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Recent studies have shown that the ion precipitation induced by EMIC waves can contribute significantly to the total energy flux deposited into the ionosphere and severely affect the magnetosphere-ionosphere coupling. During the geomagnetic storm of 27-28 May 2017, the ARASE and the RBSPa satellites observed typical signatures of EMIC waves in the inner magnetosphere. The DMSP and MetOp satellites observed enhanced proton precipitation during the main phase of the storm. In order to understand the evolution of proton precipitation into the ionosphere, its correspondence to the time and location of excitation of the EMIC waves and its relation to the source and distribution of proton temperature anisotropy, we conducted two simulations of the BATSRUS+RAMSCBE model with and without EMIC waves included. Simulation results suggest that the H- and He-band EMIC waves are excited within regions of strong temperature anisotropy of protons in the vicinity of the plasmapause. In regions where the Arase/RBSPa satellite measurements recorded EMIC wave activity, an increase in the simulated growth rates of H- and He-band EMIC waves is observed indicating that the model is able to capture the EMIC wave activity. The RAM-SCBE simulation with EMIC waves reproduces the precipitating fluxes in the premidnight sector fairly well, and is found to be in good agreement with the DMSP and MetOp satellite observations. The results suggest that the EMIC wave scattering of ring current ions gives rise to the proton precipitation in the premidnight sector at subauroral latitudes during the main phase of the 27 May 2017 storm.

G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diverse. This work investigated how the amino-acid sequences of olfactory receptors (ORs)-the largest GPCR family-encode diversified responses to various ligands. We established a proteochemometric (PCM) model based on OR sequence similarities and ligand physicochemical features to predict OR responses to odorants using supervised machine learning. The PCM model was constructed with the aid of site-directed mutagenesis

SummaryOlfactory neuroblastoma (ONB) is an uncommon malignant tumor known to originate from the olfactory epithelial. The complex tumor ecosystem of this pathology remained unclear. Here, we explored the cellular components with ONB tumors based on scRNA profiles of 96,325 single-cells derived from 10 tumors and 1 olfactory mucosa sample. We discovered 11 major cell types, including 6 immune cell, 3 stromal cell subtypes and epithelial cluster in the tumor microenvironment (TME), and identified 5 common expression programs from malignant epithelial cells. We analyzed subclusters of TME and the interactions among different cell types in the TME. An innovative three-classification of ONB was established via scRNA analysis. Markers for categorizing tumor samples into new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be inferred according to the molecular features of three tumor types. Relative abundance of immunosuppressive TAMs indicated the benefits of immunotherapies targeting myeloid cells.

Within the fully integrated magnetosphere-ionosphere system, many electrodynamic processes interact with each other. We review recent advances in understanding three major meso-scale coupling processes within the system: the transient field-aligned currents (FACs), mid-latitude plasma convection, and auroral particle precipitation. (1) Transient FACs arise due to disturbances from either dayside or nightside magnetosphere. As the interplanetary shocks suddenly compress the dayside magnetosphere, short-lived FACs are induced at high latitudes with their polarity successively changing. Magnetotail dynamics, such as substorm injections, can also disturb the current structures, leading to the formation of substorm current wedges and ring current disruption. (2) The mid-latitude plasma convection is closely associated with electric fields in the system. Recent studies have unraveled some important features and mechanisms of subauroral fast flows. (3) Charged particles, while drifting around the Earth, often experience precipitating loss down to the upper atmosphere, enhancing the auroral conductivity. Recent studies have been devoted to developing more self-consistent geospace circulation models by including a better representation of the auroral conductance. It is expected that including these new advances in geospace circulation models could promisingly strengthen their forecasting capability in space weather applications. The remaining challenges especially in the global modeling of the circulation system are also discussed.

The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here, we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons), whose firing rates display grooming-related modulation. Our study uncovers a new role of the ventral striatum's IC in regulating motor output and has important implications for the neural control of grooming.

