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The pathophysiological mechanisms involved in fibrotic interstitial lung diseases (FILDs) are akin to those observed in idiopathic pulmonary fibrosis (IPF), implying the potential for shared therapeutic approaches. Pirfenidone exhibits antifibrotic and anti-inflammatory properties, making it the first small-molecule drug approved for treating IPF. Pirfenidone has been utilized in IPF treatment for more than one decade. However, guidelines for progressive pulmonary fibrosis (PPF) treatment suggest that further research and evidence are needed to fully comprehend its efficacy and safety across various PPF subtypes. In recent years, numerous studies have explored the use of pirfenidone in treating non-IPF FILD. Herein, we provide an overview of the latest research data on application of pirfenidone in occupational-related ILD, connective tissue disease-associated ILD, post-coronavirus disease-2019 pulmonary fibrosis, and other conditions. We summarize the level of evidence and highlight challenges associated with using pirfenidone in different FILDs to offer clinical guidance.

Abstract Background Peripherally inserted central catheters (PICCs) are common vascular access devices inserted for adults undergoing intravenous treatment in the community setting. Individuals with a PICC report challenges understanding information and adapting to the device both practically and psychologically at home. There is a lack of research investigating the supportive care needs of individuals with a PICC to inform nursing assessment and the provision of additional supports they may require to successfully adapt to life with a PICC. The aim of this study was to identify the supportive care needs of adults with cancer or infection living with a PICC at home. Method Qualitative, semi-structured interviews were used to identify supportive care needs of adults living with a PICC at home. Participants were recruited from cancer and infectious diseases outpatient units. Two researchers independently analysed transcripts using content analysis. Results A total of 15 participants were interviewed (30–87 years old). There were 5 males and 10 females interviewed, 9 participants had a cancer diagnosis and most lived in a metropolitan area. Many participants lived with a partner/spouse at home and three participants had young children. Participants identified supportive care needs in the following eight categories (i (i) Adapting daily life (ii) Physical comfort (iii) Self-management (iv) Emotional impact (v) Information content (vi) Understanding information (vii) Healthcare resources and (viii) Social supports. Conclusions Adults living with a PICC at home report a broad range of supportive care needs. In addition to practical and information needs, health consumers may also require support to accept living with a device inside their body and to assume responsibility for the PICC. These findings may provide nurses with a greater understanding of individual needs and guide the provision of appropriate supports.

BackgroundAlthough Shen Gui capsules (SGCP) are widely used as an adjuvant treatment for chronic heart failure (CHF), their clinical efficacy and safety remain controversial.PurposeTo assess the efficacy and safety of SGCP in the treatment of CHF through a systematic review and meta-analysis, to provide high-quality evidence for evidence-based medicine.MethodsSeven databases were searched for randomized controlled trials (RCTs) assessing SGCP for CHF, from inception to 9 January 2023. RCT quality of evidence was evaluated using the Cochrane Handbook for the Evaluation of Intervention Systems to assess risk of bias and Grading of Recommendations Assessment, Development, and Evaluation. A meta-analysis with subgroup and sensitivity analyses was performed using Review Manager 5.4 and Stata 12.ResultsNine RCTs representing 888 patients with CHF were included in the review. Meta-analysis revealed that SGCP combined with conventional heart failure therapy is more advantageous for improving left ventricular ejection fraction [LVEF; mean difference (MD) = 5.26, 95% confidence interval (CI) (3.78, 6.74), p < 0.0000] and increasing effective rate [relative risk (RR) = 1.21, 95%CI (1.14, 1.29), p < 0.001] compared with conventional therapy alone. The experimental treatment also reduced brain natriuretic peptide [MD = −100.15, 95%CI (−157.83, −42.47), p = 0.0007], left ventricular end-diastolic diameter [MD = −1.93, 95%CI (−3.22, −0.64), p = 0.003], and hypersensitive C-reactive protein [MD = −2.70, 95%CI (−3.12,−2.28), p < 0.001] compared with the control group. However, there was not a statistically significant difference in tumor necrosis factor-α [MD = −14.16, 95%CI (−34.04, 5.73), p = 0.16] or left ventricular end-systolic diameter [MD = −1.56, 95%CI (−3.13, 0.01), p = 0.05]. Nor was there a statistically significant between-groups difference in incidence of adverse events (p > 0.05).ConclusionSGCP combined with conventional heart failure therapy can improve LVEF and increase the effective rate to safely treat patients with CHF. However, further high-quality studies are needed to confirm these findings, due to the overall low quality of evidence in this literature.Clinical Trial Registration:https://www.crd.york.ac.uk/PROSPERO/logout.php, PROSPERO [CRD42023390409].

Due to natural sedimentation and artificial filling, slopes exhibit heterogeneity in the form of multi-layer soils, namely, layered slopes. Compared with homogenous slopes, the failure mechanism of layered slopes is more complex owing to the different shear strengths of each soil layer. Therefore, it is of great importance to gain insight into the stability of layered slopes. In this study, the upper bound theorem of limit analysis incorporated with a pseudo-static approach is utilized to investigate the seismic stability of two kinds of two-layered slopes: one with a stiff lower soil layer and the other with a weak lower soil layer. Three failure patterns, namely face failure, toe failure and base failure, are taken into account. A depth coefficient (Δ) is introduced to describe the distribution of two soil layers. The layer-wise summation method is adopted to calculate the safety factor and yield acceleration coefficient more conveniently. Based on Newmark’s method, the earthquake-induced horizontal displacement is estimated. The calculated results are validated by comparisons with published literature and the numerical method in terms of safety factor, critical failure surface and yield acceleration coefficient. The results show that the depth coefficient has a significant influence on the failure mechanism of two-layered slopes by determining whether the stability of upper-layered soil is dominant in the overall slope stability or not. Inaccurately identifying the failure patterns will overestimate the seismic performance of two-layered slopes in the aspects of safety factor and yield acceleration coefficient, leading to an underestimation of earthquake-induced horizontal displacement.

