Search

Abstract Background Long-term monitoring of Electrocardiogram (ECG) recordings is crucial to diagnose arrhythmias. Clinicians can find it challenging to diagnose arrhythmias, and this is a particular issue in more remote and underdeveloped areas. The development of digital ECG and AI methods could assist clinicians who need to diagnose arrhythmias outside of the hospital setting. Methods We constructed a large-scale Chinese ECG benchmark dataset using data from 272,753 patients collected from January 2017 to December 2021. The dataset contains ECG recordings from all common arrhythmias present in the Chinese population. Several experienced cardiologists from Shanghai First People’s Hospital labeled the dataset. We then developed a deep learning-based multi-label interpretable diagnostic model from the ECG recordings. We utilized Accuracy, F1 score and AUC-ROC to compare the performance of our model with that of the cardiologists, as well as with six comparison models, using testing and hidden data sets. Results The results show that our approach achieves an F1 score of 83.51%, an average AUC ROC score of 0.977, and 93.74% mean accuracy for 6 common arrhythmias. Results from the hidden dataset demonstrate the performance of our approach exceeds that of cardiologists. Our approach also highlights the diagnostic process. Conclusions Our diagnosis system has superior diagnostic performance over that of clinicians. It also has the potential to help clinicians rapidly identify abnormal regions on ECG recordings, thus improving efficiency and accuracy of clinical ECG diagnosis in China. This approach could therefore potentially improve the productivity of out-of-hospital ECG diagnosis and provides a promising prospect for telemedicine.

Staphylococcal Enterotoxin B (SEB), produced by Staphylococcus aureus (S. aureus), is a powerful superantigen that induces severe immune disruption and toxic shock syndrome (TSS) upon binding to MHC-II and TCR. Despite its significant impact on the pathogenesis of S. aureus, there are currently no specific therapeutic interventions available to counteract the mechanism of action exerted by this toxin. In this study, we have identified a human monoclonal antibody, named Hm0487, that specifically targets SEB by single-cell sequencing using PBMCs isolated from volunteers enrolled in a phase I clinical trial of the five-antigen S. aureus vaccine. X-ray crystallography studies revealed that Hm0487 exhibits high affinity for a linear B cell epitope in SEB (SEB138–147), which is located distantly from the site involved in the formation of the MHC-SEB-TCR ternary complex. Furthermore, in vitro studies demonstrated that Hm0487 significantly impacts the interaction of SEB with both receptors and the binding to immune cells, probably due to an allosteric effect on SEB rather than competing with receptors for binding sites. Moreover, both in vitro and in vivo studies validated that Hm0487 displayed efficient neutralizing efficacy in models of lethal shock and sepsis induced by either SEB or bacterial challenge. Our findings unveil an alternative mechanism for neutralizing the pathogenesis of SEB by Hm0487, and this antibody provides a novel strategy for mitigating both SEB-induced toxicity and S. aureus infection.

Background: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. Methods and results: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac. In vivo studies confirmed that fusion with mHla significantly augmented the immunogenicity of EpiVac, and it elicited both humoral and cellular immune responses in mice, which could be further enhanced by formulation with aluminum adjuvant. Furthermore, immunization with mHla-EpiVac demonstrated enhanced protective efficacy against K. pneumoniae channeling compared to EpiVac alone, resulting in reduced bacterial burden, secretion of inflammatory factors, histopathology and lung injury. Moreover, mHla fusion facilitated antigen uptake by mouse bone marrow-derived cells (BMDCs) and provided sustained activation of these cells. Conclusions: These findings suggest that mHla-EpiVac is a promising vaccine candidate against K. pneumoniae, and further validate the potential of mHla as a versatile carrier protein and adjuvant for antigen design.

The peptidyl prolyl cis-trans isomerase Pin1 plays vital roles in diverse cellular processes and pathological conditions. NeuroD is a differentiation and survival factor for a subset of neurons and pancreatic endocrine cells. Although multiple phosphorylation events are known to be crucial for NeuroD function, their mechanisms remain elusive. In this study, we demonstrate that zebrafish embryos deficient in Pin1 displayed phenotypes resembling those associated with NeuroD depletion, characterized by defects in formation of mechanosensory hair cells. Furthermore, zebrafish Pin1 interacts with NeuroD in a phosphorylation-dependent manner. In Pin1-deficient cell lines, NeuroD is rapidly degraded. However, the protein stability of NeuroD is restored upon overexpression of Pin1. These findings suggest that Pin1 functionally regulates NeuroD protein levels by post-phosphorylation cis-trans isomerization during neuronal specification.

