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Rapid and accurate diagnostic tests are fundamental for improving patient outcomes and combating infectious diseases. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas12a‐based detection system has emerged as a promising solution for on‐site nucleic acid testing. Nonetheless, the effective design of CRISPR RNA (crRNA) for Cas12a‐based detection remains challenging and time‐consuming. In this study, we propose an enhanced crRNA design system with deep learning for Cas12a‐mediated diagnostics, referred to as EasyDesign. This system employs an optimized convolutional neural network (CNN) prediction model, trained on a comprehensive data set comprising 11,496 experimentally validated Cas12a‐based detection cases, encompassing a wide spectrum of prevalent pathogens, achieving Spearman's ρ = 0.812. We further assessed the model performance in crRNA design for four pathogens not included in the training data: Monkeypox Virus, Enterovirus 71, Coxsackievirus A16, and Listeria monocytogenes. The results demonstrated superior prediction performance compared to the traditional experiment screening. Furthermore, we have developed an interactive web server (https://crispr.zhejianglab.com/) that integrates EasyDesign with recombinase polymerase amplification (RPA) primer design, enhancing user accessibility. Through this web‐based platform, we successfully designed optimal Cas12a crRNAs for six human papillomavirus (HPV) subtypes. Remarkably, all the top five predicted crRNAs for each HPV subtype exhibited robust fluorescent signals in CRISPR assays, thereby suggesting that the platform could effectively facilitate clinical sample testing. In conclusion, EasyDesign offers a rapid and reliable solution for crRNA design in Cas12a‐based detection, which could serve as a valuable tool for clinical diagnostics and research applications. Highlights: Advanced crRNA design system: Developed EasyDesign, utilizing a convolutional neural network (CNN) trained with over 11,000 diagnostic‐target pairs to enable the creation of highly sensitive crRNAs for Cas12a‐based nucleic acid diagnostics.Proven predictive capabilities: EasyDesign demonstrates superior predictive performance for crRNA‐mediated Cas12a detection, validated through its successful application in designing diagnostics for a variety of viruses in clinical settings.User‐friendly web platform: Features an intuitive web platform that streamlines the creation of CRISPR/Cas12a‐based diagnostic tools, thereby enhancing accessibility and usability for both researchers and clinicians. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype and chemotherapy is the cornerstone treatment for TNBC. Regrettably, emerging findings suggest that chemotherapy facilitates pro‐metastatic changes in the tumour microenvironment. Extracellular vesicles (EVs) have been highly implicated in cancer drug resistance and metastasis. However, the effects of the EVs released from dying cancer cells on TNBC prognosis and corresponding therapeutic strategies have been poorly investigated. This study demonstrated that paclitaxel chemotherapy elicited CXCL1‐enriched EVs from apoptotic TNBC cells (EV‐Apo). EV‐Apo promoted the chemoresistance and invasion of co‐cultured TNBC cells by polarizing M2 macrophages through activating PD‐L1 signalling. However, baohuoside I (BHS) remarkably sensitized the co‐cultured TNBC cells to paclitaxel chemotherapy via modulating EV‐Apo signalling. Mechanistically, BHS remarkably decreased C‐X‐C motif chemokine ligand 1 (CXCL1) cargo within EV‐Apo and therefore attenuated macrophage M2 polarization by suppressing PD‐L1 activation. Additionally, BHS decreased EV‐Apo release by diminishing the biogenesis of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) of TNBC cells. Furthermore, BHS bound to the LEU104 residue of flotillin 2 (FLOT2) and interrupted its interaction with RAS oncogene family member 31 (RAB31), leading to the blockage of RAB31‐FLOT2 complex‐driven ILV biogenesis. Importantly, BHS remarkably chemosensitised paclitaxel to inhibit TNBC metastasis in vivo by suppressing EV‐ApoCXCL1‐induced PD‐L1 activation and M2 polarization of tumour‐associated macrophages (TAMs). This pioneering study sheds light on EV‐ApoCXCL1 as a novel therapeutic target to chemosensitise TNBC, and presents BHS as a promising chemotherapy adjuvant to improve TNBC chemosensitivity and prognosis by disturbing EV‐ApoCXCL1 biogenesis. [ABSTRACT FROM AUTHOR]

