Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage.

Cholesterol is an important component of plasma membranes and participates in many basic life functions, such as the maintenance of cell membrane stability, the synthesis of steroid hormones, and myelination. Cholesterol plays a key role in the establishment and maintenance of the central nervous system. The brain contains 20% of the whole body's cholesterol, 80% of which is located within myelin. A huge number of processes (e.g., the sterol regulatory element-binding protein pathway and liver X receptor pathway) participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis, intracellular transport, and efflux. Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences. Therefore, we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases. Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype, with high mortality and morbidity. Historical cholesterol levels are associated with the risk of intracerebral hemorrhage. Moreover, secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation, such as neuroinflammation, demyelination, and multiple types of programmed cell death. Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage. In this paper, we review normal cholesterol metabolism in the central nervous system, the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage, and the links between cholesterol metabolism and cell death. We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

Narcissism, perfectionism, and self-promoting behavior on social networking sites among university students in Pakistan / Narcisismo, perfeccionismo y comportamiento de autopromoción en sitios de redes sociales entre estudiantes universitarios en Pakistán

Existe un debate considerable en la literatura sobre cómo el narcisismo predice diversos comportamientos asociados con la utilidad de los sitios de redes sociales, pero los investigadores han prestado menos atención a explorar los mediadores potenciales de esta relación. Con base en la literatura existente, anticipamos que el narcisismo predice comportamientos de autopromoción en los sitios de redes sociales. El estudio actual también investigó el papel mediador del perfeccionismo multidimensional entre el narcisismo y el comportamiento de autopromoción. Se recopiló un total de 605 cuestionarios completos de estudiantes de universidades de Rawalpindi e Islamabad, Pakistán, mediante un muestreo conveniente. El estudio utilizó el Inventario de Personalidad Narcisista (Ames et al., 2006), un cuestionario de desarrollo propio sobre comportamiento de autopromoción en sitios de redes sociales y la Escala de Perfeccionismo Multidimensional (Hewitt et al., 1991). Los hallazgos indicaron que las mujeres en comparación con los hombres y las solteras en comparación con las casadas obtuvieron puntuaciones más altas en narcisismo. Los niveles educativos más altos se asociaron con tasas más altas de narcisismo. Los resultados también sugieren que el narcisismo se correlaciona con el perfeccionismo orientado a uno mismo y, más significativamente, con el narcisismo orientado a los demás. El perfeccionismo orientado a uno mismo y a los demás medió significativamente la relación entre el narcisismo y el comportamiento de autopromoción en los sitios de redes sociales.(AU)

There is considerable debate in the literature about how narcis-sism predicts various behaviors associated with the utility of social net-working sites, but researchers have paid less attention to exploring the po-tential mediators of this relationship.Based on the existing literature, we anticipated that narcissism predicts self-promoting behaviors on social networking sites. The current study also investigated the mediating role of multidimensional perfectionismbetween narcissism and self-promoting behavior. A total of 605 complete questionnaires weregathered fromstu-dents from universities from Rawalpindi and Islamabad, Pakistan using convenient sampling. The study used Narcissistic Personality Inventory (Ames et al., 2006), self-developed Self-promoting Behavior on social net-working sites questionnaire, and the Multidimensional Perfectionism Scale (Hewitt et al., 1991). Findings indicated that females as compared to males and single as comparedto married individuals scored higher on narcissism. Higher educational levels were associated with higher rates of narcissism. The results also suggestthat narcissism correlated with self-oriented per-fectionism, and more significantlywith others-oriented narcissism. Self-oriented and others-oriented perfectionism significantly mediated the rela-tionship between narcissism and self-promoting behavior on social net-working sites.(AU)

Haploidentical versus mismatched unrelated donor HCT: HLA-factors and donor age considerations.