The effect of growth promoting agents on the flavor of netted melon was evaluated. During the planting, Bacillus subtilis, Trichoderma harzianum and Streptomyces were applied to the roots for 4 times at a dosage of 0.1 g/m2 respectively. After harvest, volatile components of fruits were evaluated and compared with the untreated ones as the control based on the SPME-GC-MS and electric nose analysis. The results showed that the growth promoting agents affected the composition and concentration of volatile components in netted melon. A total of 54 volatile components were detected in Trichoderma harzianum group, whose content was 294.46 μg/kg being 22.66% higher than that of the control. A total of 13 aroma components was determined in Trichoderma harzianum group including trans-6-nonenal, cis-6-nonenol, octanal, trans-2-nonenal, trans,cis-2,6-nonenal, β-Violone, 3,6-nonyl-1-alcohol, nonanal, 1-octene-3-alcohol, heptanaldehyde, 2-methylbutyraldehyde, cis-3-hexenal and ethyl butyrate. The number and aroma activity value of the aroma components in the Trichoderma harzianum group was 33.33% and 82.53% higher than those of the control, respectively. Therefore, Trichoderma harzianum could improve the flavor richness and intensity of netted melon.

Climate change and the increasing frequency of high temperature (HT) events are significant threats to global crop yields. To address this, a comprehensive understanding of how plants respond to heat shock (HS) is essential. Signaling pathways involving calcium (Ca2+), a versatile second messenger in plants, encode information through temporal and spatial variations in ion concentration. Ca2+ is detected by Ca2+-sensing effectors, including channels and binding proteins, which trigger specific cellular responses. At elevated temperatures, the cytosolic concentration of Ca2+ in plant cells increases rapidly, making Ca2+ signals the earliest response to HS. In this review, we discuss the crucial role of Ca2+ signaling in raising plant thermotolerance, and we explore its multifaceted contributions to various aspects of the plant HS response (HSR).

Summary: Currently, due to lack of large-scale datasets containing multiple arrhythmias and acute coronary syndrome-related diseases, AI-aided diagnosis for cardiac diseases is limited in clinical scenarios. Whether AI-based ECG diagnosis can assist cardiologists to improve performance has not been reported. We constructed a large-scale dataset containing multiple high-regional-incidence arrhythmias and ACS-related diseases, including 162,622 12-lead ECGs collected between January 2018 and March 2021. We presented a deep learning model for clinical ECG diagnosis of multiple cardiac diseases. Results show that our model for diagnosing 15 cardiac abnormalities achieved 88.216% accuracy, and its average AUC ROC score reached 0.961. On the board-certified re-annotated dataset, its performance surpasses that of cardiologists in non-reference group. Moreover, with aid of labels given by our model, accuracy and efficiency for cardiologist increased by 13.5% and 69.9% than non-reference group. Our approach provides solutions for AI-aided diagnosis systems of cardiac diseases in applications.

Induction of endogenous cardiomyocyte (CM) proliferation is one of the key strategies for heart regeneration. Increasing evidence points to the potential role of microRNAs (miRNAs) in the regulation of CM proliferation. Here, we used human embryonic stem cell (hESC)-derived CMs (hESC-CMs) as a tool to identify miRNAs that promote CM proliferation. We profiled miRNA expression at an early stage of CM differentiation and identified a list of highly expressed miRNAs. Among these miRNAs, miR-25 was enriched in early-stage hESC-CMs, but its expression decreased over time. Overexpression of miR-25 promoted CM proliferation. RNA sequencing (RNA-seq) analysis revealed that genes related to cell-cycle signal were strongly influenced by miR-25 overexpression. We further showed that miR-25 promoted CM proliferation by targeting FBXW7. Finally, the function of miR-25 in the regulation of CM proliferation was demonstrated in zebrafish. Our study suggested that miR-25 is a promising molecule for heart regeneration. Keywords: miR-25, human embryonic stem cell, cardiomyocytes, proliferation

