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Background: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. Methods: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). Results: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. Conclusion: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.

Depression is one of the most common psychological problems in adolescence. Familial and school-related factors are closely related to adolescents’ depression, but their combined effects need further examination. The purpose of this study was to explore the combined effects of risk/protective factors of depression in family and school domains using a sample of Chinese adolescents differing in gender, age group and left-behind status. A total of 2455 Chinese students in primary and secondary school participated in the cross-sectional survey and reported multiple risk/protective factors in family and school environments and depressive symptoms. Association rule mining, a machine learning method, was used in the data analyses to identify the correlation between risk/protective factor combinations and depression. We found that (1) Family cohesion, family conflict, peer support, and teacher support emerged as the strongest factors associated with adolescent depression; (2) The combination of these aforementioned factors further strengthened their association with depression; (3) Female gender, middle school students, and family socioeconomic disadvantages attenuated the protective effects of positive relational factors while exacerbating the deleterious effects of negative relational factors; (4) For individuals at risk, lack of mental health education resources at school intensified the negative impact; (5) The risk and protective factors of depression varied according to gender, age stage and left-behind status. In conclusion, the findings shed light on the identification of high-risk adolescents for depression and underscore the importance of tailored programs targeting specific subgroups based on gender, age, or left-behind status.

Asphalt mixtures will inevitably be affected by rainwater and the effect of the wet temperature cycle during a pavement’s life span. Especially in coastal areas such as Guangdong and Hainan in China, asphalt pavement is particularly susceptible to the sizeable wet temperature cycle formed by the high temperature and sudden temperature drop of rainstorms in summer. For this study, we used a homemade sizeable wet temperature cycle environment simulation device to analyze the decay characteristics and the mechanical properties of asphalt pavements in this environment; modified bending and tensile strength and shear strength tests were used to study the decay patterns of shear strength, bending, and tensile strength, and the stiffness modulus of asphalt mixtures with different air voids and different pavement depths under the action of a sizeable wet temperature cycle. In addition, the Grey correlation method was used to analyze the significance of each influencing factor on the decay of mechanical properties, and mathematical fitting was used to establish the prediction equation of the mechanical properties of asphalt mixtures. The results show that with the increase in the number of sizeable wet temperature cycles, the asphalt mixture’s shear strength, flexural tensile strength, and flexural tensile modulus decrease, the degree of decay increases, and the rate of decay gradually slows down. In the case of the same number of sizeable wet temperature cycles, the degree of decay of the asphalt mixtures gradually decreases with increasing depth or decreasing void ratio. After 100 sizeable wet temperature cycles, the maximum values of the decay of shear strength, modulus of strength, and flexural tensile strength were 22.30%, 23.29%, and 32.01%. The importance of the influence of each factor on the decay of the mechanical properties is as follows: the number of sizeable wet temperature cycles > void rate > depth. The prediction equations of the established mechanical properties have a good prediction effect, and the correlation between predicted values and actual values can be up to 0.925. The prediction equations can effectively predict the mechanical properties of asphalt mixtures with different air voids and depths under the action of sizeable wet temperature cycles.

Marine soft corals are prolific sources of various natural products that have served as a wealthy reservoir of diverse chemical scaffolds with potential as new drug leads. The genus Litophyton contains almost 100 species but only a small proportion of them has been chemically investigated, which calls for more attentions from global researchers. In the current work, 175 secondary metabolites have been discussed, drawing from published data spanning almost five decades, up to July 2023. The studied species of the genus Litophyton resided in various tropical and temperate regions and encompassed a broad range of biologically active natural products including terpenes, steroids, nitrogen-containing metabolites, lipids, and other metabolites. A wide spectrum of pharmacological effects of these compounds had been evaluated, such as cytotoxic, antiviral, antibacterial, antifungal, anti-malarial, antifeedant, anti-inflammatory, molluscicidal, PTP1B inhibitory, insect growth inhibitory, and neuroprotective activities. This review aims to offer an up-to-date survey of the literature and provide a comprehensive understanding of the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available.