Spleen and lymphoid organs are important targets for messenger RNA (mRNA) delivery in various applications. Current nanoparticle delivery methods rely on drainage to lymph nodes from intramuscular or subcutaneous injections. In difficult‐to‐transfect antigen‐presenting cells (APCs), such as dendritic cells (DCs), effective mRNA transfection remains a significant challenge. In this study, a lymphatic targeting carrier using DC membranes is developed, that efficiently migrated to lymphoid organs, such as the spleen and lymph nodes. The nanoparticles contained an ionizable lipid (YK009), which ensured a high encapsulation efficacy of mRNA and assisted mRNA with endosomal escape after cellular uptake. Dendritic cell‐mimicking nanoparticles (DCMNPs) showed efficient protein expression in both the spleen and lymph nodes after intramuscular injections. Moreover, in immunized mice, DCMNP vaccination elicited Spike‐specific IgG antibodies, neutralizing antibodies, and Th1‐biased SARS‐CoV‐2‐specific cellular immunity. This work presents a powerful vaccine formula using DCMNPs, which represents a promising vaccine candidate for further research and development. [ABSTRACT FROM AUTHOR]

Baicalin (7‐d‐glucuronic acid‐5, 6‐dihydroxyflavone) derived from the root of Scutellaria baicalensis used as Traditional Chinese Medicine (TCM) has been revealed to exert potential antiviral activity via various pathways, while the molecular mechanisms have not been fully understood. Pyroptosis, an inflammatory form of programmed cell death (PCD), is reported to play a crucial role in host cell fate during viral infection. In this study, transcriptome analysis of mice lung tissue reveals that baicalin reverses the alterations of the mRNA levels of PCD‐associated genes upon H1N1 challenge, with a concomitant decrease in the population of H1N1‐induced propidium iodide (PI)+ and Annexin Ⅴ+ cells. Intriguingly, we find that baicalin contributes to the survival of infected lung alveolar epithelial cells partly through its inhibition of H1N1‐induced cell pyroptosis, which is manifested by reduced bubble‐like protrusion cells and lactate dehydrogenase (LDH) release. Moreover, the antipyroptosis effect of baicalin in response to H1N1 infection is found to be mediated by its repression on caspase‐3/Gasdermin E (GSDME) pathway. Cleaved caspase‐3 and N‐terminal fragment of GSDME (GSDME‐N) are detected in H1N1‐infected cell lines and mice lung tissues, which are markedly reversed by baicalin treatment. Furthermore, inhibition of caspase‐3/GSDME pathway by caspase‐3 inhibitor or siRNA exerts an antipyroptosis effect equal to that of baicalin treatment in infected A549 and BEAS‐2B cells, indicating a pivotal role of caspase‐3 in the antiviral activities of baicalin. Conclusively, for the first time, we demonstrate that baicalin could effectively suppress H1N1‐induced pyroptosis of lung alveolar epithelial cells via caspase‐3/GSDME pathway both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The extreme instability of mRNA makes the practical application of mRNA‐based vaccines heavily rely on efficient delivery system and cold chain transportation. Herein, a DNA‐based nanomachine, which achieves programmed capture, long‐term storage without cryopreservation, and efficient delivery of mRNA in cells, is developed. The polythymidine acid (Poly‐T) functionalized poly(N‐isopropylacrylamide) (DNA‐PNIPAM) is synthesized and assembled as the central compartment of the nanomachine. The DNA‐PNIPAM nano‐assembly exhibits reversible thermal‐responsive dynamic property: when lower than the low critical solution temperature (LCST, ≈32 °C) of PNIPAM, the DNA‐PNIPAM transforms into extension state to expose the poly‐T, facilitating the hybridization with polyadenylic acid (Poly‐A) tail of mRNA; when higher than LCST, DNA‐PNIPAM re‐assembles and achieves an efficient encapsulation of mRNA. It is remarkable that the DNA‐PNIPAM nano‐assembly realizes long‐term storage of mRNA (≈7 days) at 37 °C. Biodegradable 2‐hydroxypropyltrimethyl ammonium chloride chitosan is assembled on the outside of DNA‐PNIPAM to facilitate the endocytosis of mRNA, RNase‐H mediating mRNA release occurs in cytoplasm, and efficient mRNA translation is achieved. This work provides a new disign principle of nanosystem for mRNA delivery. [ABSTRACT FROM AUTHOR]

