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The presence or absence of sea ice introduces a substantial perturbation to surface‒atmosphere energy exchanges. Comprehending the effect of varying sea ice cover on surface‒atmosphere interactions is an important consideration for understanding the Arctic climate system. The recurring North Water Polynya (NOW) serves as a natural laboratory for isolating cloud responses to a rapid, near-step perturbation in sea ice. In this study, we employed high-resolution Arctic System Reanalysis version 2 (ASRv2) data to estimate turbulent heat fluxes over the NOW and nearby sea ice (NSI) area between 2005/2006 and 2015/2016. The results indicate that the average turbulent heat fluxes in the polynya are about 87% and 86% higher than in the NSI area over the 10 years during the entire duration of the polynya and during polar night, respectively. Enhanced turbulent heat fluxes from the polynya tend to produce more low-level clouds. The relationship between the polynya and low cloud in winter was examined based on Cloud‒Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO). The low-cloud fraction (0–2 km) was about 7%–34% larger over the polynya than the NSI area, and the ice water content below 200 m was about 250%–413% higher over the former than the latter. The correlation between cloud fraction and turbulent heat fluxes in the polynya peaks around the altitude of 200–300 m. These results suggest that the NOW affects the Arctic boundary layer cloudiness and structure in wintertime. Furthermore, higher horizontal resolution reanalysis data can advance our understanding of the cloud-polynya response.

Abstract Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis.

Abstract Transition metal‐catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late‐stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel‐catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross‐electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late‐stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process.

Abstract Large-scale screening for the risk of coronary heart disease (CHD) is crucial for its prevention and management. Physical examination data has the advantages of wide coverage, large capacity, and easy collection. Therefore, here we report a gender-specific cascading system for risk assessment of CHD based on physical examination data. The dataset consists of 39,538 CHD patients and 640,465 healthy individuals from the Luzhou Health Commission in Sichuan, China. Fifty physical examination characteristics were considered, and after feature screening, ten risk factors were identified. To facilitate large-scale CHD risk screening, a CHD risk model was developed using a fully connected network (FCN). For males, the model achieves AUCs of 0.8671 and 0.8659, respectively on the independent test set and the external validation set. For females, the AUCs of the model are 0.8991 and 0.9006, respectively on the independent test set and the external validation set. Furthermore, to enhance the convenience and flexibility of the model in clinical and real-life scenarios, we established a CHD risk scorecard base on logistic regression (LR). The results show that, for both males and females, the AUCs of the scorecard on the independent test set and the external verification set are only slightly lower (

Progress in numerical models and improved computational capabilities have significantly advanced our comprehension of how aerosol particles impact thunderstorm clouds. Yet, much of this research has focused on employing bulk microphysics models to explain the impacts of aerosol particles acting as cloud condensation nuclei (CCN) on electrical activities in thunderstorm clouds. The bulk thunderstorm models use mean sizes of particles and terminal-fall velocities. This causes calculation deviation in the electrification simulation, which in turn leads to deviations in the simulation of lightning processes. Developing this further, we established a three-dimensional high-resolution cloud–aerosol bin thunderstorm model with electrification and lightning to provide more accurate microphysics and dynamic fields for studying electrical activities. For evaluating the impacts of aerosol particles, specifically CCN, on the properties of continental thunderclouds, aerosols from both clean and polluted continental environments were selected. Cloud simulations indicate that droplets develop a narrower spectrum in polluted continental conditions, and weakened ice crystal growth increases the number of small ice crystals compared to clean conditions. Smaller droplets and ice crystals result in less effective riming and decreased graupel concentration and mass. Consequently, a significant decrease in large ice particles leads to a weakened process of charge separation under conditions of pollution. As a direct result, there is about a 43% reduction in lightning frequency and a delay of approximately 5 min in the lightning process under polluted conditions.

Summary: Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing, and mass spectrometry technology to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level, providing an important resource for understanding the relationship between transcription and translation in cells. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19,948 genes and 2,663 protein groups in single mouse oocytes. In particular, we analyzed the correlation of individual RNA and protein pairs, as well as the meiosis regulatory network with unprecedented depth, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, which could be productive for exploring transcriptional and translational regulatory features during oocyte meiosis.

