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Abstract Reporting the results of quality indicators can narrow the gap in the quality of care between hospitals. While most studies rely on outcome indicators, they may not accurately measure the quality of care. Process indicators are not only strongly associated with treatment outcomes, but are also more sensitive to whether patients are treated accurately, enabling timely intervention. Our study aims to investigate whether process indicators provide a more reasonable assessment of hospital quality of care compared to outcome indicators. Data were sourced from the Specific Disease Medical Service Quality Management and Control System in China. A total of 113,942 patients with breast cancer treated in 298 hospitals between January 2019 and April 2023 were included in this retrospective study. The rankability of 11 process indicators was calculated and used as a weight to create a new composite indicator. The composite indicators and outcome measures were compared using the O/E ratio categories. Finally, in order to determine the impact of different years on the results, a sensitivity analysis was conducted using bootstrap sampling. The rankability ( $$\rho$$ ρ ) values of the eleven process indicators showed significant differences, with the highest $$\rho$$ ρ value for preoperative cytological or histological examination before surgery (0.919). The $$\rho$$ ρ value for the outcome indicator was 0.011. The rankability-weighting method yielded a comprehensive score ( $$\rho$$ ρ = 0.883). The comparison with categorical results of the outcome indicator has different performance classifications for 113 hospitals (37.92%) for composite scores and 140 (46.98%) for preoperative cytological or histological examinationbefore surgery. Process indicators are more suitable than outcome indicators for assessing the quality of breast cancer care in hospitals. Healthcare providers can use process indicators to identify specific areas for improvement, thereby driving continuous quality improvement efforts.

Polycyclic aromatic hydrocarbons (PAHs) in semi-enclosed gulfs are influenced by physical and biochemical processes, which haven’t been well understood. This study aims to investigate the spatial distribution and vertical profiles of dissolved PAHs in the Beibu Gulf (BG) and adjacent waters of the South China Sea, along with hydrological, meteorological, and biochemical variables. Particularly relevant are the effects of atmospheric pressure, salinity, ammonium, chlorophyll-a, as well as riverine inputs (RI), sea currents, and upwelling. In surface seawater, the total concentrations of eight dissolved PAHs (∑8PAHs) were 7.76 ± 2.16 ng/L, with a distribution pattern of western Guangdong waters (WGWs) > BG > Qiongzhou Strait (QS). ∑8PAHs in the northern BG (9.10 ± 2.00 ng/L) was significantly higher than that in the southern BG (6.65 ± 1.54 ng/L) (p < 0.01), suggesting that local anthropogenic activities and unique environmental characteristics significantly influenced PAHs distribution. In water column, PAHs in BG displayed enrichment in surface and bottom but decreased in medium water, while those in WGWs and QS decreased with increasing depth. Source apportionment concluded that PAHs in QS and WGWs were primarily from petroleum sources, and PAHs in BG were mainly from coal combustion. RI, combined with circulation, coastal current, and intrusion of SCS water influenced the surface PAHs distribution in BG, with eddy impacts observed. Specifically, regarding the surface PAHs distribution, differences in atmospheric pressure may influence the air-sea exchange of PAHs, especially positively affecting 4-ring PAHs. Salinity factors further corroborated the contribution of RI to 3-ring PAHs, followed by the regulation of PAHs through biological pumps (ammonia and chlorophyll-a). Moreover, upwelling-induced biodegradation and resuspension affected the vertical distribution of PAHs. While most PAHs posed a negligible risk, coking-generated fluorene posed a moderate risk to ecosystems due to changes in the energy structure, warranting further investigation into its toxicological impacts.

Abstract Background The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0. Methods Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe −/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein. Results The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe −/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis. Conclusions Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.

Cognitive impairment is one of the most common non-motor symptoms of Parkinson’s disease (PD). Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation can significantly suppress the motor symptoms of PD. However, whether ultrasound stimulation can improve cognitive ability in PD and the related neural oscillation mechanism remain unclear to date. To evaluate the effect of ultrasound stimulation on memory ability in PD and explore its neural oscillation mechanism. Ultrasonography was used for 7-day stimulation of the CA1 in transgenic mice with PD. The working memory ability of the PD mice was then tested using novel object discrimination, and the local field potential and spikes in the mice CA1 were recorded at the same time as in the behavioral test. We found that ultrasound stimulation of the PD mice CA1 for 4 days: 1) significantly increased their learning and memory ability, although the learning and memory ability on the 7th day after the stimulation stopped was not significantly different from that before stimulation (P>0.05); 2) significantly increased the relative power of theta, low gamma, and high gamma frequency bands of the local field potential, and the phase amplitude coupling strength between theta and low gamma and between theta and high gamma; and 3) modulated the phase-locking angle between the spike of interneuron and theta wave to a 180°-360° rise cycle. Transcranial ultrasound stimulation can improve the learning and memory abilities of PD mice, and evoking neural oscillations in the CA1 is the potential mechanism.

Abstract As cities increasingly look for sustainable transportation options to alleviate congestion and solve the “first mile, last mile” problem, micro-transit has emerged as a promising solution. However, to ensure the long-term success of micro-transit programs, it’s essential to establish sustainable funding strategies. This research aims to investigate what factors influence people’s willingness to pay for micro-transit, with a particular focus on their perceptions of climate change and their commuting experiences. Additionally, the study explores the differences in experiences between current micro-transit users and non-users. Using the Downtowner service in downtown Tampa as a case study, we conducted online surveys in July 2020, gathering responses from 706 micro-transit users and 311 non-users. We then applied statistical analysis to understand the factors affecting willingness to pay. This study sheds light on the relatively underexplored topic of willingness to pay for micro-transit and its connection to climate change perceptions, contributing to existing research. Furthermore, recognizing differences in preferences between these groups provides valuable insights for tailoring strategies to encourage willingness to pay. As policymakers and transportation agencies aim to combat climate change and promote sustainable transportation, understanding these factors becomes increasingly important for developing effective and eco-friendly mobility solutions.

Background: Heading is an important agronomic feature for Chinese cabbage, cabbage, and lettuce. The heading leaves function as nutrition storage organs, which contribute to the high quality and economic worth of leafy heads. Leaf development is crucial during the heading stage, most genes previously predicted to be involved in the heading process are based on Arabidopsis leaf development studies. Aim of review: Till date, there is no published review article that demonstrated a complete layout of all the identified regulators of leaf curvature and heading. In this review, we have summarized all the identified physiological and genetic regulators that are directly or indirectly involved in leaf curvature and heading in Brassica crops. By integrating all identified regulators that provide a coherent logic of leaf incurvature and heading, we proposed a molecular mechanism in Brassica crops with graphical illustrations. This review adds value to future breeding of distinct heading kinds of cabbage and Chinese cabbage by providing unique insights into leaf development. Key scientific concepts of review: Leaf curvature and heading are established by synergistic interactions among genes, transcription factors, microRNAs, phytohormones, and environmental stimuli that regulate primary and secondary morphogenesis. Various genes have been identified using transformation and genome editing that are responsible for the formation of leaf curvature and heading in Brassica crops. A range of leaf morphologies have been observed in Brassica, which are established because of the mutated determinants that are responsible for cell division and leaf polarity.

Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.

The flow structure around limited-size vegetation patches is crucial for understanding sediment transport and vegetation succession trends. While the influence of vegetation density has been extensively explored, the impact of the relative diameter of vegetation stems remains relatively unclear. After validating the reliability of the numerical model with experimental data, this study conducted 2D-URANS simulations (SST k-ω) to investigate the impact of varying relative diameters d/D under different vegetation densities λ on the hydrodynamic characteristics and drag force of vegetation patches. The results show that increasing d/D and decreasing λ are equivalent, both contributing to increased spacing between cylinder elements, allowing for the formation of element-scale Kármán vortices. Compared to vegetation density λ, the non-dimensional frontal area aD is a better predictor for the presence of array-scale Kármán vortex streets. Within the parameter range covered in this study, array-scale Kármán vortex streets appear when aD ≥ 1.4, which will significantly alter sediment transport patterns. For the same vegetation density, increasing the relative diameter d/D leads to a decrease in the array drag coefficient C¯D and an increase in the average element drag coefficient C¯d. When parameterizing vegetation resistance using aD, all data points collapse onto a single curve, following the relationships C¯D=0.34lnaD+0.78 and C¯d=−0.42lnaD+0.82.

Recent years have ushered in a transformative era in in vitro modeling with the advent of organoids, three-dimensional structures derived from stem cells or patient tumor cells. Still, fully harnessing the potential of organoids requires advanced imaging technologies and analytical tools to quantitatively monitor organoid growth. Optical coherence tomography (OCT) is a promising imaging modality for organoid analysis due to its high-resolution, label-free, non-destructive, and real-time 3D imaging capabilities, but accurately identifying and quantifying organoids in OCT images remain challenging due to various factors. Here, we propose an automatic deep learning-based pipeline with convolutional neural networks that synergistically includes optimized preprocessing steps, the implementation of a state-of-the-art deep learning model, and ad-hoc postprocessing methods, showcasing good generalizability and tracking capabilities over an extended period of 13 days. The proposed tracking algorithm thoroughly documents organoid evolution, utilizing reference volumes, a dual branch analysis, key attribute evaluation, and probability scoring for match identification. The proposed comprehensive approach enables the accurate tracking of organoid growth and morphological changes over time, advancing organoid analysis and serving as a solid foundation for future studies for drug screening and tumor drug sensitivity detection based on organoids.

Background: Although its immunomodulatory properties make thymopentin (TP5) appealing, its rapid metabolism and inactivation in the digestive system pose significant challenges for global scientists. PEGylated niosomal nanocarriers are hypothesized to improve the physicochemical stability of TP5, and to enhance its intestinal permeability for oral administration. Methods: TP5-loaded PEGylated niosomes were fabricated using the thin film hydration method. Co-cultured Caco-2 and HT29 cells with different ratios were screened as in vitro intestinal models. The cytotoxicity of TP5 and its formulations were evaluated using an MTT assay. The cellular uptake and transport studies were investigated in the absence or presence of variable inhibitors or enhancers, and their mechanisms were explored. Results and Discussion: All TP5 solutions and their niosomal formulations were nontoxic to Caco-2 and HT-29 cells. The uptake of TP5-PEG-niosomes by cells relied on active endocytosis, exhibiting dependence on time, energy, and concentration, which has the potential to significantly enhance its cellular uptake compared to TP5 in solution. Nevertheless, cellular transport rates were similar between TP5 in solution and its niosomal groups. The cellular transport of TP5 in solution was carried out mainly through MRP5 endocytosis and a passive pathway and effluxed by MRP5 transporters, while that of TP5-niosomes and TP5-PEG-niosomes was carried out through adsorptive- and clathrin-mediated endocytosis requiring energy. The permeability and transport rate was further enhanced when EDTA and sodium taurocholate were used as the penetration enhancers. Conclusions: This research has illustrated that PEG-niosomes were able to enhance the cellular uptake and maintain the cellular transport of TP5. This study also shows this formulation’s potential to serve as an effective carrier for improving the oral delivery of peptides.

Objective To determine the validity of a hardness sensor to objectively assess skin induration in patients with systemic sclerosis, and to compare the hardness sensor with the modified Rodnan skin score (MRSS) and a durometer.Methods The skin induration was measured in two assessments: a Latin square experiment to examine the hardness sensor’s intraobserver and interobserver reliability; and a longitudinal cohort to evaluate the distribution of hardness sensor measurements, the correlation between hardness sensor, durometer and MRSS, and the sensitivity to change in skin hardness. Other outcome data collected included the health assessment questionnaire (HAQ) disability index and Keitel function test (KTF) score.Results The reliability of the hardness sensor was excellent, with high intraobserver and interobserver intraclass correlation coefficients (0.97; 0.96), which was higher than MRSS (0.86; 0.74). Interobserver reproducibility of hardness sensor was only poor in abdomen (0.38), yet for durometer it was poor in face (0.11) and abdomen (0.33). The hardness sensor score provided a greater dynamic evaluation range than MRSS. Total hardness sensor score correlated well with MRSS (r=0.90, p

Abstract Background Chinese cabbage (Brassica rapa ssp. pekinensis) experienced a whole-genome triplication event and thus has three subgenomes: least fractioned, medium fractioned, and most fractioned subgenome. Environmental changes affect leaf development, which in turn influence the yield. To improve the yield and resistance to different climate scenarios, a comprehensive understanding of leaf development is required including insights into the full diversity of cell types and transcriptional networks underlying their specificity. Results Here, we generate the transcriptional landscape of Chinese cabbage leaf at single-cell resolution by performing single-cell RNA sequencing of 30,000 individual cells. We characterize seven major cell types with 19 transcriptionally distinct cell clusters based on the expression of the reported marker genes. We find that genes in the least fractioned subgenome are predominantly expressed compared with those in the medium and most fractioned subgenomes in different cell types. Moreover, we generate a single-cell transcriptional map of leaves in response to high temperature. We find that heat stress not only affects gene expression in a cell type-specific manner but also impacts subgenome dominance. Conclusions Our study highlights the transcriptional networks in different cell types and provides a better understanding of transcriptional regulation during leaf development and transcriptional response to heat stress in Chinese cabbage.

