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The knowledge of accurate cloud heights (including cloud base height and cloud top height) information and its variation is of great importance to elucidating synoptic variation and improving climate model and prediction precision. Utilizing the theory of variation continuity and first-order discontinuity of meteorological element in frontal zone, cloud front zone is defined as transitional zone between the cloud cluster and its adjacent area in vertical direction in order to solve the problem of cloud heights uncertainties observed by different equipments. According to the humidity, scattering and turbulence properties of cloud, using observation from L-band sounding, Ka-band millimeter wave cloud radar (MMCR) and the wind profiler, the variation characteristics of temperature, humidity, radar reflectivity and signal noise ratio (SNR) as well as their differences from the ambient atmosphere are studied. In addition, the differences between convective clouds and stratified clouds are studied in terms of the characteristics of element gradient variation inside and outside clouds. Finally, the identification for cloud front zone is verified by case study and the reasonable scope and identification criterion for cloud base height and cloud top height are concluded. The results show that the first-order and second-order derivative of temperature, humidity, and radar reflectivity are discontinuous in cloud front zone (they are not equal inside and outside the cloud front region), and the vertical gradient of SNR retrieved by wind profiler is also instable, which shows that the cloud boundary range with better spatial consistency can be obtained by different devices, based on the frontal theory. In addition, there are two indicators that can be utilized to distinguish the stratiform clouds from convective clouds. The first is the difference between the vertical gradient of temperature and humidity in clouds and that in ambient atmosphere, which is larger in convective clouds than that in stratiform clouds. The second is the fluctuation amplitude of the second-order derivative of reflectivity in clouds, which is also larger in convective clouds than that in stratiform clouds. The concept of cloud front zone can be used to comprehensively identify the common range of cloud height detected by different devices, indicating that there are consistent variation characteristics in a certain area near the cloud front zone for different devices. The similarity of cloud vertical structures retrieved by multi-source equipment observation are elucidated through the characteristics of cloud front zone, which is worth applying for collaborative observation of different devices.

Ka-band cloud radar data from 2017 to 2019 in Beijing Atmosphere Observation test-bed of CMA, combining with observations of automatic weather station and ceilometer are used to analyze the variation and vertical structure of low-level clear-air echo from aspects of intensity, velocity, space scale, depolarization ratio and height of clear-air echo.Based on ceilometer and cloud radar detection sensitivity difference of particle radius and density, clouds and clear-air echo are identified, using image processing technology to distinguish the layered turbulence echo and the dot-like insect echo.Based on different scattering mechanisms, scattering characteristics of the layered turbulence echo and the dot-like insect echo are analyzed. Generally, the range of equivalent reflectivity factors in millimeter wavebands of the clear-air echo caused by atmospheric turbulence is -70 dBZ to -30 dBZ, while the dot-like insect echo reflectivity factor is greater than -30 dBZ.Results show that radar clear-air echoes mainly contain the layered turbulence echo and the dot-like insect echo in the boundary layer and the echo height is within 3000 m. The intensity and height of clear-air echoes show obvious seasonal and diurnal variation characteristics. The echo height is lower in winter and higher in summer, which is well correlated with the surface temperature. There is almost no clear-air echo when the surface temperature is below 5℃, so there is almost no clear-air echo in January, February, November and December, while the average echo height is the highest in July and August. The radar reflectivity factor of clear-air echo is within the range of -40 to -15 dBZ with mean value of -28 dBZ. As the height increases, the reflectivity factor intensity decreases gradually, the peak value of the probability density distribution function of the radar reflectivity factor for clear-air layered turbulence echo is -35 dBZ, and that of the dot-like insect echo is -30 dBZ. The vertical movement speed of clear-air echo is mainly within -1.5 to +0.5 m·s-1, and downward movement is dominant. The linear depolarization ratio value of layered turbulent echo is larger than that of dot-like insect echo, which is generally within the range of -10 to -5 dB. Within 1000 meters at the lower level, the range of linear depolarization ratio is wide and gradually narrows with the increase of height. The linear depolarization ratio of dot-like insect echoes is generally within the range of -15 to -8 dB and increases gradually with the height.