In this paper, by establishing a fragmented field of a prefabricated fragment warhead and simulating the intersection of the aircraft and the fragment field under dynamic conditions, the determination of the distribution of the vulnerable parts of a specific aircraft is realized. On this basis, the structural characteristic test pieces of the vulnerable parts were tested with the high-velocity impact experiments based on the two-stage light-gas gun. Based on the FEM-SPH self-adaptive method, a numerical simulation model with a high reduction degree was established. Combined with the experimental results, the damage mode of high-velocity prefabricated spherical fragments to typical vulnerable structures, especially the characteristics of secondary damage caused by debris clouds were studied. This paper verified the feasibility of methods for the vulnerable structure distribution of the aircraft by combing the shooting-line method and the Monte Carlo method. The FEM-SPH adaptive method simulates the damage mode and secondary damage caused by debris clouds on vulnerable aircraft structures. The study in this paper can be severed as an analysis tool in specific aircraft design and damage mode analysis under different threat sources.

Inflammatory bowel disease unclassified (IBDU) is referred to as colitis that has clinical characteristics related to inflammatory bowel disease, but cannot be clearly determined or classified as either ulcerative colitis (UC) or Crohn’s disease (CD) clinically. Over time, most patients with IBDU can be finally diagnosed as either UC or CD. Treatment of IBDU should follow a step-up strategy. This article describes the clinical characteristics, diagnosis and treatment of IBDU.

Abstract Background Soil salinization has become a global problem restricting the seed yield and quality of crops, including wheat (Triticum aestivum L.). Salinity significantly alters plant morphology and severely disrupts physiological homeostasis. Salt tolerance of wheat has been widely studied whereas core ion transporters responsive to salt stress remain elusive. Results In this study, the wheat seedlings were subjected to salinity toxicity for morpho-physiological and transcriptomic analysis of wheat salt tolerance. There was a inversely proportional relationship between salt concentrations and morpho-physiological parameters. Under the condition of 100 mM NaCl, the H2O2, O2 −, MDA content and membrane permeability were significantly increased whereas the chlorophyll content was markedly decreased. Under salt stress, a larger proportion of Na+ was partitioned in the roots than in the shoots, which had a lower Na+/K+ ratio and proline content. Salt stress also obviously affected the homeostasis of other cations. Genome-wide transcriptomic analysis showed that a total of 2,807 and 5,570 differentially expressed genes (DEGs) were identified in the shoots and roots, respectively. Functionality analysis showed that these DEGs were mainly enriched in the KEGG pathways related to carbon metabolism, phenylalanine, and amino acid biosynthesis, and were primarily enriched in the GO terms involving proline metabolism and redox processes. The Na+ transporter genes were upregulated under salt stress, which repressed the gene expression of the K+ transporters. Salt stress also significantly elevated the expression of the genes involved in osmoregulation substances biosynthesis, and obviously affected the expression profiling of other cation transporters. Co-expression network analysis identified TaNHX6-D5/TaNHX4-B7 and TaP5CS2-B3 potentially as core members regulating wheat salt tolerance. Conclusions These results might help us fully understand the morpho-physiological and molecular responses of wheat seedlings to salt stress, and provide elite genetic resources for the genetic modification of wheat salt tolerance.

Abstract Pulmonary cryptococcosis (PC) is a common fungal infectious disease, and infection can occur in patients with any immune function. To better understand PC, we compared the CT findings and histopathological results in immunocompetent and immunocompromised patients. The clinical data of 68 patients with PC were collected retrospectively and divided into the immunocompetent group and immunocompromised group. The clinical characteristics, CT manifestations and histopathological characteristics of the two groups of patients were compared. Forty-two patients (61.8%) were immunocompetent, and 26 patients (38.2%) were immunocompromised. Compared with immunocompromised patients, 57.14% (24/42) of immunocompetent patients were asymptomatic (p = 0.002). Compared with immunocompetent patients, cough (14/26, 53.9%) and fever (13/26, 50.0%) were the main symptoms in immunocompromised patients (p = 0.044, p = 0.007). Nodular lesions (97.6%, 41/42) were the most common CT type in immunocompetent patients, and the CT characteristic was a single lesion (25/42, 59.5%); the main histopathological type was nodular fibrogranuloma (30/42, 71.4%), and the main histopathological characteristic was inflammatory granuloma (31/42, 73.81%) formed by macrophage phagocytosis of Cryptococcus. Consolidation (15/26, 57.7%) was more common in the CT type of immunocompromised patients. Multiple lesions (24/26, 92.31%), air bronchial signs (19/26, 73.081%) and cavities (9/26, 34.62%) were the main CT characteristics. The mucinous colloid type (19/26, 73.1%) was its main histopathological type, which was mainly characterized by a small amount of surrounding inflammatory cell infiltration (17/26, 65.4%). There were significant differences in the classification and characteristics of CT and pathology between the two groups (p