Previous studies have demonstrated that transcranial ultrasound stimulation (TUS) not only modulates cerebral hemodynamics, neural activity, and neurovascular coupling characteristics in resting samples but also exerts a significant inhibitory effect on the neural activity in task samples. However, the effect of TUS on cerebral blood oxygenation and neurovascular coupling in task samples remains to be elucidated. To answer this question, we first used forepaw electrical stimulation of the mice to elicit the corresponding cortical excitation, and then stimulated this cortical region using different modes of TUS, and simultaneously recorded the local field potential using electrophysiological acquisition and hemodynamics using optical intrinsic signal imaging. The results indicate that for the mice under peripheral sensory stimulation state, TUS with a duty cycle of 50% can (1) enhance the amplitude of cerebral blood oxygenation signal, (2) reduce the time-frequency characteristics of evoked potential, (3) reduce the strength of neurovascular coupling in time domain, (4) enhance the strength of neurovascular coupling in frequency domain, and (5) reduce the time-frequency cross-coupling of neurovasculature. The results of this study indicate that TUS can modulate the cerebral blood oxygenation and neurovascular coupling in peripheral sensory stimulation state mice under specific parameters. This study opens up a new area of investigation for potential applicability of TUS in brain diseases related to cerebral blood oxygenation and neurovascular coupling.

Abstract The association between CO and chronic obstructive pulmonary disease (COPD) has been widely reported; however, the association among patients with type 2 diabetes mellitus (T2DM) or hypertension has remained largely unknown in China. Over‐dispersed generalized additive model was adopted to quantity the associations between CO and COPD with T2DM or hypertension. Based on principal diagnosis, COPD cases were identified according to the International Classification of Diseases (J44), and a history of T2DM and hypertension was coded as E12 and I10‐15, O10‐15, P29, respectively. A total of 459,258 COPD cases were recorded from 2014 to 2019. Each interquartile range uptick in CO at lag 03 corresponded to 0.21% (95%CI: 0.08%–0.34%), 0.39% (95%CI: 0.13%–0.65%), 0.29% (95%CI: 0.13%–0.45%) and 0.27% (95%CI: 0.12%–0.43%) increment in admissions for COPD, COPD with T2DM, COPD with hypertension and COPD with both T2DM and hypertension, respectively. The effects of CO on COPD with T2DM (Z = 0.77, P = 0.444), COPD with hypertension (Z = 0.19, P = 0.234) and COPD with T2DM and hypertension (Z = 0.61, P = 0.543) were insignificantly higher than that on COPD. Stratification analysis showed that females were more vulnerable than males except for T2DM group (COPD: Z = 3.49, P

Glutathione (GSH) is a tripeptide with potent antioxidant activity, which is involved in numerous basic biological processes and has been used for interventions in various degenerative diseases. However, oral delivery of GSH remains challenging, similarly to that of other protein and peptide drugs, because the physicochemical barriers in the gastrointestinal (GI) tract lead to low oral bioavailability. Although several approaches have been explored to improve delivery, such as co-administration with penetration enhancers and enzymatic inhibitors, or encapsulation into nanoparticles, microemulsions and liposomes, appropriate formulations with clinical therapeutic effects remain to be developed. This review discusses approaches explored to developing an oral GSH delivery system that could provide protection against proteolytic degradation in the GI tract and enhance molecular absorption across the epithelial membrane. This system may be beneficial for the design and development of an oral formulation of GSH in the future.

Abstract Background Haemophilus influenzae was the most aggressive pathogen and formed a major cause of bacterial meningitis and pneumonia in young children and infants, which need medical emergency requiring immediate diagnosis and treatment. However, From isolation to identification of H. influenzae, the traditional diagnose strategy was time-consuming and expensive. Therefore, the establishment of a convenient, highly sensitive, and stable detection system is urgent and critical. Results In this study, we used a combined method to detect H. influenzae. Six specific primers were designed on the basis of outer membrane protein P6 gene sequence of H. influenzae. The reaction condition such as the optimum temperature was 65℃, and the optimum reaction time was 30 min, respectively. Through the loop-mediated isothermal amplification (LAMP) in combination with nanoparticle-based lateral flow biosensor (LFB), the sensitivity of LAMP-LFB showed 100 fg was the lowest genomic DNA templates concentration in the pure cultures. Meanwhile, the specificity of H. influenzae-LAMP-LFB assay showed the exclusive positive results, which were detected in H. influenzae templates. In 55 clinical sputum samples, 22 samples were positive with LAMP-LFB method, which was in accordance with the traditional culture and Polymerase Chain Reaction (PCR) method. The accuracy in diagnosing H. influenzae with LAMP-LFB could reach 100%, compared to culture and PCR method, indicating the LAMP-LFB had more advantages in target pathogen detection. Conclusions Taken together, LAMP-LFB could be used as an effective diagnostic approach for H. influenzae in the conditions of basic and clinical labs, which would allow clinicians to make better informed decisions regarding patient treatment without delay.

Peptides are short chains of amino acids linked by peptide bonds. Many peptides and proteins are limited by their poor enzymatic stability and permeability across the intestinal epithelial membranes and/or blood-brain barrier (BBB). Parenteral administration of these peptides is unfavorable because of procedural complications and low patient compliance with treatments. Instead, oral delivery is the preferred route of administration because it allows for self-administration and has a high degree of patient acceptability and compliance. Oral delivery of these peptides poses a major challenge, because the peptide drug must overcome both the physical and biochemical barriers of the gastrointestinal tract and BBB. An oral drug delivery system is beneficial because it can protect peptide drugs against degradation and deliver them to the brain, where they exert their pharmacological actions. The use of active-targeting ligands and/or cell-penetrating peptides increases penetration and uptake across the BBB. This review focuses on the diverse combinations of drug delivery systems, active-targeting ligands, and cell-penetrating peptides used to deliver peptides to the brain.

