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Geomagnetic storm events have a strong influence on the ionosphere–thermosphere (I-T) coupling system. Analyzing the regional response process of the I-T system and its differences across the northern and southern hemispheres is an important but challenging task. In this study, we used a combination of multiple observations and a model simulation to examine the north–south hemispheric difference in the I-T coupling system in the American and Asian sectors during the geomagnetic superstorm that occurred in May 2024. Observations of the total electron content (TEC) showed that the Asian sector had negative storms in the northern hemisphere and positive storms in the southern hemisphere, a process that exacerbated the hemispheric differences in the TEC. However, both hemispheres of the American sector showed negative storms. The thermospheric composition changes also differed between the two sectors, and their variation could partially explain the hemispheric differences caused by positive and negative storms. Moreover, the influence of the thermospheric density change was less than that of the thermospheric composition. Finally, the dynamic effect of the thermospheric wind and the plasma transport processes strongly modulated the north–south differences in the TEC at nighttime in the American and Asian sectors, respectively, during this superstorm.

Phenolic compounds (PhCs) are aromatic compounds with benzene rings that have one or more hydroxyl groups. They are found or formed in the atmosphere due to various factors such as combustion processes, industrial emissions, oxidation of volatile organic compounds (VOCs), and other photochemical reactions. Due to properties such as relatively high Henry’s law constants and moderate/high water solubility, PhCs are vulnerable to reactions in atmospheric liquid phase conditions with high relative humidity, fog or cloudy conditions. PhCs can lead to the formation of secondary organic aerosols (SOAs), which can have negative effects on atmospheric conditions and human health. Changes in the optical properties of PhCs impact solar radiation absorption and scattering, potentially influencing climate. Additionally, PhCs may interact with other atmospheric constituents, potentially affecting cloud or fog formation and properties, which in turn can impact climate and precipitation patterns. Therefore, monitoring and controlling the emission of PhCs is essential. This paper discusses the transformation processes of PhCs in the atmosphere, including direct conversion of phenol, nitrate-induced and nitrite-induced reactions, hydroxylation reactions and oxidation processes involving triplet excited state organics, also providing a detailed analysis of the transformation processes. The findings lay a theoretical foundation for the future monitoring and control of atmospheric pollutants.

Abstract Objective Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. Methods Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. Results In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490–9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014–1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002–1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969–0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037–1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069–1.141; P

Abstract Background Secretory breast carcinoma (SBC) is a rare malignant breast neoplasm with distinct histological features, including solid, microcystic, tubular, and rarely papillary structures, traditionally characterized by a t (12;15) (p13:q25) translocation, which usually leads to ETV6-NTRK3 fusion, suggesting an early event in tumorigenesis. Due to the rarity of this disease, very few genome sequencing studies have been performed on a series of cases, especially progressive cases. Methods Seven lesions from 5 patients diagnosed at the Third Affiliated Hospital of Soochow University from 2007 to 2021 were included. Clinicopathological features and prognosis/survival data were collected. Next-generation DNA sequencing was performed on six of the seven lesions. Results In total, 3/7 (42.9%) lesions demonstrated estrogen receptor (ER) expression, including weak, moderate to strong staining, and no lesion demonstrated progesterone receptor (PR) expression. There were no cases of human epidermal growth factor (HER2) overexpression, and the Ki-67 index was low. S-100 and pan-TRK protein were diffusely positively expressed in all cases. All lesions were characterized by a t(12;15) (p13:q25) translocation, leading to ETV6-NTRK3 fusion confirmed by fluorescence in situ hybridization (FISH). The sequencing results showed that ETV6-NTRK3 fusion was the main driver of early tumorigenesis, while SBC with invasive biological behavior had more complex genomic variation in which TERT promoter mutation was detected. Conclusions Immunohistochemical staining of a biomarker panel, including ER, PR, HER2, Ki-67, S-100 and pan-TRK, can be used as an auxiliary diagnostic tool, and FISH detection can be used as a diagnostic tool. ETV6-NTRK3 gene fusion involving multiple sites may drive tumorigenesis, while mutations in the TERT promoter region may be a factor driving tumor progression.

