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Abstract Intervertebral disc degeneration (IVDD), a disease associated with ageing, is characterised by a notable increase in senescent nucleus pulposus cells (NPCs) as IVDD progresses. However, the specific mechanisms that regulate the senescence of NPCs remain unknown. In this study, we observed impaired autophagy in IVDD-NPCs, which contributed to the upregulation of NPCs senescence and the senescence-associated secretory phenotype (SASP). The dysregulated SASP disrupted NPCs viability and initiated extracellular matrix degradation. Conversely, the restoration of autophagy reversed the senescence phenotype by inhibiting GATA binding protein 4 (GATA4). Moreover, we made the novel observation that a cross-talk between histone H3 lysine 4 trimethylation (H3K4me3) modification and N6-methyladenosine(m6A)-methylated modification regulates autophagy in IVDD-NPCs. Mechanistically, lysine methyltransferase 2A (KMT2A) promoted the expression of methyltransferase-like 3 (METTL3) through H3K4me3 modification, whereas METTL3-mediated m6A modification reduced the expression of autophagy-associated 4a (ATG4a) by attenuating its RNA stability, leading to autophagy damage in NPCs. Silencing KMT2A and METTL3 enhanced autophagic flux and suppressed SASP expression in IVDD-NPCs. Therefore, targeting the H3K4me3-regulated METTL3/ATG4a/GATA4 axis may represent a promising new therapeutic strategy for IVDD.

Abstract Feeding behavior, the most fundamental physiological activity, is controlled by two opposing groups of factors, orexigenic and anorexigenic factors. The sulfakinin family, an insect analogue of the mammalian satiety factor cholecystokinin (CCK), has been shown to suppress food intake in various insects. Nevertheless, the mechanisms through which sulfakinin regulates feeding behavior remain a biological question. This study aimed to elucidate the signaling pathway mediated by the anorexigenic peptide sulfakinin in Bombyx mori. We identified the Bombyx mori neuropeptide G protein-coupled receptor A9 (BNGR-A9) as the receptor for sulfakinin through functional assays. Stimulation with sulfakinin triggered a swift increase in intracellular IP3, Ca2+, and a notable enhancement of ERK1/2 phosphorylation, in a manner sensitive to a Gαq-specific inhibitor. Treatment with synthetic sulfakinin resulted in decreased food consumption and average body weight. Additionally, administering synthetic sulfakinin to silkworms significantly elevated hemolymph trehalose levels, an effect markedly reduced by pre-treatment with BNGR-A9 dsRNA. Consequently, our findings establish the sulfakinin/BNGR-A9 signaling pathway as a critical regulator of feeding behavior and hemolymph trehalose homeostasis in Bombyx mori, highlighting its roles in the negative control of food intake and the positive regulation of energy balance.

Abstract Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence‐related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3‐rich extracellular vesicles to NPCs, thereby alleviating aging‐associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane‐bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2‐TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia‐induced BMSC exosomes deliver BNIP3‐rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Proteins, as the primary executors of physiological activity, serve as a key factor in disease diagnosis and treatment. Research into their structures, functions, and interactions is essential to better understand disease mechanisms and potential therapies. DeepMind’s AlphaFold2, a deep-learning protein structure prediction model, has proven to be remarkably accurate, and it is widely employed in various aspects of diagnostic research, such as the study of disease biomarkers, microorganism pathogenicity, antigen-antibody structures, and missense mutations. Thus, AlphaFold2 serves as an exceptional tool to bridge fundamental protein research with breakthroughs in disease diagnosis, developments in diagnostic strategies, and the design of novel therapeutic approaches and enhancements in precision medicine. This review outlines the architecture, highlights, and limitations of AlphaFold2, placing particular emphasis on its applications within diagnostic research grounded in disciplines such as immunology, biochemistry, molecular biology, and microbiology.

