A vicinal oxygen chelate protein facilitates viral infection by triggering the unfolded protein response in Nicotiana benthamiana.

Vicinal oxygen chelate (VOC) proteins are members of an enzyme superfamily with dioxygenase or non-dioxygenase activities. However, the biological functions of VOC proteins in plants are poorly understood. Here, we show that a VOC in Nicotiana benthamiana (NbVOC1) facilitates viral infection. NbVOC1 was significantly induced by infection by beet necrotic yellow vein virus (BNYVV). Transient overexpression of NbVOC1 or its homolog from Beta vulgaris (BvVOC1) enhanced BNYVV infection in N. benthamiana, which required the nuclear localization of VOC1. Consistent with this result, overexpressing NbVOC1 facilitated BNYVV infection, whereas, knockdown and knockout of NbVOC1 inhibited BNYVV infection in transgenic N. benthamiana plants. NbVOC1 interacts with the basic leucine zipper transcription factors bZIP17/28, which enhances their self-interaction and DNA binding to the promoters of unfolded protein response (UPR)-related genes. We propose that bZIP17/28 directly binds to the NbVOC1 promoter and induces its transcription, forming a positive feedback loop to induce the UPR and facilitating BNYVV infection. Collectively, our results demonstrate that NbVOC1 positively regulates the UPR that enhances viral infection in plants.

Biological characteristics of molecular subtypes of ulcerative colitis characterized by ferroptosis and neutrophil infiltration.

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.

Increased Nasal Blimp1 + Treg Cells After Sublingual Immunotherapy Reflect the Efficacy of Treatment in Allergic Rhinitis.

INTRODUCTION: Allergen-specific immunotherapy (AIT) plays a pivotal role in altering the immune status and tissue responses in allergic rhinitis (AR). This study focuses on the impact of sublingual immunotherapy (SLIT) involving dust mite drops, exploring the modulation of regulatory T cells (Treg) and their specific marker, BLIMP1, in the nasal mucosa. METHODS: Immune cells were isolated from nasal lavage fluid of patients with AR undergoing SLIT (n = 94). Treg cells were analyzed for BLIMP1 expression, and chemokine levels associated with Treg recruitment were assessed using Luminex assay. Patients were categorized on the basis of SLIT efficacy and followed for changes after discontinuation. RESULTS: SLIT induced a significant increase in nasal Treg cells (7.09 ± 2.59% vs. 0.75 ± 0.27%, P < 0.0001). BLIMP1 expression in Treg cells notably increased after SLIT (0.36 ± 0.22% to 16.86 ± 5.74%, P < 0.0001). Ineffective SLIT cases exhibited lower levels of nasal Treg and Blimp1 + Treg cells (both P < 0.0001). Receiver operating characteristic (ROC) analysis confirmed their potential as efficacy predictors (AUC = 0.908 and 0.968, respectively). SLIT discontinuation led to a significant reduction in Treg and Blimp1 + Treg cells (P < 0.001), emphasizing their maintenance during treatment. Pro-inflammatory cytokines decreased (P < 0.001), while CCL2 associated with Treg recruitment increased (P = 0.0015). CONCLUSION: Elevated nasal Blimp1 + Treg cells serve as a predictive biomarker for SLIT responsiveness in pediatric AR. Their influence on immunotherapy effectiveness contributes to a nuanced understanding of SLIT mechanisms, allowing for disease stratification and personalized treatment plans. This study offers scientific support for predicting SLIT efficacy, enhancing the prospects of improved treatment outcomes in AR.

Identification of Key Ubiquitination-Related Genes and Their Association with Immune Infiltration in Osteoarthritis Based on the mRNA-miRNA Network.