ObjectiveTo investigate the characteristics of cardiac involvement due to Immune-mediated Necrotizing Myopathy (IMNM).MethodsPatients diagnosed with Immune-mediated Necrotizing Myopathy (IMNM) who attended the Department of Neurology and the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital between February 2011 and June 2022 were collected. Clinicopathological diagnosis of IMNM was performed according to the criteria established by the European Neuromuscular Center (ENMC). All patients underwent muscle biopsy and Myositis-specific antibodies (MSAs) testing. Information included age, gender, disease duration, intramuscular and extramuscular manifestations, laboratory findings (including creatine kinase, lactate dehydrogenase levels, troponin T, myoglobin and atrial natriuretic peptide), electromyography, skeletal muscle pathology and immunohistochemical staining.ResultsA total of 57 patients were included in this study. Of the serological tests, 56.1% (32/57) were positive for SRP, 21.1% (12/57) were positive for HMGCR and 22.8% (13/57) were seronegative. Thirty patients (52.6%, 30/57) presented with varying degrees of cardiac involvement. We performed ECG in 23 patients and found 6 patients with arrhythmia (26.1%), 12 patients with myocardial ischemia (52.2%), and 7 patients with acute coronary syndrome (ST elevation and non-ST elevation myocardial infarction) (30.4%), and 4 patients with left axis deviation or left ventricular high voltage, suggesting left ventricular hypertrophy (17.4%). Cardiac ultrasound was performed in 14 patients and 3 showed pericardial effusion (21.4%); Decreased left ventricular ejection fraction and atrial enlargement were 2 each; 8 showed a decrease in left ventricular diastolic function (57.1%). In addition, one patient had myocardial edema.ConclusionCardiac involvement is not uncommon in IMNM. However, besides clearly statistically significant differences in the disease course, and in the values of troponin T and myoglobin, our data did not show any statistically significant difference in other features of cardiac involvement between patients with different subtypes of IMNM.

Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS. Therefore, pharmacological interventions have been developed to inhibit the AS via autophagy induction. Among various AS treating methods, herbal medicines and natural products have been applied as effective complementary and alternative medicines to ameliorate AS and its associated cardiovascular disease. Recently, mounting evidence revealed that natural bioactive compounds from herbs and natural products could induce autophagy to suppress the occurrence and development of AS, by promoting cholesterol efflux, reducing plaque inflammation, and inhibiting apoptosis or senescence. In the present review, we highlight recent findings regarding possible effects and molecular mechanism of natural compounds in autophagy-targeted mitigation of atherosclerosis, aiming to provide new potential therapeutic strategies for the atherosclerosis treatment preclinically and clinically.

Complex transcriptional networks regulate plant defense against pathogen attack, and plant transcription factors act as key regulators of the plant immune responses. The differences between transcription factor expression and regulation in Chinese cabbage soft rot (Pectobacterium carotovorum; Pc) have not been revealed. In this study, a total of 148 putative Chinese cabbage WRKY genes (BrWRKYs) were identified from the Chinese cabbage genome (v3.0). These genes were divided into seven subgroups (groups I, IIa–e, and III) based on phylogenomic analysis, with distinct motif compositions in each subgroup. Time-series RNA-seq was carried out to elucidate the dynamic expression patterns of the BrWRKYs on the resistant mutant (sr) and the susceptible wild-type (inbred WT) challenged by Pc. Transcriptional analysis showed that 48 WRKY transcription genes at 0–24 hpi were significantly upregulated in sr under soft rot stress. At the 12-h post-inoculation critical time point, we identified three specifically upregulated genes and two downregulated genes in the resistant mutant, which may provide potential applications for genetic improvement against soft rot. The findings improved our understanding of the WRKY-mediated soft rot stress response regulation in Chinese cabbage. The study thus lays a foundation for the genetic improvement of soft rot resistance.

Aim: The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport. Methods: Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid along with either chitosan or pectin modification. bLf cellular uptake and transport were evaluated in vitro using the human adenocarcinoma cell line Caco-2 cell model. Results and Discussion: The bLf-loaded SLPs showed no significant effect on cytotoxicity and did not induce apoptosis within the eight-hour investigation. The use of confocal laser scanning microscopy confirmed that bLf follows the receptor-mediated endocytosis, whereas the primary mechanism for the cellular uptake of SLPs was endocytosis. The bLf-loaded SLPs had significantly more cellular uptake compared to bLf alone, and it was observed that this impact varied based on the time, temperature, and concentration. Verapamil and EDTA were determined to raise the apparent permeability coefficients (App) of bLf and bLf-loaded SLPs. Conclusion: This occurred because they hindered efflux by interacting with P-glycoproteins and had a penetration-enhancing influence. These findings propose the possibility of an additional absorption mechanism for SLPs, potentially involving active transportation facilitated by the P-glycoprotein transporter in Caco-2 cells. These results suggest that SLPs have the potential to be applied as effective carriers to improve the oral bioavailability of proteins and peptides.

Graphical Abstract

Background: Evidence on the effects of the air pollutants on the hospital admissions, hospital cost and length of stay (LOS) among patients with comorbidities remains limited in China, particularly for patients with cardiovascular diseases and comorbid diabetes mellitus (CVD-DM). Methods: We collected daily data on CVD-DM patients from 242 hospitals in Beijing between 2014 and 2019. Generalized additive model was employed to quantify the associations between admissions, LOS, and hospital cost for CVD-DM patients and air pollutants. We further evaluated the attributable risk posed by air pollutants to CVD-DM patients, using both Chinese and WHO air quality guidelines as reference. Results: Per 10 ug/m3 increase of particles with an aerodynamic diameter

Dam break is an accident that may heavily threat downstream residents' life and property safety, especially in China. As revealed by accident investigation statistics, both flawed organizational behavior and inadequate downstream resident risk awareness have affected the safety risk of reservoir dams. Multiple information transferring mode and dynamic processes perform with the characteristics of social-technical systems. Based on the system dynamics approach, this study proposed a risk causation model aiming for factor interactions involving organizational, human, and technical system levels. The derived simulation model represented the historical risk evolution process of Gouhou reservoir in China and the rationality of the proposed model was verified. To further improve the efficiency of the organizational response and monitor real-time dam safety, a software tool called Dam Emergency Response Aids (DERA) was constructed to evaluate the potential safety benefits of risk control measures, and to overcome the defects of static emergency plans. By integrating relevant professional modules and data, the mobile application (APP) has been applied on the Jinniu Mountain reservoir dam in Nanjing of China and helped to maintain its excellent safety operation until now. It shows that the risk dynamics model proposed can improve the abilities of dam operating management organization for more effective responses under emergency circumstances. HIGHLIGHTS This research helps to remind the safety responsible organizations to focus their investment on publicizing and downstream resident training, which will increase their awareness of risks, enhance public understanding of the evacuation process and risk pre-judgment criteria, and maintain trusts in organization decision-making and community cohesion.;

The leaves of the Chinese cabbage which is most widely consumed come in a wide variety of colors. Leaves that are dark green can promote photosynthesis, effectively improving crop yield, and therefore hold important application and cultivation value. In this study, we selected nine inbred lines of Chinese cabbage displaying slight differences in leaf color, and graded the leaf color using the reflectance spectra. We clarified the differences in gene sequences and the protein structure of ferrochelatase 2 (BrFC2) among the nine inbred lines, and used qRT-PCR to analyze the expression differences of photosynthesis-related genes in inbred lines with minor variations in dark-green leaves. We found expression differences among the inbred lines of Chinese cabbage in photosynthesis-related genes involved in the porphyrin and chlorophyll metabolism, as well as in photosynthesis and photosynthesis-antenna protein pathway. Chlorophyll b content was significantly positively correlated with the expression of PsbQ, LHCA1_1 and LHCB6_1, while chlorophyll a content was significantly negatively correlated with the expression PsbQ, LHCA1_1 and LHCA1_2. Our results provide an empirical basis for the precise identification of candidate genes and a better understanding of the molecular mechanisms responsible for the production of dark-green leaves in Chinese cabbage.