To achieve full-band observation of solar radio emissions, the sun-planetary interstellar monitoring chain subsystem of the Phase II of Chinese Meridian Project will construct four sets of solar radio spectrometers covering the decimeter, meter, decameter, and centimeter wavebands, providing reliable data support for solar physics and space weather research and operations. The system configuration and main technical parameters of the full-band radio spectrometer are introduced, and the data products and calibration process described.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

Abstract Background Numerous studies have reported the association between tea intake and lung diseases. However, the probable relationship between tea consumption on lung diseases still remain controversial and it is unclear whether these findings are due to reverse causality or confounding factor. Methods In order to systematically investigate the causal connection between tea intake on respiratory system disorders, we employed a two-sample Mendelian randomized (MR) study. Genetic instruments for tea intake were identified from a genome-wide association study (GWAS) involving 447,385 individuals. Data on lung diseases were collected from a variety of publicly available genome-wide association studies. The main method used for MR analysis is the inverse variance weighting (IVW) method. To ensure the accuracy of the findings, further sensitivity analysis was conducted. Results The IVW method in our MR analysis revealed no evidence to support a causal relationship between tea intake and lung diseases (IPF: OR = 0.997, 95% CI = 0.994-1.000, p = 0.065; Lung cancer: OR = 1.003, 95% CI = 0.998–1.008, P = 0.261; COPD: OR = 1.001, 95% CI = 0.993–1.006, p = 0.552; acute bronchitis: OR = 0.919, 95% CI = 0.536–1.576, p = 0.759; tuberculosis: OR = 1.002, 95% CI = 0.998–1.008, p = 0.301; pneumonia: OR = 0.789, 95% CI = 0.583–1.068, p = 0.125). The reliability of the results was further demonstrated by four additional MR analysis techniques and additional sensitivity testing. Conclusion We found no evidence of a link between tea intake on lung diseases in our MR results based on genetic information.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. The strategy of using functional materials to deliver nucleic acids provides a powerful tool for ameliorating IVDD. However, the immunogenicity of nucleic acid vectors and the poor mechanical properties of functional materials greatly limit their effects. Herein, antagomir-204–3p (AM) shows low immunogenicity and effectively inhibits the apoptosis of nucleus pulposus cells. Moreover, a high-strength biohydrogel based on zinc-oxidized sodium alginate-gelatin (ZOG) is designed as a multifunctional nucleic acid delivery platform. ZOG loaded with AM (ZOGA) exhibits great hygroscopicity, antibacterial activity, biocompatibility, and biodegradability. Moreover, ZOGA can be cross-linked with nucleus pulposus tissue to form a high-strength collagen network that improves the mechanical properties of the intervertebral disc (IVD). In addition, ZOGA provides an advantageous microenvironment for genetic expression in which AM can play an efficient role in maintaining the metabolic balance of the extracellular matrix. The results of the radiological and histological analyses demonstrate that ZOGA restores the height of the IVD, retains moisture in the IVD, and maintains the tissue structure. The ZOGA platform shows the sustained release of nucleic acids and has the potential for application to ameliorate IVDD, opening a path for future studies related to IVD.

Electroencephalogram (EEG) analysis plays an indispensable role across contemporary medical applications, which encompasses diagnosis, monitoring, drug discovery, and therapeutic assessment. This work puts forth an end-to-end deep learning framework that is uniquely tailored for versatile EEG analysis tasks by directly operating on raw waveform inputs. It aims to address the challenges of manual feature engineering and the neglect of spatial interrelationships in existing methodologies. Specifically, a spatial channel attention module is introduced to emphasize the critical inter-channel dependencies in EEG signals through channel statistics aggregation and multi-layer perceptron operations. Furthermore, a sparse transformer encoder is used to leverage selective sparse attention in order to efficiently process long EEG sequences while reducing computational complexity. Distilling convolutional layers further concatenates the temporal features and retains only the salient patterns. As it was rigorously evaluated on key EEG datasets, our model consistently accomplished a superior performance over the current approaches in detection and classification assignments. By accounting for both spatial and temporal relationships in an end-to-end paradigm, this work facilitates a versatile, automated EEG understanding across diseases, subjects, and objectives through a singular yet customizable architecture. Extensive empirical validation and further architectural refinement may promote broader clinical adoption prospects.

Abstract Particle cascades induced by ultra-high-energy (UHE) cosmic rays and neutrinos impacting on the lunar regolith usually radiate Cherenkov radio emissions due to the presence of excess negative charge, which is known as Askaryan effect. Several experiments have been carried out to detect the Cherenkov radio emissions in the lunar regolith. To prepare for future lunar Ultra-Long Wavelength (ULW, frequencies below 30 MHz) radio astronomy missions, we study the detection of the Cherenkov radio emissions with the ULW radio telescope that are operating at the lunar orbit. We have carried out instrument modelling and analytic calculations for the analysis of aperture, flux and event rate, and the analyses show the detectability of the Cherenkov radiation. Based on the properties of the Cherenkov radiation, we have demonstrated that the cosmic ray and neutrino events could be reconstructed with the three ULW vector antennas onboard the lunar satellites via measurements of the Askaryan radio pulse intensity, polarizations, etc. The results obtained by this study would be useful for future lunar radio explorer mission, where the detections of UHE cosmic rays and neutrinos could be successfully attempted.