The Philippine Sea Plate is located at the convergence zone of the Eurasian Plate, the Pacific Plate, and the Indo-Australian Plate. This paper divides the Philippine Sea Plate into two second-order tectonic units and eight third-order tectonic units by summarizing the marine geological, geophysical, and submarine geomorphological data of the Philippine Sea Plate collected for years and referring to the seafloor spreading theory and the trench-arc-basin system. The two second-order tectonic units are the West Philippine Sea block and the Izu-Bonin-Mariana arc-basin system. The former includes the West Philippine Basin, the Huatung Basin, the Daito Basin, and the Palau Basin, while the latter consists of the Kyushu-Palau Ridge, the Shikoku-Parece Vela Basin, the Izu-Bonin Arc, and the Mariana Arc. Furthermore, this study concludes that the Philippine Sea Plate has undergone three stages of tectonic evolution, namely the early stage of the evolution of marginal basins with Cretaceous basement (Early Cretaceous), the middle stage of the spreading of the West Philippine Basin (Eocene), and the late stage of the subduction of the Izu-Bonin-Mariana arc-basin system (Oligocene-present). The Kyushu-Palau Ridge is a window to discover the tectonic evolution of the Philippine Sea Plate due to its unique geographical location.© 2022 China Geology Editorial Office.

The intersection of the Kyushu-Palau Ridge (KPR) and the Central Basin Rift (CBR) of the West Philippine Basin (WPB) is a relic of a trench-trench-rift (TTR) type triple-junction, which preserves some pivotal information on the cessation of the seafloor spreading of the WPB, the emplacement and disintegration of the proto-Izu-Bonin-Mariana (IBM) Arc, and the transition from initial rifting to steady-state spreading of the Parece Vela Basin (PVB). However, the structural characteristics of this triple-junction have not been thoroughly understood. In this paper, using the newly acquired multi-beam bathymetric, gravity, and magnetic data obtained by the Qingdao Institute of Marine Geology, China Geological Survey, the authors depict the topographic, gravity, and magnetic characteristics of the triple-junction and adjacent region. Calculations including the upward continuations and total horizontal derivatives of gravity anomaly are also performed to highlight the major structural features and discontinuities. Based on these works, the morphological and structural features and their formation mechanisms are analyzed. The results show that the last episode amagmatic extension along the CBR led to the formation of a deep rift valley, which extends eastward and incised the KPR. The morphological and structural fabrics of the KPR near and to the south of the triple-junction are consistent with those of the western PVB, manifesting as a series of NNE-SSW- and N-S-trending ridges and troughs, which were produced by the extensional faults associated with the initial rifting of the PVB. The superposition of the above two reasons induced the prominent discontinuity of the KPR in deep and shallow crustal structures between 15°N–15°30′N and 13°30′N–14°N. Combined with previous authors’ results, we propose that the stress produced by the early spreading of the PVB transmitted westward and promoted the final stage amagmatic extension of the CBR. The eastward propagation of the CBR destroyed the KPR, of which the magmatism had decayed or ceased at that time. The destruction mechanism of the KPR associated with the rifting of the PVB varies along strike the KPR. Adjacent to the triple-junction, the KPR was destroyed mainly due to the oblique intersection of the PVB rifting center. Whereas south of the triple-junction, the KPR was destroyed by the E-W-directional extensional faulting on its whole width.©2021 China Geology Editorial Office.