Background: As a ribosome receptor, LRRC59 was thought to regulate mRNA translation on the ER membrane. Evidence suggests that LRRC59 is overexpressed in a number of human malignancies and is associated with poor prognoses, but its primary biological function in the development of oral squamous cell carcinoma (OSCC) remains obscure. Objective: The purpose of this study is to investigate at the expression changes and functional role of LRRC59 in OSCC. Methods: LRRC59 gene expression and correlation with prognosis of OSCC patients were first examined using the data from The Cancer Genome Atlas (TCGA) databases. Following that, a series of functional experiments, including cell counting kit-8, cell cycle analysis, wound healing assays, and transwell assays, were carried out to analyze the biological roles of LRRC59 in tumor cells. Mechanistically, we employed Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach to isolate and identify protein complexes of LRRC59. Downstream regulatory proteins of LRRC59 were verified through immunoprecipitation and immunofluorescence experiments. Furthermore, we isolated exosomes from OSCC cell supernatant and conducted co-culture experiments to examine the effect of LRRC59 knockdown on OSCC cells. Results: In samples from OSCC patients, LRRC59 was highly expressed and correlated with poor prognoses. Moreover, the gene sets analysis based on TCGA RNA-seq data indicated that LRRC59 seemed to be strongly related with protein secretory and OSCC migration. Upregulated levels of LRRC59 are more prone to lymph node metastasis in OSCC patients. LRRC59 knockdown impaired the ability of OSCC cell proliferation, migration, and invasion invitro. Mechanistically, our TAP-MS data situate LRRC59 in a functional nexus for mRNA translation regulation via interactions with SRP pathway components, translational initiation factors, CRD-mediated mRNA stabilization factors. More importantly, we found that LRRC59 interacted with cytoskeleton-associated protein 4 (CKAP4) and promoted the formation of CKAP4-containing exosomes. We also revealed that the LRRC59-CKAP4 axis was a crucial regulator of CKAP4-containing exosome secretion in OSCC cells for migration and invasion. Conclusions: Therefore, based on our findings, LRRC59 may serve as a potential biomarker for OSCC patients, and LRRC59-induced exosome secretion via the CKAP4 axis may serve as a potential therapeutic target for OSCC.

Arctium lappa L. is a prevalent medicinal herb and a health supplement that is commonly used in Asia. Over the last few decades, the bioactive component arctigenin has attracted the attention of researchers because of its anti-inflammatory, antioxidant, immunomodulatory, multiple sclerosis fighting, antitumor, and anti-leukemia properties. After summarising the research and literature on arctigenin, this study outlines the current status of research on pharmacological activity, total synthesis, and structural modification of arctigenin. The purpose of this study is to assist academics in obtaining a more comprehensive understanding of the research progress on arctigenin and to provide constructive suggestions for further investigation of this useful molecule.

Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. However, the mechanisms involved are still largely unknown. Here, AWRK6 treatment presented an alleviative effect on lipid accumulation induced by oleic acid in hepatocytes. Meanwhile, miR-5100 and miR-505 were found to be elevated by oleic acid induction and reversed by AWRK6 incubation. Further, the miR-5100 inhibitor inhibited oleic acid-induced lipid accumulation, and the alleviation effect of AWRK6 was partially counteracted by miR-5100 mimics. The screening of potential target genes revealed that a catalytic subunit of G6Pase G6PC was significantly inhibited by miR-5100 mimics transfection in both mRNA and protein levels. The direct targeting of miR-5100 on G6PC was verified by a Dual-Luciferase Reporter Assay. Moreover, the mRNA and protein levels of G6PC were found to be significantly increased by AWRK6 treatment. These results suggested that the peptide AWRK6 could alleviate lipid accumulation in hepatocytes, partly through reducing miR-5100 to restore one of its targets: G6PC. Thus, AWRK6 has the potential to treat NAFLD. Additionally, miR-5100 is a mediator of lipid accumulation in hepatocytes, which could be targeted by AWRK6.

Chromatin modifications play a crucial role in the regulation of gene expression. The repressor element-1 (RE1) silencing transcription factor (REST), also known as neuron-restrictive silencer factor (NRSF) and X2 box repressor (XBR), was found to regulate gene transcription by binding to chromatin and recruiting chromatin-modifying enzymes. Earlier studies revealed that REST plays an important role in the development and disease of the nervous system, mainly by repressing the transcription of neuron-specific genes. Subsequently, REST was found to be critical in other tissues, such as the heart, pancreas, skin, eye, and vascular. Dysregulation of REST was also found in nervous and non-nervous system cancers. In parallel, multiple strategies to target REST have been developed. In this paper, we provide a comprehensive summary of the research progress made over the past 28 years since the discovery of REST, encompassing both physiological and pathological aspects. These insights into the effects and mechanisms of REST contribute to an in-depth understanding of the transcriptional regulatory mechanisms of genes and their roles in the development and progression of disease, with a view to discovering potential therapeutic targets and intervention strategies for various related diseases.

Highlights 1. Crowberry alterd expression levels of key mediators in PI3K/Akt signaling pathway. 2. Crowberry alterd expression levels of key mediators in PI3K/Akt signaling pathway. 3. Crowberry suppressed the expression of the proto-oncogene DEK in vivo and in vitro. 4. Crowberry inhibited CCA progression and migration through a molecular mechanism that includes inhibition of DEK and the Akt signaling pathway in vivo and in vitro.