Antibodies are effective alternative tools to combat infections caused by Pseudomonas aeruginosa (PA), especially multi-drug-resistant PA. Thus, to solve the urgent need for an anti-PA antibody drug, we hypothesized that anti-PA intravenous immunoglobulins could be a practical attempt. Exotoxin A (ETA) is one of the most important factors for PA infection and is also a critical target for the development of immune interventions. In this study, a total of 320 sera were collected from healthy volunteers. The concentration of ETA-specific antibodies was determined by a Luminex-based assay and then purified by affinity chromatography. The purified IgGs were able to neutralize the cytotoxicity of ETA in vitro. We showed they had a prophylactic and therapeutic protective effect in PA pneumonia and ETA toxemia models. In addition, administration of nonspecific IgGs also provided partial protection. Collectively, our results provide additional evidence for IVIG-based treatment of infections caused by multi-drug-resistant PA and suggest that patients at high risk of PA pneumonia could be prophylactically treated with anti-ETA IgGs or even with nonspecific IgGs.

The wall-associated kinase (WAK) multigene family plays critical roles in various cellular processes and stress responses in plants, however, whether WAKs are involved in salt tolerance is obscure. Herein, we report the functional characterization of a rice WAK, WAK112, whose expression is suppressed by salt. Overexpression of OsWAK112 in rice and heterologous expression of OsWAK112 in Arabidopsis significantly decreased plant survival under conditions of salt stress, while knocking down the OsWAK112 in rice increased plant survival under salt stress. OsWAK112 is universally expressed in plant and associated with cell wall. Meanwhile, in vitro kinase assays and salt tolerance analyses showed that OsWAK112 possesses kinase activity and that it plays a negative role in the response of plants to salt stress. In addition, OsWAK112 interacts with S-adenosyl-L-methionine synthetase (SAMS) 1/2/3, which catalyzes SAM synthesis from ATP and L-methionine, and promotes OsSAMS1 degradation under salt stress. Furthermore, in OsWAK112-overexpressing plants, there is a decreased SAMS content and a decreased ethylene content under salt stress. These results indicate that OsWAK112 negatively regulates plant salt responses by inhibiting ethylene production, possibly via direct binding with OsSAMS1/2/3.

We previously reported the involvement of cyclic nucleotide-gated ion channel 6 (CNGC6) and hydrogen peroxide (H2O2) in plant responses to heat shock (HS). To demonstrate their relationship with plant thermotolerance, we assessed the effect of HS on several groups of Arabidopsis (Arabidopsis thaliana) seedlings: wild-type, cngc6 mutant, and its complementation line. Under exposure to HS, the level of H2O2 was lower in the cngc6 mutant seedlings than in the wild-type (WT) seedlings but obviously increased in the complementation line. The treatment of Arabidopsis seeds with calcium ions (Ca2+) increased the H2O2 levels in the seedlings under HS treatment, whereas treatment with a Ca2+ chelator (EGTA) inhibited it, indicating that CNGC6 may stimulate the accumulation of H2O2 in a manner dependent on an increase in cytosolic Ca2+ ([Ca2+]cyt). This point was verified by phenotypic observations and thermotolerance testing with transgenic plants overexpressing AtRbohB and AtRbohD (two genes involved in HS-responsive H2O2 production), respectively, in a cngc6 background. Real-time reverse transcription-polymerase chain reactions and Western blotting suggested that CNGC6 enhanced the gene transcription of HS factors (HSFs) and the accumulation of HS proteins (HSPs) via H2O2. These upon results indicate that H2O2 acts downstream of CNGC6 in the HS signaling pathway, increasing our understanding of the initiation of plants responses to high temperatures.

