Aqueous Cellulose Solution Adhesive.

In the context of sustainable development, research on a biomass-based adhesive without chemical modification as a substitute for petroleum-based adhesive is now crucial. It turns out to be challenging to guarantee a simple and sustainable method to produce high-quality adhesives and subsequently manufacture multifunctional composites. Herein, the inherent properties of cellulose were exploited to generate an adhesive based on a cellulose aqueous solution. The adhesion is simple to prepare structurally and functionally complex materials in a single process. Cellulose-based daily necessities including straws, bags, and cups were prepared by adhering cellulose films, and smart devices like actuators and supercapacitors assembled by adhering hydrogels were also demonstrated. In addition, the composite boards bonded with natural biomass wastes, such as wood chips, displayed significantly stronger mechanical properties than the natural wood or commercial composite boards. Cellulose aqueous adhesives provide a straightforward, feasible, renewable, and inventive bonding technique for material shaping and the creation of multipurpose devices.

Identification of a membrane-associated element (MAE) in the C-terminal region of SARS-CoV-2 nsp6 that is essential for viral replication.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has rapidly spread worldwide since its emergence in late 2019. Its ongoing evolution poses challenges for antiviral drug development. Coronavirus nsp6, a multiple-spanning transmembrane protein, participates in the biogenesis of the viral replication complex, which accommodates the viral replication-transcription complex. The roles of its structural domains in viral replication are not well studied. Herein, we predicted the structure of the SARS-CoV-2 nsp6 protein using AlphaFold2 and identified a highly folded C-terminal region (nsp6C) downstream of the transmembrane helices. The enhanced green fluorescent protein (EGFP)-fused nsp6C was found to cluster in the cytoplasm and associate with membranes. Functional mapping identified a minimal membrane-associated element (MAE) as the region from amino acids 237 to 276 (LGV-KLL), which is mainly composed of the α-helix H1 and the α-helix H2; the latter exhibits characteristics of an amphipathic helix (AH). Mutagenesis studies and membrane flotation experiments demonstrate that AH-like H2 is required for MAE-mediated membrane association. This MAE was functionally conserved across MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63, all capable of mediating membrane association. In a SARS-CoV-2 replicon system, mutagenesis studies of H2 and replacements of H1 and H2 with their homologous counterparts demonstrated requirements of residues on both sides of the H2 and properly paired H1-H2 for MAE-mediated membrane association and viral replication. Notably, mutations I266A and K274A significantly attenuated viral replication without dramatically affecting membrane association, suggesting a dual role of the MAE in viral replication: mediating membrane association as well as participating in protein-protein interactions.IMPORTANCESevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) assembles a double-membrane vesicle (DMV) by the viral non-structural proteins for viral replication. Understanding the mechanisms of the DMV assembly is of paramount importance for antiviral development. Nsp6, a multiple-spanning transmembrane protein, plays an important role in the DMV biogenesis. Herein, we predicted the nsp6 structure of SARS-CoV-2 and other human coronaviruses using AlphaFold2 and identified a putative membrane-associated element (MAE) in the highly conserved C-terminal regions of nsp6. Experimentally, we verified a functionally conserved minimal MAE composed of two α-helices, the H1, and the amphipathic helix-like H2. Mutagenesis studies confirmed the requirement of H2 for MAE-mediated membrane association and viral replication and demonstrated a dual role of the MAE in viral replication, by mediating membrane association and participating in residue-specific interactions. This functionally conserved MAE may serve as a novel anti-viral target.

Prevalence of Neutralizing Autoantibodies Against Type I Interferon in a Multicenter Cohort of Severe or Critical COVID-19 Cases in Shanghai.

OBJECTIVE: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2. METHODS: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted. RESULTS: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts. CONCLUSION: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.