Abstract Radiofrequency catheter ablation (RFCA) is widely used to treat atrial fibrillation (AF), but its effect on left atrial (LA) remodeling in patients with AF is not completely clarified. Few studies have reported the changes in structure and function of the left atrium in patients with different types of AF after RFCA. To analyze the effect of RFCA on the LA structure and function in patients with nonvalvular paroxysmal AF, persistent AF and long-standing persistent AF (LSPAF). RFCA was performed in 180 patients with paroxysmal AF, persistent AF and LSPAF. The changes of LA structure and function in echocardiogram and speckle-tracking echocardiography findings were compared before the procedure, and at 1, 2, 3, 4 weeks, and 2, 3, 6, and 9–12 months after the procedure. There were 60 patients in the paroxysmal AF group, 60 in the persistent AF group and 60 patients in LSPAF group. The pre-procedure LA diameter and volume were smaller in the paroxysmal AF group than persistent AF and LSPAF group. There was no significant change of in the LA structure and function in the paroxysmal AF group within 1 year. In the persistent AF and LSPAF groups, LA structure (anteroposterior diameter, LA volume) significantly decreased, but remained larger than that in paroxysmal AF group. In persistent and LSPAF, function (LA ejection fraction, strain, strain rate) increased significantly within 1 week, then gradually increased. RFCA improved the LA structure and function and resulted in heart reverse remodeling, especially for persistent AF and LSPAF.

Salvia miltiorrhiza (S. miltiorrhiza), which has been used for thousands of years to treat cardiovascular diseases, is a well-known Chinese medicinal plant. The fat-soluble tanshinones in S. miltiorrhiza are important biologically active ingredients including tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone. Tanshinone I, a natural diterpenoid quinone compound widely used in traditional Chinese medicine, has a wide range of biological effects including anti-cancer, antioxidant, neuroprotective, and anti-inflammatory activities. To further improve its potency, water solubility, and bioavailability, tanshinone I can be used as a platform for drug discovery to generate high-quality drug candidates with unique targets and enhanced drug properties. Numerous derivatives of tanshinone I have been developed and have contributed to major advances in the identification of new drugs to treat human cancers and other diseases and in the study of related molecular mechanisms. This review focuses on the structural modification, total synthesis, and pharmacology of tanshinone I. We hope that this review will help understanding the research progress in this field and provide constructive suggestions for further research on tanshinone I.

The leaf area index (LAI) is a crucial parameter for analyzing terrestrial ecosystem carbon cycles and global climate change. Obtaining high spatiotemporal resolution forest stand vegetation LAI products over large areas is essential for an accurate understanding of forest ecosystems. This study takes the northwestern part of the Inner Mongolia Autonomous Region (the northern section of the Greater Khingan Mountains) in northern China as the research area. It also generates the LAI time series product of the 8-day and 30 m forest stand vegetation growth period from 2013 to 2017 (from the 121st to the 305th day of each year). The Simulated Annealing-Back Propagation Neural Network (SA-BPNN) model was used to estimate LAI from Landsat8 OLI, and the multi-period GaoFen-1 WideField-View satellite images (GF-1 WFV) and the spatiotemporal adaptive reflectance fusion mode (STARFM) was used to predict high spatiotemporal resolution LAI by combining inversion LAI and Global LAnd Surface Satellite-derived vegetation LAI (GLASS LAI) products. The results showed the following: (1) The SA-BPNN estimation model has relatively high accuracy, with R2 = 0.75 and RMSE = 0.38 for the 2013 LAI estimation model, and R2 = 0.74 and RMSE = 0.17 for the 2016 LAI estimation model. (2) The fused 30 m LAI product has a good correlation with the LAI verification of the measured sample site (R2 = 0.8775) and a high similarity with the GLASS LAI product. (3) The fused 30 m LAI product has a high similarity with the GLASS LAI product, and compared with the GLASS LAI interannual trend line, it accords with the growth trend of plants in the seasons. This study provides a theoretical and technical reference for forest stand vegetation growth period LAI spatiotemporal fusion research based on high-score data, and has an important role in exploring vegetation primary productivity and carbon cycle changes in the future.

Various lung diseases endanger people’s health. Side effects and pharmaceutical resistance complicate the treatment of acute lung injury, pulmonary fibrosis, and lung cancer, necessitating the development of novel treatments. Antimicrobial peptides (AMPs) are considered to serve as a viable alternative to conventional antibiotics. These peptides exhibit a broad antibacterial activity spectrum as well as immunomodulatory properties. Previous studies have shown that therapeutic peptides including AMPs had remarkable impacts on animal and cell models of acute lung injury, pulmonary fibrosis, and lung cancer. The purpose of this paper is to outline the potential curative effects and mechanisms of peptides in the three types of lung diseases mentioned above, which may be used as a therapeutic strategy in the future.

AimAfter successful cardiopulmonary resuscitation (CPR), most survivors will develop acute kidney injury and intestinal barrier dysfunction, both of which contribute to the poor outcomes of cardiac arrest (CA) victims. Recently, the aldehyde dehydrogenase 2 (ALDH2) agonist, Alda-1 was shown to effectively alleviate regional ischemia/reperfusion injury of various organs. In the present study, we investigated the effects of Alda-1 treatment on renal and intestinal injuries after CA and resuscitation in pigs.MethodsTwenty-four male domestic pigs were randomly divided into one of the three groups: sham (n = 6), CPR (n = 10), or CPR+Alda-1 (n = 8). CA was induced and untreated for 8 min, and then CPR was performed for 8 min in the CPR and CPR+Alda-1 groups. At 5 min after resuscitation, a dose of 0.88 mg/kg of Alda-1 was intravenously administered in the CPR+Alda-1 group. The biomarkers of renal and intestinal injuries after resuscitation were regularly measured for a total of 24 h. Subsequently, the animals were euthanized, and then renal and intestinal tissues were obtained for the measurements of ALDH2 activity and expression, and cell apoptosis and ferroptosis.ResultsFive of the 10 animals in the CPR group and six of the eight animals in the CPR+Alda-1 group were successfully resuscitated. After resuscitation, the levels of biomarkers of renal and intestinal injuries were significantly increased in all animals experiencing CA and resuscitation compared with the sham group; however, Alda-1 treatment significantly alleviated renal and intestinal injuries compared to the CPR group. Post-resuscitation ALDH2 activity was significantly decreased and its expression was markedly reduced in the kidney and intestine in those resuscitated animals compared with the sham group; nevertheless, both of them were significantly greater in those animals receiving Alda-1 treatment compared to the CPR group. In addition, renal, intestinal apoptosis and ferroptosis after resuscitation were observed in the CPR and CPR+Alda-1 groups, in which both of them were significantly milder in the CPR+Alda1 group than in the CPR group.ConclusionsThe activation of ALDH2 by Alda-1 treatment significantly alleviated post-resuscitation renal and intestinal injuries through the inhibition of cell apoptosis and ferroptosis in a pig model of CA and resuscitation.