HLA-mismatched unrelated donors and haploidentical related donors are suitable stem cell sources for hematopoietic cell transplantation (HCT) when patients lack HLA-matched donors. Clinical outcome after mismatched HCT is influenced by HLA factors including the similarity of peptide-binding motifs (PBMs) between the patient and unrelated donor, and of the HLA-B leader in unrelated and haploidentical donors. Whether these factors can aid in the selection between mismatched unrelated and haploidentical donors is not known. To address this question, we investigated outcomes between the two donor types defined by matching for the PBM and leader peptide. We compared PBM-matched (n=614) and mismatched (n=958) MMUDs with calcineurin-inhibitor-based prophylaxis to four haploidentical groups that received post-transplant cyclophosphamide (PTCy)-based prophylaxis. The haploidentical groups were B-leader matched/DRB1-mismatched (n=722), B-leader matched/DRB1-matched (n=154), B-leader mismatched/DRB1-mismatched (n=493), and B-leader mismatched/DRB1-matched (n=63). Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, while other haploidentical groups had comparable OS. The PBM-mismatched MMUD showed the poorest outcomes, similar to the B-leader mismatched/DRB1-matched haploidentical group. Among non-HLA factors, donor age was the most significant predictor of OS. These results suggest that a B-leader matched/DRB1 mismatched haploidentical donor might be the preferred choice among donors of similar age. If such a donor is not available, the youngest donor from either PBM-matched unrelated or other haploidentical groups could be a beneficial choice. These findings need validation with both donor groups receiving PTCy-based GVHD prophylaxis.

Repurposing cyclovirobuxine D as a novel inhibitor of colorectal cancer progression via modulating the CCT3/YAP axis.

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities. EXPERIMENTAL APPROACH: Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated ß-galactosidase (SA-ß-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies. KEY RESULTS: CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3. CONCLUSIONS AND IMPLICATIONS: Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.

Harnessing the Missing Spectral Correlation for Metasurface Inverse Design.

A long-held tenet in computer science asserts that the training of deep learning is analogous to an alchemical furnace, and its "black box" signature brings forth inexplicability. For electromagnetic metasurfaces, the related intelligent applications also get stuck into such a dilemma. Although the past 5 years have witnessed a proliferation of deep learning-based works across complex photonic scenarios, they neglect the already existing but untapped physical laws. Here, the intrinsic correlation between the real and imaginary parts of the spectra are revealed using Kramers-Kronig relations, which is then mimicked by bidirectional information flow in neural network space. Such consideration harnesses the missing spectral connection to extract crucial features effectively. The bidirectional recurrent neural network is benchmarked in metasurface inverse design and compare it with a fully-connected neural network, unidirectional recurrent neural network, and attention-based transformer. Beyond the improved accuracy, the study examines the intermediate information products and physically explains why different network structures yield different performances. The work offers explicable perspectives to utilize physical information in the deep learning field and facilitates many data-intensive research endeavors.

A cargo sorting receptor mediates chloroplast protein trafficking through the secretory pathway.

Nucleus-encoded chloroplast proteins can be transported via the secretory pathway. The molecular mechanisms underlying the trafficking of chloroplast proteins between the intracellular compartments are largely unclear, and a cargo sorting receptor has not previously been identified in the secretory pathway. Here we report a cargo sorting receptor that is specifically present in Viridiplantae and mediates the transport of cargo proteins to the chloroplast. Using a forward genetic analysis, we identified a gene encoding a transmembrane protein (MtTP930) in barrel medic (Medicago truncatula). Mutation of MtTP930 resulted in impaired chloroplast function and a dwarf phenotype. MtTP930 is highly expressed in the aerial parts of the plant and is localized to the ER exit sites (ERESs) and Golgi. MtTP930 contains typical cargo sorting receptor motifs, interacts with Sar1, Sec12 and Sec24, and participates in coat protein II (COPII) vesicular transport. Importantly, MtTP930 can recognize the cargo proteins plastidial N-glycosylated nucleotide pyrophosphatase/ phosphodiesterase (MtNPP) and α-carbonic anhydrase (MtCAH) in the ER, and then transport them to the chloroplast via the secretory pathway. Mutation of a homolog of MtTP930 in Arabidopsis (Arabidopsis thaliana) resulted in a similar dwarf phenotype. Furthermore, MtNPP-GFP failed to localize to chloroplasts when transgenically expressed in Attp930 protoplasts, implying that these cargo sorting receptors are conserved in plants. These findings fill a gap in our understanding of the mechanism by which chloroplast proteins are sorted and transported via the secretory pathway.