Methyl rosmarinate is an allosteric inhibitor of SARS-CoV-2 3 CL protease as a potential candidate against SARS-cov-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a new approach by integrating the experimental assay, virtual screening, and the experimental verification, exploring the rapid discovery of active ingredients from TCM prescriptions. To achieve this goal, 4 TCM prescriptions in clinical use for different indications were selected to find the antiviral active ingredients in TCMs. The 3-chymotrypsin-like protease (3CLpro), an important target for fighting COVID-19, was utilized to determine the inhibitory activity of the TCM prescriptions and single herb. It was found that 10 single herbs had better inhibitory activity than other herbs by using a fluorescence resonance energy transfer (FRET) - based enzymatic assay of SARS-CoV-2 3CLpro. The ingredients contained in 10 herbs were thus virtually screened and the predicted active ingredients were experimentally validated. Thus, such a research strategy firstly removed many single herbs with no inhibitory activity against SARS-CoV-2 3CLpro at the very beginning by FRET-based assay, making our subsequent virtual screening more effective. Finally, 4 active components were found to have stronger inhibitory effects on SARS-CoV-2 3CLpro, and their inhibitory mechanism was subsequently investigated. Among of them, methyl rosmarinate as an allosteric inhibitor of SARS-CoV-2 3CLpro was confirmed and its ability to inhibit viral replication was demonstrated by the SARS-CoV-2 replicon system. To validate the binding mode via docking, the mutation experiment, circular dichroism (CD), enzymatic inhibition and surface plasmon resonance (SPR) assay were performed, demonstrating that methyl rosmarinate bound to the allosteric site of SARS-CoV-2 3CLpro. In conclusion, this paper provides the new ideas for the rapid discovery of active ingredients in TCM prescriptions based on a specific target, and methyl rosmarinate has the potential to be developed as an antiviral therapeutic candidate against SARS-CoV-2 infection.

Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma.

Multiple myeloma (MM), a stage-developed plasma cell malignancy, evolves from monoclonal gammopathy of undetermined significance (MGUS) or smoldering MM (SMM). Emerging therapies including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, chimeric antigen-T/natural killer (NK) cells, bispecific T-cell engagers, selective inhibitors of nuclear export, and small-molecule targeted therapy have considerably improved patient survival. However, MM remains incurable owing to inevitable drug resistance and post-relapse rapid progression. NK cells with germline-encoded receptors are involved in the natural evolution of MGUS/SMM to active MM. NK cells actively recognize aberrant plasma cells undergoing malignant transformation but are yet to proliferate during the elimination phase, a process that has not been revealed in the immune editing theory. They are potential effector cells that have been neglected in the therapeutic process. Herein, we characterized changes in NK cells regarding disease evolution and elucidated its role in the early clinical monitoring of MM. Additionally, we systematically explored dynamic changes in NK cells from treated patients who are in remission or relapse to explore future combination therapy strategies to overcome drug resistance.

Astragaloside IV induces endothelial progenitor cell angiogenesis in deep venous thrombosis through inactivation of PI3K/AKT signaling.

BACKGROUND: Deep vein thrombosis (DVT), referred to as venous thromboembolism, is the third most frequent cardiovascular disease. Endothelial progenitor cells (EPCs) contribute to the recanalization of DVT. Astragaloside IV (AS-IV) has been suggested to have angiogenesis-enhancing effects. Here, we investigate the roles and mechanisms of AS-IV in EPCs and DVT. METHODS: The experimental DVT model was established by inferior vena cava stenosis in rats. EPCs were collected from patients with DVT. Transwell assays were performed to detect cell migration. Tube formation was determined using Matrigel basement membrane matrix and ImageJ software. The thrombus weight and length were measured. Pathological changes were examined by hematoxylin-eosin staining. The production of proinflammatory cytokines was estimated by ELISA. The level of PI3K/AKT-related proteins was measured by western blotting. RESULTS: AS-IV administration facilitated the migrative and angiogenic functions of human EPCs in vitro. Additionally, AS-IV inhibited thrombosis and repressed the infiltration of leukocytes into the thrombus and the production of proinflammatory cytokines in rats. Mechanistically, AS-IV inactivated PI3K/AKT signaling in rats. CONCLUSION: AS-IV prevents thrombus in an experimental DVT model by facilitating EPC angiogenesis and decreasing inflammation through inactivation of PI3K/AKT signaling.

Zika virus infection triggers caspase cleavage of STAT1.

IMPORTANCE: Zika virus (ZIKV) is a re-emerging flavivirus. Similar to other flaviviruses, ZIKV antagonizes the host interferon (IFN) signaling pathway to establish infection. Understanding the molecular mechanism by which ZIKV antagonizes IFN-induced antiviral signaling may lead to a new antiviral strategy by cracking the IFN antagonism. Flaviviruses have been reported to employ NS5-dependent and -independent mechanisms to block STAT2-mediated signaling, whereas whether flaviviruses target STAT1 remains controversial. Herein, we found that ZIKV infection triggered caspase-dependent cleavage of STAT1 at the aspartic acid 694 during late infection, whereas murine STAT1 (mSTAT1) was resistant to cleavage. Intriguingly, ectopically expressed cleavage-resistant human STAT1.D694A or complementation of cleavable mSTAT1.D695G exerted comparable anti-ZIKV activity with their counterparts, challenging the role of caspase-mediated STAT1 cleavage in the IFN antagonism in ZIKV-infected cells. These data may also imply a dominant role of the antagonism of STAT2 but not STAT1 in ZIKV-infected cells.

Gut microbiota deficiency ameliorates multiple myeloma and myeloma-related bone disease by Th17 cells in mice models.

Purpose: Multiple myeloma, the second most common hematological tumor, is currently incurable. Multiple myeloma-related bone disease is a characteristic clinical symptom that seriously affects the survival and prognosis of patients. In recent years, gut microbiota has been shown to play an important role in the occurrence and development of multiple myeloma. However, whether and how it affects the development of myelomatous bone disease is unclear. Methods: To investigate the mechanism and influence of the microbiota on multiple myeloma and myeloma bone disease, a myeloma-gut microbiota deletion mice model was established. 16S rRNA sequencing was used to analysis of bacterial flora changes. Histochemical staining and bone micro-CT were used to assess the severity of bone disease. Bone marrow tumor load and spleen Th17 cells were detected by flow cytometry. Results: Histochemical staining revealed a reduced tumor burden after eliminating gut microbial communities in mice by administering a mixture of antibiotics. According to the 16S rRNA sequencing of intestinal contents, antibiotic treatment resulted in a significant change in the microbiota of the mice. Bone micro-CT demonstrated that antibiotic treatment could reduce bone lesions caused by myeloma while increasing mineral density, bone volume fraction, trabecular bone thickness, and trabecular number. Meanwhile, histochemical staining of the bone found that the enhanced bone resorption was weakened by the change of flora. These results were consistent with the concentration of IL17 in serum and the frequency of Th17 cells in spleen. Conclusions: Herein, the effects of the gut microbiome on myeloma bone disease are investigated for the first time, providing new insight into its pathogenesis and suggesting that gut microbiota may serve as a therapeutic target in multiple myeloma-associated bone diseases.

FeS and Fe3O4 Co-modified biochar to build a highly resistant advanced oxidation process system for quinclorac degradation in irrigation water.

Advanced oxidation processes (AOPs), based on sulfate radical (SO4·-) produced by peroxymonosulfate (PMS), can effectively mineralize refractory organic pollutants. However, the coexistence of anions and natural organic matters in actual wastewater prevents the application of AOPs. A simple one-step method was used to prepare FeS/Fe3O4 co-modified biochar materials (FFB) that could activate PMS to degrade quinclorac (QNC) with a removal rate of 100%, even exhibiting optimum degradation of QNC reached 99.31% in irrigation water, demonstrating excellent anti-interference performance for co-existing anions and natural organic matter. Meanwhile, ecotoxicity analysis showed that the toxicity of degradation intermediates was lower than that of QNC. Characterization results demonstrated the even distribution of FeS and Fe3O4 onto biochar, supplying abundant Fe2+ to activate PMS producing reactive oxygen species (ROS), while the generated Fe3+ after reactive continue to be reduced with sulfur species to promote the cycle of Fe2+/Fe3+. The coexistence of ·OH, SO4·-, 1O2, and O2·- in the FFB/PMS-QNC system suggest the possession of two pathway with free radical and non-free radical pathways to degrade QNC. The density functional theory (DFT) was used to analyze the adsorption sites and adsorption energy of PMS, as well as the differential charge density, which further proved the generation of SO4·-, O2·- and 1O2. In addition, the electrochemical test results showed that electron transfer also played an important role in the degradation of QNC. This study provides a feasible approach for the removal of organic pollutants in actual water.

Hg2+-triggered cascade strand displacement assisted CRISPR-Cas12a for Hg2+ quantitative detection using a portable glucose meter.