Dust in sand dunes is an effective and important source of dust emission. The Taklimakan Desert (TD) is one of the main sources of global dust: the sand dunes account for approximately 85% of the total area of the TD. However, the dust concentration, emission characteristics, and physical factors of different parts of the sand dunes in the TD during the day and night, as well as dust and non-dust days, remain unclear. In this study, dust observations were collected over a 3 month period in the TD to investigate the physical processes by which dust moves across a surface and generates PM10 and PM2.5 from the top and bottom of sand dunes. The results showed that the daily average maximum concentrations of particulate matter with diameters below 2.5 and 10 µm (PM2.5 and PM10) in the dune during the observation period reach ~90 and ~190 µg·m−3, respectively. Dust emission generated in the saltation process (maximum emission of PM10 was 3–5 mg·m−2·s−1) in the TD dunes was larger than that in other areas and had a good correlation with u* (friction velocity), where u* = 0.4 m·s−1 was the threshold of sand dune dust emission. The wind speed at the top of dunes was larger than that at the bottom, which was conducive to the accumulation of PM10 at the top of the dune. Furthermore, the MLH (mixed layer height) decreased after sunset and the turbulence weakens, which was conducive to the retention of dust in the air. Moreover, the dust made the solar radiation at the top of the dune −15 W·m−2 (average) lower than at the bottom. These results provided a new understanding of dune emissions in the TD and could be used for dust modeling in regional and global models.

The variation of solar radiation has a profound effect on the surface energy balance and hydrological cycle. Although the relationship between solar radiation variation and its influencing factors has been extensively studied, they are seldom used in Xinjiang, the largest province in China. In this study, we investigated the spatial distribution and temporal variation in global radiation (Eg), water vapor content (WVC), aerosol optical depth (AOD), total cloud cover (TCC), and low-level cloud cover (LCC) in Xinjiang, northwestern China, between 1961 and 2015. The annual average Eg reported at all stations was 5126.3–6252.8 MJ·m−2 with a mean of 5672 MJ·m−2. The highest annual mean Eg of 6252.8 MJ·m−2 occurred in Hami, eastern Xinjiang, whereas the lowest annual mean Eg of 5126.3 MJ·m−2 occurred in Urumqi, northern Xinjiang. The annual Eg variation was mainly affected by WVC, AOD, TCC, and LCC. Decreases in annual, spring, summer, autumn, and winter Eg trends were recorded in Xinjiang at rates of −33.88 × 10−2, −1.92 × 10−2, −1.89 × 10−2, −3.47 × 10−2, and −3.56 × 10−2 MJ·m−2·decade−1, respectively, with decreasing ratios of 9.43%, 5.85%, 0.14%, 8%, and 20.55%, respectively. Increasing trends in annual WVC, AOD, TCC, and LCC were noted in Xinjiang at rates of 7.12 × 10−5 mm·decade−1, 2.74 × 10−6 decade−1, 8.77 × 10−5 % decade−1, and 5.73 × 10−5% decade−1, respectively. In addition, increasing trends in the annual Eg at Yining and Yanqi stations were observed. The Eg spatial distribution was complex in Xinjiang at the stations observed in this study, which were divided into six groups. Eg at group 1 showed an increasing trend associated with decreases in the WVC and TCC, whereas decreases in Eg were observed at groups 2–6, which could have been influenced by increases in AOD, TCC, and LCC.

The characteristics of solar radiation and the influence of sand and dust on solar radiation in the northern margin of Taklimakan Desert were analyzed using radiation observation data from 2018. The results showed that the annual total radiation, direct radiation, and scattered radiation at Xiaotang were 5,781.8, 2,337.9, and 3,323.8 MJ m−2, respectively. The maximum monthly total radiation, direct radiation, and scattered radiation were observed in July (679.8 MJ m−2), August (317.3 MJ m−2), and May (455.7 MJ m−2), respectively. The aerosol optical depth corresponded well with the scattered radiation, and the maximum value was in May. Further analysis showed a significant correlation between the total radiation and solar height angle under different weather conditions. Under the same solar height angle, total radiation was higher during clear days but lower on sandstorm days. Calculation of atmospheric transmittance showed that the average atmospheric transmittance on a clear day was 0.67; on sand-and-dust days, it was 0.46. When the atmospheric transmittance was 0.5, the increase in scattering radiation by aerosol in the air began to decrease. Probability analysis of radiation indicated the following probabilities of total radiation

Both the Pearson correlation and partial correlation methods have been widely used in the resting-state functional MRI (rs-fMRI) studies. However, they can only measure linear relationship, although partial correlation excludes some indirect effects. Recent distance correlation can discover both the linear and non-linear dependencies. Our goal was to use the multivariate pattern analysis to compare the ability of such three correlation methods to distinguish between the patients with obsessive-compulsive disorder (OCD) and healthy control subjects (HCSs), so as to find optimal correlation method. The main process includes four steps. First, the regions of interest are defined by automated anatomical labeling (AAL). Second, functional connectivity (FC) matrices are constructed by the three correlation methods. Third, the best discriminative features are selected by support vector machine recursive feature elimination (SVM-RFE) with a stratified N-fold cross-validation strategy. Finally, these discriminative features are used to train a classifier. We had a total of 128 subjects out of which 61 subjects had OCD and 67 subjects were normal. All the three correlation methods with SVM have achieved good results, among which distance correlation is the best [accuracy = 93.01%, specificity = 89.71%, sensitivity = 95.08%, and area under the receiver-operating characteristic curve (AUC) = 0.94], followed by Pearson correlation and partial correlation is the last. The most discriminative regions of the brain for distance correlation are right dorsolateral superior frontal gyrus, orbital part of left superior frontal gyrus, orbital part of right middle frontal gyrus, right anterior cingulate and paracingulate gyri, left the supplementary motor area, and right precuneus, which are the promising biomarkers of OCD.