Abstract This study employed traditional and advanced echocardiographic techniques to assess comprehensively age- and sex-related changes in cardiovascular structure and function in wildtype (WT) mice. Forty-five normal adult wildtype mice were apportioned to groups based on age and sex: 2-month (young) male or female, and 24-month (old) male or female (n = 13, 13, 13, and 6, respectively). Each underwent 2-dimensional (2D) imaging echocardiography, Doppler, tissue Doppler imaging echocardiography, and speckle-tracking echocardiography (STE) for comparison of cardiovascular structure and function parameters. Compared to the young mice, the old had significantly higher body weight (BW), and lower diastolic and mean arterial pressure. The left ventricular (LV) end-diastolic and end-systolic volumes, and left ventricular mass, were significantly higher in the old mice. Within each sex, the cardiac diastolic and systolic function parameters were comparable between the young and old. Isovolumetric relaxation time (IVRT)/diastolic time interval (DT) and the maximum drop rate of pressure in LV (− dP/dtmax) were significantly lower in the old mice, while the LV relaxation time constant (Tau) was significantly higher. Spearman’s rank correlation showed a positive association between IVRT/DT and − dp/dtmax (male r = 0.663; female r = 0.639). Among the males, the maximum rise rate of pressure in LV (+ dp/dtmax), and systolic global longitudinal strains and rates (S-GLS, S-GLSR) were significantly different between the young and old. Spearman’s rank correlation showed positive association between S-GLS, S-GLSR and + dp/dtmax (r = 0.709 and r = 0.499). Regarding vascular structure, the ascending aorta systolic and diastolic diameters were significantly higher in the old mice compared with the young. The male mice had progressive, age-related aortic stiffness. Ageing in mice leads to changes in cardiovascular structure and cardiac diastolic function, but systolic function is relatively well preserved in females. Changes in cardiac function and arterial stiffness were more significant in males than females. Traditional ECG is better than STE for evaluating LV diastolic function; STE is better for LV systolic function.

Abstract Background Oilseed rape (B. napus L.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd. Results The aim of our study was to reveal the differential responses of B. napus to different Cd abundances. Herein, we found that high Cd (50 μM) severely inhibited the growth of B. napus, which was not repressed by low Cd (0.50 μM) under hydroponic culture system. ICP-MS assays showed that the Cd2+ concentrations in both shoots and roots under 50 μM Cd were over 10 times higher than those under 0.50 μM Cd. Under low Cd, the concentrations of only shoot Ca2+/Mn2+ and root Mn2+ were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca2+ and Mg2+. High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake (NRAMPs), transport (IRTs and ZIPs), sequestration (HMAs, ABCs, and CAXs), and detoxification (MTPs, PCR, MTs, and PCSs), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especially NRAMPs and IRTs, showed opposite responsive patterns between high Cd and low Cd conditions. Conclusions Our findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.

On analyzing the details of kinetic links of parts and structures of aircrafts, one can find few bad links. But fastener hole is the weakest link where abnormal stress is produced and initiation of crack occurs. The initial fatigue quality of aircraft wing flange fastener is the key parameter, which affects the durability of aircraft structure. The initial fatigue quality of structural details is usually characterized by the equivalent initial defect size (EIFS) and the time to crack initiation (TTCI). To evaluate the initial fatigue quality of aircraft wing flange fastener hole details, this paper first carried out fatigue tests at high-, medium- and low-stress levels on the BXXX aluminum alloy fastener hole specimens generally used in aircraft wing flange structures, and obtained three groups of (a−t) datasets about crack length a and fatigue life t through fracture interpretation and back stepping. On this basis, the EIFS governing equation was used to evaluate the EIFS value of each specimen, and it is found out that there is no significant difference in equivalent initial flaw size under different stress levels; TTCI distribution of structural details is obtained, and the economic life of specified stress level under 95% confidence level of fastener hole structural details was predicted, and compared with the design life; a structural detail equivalent to initial flaw size model under different exceedance probability P was proposed. Based on the given 5% crack exceedance probability, the general EIFS distribution of structural details was evaluated. The comprehensive evaluation results were obtained through the above triple evaluation of the initial fatigue quality of the fastener hole details: the general EIFS distribution and the EIFS value of each test piece are less than the allowable value, and the economic life is greater than the allowable value, so the original fatigue quality of the details of the fastening holes of the aircraft flange meets the stringent requirements.