The core of the nuclear reactor will melt during severe accidents, which may damage the integrity of the reactor pressure vessel and containment, and release radioactive materials to the environment. The third-generation pressurized water reactor is equipped with severe accident mitigation systems to prevent the high temperature (3000K) corium from melting through the reactor pressure vessel. The severe accident mitigation system mainly includes: primary depressurization system, reactor pit flooding system, containment combustible system, containment heat removal system, etc.. Benefit from these systems, large release frequency (LRF) is restricted to a low level. However, these systems cannot stop the process of core degradation. If severe accident happens, the core will melt and the whole reactor cannot be reused again, causing irreversible economic losses. In order to improve the economy and safety of nuclear power plants, this paper proposes in-vessel-injection (IVI) in the early stage of severe accident, and proves the effectiveness of this measure. According to the analysis, in-vessel-injection in the early stage of severe accident can prevent the large-scale melting of the core during severe accident, and the risk of hydrogen and source items will be greatly reduced.

The interplanetary magnetic field (IMF) By component can cause asymmetric features in the magnetosphere-ionosphere system and influence the electromagnetic energy input. In this study, we use the Space Weather Modeling Framework (SWMF) to study the transient dynamics after a sudden change in the IMF By component exerts on the magnetosphere system. Simulation results reveal that under northward IMF conditions, an abrupt change of the IMF By from duskward to dawnward induces a dawnward geomagnetic field firstly in the cusp region and then in both the near-Earth and magnetotail regions. The signal of the new y-component of the geomagnetic field in the near-Earth region extends tailward while that in the magnetotail moves Earthward, leading the middle-tail region to react last. We investigate in detail the transitional change of the y-component of the geomagnetic field and compare it to the scenario under southward IMF conditions, and find that the latter case reacts in a much simpler manner and the responses are faster globally.

These simulationswere performed for and used in the paper “Ionospheric modulation by EMIC wave driven proton precipitation: observations and simulations” , submitted to JGR, 2022.

These simulationswere performed for and used in the paper “Ionospheric modulation by EMIC wave driven proton precipitation: observations and simulations” , submitted to JGR, 2022.

The adult olfactory epithelium (OE) regenerates sensory neurons and nonsensory supporting cells from resident stem cells after injury. How supporting cells contribute to OE regeneration remains largely unknown. In this study, we elucidated a novel role of Ym2 (also known as Chil4 or Chi3l4), a chitinase-like protein expressed in supporting cells, in regulating regeneration of the injured OE in vivo in both male and female mice and cell proliferation/differentiation in OE colonies in vitro. We found that Ym2 expression was enhanced in supporting cells after OE injury. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE, while Ym2 overexpression by lentiviral infection accelerated OE regeneration. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Furthermore, anti-inflammatory treatment reduced Ym2 expression and delayed OE regeneration in vivo and cell proliferation/differentiation in vitro, which were counteracted by Ym2 overexpression. Collectively, this study revealed a novel role of Ym2 in OE regeneration and cell proliferation/differentiation of OE colonies via interaction with inflammatory responses, providing new clues to the function of supporting cells in these processes. SIGNIFICANCE STATEMENT The mammalian olfactory epithelium (OE) is a unique neural tissue that regenerates sensory neurons and nonsensory supporting cells throughout life and postinjury. How supporting cells contribute to this process is not entirely understood. Here we report that OE injury causes upregulation of a chitinase-like protein, Ym2, in supporting cells, which facilitates OE regeneration. Moreover, anti-inflammatory treatment reduces Ym2 expression and delays OE regeneration, which are counteracted by Ym2 overexpression. This study reveals an important role of supporting cells in OE regeneration and provides a critical link between Ym2 and inflammation in this process.

Background Several pharmacological agents, such as chloroquine/hydroxychloroquine, have been promoted for COVID-19 treatment or pre-exposure prophylaxis. However, no comprehensive evaluation of the safety of these possible agents is available, and is urgently needed. Objective The purpose of this study was to investigate the risks of cardiac adverse events associated with the possible pharmacotherapies for COVID-19, including certain antimalarial, antiviral, and antibiotic drugs. Patients and Methods We conduced retrospective pharmacovigilance analyses of the US Food and Drug Administration Adverse Event Reporting System database. The reporting odds ratio (ROR), a data mining algorithm commonly used in pharmacovigilance assessment, was generated to quantify the detection signal of adverse events. Results Among individuals without coronavirus infection from 2015 Q1 to 2020 Q1, increased risks for cardiac disorders were found for antiviral agents such as chloroquine/hydroxychloroquine (ROR: 1.68; 95% confidence interval [CI] 1.66–1.70), lopinavir/ritonavir (ROR: 1.52; 95% CI 1.39–1.66), and antibiotics such as azithromycin (ROR: 1.37; 95% CI 1.30–1.44) and ceftriaxone (ROR: 1.92; 95% CI 1.80–2.05). Increased serious cardiac adverse events, including myocardial infarction, arrhythmia, and cardiac arrest, were also reported for these drugs. Further analyses of individuals with coronavirus infections revealed that 40% of individuals receiving chloroquine/hydroxychloroquine reported serious cardiac adverse events. Two cases resulted in QT prolongations and one case resulted in cardiac arrest. Chloroquine/hydroxychloroquine and azithromycin contributed to all the QT prolongation and cardiac arrest cases. Conclusions The current pharmacotherapies for COVID-19 are associated with increased risks of cardiac adverse events. Variations in the cardiac safety profiles of these pharmacotherapies were also observed. Clinicians should closely monitor patients with COVID-19, especially those at high risk, using chloroquine/hydroxychloroquine and azithromycin.