Combinations of two different therapeutic modalities of VEGF inhibitors against angiogenesis can cooperatively impede breast cancer tumor growth and enhance therapeutic efficacy. Itraconazole (ITZ) is a conventional antifungal drug with high safety; however, it has been repurposed to be a multi target anti-angiogenesis agent for cancer therapy in recent years. In the present study, composite nanoparticles co-loaded with ITZ and VEGF siRNA were prepared in order to investigate their anti-angiogenesis efficacy and synergistic anticancer effect against breast cancer. The nanoparticles had a suitable particle size (117.9 ± 10.3 nm) and weak positive surface charge (6.69 ± 2.46 mV), as well as good stability and drug release profile in vitro. Moreover, the nanoparticles successfully escaped from endosomes and realized cell apoptosis and cell proliferation inhibition in vitro. In vitro and in vivo experiments showed that the nanoparticles could induce the silencing of VEGF-related expressions as well as anti-angiogenesis efficacy, and the co-loaded ITZ-VEGF siRNA NPs could inhibit tumor growth effectively with low toxicity and side effects. Taken together, the as-prepared delivery vehicles are a simple and safe nano-platform that improves the antitumor efficacy of VEGF siRNA and ITZ, which allows the repositioning of the generic drug ITZ as a great candidate for antitumor therapy.

Aerosol optical depth (AOD), which represents the optical attenuation, poses a major threat to the production activity, air quality, human health and regional sustainable development of arid and semi-arid areas. To some degree, AOD shows areal air pollution level and possesses obvious spatio-temporal characteristics. However, long-time sequences and detailed AOD information can not be provided due to currently limited monitoring technology. In this paper, a daily AOD product, MODIS-based Multi-angle Implementation of Atmospheric Correction (MAIAC), is deployed to analyze the spatio-temporal characteristics in Xinjiang Uygur Autonomous Region from 2000 to 2019. In addition, the importance of influencing factors for AOD is calculated through Random Forest (RF) Model and the propagation trajectories of pollutants are simulated through Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) Model. Spatio distribution of AOD presents a tendency that AOD value in northern Xinjiang is low while the value in southern Xinjiang is high. Regions with high AOD values are mainly concentrated in Tarim Basin. AOD in southern Xinjiang is the highest, followed by that in eastern Xinjiang and AOD value in northern Xinjiang is the lowest. Seasonal variation of AOD is significant: Spring (0.309) > summer (0.200) > autumn (0.161) > winter (0.158). Average AOD value in Xinjiang is 0.196. AOD appears wavy from 2000 to 2014 with its low inflection point (0.157) appearing in 2005, and then increases, reaching its peak in 2014 (0.223). The obvious downward tendency after 2014 shows that the use of coal to natural gas (NG) conversion project improves the conditions of local environment. According to RF Model, NG contributes most to AOD. HYSPLIT Model reveals that aerosol in southern Xinjiang is related to the short-distant carriage of dust aerosol from the Taklimakan Desert. Aerosol there can affect Inner Mongolia through long-distant transport. Blocked by the Tianshan Mountains, fine dust particles can not cross the Tianshan Mountains to become a factor contributing to AOD in northern Xinjiang.

Reactive gases (O3, CO, NO2, and SO2) were collected hourly at the Akedala regional background station in northwestern China during September 2017 to August 2018. Wind rose, cluster analysis, potential source contribution function (PSCF), and concentration-weighted trajectory (CWT) methods were adopted for identifying the transport pathways and potential source regions of these atmosphere components at Akedala. The average O3, CO, NO2, and SO2 mixing ratios detected were 29.65 ± 11.44 ppb, 123.78 ± 73.35 ppb, 3.79 ± 0.98 ppb, and 4.59 ± 0.88 ppb during the observation period, and the statistical results of the monthly mean values revealed that there were differences during the highest pollution period, with O3 and CO mainly peaking in February, with mixing ratios of 38.03 ± 7.10 ppb and 208.50 ± 106.50 ppb, respectively. Meanwhile, NO2 peaked in March (4.51 ± 0.54 ppb) and SO2 in January (5.70 ± 1.92 ppb). The most obvious diurnal variation of CO and SO2 was observed in the winter, with maximum levels reaching between 13 : 00 and 14 : 00. The diurnal variations of O3 exhibited low values during the night and maximum values in the afternoon (16 : 00–18 : 00). Diurnal variation was not significant in the case of NO2. Cluster analysis showed that six main paths affected the Akedala atmosphere. In turn, the PSCF and CWT analysis results indicated that the Akedala reactive gas was affected by both local and foreign sources. The high PSCF value of the reactive gas potential source areas appeared in eastern Kazakhstan, northern Xinjiang, Western Mongolia, and Southern Russia. The WCWT (weighted concentration-weight trajectory) values of CO and SO2 in winter were the highest, totaling 180–240 ppb and 5–6.5 ppb, respectively. The WCWT value of O3 in the spring and summer was higher than that in the autumn and winter. The main source area of O3 was about 32–36 ppb in the spring and summer, and the main source area of NO2 in the summer had a low WCWT value of 3–3.5 ppb, whereas the NO2 WCWT value was concentrated at 4–4.5 ppb in the other seasons.