The UPR sensor GRP78 had been reported to translocate toward the cell membrane to bind with ligands and facilitate cell survival.[9] Correspondingly, GRP78 presented colocalisation with cefoselis at the cell surface upon paclitaxel treatment (Figure 2E). Previous studies have indicated that GRP78 shifts to the cell membrane under ER stress.[[6], [8]] Herein, it was also observed that paclitaxel treatment induced GRP78 translocation to the cell surface (Figure 1F). Stress-induced cellular defence machinery is significant for regulating breast cancer stem cells (CSCs).[[1], [3]] GRP78 is an endoplasmic reticulum (ER) stress protein and has been reported to be overexpressed in multiple malignancies.[4] In this study, we shed novel light on the role of GRP78 in regulating breast CSCs via LRP5/ -catenin signalling. [Extracted from the article]

To rapidly identify individuals infected with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) and control the spread of coronavirus disease (COVID‐19), there is an urgent need for highly sensitive on‐site virus detection methods. A clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein (Cas)‐based molecular diagnostic method was developed for this purpose. Here, a CRISPR system‐mediated lateral flow assay (LFA) for SARS‐CoV‐2 was established based on multienzyme isothermal rapid amplification, CRISPR‐Cas13a nuclease, and LFA. To improve the limit of detection (LoD), the crispr RNA, amplification primer, and probe were screened, in addition to concentrations of various components in the reaction system. The LoD of CRISPR detection was improved to 0.25 copy/μl in both fluorescence‐ and immunochromatography‐based assays. To enhance the quality control of the CRISPR‐based LFA method, glyceraldehyde‐3‐phosphate dehydrogenase was detected as a reference using a triple‐line strip design in a lateral flow strip. In total, 52 COVID‐19‐positive and 101 COVID‐19‐negative clinical samples examined by reverse transcription polymerase chain reaction (RT‐PCR) were tested using the CRISPR immunochromatographic detection technique. Results revealed 100% consistency, indicating the comparable effectiveness of our method to that of RT‐PCR. In conclusion, this approach significantly improves the sensitivity and reliability of CRISPR‐mediated LFA and provides a crucial tool for on‐site detection of SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

The pseudovirus neutralization assays showed that XBB.1 and BQ.1.1 could not be blocked by Bebtelovimab, while BA.2.3.20 was approximately seven fold resistant to Bebtelovimab (Figure 1B). Bebtelovimab (LY-CoV1404) is a monoclonal antibody showing remarkable neutralizing capacity against all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) as of June 2022, including the Omicron variant and its subvariants (BA.1, BA.2, BA.4, and BA.5).[[1]] However, SARS-CoV-2 continues to acquire mutations in the spike that impact antibody recognition and neutralization.[[3]] It is important to evaluate the efficiency of Bebtelovimab against new SARS-CoV-2 variants and provide a reference for the application of Bebtelovimab. In summary, the neutralizing antibody Bebtelovimab was escaped by more and more SARS-CoV-2 variants, including new-emerging variants BQ.1.1, XBB.1, and potential future variants. [Extracted from the article]

In the era of knowledge economy, human resources as the first resource of enterprises have long become a consensus. However, human resource management in my country is still in its infancy. There are few studies on the relationship between the two, and the research conclusions are inconsistent. There are very few subjects for research. As the core of my country is banking industry, state-owned commercial banks affect the development direction of my country's banking industry, and their human resource management has its own unique features. However, due to my country's special national conditions, state-owned commercial banks have not been fully market-oriented, lacking a certain degree of independence and autonomy, and the impact of administrative intervention has led to human resource management in state-owned commercial banks that have not been developed as they should be. In a series of questions, in today's turbulent global financial environment, state-owned commercial banks need to improve their human resource management to enhance their sustainable competitiveness. Based on combing the research on the relationship between human resource management and corporate performance by domestic and foreign scholars and analyzing the status quo and problems of human resource management of state-owned commercial banks, this paper collects data through questionnaires and analyzes the reliability and validity of the data. Then use empirical analysis methods to study the relationship between human resource management of state-owned commercial banks and corporate performance. The research results show that there is a significant positive correlation between the human resource management practices of state-owned commercial banks and corporate performance, that is, improving the level of human resource management can promote the improvement of corporate performance. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID‐19) pandemic has focused attention on the need to develop effective therapeutics against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), and also against other pathogenic coronaviruses. In this study, we report on a kind of bisbenzylisoquinoline alkaloid, neferine, as a pan‐coronavirus entry inhibitor. Neferine effectively protected HEK293/hACE2 and HuH7 cell lines from infection by different coronaviruses pseudovirus particles (SARS‐CoV‐2, SARS‐CoV‐2 [D614G, N501Y/D614G, 501Y.V1, 501Y.V2, 501Y.V3 variants], SARS‐CoV, MERS‐CoV) in vitro, with median effect concentration (EC50) of 0.13–0.41 μM. Neferine blocked host calcium channels, thus inhibiting Ca2+‐dependent membrane fusion and suppressing virus entry. This study provides experimental data to support the fact that neferine may be a promising lead for pan‐coronaviruses therapeutic drug development. [ABSTRACT FROM AUTHOR]