A particle-in-cell simulation of symmetric reconnection with zero guide field is carried out to understand the dynamics of ions along the separatrices. Through the investigation of ion velocity distributions at different moments and locations along the separatrices, a typical distribution is found: two counter-streaming populations in the perpendicular direction, with another two populations accelerated into distinct energy levels in the parallel direction. Backward tracing of ions reveals that the counter-streaming cores are mostly composed of ions initially located at the same side of the separatrix, while the other two accelerated populations in the parallel direction are composed of ions crossing through the neutral sheet. Through analysis of energy conversion of these populations, it is found that the ion energization along the separatrix is attributable primarily to the Hall electric field, while that in the region between the two separatrices is caused primarily by the induced reconnection electric field. For the counter-streaming population, the low-energy ions that cross the separatrix twice are affected by both Hall and reconnection electric fields, while the high-energy ions that directly enter the separatrix from the unperturbed plasma are energized mainly by the Hall electric field. For the two energized populations in the parallel direction, the ions with lower-energy are accelerated mainly by the in-plane electric field and the Hall electric field on the opposite side of the separatrix, whereas the ions with higher-energy not only experience the same energization process but also are constantly accelerated by the reconnection electric field.

Odorant receptors (ORs) expressed in mammalian olfactory sensory neurons are essential for the sense of smell. However, structure-function studies of many ORs are hampered by unsuccessful heterologous expression. To understand and eventually overcome this bottleneck, we performed heterologous expression and functional assays of over 80 OR variants and chimeras. Combined with literature data and machine learning, we found that the transmembrane domain 4 (TM4) and its interactions with neighbor residues are important for OR functional expression. The data highlight critical roles of T(4.62) therein. ORs that fail to reach the cell membrane can be rescued by modifications in TM4. Consequently, such modifications in MOR256–3 (Olfr124) also alter OR responses to odorants. T161(4.62)P causes the retention of MOR256–3 in the endoplasmic reticulum (ER), while T161(4.62)P/T148(4.49)A reverses the retention and makes receptor trafficking to cell membrane. This study offers new clues toward wide-range functional studies of mammalian ORs.

These simulations and observations were performed for and used in the paper “Evidences of the chain effect from EMIC wave-driven proton precipitation to ionospheric ionization” Tian, X., Yu, Y., Ma, L., Cao J., submitted to GRL, 2022.

Protons of tens of keV can be resonantly scattered by EMIC waves excited in the magnetosphere and further precipitate down to the upper atmosphere. In this study, we show a case event that shows direct linkage of the EMIC waves, proton precipitation, and ionospheric ionization using space-borne and ground-based measurements. On Oct 11, 2012, the POES observed that the precipitating flux of the proton much larger than that of the electrons in the night sector around magnetic latitude of 65°. Around the same time and location, ground-based magnetometer detected clear signature of EMIC waves, indicating the causal relation to the proton precipitation. We further simulate the impact of this tens of keV proton precipitation on the upper atmosphere, and found good agreement with PFISR observations of electron density and conductivity. On the other hand, the large ionization rate cannot be accounted for by the electron precipitation at that location. This study shows a clear evidence of the precipitating coupling processes within the magnetosphere-ionosphere system.