The transition region is a very thin but most peculiar layer in the solar atmosphere located between the solar chromosphere and the corona. It is a key region for understanding coronal heating, solar eruption triggers, and the origin of solar winds. Here, almost all physical parameters (density, temperature, and magnetic fields) have the maximum gradient. Therefore, this region should be highly dynamic, including fast energy releasing and transporting, plasma heating, and particle accelerating. The physical processes can be categorized into two classes: thermal and non-thermal processes. Thermal processes can be observed at ultraviolet (UV) and extreme ultraviolet (EUV) wavelengths via multi-wavelength images. Non-thermal processes accelerate non-thermal electrons and produce radio emissions via the gyrosynchrotron mechanism resulting from the interaction between the non-thermal electrons and magnetic fields. The frequency range spans from several GHz to beyond 100 GHz, in great number of bursts with narrowband, millisecond lifetime, rapid frequency drifting rates, and being referred to as transition region small-scale microwave bursts (TR-SMBs). This work proposes a new type of Solar Ultra-wide Broadband Millimeter-wave Spectrometer (SUBMS) that can be used to observe TR-SMBs. From SUBMS observations, we can derive rich dynamic information about the transition region, such as information about non-thermal energy release and propagation, the flows of plasma and energetic particles, the magnetic fields and their variations, the generation and transportation of various waves, and the formation and evolution of the source regions of solar eruptions. Such an instrument can actually detect the non-thermal signals in the transition region during no flare as well as the eruptive high-energy processes during solar flares.

To study the potential disasters caused by tunnels crossing water-abundant fault areas, this study takes the Jinyunshan Tunnel as an example, and studies the groundwater flow law between different rock layers, the interaction between surrounding rock hydrostatic pressure and soil pressure, and the mechanical features and safety of the lining during construction by combining field tests and finite element simulation analysis. The results show that the displacement change rate of the tunnel vault reaches 2.8 mm/d, and the maximum earth pressure and hydrostatic pressure are 2.3 MPa and 1.15 MPa, respectively, both at the bottom of the tunnel in section II. When the tunnel enters the fault fracture zone from the V surrounding rock, the bending moment of the lining increases by 222.78% at the left haunch and 60.87% at the bottom of the right wall. The axial force of the right spandrel increases by 2579.2%, and the left spandrel increases by 221.18%. The safety factor of the two sections is greater than 2.4, indicating that the overall structure is in a safe state, but the safety factor of the second right shoulder is 2.54, which is close to the safety threshold of 2.4. The research results provide a basis for the safety design and construction safety of tunnels through water-rich sections in similar fault fracture zones, and provide a reference for reducing groundwater loss and protecting ecological vegetation.

In order to realize the accurate and reliable prediction of the change trend of dissolved oxygen (DO) content in California perch aquaculture water, this paper proposes a second-order hybrid optimization support vector machine (SVR) model based on Differential Evolution (DE) and Gray Wolf Optimizer (GWO), shortened to DE-GWO-SVR, to predict the DO content with the characteristics of nonlinear and non-smooth water quality data. Experimentally, data for the water quality, including pH, water temperature, conductivity, salinity, total dissolved solids, and DO, were collected. Pearson’s correlation coefficient (PPMCC) was applied to explore the correlation between each water quality parameter and DO content. The optimal DE-GWO-SVR model was established and compared with models based on SVR, back-propagation neural network (BPNN), and their optimization models. The results show that the DE-GWO-SVR model proposed in this paper can effectively realize the nonlinear prediction and global optimization performance. Its R2, MSE, MAE and RMSE can be up to 0.94, 0.108, 0.2629, and 0.3293, respectively, which is better than those of other models. This research provides guidance for the efficient prediction of DO in perch aquaculture water bodies for increasing the aquaculture effectiveness and reducing the aquaculture risk, providing a new exploratory path for water quality monitoring.

Abstract Background To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. Methods In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48. Results Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group (n = 183) or the placebo group (n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses. Conclusions HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo. Trial registration ClinicalTrials.gov , NCT03522415 . Registered on 11 May 2018.