Synergistic solidification and mechanism research of electrolytic manganese residue and coal fly ash based on C-A-S-H gel material.

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.

The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.

Causal relationship between bone mineral density and intervertebral disc degeneration: a univariate and multivariable mendelian randomization study.

BACKGROUND: Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. OBJECTIVES: This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). METHODS: Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. RESULTS: In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. CONCLUSIONS: The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.

The antibodies against the A137R protein drive antibody-dependent enhancement of African swine fever virus infection in porcine alveolar macrophages.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious disease that can kill up to 100% of domestic pigs and wild boars. It has been shown that the pigs inoculated with some ASF vaccine candidates display more severe clinical signs and die earlier than do pigs not immunized. We hypothesize that antibody-dependent enhancement (ADE) of ASFV infection may be caused by the presence of some unidentified antibodies. In this study, we found that the ASFV-encoded structural protein A137R (pA137R) can be recognized by the anti-ASFV positive sera, indicating that the anti-pA137R antibodies are induced in the ASFV-infected pigs. Interestingly, our results demonstrated that the anti-pA137R antibodies produced in rabbits or pigs enhanced viral replication of different ASFV strains in primary porcine alveolar macrophages (PAMs), the target cells of ASFV. Mechanistic investigations revealed that anti-pA137R antibodies were able to promote the attachment of ASFV to PAMs and two types of Fc gamma receptors (FcγRs), FcγRII and FcγRIII, mediated the ADE of ASFV infection. Taken together, anti-pA137R antibodies are able to drive ASFV ADE in PAMs. These findings shed new light on the roles of anti-ASFV antibodies and have implications for the pathophysiology of the disease and the development of ASF vaccines.

Accurately deciphering spatial domains for spatially resolved transcriptomics with stCluster.

Spatial transcriptomics provides valuable insights into gene expression within the native tissue context, effectively merging molecular data with spatial information to uncover intricate cellular relationships and tissue organizations. In this context, deciphering cellular spatial domains becomes essential for revealing complex cellular dynamics and tissue structures. However, current methods encounter challenges in seamlessly integrating gene expression data with spatial information, resulting in less informative representations of spots and suboptimal accuracy in spatial domain identification. We introduce stCluster, a novel method that integrates graph contrastive learning with multi-task learning to refine informative representations for spatial transcriptomic data, consequently improving spatial domain identification. stCluster first leverages graph contrastive learning technology to obtain discriminative representations capable of recognizing spatially coherent patterns. Through jointly optimizing multiple tasks, stCluster further fine-tunes the representations to be able to capture complex relationships between gene expression and spatial organization. Benchmarked against six state-of-the-art methods, the experimental results reveal its proficiency in accurately identifying complex spatial domains across various datasets and platforms, spanning tissue, organ, and embryo levels. Moreover, stCluster can effectively denoise the spatial gene expression patterns and enhance the spatial trajectory inference. The source code of stCluster is freely available at https://github.com/hannshu/stCluster.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Phage-displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against Staphylococcus aureus.

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway.