To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, six new steroids, namely lobosteroids A–F (1–6), along with four known compounds 7–10, were obtained. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis using Cu Kα radiation. These steroids were characterized by either the presence of an α,β-α′,β′-unsaturated carbonyl, or an α,β-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation of side chains. The antibacterial bioassays showed that all isolated steroids exhibited significant inhibitory activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28, Phoyobacterium damselae FP2244, and Streptococcus parauberis SPOF3K, with IC90 values ranging from 0.1 to 11.0 µM. Meanwhile, compounds 2 and 6–10 displayed potent inhibitory effects against the vancomycin-resistant Enterococcus faecium bacterium G7 with IC90 values ranging from 4.4 to 18.3 µM. Therefore, ten highly oxidized steroids with strong antibacterial activities were isolated from the Chinese soft coral Lobophytum sp., which could be developed as new chemotypes of antibacterial drug leads.

Materials for the selective transport of K+ have application in a variety of fields including water desalination and separation processes. Here the authors report charged porous subnanometer cages that are inspired in biological KcsA channels; high K+ transport rates and high K+/Li+ and K+/Na+ selectivity ratios are obtained, showing great potential in advanced sieving processes and efficient water treatments.

Background. Washed microbiota transplantation (WMT) as the improved methods of fecal microbiota transplantation has been employed as a therapeutic approach for ameliorating symptoms associated with autism spectrum disorder (ASD). In this context, colonic transendoscopic enteral tubing (TET) has been utilized as a novel procedure for administering WMT. Methods. Data of children with ASD who received WMT by TET were retrospectively reviewed, including bowel preparation methods, TET operation time, success rate, tube retention time, the comfort of children, adverse events, and parent satisfaction. Results. A total of 38 participants underwent 124 colonic TET catheterization procedures. The average time of TET operation was 15 minutes, and the success rate was 100% (124/124). There was no significant difference in TET operation time between high-seniority physicians and low-seniority physicians. In 123 procedures (99%), the TET tube allowed the completion of WMT treatment for 6 consecutive days. In 118 procedures (95.2%), the tube was detached spontaneously after the end of the treatment course, and the average TET tube retention time was 8 days. There was no incidence of tube blockage during the treatment course. No severe adverse events occurred during follow-up. Parents of all participants reported a high level of satisfaction with TET. Conclusion. Colonic TET is a safe and feasible method for WMT in children with ASD.

A statistical shape model (SSM) based analysis was conducted in our study. We indicated the morphological differences of the first trapezoid-metacarpal (TMC) bone between the region-based statistical shape model (rSSM) and the nonregion-based statistical shape model (nrSSM). We aimed to characterize more specific and accurate variation results to detect and prevent osteoarthritis in an early way. CT image data of TMC from 31 healthy volunteers were simulated with 3D models. A training set of models was analyzed with principal component analysis, with both then- rSSM and rSSM. The region was identified automatically with Gaussian curvature analysis. We found four dominant shape variations from both nrSSM and rSSM. The rSSM showed more variations with fewer components compared with nrSSM. The first principal component revealed the size variation as the biggest component. A significant difference was presented in the second and the fourth principal component from rSSM, showing the torsion of the distal head of the first metacarpal which may increase the risk of osteoarthritis.