Primary ovarian insufficiency (POI) is among the foremost causes of women infertility due to premature partial or total loss of ovarian function. Resistant ovary syndrome (ROS) is a subtype of POI manifested as normal ovarian reserve but insensitive to gonadotropin stimulation. Inactivating variants of follicle-stimulating hormone receptor (FSHR), a class A G-protein coupled receptor, have been associated with POI and are inherited via an autosomal recessive pattern. In this study, we investigated the genetic causes of a primary infertility patient manifested as POI with ROS, and elucidated the structural and functional impact of variants of uncertain significance. Next-generation sequencing (NGS) combined with Sanger sequencing revealed novel compound heterozygous FSHR variants: c.1384G>C/p.Ala462Pro and c.1862C>T/p.Ala621Val, inherited from her father and mother, respectively. The two altered amino acid sequences, localized in the third and seventh transmembrane helix of FSHR, were predicted as deleterious by in silico prediction. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression. In conclusion, two unreported inactivating FSHR variants potentially responsible for POI with ROS were first identified. This study expands the current phenotypic and genotypic spectrum of POI.

The Cishan gold deposit is a newly discovered medium-scale independent skarn gold deposit located in the Tongling ore cluster area of the Middle-Lower Yangtze Metallogenic Belt, and the ore-related intrusion is the Cishan pyroxene diorite. In this study, we investigated the zircon U–Pb Geochronology, whole-rock geochemistry of the Cishan ore-related pyroxene diorite, and C–O–S isotope compositions of hydrothermal calcites and metal sulfides in the ores. The pyroxene diorite was emplaced at ca. 141.7 ± 0.36 Ma. They are metaluminous and record high-K calc alkaline and shoshonite series with the characteristics of high Al and alkali (K, Na), enriched in LREEs and LILEs (Rb, K, Ba, Sr), depleted in HREEs and HFSEs (Th, U), without significant Eu anomalies. We suggest that the magma of the Cishan pyroxene diorite was probably derived from partial melting of the enriched lithospheric mantle mixed with a small amount of crustal derived melts, and then underwent crystallization differentiation and weakly upper crustal contamination during the magmatic ascending. The δ13CV-PDB and δ18OV-SMOW values of the hydrothermal calcites range from −5.1‰ to −0.5‰ and 11.7‰ to 16.2‰ respectively, and the δ34SV-CDT values of sulfide ore minerals range from −0.7‰ to 6.0‰, showing that the ore-forming fluids and materials were derived from the magma. Combined with previous studies, we proposed that both the Cishan intrusion and skarn gold deposit were formed under the tectonic transition period from compressional to extensional setting, and the Middle–Lower Yangtze Metallogenic Belt was located in the inland side of the continental margin arc under the subduction of the paleo-Pacific plate.

Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.

The emergence of novel coronavirus mutants is a main factor behind the deterioration of the epidemic situation. Further studies into the pathogenicity of these mutants are thus urgently needed. Binding of the spinous protein receptor binding domain (RBD) of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor was shown to initiate coronavirus entry into host cells and lead to their infection. The receptor-binding motif (RBM, 438–506) is a region that directly interacts with ACE2 receptor in the RBD and plays a crucial role in determining affinity. To unravel how mutations in the non-RBM regions impact the interaction between RBD and ACE2, we selected three non-RBM mutant systems (N354D, D364Y, and V367F) from the documented clinical cases, and the Q498A mutant system located in the RBM region served as the control. Molecular dynamics simulation was conducted on the mutant systems and the wild-type (WT) system, and verified experiments also performed. Non-RBM mutations have been shown not only to change conformation of the RBM region but also to significantly influence its hydrogen bonding and hydrophobic interactions. In particular, the D364Y and V367F systems showed a higher affinity for ACE2 owing to their electrostatic interactions and polar solvation energy changes. In addition, although the binding free energy at this point increased after the mutation of N354D, the conformation of the random coil (Pro384-Asp389) was looser than that of other systems, and the combined effect weakened the binding free energy between RBD and ACE2. Interestingly, we also found a random coil (Ala475-Gly485). This random coil is very sensitive to mutations, and both types of mutations increase the binding free energy of residues in this region. We found that the binding loop (Tyr495-Tyr505) in the RBD domain strongly binds to Lys353, an important residue of the ACE2 domain previously identified. The binding free energy of the non-RBM mutant group at the binding loop had positive and negative changes, and these changes were more obvious than that of the Q498A system. The results of this study elucidate the effect of non-RBM mutation on ACE2-RBD binding, and provide new insights for SARS-CoV-2 mutation research.