Objective Lumbar spondylolisthesis (LS) is a common lumbar disease, and the prevalence of LS in different countries or regions was not consistent in the past. This study intends to make statistics on the prevalence of lumbar spondylolisthesis in middle‐aged people in Beijing community. Methods This is an epidemiological study. 4548 people in Beijing community aged 50 to 64 years were recruited from the local communities by advertisements placed in housing estates and community centres for people to take part in a prospective cohort study from August from September 2013 to March 2014. There is no intervention on the subjects. RadiAnt DICOM Viewer is adopted to read the lateral CT positioning images of all the studied objects, adjust the image as bone window, observe and evaluate the slide of L1 to L5 vertebra in the lateral CT positioning image. Results Among the 4,548 subjects included in the study, 2,490 (54.75%) were male and 2,058 (45.25%) were female. A total of 785 subjects had lumbar spondylolisthesis, with a total incidence of 17.26%. There was no significant difference between prevalence of males and females in the subgroup 50‐54 years old (13.55% males / 12.53% females) and 55‐59 years old (14.77% males / 14.93% females). But the prevalence of LS in 60‐64 years old females (28.57%) increased significantly, compared with 55‐59 years old females (14.93%) and 60‐64 years old males (18.76%). There were 847 levels that had slipped, L5S1 > L4/5 > L3/4 > L2/3 > L1/2. The retrolisthesis was the most, accounting for 61.51% (521/847), and the anterolisthesis was 38.49% (326/847), including anterolisthesis gradeI for 95.71% (312/326), anterolisthesis gradeII for 4.29% (14/326). Neither of anterolisthesis and retrolisthesis presented more than grade III. Among all the subjects, 318 had anterolisthesis, with a total incidence of 6.99%, and 467 subjects only had retrolisthesis. Conclusion The total prevalence of LS in the middle‐aged people in Beijing community was 17.26%, 15.98% in males and 18.80% in females, and women are more likely to suffer from LS after 60 years old.

Abstract Background Vertebral augmentation is the first-line treatment for the osteoporosis vertebral compression fractures. Bone cement leakage is the most common complication of this surgery. This study aims to assess the risk factors for different types of cement leakage and provides a nomogram for predicting the cement intradiscal leakage. Methods We retrospectively reviewed 268 patients who underwent vertebral augmentation procedure between January 2015 and March 2019. The cement leakage risk factors were evaluated by univariate analysis. Different types of cement leakage risk factors were identified by the stepwise logistic analysis. We provided a nomogram for predicting the cement intradiscal leakage and used the concordance index to assess the prediction ability. Results A total of 295 levels of vertebrae were included, with a leakage rate of 32.5%. Univariate analysis showed delayed surgery and lower vertebral compression ratio were the independent risk factors of cement leakage. The stepwise logistic analysis revealed percutaneous vertebroplasty was a risk factor in vein cement leakage; delayed surgery, preoperative compression ratio, and upper endplate disruption were in intradiscal cement leakage; age, preoperative fracture severity, and intravertebral vacuum cleft were in perivertebral soft tissue cement leakage; no factor was in spinal canal cement leakage. The nomogram for intradiscal cement leakage had a precise prediction ability with an original concordance index of 0.75. Conclusions Delayed surgery and more vertebral compression increase the risk of cement leakage. Different types of cement leakage have different risk factors. We provided a nomogram for precise predicting the intradiscal cement leakage.