PurposeErythrodermic psoriasis (EP) is a severe form of psoriasis that affects multiple organs, including the cardiovascular system. However, few studies have focused on this condition.This study is aimed to assess the prevalence and factors associated with heart failure in EP patient, and to the measure the serum concentrations of fibroblast growth factor 23 (FGF23), a potential predictor of chronic heart failure.MethodsWe retrospectively studied patients with EP hospitalized at Peking Union Medical College Hospital between January 2005 to October 2021. The prevalence of heart failure and associated factors was measured. In addition, peripheral blood samples were collected from 17 patients and matched with samples from eight healthy controls, and their serum concentrations of FGF23 were measured by ELISA.ResultsWe studied 225 patients with EP, with a male: female ratio of 2.7:1 and a mean age of 47.6 ± 16.7 years. Twenty-five (11.1%) participants were diagnosed with heart failure during their hospital stay. The patients with EP and heart failure were older (58.2 years vs. 46.2 years, p = 0.001); had a higher prevalence of a history of coronary heart disease (32.0% vs. 21.5%, p

The construction of a power system including renewable energy has become the direction of development for the power industry as a result of the “carbon peaking and carbon neutrality” targets. Yet because the electricity market (EM), carbon market (CM), and green certificate market (GCM) have traditionally operated independently, with little interaction among them. To explore the interaction and correlation among the three markets, this paper analyzes the trading patterns and mutual influencing factors of the EM, CM and GCM and proposes the optimal decision-making model of “carbon-electricity-certificate” integration of multiple markets based on the decision-making behavior of power producers in each market. Finally, the golden jackal optimization algorithm (GJO) is used to solve the problem under the condition of network security. The simulation results show that the integration of multiple markets is more conducive to promoting the consumption of renewable energy source (RES), and also verify the feasibility and effectiveness of GJO in solving the optimal decision-making problem of power producers in EM.

Background: Erythrodermic psoriasis (EP) remains challenging to manage because it is rare and has complex complications. Although acitretin is recommended as an appropriate choice for EP, there is a lack of large-scale evidence. Objectives: This study aims to assess the efficacy and safety of acitretin as systemic monotherapy in EP patients. Design: We retrospectively analyzed data from patients with EP who received at least 3 months of acitretin as systemic monotherapy during hospitalization and out-patient follow-up from January 2005 to May 2021 at the Peking Union Medical College Hospital, China. Methods: The efficacy was clinically evaluated after 1, 2, 4, and 12 weeks of treatment, which was classified as a good response (>75% of lesions cleared), partial response (50%–75% cleared), moderate response (25–50% cleared), or no response (

Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases, including acquired hemophilia A, hypereosinophilic syndrome, aplastic anemia, autoimmune thrombocytopenia, and hematological malignancies. Early identification of these comorbidities contributes to a better control and reduced mortality. This article details the atypical clinical manifestations of BP when associated with hematological diseases, specific diagnostic strategies, underlying mechanistic connections, and possible treatments. Cross-reactivity between autoantibodies and exposed abnormal epitopes, shared cytokines and immune cells, together with genetic susceptibility are the most common connections between BP and hematological diseases. Patients were most often successfully treated with oral steroids combined with medications specifically targeting the hematological disorders. However, the individual comorbidities require specific considerations.

Abstract Boron neutron capture therapy (BNCT) was first proposed as early as 1936, and research on BNCT has progressed relatively slowly but steadily. BNCT is a potentially useful tool for cancer treatment that selectively damages cancer cells while sparing normal tissue. BNCT is based on the nuclear reaction that occurs when 10B capture low-energy thermal neutrons to yield high-linear energy transfer (LET) α particles and recoiling 7Li nuclei. A large number of 10B atoms have to be localized within the tumor cells for BNCT to be effective, and an adequate number of thermal neutrons need to be absorbed by the 10B atoms to generate lethal 10B (n, α)7Li reactions. Effective boron neutron capture therapy cannot be achieved without appropriate boron carriers. Improvement in boron delivery and the development of the best dosing paradigms for both boronophenylalanine (BPA) and sodium borocaptate (BSH) are of major importance, yet these still have not been optimized. Here, we present a review of this treatment modality from the perspectives of radiation oncology, biology, and physics. This manuscript provides a brief introduction of the mechanism of cancer-cell-selective killing by BNCT, radiobiological factors, and progress in the development of boron carriers and neutron sources as well as the results of clinical study.

The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes and diseases, such as depression. Oxidative stress can result in or aggravate a battery of pathological processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder and ferroptosis, which have been found to be involved in the development of depression. Inhibition of oxidative stress and related pathological processes can help improve depression. In this regard, the nuclear factor erythroid 2-related factor 2 (Nrf2) in the antioxidant defense system may play a pivotal role. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damages, but also directly regulate the genes related to the above pathological processes to combat the corresponding alterations. Therefore, targeting Nrf2 has great potential for the treatment of depression. Activation of Nrf2 has antidepressant effect, but the specific mechanism remains to be elucidated. This article reviews the key role of Nrf2 in depression, focusing on the possible mechanisms of Nrf2 regulating oxidative stress and related pathological processes in depression treatment. Meanwhile, we summarize some natural and synthetic compounds targeting Nrf2 in depression therapy. All the above may provide new insights into targeting Nrf2 for the treatment of depression and provide a broad basis for clinical transformation.

Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenerative disease worldwide. The primary pathological hallmarks of AD are the deposition of β-amyloid plaques and neurofibrillary tangles. Autophagy, a pathway of clearing damaged organelles, macromolecular aggregates, and long-lived proteins via lysosomal degradation, has emerged as critical for proteostasis in the central nervous system (CNS). Studies have demonstrated that defective autophagy is strongly implicated in AD pathogenesis. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, enhances the expression of related genes that control autophagosome formation, lysosome function, and autophagic flux. The study of TFEB has greatly increased over the last decade, and the dysfunction of TFEB has been reported to be strongly associated with the pathogenesis of many neurodegenerative disorders, including AD. Here, we delineate the basic understanding of TFEB dysregulation involved in AD pathogenesis, highlighting the existing work that has been conducted on TFEB-mediated autophagy in neurons and other nonneuronal cells in the CNS. Additionally, we summarize the small molecule compounds that target TFEB-regulated autophagy involved in AD therapy. Our review may yield new insights into therapeutic approaches by targeting TFEB and provide a broadly applicable basis for the clinical treatment of AD.

Energy-saving and emission reduction will become the focus of the energy industry in the future. The coordination of the carbon and electricity markets can help achieve the goals of carbon reduction. With the establishment of the carbon market, carbon emitting power generation units (CEPGU) need to consider the trading strategy and comprehensive benefits in the electricity and carbon markets. To further explore the mechanism and interaction process of electricity price and carbon price, the day-ahead electricity market model and carbon market trading model are developed in this study. Based on the deviation between the bid-winning power output in the electricity market and the quota plan in the carbon market, the generation cost model and the carbon quota trading decision model of the units are constructed. Finally, a case study is provided to simulate the coordinated trading process of the carbon and electricity markets. The transaction time scales of the two markets are matched. The results prove that the generation plan of the units can coordinate with the carbon quota level and provide a trading strategy for the power generation enterprises.

Objective: Glutamate mediated excitotoxicity, such as oxidative stress, neuroinflammation, synaptic loss and neuronal death, is ubiquitous in Alzheimer's disease (AD). Our previous study found that 15 Hz repetitive transcranial magnetic stimulation (rTMS) could reduce cortical excitability. The purpose of this study was to explore the therapeutic effect of higher frequency rTMS on 3xTg-AD model mice and further explore the mechanisms of rTMS. Methods: First, WT and 3xTg-AD model mice received 25 Hz rTMS treatment for 21 days. The Morris water maze test was used to evaluate the cognitive function. The levels of Aβ and neuroinflammation were assessed by ELISA and immunofluorescence. Oxidative stress was quantified by biochemical assay kits. Brain glucose metabolism was assessed by 18F-FDG PET. Apoptosis was assessed by western blot and TUNEL staining. Synaptic plasticity and PI3K/Akt/GLT-1 pathway related protein expression were assessed by western blot. Next, to explore the activity of PI3K/Akt in the therapeutic effect of rTMS, 3xTg-AD model mice were given LY294002 intervention and rTMS treatment for 21 days, the experimental method was the same as before. Results: We found that 25 Hz rTMS could improve cognitive function of 3xTg-AD model mice, reduce hippocampal Aβ1-42 levels, ameliorate oxidative stress and improve glucose metabolism. rTMS alleviated neuroinflammatory response, enhanced synaptic plasticity and reduced neuronal loss and cell apoptosis, accompanied by activation of PI3K/Akt/GLT-1 pathway. After administration of PI3K/Akt inhibitor LY294002, 25 Hz rTMS could not improve the cognitive function and reduce neuron damage of 3xTg-AD model mice, nor could it upregulate the expression of GLT-1, indicating that its therapeutic and protective effects required the involvement of PI3K/Akt/GLT-1 pathway. Conclusion: rTMS exerts protective role for AD through regulating multiple pathological processes. Meanwhile, this study revealed the key role of PI3K/Akt/GLT-1 pathway in the treatment of AD by rTMS, which might be a new target.

Abstract Background Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib. Methods A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib. Results Compound heterozygous variants of TREX1 were observed in the patient’s genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient’s father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient’s mother. One of the proband’s elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement. Conclusions We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease.