CRISPR-Cas12a is a powerful and programmable tool that has revolutionized the field of biosensing. However, the construction of a CRISPR-Cas12a-mediated portable system for on-site and quantitative detection of mercury ion (Hg2+) has yet to be explored. By integrating a target-triggered cascade toehold-mediated strand displacement reaction (TSDR) and CRISPR-Cas12a, we herein construct a portable on-site biosensor for the quantitative, sensitive, and selective detection of Hg2+ with a glucose meter. The Hg2+ initiates two cascade TSDRs through the T-Hg2+-T interaction to produce multiple double-stranded DNAs that can activate Cas12a's trans-cleavage activity. The Cas12a cleaves the sucrase-modified DNA on the electrode, resulting in the liberation of sucrase into the solution. The freed sucrase can catalyze sucrose to generate glucose, which can be quantitatively monitored by a glucometer. The developed portable biosensor provides a dynamic range of 5 orders of magnitude with a detection limit of 40 fM. This biosensor also displays excellent selectivity and stability for detecting Hg2+. Moreover, environmental water samples are utilized to further verify the robustness and effectiveness of the developed biosensor, highlighting its potential application in environmental monitoring and food safety analysis.

Obesity as a risk factor for multiple myeloma: insight on the role of adipokines.

Multiple myeloma (MM) is a hematologic disorder characterized by the accumulation of malignant plasma cells in the bone marrow. Genetic and environmental factors are contributed to the etiology of MM. Notably, studies have shown that obesity increases the risk of MM and worsens outcomes for MM patients. Adipokines play an important role in mediating the close association between MM and metabolic derangements. In this review, we summarize the epidemiologic studies to show that the risk of MM is increased in obese. Accumulating clinical evidence suggests that adipokines could display a correlation with MM. In vitro and in vivo studies have shown that adipokines are linked to MM, including roles in the biological behavior of MM cells, cancer-associated bone loss, the progression of MM, and drug resistance. Current and potential therapeutic strategies targeted to adipokines are discussed, proposing that adipokines can guide early patient diagnosis and treatment.

BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.

The bromodomain and extra-terminal (BET) proteins act as "readers" for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes. BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2, and is involved in the regulation of cell cycle and apoptosis. Meanwhile, BET inhibitors (BETi) have regulatory effects on immune checkpoints, immune cells, and cytokine expression. The role of BET proteins and BETi in a variety of tumors has been studied. This paper reviews the recent research progress of BET and BETi in hematologic tumors (mainly leukemia, lymphoma and multiple myeloma) from cellular level studies, animal studies, clinical trials, drug combination, etc. BETi has a promising future in hematologic tumors, and future research directions may focus on the combination with other drugs to improve the efficacy.

LGR4 promotes tumorigenesis by activating TGF-ß1/Smad signaling pathway in multiple myeloma.

Multiple myeloma (MM) is a common hematologic malignancy that remains incurable. Although accumulating evidence suggests that the leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays a biological function in a variety of cancers, its biological function and molecular mechanisms in MM are unclear. In the present study, we found that LGR4 was significantly upregulated in MM tissues and cells. In vitro and in vivo experiments showed that knockdown of LGR4 significantly inhibited proliferation of MM cells, promoted apoptosis and arrested cell cycle in G1. Overexpression showed the opposite effect. Mechanistic studies revealed that LGR4 could interact with TGF-ß1 and regulate TGF-ß1 expression, thereby activating the TGF-ß1/Smad signaling pathway and promoting MM progression. LGR4 may be a potential new target for MM diagnosis and treatment.

Transient interaction effects of temperature and light intensity on isoprene and monoterpene emissions from Schima superba and Phoebe bournei.