AIM: To investigate the alleviation of scutellarein (SN) against inner blood-retinal-barrier (iBRB) dysfunction in microglia cells stimulated by hyperglycemia and to elucidate the engaged mechanism. METHODS: Microglia BV2 cells were stimulated by using 25 mmol/L D-glucose. The same concentration of mannitol (25 mmol/L) was applied as an isotonic contrast. Real-time PCR, Western-blot assay and immunofluorescence staining assay was performed. The dysfunction of iBRB in vitro was detected by using transendothelial electrical resistance (TEER) assay. Additionally, the leakage of fluorescein isothiocyanate (FITC)-conjugated dextran (70 kDa) was detected. RESULTS: SN abrogated microglia BV2 cells activation and reduced the phosphorylated activation of extracellular signal-regulated protein kinase (ERK)1/2. SN also decreased the transcriptional activation of nuclear factor κB (NFκB) and the elevated expression of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β in BV2 cells treated with D-glucose (25 mmol/L). SN attenuated iBRB dysfunction in human retinal endothelial cells (HRECs) or choroid-retinal endothelial RF/6A cells when those cells were treated with TNFα, IL-1β or IL-6, or co-cultured with microglia cells stimulated by D-glucose. Moreover, SN restored the decreased protein expression of tight junctions (TJs) in TNFα-treated HRECs and RF/6A cells. CONCLUSION: SN not only alleviate iBRB dysfunction via directly inhibiting retinal endothelial injury caused by TNFα, IL-1β or IL-6, but also reduce the release of TNFα, IL-1β and IL-6 from microglia cells by abrogating hyperglycemia-mediated the activation of microglia cells.

Abstract Background Adipose-derived stem cells (ADSCs) promote tissue regeneration and repair. Cryoprotective agents (CPAs) protect cells from cryodamage during cryopreservation. Safe and efficient cryopreservation of ADSCs is critical for cell-based therapy in clinical applications. However, most CPAs are used at toxic concentrations, limiting their clinical application. Objective The aim of this study is to develop a non-toxic xeno-free novel CPA aiming at achieving high-efficiency and low-risk ADSC cryopreservation. Methods We explored different concentrations of trehalose (0.3 M, 0.6 M, 1.0 M, and 1.25 M) and glycerol (10%, 20%, and 30% v/v) for optimization and evaluated and compared the outcomes of ADSCs cryopreservation between a combination of trehalose and glycerol and the commonly used CPA DMSO (10%) + FBS (90%). All samples were slowly frozen and stored in liquid nitrogen for 30 days. The effectiveness was evaluated by the viability, proliferation, migration, and multi-potential differentiation of the ADSCs after thawing. Results Compared with the groups treated with individual reagents, the 1.0 M trehalose (Tre) + 20% glycerol (Gly) group showed significantly higher efficiency in preserving ADSC activities after thawing, with better outcomes in both cell viability and proliferation capacity. Compared with the 10% DMSO + 90% FBS treatment, the ADSCs preserved in 1.0 M Tre + 20% Gly showed similar cell viability, surface markers, and multi-potential differentiation but a significantly higher migration capability. The results indicated that cell function preservation can be improved by 1.0 M Tre + 20% Gly. Conclusions The 1.0 M Tre + 20% Gly treatment preserved ADSCs with a higher migration capability than 10% DMSO + 90% FBS and with viability higher than that with trehalose or glycerol alone but similar to that with 10% DMSO + 90% FBS and fresh cells. Moreover, the new CPA achieves stemness and multi-potential differentiation similar to those in fresh cells. Our results demonstrate that 1.0 M Tre + 20% Gly can more efficiently cryopreserve ADSCs and is a non-toxic CPA that may be suitable for clinical applications.

BackgroundEndolymphatic hydrops (EH) is considered as the pathological correlate of Menière’s disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials.ObjectiveThis study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models.MethodsIn this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells.ResultsThe RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL).ConclusionEndolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