BackgroundA few studies found that the complement system may be involved in the onset and progression of community-acquired pneumonia (CAP). However, the role of the complement system in CAP was obscure. The goal of this study was to analyze the association of serum complement C3a with CAP severity scores based on a cross-sectional study.MethodsAll 190 CAP patients and 95 control subjects were enrolled. Demographic information and clinical data were extracted. Peripheral blood samples were collected on admission.ResultsSerum complement C3a on admission was elevated in CAP patients compared with healthy subjects. The level of complement C3a was gradually elevated in parallel with CAP severity scores (CURB-65, CRB-65, PSI, SMART-COP, and CURXO). Complement C3a was positively correlated with blood routine parameters, renal function markers, and inflammatory cytokines in CAP patients. Furthermore, multivariate linear and logistic regression models found that serum complement C3a on admission was positively associated with CAP severity scores. Mechanistic research suggested that complement system inhibition alleviated Streptococcus pneumoniae-induced upregulation of IL-1β, TNF-α, IL-6, and CRP in MLE-12 cells.ConclusionsSerum complement C3a on admission is positively associated with the severity of CAP patients. Inhibiting complement system attenuates S. pneumoniae-elevated secretion of inflammatory cytokines in pulmonary epithelial cells, indicating that complement C3a is involved in the pathophysiology of CAP. Serum complement C3a may serve as an earlier diagnostic biomarker for CAP.

The development of coagulation factor VIII (FVIII) inhibitory antibodies is a serious complication in hemophilia A (HA) patients after FVIII replacement therapy. Inhibitors render regular prophylaxis ineffective and increase the risk of morbidity and mortality. Immune tolerance induction (ITI) regimens have become the only clinically proven therapy for eradicating these inhibitors. However, this is a lengthy and costly strategy. For HA patients with high titer inhibitors, bypassing or new hemostatic agents must be used in clinical prophylaxis due to the ineffective ITI regimens. Since multiple genetic and environmental factors are involved in the pathogenesis of inhibitor generation, understanding the mechanisms by which inhibitors develop could help identify critical targets that can be exploited to prevent or eradicate inhibitors. In this review, we provide a comprehensive overview of the recent advances related to mechanistic insights into anti-FVIII antibody development and discuss novel therapeutic approaches for HA patients with inhibitors.

A method is proposed for the prospecting prediction of subsurface mineral deposits based on soil geochemistry data and a deep convolutional neural network model. This method uses three techniques (window offset, scaling, and rotation) to enhance the number of training data for the model. A window area is used to extract the spatial distribution characteristics of soil geochemistry and measure their correspondence with the occurrence of known subsurface deposits. Prospecting prediction is achieved by matching the characteristics of the window area of an unknown area with the relationships established in the known area. This method can efficiently predict mineral prospective areas where there are few ore deposits used for generating the training dataset, meaning that the deep-learning method can be effectively used for deposit prospecting prediction. Using soil active geochemical measurement data, this method was applied in the Daqiao area, Gansu Province, for which seven favorable gold prospecting target areas were predicted. The Daqiao orogenic gold deposit of latest Jurassic and Early Jurassic age in the southern domain has more than 105 t of gold resources at an average grade of 3–4 g/t. In 2020, the project team drilled and verified the K prediction area, and found 66 m gold mineralized bodies. The new method should be applicable to prospecting prediction using conventional geochemical data in other areas.© 2022 China Geology Editorial Office.

Objectives Methods Results Conclusion The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME‐BLI) examination.Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B‐type LSTs using ME‐BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B‐low (n = 178) and JNET2B‐high (n = 53) LSTs. The JNET2B‐low and JNET2B‐high LSTs were compared based on their histopathological and morphological classifications.Among the 178 JNET2B‐low LSTs, 86 (48.3%) were histopathologically classified as low‐grade intraepithelial neoplasia, 54 (30.3%) as high‐grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B‐high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B‐low and JNET2B‐high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592–0.804) between the two endoscopists who reassessed the endoscopic images.The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision‐making. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis. [ABSTRACT FROM AUTHOR]