Flavones predominantly accumulate as O- and C-glycosides in kumquat plants. Two catalytic mechanisms of flavone synthase II (FNSII) support the biosynthesis of glycosyl flavones, one involving flavanone 2-hydroxylase (which generates 2-hydroxyflavanones for C-glycosylation) and another involving the direct catalysis of flavanones to flavones for O-glycosylation. However, FNSII has not yet been characterized in kumquats. In this study, we identified two kumquat FNSII genes (FcFNSII-1 and FcFNSII-2), based on transcriptome and bioinformatics analysis. Data from in vivo and in vitro assays showed that FcFNSII-2 directly synthesized apigenin and acacetin from naringenin and isosakuranetin, respectively, whereas FcFNSII-1 showed no detectable catalytic activities with flavanones. In agreement, transient overexpression of FcFNSII-2 in kumquat peels significantly enhanced the transcription of structural genes of the flavonoid-biosynthesis pathway and the accumulation of several O-glycosyl flavones. Moreover, studying the subcellular localizations of FcFNSII-1 and FcFNSII-2 demonstrated that N-terminal membrane-spanning domains were necessary to ensure endoplasmic reticulum localization and anchoring. Protein–protein interaction analyses, using the split-ubiquitin yeast two-hybrid system and bimolecular fluorescence-complementation assays, revealed that FcFNSII-2 interacted with chalcone synthase 1, chalcone synthase 2, and chalcone isomerase-like proteins. The results provide strong evidence that FcFNSII-2 serves as a nucleation site for an O-glycosyl flavone metabolon that channels flavanones for O-glycosyl flavone biosynthesis in kumquat fruits. They have implications for guiding genetic engineering efforts aimed at enhancing the composition of bioactive flavonoids in kumquat fruits.

Wheat can be cultivated by hole sowing, but its border effect has not yet been studied. Therefore, we carried out a field experiment from 2021 to 2022 at the Doukou Crop Experimental Demonstration Station (108°52′ E, 34°37′ N) of Northwest A&F University in Jingyang County, Xianyang City, Shaanxi Province, China. The response of dry matter, photosynthetic characteristics, and yield components of wheat to the border effects under the hole sowing method was studied. The results showed specific border effects on each index of five wheat varieties (XN136, XN175, XN527, XN536, and XN765), among which the border effects of XN175 and XN765 were the most significant, with the highest yield. Subsequent correlation analysis revealed that only grain per spike and intercellular carbon dioxide concentration responded negatively to the border effects, and the rest were positively correlated. Finally, we conducted a random forest model analysis of different indicators of wheat varieties with significant border effects. We found that net photosynthetic rate and aboveground dry matter per plant had the most significant impact and contribution to the border effects. In contrast, grain per spike had the most negligible impact on the border effects. Our results fill a gap in the study of the border effects of wheat under hole sowing cultivation for future researchers.

BackgroundBullous pemphigoid (BP) is a senile chronic autoimmune bullous skin disease with a high relapse rate, which significantly impairs patients’ quality of life and contributes to disease mortality. This observational case-control study explores the gene polymorphisms of cytokines and their clinical significance in Chinese patients with BP.MethodsIL-1α (rs1800587), IL-1β (rs16944, rs1143627, rs1143634), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, rs1800872), IL-13 (rs1800925, rs20541), TNF-α (rs1799964, rs1800630, rs1799724, rs361525), IFN-γ (rs1799964, rs1800630, rs361525, rs1800629, rs4248160, rs1800750), and TGF-β1 (rs2317130, rs1800469, rs4803457) genes were genotyped in the healthy controls and BP patients, respectively. Expression of these cytokines in serum was measured. Medical profiles of patients, including baseline characteristics and prognosis, were statistically analyzed.ResultsWe found that IL-1 β and IL-13 concentrations were higher in the BP patients’ sera compared to those in the controls. For IL-13, significant differences were found in the nucleotide ratio/genotype/haploid frequency/haplotype, respectively. IL-13 (rs20541, rs1800925) is related to gender, and the IL-13 genotype was significantly associated with recurrence.ConclusionsBP is associated with IL-13 gene polymorphism and IL-13 concentration is elevated in blood circulation in patients with BP. Our results support that IL-13 is relevant in the pathogenesis of BP, suggesting that IL-13 could potentially represent a promising target for BP therapy and a prognostic marker.