Data mining is currently a frontier research topic in the field of information and database technology. It is recognized as one of the most promising key technologies. Data mining involves multiple technologies, such as mathematical statistics, fuzzy theory, neural networks, and artificial intelligence, with relatively high technical content. The realization is also difficult. In this article, we have studied the basic concepts, processes, and algorithms of association rule mining technology. Aiming at large-scale database applications, in order to improve the efficiency of data mining, we proposed an incremental association rule mining algorithm based on clustering, that is, using fast clustering. First, the feasibility of realizing performance appraisal data mining is studied; then, the business process needed to realize the information system is analyzed, the business process-related links and the corresponding data input interface are designed, and then the data process to realize the data processing is designed, including data foundation and database model. Aiming at the high efficiency of large-scale database mining, database development tools are used to implement the specific system settings and program design of this algorithm. Incorporated into the human resource management system of colleges and universities, they carried out successful association broadcasting, realized visualization, and finally discovered valuable information. [ABSTRACT FROM AUTHOR]

As one of the most abundant immune cell populations in the tumor microenvironment (TME), tumor‐associated macrophages (TAMs) play important roles in multiple solid malignancies, including breast cancer, prostate cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, pancreatic cancer, and colorectal cancer. TAMs could contribute to carcinogenesis, neoangiogenesis, immune‐suppressive TME remodeling, cancer chemoresistance, recurrence, and metastasis. Therefore, reprogramming of the immune‐suppressive TAMs by pharmacological approaches has attracted considerable research attention in recent years. In this review, the promising pharmaceutical targets, as well as the existing modulatory strategies of TAMs were summarized. The chemokine–chemokine receptor signaling, tyrosine kinase receptor signaling, metabolic signaling, and exosomal signaling have been highlighted in determining the biological functions of TAMs. Besides, both preclinical research and clinical trials have suggested the chemokine–chemokine receptor blockers, tyrosine kinase inhibitors, bisphosphonates, as well as the exosomal or nanoparticle‐based targeting delivery systems as the promising pharmacological approaches for TAMs deletion or reprogramming. Lastly, the combined therapies of TAMs‐targeting strategies with traditional treatments or immunotherapies as well as the exosome‐like nanovesicles for cancer therapy are prospected. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that caveolin‐1 (CAV‐1) is a stress‐related oncotarget and closely correlated to chemoresistance. Targeting CAV‐1 might be a promising strategy to improve chemosensitivity for breast cancer treatment. Astragaloside IV (AS‐IV), a bioactive compound purified from Astragalus membranaceus, has been shown to exhibit multiple bioactivities, including anticancer. However, the involved molecular targets are still ambiguous. In this study, we investigated the critical role of CAV‐1 in mediating the chemosensitizing effects of AS‐IV to Taxol on breast cancer. We found that AS‐IV could enhance the chemosensitivity of Taxol with minimal direct cytotoxicity on breast cancer cell lines MCF‐7 and MDA‐MB‐231, as well as the nontumor mammary epithelial cell line MCF‐10A. AS‐IV was further demonstrated to aggravate Taxol‐induced apoptosis and G2/M checkpoint arrest. The phosphorylation of mitogen‐activated protein kinase (MAPK) signaling extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal Kinase (JNK), except p38, was also abrogated by a synergistic interaction between AS‐IV and Taxol. Moreover, AS‐IV inhibited CAV‐1 expression in a dose‐dependent manner and reversed CAV‐1 upregulation induced by Taxol administration. Mechanism study further demonstrated that AS‐IV treatment triggered the eNOS/NO/ONOO− pathway via inhibiting CAV‐1, which led to intense oxidant damage. CAV‐1 overexpression abolished the chemosensitizing effects of AS‐IV to Taxol by inhibiting oxidative stress. In vivo experiments further validated that AS‐IV increased Taxol chemosensitivity on breast cancer via inhibiting CAV‐1 expression, followed by activation of the eNOS/NO/ONOO− pathway. Taken together, our findings not only suggested the potential of AS‐IV as a promising candidate to enhance chemosensitivity, but also highlighted the significance of CAV‐1 as the target to reverse cancer drug resistance. Astragaloside IV (AS‐IV) promotes chemosensitivity via downregulating the expression of caveolin‐1 (CAV‐1) and subsequently activates nitrative stress response. Decreased level of CAV‐1 overexpresses eNOS and facilitates NO formation, thereby improving ONOO− production and leading to cell death. Taken together, our findings not only suggested the potential of AS‐IV as a promising candidate to enhance chemosensitivity, but also highlighted the significance of CAV‐1 as the target to reverse cancer drug resistance. [ABSTRACT FROM AUTHOR]