Abstract Background Prior studies have investigated the association of PM2.5 exposure with arterial stiffness measured by ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV), of which conclusions are inconsistent. Moreover, limited evidence is available on the contributory role of PM2.5 exposure on the arterial stiffness index. Methods We used the population data from the Beijing Health Management Cohort and conducted a longitudinal analysis. The annual average concentration of PM2.5 for 35 air pollutant monitoring sites in Beijing from 2014 to 2018 was used to estimate individual exposure by different interpolation methods. Multivariate logistic regression and linear regression were conducted to assess the association of annual average PM2.5 concentration with the incidence of higher baPWV, the progression of ABI, and baPWV, respectively. Results The association between PM2.5 exposure and incidence of higher baPWV was not significant (OR = 1.11, 95% CI: 0.82–1.50, P = 0.497). There was − 0.16% (95% CI: − 0.43-0.11%) decrease in ABI annually and 1.04% (95% CI: 0.72–1.37%) increase in baPWV annually with each increment of 10 μg/m3 average PM2.5 concentration. Conclusions Long-term exposure to PM2.5 was associated with the progression of arterial stiffness in Beijing. This study suggests that improvement of air quality may help to prevent arterial stiffness.

Liang, Gu and other colleagues develop a convoluted neural network (CNN)-based framework to diagnose COVID-19 infection from chest X-ray and computed tomography images, and comparison with other upper respiratory infections. Compared to expert evaluation of the images, the neural network achieved upwards of 99% specificity, showing promise for the automated detection of COVID-19 infection in clinical settings.

Radix Paeoniae Rubra (Chishao), a typical multi-origin Chinese medicinal material, originates from the dried roots of Paeonia lactiflora or P. veitchii. The previous study suggested that these two commonly used Chishao showed variation in their chemical compositions and clinical efficacies. Therefore, accurate identification of different Chishao species was of great significance for the guide of clinical medication, and timely treatment of patients. In this study, the chloroplast genome sequences of P. lactiflora and P. veitchii were obtained by next-generation sequencing (NGS) technology, and then the hypervariable regions were selected to design two mini-barcode candidates for species identification. Combined with DNA metabarcoding technology, we performed qualitative and quantitative analysis on the artificially mixed samples of P. lactiflora and P. veitchii and evaluated the identification ability of these mini-barcode candidates. Furtherly, the mini-barcode with good performance was applied to distinguish the Chinese patent medicine “cerebral thrombosis tablets” containing Chishao. The results indicated that the chloroplast genomes of P. lactiflora and P. veitchii were 152,750 and 152,527 bp, respectively. As published previously, they exhibited a typical quadripartite structure including a large single-copy region (LSC), a small single-copy region (SSC) and a pair of inverted repeat regions (IRs). The nucleotide polymorphism analysis revealed seven variable protein-coding regions as petL, psaI, psbJ, rpl16, ycf1b, psaC, and ndhF, and two mini-barcodes were developed from ycf1b and ndhF respectively. The result suggested that both two mini-barcodes performed well distinguishing P. lactiflora from P. veitchii. Besides, P. lactiflora was the only raw material of Chishao in all collected “cerebral thrombosis tablets” samples. In general, this study has established a method to realize the qualitative and quantitative identification of Chishao as multi-origin Chinese medicinal materials, which can be applied to Chinese patent medicines containing Chishao.

Abstract Background Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders. Methods The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model. Results Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression. Conclusion Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment.

Deep Learning based image quality assessment (IQA) has been shown to greatly improve the quality score prediction accuracy of images with single distortion. However, because these models lack generalizability and the accuracy of multidistortion-based image data is relatively low, designing reliable IQA systems is still an open issue. In this paper, we propose to introduce long-range dependencies between local artifacts and high-order spatial pooling into a convolutional neural network (CNN) model to improve the performance and generalizability of the full-reference IQA (FR-IQA). This long-range dependencies model is based on the hypothesis that local apparent artifacts can affect the overall image quality. The proposed network architecture adopts a non-local means algorithm to establish connections between all positions in the deep feature space and uses the Minkowski function to improve the non-linearity of the spatial pooling. Based on this architecture, a robust FR-IQA system has been constructed and evaluated on three well-known single-distortion-based IQA databases (LIVE, CSIQ, and TID2013) and a multidistortion-based IQA database (MDID). Experimental results demonstrate that, compared with the latest FR-IQA systems, the proposed long-range dependencies-boosted CNN-based FR-IQA system can achieve state-of-the-art performance. A comprehensive cross-database evaluation also shows that the proposed system is sufficiently generalized between different databases and multidistortion-based image data is more useful for training robust image quality metrics.

Accumulating evidence indicates that aquatic organisms ingest microplastics (MPs), which may be a threat to essentially the entire global ecosystem. In current detection methods, even in cutting-edge nanoplastic technology, a major challenge for detecting microplastics (MPs) in aquatic organisms is removing complex biological matrices, such as fat. Herein we report combining HNO3 and H2O2 to form a binary digestive reagent system to determine MPs in biological tissue. With insights obtained from a Gaussian model, the adding manners of two reagents were discussed. Thus, in the final protocol, we mixed MPs and tissue with 20 mL of 30% (v/v) aqueous H2O2, 10 mL 0.5 M NaOH,1 mL 5 mM Fe2+, and 40 mL 11.5% (v/v) aqueous HNO3, in sequence at different time intervals. What’s more, sodium dodecyl sulfate (SDS) and ultrasound—alone or together—were explored to solve the problem of removing fat residues and thus membrane blockage during filtration. In this paper, we used the O-PTIR microscope to verify the feasibility of the protocol. Compared with traditional detection methods, the O-PTIR spectroscopy can significantly improve the lateral resolution, down to sub and super-micrometer, and the ability to quickly obtain high spatial resolution far-field non-contact infrared spectra, which provide a novel method for qualitative analysis of MPs. In field applications, in our attempt, the fixed wavenumber image by O-PTIR can realize sub and super-micrometer MPs in situ, far-field measurements. The present method is highly efficient, and facilitates the identification of plastic particles.