The mammalian olfactory system enables to sense and distinguish a large number of odors, which is essential to find food, avoid predators, communicate and reproduce, while the human olfactory system can even avoid potential hazard by discriminating the smell quality. Olfactory dysfunction is a common disease symptom which seriously affects the life quality of patients. In addition, many studies have revealed that olfactory dysfunction can also indicate many other potential diseases, such as neurodegenerative diseases and mental diseases. Olfactory dysfunction is an early common symptom of a variety of diseases, such as inflammation, viral infection, neurodegenerative diseases, and the current epidemic of COVID-19. Researchers have indicated that some patients with certain diseases already have suffered from symptoms of olfactory dysfunction early in the clinic. For instance, one of the early clinical symptoms of SARS-CoV-2 virus infection is the loss of smell. Besides, patients suffered from Alzheimer's disease and Parkinson's disease usually have an increased threshold of olfactory perception and even endure anosmia. Therefore, research on early screening and diagnosis of dysosmia diseases on the basis of olfactory function detection is of great significance to control and slow the disease's progression and to improve the health of human body. At present, olfactory function detection technologies mainly contain olfactory neuropsychological testing, electrophysiological detection, olfaction system structure or functional imaging, etc. Although these technologies have played an important role in the study of dysosmia, there have been no standardized detection indicators established so far. Therefore, the establishment and improvement of early olfactory dysfunction disease diagnosis technology based on the detection of olfactory function requires a novel approach in principle and technology. By utilizing the bionic olfactory sensing technologies such as bioelectronic noses, the olfactory analog sensing system with high sensitivity, high specificity and short response time, and even simulating biological olfactory systems, can be expected to be realized. Based on the current understanding of the mechanism of olfactory dysfunction, our team is committed to breaking through the traditional odor-induced olfactory function detection method. By combining with the bionic olfactory perception technology, three original methods which include olfactory neural network chip, organoid chip and neural interactive olfaction detection technology have been proposed. These three technologies essentially construct and simulate the olfactory nervous system in vitro or in vivo, by means of the sensing technique to detect physiological signals changes that correspond with the alternations in the nervous system. However, the difficulties currently lie in how to determine the characteristic physiological signal, and how to establish the correlation between the characteristic signals and the degree of dysosmia for the ultimate goal of further screening the olfactory dysfunction related diseases through the detection parameters. The clarification of these difficulties and in-depth progress of research will promote the innovation and development of olfactory function detection technology, and provide reliable theoretical technical support and experimental basis. This review comprehensively interpreted the current research status of dysosmia diseases, as well as analyzed the principles of bionic olfactory perception technology and its research progress in the detection and diagnosis of dysosmia and related diseases. With the development of multidisciplinary intersection in the field of biomedical engineering, the transformation and application of cell network chips, organoid bionic chips and braincomputer interaction technology will promote the progress of bionic olfactory perception technology in the research of olfactory dysfunction diseases and the innovation of clinical diseases diagnosis. © 2021, Science Press. All right reserved.

A three-dimensional four species multi-fluid magnetohydrodynamic (MHD) model was constructed to simulate the solar wind global interaction with Mars. The model was augmented to consider production and loss of the significant ion species in the Martian ionosphere, i.e., H+, O2+, O+, CO2+, associated with chemical reactions among all species. An ideal dipole-like local crustal field model was used to simplify the empirically measured Martian crustal field. Results of this simulation suggest that the magnetic pile-up region (MPR) and the velocity profile in the meridian plane are asymmetric, which is due to the nature of the multi-fluid model to decouple individual ion velocity resulting in occurrence of plume flow in the northern Martian magnetotail. In the presence of dipole magnetic field model, boundary layers, such as bow shock (BS) and magnetic pile-up boundary (MPB), become protuberant. Moreover, the crustal field has an inhibiting effect on the flux of ions escaping from Mars, an effect that occurs primarily in the region between the terminator (SZA 90°) and the Sun–Mars line of the magnetotail (SZA 180°), partially around the terminator region. In contrast, near the tailward central line the crustal field has no significant impact on the escaping flux.