Biogenic volatile organic compound (BVOC) (such as isoprene (ISO) and monoterpenes (MTs)) emissions from plants play a great role in the atmospheric chemistry. Now frequency of dramatic changes of weather such as transient temperature changing increases, most current studies focus on the effects of simulating climate change (long-term) on BVOC emissions. While studies of transient effects on that are less reported. This study aimed to identify the ISO and MT emissions and the related physiological processes in the short-term scale at different temperature (T) and light intensity (PAR), in seeding stage of Schima superba and Phoebe bournei belonging to typical subtropical tree species. The results showed that the ISO and MT emissions were significantly affected by T and PAR, either independently or interactively. With the increase of T and PAR, the ISO and MT emissions increased, with the maximum rates of ISO and MTs of 39.39 and 1042.35 pmol m-2 s-1 for S. superba under 40 °C × 500 µmol m-2 s-1 condition, while the maximum rates reached 18.73 and 6737.41 pmol m-2 s-1 at 30 °C × 1500 µmol m-2 s-1 for P. bournei. The increase of ISO and MT emissions with T and PAR increasing that was related to the promotion of Pn and gs in plants. Regarding MT components, the proportion of α-pinene decreased with T and PAR increasing, with the lowest ratios of 4.91 % and 21.16 % for S. superba and P. bournei under 40 °C × 1500 µmol m-2 s-1 condition. However, the proportion of ß-pinene significantly increased, with the highest ratios of 67.42 % and 57.93 % for S. superba and P. bournei under 30 °C × 1500 µmol m-2 s-1 condition, which is attributed to differences in light tolerance between the two plants. Our study provides basis for evaluating the transient changes of environmental factors on BVOC emissions and optimizing regional BVOC emission models.

High-Resolution Genomic Profiling of a Genotype 3b Hepatitis C Virus from a Flare of an Occult Hepatitis Patient with Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is defined as a syndrome of acutely decompensated cirrhosis in patients with chronic liver disease (CLD). Here we report an ACLF case caused by a flare of occult hepatitis C infection. This patient was infected with hepatitis C virus (HCV) more than a decade ago and hospitalized due to alcohol-associated CLD. Upon admission, the HCV RNA in the serum was negative and the anti-HCV antibody was positive, whereas the viral RNA in the plasma dramatically increased during hospitalization, which suggests an occult hepatitis C infection. Overlapped fragments encompassing the nearly whole HCV viral genome were amplified, cloned, and sequenced. Phylogenetic analysis indicated an HCV genotype 3b strain. Sanger sequencing to 10-fold coverage of the 9.4-kb nearly whole genome reveals high diversity of viral quasispecies, an indicator of chronic infection. Inherent resistance-associated substitutions (RASs) in the NS3 and NS5A but not in the NS5B regions were identified. The patient developed liver failure and accepted liver transplantation, followed by direct-acting antiviral (DAA) treatment. The hepatitis C was cured by the DAA treatment despite the existence of RASs. Thus, care should be taken for occult hepatitis C in patients with alcoholic cirrhosis. The analysis of viral genetic diversity may help to identify an occult hepatitis C virus infection and predict the efficacy of anti-viral treatment.

Illuminating the Live-Cell Dynamics of Hepatitis B Virus Covalently Closed Circular DNA Using the CRISPR-Tag System.

The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major obstacle to curing chronic hepatitis B (CHB). Current cccDNA detection methods are mostly based on biochemical extraction and bulk measurements. They nevertheless generated a general sketch of its biological features. However, an understanding of the spatiotemporal features of cccDNA is still lacking. To achieve this, we established a system combining CRISPR-Tag and recombinant HBV minicircle technology to visualize cccDNA at single-cell level in real time. Using this system, we found that the observed recombinant cccDNA (rcccDNA) correlated quantitatively with its active transcripts when a low to medium number of foci (<20) are present, but this correlation was lost in cells harboring high copy numbers (≥20) of rcccDNA. The disruption of HBx expression seems to displace cccDNA from the dCas9-accessible region, while HBx complementation restored the number of observable cccDNA foci. This indicated regulation of cccDNA accessibility by HBx. Second, observable HBV and duck HBV (DHBV) cccDNA molecules are substantially lost during cell division, and the remaining ones were distributed randomly to daughter cells. In contrast, Kaposi's sarcoma-associated herpesvirus (KSHV)-derived episomes can be retained in a LANA (latency-associated nuclear antigen)-dependent manner. Last, the dynamics of rcccDNA episomes in nuclei displayed confined diffusion at short time scales, with directional transport over longer time scales. In conclusion, this system enables the study of physiological kinetics of cccDNA at the single-cell level. The differential accessibility of rcccDNA to dCas9 under various physiological conditions may be exploited to elucidate the complex transcriptional and epigenetic regulation of the HBV minichromosome. IMPORTANCE Understanding the formation and maintenance of HBV cccDNA has always been a central issue in the study of HBV pathobiology. However, little progress has been made due to the lack of robust assay systems and its resistance to genetic modification. Here, a live-cell imaging system by grafting CRISPR-Tag into the recombinant cccDNA was established to visualize its molecular behavior in real time. We found that the accessibility of rcccDNA to dCas9-based imaging is related to HBx-regulated mechanisms. We also confirmed the substantial loss of observable rcccDNA in one-round cell division and random distribution of the remaining molecules. Molecular dynamics analysis revealed the confined movement of the rcccDNA episome, suggesting its juxtaposition to chromatin domains. Overall, this novel system offers a unique platform to investigate the intranuclear dynamics of cccDNA within live cells.