In this paper, the high-temperature rheological behavior of 1420 aluminum–lithium alloy under experimental conditions (temperatures of 350–475 °C and strain rates of 0.01–10 s−1) was systematically investigated using a Gleeble-3500 thermal simulation tester (temperature 350~475 °C, strain rate of 0.01~10 s−1). Based on the flow stress curves of this alloy, four different types of high-temperature constitutive models of the alloy were constructed: the Arrhenius (AR) model, the Modified Johnson–Cook (MJC) model, the Modified Zerilli–Armstrong (MZA) model, and the VOCE model. The prediction accuracy of the four constitutive models was compared, and the response of the accuracy of the four constitutive models to the deformation parameters (temperature, deformation rate, and strain) was analyzed. The results showed that the VOCE, AR, and MZA models had high overall prediction accuracy with average absolute relative error (AARE) of 1.8933%, 3.9912%, and 7.8422%, respectively. The VOCE model could achieve the prediction of large strain deformation resistance under small strain with small batch experimental conditions for the corresponding conditions. The AR model had optimal prediction accuracy for the high-rate deformation process. The MJC model had the optimal prediction accuracy for the low-temperature low-rate deformation process. The MZA model had better prediction accuracy for the low-rate high-temperature deformation process. The 1420 aluminum–lithium alloy process parameters selection area constitutive model matching diagram was constructed.

Background: Residential airborne fungi may present obvious risk to human health. However, many countries do not recognize the necessarily need to control residential airborne culturable fungi (RAF). In China, few systemic investigations have been conducted to illustrate the distribution of residential airborne fungi and identify the association between indoor influencing variables and RAF under general living scenario in China. Objective: This study aimed to investigate RAF with the on-site research of 12 typical cities in China, and provided the latest characteristics and potential influencing factors of RAF under general living scenario. Methods: We measured RAF and investigated residential characteristics in 12 typical cities in China, 2018. At least 50 resident families were randomly selected both from downwind and upwind districts in each city with pre-proposed requirements. The RAF were sampled by the six-stage Anderson impactor. PM2.5 and PM10 were monitored by calibrated light-scattering dust meters. CO and CO2 were monitored by non-dispersive infrared analyzer method. NO2 was determined by Saltzman method. General linear model was used to evaluate the association between RAF exposure and residential characteristics with adjustment for potential confounders. Results: The RAF concentrations ranged from 0 to 9371 CFU/m3 with a median concentration of 396 CFU/m3. The median concentrations of RAF in the warm season were statistically higher than the cold season in Panjin, Qingdao, Lanzhou and Luoyang, but lower than the cold season in Shijiazhuang, Ningbo and Nanning. RAF in the bedrooms were more than the living rooms in all cities except Xi'an. Temperature and humidity had an interactive effect on the RAF (OR = 1.0006, 95% CI: 1.0005, 1.0006). Some residential environmental pollutants, including PM2.5 (OR = 0.9989, 95% CI: 0.9988, 0.9989), PM10 (OR = 0.9993, 95% CI: 0.9993, 0.9993), and CO2 (OR = 0.0236, 95% CI: 0.0230, 0.0243), were negatively correlated with RAF. CO (OR = 1.1450, 95% CI: 1.1433, 1.1467) and NO2 (OR = 1.0026, 95% CI: 1.0024, 1.0028) were positively correlated with RAF. Architectural characteristics (sunlight exposure, building history, longitude, latitude, total living area, living floor, distance from the road, house type, the layers of window glass and decoration), family-related information (income) and lifestyle behaviors (keeping pets, growing plants, cooking, using insecticide, burning incense, heating, using air conditioner and cleaning frequencies) were also significantly related with RAF. Conclusions: This study reported nation-wide baseline condition of RAF and related influencing factors under general living scenario with quantitative details, which are exceedingly promising for evidence-driven standard and reasonable control strategy of residential airborne culturable in China.

Abstract Background Sulfur mustard (SM) is a notorious chemical warfare agent that can cause severe acute lung injury (ALI), in addition to other lesions. Currently, effective medical countermeasures for SM are lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs) possess self-renewal and multipotent differentiation capacity. BMSCs can also migrate to inflammation and injury sites and exert anti-inflammatory and tissue repair functions. Here, we report the curative effect of BMSCs on SM-induced ALI in a mouse model. Methods Mice BMSCs were injected into mice via the tail vein 24 h after SM exposure. The distribution of BMSCs in mice was detected by fluorescence imaging. The therapeutic potential of BMSCs was evaluated by the calculating survival rate. The effects of BMSCs on lung tissue injury and repair assessment were examined by staining with H&E and measuring the lung wet/dry weight ratio, BALF protein level, and respiratory function. The effects of BMSCs on the infiltration and phenotypic alteration of inflammatory cells were analyzed by immunohistochemistry and flow cytometry. The levels of chemokines and inflammatory cytokines were examined using the Luminex Performance Assay and ELISA. RNA interference, western blotting, and ELISA were applied to explore the role of the TLR4 signaling pathway in the anti-inflammatory effects of BMSCs. The extent of tissue repair was analyzed by ELISA, western blotting, and immunohistochemistry. Results Fluorescence imaging indicated that the lung is the major target organ of BMSCs after injection. The injection of BMSCs significantly improved the survival rate (p