Osteoarthritis (OA) is a prevalent degenerative joint disease that is closely associated with functions of ubiquitination and immune cells, yet the mechanism remains ambiguous. This study aimed to find core ubiquitination-related genes and their correlative immune infiltration in OA using weighted gene co-expression network analysis (WGCNA). The ubiquitination-related genes, datasets GSE55235 and GSE143514 were obtained from open databases. WGCNA got used to investigate key co-expressed genes. Then, we screened differentially expressed miRNAs by "limma" package in R, and constructed mRNA-miRNA network. We conducted function enrichment analysis on the identified genes. CIBERSORT was then utilized to analyze the relevance between immune infiltration and genes. Lastly, RT-qPCR was further used to verify the prediction of bioinformatics. A sum of 144 ubiquitination-related genes in OA were acquired. Enrichment analysis indicated that obtained genes obviously involved in mTOR pathway to regulate the OA development. GRB2 and SEH1L and L-arginine synergistically regulate the mTOR signaling pathway in OA. Moreover, GRB2 and SEH1L were remarkably bound up with immune cell infiltration. Additionally, GRB2 expression was upregulated and SEH1L level was downregulated in the OA development by RT-qPCR experiment. The present study identified GRB2 and SEH1L as key ubiquitination-related genes which were involved in immune infiltration in OA patients, thereby providing new drug targets for OA.

Development of full-length infectious cDNA clones and host range identification of an echinacea strain of tobacco streak virus.

Tobacco streak virus induces severe diseases on a wide range of plants and becomes an emerging threat to crop yields. However, the infectious clones of TSV remain to be developed for reverse genetics studies. Here, we obtained the full genome sequence of a TSV-CNB isolate and analyzed the phylogenetic characteristics. Subsequently, we developed the full-length infectious cDNA clones of TSV-CNB driven by 35 S promoter using yeast homologous recombination. Furthermore, the host range of TSV-CNB isolate was determined by Agrobacterium infiltration and mechanical inoculation. The results reveal that TSV-CNB can infect 10 plant species in 5 families including Glycine max, Vigna radiate, Lactuca sativa var. Ramosa, Dahlia pinnate, E. purpurea, Calendula officinalis, Helianthus annuus, Nicotiana. Benthamiana, Nicotiana tabacum and Chenopodium quinoa. Taken together, the TSV infectious clones will be a useful tool for future studies on viral pathogenesis and host-virus interactions.

Relationship between Fear-Avoidance Beliefs and Reaction Time Changes Prior to and following Exercise-Induced Muscle Fatigue in Chronic Low Back Pain.

Background: Reaction time is a reliable indicator of the velocity and efficiency of neuromuscular control and may be associated with fear-avoidance beliefs. However, the effect of exercise-induced muscle fatigue on reaction time in chronic low back pain (cLBP) and its relationship with fear-avoidance beliefs remains poorly understood. Objectives: This study aimed to reveal the relationship between fear-avoidance beliefs and reaction time changes before and after exercise-induced muscle fatigue in cLBP. Methods: Twenty-five patients with cLBP were tested by the Biering-Sorensen test (BST) to induce exhaustive muscle fatigue. Total reaction time (TRT), premotor time (PMT), and electromechanical delay (EMD) of dominated deltoid muscle were recorded by surface electromyography during the arm-raising task with visual cues before and after muscle fatigue. The mean difference (MD) of TRT (MDTRT), PMT (MDPMT), and EMD (MDEMD) was calculated from the changes before and after muscle fatigue. Fear-avoidance beliefs questionnaire (FABQ) was applied to evaluate fear-avoidance beliefs before muscle fatigue. In addition, the duration time of BST was recorded for each subject. Results: TRT and PMT of dominated deltoid muscle were prolonged after exercise-induced muscle fatigue (Z = 3.511, p < 0.001; t = 3.431, p = 0.001), while there was no statistical difference in EMD (Z = 1.029, p = 0.304). Correlation analysis showed that both the MDTRT and MDPMT were positively correlated with FABQ (r = 0.418, p = 0.042; r = 0.422, p = 0.040). Conclusions: These findings suggested that we should pay attention to both muscle fatigue-induced reaction time delay in cLBP management and the possible psychological mechanism involved in it. Furthermore, this study implied that FABQ-based psychotherapy might serve as a potential approach for cLBP treatment by improving reaction time delay. This trial is registered with ChiCTR2300074348.

The warming-up effects of quantum-dot light emitting diodes: A reversible stability issue related to shell traps.