The solar minimum is a period with a relatively smaller number of sunspots and solar eruptions, and has been less studied before. Since the radio signal rapidly responds to the change of solar plasma and magnetic field, we perform a comprehensive analysis of high resolution spectrum data from SBRS and MUSER: 1) a search for solar radio bursts of different kinds in recent solar minima (2007–2009 and 2016–2018); 2) an analysis of several typical radio burst events, negative and positive drifting bursts, for example the November 22, 2015 and August 29, 2016 events; superfine spectral structure events with mini-flares and even without sunspots, for example the March 28, 2008 and July 04, 2017 events. These results show that there were many radio bursts with a fine structure during solar minima. These events occurred not only in powerful flares, but also in faint flares (class C and B by GOES) or even without flares, but in regions related to weak brightenings or ejecta. We assume that the weak solar radio bursts observed by telescopes with high sensitivity and low interference will help us to understand the basic physical characteristics of small-scale solar eruptions.

Abstract In this paper, by applying Kronecker product and vectorization operator, we extend two mathematical equivalent forms of the conjugate residual squared (CRS) method to solve the periodic Sylvester matrix equation AjXjBj+CjXj+1Dj=Ejfor j=1,2,…,λ. $$\begin{aligned} A_{j} X_{j} B_{j} + C_{j} X_{j+1} D_{j} = E_{j} \quad \text{for } j=1,2, \ldots ,\lambda . \end{aligned}$$ We give some numerical examples to compare the accuracy and efficiency of the matrix CRS iterative methods with other methods in the literature. Numerical results validate that the proposed methods are superior to some existing methods and that equivalent mathematical methods can show different numerical performance.

Spikes are typical radio bursts in solar flares, which are proposed to be the signal of energy release in the solar corona. The whole group of spikes always shows different spectral patterns in the dynamic spectrum. Here, we present a special new feature at 0.6–2 GHz in a confined flare. Each group of spikes is composed of many quasi-periodic sub-clusters, which are superposed on the broadband quasi-periodic pulsations (QPPs). The quasi-periodic cluster of spikes (QPSs) have very intense emissions, and each cluster includes tens of individual spikes. When the intensity of background pulsation is increased, the intensity, duration and bandwidth of the spike cluster are also enlarged. There are 21 groups of QPSs throughout the confined flare. The central frequency of the whole group shifts from 1.9 to 1.2 GHz, and the duration of each cluster shows a negative exponential decay pattern. We propose that nonthermal electron beams play a crucial role in emitting both pulsations and spikes. The tearing-mode oscillations of a confined flux rope produce periodic accelerated electron beams. These electron beams travel inside the closed magnetic structure to produce frequency drifting pulsations via plasma emission and scattered narrowband spikes by electron-cyclotron maser emission (ECME). The slow rise of flux rope makes the source region move upward, and thus, QPSs shift towards low frequency. We propose that the confined flux rope may provide the essential conditions for the formation of QPSs.

The Chinese Spectral Radioheliograph (CSRH) covering 400 MHz-15 GHz frequency range was constructed during 2009–2016 in Mingantu Observing Station, National Astronomical Observatories, Chinese Academy of Sciences at Zhengxiangbaiqi, Inner Mongolia of China. The CSRH is renamed as MingantU SpEctral Radioheliograph (MUSER) after its accomplishment. Currently, MUSER consists of two arrays spreading over three spiral-shaped arms. The maximum baseline length is ∼3 km in both east-west and north-south directions. The MUSER array configuration is optimized to meet the needs of observing the full-disk Sun over ultrawide wavebands with images of high temporal, spatial and spectral resolutions and high dynamic range. The low frequency array, called MUSER-I, covers 400 MHz-2.0 GHz with 40 antennas of 4.5-m-diameter each and the high frequency array, called MUSER-II, covers 2–15 GHz with 60 antennas of 2-m-diameter each. The MUSER-I can obtain full-disk solar radio images in 64 frequency channels with a time cadence of 25 ms and a spatial resolution of 51.6″ to 10.3″ (corresponding to the frequency range 400 MHz to 2 GHz), whereas the MUSER-II can obtain full-disk solar images in 520 channels with a time cadence of 206.25 ms and a spatial resolution of 10.3″ to 1.3 (corresponding to the frequency range 2 to 15 GHz). A dynamic range of 25 dB can be obtained with snapshot images produced with the MUSER. An extension of MUSER in the further lower frequency range covering 30–400 MHz with an array of 224 logarithm-periodic dipole antennas (LPDAs) has been approved and will be completed during the next 4 years. The MUSER, as a dedicated solar instrument, has the following advantages providing simultaneous images over a wide frequency range with a unique high temporal-spatial-spectral resolutions; high-performing ultrawide-band dual-polarization feeds for wide-band signal collection; advanced high data-rate, large-scale digital correlation receiver for multiple-frequency and faster snapshot observations; and applications of new technologies such as using optical fiber to obtain remote antenna and wide-band analog signal transmission. The MUSER thus provides a unique opportunity to measure solar magnetic fields and trace dynamic evolution of energetic electrons in several radio frequencies, which, in turn, will help to have better understandings of the origin of various solar activities and the basic drivers of space weather.