International audience; G protein-coupled olfactory receptors (ORs) enable us to detect innumerous odorants. They are also ectopically expressed in non-olfactory tissues and emerging as attractive drug targets. ORs can be promiscuous or highly specific, which is part of a larger mechanism for odor discrimination. Here, we demonstrate that the OR extracellular loop 2 (ECL2) plays critical roles in OR promiscuity and specificity. Using site-directed mutagenesis and molecular modeling, we constructed 3D OR models in which ECL2 forms a lid over the orthosteric pocket. We demonstrate using molecular dynamics simulations that ECL2 controls the shape and the volume of the odorant-binding pocket, maintains the pocket hydrophobicity, and acts as a gatekeeper of odorant binding. Therefore, we propose the interplay between the specific orthosteric pocket and the variable, less specific ECL2 controls OR specificity and promiscuity. Furthermore, the 3D models created here enabled virtual screening of new OR agonists and antagonists, which exhibited a 70% hit rate in cell assays. Our approach can potentially be generalized to structure-based ligand screening for other GPCRs that lack high-resolution 3D structures.

Electric field impulses generated by interplanetary shocks can cause a series of dynamic processes in the Earth’s magnetosphere and were previously explained by either fast-mode wave propagation or flow related to compression of the magnetopause. Based on a Space Weather Modeling Framework simulation, we suggest a new scenario in which the evolution of the impulse is due to both the propagation of the fast-mode wave and the compression of the magnetopause, which can explain the simulation and observations in previous related studies. The onset of the electric field impulse is determined by the propagation of the fast-mode wave in the magnetosphere while the peak of the impulse is determined by the propagation of the compression of the magnetopause. The new understanding of the impulse is important for the generation of subsequent ultralow frequency waves through the coupling of the fast-mode to Alfvén waves and field line resonances and related radiation-belt electron acceleration.

Objective. To determine whether arthrographic distention combined with manipulation for frozen shoulder provides additional benefits. Methods. A total of 180 participants from five clinical centers with pain and stiffness in predominantly 1 shoulder for >3 months entered the study, and 165 completed the study. The control group was treated with arthrographic distention alone, and the treatment group underwent manipulation after resting for 5 minutes following arthrographic distention. Patients were followed up at the one and two weeks and at three and six months. For the clinical evaluation, shoulder-specific disability measure (SPADI) score, the visual analog scales (VASs) for pain, and range of active motion were used. Results. 83 patients out of 90 in the treatment group and 82 out of 90 in the control finished the entire study period. SPADI, VAS, Constant-Murley (CM), and range of motion (ROM) were improved after treatments in both groups. The statistical differences were not observed in the CM, adduction, internal rotation, and posterior extension function between groups ( P > .05 ) after the first treatment. And the statistical differences were not observed in the internal rotation, the extorsion, and posterior extension function ( P > .05 ) after the second treatment. Conclusion. Distention arthrography plus manual therapy provided faster pain relief, a higher level of patient satisfaction, and an earlier improvement in AROM of the shoulder than distention arthrography alone in patients with frozen shoulder.

While subauroral polarization streams (SAPS) are well recognized as representatively one of the most important features of magnetosphere-ionosphere (M-I) coupling processes in the subauroral region, the double-peak subauroral ion drifts (DSAIDs) is a newly recognized ionospheric phenomenon, categorized as a subset of subauroral ion drifts (SAIDs). In this study, we investigate both SAPS and DSAIDs that appear during the storm main phase of the 17 March 2015 event through a combination of multi-point observations and numerical simulations. We find that when SAPS/DSAIDs are observed by the DMSP spacecraft near the dusk subauroral region, strong electric fields are detected minutes later by the Van Allen Probes almost in the same conjugate region near the equatorial plane. Numerical simulations are carried out not only to reveal the global context and dynamic evolution of the SAPS in both the magnetospheric and ionospheric systems, but also to aid the understanding of the effect of conductance on the DSAIDs. Our results confirm that SAPS are indeed associated with Region 2 field-aligned currents (FACs) flowing into the low conductance region. On the other hand, the DSAIDs may be related to the double-conductance-trough in the subauroral region.

Spacecraft surface charging during geomagnetically disturbed times is one of the most important causes of satellite anomalies. Predicting the surface charging environment is one prevalent task of the geospace environment models. Therefore, the Geospace Environment Modeling (GEM) Focus Group "Inner Magnetosphere Crossenergy/Population Interactions" initiated a communitywide challenge study to assess the capability of several inner magnetosphere ring current models in determining surface charging environment for the Van Allen Probes orbits during the 17 March 2013 storm event. The integrated electron flux between 10 and 50 keV is used as the metrics. Various skill scores are applied to quantitatively measure the modeling performance against observations. Results indicate that no model consistently perform the best in all of the skill scores or for both satellites. We find that from these simulations the ring current model with observational flux boundary condition and Weimer electric potential driver generally reproduces the most realistic flux level around the spacecraft. A simple and weaker VollandStern electric field is not capable of effectively transporting the same plasma at the boundary toward the Earth. On the other hand, if the ring current model solves the electric field selfconsistently and obtains similar strength and pattern in the equatorial plane as the Weimer model, the boundary condition plays another crucial role in determining the electron flux level in the inner region. When the boundary flux spectra based on magnetohydrodynamics (MHD) model/empirical model deviate from the shape or magnitude of the observed distribution function, the simulation produces poor skill scores along Van Allen Probes orbits.

Olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) detect thousands of volatile environmental odors to form the sense of smell. OSNs are generated from basal cells, which show the characteristics of progenitor/stem cells. In the mammalian OE, persistent neurogenesis occurs during lifetime, providing a unique model to study the tissue turnover and fate determination of stem cells.

Satellite surface charging often occurs in the inner magnetosphere from the pre-midnight to the dawn sector when electron fluxes of hundreds of eV to tens of keV are largely enhanced. Inner magnetosphere ring current models can be used to simulate/predict the satellite surface charging environment, with their flux outer boundary conditions specified either based on observations or provided by other models, such as MHD models. In the latter approach, the flux spectrum at the outer boundary is usually assumed to follow a Kappa or Maxwellian distribution, which however often departs greatly from, or underestimates, the realistic distribution below tens of keV, the energy range that is crucial in the spacecraft surface charging anomaly. This study aims to optimize the electron flux boundary condition of the inner magnetosphere ring current model to achieve a better representation of the surface charging environment. The MHD-parameterized flux spectrum is combined with an empirical electron flux model that specifies the < 40 keV electron flux spectrum. New simulation results indicate that the surface charging environment, monitored by an integrated electron flux between 10

During geomagnetically disturbed times the surface geomagnetic field often changes abruptly, producing geomagnetically induced currents (GICs) in a number of ground based systems. There are, however, few studies reporting GIC effects which are driven directly by bursty bulk flows (BBFs) in the inner magnetosphere. In this study, we investigate the characteristics and responses of the magnetosphere-ionosphere-ground system during the 7 January 2015 storm by using a multi-point approach which combines space-borne measurements and ground magnetic observations. During the event, multiple BBFs are detected in the inner magnetosphere while the magnetic footprints of both magnetospheric and ionospheric satellites map to the same conjugate region surrounded by a group of magnetometer ground stations. It is suggested that the observed, localized substorm currents are caused by the observed magnetospheric BBFs, giving rise to intense geomagnetic perturbations. Our results provide direct evidence that the wide-range of intense dB/dt (and dH/dt) variations are associated with a large-scale, substorm current system, driven by multiple BBFs.

During geomagnetic storms, magnetospheric wave activity drives the ion precipitation which can become an important source of energy flux into the ionosphere and strongly affect the dynamics of the ...

The reconnection front (RF), one of the most efficient accelerators of particles in the terrestrial magnetosphere, is a sharp plasma boundary resulting from transient magnetic reconnection. It has been both theoretically predicted and observationally confirmed that electron-scale substructures can develop at the RFs. How such electron-scale structures modulate the electron energization and transport has not been fully explored. Based on high-resolution data from MMS spacecraft and particle tracing simulations, we investigate and compare the electron acceleration across two typical RFs with or without rippled electron-scale structures. Both observations and simulations reveal that high-energy electron flux behind the RF increases more dramatically if the electrons encounter a rippled RF surface, as compared to a smooth RF surface. The main acceleration mechanism is electron surfing acceleration, in which electrons are trapped by the ripples, due to the large local magnetic field gradient, and therefore undergo surfing motion along the motional electric field.

Ion escape from the atmosphere to space is one of the most likely reasons to account for the evolution of the Martian climate. Based on three-dimensional multifluid magnetohydrodynamic simulations, we investigated the impact of the magnetic inclination angle on O+ escape at low altitudes of 275–1000 km under the typical solar wind conditions. Numerical results showed that an outward ion velocity in the direction opposite to the electromagnetic (EM) force results in weak outward flux and leads to ions becoming trapped by the horizontal magnetic field lines at the local horizontal magnetic equator. Much of the EM force can be attributed to the Hall electric force. In the region of high absolute magnetic inclination angle, the outward ion velocity has the same direction as the EM force, which increases the outward flux and causes ions to diffuse upward along open magnetic field lines to higher altitude. In addition, the EM force is mainly provided by the electron pressure gradient force and the motional electric force. Global results for the magnetic inclination angle indicate that the strong crustal field regions in the southern hemisphere are mainly occupied by magnetic field lines with high absolute magnetic inclination angle, while horizontal field lines are dominant in the northern hemisphere, which leads to a higher O+ escape rate in the Martian southern hemisphere than in the northern, from altitudes of 275 to 1000 km. This is a significant advance in understanding the impact and mechanism of the Martian magnetic field directions on ion escape.

In China, residential building is a major energy consumer and retrofitting of existing residential buildings is considered as an effective method in achieving energy savings. This study examined a high-rise residential building located in northern China. The target-building’s electricity consumption and indoor temperature were gathered and analysed. DesignBuilder software was used to conduct a numerical study on the target-building where we studied the feasibility and energy-saving potentials in retrofitting the target-building to Passivhaus standard. It was found that the energy consumption of the building reduced by 96% for heating and 8.7% for cooling; totally reduced by 78.9%. The cost for the retrofitting was estimated approximately as 18.4 years using the simple payback period method and the current price of the materials in the market. The residents could start to get profit for the remaining lifetime of the building.

The risk of drug-induced liver injury (DILI) poses a major challenge for development of natural products derived from traditional Chinese medicines (NP-TCMs). It is urgent to find a new method for the safety assessment of the NP-TCMs. Recent study has reported an in vitro/in silico method to estimate the acceptable daily intake of hepatotoxic compounds using support vector machine (SVM) classifier and physiologically based pharmacokinetic (PBPK) modeling. However, this method is not suitable for estimating the dosing schedule of compounds which are administered in multiple daily doses. Thus, in this study, the method mentioned above was in particular optimized, and used to estimate the hepatotoxic plasma concentrations of 17 NP-TCMs. Additionally, the oral dosing schedules of the triptolide, emodin, matrine and oxymatrine were also predicted by the SVM classifier and PBPK modeling. The optimization included that: (1) in vitro cytotoxicity data of 28 training set compounds was optimized using benchmark concentrations (BMC) modeling; (2) AUC of the training set compound was used as the in vivo metric instead of Cmax to better reflect the total daily exposure of compounds which are administered in multiple daily doses; (3) using the mean AUC in plasma as in vivo metric and BMC value as in vitro metric could achieve the better toxicity separation index (0.962 vs. 0.938); (4) The TSI for Cmax and BMC values was 0.985 calculated in this study, and the results indicated that BMC modeling improved the separation performance. This optimized in vitro-in vivo extrapolation (IVIVE) workflow could extrapolate in vitro BMC to blood concentrations and the oral dosing schedule which are corresponding to certain risk of hepatotoxicity. The estimated safe dosing schedule of oxymatrine by this optimized method was close to the clinical recommended dosing regimen. The results indicate that the optimized method could be used to predict the dosing schedule of compounds administered in multiple daily doses, and our optimized workflow could be helpful for the safety assessment as well as the research and development on NP-TCMs.

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor with high incidence in East and Southeast Asia. A proper and effective model is urgently needed to explore the mechanisms of tumorigenesis and provide new ideas and methods of cancer treatment.Methods: In this study, we established a three-dimensional (3D) organoid model by patient-derived NPC tissues and adjacent tissues. We described a detailed protocol for culturing of human NPC organoids (including tissue preparation, digestion, culture, subculture, section and immunostaining). The organoids were identified by immunostaining against NPC biomarkers. The drug sensitivity against cisplatin was tested by immunostaining against Ki67 and cleaved Caspase 3.Results: This method was proved to be feasible due to the presence of biomarkers including Vimentin, P63, EGFR and CK34βE12 as well as proliferative/progenitor characteristics such as Ki67, Sox2 and CD54 in NPC organoids. The chemotherapy sensitivity of NPC organoids to cisplatin treatment showed that NPC organoids may be utilized as a platform to verify the effectiveness of different antineoplastic drugs, facilitating to achieve personalized treatment.Conclusions: The NPC organoid may inspire a personalized approach to the management of NPC and expand the repertoire of anti-NPC drugs.