The aging phenomenon is commonly observed in quantum-dot light emitting diodes (QLEDs), involving complex chemical or physical processes. Resolving the underlying mechanism of these aging issues is crucial to deliver reliable electroluminescent devices in future display applications. Here, we report a reversible positive aging phenomenon that the device brightness and efficiency significantly improve after device operation, but recover to initial states after long-time storage or mild heat treatment, which can be termed as warming-up effects. Steady and transient equivalent circuit analysis suggest that the radiative recombination current dramatically increases but electron leakage from the quantum dots (QDs) to hole transport layer becomes more accessible during the warming-up process. Further analysis discloses that the notable enhancement of device efficiency can be ascribed to the filling of shell traps in gradient alloyed QDs. This work reveals a distinct positive aging phenomenon featured with reversibility, and further guidelines would be provided to achieve stable QLED devices in real display applications.

Soluble dietary fibers from solid-state fermentation of wheat bran by the fungus Cordyceps cicadae and their effects on colitis mice.

Ulcerative colitis is a chronic inflammatory disease with a complex pathogenesis for which there is no definitive therapeutic agent. Fermentation, as a green and efficient bioprocessing technique, has been shown to enhance the biological activity of food ingredients. Soluble dietary fiber isolated from plants is thought to have the potential to prevent and alleviate ulcerative colitis. This work was designed to study the differences in the chemical properties of the soluble dietary fiber from wheat bran fermented by Isaria cicadae Miq. (FSDF) and the unfermented soluble dietary fiber from wheat bran (UFSDF) and their effects on colitis mice. The results showed that FSDF and UFSDF differed in molecular weight, monosaccharide compositions, and surface morphology. In addition, supplementation with UFSDF and FSDF ameliorated the symptoms of DSS-induced colitis in mice by attenuating body weight loss, decreasing the disease activity index and splenic index, shortening the length of the colon, and attenuating colonic tissue damage. UFSDF and FSDF also increased the production of the anti-inflammatory cytokine IL-10 and inhibited the expression of IL-6, IL-1ß, and TNF-α. The results of gut flora and short-chain fatty acid analyses showed that UFSDF and FSDF improved the diversity of gut microbiota, up-regulated the abundance of some beneficial bacteria such as Akkermansia and Muribaculaceae, increased the levels of acetic acid, propionic acid, and butyric acid, and restored dextran sodium sulfate (DSS)-induced dysbiosis of the intestinal flora in mice. These findings provide guidance for the development of FSDF and UFSDF as functional foods for the relief of ulcerative colitis.

Risk assessment and prevention of urolithiasis in urban areas of Baoding, China.

Urolithiasis, or the formation of calculi in the urinary system, represents a prevalent urological condition frequently encountered among individuals aged 30 to 55 years. An in-depth analysis of the composition of these calculi holds significant promise in shedding light on the underlying etiological and pathogenic factors contributing to this ailment. The primary objective of this study was to delineate the principal components comprising urinary system calculi within a cohort of patients who sought medical intervention at a tertiary grade A hospital located in Baoding City. Furthermore, our investigation entailed a comprehensive examination of the physical and morphological characteristics exhibited by these calculi. In this study, a total of 2307 individuals afflicted with urinary system calculi were recruited as participants, and a corresponding number of 2307 calculous specimens were subjected to thorough examination. The specimens were examined using infrared spectroscopy. We collected and examined patient data including gender, age, location of the calculi, employment status, residential area, and other factors. The middle-aged demographic exhibited a conspicuous predilection for urinary system calculi, wherein a notable gender disparity was observed, with a male-to-female ratio of 1.63 to 1. Among the enrolled patients, kidney calculi were prevalent in 1270 cases, ureteral calculi were documented in 983 cases, and bladder calculi were encountered in 46 instances. Notably, the principal components comprising these calculi were identified as calcium oxalate and apatite, while uric acid and ammonium magnesium phosphate were comparatively less frequently encountered. Furthermore, the analysis of calculus composition across patients residing in distinct geographical regions did not reveal any statistically significant variations. The identification of components within upper urinary tract calculi plays a pivotal role in elucidating the root causes of calculus formation. This valuable information empowers healthcare professionals, particularly nursing staff, to provide personalized dietary and health guidance to patients, thereby enhancing the quality of care and promoting more effective management of this condition.

Effect of Echinacea purpurea (L.) Moench and its extracts on the immunization outcome of avian influenza vaccine in broilers.

ETHNOPHARMACOLOGICAL RELEVANCE: Echinacea purpurea (L.) Moench (EP) is a perennial herbaceous flowering plant with immunomodulatory effects. However, the immunomodulatory effects of EP on broilers after vaccination are still unclear. AIM OF THE STUDY: The aim is to study the effect of EP and Echinacea purpurea (L.) Moench extracts(EE) on avian influenza virus (AIV) immunity, and further explore the potential mechanism of immune regulation. MATERIALS AND METHODS: Broilers were fed with feed additives containing 2% EP or 0.5% EE, and vaccinated against avian influenza. The samples were collected on the 7th, 21st, and 35th day after vaccination, and the feed conversion ratio (FCR) was calculated. Blood antibody titer, jejunal sIgA content, tight junction protein, gene and protein expression of TLR4-MAPK signaling pathway were also detected. RESULTS: The results showed that vaccination could cause immune stress, weight loss, increase sIgA content, and up-regulate the expression of tight junction proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1, as well as the genes of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), receptor-associated factor 6 (TRAF6), activator protein 1 (AP-1) protein gene expression on TLR4-mitogen-activated protein kinase (MAPK) signaling pathway, and the protein expression of MyD88, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). EP and EE could increase the body weight of broilers, further improve antibody titers, decrease FCR, increase sIgA levels, up-regulate the expression of tight junction proteins, including ZO-1, Occludin, and Claudin-1, as well as the genes of TLR4, MyD88, TRAF6, and AP-1 and the protein expression of MyD88, ERK, and JNK in the TLR4-MAPK signaling pathway. CONCLUSION: In conclusion, EP and EE can increase the broiler's production performance and improve vaccine immune effect through the TLR4-MAPK signaling pathway.

Short-term dietary choline supplementation alters the gut microbiota and liver metabolism of finishing pigs.

Choline is an essential nutrient for pig development and plays a role in the animal's growth performance, carcass characteristics, and reproduction aspects in weaned pigs and sows. However, the effect of choline on finishing pigs and its potential regulatory mechanism remains unclear. Here, we feed finishing pigs with 1% of the hydrochloride salt of choline, such as choline chloride (CHC), under a basic diet condition for a short period of time (14 days). A 14-day supplementation of CHC significantly increased final weight and carcass weight while having no effect on carcass length, average backfat, or eye muscle area compared with control pigs. Mechanically, CHC resulted in a significant alteration of gut microbiota composition in finishing pigs and a remarkably increased relative abundance of bacteria contributing to growth performance and health, including Prevotella, Ruminococcaceae, and Eubacterium. In addition, untargeted metabolomics analysis identified 84 differently abundant metabolites in the liver between CHC pigs and control pigs, of which most metabolites were mainly enriched in signaling pathways related to the improvement of growth, development, and health. Notably, there was no significant difference in the ability of oxidative stress resistance between the two groups, although increased bacteria and metabolites keeping balance in reactive oxygen species showed in finishing pigs after CHC supplementation. Taken together, our results suggest that a short-term supplementation of CHC contributes to increased body weight gain and carcass weight of finishing pigs, which may be involved in the regulation of gut microbiota and alterations of liver metabolism, providing new insights into the potential of choline-mediated gut microbiota/metabolites in improving growth performance, carcass characteristics, and health.

Genome-Wide Analysis of Q-Type C2H2 ZFP Genes in Response to Biotic and Abiotic Stresses in Sugar Beet.