Background: Scientific studies have identified various adverse effects of particulate matter (PM) on respiratory disease (RD) and type 2 diabetes (T2D). However, whether short-term exposure to PM triggers the onset of RD with T2D, compared with RD without T2D, has not been elucidated. Methods: A two-stage time-series study was conducted to evaluate the acute adverse effects of PM on admission for RD and for RD with and without T2D in Beijing, China, from 2014 to 2020. District-specific effects of PM2.5 and PM10 were estimated using the over-dispersed Poisson generalized addictive model after adjusting for weather conditions, day of the week, and long-term and seasonal trends. Meta-analyses were applied to pool the overall effects on overall and cause-specific RD, while the exposure-response (E-R) curves were evaluated using a cubic regression spline. Results: A total of 1550,154 admission records for RD were retrieved during the study period. Meta-analysis suggested that per interquartile range upticks in the concentration of PM2.5 corresponded to 1.91% (95% CI: 1.33–2.49%), 2.16% (95% CI: 1.08–3.25%), and 1.92% (95% CI: 1.46–2.39%) increments in admission for RD, RD with T2D, and RD without T2D, respectively, at lag 0–8 days, lag 8 days, and lag 8 days. The effect size of PM2.5 was statistically significantly higher in the T2D group than in the group without T2D (z = 3.98, P

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, and its prevalence is still growing rapidly. However, the efficient therapies for this liver disease are still limited. Mitochondrial dysfunction has been proven to be closely associated with NAFLD. The mitochondrial injury caused reactive oxygen species (ROS) production, and oxidative stress can aggravate the hepatic lipid accumulation, inflammation, and fibrosis. which contribute to the pathogenesis and progression of NAFLD. Therefore, pharmacological therapies that target mitochondria could be a promising way for the NAFLD intervention. Recently, natural products targeting mitochondria have been extensively studied and have shown promising pharmacological activity. In this review, the recent research progress on therapeutic effects of natural-product-derived compounds that target mitochondria and combat NAFLD was summarized, aiming to provide new potential therapeutic lead compounds and reference for the innovative drug development and clinical treatment of NAFLD.

Reanalysis precipitation products (RPPs) are frequently used for studying the water cycle changes from short to long-term scale globally. In the current study, ERA-5 produced by the European Centre for Medium-Range Weather Forecasts (ECMWF), the Japanese 55-year Reanalysis (JRA-55), the Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2), and the Climate Forecast System version 2 (CFS-2) precipitation products were evaluated with the rain-gauge data as a reference during 1981–2019 over Pakistan. The performance was assessed using statistical error metrics on daily, monthly, and annual timescales. The reanalysis precipitation products (RPPs) captured the precipitation intensities and the extreme precipitation events (75th to 99th percentile) across climatic classes. On a daily scale, the ERA-5 follows rain-gauges very closely (RC: 0.67, R: 0.81, RMSE: 1.69 mm), consistently capturing the precipitation intensities (light to violent) and extreme precipitation events (95th percentile), followed by CFS-2. The MERRA-2 captured precipitation intensity but did not detect extreme precipitation events in some regions. The JRA-55 produced good results in the central area while overestimated the precipitation in the northern and southern parts of the study area. On a monthly time scale, ERA-5 performed well as compared to the rest of RPPs, with regression coefficient values of 0.91, correlation coefficient (0.96), and a lower value of RMSE (11.09 mm), followed by JRA-55, MERRA-2, and CFS-2. All the RPPs performed better in winter, pre-monsoon, and post-monsoon seasons with slight deviations/differences, but in monsoon season, the ERA-5 and JRA-55 (MERRA-2, CFS-2) overestimated (underestimated) precipitation mean. The findings can help the researchers select reliable datasets for bias correction of the projections and real-time application in flood, drought estimation, and prediction.

Haemophilus influenzae is a major human pathogenic bacterium, resulting in a series of diseases, such as pneumonia, bacteremia, meningitis. However, it is hard to diagnose H. influenzae quickly. In this study, the multiple cross displacement amplification (MCDA) and nanoparticle-based lateral flow biosensor (LFB) (MCDA-LFB) were combined to detect H. influenzae, which has been proven to be reliable, rapid, and not complicated. On the basis of H. influenzae outer membrane protein P6 gene, 10 specific primers were designed. The best MCDA condition was 61°C for 1 h. The sensitivity of H. influenzae-MCD-LFB assay showed, in the pure cultures, the minimum concentration of genomic DNA templates was 100 fg. The specificity of H. influenzae-MCD-LFB assay showed only H. influenzae templates were detected, and no cross-reactivity was found in non-H. influenzae isolates and other Haemophilus species. In 56 sputum samples, with MCDA-LFB method and PCR detection, 21 samples were positive, which was in consistent with the traditional culture method. The accuracy of diagnosis of MCDA-LFB, in comparison with the traditional culture method and PCR detection, can reach 100%, indicating that the MCDA-LFB assay gains an advantage over the cultured-based method for target pathogen detection. In conclusion, the MCDA-LFB assay is suitable for the sensitive, rapid, and specific detection of H. influenzae, which might be used as a potential diagnostic tool for H. influenzae in basic and clinical laboratories.

In this work, a novel fiber optic sensor based on Fabry–Pérot interferometry is adopted in an optical coherence photoacoustic microscopy (OC-PAM) system to enable high-resolution in vivo imaging. The complete OC-PAM system is characterized using the fiber optic sensor for photoacoustic measurement. After characterization, the performance of the system is evaluated by imaging zebrafish larvae in vivo. With a lateral resolution of 3.4 μm and an axial resolution of 3.7 μm in air, the optical coherence microscopy subsystem visualizes the anatomy of the zebrafish larvae. The photoacoustic microscopy subsystem reveals the vasculature of the zebrafish larvae with a lateral resolution of 1.9 μm and an axial resolution of 37.3 μm. As the two modalities share the same sample arm, we obtain inherently co-registered morphological and vascular images. This OC-PAM system provides comprehensive information on the anatomy and vasculature of the zebrafish larvae. Featuring compactness, broad detection bandwidth, and wide detection angle, the fiber optic sensor enables a large field of view with a static sensor position. We verified the feasibility of the fiber optic sensor for dual-modality in vivo imaging. The OC-PAM system, as a non-invasive imaging method, demonstrates its superiority in the investigation of zebrafish larvae, an animal model with increasing significance in developmental biology and disease research. This technique can also be applied for functional as well as longitudinal studies in the future.

