higher than that in the diploid progenitors, and the IR type increases the most during allopolyploidy. In addition, we studied the fate changes of duplicated genes after allopolyploidization in B. napus. We found that the fate of most duplicated genes is conserved, but the number of neofunctionalization and specialization is also large. The genetic fate of B. napus was classified according to five replication types (WGD, PD, DSD, TD, TRD). This study also analyzed generational transmission analysis of expression and DNA methylation patterns. Our study provides a reference for the fate differentiation of duplicated genes during allopolyploidization.

Mechanical models and measurement methods of solid stress in tumors.

In addition to genetic mutations, biomechanical factors also affect the structures and functions of the tumors during tumor growth, including solid stress, interstitial fluid pressure, stiffness, and microarchitecture. Solid stress affects tumors by compressing cancer and stromal cells and deforming blood and lymphatic vessels which reduce supply of oxygen, nutrients and drug delivery, making resistant to treatment. Researchers simulate the stress by creating mechanical models both in vitro and in vivo. Cell models in vitro are divided into two dimensions (2D) and three dimensions (3D). 2D models are simple to operate but exert pressure on apical surface of the cells. 3D models, the multicellular tumor spheres, are more consistent with the actual pathological state in human body. However, the models are more difficult to establish compared with the 2D models. Besides, the procedure of the animal models in vivo is even more complex and tougher to operate. Then, researchers challenged to quantify the solid stress through some measurement methods. We compared the advantages and limitations of these models and methods, which may help to explore new therapeutic targets for normalizing the tumor's physical microenvironment. KEY POINTS: •This is the first review to conclude the mechanical models and measurement methods in tumors. •The merit and demerit of these models and methods are compared. •Insights into further models are discussed.

[New drug discovery and prospect of small nucleic acids derived from traditional Chinese medicine and natural medicine].

Small nucleic acid drugs mainly include small interfering RNA(siRNA), antisense oligonucleotide(ASO), microRNA(miRNA), messenger RNA(mRNA), nucleic acid aptamer(aptamer), and so on. Its translation or regulation can be inhibited by binding to the RNA of the target molecule. Due to its strong specificity, persistence, and curability, small nucleic acid drugs have received considerable attention in recent years. Recent studies have shown that some miRNAs from animal and plant sources can stably exist in the blood, tissue, and organs of animals and human beings and exert pharmacological action by regulating the expression of various target proteins. This paper summarized the discovery of small nucleic acids derived from traditional Chinese medicine(TCM) and natural drugs and their cross-border regulatory mechanisms and discussed the technical challenges and regulatory issues brought by this new drug, which can provide new ideas and methods for explaining the complex mechanism of TCM, developing new drugs of small nucleic acids from TCM and natural medicine, and conducting regulatory scientific research.

An activated near-infrared mitochondrion-targetable fluorescent probe for rapid detection of NADH.

A novel NIR fluorescent probe based on quinoline-conjugated benzo[cd]indol dual-salt for NADH was developed. This probe swiftly detects and responds sensitively to both endogenous and exogenous NADH alterations, enabling imaging of NADH fluctuations in type II diabetic and AD model cells.

ADAM17 variant causes hair loss via ubiquitin ligase TRIM47 mediated degradation.

Hypotrichosis is a genetic disorder which characterized by a diffuse and progressive loss of scalp and/or body hair. Nonetheless, the causative genes for several affected individuals remain elusive, and the underlying mechanisms have yet to be fully elucidated. Here, we discovered a dominant variant in ADAM17 gene caused hypotrichosis with woolly hair. Adam17 (p.D647N) knock-in mice model mimicked the hair abnormality in patients. ADAM17 (p.D647N) mutation led to hair follicle stem cells (HFSCs) exhaustion and caused abnormal hair follicles, ultimately resulting in alopecia. Mechanistic studies revealed that ADAM17 binds directly to E3 ubiquitin ligase TRIM47. ADAM17 (p.D647N) variant enhanced the association between ADAM17 and TRIM47, leading to an increase in ubiquitination and subsequent degradation of ADAM17 protein. Furthermore, reduced ADAM17 protein expression affected Notch signaling pathway, impairing the activation, proliferation, and differentiation of HFSCs during hair follicle regeneration. Overexpression of NICD rescued the reduced proliferation ability caused by Adam17 variant in primary fibroblast cells.

Diagnostic Value of Combined-Diagnostic Methods of Brain Tuberculoma Tissue Specimens: A Case Series.

Background: The diagnosis of brain tuberculoma (BT) is sometimes challenging. Herein, we presented a case series to evaluate the combined-diagnostic methods, including acid-fast bacilli (AFB) stain, polymerase chain reaction (PCR), Gene Xpert, and histopathology, of tuberculoma tissue specimens (TTSs). Patients and Methods: A total of 16 patients (11 human immunodeficiency virus [HIV]-positive, 5 HIV-negative) with BT confirmed by combined-diagnostic methods of TTS were included in this study. Clinical data, including clinical symptoms, laboratory tests, neuroimaging features, histopathology, treatment, and prognosis, were assessed in all patients. Results: There were 10 male and 6 female patients (range, 18-73 years). Acid-fast bacilli stain and PCR of TTSs were positive in 11 and 10 patients, respectively. The sensitivity of Gene Xpert of TTSs was (80.0%; 8/10). Nine (56.3%; 9/16) patients were diagnosed with BT by histopathology. After receiving antituberculosis treatment, 12 (75.0%; 12/16) patients improved clinically to a considerable extent. Conclusions: The combined-diagnostic methods of TTS may improve the diagnostic efficiency of BT.