The objective of the study was to observe the results of bone marrow flow cytometric (BMFC) typing and pathological immunohistochemical (PI) of lymphoma cell leukemia (LCL), and then provide scientific data for clinical typing of lymph node cell leukemia. The BMFC typing and PI data of 86 patients with LCL admitted to our hospital from January 2018 to January 2022 were retrospectively analyzed to compare the BMFC typing and PI expression, and investigate the differences in PI results among patients with different BMFC typing. There were significant differences in bone marrow flow cytometry immunogen level between T lymphocyte type and B lymphocyte type (P<0.05). CD3, BCL-2, CD7, TDT and CD34 were the dominant PI typing of T cell type. The expression rate of BCL-2 was 100.00% and that of CD3 was 91.67% (33/36), followed by TDT, CD7 and CD34. CD20, CD79a, BCL-6 and BCL-2 were the dominant PI typing of B-cell type. CD20 had the highest expression rate (100.00%), followed by CD79a and BCL-6. There were significant differences in PI typing antigen level between T lymphocyte type and B lymphocyte type (P<0.05). Regarding the correlation between the same antigen of BMFC typing and PI typing, only CD3, CD7 and CD20 were correlated (r>0, P<0.05). CD5 exhibited no correlation (P>0.05). BMFC typing and PI antigen typing of LCL are only correlated in terms of CD3, CD7 and CD20 antigens, with complementary effects shown in other antigens. It was concluded that clinical selection should be made by comprehensive consideration of patients' conditions. [ABSTRACT FROM AUTHOR]

In this work, we employ well-established relations for compressible turbulent mean flows, including the velocity transformation and algebraic temperature-velocity (TV) relation, to systematically improve the algebraic Baldwin-Lomax (BL) wall model for high-speed zero-pressure-gradient air boundary layers. Any new functions or coefficients fitted by ourselves are avoided. Twelve published direct numerical simulation (DNS) datasets are employed for a priori inspiration and a posteriori examination, with Mach numbers up to 14 under adiabatic, cold and heated walls. The baseline BL model is the widely used one with semilocal scalings. Three targeted modifications are made. First, we employ a total-stress-based transformation (Griffin et al., Proc. Natl Acad. Sci. USA, vol. 118, issue 34, 2021, e2111144118) to the inner-layer eddy viscosity for improved scaling up to the logarithmic region. Second, we utilize the van Driest transformation in the outer layer based on the compressible defect velocity scaling. Third, considering the difficulty in modelling the rapidly varying and singular turbulent Prandtl number near the temperature peak in cold-wall cases, we design a two-layer strategy and use the TV relation to formulate the inner-layer temperature. Numerical results prove that the modifications take effect as designed. The prediction accuracy for mean streamwise velocity is notably improved for diabatic cases, especially in the logarithmic region. Moreover, a significant improvement in mean temperature is realized for both adiabatic and diabatic cases. The mean relative errors of temperature to DNS for all cases are down to 0.4%in the logarithmic wall-normal coordinate and 3.4% in the outer coordinate, around one-third of those in the baseline model. [ABSTRACT FROM AUTHOR]

The Hutoubi Reservoir and its mainstream, Huyuan Stream, in the southern mountainous region of Taiwan, have experienced riverbed sedimentation and flood disasters for the past 150 years. In addition to climate change, it is necessary to scientifically consider its regulation for the next hundred years. This study adopted a collaborative approach, involving industry, government, and academia, using Nature-based Solutions (NbS) to enhance ecosystem services. The solution layout is constructed by widening the channel and constructing additional farm ponds and wetlands. An hydraulic simulation indicated that flood control was addressed. The restoration project would create diverse aquatic habitats by simulating and evaluating the distribution of ecological biotopes, using porous materials as revetments. It provided urban residents with forest leisure and recreational sites and supported the local agricultural and forestry products. The restoration has propagated local culture and created environmental and professional education. Therefore, ecological services are enhanced regarding regulation, support, provision, and culture. This pilot study, led by researchers, aimed to promote comprehensive management concepts considering all stakeholders and their active participation. We integrated NbS into the watershed and its river system as a pathway for facing the challenges of rapid urbanization and climate change and improving ecosystem services.