Based on continuous observations of aerosol optical properties from sun-photometer and PM2.5 concentration, the variation of aerosol optical depth, single scattering albedo and asymmetry factor during a pollution episode in Beijing from 25 January to 28 January in 2018 are analyzed. Combined with Raman-Mie Lidar vertical detection, the vertical variation of aerosol extinction coefficient is analyzed in detail. Based on ground-based observations, using a shortwave radiative transfer model, the shortwave radiative heating rates under the clear sky background during the pollution episode are calculated. Results show that under clean condition (25 January 2018), the average daily PM2.5 concentration is 19.00 μg·m-3, aerosol optical depth at 440 nm is 0.13, single scattering albedo is 0.87, and the extinction coefficient of aerosol is less than 0.10 km-1. During the pollution episode (26-27 January 2018), the average daily PM2.5 concentration is 83.21 μg·m-3, aerosol optical depth is 2.48, single scattering albedo increases to 0.94, the main aerosol extinction layer height increases to 3.00 km and the mean extinction coefficient of the whole layer is 0.43 km-1. The aerosol layer can heat the atmosphere evidently, the magnitude of radiative heating rates by aerosol depends on distribution of the aerosol in the vertical direction, and the heating rate under the concentrated heating layer decreases rapidly. Under clean condition, extinction coefficient is less than 0.1 km-1 which causes the shortwave radiative heating rate of aerosol layer within 10.00 K·day-1. During the pollution episode, the strong heating effect in the middle and upper aerosol layers (1.50-3.00 km) where the average shortwave radiative heating rate reaches 13.89 K·day-1, while the lower aerosol layer (within 1.50 km) has a weak heating effect, and the average shortwave radiative heating rate within 1.50 km is only 0.99 K·day-1. Heating rate accuracy is affected by single scattering albedo, the increased aerosol scattering ability would weaken the heating effect on the atmosphere, and the heating rate in pollution condition is more sensitive to changes of aerosol scattering ability. With the mean extinction coefficient of the whole layer being 0.43 km-1, the increase of single scattering albedo from 0.87 to 0.94 cause the heating rate of the upper and middle aerosol layers decreases by 3.74 K·day-1, while the heating rate of the lower aerosol layer increases by 0.81 K·day-1 on 27 January 2018.

Ground-based microwave radiometer (MWR) has a crucial role in scientific researches, weather modification service and climate change studies. MWR adopts passive remote sensing technology which has smaller volume, lower power consumption. Ground-based microwave radiometer detects atmospheric temperature and humidity by receiving atmospheric microwave radiation, which can conduct 24-hour unattended, high-resolution observation. It can detect short-time variation of atmospheric elements. Many studies show that different seasons, different weather conditions, quality control algorithms, and changes in environments have certain effects on retrieval results of MWR. In the case of cloudy condition, the uncertainty of cloud absorption coefficient leads to the increase of retrieval error and incorrect data of MWR especially. In order to improve temperature and relative humidity detection capabilities of MWR, the experiment builds BP neural network algorithm with 6 years(from 2011 to 2016) sounding data. The experiment builds two types of retrieval methods because there are some differences of microwave radiation transfer between clear and cloudy samples. The test uses measured brightness temperature data (requiring correction) and cloud data of millimeter-wavelength cloud radar as model inputs and then uses sounding data to evaluate model outputs (temperature and relative humidity profiles) from 2017 to 2018.Results show that correlation coefficients between outputs of 4 models (clear sky sample temperature model, cloudy sample temperature model, clear sky sample relative humidity model and the cloudy sample relative humidity model) and sounding data are 0.99, 0.99, 0.80 and 0.78. Taking sounding profiles as reference, root mean square errors (RMSE) of retrieval results of 4 models are 2.3℃, 2.3℃, 9%, 16%. Comparing with the MWR original profiles, RMSEs of 4 models are reduced by 0.4℃, 0.3℃, 11% and 9%, accuracies are improved by about 30%, 28%, 64% and 45%. In particular, the deviation of temperature model and humidity model within ±2℃ and ±20% account for 68%, 70% and 95%, 78%, which are 7%, 5% and 27%, 23% higher than MWR original profiles. The bias correction of brightness temperature and the training retrieval model of distinguishing weather samples are helpful to improve the retrieval accuracy of MWR temperature and humidity profiles. The network model combined with cloud radar information has obviously better effects on the retrieval result under cloudy samples.Through these experiments, the quality control of brightness temperature, combination of active and passive retrieval algorithms are well improved. The combination of active and passive retrieval effectively improves the performance of MWR, which will lay a foundation for the development of the comprehensive observation system of atmospheric profiles.

The deformation behavior in the U-Nb shape memory alloys (SMAs) is significantly sensitive to the aging effect, where the underlying mechanism remains unclear. In the present work, in-situ neutron diffraction is used to investigate simultaneously the macroscopic and microscopic stress-strain behaviors as well as the microstructure evolution in α″-martensitic U-Nb SMAs. The aging-effect-modulated mechanical properties are achieved through the modified twinning-detwinning process. The initial yielding strength is significantly increased from about 330 to 650 MPa at room temperature, while from approximately 440 to 700 MPa at 100 °C. The in-situ observations show that the strength enhancement arises from the aging-induced resistance during the twinning-detwinning process. High resolution neutron diffraction patterns indicate that the α″ phase structure is unchanged after aging. The aging effect is therefore understood by employing the defect migration mechanism, which explains well the enhanced yielding strength and twinning-detwinning resistance. It also suggests that the controllable properties could be realized by engineering the defect migration process and thus tuning the aging effect. These findings might shed some light on materials design and properties controlling for α″-martensitic U-Nb and other SMAs (e.g., Ni-Ti). Keywords: Shape memory alloys, Aging effect, Micromechanism, Twinning-detwinning, Properties tailoring