Abstract Background We previously reported the involvement of nitric oxide (NO) and cyclic nucleotide-gated ion channel 6 (CNGC6) in the responses of plants to heat shock (HS) exposure. To elucidate their relationship with heat tolerance in Arabidopsis thaliana, we examined the effects of HS on several groups of seedlings: wild type, cngc6, and cngc6 complementation and overexpression lines. Results After HS exposure, the level of NO was lower in cngc6 seedlings than in wild-type seedlings but significantly elevated in the transgenic lines depending on CNGC6 expression level. The treatment of seeds with calcium ions (Ca2+) enhanced the NO level in Arabidopsis seedlings under HS conditions, whereas treatment with EGTA (a Ca2+ chelator) reduced it, implicating that CNGC6 stimulates the accumulation of NO depending on an increase in cytosolic Ca2+ ([Ca2+]cyt). This idea was proved by phenotypic observations and thermotolerance testing of transgenic plants overexpressing NIA2 and NOA1, respectively, in a cngc6 background. Western blotting indicated that CNGC6 stimulated the accumulation of HS proteins via NO. Conclusion These data indicate that CNGC6 acts upstream of NO in the HS pathway, which improves our insufficient knowledge of the initiation of plant responses to high temerature.

The gas nitric oxide (NO) plays an important role in several biological processes in plants, including growth, development, and biotic/abiotic stress responses. Salinity has received increasing attention from scientists as an abiotic stressor that can seriously harm plant growth and crop yields. Under saline conditions, plants produce NO, which can alleviate salt-induced damage. Here, we summarize NO synthesis during salt stress and describe how NO is involved in alleviating salt stress effects through different strategies, including interactions with various other signaling molecules and plant hormones. Finally, future directions for research on the role of NO in plant salt tolerance are discussed. This summary will serve as a reference for researchers studying NO in plants.

Because of the nano-scale tunnel constructed by the active Mn-O octahedron in cryptomelane, cryptomelane-type manganese oxides have high activity in the oxidation of several volatile organic compounds (VOCs). Natural cryptomelane, in the form of supergene oxide manganese ore, carpets much of South China. In the lower part of the Datangpo Formation of Nanhua System on the southeastern Yangtze Platform, cryptomelane is one of the major manganese oxides in black shale of the Xiangtan manganese deposit in this deposit. Formaldehyde is a dominant indoor pollutant among volatile organic compounds (VOCs), and applications of synthetic cryptomelane have been reported to eliminate it. To study the removal capacity of naturally outcropping cryptomelane, representative samples of manganese oxide (the primary mineral component of cryptomelane) from the Xiangtan Mn deposit were analyzed in this study. The chemical composition, crystal structure and micromorphology of the manganese oxide minerals were explored using ICP-AES, XRD, EPMA, SEM and HR-TEM techniques. Fine-grained and poorly crystalline, these minerals consist primarily of cryptomelane, along with minor amounts of pyrolusite, hollandite, lithiophorite, limonite and quartz. Natural cryptomelane is a monoclinic crystal, and its cell parameters are refined. The results of catalytic tests revealed that natural cryptomelane has obvious catalytic activity in the oxidation of formaldehyde in a static environment under room temperature. This study may provide a natural mineral material as an inexpensive and efficient catalyst for the purification of formaldehyde in industrial or indoor air treatment.

Device-to-device (D2D) communications underlying cellular networks are a novel approach for providing IoT services, in which D2D communication links and cellular communication links share the same channels. Unfortunately, various kinds of devices are randomly distributed in cellular networks and potentially result in critical interferences. To solve the interference problem, we propose a novel greedy-based channel assignment algorithm in this paper. First, we construct a novel interference graph that describes the interferences between pairs of communication links when they simultaneously share the same channel. Then, a novel channel assignment algorithm is proposed to alleviate system interferences by greedily assigning the best channel to each communication link, which is simple and feasible to implement. Moreover, we convert the channel assignment problem into a robust graph coloring problem and search for a near-optimal solution to minimize the system interferences. Numerical results indicate that the proposed algorithm not only dramatically improves the network capacity but also enhances the fairness among devices.

The Guangxi Zhuang Autonomous Region is an important manganese ore district in Southwest China, with manganese ore resource reserves accounting for 23% of the total manganese ore resource reserves in China. The Xialei manganese deposit (Daxin County, Guangxi) is the first super-large manganese deposit discovered in China. The Mn oxide in the supergene oxidation zone of the Xialei deposit was characterized using scanning electron microscopy (SEM), energy spectrometer (EDS), transmission electron microscopy (TEM, HRTEM), and X-ray diffraction analysis (XRD). The Mn oxides have a gray-black/steel-gray color, a semi-metallic-earthy luster, and appear as oolitic, pisolitic, banded, massive, and cellular textures. Scanning electron microscopy images show that the manganese oxide minerals are present as fine-spherical particles with an earthy surface. TEM and HRTEM indicate the presence of oriented bundled and staggered nanorods, and nanopores between the crystals. The Mn oxide ore can be classified into two textural types: (1) oolitic and pisolitic (often with annuli) Mn oxide, and (2) massive Mn oxide. Pyrolusite, cryptomelane, and hollandite are the main Mn oxide minerals. The potassium contents of cryptomelane and pyrolusite are discussed. The unit cell parameters of pyrolusite are refined.