NIR-II Fluorescence Sensor Based on Steric Hindrance Regulated Molecular Packing for In Vivo Epilepsy Visualization.

Fluorescence sensing is crucial to studying biological processes and diagnosing diseases, especially in the second near-infrared (NIR-II) window with reduced background signals. However, it's still a great challenge to construct "off-on" sensors when the sensing wavelength extends into the NIR-II region to obtain higher imaging contrast, mainly due to the difficult synthesis of spectral overlapped quencher. Here, we present a new fluorescence quenching strategy, which utilizes steric hindrance quencher (SHQ) to tune the molecular packing state of fluorophores and suppress the emission signal. Density functional theory (DFT) calculations further reveal that large SHQs can competitively pack with fluorophores and prevent their self-aggregation. Based on this quenching mechanism, a novel activatable "off-on" sensing method is achieved via bio-analyte responsive invalidation of SHQ, namely the Steric Hindrance Invalidation geNerated Emission (SHINE) strategy. As a proof of concept, the ClO--sensitive SHQ lead to the bright NIR-II signal release in epileptic mouse hippocampus under the skull and high photon scattering brain tissue, providing the real-time visualization of ClO- generation process in living epileptic mice.

Near-infrared Rhodols-based fluorescent probe with large Stokes shift for tracking of H2S in food spoilage and living cells.

Hydrogen sulfide (H2S), as a biomarker signaling gas, is not only susceptible to food spoilage, but also plays a key function in many biological processes. In this work, an activated near infrared (NIR) H2S fluorescent probe was designed and synthesized with quinoline-conjugated Rhodols dye as fluorophore skeleton and a dinitrophenyl group as the responsive moiety. Due to the quenching effect of dinitrophenyl group and the closed-loop structure of Rhodols fluorophore, probe itself has a very weak absorption and fluorescence background signal. After the H2S-induced thiolysis reaction, the probe exhibits a remarkable colormetric change and NIR fluorescent enhancement response at 716 nm with large Stokes shift (116 nm), and possesses high sensing selectivity and sensitivity with a low detection limits of 330 nM. The response mechanism is systematically characterized by 1H NMR, MS and DFT calculations. The colorimetric change allows the probe to be used as a test strips to detect H2S in food spoilage, while NIR fluorescent response helps the probe monitor intracellular H2S.

Acoustic Wave-Induced FeRh Magnetic Phase Transition and Its Application in Antiferromagnetic Pattern Writing and Erasing.

We explore the FeRh magnetic phase transition (MPT) and magnetic phase domain (MPD) with the introduction of surface acoustic waves (SAWs). The effects of the SAW pulses with different pulse widths and powers on resistance-temperature loops are investigated, revealing that the SAW can reduce the thermal hysteresis. Meanwhile, the SAW-induced comb-like antiferromagnetic (AFM) phase domains are observed. By changing the pulse width and SAW frequency, we further realize a writing-erasing process of the different comb-like AFM phase domains in the mixed-phase regime of the cooling transition branch. Resistance measurements also display the repeated SAW writing-erasing and the nonvolatile characteristic clearly. MPT paths are measured to demonstrate that short SAW pulses induce isothermal MPT and write magnetic phase patterns via the dynamic strain, whereas long SAW pulses erase patterns via the acoustothermal effect. The Preisach model is introduced to model the FeRh MPT under the SAW pulses, and the calculated results correspond well with our experiments, which reveals the SAW-induced energy modulation promotes FeRh MPT. COMSOL simulations of the SAW strain field also support our results. Our study not only can be used to reduce the thermal hysteresis but also extends the application of the SAW as a tool to write and erase AFM patterns for spintronics and magnonics.

A clinical consensus-compliant deep learning approach to quantitatively evaluate human in vitro fertilization early embryonic development with optical microscope images.

The selection of embryos is a key for the success of in vitro fertilization (IVF). However, automatic quality assessment on human IVF embryos with optical microscope images is still challenging. In this study, we developed a clinical consensus-compliant deep learning approach, named Esava (Embryo Segmentation and Viability Assessment), to quantitatively evaluate the development of IVF embryos using optical microscope images. In total 551 optical microscope images of human IVF embryos of day-2 to day-3 were collected, preprocessed, and annotated. Using the Faster R-CNN model as baseline, our Esava model was constructed, refined, trained, and validated for precise and robust blastomere detection. A novel algorithm Crowd-NMS was proposed and employed in Esava to enhance the object detection and to precisely quantify the embryonic cells and their size uniformity. Additionally, an innovative GrabCut-based unsupervised module was integrated for the segmentation of blastomeres and embryos. Independently tested on 94 embryo images for blastomere detection, Esava obtained the high rates of 0.9940, 0.9121, and 0.9531 for precision, recall, and mAP respectively, and gained significant advances compared with previous computational methods. Intraclass correlation coefficients indicated the consistency between Esava and three experienced embryologists. Another test on 51 extra images demonstrated that Esava surpassed other tools significantly, achieving the highest average precision 0.9025. Moreover, it also accurately identified the borders of blastomeres with mIoU over 0.88 on the independent testing dataset. Esava is compliant with the Istanbul clinical consensus and compatible to senior embryologists. Taken together, Esava improves the accuracy and efficiency of embryonic development assessment with optical microscope images.

Glucuronidation dynamics of curcumin and tetrahydrocurcumin for differential structures and chemical reactivities in human liver microsome and uridine diphosphate glucuronosyltransferase 2B7.

THC is the main metabolite of curcumin with better bioactivity. This study aimed to explore the factors that cause differences in the bioactivity of curcumin and THC. We analyzed the metabolic activities of curcumin and THC and the factors responsible for the differences in their activities by glucuronidation activity assay, LC-MS, HPLC, homologous sequence comparisons, and molecular docking. Curcumin has higher metabolic activity than THC in HLM and UGT2B7, while the keto-enol isomers of curcumin and THC were distinctly different under different pH, and their structural transformations were hypothesized. Furthermore, UGT1A and UGT2B are differential sequences of curcumin and THC in UGTs. The binding sites and patterns of curcumin and THC in UGT2B7 are markedly different. In summary, the difference in keto-enolic interconversion isomerism between curcumin and THC is the main factor causing the difference in their activities, which provides a scientific basis for the development of curcumin.

Finite Element Simulation and Microstructural Evolution Investigation in Hot Stamping Process of Ti6Al4V Alloy Sheets.

Titanium alloy hot stamping technology has a wide range of application prospects in the field of titanium alloy part processing due to its high production efficiency and low manufacturing cost. However, the challenges of forming titanium alloy parts with large depths and deformations have restricted its development. In this study, the hot stamping process of a Ti6Al4V alloy box-shaped part was investigated using ABAQUS 2020 software. The thermodynamic properties of a Ti6Al4V alloy sheet were explored at different temperatures (400 °C, 500 °C, 600 °C, 700 °C, 800 °C) and different strain rates (0.1 s-1, 0.05 s-1, 0.01 s-1). In addition, the influence law of hot stamping process parameters on the minimum thickness of the formed part was revealed through the analysis of response surface methodology (RSM), ultimately obtaining the optimal combination of process parameters for Ti6Al4V alloy hot stamping. The experimental results of the hot stamping process exhibited a favorable correlation with the simulated outcomes, confirming the accuracy of the numerical simulation. The study on the microstructure evolution of the formed parts showed that grain refinement strengthening occurred in the part with large deformation, and the formed box-shaped parts exhibited a uniform and fine microstructure overall, demonstrating high forming quality. The achievements of the work provide important guidance for the fabrication of titanium alloy parts with large depths and deformations used in heavy industrial production.

Molecular characteristics and prognostic significances of lysosomal-dependent cell death in kidney renal clear cell carcinoma.

Lysosomal-dependent cell death (LDCD) has an excellent therapeutic effect on apoptosis-resistant and drug-resistant tumors; however, the important role of LDCD-related genes (LDCD-RGs) in kidney renal clear cell carcinoma (KIRC) has not been reported. Initially, single-cell atlas of LDCD signal in KIRC was comprehensively depicted. We also emphasized the molecular characteristics of LDCD-RGs in various human neoplasms. Predicated upon the expressive quotients of LDCD-RGs, we stratified KIRC patients into tripartite cohorts denoted as C1, C2, and C3. Those allocated to the ambit of C1 evinced the most sanguine prognosis within the KIRC cohort, underscored by the acme of LDCD-RGs scores. This further confirms the significant role that LDCD-RGs play in both the pathophysiological foundation and clinical implications of KIRC. In culmination, by virtue of employing the LASSO-Cox analytical modality, we have ushered in an innovative and avant-garde prognostic framework tailored for KIRC, predicated on the bedrock of LDCD-RGs. The assemblage of KIRC instances was arbitrarily apportioned into constituents inclusive of a didactic cohort, an internally wielded validation cadre, and an externally administered validation cohort. Concurrently, patients were dichotomized into strata connoting elevated jeopardy synonymous with adverse prognostic trajectories, and conversely, diminished risk tantamount to favorable prognoses, contingent on the calibrated expressions of LDCD-RGs. Succinctly, our investigative findings serve to underscore the cardinal capacity harbored by LDCD-RGs within the KIRC milieu, concurrently birthing a pioneering prognostic schema intrinsically linked to the trajectory of KIRC and its attendant prognoses.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

[Genetic analysis of a child with Hypotrichosis simplex].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14. METHODS: A child who had presented at the Henan Provincial People's Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c.1609G>A (p.V537M) in exon 17 and c.802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+PP3+PP4). CONCLUSION: The c.1609G>A (p.V537M) and c.802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.