Abstract Background CD4+ T cells are critical effectors of anti-tumor immunity, but how tumor cells influence CD4+ T cell effector function is not fully understood. Tumor cell-released autophagosomes (TRAPs) are being recognized as critical modulators of host anti-tumor immunity during tumor progression. Here, we explored the mechanistic aspects of TRAPs in the modulation of CD4+ T cells in the tumor microenvironment. Methods TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4+ T cells to examine the function and mechanism of TRAPs in CD4+ T cell differentiation and function. TRAPs-elicited CD4+ T cells were tested for their suppression of effector T cell function, induction of regulatory B cells, and promotion of tumorigenesis and metastasis in a mouse model. Results Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4+ T cell production of IL-6 via a TLR2–MyD88–NF-κB signal cascade. TRAPs-induced autocrine IL-6 further promoted CD4+ T cells secretion of IL-10 and IL-21 via STAT3. Notably, TRAPs-elicited CD4+ T cells inhibited CD4+ and CD8+ effector T cell function in an IL-6- and IL-10-dependent manner and induced IL-10-producing regulatory B cells (Bregs) via IL-6, IL-10 and IL-21, thereby promoting tumor growth and metastasis. Consistently, inhibition of tumor autophagosome formation or IL-6 secretion by CD4+ T cells markedly retarded tumor growth. Furthermore, B cell or CD4+ T cell depletion impeded tumor growth by increasing effector T cell function. Conclusions HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD4+ T cells to promote tumor growth and metastasis. TRAPs or their membrane-bound HSP90α represent important therapeutic targets to reverse cancer-associated immunosuppression and improve immunotherapy.

Fungal species in the family Mortierellaceae are important for their remarkable capability to synthesize large amounts of polyunsaturated fatty acids, especially arachidonic acid (ARA). Although many genomes have been published, the quality of these data is not satisfactory, resulting in an incomplete understanding of the lipid pathway in Mortierellaceae. We provide herein two novel and high-quality genomes with 55.32% of syntenic gene pairs for Mortierella alpina CGMCC 20262 and M. schmuckeri CGMCC 20261, spanning 28 scaffolds of 40.22 Mb and 25 scaffolds of 49.24 Mb, respectively. The relative smaller genome for the former is due to fewer protein-coding gene models (11,761 vs. 13,051). The former yields 45.57% of ARA in total fatty acids, while the latter 6.95%. The accumulation of ARA is speculated to be associated with delta-5 desaturase (Delta5) and elongation of very long chain fatty acids protein 3 (ELOVL3). A further genomic comparison of 19 strains in 10 species in three genera in the Mortierellaceae reveals three types of fatty acid synthase (FAS), two of which are new to science. The most common type I exists in 16 strains of eight species of three genera, and was discovered previously and consists of a single unit with eight active sites. The newly revealed type II exists only in M. antarctica KOD 1030 where the unit is separated into two subunits α and β comprised of three and five active sites, respectively. Another newly revealed type III exists in M. alpina AD071 and Dissophora globulifera REB-010B, similar to type II but different in having one more acyl carrier protein domain in the α subunit. This study provides novel insights into the enzymes related to the lipid metabolism, especially the ARA-related Delta5, ELOVL3, and FAS, laying a foundation for genetic engineering of Mortierellaceae to modulate yield in polyunsaturated fatty acids.

Manipulating droplet dynamics is of great importance in condensation heat transfer enhancement. Cavity topography was believed to be able to regulate droplet merging and self-removal via Laplace force imbalance by the cavity wall and the effect of spatial confinement and isolation. However, the size effect of the microcavity on the droplet dynamics behavior, droplet size distribution and condensation heat transfer performance are not sufficiently understood. In this paper, hierarchical microcavity-arrayed superhydrophobic surfaces with a nominal cavity diameter of 20, 35, 50 and 70 μm were fabricated. Condensation experiments were first carried out in the atmosphere under an optical microscope, and then in pure steam in a self-designed environmental chamber at 4000 Pa. Local dynamic behaviors and time-lapsed evolutions of droplets during condensation were observed. Droplet size distribution and jumping rate were statistically analyzed using ImageJ software. It was proved the smaller cavity size of 20 μm is beneficial to facilitate condensate droplet jumping and increase the density of small droplets. The surface coverage ratio on the microcavity-arrayed superhydrophobic surfaces was only half of that on the hydrophobic surface at steady state. Enhancement of pure steam condensation heat transfer can be realized by effectively regulating droplet dynamics using microcavity topographies at limited subcooling degrees.

AIM: To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE) against diabetic retinopathy (DR) and its engaged mechanism. METHODS: C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg) for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg) for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB) breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. RESULTS: SE (100, 200 mg/kg) reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ) proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1). SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB) p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1) demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION: SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.