Diabetic kidney disease (DKD) is a common and devastating complication in diabetic patients, which is recognized as a large and growing problem leading to end-stage kidney disease. As dietary-mediated therapies are gradually becoming more acceptable to patients with DKD, we planned to find active compounds on preventing DKD progression from dietary material. The present paper reports the renoprotective properties and underlying mechanisms of ginsenoside compound K (CK), a major metabolite in serum after oral administration of ginseng. CK supplementation for 16 weeks could improve urine microalbumin, the ratio of urinary albumin/creatinine and renal morphological abnormal changes in db/db mice. In addition, CK supplementation reshaped the gut microbiota by decreasing the contents of Bacteroides and Paraprevotella and increasing the contents of Lactobacillu and Akkermansia at the genus level, as well as reduced histidine-derived microbial metabolite imidazole propionate (IMP) in the serum. We first found that IMP played a significant role in the progression of DKD through activating toll-like receptor 4 (TLR4). We also confirmed CK supplementation can down-regulate IMP-induced protein expression of the TLR4 signaling pathway in vivo and in vitro. This study suggests that dietary CK could offer a better health benefit in the early intervention of DKD. From a nutrition perspective, CK or dietary material containing CK can possibly be developed as new adjuvant therapy products for DKD.

Aquatic plants widely exist in rivers, which can affect the flow structure in rivers and have an important impact on the evolution of river morphology. The emerged vegetation is an important member of aquatic vegetation in the river, so studying the flow structure around the emerged vegetation patches is of great significance. Computational fluid dynamics (CFD) simulation provides support for the related research works. Applying the appropriate turbulence model is crucial to achieving realistic numerical simulation results. In this study, two-dimensional numerical simulations were carried out and compared with experimental data by six different Reynolds-Averaged Navier–Stokes (RANS) turbulence models, i.e., Standard k-ε model, Renormalization group (RNG) k-ε model, Realizable k-ε model, Standard k-ω model, Shear-stress transport (SST) k-ω Model, and the Reynolds stress model (RSM). CFD is an effective research method, and the results showed that there are different simulation performances with different turbulence models. The shear stress transport k-ω model achieves the most consistent numerical simulation results with the experimental data for the longitudinal mean flow velocity distribution at the centerline, and the Reynolds stress model provides the least consistent numerical simulation with the experimental data. Then the performance of the six models in simulating the flow field characteristics and longitudinal outflow after vegetation patch was compared.

Background: The health effect of particulate matter pollution on stroke has been widely examined; however, the effect among patients with comorbid type 2 diabetes (T2D) in developing countries has remained largely unknown. Methods: A time-series study was conducted to investigate the short-term effect of fine particulate matter (PM2.5) and inhalable particulate matter (PM10) on hospital admissions for stroke among patients with T2D in Beijing, China, from 2014 to 2018. An over-dispersed Poisson generalized additive model was employed to adjust for important covariates, such as weather conditions and long-term and seasonal trends. Results: A total of 159,298 hospital admissions for stroke comorbid with T2D were reported. Approximately linear exposure-response curves were observed for PM2.5 and PM10 in relation to stroke admissions among T2D patients. A 10 μg/m3 increase in the four-day moving average of PM2.5 and PM10 was associated with 0.14% (95% confidence interval [CI]: 0.05–0.23%) and 0.14% (95% CI: 0.06–0.22%) incremental increases in stroke admissions among T2D patients, respectively. A 10 μg/m3 increase in PM2.5 in the two-day moving average corresponded to a 0.72% (95% CI: 0.02–1.42%) incremental increase in hemorrhagic stroke, and a 10 μg/m3 increase in PM10 in the four-day moving average corresponded to a 0.14% (95% CI: 0.06–0.22%) incremental increase in ischemic stroke. Conclusions: High particulate matter might be a risk factor for stroke among patients with T2D. PM2.5 and PM10 have a linear exposure-response relationship with stroke among T2D patients. The study provided evidence of the risk of stroke due to particulate matter pollution among patients with comorbid T2D.

Riverine outflow is one of the major pathways for microplastic transportation to coastal environments. Research on the output of microplastics in small- or medium-sized rivers will help accurately understand the status of their marine loads. In this study, we used both trawling and pumping methods to collect microplastics of different sizes in the Jiulong River Estuary and Xiamen Bay. We found that the abundance of small microplastics (44 μm–5.0 mm) was at least 20 times higher than the large particles (0.33–5.0 mm). The abundance of the large particles ranges from 4.96 to 16.3 particles/m3, and that of the small particles ranged from 82.8 to 918 particles/m3. Granule was the dominant shape (>60%), and polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) were the most common components. The riverine flux of small microplastics (44 μm–5 mm, 472 ± 230 t/y) was at a medium level and was eight times greater than that of large particles (0.33–5.0 mm, 61.2 ± 2.6 t/y). The behavior of the large microplastics was relatively conservative, whose abundance had a significant correlation with salinity (R2 = 0.927) and was mainly influenced by physical factors. In contrast, results of statistical analysis revealed that more complicated factors influenced the small microplastics.

Accelerated blood clearance (ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells (KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside (APM) lipid derivative DSPE-PEG2000-APM (DPM), and 4-aminophenyl-β-L-fucopyranoside (APF) lipid derivative DSPE-PEG2000-APF (DPF) were conjugated and modified on alendronate sodium (AD) liposomes to specifically target and deplete KCs. The dual-ligand modified PEGylated liposomes (MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes (PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What's more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs. Most important of all, KCs-targeted liposomes could induce a stronger ABC phenomenon than PL in normal rats, which declared that based on the same IgM concentration, the more the KCs were stimulated, the stronger ABC phenomenon was induced. However, in depletion rats, this difference of ABC phenomenon between PL and MFPL could no more exist, further demonstrating that KCs could participate and play a certain role in the ABC phenomenon. Keywords: Accelerated blood clearance (ABC) phenomenon, Kupffer cells, Depletion, Liposomes, Bio-distribution

Abstract Pectobacterium carotovorum ssp. carotovorum (Pcc) is a necrotrophic bacterial species that causes soft rot disease in Chinese cabbage. In this study, plants harboring the resistant mutant sr gene, which confers resistance against Pcc, were screened from an 800 M2 population mutated by ethyl methane sulfonate (EMS) and scored in vitro and in vivo for lesion size. The transcript profiles showed ~512 differentially expressed genes (DEGs) between sr and WT plants occurring between 6 and 12 h postinoculation (hpi), which corresponded to the important defense regulation period (resistance) to Pcc in Chinese cabbage. The downstream defense genes (CPK, CML, RBOH MPK3, and MPK4) of pathogen pattern-triggered immunity (PTI) were strongly activated during infection at 12 hpi in resistant mutant sr; PTI appears to be central to plant defense against Pcc via recognition by three putative pattern recognition receptors (PRRs; BrLYM1-BrCERK1, BrBKK1/SERK4-PEPR1, BrWAKs). Pcc triggered the upregulation of the jasmonic acid (JA) and ethylene (ET) biosynthesis genes in mutant sr, but auxins and other hormones may have affected some negative signals. Endogenous hormones (auxins, JAs, and SA), as well as exogenous auxins (MEJA and BTH), were also verified as functioning in the immune system. Concurrently, the expression of glucosinolate and lignin biosynthesis genes was increased at 12 hpi in resistant mutant sr, and the accumulation of glucosinolate and lignin also indicated that these genes have a functional defensive role against Pcc. Our study provides valuable information and elucidates the resistance mechanism of Chinese cabbage against Pcc infection.