Abstract Object Obsessive–compulsive disorder (OCD) is a mental disease in which people experience uncontrollable and repetitive thoughts or behaviors. Clinical diagnosis of OCD is achieved by using neuropsychological assessment metrics, which are often subjectively affected by psychologists and patients. In this study, we propose a classification model for OCD diagnosis using functional MR images. Methods Using functional connectivity (FC) matrices calculated from brain region of interest (ROI) pairs, a novel Riemann Kernel principal component analysis (PCA) model is employed for feature extraction, which preserves the topological information in the FC matrices. Hierarchical features are then fed into an ensemble classifier based on the XGBoost algorithm. Finally, decisive features extracted during classification are used to investigate the brain FC variations between patients with OCD and healthy controls. Results The proposed algorithm yielded a classification accuracy of 91.8%. Additionally, the well‐known cortico–striatal–thalamic–cortical (CSTC) circuit and cerebellum were found as highly related regions with OCD. To further analyze the cerebellar‐related function in OCD, we demarcated cerebellum into three subregions according to their anatomical and functional property. Using these three functional cerebellum regions as seeds for brain connectivity computation, statistical results showed that patients with OCD have decreased posterior cerebellar connections. Conclusions This study provides a new and efficient method to characterize patients with OCD using resting‐state functional MRI. We also provide a new perspective to analyze disease‐related features. Despite of CSTC circuit, our model‐driven feature analysis reported cerebellum as an OCD‐related region. This paper may provide novel insight to the understanding of genetic etiology of OCD.

AWRK6 was a synthesized peptide developed based on the natural occurring peptide dybowskin-2CDYa, which was discovered in frog skin in our previous study. Here, a quantitative determination method for AWRK6 analysis in rat plasma by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and validated following U.S. FDA guidelines. A combination of plasma precipitation and liquid–liquid extraction was applied for the extraction. For pharmacokinetics study, the rats were administrated with AWRK6 via intraperitoneal and intravenous injection. The prepared plasma samples were separated on an ODS column and analyzed by tandem MS using precursor-to-product ion pairs of m/z: 533.4→84.2 for AWRK6 and m/z: 401.9→101.1 for internal standard Polymyxin B sulfate in multiple reaction monitoring mode. AWRK6 concentrations in rat plasma peaked at about 1.2 h after intraperitoneal injections at 2.35, 4.7 and 9.4 mg/kg bodyweight. The terminal half-life was around 2.8 h. The absolute bioavailability of AWRK6 was 50% after 3 doses via injection, and the apparent volume of distribution was 4.884 ± 1.736 L. The obtained determination method and pharmacokinetics profiles of AWRK6 provides a basis for further development, and forms a benchmark reference for peptide quantification.

Land surface temperature (LST) is an important parameter that affects the water cycle, environmental changes, and energy balance at global and regional scales. Herein, a time series analysis was conducted to estimate the monthly, seasonal, and interannual variations in LST during 2001–2019 in the Tarim Basin, China. Based on Moderate Resolution Imaging Spectroradiometer (MODIS) LST, air temperature, air pressure, relative humidity, wind speed, precipitation, elevation, and land-cover type data, we analyzed the spatio-temporal change characteristics of LST and the influencing factors. High LSTs occurred in the desert and plains and low LSTs occurred in surrounding mountain regions. The highest LST was recorded in July (25.1 °C) and the lowest was in January (−9.5 °C). On a seasonal scale, LST decreased in the order: summer > spring > autumn > winter. Annual LST showed an increasing trend of 0.2 °C/10 a in the desert and mountain areas, while the plains indicated a decreasing trend. In spring and autumn, western regions were dominated by a downward trend, whereas in winter a downward trend occurred in eastern regions. In summer, areas covered by vegetation were dominated by a downward trend, and desert and bare lands were dominated by an upward trend. Random forest (RF) model analysis showed that elevation was the most significant influencing factor (22.1%), followed by mean air temperature (20.1%). Correlation analysis showed that the main climatic factors air temperature, relative humidity, and elevation have a good correlation with the LST. Land-cover type also affected LST; during February–December the lowest LST was observed for permanent glacier snow and the highest was observed in the desert. El Nino and La Nina greatly influenced the LST variations. The North Atlantic Oscillation and Pacific Decadal Oscillation indices were consistent with the mean LST anomaly, indicating their considerable influence on LST variations.

Abstract In this study, surface enhanced Raman spectroscopy (SERS) in combination with multiplexed polymerase chain reaction (PCR) was utilized to detect mutations of exons 19 and 21 of the epidermal growth factor receptor (EGFR) gene. Through the use of multiplexed PCR, the two mutation types were amplified in a single reaction. SERS was used on the PCR products to detect mutations. DNA mixtures with increasing mutation percentages showed good linear relationship between mutation rates and peak height. Then, this PCR-SERS method was used on the plasma of 48 patients with non-small cell lung cancer (NSCLC) to detect EGFR mutations. Analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis revealed that the peak height ratios were significant for identifying different mutation types. The specificity, sensitivity and accuracy obtained were all 100%. The proposed method was then validated through comparison with high resolution melting (HRM) and showed high concordance with HRM (Pearson correlation is 0.92). Finally, logistic regression was performed on EGFR mutation status and the clinical features of the 48 patients. Our study indicates that PCR-SERS is an effective, noninvasive, and economical method for the detection and monitoring of EGFR mutations in the plasma of patients with NSCLC.

Kidney ischemia-reperfusion (I/R) accounts for the majority of acute kidney injury cases, whose consequences are commonly encountered after kidney transplantation. Optical coherence tomography (OCT) has been applied to image changes in kidney microanatomy and microcirculation. In this paper, we demonstrate a quantitative method for monitoring kidney status during I/R process using texture properties of OCT images. This approach employs skewness to measure the distribution of en face OCT image intensities at different depths, thus allowing differentiating I/R status of kidney. The skewness analysis based on quantitative intensity shows promise for monitoring kidney status during I/R and the potential for evaluating the viability of transplant kidney.