Four new series of curcumin derivatives bearing NO-donating moiety were synthesized via etherification, nucleophilic substitution, and Knoevenagel condensation etc. The cytotoxicity activity of curcumin derivatives against five human tumor cell lines (A549, Hela, HepG2, MCF-7 and HT-29) and two normal cell lines (LO-2 and HK-2) has been studied. The results showed that compound 6a could inhibit the proliferation of MCF-7 cells remarkably and exhibit low toxicity to normal cells. Also, the underlying mechanism in vitro of compound 6a on MCF-7 was investigated. It has been found that compound 6a induced G2/M arrest and apoptosis of MCF-7 in a dose-dependent manner. Compound 6a-induced the fluorescence changes of ROS in MCF-7 cells confirmed the occurrence of apoptosis. Western Blot suggested that compound 6a decreased the expression of PI3K, as well as increased the expression of p53, cleaved caspase-9 and cleaved caspase-3. Furthermore, molecular docking revealed that compound 6a could bind well at active site of PI3K (3zim) with total score 9.59. Together, compound 6a, a potential PI3K inhibitor, may inhibit the survival of MCF-7 cells via interfering with PI3K/Akt/p53 pathway.

Combined application of myo-inositol and corn steep liquor enhances seedling growth and cold tolerance in cucumber and tomato.

Low temperatures pose a common challenge in the production of cucumbers and tomatoes, hindering plant growth and, in severe cases, leading to plant death. In our investigation, we observed a substantial improvement in the growth of cucumber and tomato seedlings through the application of corn steep liquor (CSL), myo-inositol (MI), and their combinations. When subjected to low-temperature stress, these treatments resulted in heightened levels of photosynthetic pigments, thereby fostering enhanced photosynthesis in both tomato and cucumber plants. Furthermore, it contributed to a decrease in malondialdehyde (MDA) levels and electrolyte leakage (REP). The effectiveness of the treatment was further validated through the analysis of key gene expressions (CBF1, COR, MIOX4, and MIPS1) in cucumber. Particularly, noteworthy positive outcomes were noted in the treatment involving 0.6 mL L-1 CSL combined with 72 mg L-1 MI. This study provides valuable technical insights into leveraging the synergistic effects of inositol and maize leachate to promote early crop growth and bolster resistance to low temperatures.

Rapid and Amplification-free Nucleic Acid Detection with DNA Substrate-Mediated Autocatalysis of CRISPR/Cas12a.

To enable rapid and accurate point-of-care DNA detection, we have developed a single-step, amplification-free nucleic acid detection platform, a DNA substrate-mediated autocatalysis of CRISPR/Cas12a (DSAC). DSAC makes use of the trans-cleavage activity of Cas12a and target template-activated DNA substrate for dual signal amplifications. DSAC employs two distinct DNA substrate types: one that enhances signal amplification and the other that negatively modulates fluorescent signals. The positive inducer utilizes nicked- or loop-based DNA substrates to activate CRISPR/Cas12a, initiating trans-cleavage activity in a positive feedback loop, ultimately amplifying the fluorescent signals. The negative modulator, which involves competitor-based DNA substrates, competes with the probes for trans-cleaving, resulting in a signal decline in the presence of target DNA. These DNA substrate-based DSAC systems were adapted to fluorescence-based and paper-based lateral flow strip detection platforms. Our DSAC system accurately detected African swine fever virus (ASFV) in swine's blood samples at femtomolar sensitivity within 20 min. In contrast to the existing amplification-free CRISPR/Dx platforms, DSAC offers a cost-effective and straightforward detection method, requiring only the addition of a rationally designed DNA oligonucleotide. Notably, a common ASFV sequence-encoded DNA substrate can be directly applied to detect human nucleic acids through a dual crRNA targeting system. Consequently, our single-step DSAC system presents an alternative point-of-care diagnostic tool for the sensitive, accurate, and timely diagnosis of viral infections with potential applicability to human disease detection.

Carotid revascularisation versus medical treatment for asymptomatic carotid artery stenosis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the safety and efficacy of carotid revascularisation plus best medical treatment with best medical treatment alone in people with asymptomatic carotid artery stenosis.

Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System.

We present a PPh3/DDQ-mediated regiospecific selective N-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N1-benzyl arylhydrazines and N2-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N1-benzlated products have also been successfully applied to the concise synthesis of N-substituted indoles and anticancer drug MDM2 inhibitor.