Pancreatic cancer stem cells (CSCs) play an important role in the promotion of invasion and metastasis of pancreatic cancer. Protease activation receptor 1 (PAR1) is closely related to malignant progression of tumors, however, its effects on pancreatic cancer stem cell-like (CSC-like) properties formation have not been reported. In this work, the effects of PAR1 on pancreatic cancer stem cell-like (CSC-like) properties formation were studied. PAR1 overexpression can induce CSC-like properties in Aspc-1 cells, whereas interference of PAR1 in Panc-1 cells showed the contrary results. Data on patients with pancreatic cancer obtained from TCGA showed that high PAR1 expression and focal adhesion kinase (FAK) protein considerably affect the prognosis of patients. Further experiments showed that PAR1 could regulate FAK, PI3K, and AKT phosphorylation and the epithelial–mesenchymal transformation (EMT) in Aspc-1 and Panc-1 cells. Doxycycline, as a PAR1 inhibitor, could effectively inhibit the CSC-like properties of pancreatic cancer cells and the FAK/PI3K/AKT pathway activation. Doxycycline inhibits the growth of pancreatic cancer and enhances the treatment effect of 5-fluorouracil (5-FU) in Panc-1 xenograft mouse model. In conclusion, PAR1 promotes the CSC-like properties and EMT of pancreatic cancer cells via the FAK/PI3K/AKT pathway. Doxycycline inhibits the pancreatic cancer through the PAR1/FAK/PI3K/AKT pathway and enhances the therapeutic effect of 5-FU.

This study reports unexpected strong longitudinal structures from Global Navigation Satellite System (GNSS) derived total electron content (TEC) observations in the low-latitude ionosphere over Asia. The observations during 2019–2020 show diverse patterns in the zonal difference of regional TEC, even under geomagnetically quiet conditions. The TEC in the northern hemisphere occasionally exhibits drastic zonal gradients. The intense regional gradients in TEC span a longitudinal extent of about 20°. The higher values may appear on the east or the west side. Strong zonal gradients may appear in all seasons, regardless of geomagnetically quiet or active conditions. The 15 December 2019 and 16 March 2020 cases depict an intense zonal differences cluster in the narrow latitudinal band of 16°N to 28°N, spanning a regional scale smaller than the normal longitudinal structures. In contrast, the Global Ionospheric Maps (GIMs) with a longitudinal resolution of 5° show a much flatter zonal picture. Such intense and regional-scale zonal structures in the low-latitude ionosphere call for a high zonal resolution of GIMs in terms of better geographically distributed observations. Notably, no counterpart regional structures are found at the conjugated points in the southern hemisphere during the two cases. Although the physical drivers are not certain, the appearance only in the northern hemisphere possibly excludes the dominant contribution to forming the regional structures from the equatorial electric field.

Abstract Natural killer (NK) cells are a specialised population of innate lymphoid cells (ILCs) that help control local immune responses. Through natural cytotoxicity, production of cytokines and chemokines, and migratory capacity, NK cells play a vital immunoregulatory role in the initiation and chronicity of inflammatory and autoimmune responses. Our understanding of their functional differences and contributions in disease settings is evolving owing to new genetic and functional murine proof‐of‐concept studies. Here, we summarise current understanding of NK cells in several classic autoimmune disorders, particularly in rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes mellitus (T1DM), but also less understood diseases such as idiopathic inflammatory myopathies (IIMs). A better understanding of how NK cells contribute to these autoimmune disorders may pave the way for NK cell‐targeted therapeutics.