Field observations made with unmanned aerial vehicles of the particulate matter (PM) concentration from the ground to a height of 500 m were conducted at Xiaotang and Tazhong in the Taklimakan Desert (TD), China, from 7 to 15 November 2019. The vertical structures of the PM concentrations were studied. Pulsed lidar observations showed that dust aerosols in the TD can reach heights of 4 km. Within 500 m above the ground, the PM1.0, PM2.5, and PM10 concentrations were −3, respectively, in the TD. On days containing sand-blowing periods (e.g., at 18:00 on 11 November), the PM1.0, PM2.5, and PM10 concentrations were 10–17.7 times higher than on clear days. The northern margin of the TD (Xiaotang) was dominated by fine particles, while the hinterland (Tazhong) was dominated by coarse particles, because there was sparse vegetation around Xiaotang and the surface was sand and clay, while there was no vegetation around Tazhong and the surface was sand. During floating dust periods, the boundary layer was dominated by fine particles. The average PM1.0/PM2.5 ratios were 0.25–0.65 and 0.40–0.80 at Tazhong and Xiaotang, respectively, while, during sand blowing periods, these ratios were 0.40–0.55 and 0.40–0.45, respectively. The critical condition in the atmospheric boundary layer for PM concentration was revealed with the enhanced momentum flux and sensible heat flux up to 0.52 kg∙m−1∙s−2, 0.69 m∙s−1, and 6.7 W∙m2, respectively, and the low mixed layer was high in the lower atmosphere.

The relationship between strain fatigue life and evolution of meso-deformation inhomogeneity was studied, through the cyclic process of numerical simulation of crystal plasticity compared with the fatigue test of steel hot-rolled ribbed-steel bar 400 (HRB400). The statistical characterization parameters at grain level, including the standard deviation of the dot product of longitudinal stress and strain, the product of the macro stress and the standard deviation of the longitudinal strain, and the product of the macro stress ratio and the standard deviation of the longitudinal strain, were proposed and respectively applied to measure the meso-deformation inhomogeneity of materials. These parameters take the effect of peak stress into account, distinct from the pure strain statistical parameters. The numerical results demonstrate that the low-cycle fatigue life curves of materials are predictable using the new parameters as FIPs (fatigue indicator parameters), and the predictions are more rational than by utilizing the FIPs without considering the peak stress effect.

The incidence of oral cancer is increasing due to smoking, drinking, and human papillomavirus (HPV) infection, while the current treatments are not satisfactory. Small interfering RNA (siRNA)-based therapy has brought hope, but an efficient delivery system is still needed. Here, polyethyleneimine (PEI)-modified magnetic Fe3O4 nanoparticles were prepared for the delivery of therapeutic siRNAs targeting B-cell lymphoma-2 (BCL2) and Baculoviral IAP repeat-containing 5 (BIRC5) into Ca9-22 oral cancer cells. The cationic nanoparticles were characterized by transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). By gel retardation assay, the nanoparticles were found to block siRNA in a concentration-dependent manner. The cellular uptake of the nanoparticle/siRNA complexes under a magnetic field was visualized by Perl’s Prussian blue staining and FAM labeling. High gene silencing efficiencies were determined by quantitative real-time PCR and western blotting. Furthermore, the nanoparticle-delivered siRNAs targeting BCL2 and BIRC5 were found to remarkably inhibit the viability and migration of Ca9-22 cells, by cell counting kit-8 assay and transwell assay. In this study, we have developed a novel siRNA-based therapeutic strategy targeting BCL2 and BIRC5 for oral cancer.

An observational data set of the year 2010 at a site in the northern marginal zone of the Taklimakan Desert (TD) was used to analyse the key surface parameters in land⁻atmospheric interactions in the desert climate of northwest China. We found that the surface albedo (α) and emissivity (ε) were 0.27 and 0.91, respectively, which were consistent with the values obtained based on observations in the hinterland of the TD as well as being similar to the dry parts of the Great Basin desert in North America, where they were comparable to the α and ε values retrieved from remote sensing products. Peak frequency value of z0m was 5.858 × 10−3 m, which was similar to the Mojave Desert, Peruvian desert, Sonoran Desert, HEIFE (Heihe region) Desert, and Badain Jaran Desert. The peak frequency value of z0h was 1.965 × 10−4 m, which was different from those obtained in the hinterland of the TD. The average annual value of excess resistance to heat transfer (kB−1) was 2.5, which was different from those obtained in the HEIFE Gobi and desert, but they were similar to those determined for the Qinghai⁻Tibetan Plateau and HAPEX-Sahel. Both z0m and z0h varied less diurnally but notably seasonally, and kB−1 exhibited weak diurnal and seasonal variations. We also found that z0m was strongly influenced by the local wind direction. There were many undulating sand dunes in the prevailing wind and opposite to the prevailing wind, which were consistent with the directions of the peak z0m value. The mean values calculated over 24 h for Cd and Ch were 6.34 × 10−3 and 5.96 × 10−3, respectively, which were larger than in the Gobi area, hinterland of the TD and semiarid areas, but similar to HEIFE desert. Under the normal prevailing (NNE⁻ESE) wind, the mean bulk transfer coefficient Cd and Ch were of the same order of magnitude as expected based on similarity theory. Using the data obtained under different wind directions, we determined the relationships between Cd, Ch, the wind speed U, and stability parameter z/L, and the results were different. Cd and Ch decreased rapidly as the wind speed dropped below 3.0 m s−1 and their minimum values reached around 1⁻2 m s−1. It should also be noted that the ε values estimated using the sensible heat flux (H) were better compared with those produced using other estimation methods.