PAM-free cascaded strand displacement coupled with CRISPR-Cas12a for amplified electrochemical detection of SARS-CoV-2 RNA.

The early diagnosis of coronavirus disease 2019 (COVID-19) is dependent on the specific and sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Herein, we develop a highly sensitive and specific electrochemical biosensor for SARS-CoV-2 target RNA detection based on the integration of protospacer adjacent motif (PAM)-free cascaded toehold-mediated strand displacement reaction (TSDR) and CRISPR-Cas12a (PfTSDR-CRISPR). In this study, each target is transformed into multiple DNA substrates with bubble structure in the seed region by the cascaded TSDR, which can directly hybridize with guide RNA (gRNA) without PAM requirement and then activate CRISPR-Cas12a's trans-cleavage activity. Subsequently, the hairpin DNA modified with methylene blue (MB-HP) is cleaved by activated CRISPR-Cas12a. Therefore, as MB leaves the electrode surface, a decreased current signal is obtained. With the involvement of PAM-free cascaded TSDRs and CRISPR-Cas12a amplification strategy, the PfTSDR-CRISPR-based electrochemical biosensor achieves the detection of target RNA as low as 40 aM. The biosensor has high sequence specificity, reliability and robustness. Thanks to the PAM-free cascaded TSDR, the biosensor can achieve universal detection of different target RNA without redesigning gRNA sequence of CRISPR-Cas12a. In addition, this biosensor successfully detects SARS-CoV-2 target RNA in complex samples, which highlights its potential for diagnosing COVID-19.

NORAD promotes multiple myeloma cell progression via BMP6/P-ERK1/2 axis.

Multiple myeloma (MM) is one of the most common tumors of the hematological system and remains incurable. Recent studies have shown that long noncoding RNA NORAD is a potential oncogene in a variety of tumors. However, the general biological role and clinical value of NORAD in MM remains unknown. In this study, we measured NORAD expression in bone marrow of 60 newly diagnosed MM, 30 post treatment MM and 17 healthy donors by real-time quantitative polymerase chain reaction (qPCR). The NORAD gene was knockdown by lentiviral transfection in MM cell lines, and the effects of NORAD on apoptosis, cell cycle and cell proliferation in MM cells were examined by flow cytometry, CCK8 assay, EDU assay and Western blot, and the differential genes after knockdown of NORAD were screened by mRNA sequencing, followed by in vivo experiments and immunohistochemical assays. We found that knockdown of NORAD promoted MM cell apoptosis, induced cell cycle G1 phase arrest, and inhibited MM cell apoptosis in in vivo and in vitro experiments. Mechanistically, NORAD plays these roles through the BMP6/P-ERK1/2 axis. We discuss a novel mechanism by which NORAD acts pro-tumorigenically in MM via the BMP6/P-ERK1/2 axis.

The yin-yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma.

Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules.

An Overview of the Isoprenoid Emissions From Tropical Plant Species.

Terrestrial vegetation is the largest contributor of isoprenoids (a group of biogenic volatile organic compounds (BVOCs)) to the atmosphere. BVOC emission data comes mostly from temperate regions, and less is known about BVOC emissions from tropical vegetation, even though it is estimated to be responsible for >70% of BVOC emissions. This review summarizes the available data and our current understanding of isoprenoid emissions from tropical plant species and the spatial and temporal variation in emissions, which are strongly species-specific and regionally variable. Emission models lacking foliar level data for tropical species need to revise their parameters to account for seasonal and diurnal variation due to differences in dependencies on temperature and light of emissions from plants in other ecosystems. More experimental information and determining how emission capacity varies during foliar development are warranted to account for seasonal variations more explicitly.