Determining crustal stress is crucial in the design and construction of underground engineering projects, particularly in fault fracture zones. This paper aims to identify the characteristic factors that influence the crustal stress of faults, including the difference in deformation characteristics between faults and ordinary formations (expressed by the elastic modulus ratio Er/Ef), the degree of fault fragmentation P, and the angle α between fault tendency and the principal stress direction. Numerical simulations are conducted to investigate the impact of these three factors on the magnitude and direction of the principal stress. Additionally, measured stress values from a specific tunnel are analyzed to validate the findings. The results demonstrate the crucial role of α in determining the increase or decrease of principal stress and the direction of the offset. When α is less than 45°, σ1 and σ3 within the fault experience an increase, while σ1 and σ3 in the ordinary surrounding rock area near the fault exhibit a slight decrease. Moreover, the σ1 direction inside the fault deviates towards the parallel fault, whereas σ1 near the outside slightly deviates towards the vertical fault. Conversely, when α is greater than 45°, the trend of principal stress is reversed. Er/Ef affects the magnitude of the principal stress change, with larger values resulting in more pronounced changes. P only affects the stress distribution inside the fault.

The rapid spread of capitalism in rural areas has facilitated rural land commodification (RLC). While some scholars have studied RLC, few have analyzed its spatial characteristics. Taking Shijiazhuang city as a study area, this paper applies Moran’s I method and spatial regression models to analyze township-scale RLC patterns and driving factors. The study investigates four common pathways of RLC: production-oriented farmland, tourism-oriented farmland, rural homesteads, and construction land commodification which are predominantly found in urban fringe areas. The distribution of RLC demonstrates positive spatial autocorrelation, characterized by spatial aggregation and polarization. Population, economic level, agriculture, and location conditions are identified as key drivers, and their specific mechanisms vary across development pathways. Future efforts should focus on ensuring balanced and coordinated RLC development in accordance with regional conditions and capacity, while also addressing the implications arising from the coexistence of RLC with rural aging and poverty.

The Electrocardiogram (ECG) is one of the important tools for diagnosing myocardial infarction. The ECG training course aims to help nurses establish basic competence in interpreting ECG readings. However, in traditional instruction, learners usually have difficulty memorizing the meanings of different ECG wave forms, which could represent clinical symptoms, or even life-threatening conditions/arrhythmia. Some serious problems could cause death if the nursing staff do not make correct judgments in time. This paper reports an explorative study which investigated a novel pedagogy for nursing school students' ECG learning performance using a contextual game. A 2 week experiment was conducted to compare the learning performances of the nursing students who played the ECG contextual game and those who learned with traditional instruction. The experimental results show that the students learning with the contextual game showed better learning performance, attitude, motivation, and critical thinking tendency than those who received the traditional instruction.

In order to study the effect of the symmetry error generated by processing on the herringbone character gear meshing transmission， improve the stability of the transmission， according to the structural characteristics of herringbone gear and gear geometry contact model， consider the tooth surface gap， force equilibrium conditions and axial displacement， the herringbone gear bearing contact analysis model of symmetry error is established. The influence of different symmetry error on the gear contact and axial vibration of a pair of herringbone gear is analyzed， and then a compensation method that uses coupling effect of axial assembling error and symmetry error is put forward. The research result shows that symmetry error seriously reduces the stability and reliability of herringbone gear transmission. The error coupling compensation can lower partial loaded and axial vibration caused by symmetry error which provides new methods for the optimization of transmission process and is of greatly significant to improve the dynamic characteristics of herringbone gear system.