Diabetes is a metabolic disorder leading to many complications. The treatment of diabetes mainly depends on hypoglycemic drugs, often with side effects, which drive us to develop novel agents. AWRK6 was a peptide developed from the antimicrobial peptide Dybowskin-2CDYa in our previous study, and the availability of AWRK6 on diabetes intervention was unknown. Here, in vivo and in vitro experiments were carried out to investigate the effects of AWRK6 against diabetes. In diabetic mice, induced by high-fat diet followed by streptozocin (STZ) administration, the daily administration of AWRK6 presented acute and sustained hypoglycemic effects. The plasma insulin was significantly elevated by AWRK6 during an oral glucose tolerance test (OGTT). The relative β cell mass in diabetic mice was increased by AWRK6 treatment. The body weight and food intake were remarkably reduced by AWRK6 administration. In the mouse pancreatic β cell line Min6 cells, the intracellular calcium concentration was found to be enhanced under the treatment with AWRK6, and protein kinase A (PKA) inhibitor H-89 and Epac2 inhibitor HJC0350 represented inhibitory effects of the insulinotropic function of AWRK6. By FITC-AWRK6 incubation and GLP-1 receptor (GLP-1R) knockdown, AWRK6 proved to be a novel GLP-1R agonist. In addition, AWRK6 showed no toxicity in cell viability and membrane integrity in Min6 cells, and no hypoglycemia risk and no lethal toxicity in mice. In summary, AWRK6 was found as a novel agonist of GLP-1R, which could stimulate insulin secretion to regulate blood glucose and energy metabolism, via cAMP-calcium signaling pathway, without significant toxicity. The peptide AWRK6 might become a novel candidate for diabetes treatment.

We have previously identified an antimicrobial peptide called dybowskin2-CDYa (Dy2) in the cutaneous secretion from the Chinese frog Rana dybowskii. In this study, we used Dy2 as a template to prepare some novel peptides with improved stability and hydrophobicity. The antimicrobial activities exerted by these peptides against Gram positive and Gram negative bacteria were evaluated by MIC and CFU assays under physiological conditions. One peptide, AWRK6, was 2-4 fold more potent than Dy2, and was toxic to most of the bacterial strains tested, exhibiting a faster killing rate. AWRK6 was most potent in alkaline environments, and this was related to the more highly organized secondary structure of the peptide, as revealed by circular dichroism spectroscopy. Furthermore, AWRK6 was more resistant than Dy2 to degradation by trypsin. The improved properties of AWRK6 suggested that the peptide could potentially be further developed into an antibiotic.

During lipopolysaccharide (LPS)-induced sepsis, the liver plays central roles in toxins phagocytosis and clearance to protect the whole body. The liver cells were constantly irritated by LPS which leads to liver injury. While most anti-LPS agents showed little clinical activity against LPS-induced liver injury. Here, the protective effects of the synthetic peptide AWRK6 against LPS-induced liver injury have been investigated in vivo and in vitro. In mice liver homogenate, LPS administration elevated ALT (alanine aminotransferase), iNOS (inducible nitric oxide synthase) and repressed SOD (superoxide dismutase) activities and these changes were remarkably reversed by AWRK6. Histologically, AWRK6 effectively alleviated the histological changes and repressed LPS-induced neutrophils infiltration. By TUNEL assay on liver sections, AWRK6 was proven to inhibit apoptosis induced by LPS in mice livers, which was also verified by the protein levels of cleaved-caspase 9, Bax and Bcl-2. In addition, by in vitro study using HepG2 cells, AWRK6 was found to recover the LPS-reduced cell viability and reduce LPS-induced apoptosis. For mechanisms, AWRK6 was demonstrated to alleviate the LPS-induced phosphorylation of ERK, JNK and p38 MAPK, indicating the involvement of MAPKs in the protection of AWRK6 against liver injury. In summary, we have found the synthetic peptide AWRK6 as a promising novel agent for LPS-induced liver injury, by inhibiting cell apoptosis through MAPK signaling pathways, which might bring new strategies for the treatment of acute and chronic liver injuries.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria and produce strong inflammatory responses in animals. Most antibiotics have shown little clinical anti-endotoxin activity while some antimicrobial peptides have proved to be effective in blocking LPS. Here, the anti-LPS activity of the synthetic peptide AWRK6, which is derived from antimicrobial peptide dybowskin-2CDYa, has been investigated in vitro and in vivo. The positively charged α-helical AWRK6 was found to be effective in blocking the binding of LBP (LPS binding protein) with LPS in vitro using ELISA. In a murine endotoxemia model, AWRK6 offered satisfactory protection efficiency against endotoxemia death, and the serum levels of LPS, IL-1β, IL-6, and TNF-α were found to be attenuated using ELISA. Further, histopathological analysis suggested that AWRK6 could improve the healing of liver and lung injury in endotoxemia mice. The results of real-time PCR and Western blotting showed that AWRK6 significantly reversed LPS-induced TLR4 overexpression and IκB depression, as well as the enhanced IκB phosphorylation. Additionally, AWRK6 did not produce any significant toxicity in vivo and in vitro. In summary, AWRK6 showed efficacious protection from LPS challenges in vivo and in vitro, by blocking LPS binding to LBP, without obvious toxicity, providing a promising strategy against LPS-induced inflammatory responses.

Abstract The objective of this study was to investigate the culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery. The selected time points of the perioperative period included before the use of antibiotic eye drops, before eye wash (after the use of antibiotic eye drops), after eye wash, and immediately after surgery. Conjunctival specimens obtained at the four time points were cultured to detect the positivity and distribution of bacteria. Before prophylactic antibiotic eye drops were administered, 49 eyes (50%) had positive bacterial culture results, with 45 isolates (91.8%) identified as Staphylococcus epidermidis. The culture positivity rates of the conjunctival sac specimens before eye wash, after eye wash, and immediately after surgery were 19.4%, 3.1%, and 4.1%, respectively. The difference was significant before and after the use of antibiotics and before and after eye wash (both P 0.05). The judicious preoperative use of antibiotic eye drops combined with the surgical sterile eye wash procedure maximised the removal of conjunctival sac bacteria. Skilled surgical manipulations generally did not increase the risk of infection.