Pseudomonas aeruginosa (PA) is a major cause of nosocomial infections, which remain an unsolved problem in the clinic despite conventional antibiotic treatment. A PA vaccine could be both an effective and economical strategy to address this issue. Many studies have shown that PcrV, a structural protein of the type 3 secretion system (T3SS) from PA, is an ideal target for immune prevention and therapy. However, difficulties in the production of high-quality PcrV likely hinder its further application in the vaccine industry. Thus, we hypothesized that an optimized PcrV derivative with a rational design could be produced. In this study, the full-length PcrV was divided into four domains with the guidance of its structure, and the Nter domain (Met1-Lys127) and H12 domain (Leu251-Ile294) were found to be immunodominant. Subsequently, Nter and H12 were combined with a flexible linker to generate an artificial PcrV derivative (PcrVNH). PcrVNH was successfully produced in E. coli and behaved as a homogenous monomer. Moreover, immunization with PcrVNH elicited a multifactorial immune response and conferred broad protection in an acute PA pneumonia model and was equally effective to full-length PcrV. In addition, passive immunization with anti-PcrVNH antibodies alone also showed significant protection, at least based on inhibition of the T3SS and mediation of opsonophagocytic killing activities. These results provide an additional example for the rational design of antigens and suggest that PcrVNH is a promising vaccine candidate for the control of PA infection.

In this paper, the effect of HPMC (hydroxypropyl methyl cellulose ether) on the cement mortar water retention (WR) and composition was studied. The relationship between the plastic viscosity and water retention of cement mortar was revealed. The results showed that HPMC formed a colloidal film with a 3D network structure in water, which changed the ability of water to migrate. The HPMC colloid adsorbed on the surface of cement and sand particles and played a bridging role due to the influence of the spatial network structure of the thin film. Fine particles formed a grid-like distribution, and the hydration products formed a unique fibrous tree-like structure. A positive correlation was observed between the plastic viscosity and the water holding capacity of cement mortar. Finally, the mechanism responsible for the improved water retention of cement mortar by HPMC was analyzed using the changing water migration capacity, migration channels, and mortar cohesion.

Salt is a major threat to plant growth and crop productivity. Calmodulin (CaM), the most important multifunctional Ca2+ sensor protein in plants, mediates reactions against environmental stresses through target proteins; however, direct proof of the participation of CaM in salt tolerance and its corresponding signaling pathway in vivo is lacking. In this study, we found that AtCaM1 and AtCaM4 produced salt-responsive CaM isoforms according to real-time reverse transcription-polymerase chain reaction analyses; this result was verified based on a phenotypic analysis of salt-treated loss-of-function mutant and transgenic plants. We also found that the level of nitric oxide (NO), an important salt-responsive signaling molecule, varied in response to salt treatment depending on AtCaM1 and AtCaM4 expression. GSNOR is considered as an important and widely utilized regulatory component of NO homeostasis in plant resistance protein signaling networks. In vivo and in vitro protein-protein interaction assays revealed direct binding between AtCaM4 and S-nitrosoglutathione reductase (GSNOR), leading to reduced GSNOR activity and an increased NO level. Overexpression of GSNOR intensified the salt sensitivity of cam4 mutant plants accompanied by a reduced internal NO level, whereas a gsnor deficiency increased the salt tolerance of cam4 plants accompanied by an increased internal NO level. Physiological experiments showed that CaM4-GSNOR, acting through NO, reestablished the ion balance to increase plant resistance to salt stress. Together, these data suggest that AtCaM1 and AtCaM4 serve as signals in plant salt resistance by promoting NO accumulation through the binding and inhibition of GSNOR. This could be a conserved defensive signaling pathway in plants and animals.