A plant's Q-type C2H2-type ZFP plays key roles in plant growth and development and responses to biotic and abiotic stresses. Sugar beet (Beta vulgaris L.) is an important crop for sugar production. Salt stress and viral infection significantly reduce the root yield and sugar content of sugar beet. However, there is a lack of comprehensive genome-wide analyses of Q-type C2H2 ZFPs and their expression patterns in sugar beet under stress. In this study, 35 sugar beet Q-type C2H2 ZFPs (BvZFPs) containing at least one conserved "QALGGH" motif were identified via bioinformatics techniques using TBtools software. According to their evolutionary relationship, the BvZFPs were classified into five subclasses. Within each subclass, the physicochemical properties and motif compositions showed strong similarities. A Ka/Ks analysis indicated that the BvZFPs were conserved during evolution. Promoter cis-element analysis revealed that most BvZFPs are associated with elements related to phytohormone, biotic or abiotic stress, and plant development. The expression data showed that the BvZFPs in sugar beet are predominantly expressed in the root. In addition, BvZFPs are involved in the response to abiotic and biotic stresses, including salt stress and viral infection. Overall, these results will extend our understanding of the Q-type C2H2 gene family and provide valuable information for the biological breeding of sugar beet against abiotic and biotic stresses in the future.

Scutellarin Rescued Mitochondrial Damage through Ameliorating Mitochondrial Glucose Oxidation via the Pdk-Pdc Axis.

Mitochondrial bioenergetic deficits and their resulting glucose hypometabolism are the key pathophysiological modulators that promote neurodegeneration. However, there are no specific potential molecules that have been identified to treat neurological diseases by regulating energy metabolism and repairing mitochondrial damage. Pyruvate dehydrogenase (PDH) complex (PDC), which can be phosphorylated by pyruvate dehydrogenase kinase (PDK), is the gate-keeping enzyme for mitochondrial glucose oxidation. In this study, a small-molecule scutellarin (SG) is discovered that can significantly alleviate the neuropathological changes in hippocampal CA1 of cerebral hypoperfusion model rats, rescued the morphological changes of abnormal mitochondria, and restored mitochondrial homeostasis. Mitochondrial proteomics, energy metabolism monitoring, and 13 C-metabolic flux analysis targeted SG activity on PDK2, thus regulating PDK-PDC-mediated glycolytic metabolism to TCA cycle during mitochondrial OXPHOS damage. The knockdown of PDK2 in the SK-N-SH cells validated that SG could rescue mitochondrial damage via the PDK-PDC axis, promote the MMP level and reduce the mitochondria-dependent apoptosis. Collectively, this study explored the novel therapeutic approach: the PDK-PDC axis for neurological injury and cognitive impairment and uncovered the effect of SG on mitochondrial protection via the PDK-PDC axis and mitochondrial glucose oxidation. The findings indicate that active components ameliorating mitochondrial bioenergetic deficits could be of significant value for neurological disease therapy.

Integration of eQTL and machine learning to dissect causal genes with pleiotropic effects in genetic regulation networks of seed cotton yield.

The dissection of a gene regulatory network (GRN) that complements the genome-wide association study (GWAS) locus and the crosstalk underlying multiple agronomical traits remains a major challenge. In this study, we generate 558 transcriptional profiles of lint-bearing ovules at one day post-anthesis from a selective core cotton germplasm, from which 12,207 expression quantitative trait loci (eQTLs) are identified. Sixty-six known phenotypic GWAS loci are colocalized with 1,090 eQTLs, forming 38 functional GRNs associated predominantly with seed yield. Of the eGenes, 34 exhibit pleiotropic effects. Combining the eQTLs within the seed yield GRNs significantly increases the portion of narrow-sense heritability. The extreme gradient boosting (XGBoost) machine learning approach is applied to predict seed cotton yield phenotypes on the basis of gene expression. Top-ranking eGenes (NF-YB3, FLA2, and GRDP1) derived with pleiotropic effects on yield traits are validated, along with their potential roles by correlation analysis, domestication selection analysis, and transgenic plants.

Chemically bonded multi-nanolayer inorganic aerogel with a record-low thermal conductivity in a vacuum.

Inorganic aerogels have exhibited many superior characteristics with extensive applications, but are still plagued by a nearly century-old tradeoff between their mechanical and thermal properties. When reducing thermal conductivity by ultralow density, inorganic aerogels generally suffer from large fragility due to their brittle nature or weak joint crosslinking, while enhancing the mechanical robustness by material design and structural engineering, they easily sacrifice thermal insulation and stability. Here, we report a chemically bonded multi-nanolayer design and synthesis of a graphene/amorphous boron nitride aerogel to address this typical tradeoff to further enhance mechanical and thermal properties. Attributed to the chemically bonded interface and coupled toughening effect, our aerogels display a low density of 0.8 mg cm-3 with ultrahigh flexibility (elastic compressive strain up to 99% and bending strain up to 90%), and exceptional thermostability (strength degradation <3% after sharp thermal shocks), as well as the lowest thermal conductivities in a vacuum (only 1.57 mW m-1 K-1 at room temperature and 10.39 mW m-1 K-1 at 500°C) among solid materials to date. This unique combination of mechanical and thermal properties offers an attractive material system for thermal superinsulation at extreme conditions.