Abstract Background The incidence of tuberculosis (TB) remains high worldwide. Current strategies will not eradicate TB by 2035; instead, by 2182 is more likely. Therefore, it is urgent that new risk factors be identified. Methods An ecological study was conducted in 340 prefectures in China from 2005 to 2015. The spatial distribution of TB incidence was shown by clustering and hotspot analysis. The relationship between the distribution patterns and six meteorological factors was evaluated by the geographically weighted regression (GWR) model. Results During the 11 years of the study period, TB incidence was persistently low in the east and high in the west. Local coefficients from the GWR model showed a positive correlation between TB incidence and yearly average rainfall (AR) but a negative correlation with other meteorological factors. Average relative humidity (ARH) was negatively correlated with the incidence of TB in all prefectures (p

Turnips: “Neeps” show early differences from non-tuber–forming relative Turnips show physiological and molecular signs of hypocotyl-tuber development as early as 16 days after sowing, a finding that could help farmers improve the performance of this important food and feed crop. A team led by Guusje Bonnema from Wageningen University and Research in the Netherlands compared the early anatomy of turnips and another closely related subspecies of Brassica rapa, the non-tuber–forming pak choi. They documented differences in the cellular organization of the xylem by day-16 after seed planting. Gene expression profiling between 1–6 weeks after sowing revealed many genes involved in hypocotyl-tuber initiation and growth. These genes affect a range of biological processes, from carbohydrate transport and metabolism to cell-wall growth to hormone regulation. Tissue culture experiments also showed that auxin, a plant growth hormone, promoted early hypocotyl-tuber development.

Deep learning based image hashing methods learn hash codes by using powerful feature extractors and nonlinear transformations to achieve highly efficient image retrieval. For most end-to-end deep hashing methods, the supervised learning process relies on pair-wise or triplet-wise information to provide an internal relationship of similarity data. However, the use of pair-wise and triplet loss function is limited not only by expensive training costs but also by quantization errors. In this paper, we propose a novel semantic learning based hashing method for image retrieval to optimize the deep features structure in the hash space from a perspective of angular view. Specifically, we proposed an angular hashing loss function that explicitly improve intra-class compactness and inter-class separability between features in hash space. Geometrically, angular hashing loss can be regarded as imposing hash constraints on hypersphere manifold. In order to solve the training problem on the multi-label case, we further designed a dynamic Softmax training strategy that can directly train the network using gradient descent method. Extensive experiments on two well-known datasets of CIFAR-10 and NUS-WIDE demonstrate that the proposed Angular Deep Supervised Hashing (ADSH) method can generate high-quality and compact binary codes, which can achieve state-of-the-art performance as compared with conventional image hashing and deep learning-based hashing methods.

Hyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated ApoE−/−−/− mice, atherosclerosis was accelerated along with elevated serum cholesterol levels in the hyperuricemic state, which can be ameliorated by dioscin. Together with the in vitro assays, we found that the effect of dioscin was at least partially through the regulation of the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7α-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin (a metabolite of dioscin) suppressed FXR activation and increased CYP7A1, resulting in an increased conversion rate of cholesterols into bile acids. Further clinical study revealed that treatment with a dioscin-enriched preparation decreased serum cholesterol levels in individuals with hyperuricemia. In summary, this study demonstrated a slowdown effect of dioscin on the progression of hyperuricemia-induced atherosclerosis.

In Chinese cabbage (Brassica rapa L. ssp. pekinensis), leaf adaxial-abaxial (ad-ab) polarity is tightly related to leaf incurvature, an essential factor for the formation of leafy heads. Therefore, identification of the genes responsible for leaf ad-ab polarity and studying their genetic variation may clarify the mechanism of leafy head formation. By comparing the sequences of the genes regulating leaf ad-ab polarity development in Arabidopsis thaliana (A. thaliana), 41 candidate genes distributed on 10 chromosomes were found to be responsible for the establishment of ad-ab polarity in Chinese cabbage. Orthologous genes, including 10 single copies, 14 double copies, and one triple copies, were detected in the Chinese cabbage. The gene structure and conserved domain analyses showed that the number of exons of the 41 candidate genes range from one to 25, and that most genes share the conserved motifs 1, 6, and 10. Based on the 41 candidate genes, 341 simple sequence repeats (SSRs) were detected, including five replicated types: single, double, triple, quintuple, and sextuple nucleotide replications. Among these sequence repeat (SSR) loci, 323 loci were used to design 969 specific primers, and 362 primer pairs were selected randomly and evaluated using 12 Chinese cabbage accessions with different heading types. 23 primer pairs resulting with clear, polymorphic bands, combined with other 127 markers, was used to construct a linkage map by using an F2 population containing 214 lines derived from the hybrid of the overlapping heading Chinese cabbage “14Q-141” and the outward curling heading Chinese cabbage “14Q-279.” The result showed that the sequences of markers in the genetic linkage map and the physical map was consistent in general. Our study could help to accelerate the breeding process of leafy head quality in Chinese cabbage.

Ultrasound-mediated neuromodulation is emerging as a key technology for targeted noninvasive brain stimulation, but key insights into its effects and dose-response characteristics are still missing. The purpose of this study is to systematically evaluate the effect of low-intensity transcranial ultrasound stimulation (TUS) on complementary aspects of cerebral hemodynamic. We simultaneously record the EMG signal, local field potential (LFP) and cortical blood flow (CBF) using electrophysiological recording and laser speckle contrast imaging under ultrasound stimulation to simultaneously monitor motor responses, neural activities and hemodynamic changes during the application of low-intensity TUS in mouse motor cortex, using excitation pulses which caused whisker and tail movement. Our experimental results demonstrate interdependent TUS-induced motor, neural activity and hemodynamic responses that peak approximately 0.55s, 1.05s and 2.5s after TUS onset, respectively, and show a linear coupling relationship between their respective varying response amplitudes to repeated stimuli. We also found monotonic dose-response parametric relations of the CBF peak value increase as a function of stimulation intensity and duration, while stimulus duty-cycle had only a weak effect on peak responses. These findings demonstrate that TUS induces a change in cortical hemodynamics and LSCI provide a high temporal resolution view of these changes.