In recent years, the identification of the essential nodes in complex networks has attracted significant attention because of their theoretical and practical significance in many applications, such as preventing and controlling epidemic diseases and discovering essential proteins. Several importance measures have been proposed from diverse perspectives to identify crucial nodes more accurately. In this paper, we propose a novel importance metric called node propagation entropy, which uses a combination of the clustering coefficients of nodes and the influence of the first- and second-order neighbor numbers on node importance to identify essential nodes from an entropy perspective while considering the local and global information of the network. Furthermore, the susceptible–infected–removed and susceptible–infected–removed–susceptible epidemic models along with the Kendall coefficient are used to reveal the relevant correlations among the various importance measures. The results of experiments conducted on several real networks from different domains show that the proposed metric is more accurate and stable in identifying significant nodes than many existing techniques, including degree centrality, betweenness centrality, closeness centrality, eigenvector centrality, and H-index.

We report a Raman characterization of the α borophene polymorph by scanning tunneling microscopy combined with tip-enhanced Raman spectroscopy. A series of Raman peaks were discovered, which can be well related with the phonon modes calculated based on an asymmetric buckled α structure. The unusual enhancement of high-frequency Raman peaks in TERS spectra of α borophene is found and associated with its unique buckling when landed on the Ag(111) surface. Our paper demonstrates the advantages of TERS, namely high spatial resolution and selective enhancement rule, in studying the local vibrational properties of materials in nanoscale.

Overexposure may happen for imaging of solar observation as extremely violet solar bursts occur, which means that signal intensity goes beyond the dynamic range of imaging system of a telescope, resulting in loss of signal. For example, during solar flare, Atmospheric Imaging Assembly (AIA) of Solar Dynamics Observatory (SDO) often records overexposed images/videos, resulting loss of fine structures of solar flare. This paper makes effort to retrieve/recover missing information of overexposure by exploiting deep learning for its powerful nonlinear representation which makes it widely used in image reconstruction/restoration. First, a new model, namely, mask-Pix2Pix network, is proposed for overexposure recovery. It is built on a well-known Pix2Pix network of conditional generative adversarial network (cGAN). In addition, a hybrid loss function, including an adversarial loss, a masked L1 loss and a edge mass loss/smoothness, are integrated together for addressing challenges of overexposure relative to conventional image restoration. Moreover, a new database of overexposure is established for training the proposed model. Extensive experimental results demonstrate that the proposed mask-Pix2Pix network can well recover missing information of overexposure and outperforms the state of the arts originally designed for image reconstruction tasks.

To this end, many laws and regulations on privacy protection have been introduced, and the phenomenon of data-island has become a major bottleneck hindering the development of big data and artificial intelligence technology.Federated learning has received widespread attention to break this phenomenon.Started with the historical development of federated learning, the definition, and architecture and classification of federated learning, the advantages of federated learning in privacy protection domainwere introduced.At the same time, various attack methods and their classification aboutfederated learning were introduced in detail.The classification of various encryption algorithms in federated learning were summarized.In conclusion, the contribution of federated learning in privacy protection and security mechanism were summarized and the new challenges in these domains were proposed.