Effects of dietary L-Citrulline supplementation on growth performance, meat quality, and fecal microbial composition in finishing pigs.

Gut microbiota play an important role in the gut ecology and development of pigs, which is always regulated by nutrients. This study investigated the effect of L-Citrulline on growth performance, carcass characteristics, and its potential regulatory mechanism. The results showed that 1% dietary L-Citrulline supplementation for 52 days significantly increased final weight, liveweight gain, carcass weight, and average backfat and markedly decreased drip loss (p < 0.05) of finishing pigs compared with the control group. Microbial analysis of fecal samples revealed a marked increase in α-diversity and significantly altered composition of gut microbiota in finishing pigs in response to L-Citrulline. In particular, these altered gut microbiota at the phylum and genus level may be mainly involved in the metabolic process of carbohydrate, energy, and amino acid, and exhibited a significant association with final weight, carcass weight, and backfat thickness. Taken together, our data revealed the potential role of L-Citrulline in the modulation of growth performance, carcass characteristics, and the meat quality of finishing pigs, which is most likely associated with gut microbiota.

A protospacer adjacent motif-free, multiplexed, and quantitative nucleic acid detection platform with barcode-based Cas12a activity.

Clustered regularly interspaced short palindromic repeat (CRISPR)-based biosensors have been developed to facilitate the rapid and sensitive detection of nucleic acids. However, most approaches using CRISPR-based detection have disadvantages associated with the limitations of CRISPR RNA (crRNA), protospacer adjacent motif (PAM) or protospacer flanking sequence restriction, single channel detection, and difficulty in quantitative detection resulting in only some target sites being detected qualitatively. Here, we aimed to develop a barcode-based Cas12a-mediated DNA detection (BCDetection) strategy, which overcomes the aforementioned drawbacks and enables (1) detection with a universal PAM and crRNA without PAM or crRNA restriction, (2) simultaneous detection of multiple targets in a single reaction, and (3) quantitative detection, which can significantly distinguish copy number differences up to as low as a two-fold limit. We could efficiently and simultaneously detect three ß-thalassemia mutations in a single reaction using BCDetection. Notably, samples from normal individuals, spinal muscular atrophy (SMA) carriers, and SMA patients were significantly and accurately distinguished using the quantitative detection ability of BCDetection, indicating its potential application in ß-thalassemia and SMA carrier screening. Therefore, our findings demonstrate that BCDetection provides a new platform for accurate and efficient quantitative detection using CRISPR/Cas12a, highlighting its bioanalytical applications.

The fatigue effects in red emissive CdSe based QLED operated around turn-on voltage.

The operational stability is a current bottleneck facing the quantum dot light-emitting diodes (QLEDs). In particular, the device working around turn-on voltage suffers from unbalanced charge injection and heavy power loss. Here, we investigate the operational stability of red emissive CdSe QLEDs operated at different applied voltages. Compared to the rising luminance at higher voltages, the device luminance quickly decreases when loaded around the turn-on voltage, but recovers after unloading or slight heat treatment, which is termed fatigue effects of operational QLED. The electroluminescence and photoluminescence spectra before and after a period of operation at low voltages show that the abrupt decrease in device luminance derives from the reduction of quantum yield in quantum dots. Combined with transient photoluminescence and electroluminescence measurements, as well as equivalent circuit model analysis, the electron accumulation in quantum dots mainly accounts for the observed fatigue effects of a QLED during the operation around turn-on voltage. The underlying mechanisms at the low-voltage working regime will be very helpful for the industrialization of QLED.

[Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies].

OBJECTIVE: To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. METHODS: The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. RESULTS: A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the ß2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). CONCLUSION: The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.