By means of ab initio molecular dynamics (AIMD), we have evidenced the formation of the localized Nb clusters in the U-Nb liquid alloys even with the very low Nb concentrations. These localized Nb clusters are characterized, qualitatively and quantitatively, in terms of the pair correlation function, structure factor, coordination number and chemical short-range order parameters. The existence of the first highest peaks of the partial Nb-Nb pairs in both their pair correlation functions and structure factors reveals that the Nb atoms prefer to accumulate themselves together to form various localized clusters with three typical Nb networks of Nb2 dimers, opening chains (Nb3 or Nb4 chains) and closed triangles (Nb3 triangles) in the U-Nb liquid alloys. These Nb-Nb affinitive facts are further supported by the derived negative Nb-Nb chemical short-range order parameters. In contrast, both U-U and U-Nb interactions in these liquid alloys are further revealed to have the nearly zero, or positive, chemical short-range order parameters, corresponding to a relatively weak U-U, or repulsive U-Nb, interactions in the U-Nb liquid alloys.

Magnesium and its alloys show strong mechanical anisotropy due to their hexagonal close-packed structure. This paper processed ambient extrusion and subsequent annealing on AZ31 magnesium alloy bars to investigate the effect of working hardening and texture weakening on yield anisotropy of magnesium alloy. After ambient extrusion, yield strength on different loading direction are improved due to working hardening. ED-yield strength has the highest increment because work hardening has a higher effect on prismatic slip. Then, yield anisotropy becomes stronger with the increase of extrusion train. During annealing, static recrystallization occurs firstly in {101‾1} twinning zones and producing recrystallized grains with random orientation. With the growth of recrystallized grains, basal fiber texture is weakened gradually. Such weak basal texture can promote the activation of basal slip when loading along ED, so ED-yield strength shows a high decrement. On this way, the yield anisotropy in AZ31 magnesium alloy bars is weakened through ambient extrusion and subsequent annealing.

Abstract Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group of T lymphocytes with the ability to suppress immune responses and maintain immune homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity and facilitate cancer progression by weakening functions of effector T cells (Teffs). Consequently, targeting Tregs to eliminate them from tumor microenvironments to improve Teffs’ activity could emerge as an effective strategy for cancer immunotherapy. This review outlines the biology of Tregs, detailing their origins, classification, and crucial markers. Our focus lies on the complex role of Tregs in cancer’s development, progression and treatment, particularly on their suppressive role upon antitumor responses via multiple mechanisms. We delve into Tregs’ involvement in immune checkpoint blockade (ICB) therapy, their dual effect on cancer immunotherapy and their potential biomarkers for ICB therapy effectiveness. We also summarize advances in the therapies that adjust Tregs to optimize ICB therapy, which may be crucial for devising innovative cancer treatment strategies.

Background: The reportedly high mutation rate of mitochondrial DNA (mtDNA) may be attributed to the absence of histone protection and complete repair mechanisms. Mitochondrial heteroplasmy refers to the coexistence of wild-type and mutant mtDNA. Most healthy individuals carry a low point mutation load (

Abstract The occurrence of multiple primary lung cancer (MPLC) has witnessed a significant surge in recent years within the Chinese population. MPLC is distinguished by its potential genetic susceptibility and notable genetic heterogeneity. Investigating the etiology of MPLC holds substantial clinical importance.The whole genome sequencing (WGS) and genome-wide linkage analysis were performed in a family affected by a dominant form of lung abnormalities. Specifically, five family members were diagnosed with MPLC, while nine members had pulmonary nodules and one normal member. To confirm the potential pathogenic germline mutations sites, Sanger sequencing was performed in an additional 162 MPLC family patients. Furthermore, molecular biology experiments were conducted to investigate the function and the mechanism of the identified pathogenic mutation site in lung cancer A549 and H322, both in vitro and in vivo. Linkage analysis revealed the presence of shared genomic regions among affected family members. Subsequent exome sequencing identified a deleterious variant within these linkage intervals, specifically a heterozygous mutation in ETS-oncogene transcription factors 4 (ETV4). This particular variant was found in affected family members at a rate of 13 out of 15 individuals. Furthermore, ETV4 P433L mutation could be detected in an additional MPLC family patients and mutation frequency was 3.7% (6 out of 162). The ETV4 P433L mutations site was introduced into lung cancer cell lines, resulting in altered migration and stem-like properties of the cancer cells. Further investigation revealed that the activation of the Wnt/β-catenin signaling pathway, which is associated with stemness, could be attributed to the presence of the ETV4 P433L mutation, suggesting its involvement in tumor promotion. A novel pathogenic germline mutation, ETV4 P433L, was identified in a dominant MPLC family, with a mutation rate of 3.7% among MPLC family patients. The ETV4 P433L mutation was found to impact the stem-like properties and migration of tumors through Wnt/β-catenin signaling pathway.