Abstract Background Acromicric dysplasia is a rare heritable short‐stature syndrome with joint stiffness and varying degrees of cutaneous hardness. Stiff skin syndrome is a rare connective tissue disorder characterized by diffusely thick and hard skin from the time of birth. Heterozygous point mutations in the FBN1 have been proposed as the predominant cause of both diseases. Methods By performing skin biopsy, X‐ray imaging, electrocardiography, as well as whole‐genome sequencing and Sanger sequencing, we diagnosed an 8‐year‐old Chinese boy as acromicric dysplasia with severe skin stiffness caused by a heterogeneous mutation in the FBN1. Results The patient presented with skin tightness, wrist and ankle stiffness, short stature and limbs, several deformed joints in the extremities, cone‐shaped epiphyses, and distinct facial features. He also had a patent foramen ovale and frequent respiratory infections. Skin biopsy showed thickened dermis and excessive collagen aggregation. Alcian blue staining indicated dermal mucopolysaccharide deposition. Mutation analysis revealed a heterozygous missense mutation, c.5243G>A (p.Cys1748Tyr), in exon 42 of the FBN1. Conclusion This is a report about acromicric dysplasia with stiff skin syndrome‐like severe cutaneous presentation caused by a single hotspot mutation, further revealing the gene pleiotropy of FBN1.

The common cold is an acute, self-limited viral infection of the upper respiratory tract, it is a heterogeneous group of diseases caused by numerous viruses that belong to several different families. A total of 292 households with children aged 7–9 years from Harbin, Xi’an, Ningbo, Nanning, and Shenzhen, China were investigated and 877 air samples from both bedrooms and living rooms in study area were tested to reveal indoor air quality level in 2017. The mean indoor temperature, relative humidity, CO, CO2, NO2, formaldehyde, total count of colonies, and total count of fungi levels were 21.00 ​± ​4.05 ​°C, 54.66 ​± ​16.28%, 0.85±+2.99 mg/m3, 0.08 ​± ​0.06%, 0.03 ​± ​0.02 ​mg/m3, 0.03 ​± ​0.02 ​mg/m3, 173.14 ​± ​4.28 ​cfu/m3, and 241.21 ​± ​4.20 ​cfu/m3, respectively. Of the 292 children, 1.72% had >5 common colds in the past year, 12.04% 3–5 per year, and rest

The Martian ionosphere was actively detected by Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) aboard the Mars Express. The detected echo signal of the MARSIS at an epoch is presented as a function of frequency and time delay to form an ionogram. Some MARSIS ionograms have been processed to obtain the electron density profiles of the Martian topside ionosphere. Unfortunately, more than half of the records cannot be processed with current methods due to the lack of local plasma density information at spacecraft altitude. In this work, we employ a piece-wise exponent to describe the electron density profile of the Martian topside ionosphere. The piece-wise exponent used in our method can reasonably capture the altitude structure of the Martian topside ionosphere, which has been validated with the MGS and MAVEN data. In an altitude regime of lower than 200 km, the average absolute height error of the same electron density between MGS data and fitted profiles is 0.006 km, and the average relative error is 0.008%. In an altitude regime of higher than 200 km, the average absolute height error of the same electron density between MGS data and fitted profiles is 0.55 km, and the average relative error is −0.1%. Based on the altitude structure knowledge of the Martian topside ionosphere, we put forward a new method to invert electron density profiles from MARSIS ionograms with/without local plasma density information. Compared with the previous results, the average absolute difference in the peak height of the retrieved profile is 7.38 km, within the margin of the MARSIS height resolution of 13.8 km. The average relative difference is only 3%. The application of the new method can greatly improve the utilization rate of MARSIS ionogram records.

In this study, two ionospheric nighttime enhancement (INE) events at low latitudes are selected to investigate their spatial features through the observations from Global Navigation Satellite System (GNSS) receivers and ionosondes. For the first time, we present the detailed spatial pictures of premidnight and postmidnight INEs under geomagnetically quiet conditions. The two INE events have the maximum extents of about 11° × 34° and 17° × 25° (longitude × latitude), respectively. Dramatic latitudinal and longitudinal features are revealed in the two INEs. We perform a comparison between the products of Global Ionospheric Maps (GIMs) and total electron content (TEC) measurement from GNSS receivers. However, GIMs fail to capture the TEC distribution during INEs owing to their limited spatial and temporal resolution. Considering the extent of INEs from the observations, the spherical harmonic (SH) expansion adopted by the GIM models needs to upgrade the degree and order to 36. The pixel-based methods developed from two GIM models are required to reduce their grid size for higher spatial resolution. The recommended time interval is shorter than 30 min. Among seven GIMs, CODG and JPLG maps generally have the best performance in reproducing the latitudinal structure of the ionosphere.