Objective Shenling Baizhu powder (SBP) has been shown to reverse the abnormal expression of the aromatic hydrocarbon receptor (AHR) mediated by air pollution. Our study aimed to understand the main ingredient of SBP and investigate its action mechanism in preventing polycystic ovary syndrome (POCS) and postmenopausal osteoporosis (PMO). Methods The active ingredients of SBP with the highest binding affinity to AHR were screened using a Chinese medicine database, and their binding mechanism was simulated using molecular dynamics simulation (MDS). Rutin was utilized to treat ovarian granulosa cell lines and osteoblast cell lines. The cell lines were treated with a gradient of rutin concentration (0.01 mmol/L, 0.05 mmol/L and 0.1 mmol/L) to find the optimal drug dose. PCR was used to detect AHR and apoptosis-related proteins, and WB to detect the expression of AHR, caspase-3 and cleaved-caspase-3. Finally, the CCK-8 cell proliferation assay detected the proliferation of cells. Results We obtained Rutin through the Chinese medicine database, and dynamics simulation determined its binding sites. Ovarian granulosa cell lines and osteoblast cell lines were treated with Rutin. RT-PCR and western blotting revealed that the expression of apoptosis-associated protein Bcl-2 was elevated, and the expression of AHR, Bax, caspase-3 and PARP were decreased. CCK-8 results showed accelerated proliferation in both cell types. Conclusion Rutin, the main ingredient of SBP compound, works by binding to AHR, which can improve POCS and PMO by inhibiting cell apoptosis and by promoting cell proliferation.

Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.

BackgroundCysteine-rich 61 (CYR61) is implicated in many pulmonary diseases. However, the relationship between CYR61 and community-acquired pneumonia (CAP) patients was unknown. This research aimed to estimate the correlations of serum CYR61 with severity and prognosis in CAP patients through a prospective cohort study.MethodsAll 541 CAP patients were enrolled in this study. Fasting venous blood was collected. Clinical characteristics and demographic information were obtained. CYR61 and inflammatory cytokines were detected in serum using ELISA.ResultsSerum CYR61 was gradually increased in parallel with severity scores in CAP patients. Correlative analysis indicated that serum CYR61 was strongly associated with many clinical parameters in CAP patients. Moreover, mixed logistic and linear regression models found that there were positive correlations between serum CYR61 and CAP severity scores after adjusted for age, BMI, and respiratory rate. Stratified analyses suggested that age affected the associations between serum CYR61 and severity scores. On admission, higher serum CYR61 levels elevated the risks of mechanical ventilation, vasoactive agent, ICU admission, death, and longer hospital stays during hospitalization. Moreover, serum CYR61 in combination with severity scores upregulated the predictive capacities for severity and death than single serum CYR61 or severity scores in CAP patients.ConclusionThere are significantly positive dose-response associations of serum CYR61 on admission with the severity and adverse prognostic outcomes, demonstrating that CYR61 is involved in the pathophysiology of CAP. Serum CYR61 may be used as a potential biomarker for the diagnosis and prognosis in CAP patients.

Apple fruits are susceptible to infection by postharvest fungal pathogens, which may cause fruit decay and severe economic losses. This study investigated the antifungal spectrum of vanillin against common decay pathogens of apple and explored the antifungal mechanisms of vanillin in vitro. In vivo experiments were carried out to evaluate the effects of vanillin on apple postharvest disease control and fruit quality. Moreover, the induced resistance mechanism of vanillin on apple fruit was preliminarily explored. The results showed that vanillin has broad-spectrum antifungal effects, especially on Alternaria alternata. Vanillin could significantly inhibit the growth rate, mycelium biomass, and spore germination of pathogenic fungi by increasing the cell membrane permeability and lipid peroxidation. Importantly, vanillin treatment reduced the incidence of apple decay caused by A. alternata and Penicillium expansum, and contributed to improve fruit quality. Further studies indicated that vanillin could induce elevation in the activities of defense-related enzymes in apple fruit, such as phenylalanine ammonia-lyase (PAL), chitinase (CHI) and β-1,3-glucanase (β-1,3-GA), and increase total phenols and flavonoids contents. Generally, these results suggest that vanillin may contribute to the induced resistance of apple fruits to pathogenic fungi. To conclude, the results of this research provide theoretical foundations for the application of vanillin in the control of apple postharvest decay caused by fungal pathogens.