In recent years,federated learning has been proposed and received widespread attention to overcome data isolated island challenge.Federated learning related researches were adopted in areas such as financial field,healthcare domain and smart city related application.Federated learning concept was introduced into three different layers.The first layer introduced the definition,architecture,classification of federated learning and compared the federated learning with traditional distributed learning.The second layer presented comparison and analysis of federated learning algorithms from machine learning and deep learning aspects.The third layer separated federated learning optimization algorithms into three aspects to optimize federated learning algorithm through reducing communication cost,selecting proper clients and different aggregation method.Finally,the current research status and three main challenges on communication,heterogeneity of system and data to be solved were concluded,and the future prospects in federated learning domain were proposed.

Magnetotactic bacteria (MTB) are a diverse group of microorganisms capable of using geomagnetic fields for navigation. This magnetotactic behavior can help microorganisms move toward favorable habitats for optimal growth and reproduction. A comprehensive understanding of the magnetotactic mechanism at molecular levels requires highly efficient genomic editing tools, which remain underdeveloped in MTB. Here, we adapted an engineered CRISPR-Cas9 system for efficient inactivation of genes in a widely used MTB model strain, Magnetospirillum magneticum AMB-1. By combining a nuclease-deficient Cas9 (dCas9) and single-guide RNA (sgRNA), a CRISPR interference system was successfully developed to repress amb0994 expression. Furthermore, we constructed an in-frame deletion mutant of amb0994 by developing a CRISPR-Cas9 system. This mutant produces normal magnetosomes; however, its response to abrupt magnetic field reversals is faster than wild-type strain. This behavioral difference is probably a consequence of altered flagella function, as suggested with our dynamics simulation study by modeling M. magneticum AMB-1 cell as an ellipsoid. These data indicate that, Amb0994 is involved in the cellular response to magnetic torque changes via controlling flagella. In summary, this study, besides contributing to a better understanding of magnetotaxis mechanism, demonstrated the CRISPR-(d)Cas9 system as a useful genetic tool for efficient genome editing in MTB.

Autoantibodies can be either harmful or beneficial to the body. The beneficial autoantibodies play important roles in immunosurveillance, clearance of body waste and maintenance of immune homeostasis. Despite their importance, however, people's knowledge on the protective autoantibodies is still very limited. In the current study, we examined two autoantibodies that recognized epitopes with only one amino acid. One was against mono-methylated lysine (Kme) and the other was against tri-methylated lysine (Kme3). We found that the antibodies were highly specific and not polyreactive. They did not cross-react each other. Although anti-Kme antibodies were IgM only, a large proportion of the anti-Kme3 antibodies were switched to the IgG isotype. Mass spectrometric analysis showed that both of the antibodies were mainly derived from IGHV 3-7 and/or IGHV3-74 germ line genes with conserved CDR2. De novo sequencing showed that there was a mutation at either of the SS positions on the CDR1 region, which changed one of the serine residues to a basic amino acid, i.e., arginine or lysine. We also found that neither of the antibodies was expressed at birth, and their earliest appearance was approximately 5 months after birth. All healthy human beings expressed the antibodies when they reached age two and maintained the expression thereafter throughout their life. Patients with systemic lupus erythematosus had lower levels of the IgM isotype antibodies. Serum levels of the two IgM antibodies were closely correlated, implying that they were produced by cells from the same B cell subset. We also found that both anti-Kme and anti-Kme3 antibodies could bind and might take part in the clearance of neutrophil extracellular traps released from activated cells. In conclusion, although anti-Kme and anti-Kme3 antibodies share many similarities in their origins, they are different antibodies and have different characteristics.

The major effects of cannabinoids and endocannabinoids are mediated via two G protein-coupled receptors, CB1 and CB2, elucidation of the mechanism and structural determinants of the CB2 receptor coupling with G proteins will have a significant impact on drug discovery. In the present study, we systematically investigated the role of the intracellular loops in the interaction of the CB2 receptor with G proteins using chimeric receptors alongside the characterization of cAMP accumulation and ERK1/2 phosphorylation. We provided evidence that ICL2 was significantly involved in G protein coupling in coordination with the C-terminal end. Moreover, a single alanine substitution of the Pro-139 in the CB2 receptor that corresponds to Leu-222 in the CB1 receptor resulted in a moderate impairment in the inhibition of cAMP accumulation, whereas mutants P139F, P139M and P139L were able to couple to the Gs protein in a CRE-driven luciferase assay. With the ERK activation experiments, we further found that P139L has the ability to activate ERK through both Gi- and Gs-mediated pathways. Our findings defined an essential role of the second intracellular loop of the CB2 receptor in coordination with the C-terminal tail in G protein coupling and receptor activation.

By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.