Abstract Background This paper investigates the properties and performance of the two generic measures, EQ-5D and SF-12, for Health-Related Quality of Life (HRQoL) assessments of pregnant women living with HIV in Kunming City, Yiliang County, Daguan County, Longchuan County, Tengchong County, Longling County and Fengqing County in Yunnan Province, China. Methods As part of a screening programme for the prevention of mother-to-child transmission of HIV (PMTCT), a retrospective cross-sectional survey was conducted in the seven Maternal and Infant Health Care centers in Yunnan Province, China, between April and June of 2016. The demographic and HIV infection-related information used in the study was collected through questionnaires designed by the study’s staff. HRQoL information was collected using two generic scales: EQ-5D and SF-12. Results A total sample of one hundred and one pregnant women with a mean age of 30.4 ± 5.1 years was investigated. Average time elapsed since infection diagnoses was 5.8 ± 3.4 years. Only one infant (1.0%) was HIV positive, and 56 (55.4%) infants were HIV negative. The HIV status of 44 (43.6%) infants was unknown. The relationship between the EQ-5D functional dimensions and the PCS-12 and the relationship between the EQ-5D anxiety/depression dimension and the MCS-12 were stronger. Those whose PCS-12 and MCS-12 scores were at the median or lower were classified as being in worse health, while those over the median were classified as being in better health. Respondents who reported no problem on each of the EQ-5D dimensions was divided according to the median SF-12 component scores. Those who scored at the median or lower than the median were classified as being in worse health, while those higher than the median were classified as being in better health. The VAS scores were also significantly different than the median split of the SF-12 scores for these subjects. Conclusion EQ-5D and SF-12 showed a discrimination ability in measuring the HRQoL of pregnant women living with HIV. The construct validity was identified for EQ-5D and SF-12 in the study. The respective constructs of EQ-5D and EQ-VAS may not overlap. Pregnant women living with HIV in the study gave more weight to their mental health when they provided a total health rating in EQ-VAS. EQ-VAS could explain the limitations of the EQ-5D dimension scores with ceiling effects in the survey. The results of our study could help to determine the suitable HRQoL instruments for pregnant women living with HIV and provide evidence for the proper comparison of EQ-5D and SF-12.

Monitoring the dynamics of the productivity of ocean water and how it affects fisheries is essential for management. It requires data on proper spatial and temporal scales, which can be provided by operational ocean colour satellites. However, accurate productivity data from ocean colour imagery is only possible with proper validation of, for instance, the atmospheric correction applied to the images. In situ water reflectance data are of great value due to the requirements for validation and reflectance is traditionally measured with the Surface Acquisition System (SAS) solar tracker system. Recently, an application for mobile devices, “HydroColor”, was developed to acquire water reflectance data. We examined the accuracy of the water reflectance measures acquired by HydroColor with the help of both trained and untrained citizens, under different environmental conditions. We used water reflectance data acquired by SAS solar tracker and by HydroColor onboard the BC ferry Queen of Oak Bay from July to September 2016. Monte Carlo permutation F tests were used to assess whether the differences between measurements collected by SAS solar tracker and HydroColor with citizens were significant. Results showed that citizen HydroColor measurements were accurate in red, green, and blue bands, as well as red/green and red/blue ratios under different environmental conditions. In addition, we found that a trained citizen obtained higher quality HydroColor data especially under clear skies at noon.

Context: Immune checkpoint inhibitors have advanced immunotherapy for melanoma patients. Objective: This study evaluates efficacy and safety of ipilimumab and nivolumab combination (IN) for melanoma brain metastases (MBM) patients. Materials and Methods: Literature search was conducted in electronic databases and studies were included if they reported efficacy and safety of IN in MBM patients or prognostic information related to brain metastases. Outcomes evaluated were objective response rate (ORR), complete remission/stable disease/progressive disease rates, progression-free survival (PFS), overall survival (OS), incidence rates of adverse events, and hazard ratios of disease progression or mortality between IN-treated patients with and without brain metastasis. Results: Intracranial ORR was higher in IN-treated MBM patients than with control therapies (nivolumab or ipilimumab plus fotemustine). IN treatment led to longer PFS and OS in than control treatments. Five-year OS of IN-treated MBM patients was up to 51% compared to 34% for nivolumab. Outcomes were better for treatment naïve and asymptomatic patients. Whereas many studies reported significantly higher mortality or progression risk with IN treatment in MBM patients compared to non-MBM melanoma patients, many others did not find this risk significant. Incidence of grade 3/4 adverse events in IN-treated MBM patients was: diarrhea or colitis (16%), hepatitis (15%), rash (8%), increased alanine transaminase (8%), increased aspartate aminotransferase (7%), increased lipase (6%), increased amylase (4%), fatigue (3%), hypophysitis (2%), pneumonitis (2%), headache (2%), nausea or vomiting (1%), and neutropenia (1%). Conclusion: IN is an efficacious and safer treatment option for MBM patients, especially for asymptomatic and treatment naïve patients. [ABSTRACT FROM AUTHOR]