Background. Helicobacter pylori (H. pylori) is one of the most frequent and persistent bacterial infections that affect nearly half of the world’s population. Antibiotic resistance is a constantly evolving process and local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. The aim of this study was to establish a microarray-based detection to identify H. pylori infection, clarithromycin and levofloxacin susceptibility, and CYP2C19 genetic polymorphism and guide to potential choice of proton pump inhibitor (PPI), antibiotic administration for tailored H. pylori eradication therapy. Methods. By analyzing the sequence of human genomic CYP2C19⁎2 and CYP2C19⁎3 and mutations within the 23S rRNA and gyrA gene regions conferring clarithromycin and levofloxacin resistance, respectively, we developed a microarray for individual therapy detection of H. pylori infection. Plasmids were established as positive or limit of detection (LOD) reference materials. The specificity and sensitivity of the microarray had been performed. And a total of 1083 gastric biopsy samples were tested and the Kappa value had been calculated between the array and Sanger sequencing. We also analyzed the resistance to clarithromycin and levofloxacin in China, as well as the CYP2C19 polymorphisms. Results. The LOD of detecting H. pylori was 103 CFU/mL and human genome DNA was 2 ng/μL. The detection results of 1083 gastric biopsy samples showed that 691 (63.80%) were H. pylori positive, of which 266 (38.49%) were resistant to clarithromycin, 192 (27.79%) were resistant to levofloxacin, and 61 (8.83%) were resistant to both of them. For the type of CYP2C19 polymorphism, 412 (38.04%) were homozygous fast type (HomEM), 574 (53%) were heterozygous EM (HetEM), and 97 (8.96%) were poor metabolizer (PM). Conclusions. The proposed microarray-based detection has high specificity, sensitivity, and reproducibility for detecting the resistance of clarithromycin or levofloxacin as well as CYP2C19 polymorphism, which may help to improve the clinical eradication rate of H. pylori. [ABSTRACT FROM AUTHOR]

Abstract: DNA is often difficult to extract from old bones and teeth due to low levels of DNA and high levels of degradation. This study established a simple yet efficient method for extracting DNA from 20 aged bones and teeth (approximately 60 years old). Based on the concentration and STR typing results, the new method of DNA extraction (OM) developed in this study was compared with the PrepFiler™ BTA Forensic DNA Extraction Kit (BM). The total amount of DNA extracted using the OM method was not significantly different from that extracted using the commercial kit (p > 0.05). However, the number of STR loci detected was significantly higher in the samples processed using the OM method than using the BM method (p < 0.05). This study aimed to establish a DNA extraction method for aged bones and teeth to improve the detection rate of STR typing and reduce costs compared to the BM technique. [ABSTRACT FROM AUTHOR]

Front Cover Caption: The cover image is based on the Research Article Baicalin inhibits influenza A (H1N1)‐induced pyroptosis of lung alveolar epithelial cells via caspase‐3/GSDME pathway by Zhenqiao Wei et al., https://doi.org/10.1002/jmv.28790. [ABSTRACT FROM AUTHOR]

The title compound, C(7)H(13)NO(5), was prepared by the condensation of O-(carb-oxy-meth-yl)hydroxyl-amine and (Boc)(2)O (Boc = but-oxy-carbon-yl).In the crystal, mol-ecules are linked by weak inter-molecular N-H⋯O hydrogen bonds.