Abstract Background Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn’s disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences. Methods ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab. Results In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004–2.320; P

Abstract Background Congenital craniovertebral deformity, including basilar invagination (BI) and atlantoaxial instability (AAI), are often associated with three-dimensional (3D) deformity, such as C1-2 rotational deformity, craniocervical kyphosis, C1 lateral inclination, among other abnormalities. Effective management of these conditions requires the restoration of the 3D alignment to achieve optimal reduction. Recently, 3D printing technology has emerged as a valuable tool in spine surgery, offering the significant advantage of allowing surgeons to customize the prosthesis design. This innovation provides an ideal solution for precise 3D reduction in the treatment of craniovertebral deformities. Objective This study aims to describe our approach to individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cages for the quantitative correction of craniovertebral junction deformities. Methods A retrospective analysis was conducted on patients with craniovertebral deformities treated at our institution using individualized 3D-printed porous titanium alloy cages. Preoperative CT data were used to construct models for 3D realignment simulations. Cage designs were tailored to the simulated joint morphology following computer-assisted realignment. Preoperative and postoperative parameters were statistically analyzed. Results Fourteen patients were included in the study, with a total of 28 3D-printed porous titanium alloy cages implanted. There were no cases of C2 nerve root resection or vertebral artery injury. All patients experienced symptom relief and stable implant fixation achieved in all cases. No implant-related complications were reported. Conclusion The use of individualized computer-simulated reduction and the design of C1-2 intra-articular 3D printed porous titanium alloy cage facilitates precise 3D realignment in patients with craniovertebral deformities, demonstrating effectiveness in symptom relief and stability.

Abstract In this study, SiO2 coating was electrodeposited on Ti45Al8.5Nb alloy to enhance its oxidation resistance at 900 °C. The focus was on the interaction between SiO2 coating and the alloy substrate, and specifically, the role of the Nb element in this context. The formation of a SiO2/(Ti, Nb)O2/Ti5Si3 + Al2O3 three-layer oxide scale significantly inhibits the inward diffusion of oxygen. Beyond the characteristic Ti5Si3 + Al2O3 layer at the interface, the Nb2Al phase embedded within Ti5Si3 was observed. Concurrently, the presence of a (Ti, Nb)O2 layer was confirmed. The relationship between the coating thickness and oxidation resistance was also investigated. It was found that the thickness of the SiO2 coating affects the density of the oxide scale and the inward diffusion rate of oxygen. Moreover, due to the good adhesion to the substrate, the derived oxide scale exhibited good anti-peeling performance when subjected to a cyclic oxidation test.

Abstract In underwater acoustic communication (UWA), there is a significant presence of multipath and Doppler spread. The integration of orthogonal frequency division multiplexing (OFDM) with index modulation (IM), utilizing subcarrier index modulation to enhance system performance underwater, has garnered considerable interest from researchers. Multiple mode modulation can enhance utilization by transmitting symbols of different modes on different subcarriers. Inspired by the concepts of index modulation and multiple mode modulation, this paper proposes a method that combines multiple mode indexing with the filter bank multicarrier system (MM-FBMC-IM), enabling the transmission of different modulation orders on each subcarrier to increase system flexibility. Simulations demonstrate that under the same spectral efficiency, multiple mode indexing FBMC offers superior bit error rate (BER) performance compared to conventional FBMC and index modulation FBMC.

Abstract Background Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. Methods A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). Results In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P

Abstract Mapping neuronal networks is a central focus in neuroscience. While volume electron microscopy (vEM) can reveal the fine structure of neuronal networks (connectomics), it does not provide molecular information to identify cell types or functions. We developed an approach that uses fluorescent single-chain variable fragments (scFvs) to perform multiplexed detergent-free immunolabeling and volumetric-correlated-light-and-electron-microscopy on the same sample. We generated eight fluorescent scFvs targeting brain markers. Six fluorescent probes were imaged in the cerebellum of a female mouse, using confocal microscopy with spectral unmixing, followed by vEM of the same sample. The results provide excellent ultrastructure superimposed with multiple fluorescence channels. Using this approach, we documented a poorly described cell type, two types of mossy fiber terminals, and the subcellular localization of one type of ion channel. Because scFvs can be derived from existing monoclonal antibodies, hundreds of such probes can be generated to enable molecular overlays for connectomic studies.

Abstract Background Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. Methods We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. Results In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. Conclusions miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.

Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg