Perphenazine modified pillar[5]arene based nano-assemblies for synergistic photothermal and photodynamic cancer therapy.

Nano-assemblies based on perphenazine modified pillar[5]arene were constructed successfully for synergistic photothermal and photodynamic (I&II) cancer therapy.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

A study of environmental pollution and risk of heavy metals in the bottom water and sediment of the Chaohu Lake, China.

Most of the existing research for heavy metals in water at present is focusing on surface water. However, potential environmental risk of heavy metals in the bottom water of lakes cannot be ignored. In this study, the content, distribution, and speciation of nine heavy metals (As, V, Cr, Co, Ni, Cu, Zn, Cd, and Pb) in the bottom water and sediment of Chaohu Lake were studied. Some pollution assessment methods were used to evaluate the environmental effect of heavy metals. Positive matrix factorization was conducted to investigate the potential sources of heavy metals in sediment. The contents of heavy metals in the bottom water of Chaohu Lake mean that its environmental pollution can be ignored. In sediment, Cd and Zn have showed stronger ecological risk. pH and redox potential are more likely to affect the stability of heavy metals in the bottom water of Chaohu Lake during the dry reason. Industrial sources (16%) are no longer the largest source of heavy metal pollution; traffic sources (33.6%) and agricultural sources (23.4%) have become the main sources of pollution at present. This study can provide some support and suggestions for the treatment of heavy metals in lakes.

Pulmonary function outcomes after tuberculosis treatment in children: a systematic review and meta-analysis.

BACKGROUND: Despite tuberculosis (TB) being a curable disease, current guidelines fail to account for the long-term outcomes of post-tuberculosis lung disease-a cause of global morbidity despite successful completion of effective treatment. Our systematic review aimed to synthesise the available evidence on the lung function outcomes of childhood pulmonary tuberculosis (PTB). METHODS: PubMed, ISI Web of Science, Cochrane Library and ProQuest databases were searched for English-only studies without time restriction (latest search date 22 March 2023). Inclusion criteria were (1) patients who had TB with pulmonary involvement at age ≤18 years; (2) pulmonary function tests (PFTs) performed on patients after treatment completion; and (3) observational studies, including cohort and cross-sectional studies. We adhered to the recommendations of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: From 8040 records, 5 studies were included (involving n=567 children), with spirometry measures from 4 studies included in the meta-analyses. The effect sizes of childhood TB on forced expiratory volume in the first second and forced vital capacity z-scores were estimated to be -1.53 (95% CI -2.65, -0.41; p=0.007) and -1.93 (95% CI -3.35, -0.50; p=0.008), respectively. DISCUSSION: The small number of included studies reflects this under-researched area, relative to the global burden of TB. Nevertheless, as childhood PTB impacts future lung function, PFTs (such as spirometry) should be considered a routine test when evaluating the long-term lung health of children beyond their completion of TB treatment. PROSPERO registration number CRD42021250172.

MXene-Based Mixed Conductor Interphase for Dendrite-Free Flexible Al Organic Battery.

Al batteries are promising post-Li battery technologies for large-scale energy storage applications owing to their low cost and high theoretical capacity. However, one of the challenges that hinder their development is the unsatisfactory plating/stripping of the Al metal anode. To circumvent this issue, an ultrathin MXene layer is constructed on the surface of Al by in situ chemical reactions at room temperature. The as-prepared flexible MXene film acts like armor to protect the Al-metal by its high ionic conductivity and high mechanical flexibility. The MXene endow the Al anode with a long cyclic life of more than 5000 h at ultrahigh current density of 50 mA cm-2 for Al//Al batteries and a retention of 100% over 200 cycles for 355 Wh kg-1 PTO//Al batteries. This work provides fresh insights into the formation and regulation of stable electrode-electrolyte interfaces as well as effective strategies for improving Al metal batteries.

Changes in coagulation indices and D-dimer levels in hypertriglyceridemic acute pancreatitis and their value in predicting disease severity. / é«˜ç”˜æ²¹ä¸‰é ¯è¡€ç—‡æ€§æ€¥æ€§èƒ°è ºç‚Žå‡è¡€æŒ‡æ ‡ä¸ŽD-äºŒèšä½“æ°´å¹³å˜åŒ–åŠå ¶é¢„æµ‹ç–¾ç— ä¸¥é‡ç¨‹åº¦çš„ä»·å€¼.

OBJECTIVES: Hypertriglyceridemic acute pancreatitis (HTG-AP) is one of the common acute and severe cases of digestive system. Incidence of HTG-AP is increasing year by year, and there is a trend of younger and severe cases. Early identification of severe patients and timely intervention are conducive to improve the prognosis. Dysfunction of coagulation and fibrinolysis systems plays an important role in the development of HTG-AP. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are sensitive indicators of exogenous and endogenous coagulation system, respectively. Fibrinogen (FIB) is an acute reactive protein with coagulation function. D-dimer is a sensitive index to judge the abnormality of coagulation and fibrinolysis system. This study aims to investigate the changes of coagulation parameters and D-dimer level in patients with HTG-AP and their value in predicting the severity of the disease. METHODS: The clinical data of 189 HTG-AP patients admitted to Jiangjin Hospital Affiliated to Chongqing University (Jiangjin District Central Hospital of Chongqing) from January 2019 to December 2020 were collected, including gender, age, medical history, complications, causes, and acute physiology and chronic health evaluation II (APACHE II) scores. According to the severity of the disease, the patients were divided into a mild HTG-AP group and a severe HTG-AP group. The changes of coagulation indexes (PT, APTT and FIB), D-dimer and C-reactive protein (CRP) levels were detected. Coagulation indexes, D-dimer level and disease severity (CRP level, APACHE II scores) were compared between the 2 groups. Spearman correlation analysis was used to analyze the correlation between the above indexes. Univariate and multivariate binary logistic regression analysis were used to identify the independent risk factors for severe HTG-AP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of PT, FIB, and D-dimer for the severity of HTG-AP. RESULTS: There were significant differences in gender between the mild HTG-AP group and the severe HTG-AP group (P<0.05). There was no significant difference in age, recurrence rate and incidence of complications between the 2 groups (all P>0.05). The basic conditions of the 2 groups were similar and comparable. PT, FIB and D-dimer levels in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.001). There was no significant difference in APTT between the 2 groups (P>0.05). The CRP level and APACHE II scores in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.05). Spearman correlation analysis showed that PT, FIB and D-dimer were positively correlated with CRP and APACHE II scores (all P<0.05), while APTT was not correlated with CRP and APACHE II scores (all P>0.05). Logistic regression analysis showed that prolonged PT and elevated D-dimer level were independent risk factors for severe HTG-AP (both P<0.05). ROC curve analysis showed that the AUC of PT for predicting severe HTG-AP was 0.764 (95% CI 0.690 to 0.837, P<0.001), when PT>14.40 s, the sensitivity, specificity, positive predictive value, and negative predictive value were 63.07%, 79.03%, 59.42%, and 80.00%, respectively. TheAUC of FIB for predicting severe HTG-AP was 0.669 (95% CI 0.588 to 0.751, P<0.001), when FIB>4.18 g/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 61.53%, 70.17%, 49.38%, and 76.85%, respectively. The AUC of D-dimer for predicting severe HTG-AP was 0.753 (95% CI 0.680 to 0.826, P<0.001), when D-dimer>1.28 µg/mL, the sensitivity, specificity, positive predictive value, and negative predictive value were 73.84%, 66.12%, 53.33%, and 82.82%, respectively. The AUC of PT combined with D-dimer for predicting severe HTG-AP was 0.797. CONCLUSIONS: There are abnormalities in coagulation and fibrinolytic system in patients with HTG-AP in the early stage. PT, FIB and D-dimer levels are increased with the aggravation of the AP, and have a positively correlation with it. Elevated PT and D-dimer level are independent risk factors for severe HTG-AP. PT combined with D-dimer may be a sensitive indicator for prediction of the severity of HTG-AP in early phase.

A Contrastive Learning Network for Performance Metric and Assessment of Physical Rehabilitation Exercises.

Human activity analysis in the legal monitoring environment plays an important role in the physical rehabilitation field, as it helps patients with physical injuries improve their postoperative conditions and reduce their medical costs. Recently, several deep learning-based action quality assessment (AQA) frameworks have been proposed to evaluate physical rehabilitation exercises. However, most of them treat this problem as a simple regression task, which requires both the action instance and its score label as input. This approach is limited by the fact that the annotations in this field usually consist of healthy or unhealthy labels rather than quality scores provided by professional physicians. Additionally, most of these methods cannot provide informative feedback on a patient's motion defects, which weakens their practical application. To address these problems, we propose a multi-task contrastive learning framework to learn subtle and critical differences from skeleton sequences to deal with the performance metric and AQA problems of physical rehabilitation exercises. Specifically, we propose a performance metric network that takes triplets of training samples as input for score generation. For the AQA task, the same contrast learning strategy is used, but pairwise training samples are fed into the action quality assessment network for score prediction. Notably, we propose quantifying the deviation of the joint attention matrix between different skeleton sequences and introducing it into the loss function of our learning network. It is proven that considering both score prediction loss and joint attention deviation loss improves physical exercises AQA performance. Furthermore, it helps to obtain informative feedback for patients to improve their motion defects by visualizing the joint attention matrix's difference. The proposed method is verified on the UI-PRMD and KIMORE datasets. Experimental results show that the proposed method achieves state-of-the-art performance.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Facile and Simple Post Treatment Ball Milling Strategy for the Production of Low-Cost TiO2 Composites with Enhanced Photocatalytic Performance and Applicability to Construction Materials.

A facile and cost-effective approach assisted by ball milling (BM) of commercial titanium dioxide (TiO2), has been utilized to develop cheaper and efficient construction materials. At least three of the commercial and cheaper TiO2 samples (BA01-01, BA01-01+ and R996, designated as A1, A4 and R1, respectively) were selected and subjected to BM treatment to enhance their photocatalytic efficiencies, if possible. It was noted, that the samples A1, A4 and R1 were typical composites of TiO2 and calcium carbonate (CaCO3) and contained varying proportions of anatase, and rutile phases of TiO2 and CaCO3. Two of the highly efficient commercial TiO2 samples, Degussa P25 (simply designated as P25) and ST01 (Ishihara Ind.) were selected for making benchmark comparisons of photocatalytic efficiencies. The BM treated TiO2 samples (designated as TiO2-BM with respect to A1, A4 and R1) were evaluated for photocatalytic efficiencies both in both aqueous (methylene blue (MB)) and gaseous (NOx) photodegradation reactions. Based on detailed comparative investigations, it was observed that A1-BM photocatalyst exhibited superior photocatalytic performances over A4-BM and R1-BM, towards both MB and NOx photodegradation reactions. The difference of NOx photodegradation efficiency between the mortar mixed with A1-BM and that mixed with ST01, and P-25 at 15% were 16.6%, and 32.4%, respectively. Even though the mortar mixed with A1-BM at 15% composition exhibited a slightly lower NOx photodegradation efficiency as compared to mortar mixed with the expensive ST01 and P-25 photocatalysts, the present work promises an economic application in the eco-friendly construction materials for air purification considering the far lower cost of A1. The reasons for the superior performance of A1-BM were deduced through characterization of optical properties, surface characteristics, phase composition, morphology, microstructure and particle size distribution between pristine and BM treated A1 using characterization techniques such as diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction analysis, field emission scanning electron microscopy and particle size analysis.

Frequency-selective valley edge routing of elastic wave in topological phononic crystals with different symmetries.

The control of propagation direction or path of edge states is difficult when the chirality of the excitation source and the boundary structures are determined. Here, we studied a frequency-selective routing for elastic wave based on two types of topological phononic crystals (PnCs) with different symmetries. By constructing multiple types of interfaces between different PnCs structures with distinct valley topological phases, the valley edge states of elastic wave could be realized at different frequencies in the band gap. Meanwhile, based on the simulation of topological transport, it is found that the routing path of elastic waves valley edge states highly depends on the operating frequency and the inputting port of the excitation source. By varying the excitation frequency, the transport path can be switched. The results provide a paradigm for the control of elastic wave propagation paths that could be employed for designing the frequency-dependent ultrasonic division devices.

Evaluation of a point-of-care haemozoin assay (Gazelle device) for rapid detection of Plasmodium knowlesi malaria.

Plasmodium knowlesi is the major cause of zoonotic malaria in Southeast Asia. Rapid and accurate diagnosis enables effective clinical management. A novel malaria diagnostic tool, Gazelle (Hemex Health, USA) detects haemozoin, a by-product of haem metabolism found in all Plasmodium infections. A pilot phase refined the Gazelle haemozoin identification algorithm, with the algorithm then tested against reference PCR in a larger cohort of patients with P. knowlesi mono-infections and febrile malaria-negative controls. Limit-of-detection analysis was conducted on a subset of P. knowlesi samples serially diluted with non-infected whole blood. The pilot phase of 40 P. knowlesi samples demonstrated 92.5% test sensitivity. P. knowlesi-infected patients (n = 203) and febrile controls (n = 44) were subsequently enrolled. Sensitivity and specificity of the Gazelle against reference PCR were 94.6% (95% CI 90.5-97.3%) and 100% (95% CI 92.0-100%) respectively. Positive and negative predictive values were 100% and 98.8%, respectively. In those tested before antimalarial treatment (n = 143), test sensitivity was 96.5% (95% CI 92.0-98.9%). Sensitivity for samples with ≤ 200 parasites/µL (n = 26) was 84.6% (95% CI 65.1-95.6%), with the lowest parasitaemia detected at 18/µL. Limit-of-detection (n = 20) was 33 parasites/µL (95% CI 16-65%). The Gazelle device has the potential for rapid, sensitive detection of P. knowlesi infections in endemic areas.

Different femoral tunnel placement in posterior cruciate ligament reconstruction: a finite element analysis.

BACKGROUND: At present, there is no consensus on the optimal biomechanical method for Posterior cruciate ligament (PCL) reconstruction, and the "critical corner" that is produced by the femoral tunnel is currently considered to be one of the main reasons for PCL failure. Thus, the purpose of this study was to identify one or several different tunnels of the femur, thereby reducing the influence of the "critical corner" without reducing the posterior stability of the knee. METHODS: CT and MRI data of the knee joint of a healthy adult man were collected, and computer-related software was used to reconstruct the finite element model of the knee joint, to provide different properties to different materials and to allow for the performance of a finite element analysis of the reconstructed model. The position of the femoral tunnel was positioned and partitioned according to anatomical posture, and three areas were divided (the antero-proximal region, the antero-distal region and the posterior region). In addition, we applied a posterior tibial load of 134 N to the reconstructed model, recorded and compared different tunnels of the femur, conducted peak stress at the flexion of the knee joint of 0°, 30°, 60° and 90°, and elicited the displacement of the proximal tibia. RESULTS: Among the 20 different femoral tunnels, the graft peak stress was lower in tunnels 4, 12 and 18 than in the PCL anatomical footpath tunnel 13, especially at high flexion angles (60° and 90°). These three tunnels did not increase the posterior displacement of the proximal tibia compared with the anatomical footpath tunnel 13. CONCLUSION: In summary, among the options for PCL reconstruction of the femoral tunnel, the tunnels located 5 mm distal to the footprint and 5 mm anterior to the footprint could reduce the peak stress of the graft; additionally, it may reduce the "critical corner" and was shown to not reduce the posterior stability of the knee joint.

Urban ecological security pattern construction coupled with risk and service: A case study of Xianyang City, Shaanxi Province, China.

How to combine regional ecological risks and local ecological needs to construct ecological security is one of the main issues of its application in territorial spatial governance and associated with whether it can be effectively applied. Based on the "source" accessibility and the quality of space, we constructed the ecological security pattern of Xianyang City through the way of source-corridor-node. During the construction processes, we combined the cha-racteristics of topography, influencing factors of regional ecological security, and landscape characteristics. We coupled them with morphological spatial pattern analysis (MSPA) and comprehensive evaluation results of ecological resistance, ecological connectivity and ecosystem service value, and superimposed with ecological gradient ana-lysis. The results showed that there were 66 ecological sources, with a total area of 2506.65 km2, accounting for 24.6% of the total area of Xianyang City, which were mainly distributed in the northeast, west and central mountainous areas. There were 106 ecological corridors with a total length of 823.5 km, including potential corridors, water systems, irrigation canal sites, Qinzhidao and other natural and cultural systems, which extended along the ecological source to the northwest and south Weihe River. There were 20 ecological nodes to improve ecological connectivity, which were mainly distributed between second layers of loess tableland and arid mountainous areas with banded distribution in the north part of the city.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

Solar-Driven Reversible Hydrogen Storage.

The lack of safe and efficient hydrogen storage is a major bottleneck for large-scale application of hydrogen energy. Reversible hydrogen storage of light-weight metal hydrides with high theoretical gravimetric and volumetric hydrogen density is one ideal solution but requires extremely high operating temperature with large energy input. Herein, taking MgH2 as an example, a concept is demonstrated to achieve solar-driven reversible hydrogen storage of metal hydrides via coupling the photothermal effect and catalytic role of Cu nanoparticles uniformly distributed on the surface of MXene nanosheets (Cu@MXene). The photothermal effect of Cu@MXene, coupled with the "heat isolator" role of MgH2 indued by its poor thermal conductivity, effectively elevates the temperature of MgH2 upon solar irradiation. The "hydrogen pump" effect of Ti and TiHx species that are in situ formed on the surface of MXene from the reduction of MgH2 , on the other hand, plays a catalytic role in effectively alleviating the kinetic barrier and hence decreasing the operating temperature required for reversible hydrogen adsorption and desorption of MgH2 . Based on the combination of photothermal and catalytic effect of Cu@MXene, a reversible hydrogen storage capacity of 5.9 wt% is achieved for MgH2 after 30 cycles using solar irradiation as the only energy source.

Control of Grain Weight and Size in Rice (Oryza sativa L.) by OsPUB3 Encoding a U-Box E3 Ubiquitin Ligase.

Grain weight and size, mostly determined by grain length, width and thickness, are crucial traits affecting grain quality and yield in rice. A quantitative trait locus controlling grain length and width in rice, qGS1-35.2, was previously fine-mapped in a 57.7-kb region on the long arm of chromosome 1. In this study, OsPUB3, a gene encoding a U-box E3 ubiquitin ligase, was validated as the causal gene for qGS1-35.2. The effects were confirmed firstly by using CRISPR/Cas9-based mutagenesis and then through transgenic complementation of a Cas9-free knock-out (KO) mutant. Two homozygous KO lines were produced, each having a 1-bp insertion in OsPUB3 which caused frameshift mutation and premature termination. Compared with the recipient and a transgenic-negative control, both mutants showed significant decreases in grain weight and size. In transgenic complementation populations derived from four independent T0 plants, grain weight of transgenic-positive plants was significantly higher than transgenic-negative plants, coming with increased grain length and a less significant decrease in grain width. Based on data documented in RiceVarMap V2.0, eight haplotypes were classified according to six single-nucleotide polymorphisms (SNPs) found in the OsPUB3 coding region of 4695 rice accessions. Significant differences on grain size traits were detected between the three major haplotypes, Hap1, Hap2 and Hap3 that jointly occupy 98.6% of the accessions. Hap3 having the largest grain weight and grain length but intermediate grain width exhibits a potential for simultaneously improving grain yield and quality. In another set of 257 indica rice cultivars tested in our study, Hap1 and Hap2 remained to be the two largest groups. Their differences on grain weight and size were significant in the background of non-functional gse5, but non-significant in the background of functional GSE5, indicating a genetic interaction between OsPUB3 and GSE5. Cloning of OsPUB3 provides a new gene resource for investigating the regulation of grain weight and size.

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway.

CONTEXT: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases. OBJECTIVE: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP. MATERIALS AND METHODS: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3ß/mTOR signalling pathway. RESULTS: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway. DISCUSSION AND CONCLUSION: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

Long non-coding RNA GAS6-AS1 enhances breast cancer cell aggressiveness by functioning as a competing endogenous RNA of microRNA-215-5p to enhance SOX9 expression.

Long non-coding (lnc) RNAs play crucial functions in human cancer. However, until recently, the involvement of the lncRNA GAS6-AS1 in breast cancer (BCa) malignancy has not been studied exhaustively. The roles and underlying mode of action of GAS6-AS1 action in BCa progression were examined through functional experiments. A decline in GAS6-AS1 level led to a significant decrease in BCa cell proliferation, and the ability for colony formation. Here, GAS6-AS1 competed as endogenous RNA by sequestering microRNA-215-5p (miR-215-5p) causing an enhanced expression of SRY-box transcription factor 9 (SOX9). The effects of silencing GAS6-AS1 on BCa malignant phenotypes could be ameliorated by inhibiting miR-215-5p or restoring SOX9. Thus, GAS6-AS1 acted as a lncRNA that drives tumor in BCa, and enabled progression of BCa through miR-215-5p /SOX9 axis regulation. These outcomes show that the GAS6-AS1/miR-215-5p/SOX9 axis is a potentially effective target for cancer treatment and management.