Blocking the TRAIL-DR5 Pathway Reduces Cardiac Ischemia-Reperfusion Injury by Decreasing Neutrophil Infiltration and Neutrophil Extracellular Traps Formation.

PURPOSE: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release. METHODS: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice. RESULTS: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils. CONCLUSION: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Surface molecularly imprinted polymers based on magnetic multi-walled carbon nanotubes for the highly selective purification of resveratrol from crude extracts of Vitis vinifera, Arachis hypogaea, and Polygonum cuspidatum.

In this work, surface molecularly imprinted polymers based on magnetic multi-walled carbon nanotubes were prepared for the specific recognition and adsorption of resveratrol. The functionalization of magnetic multi-walled carbon nanotubes and the synthesis process of surface molecularly imprinted polymers were optimized. Characterizations were performed to demonstrate the successful synthesis of the imprinted materials. The imprinted materials showed satisfactory adsorption capacity of resveratrol (45.73 ± 1.72 mg/g) and excellent selectivity (imprinting factor 2.89 ± 0.15). In addition, the imprinted materials were used as adsorbents in molecularly imprinted solid-phase extraction for the purification of resveratrol from crude extracts of some food and medicinal resources, achieving recoveries of 93.69%-95.53% with high purities of 88.37%-92.33%. Moreover, the purified products exhibited extremely strong free radical scavenging activity compared with crude extracts. Overall, this work provided a promising approach for the highly selective purification of resveratrol from natural resources, which would contribute to the application of this valuable compound in the food/nutraceutical fields.

Cocultivation of pigeon pea hairy root cultures and Aspergillus for the enhanced production of cajaninstilbene acid.

Pigeon pea hairy root cultures (PPHRCs) have been proven to be a promising alternative for the production of health-beneficial phenolic compounds, such as the most important health-promoting compound, i.e., cajaninstilbene acid (CSA). In this study, PPHRCs were cocultured with live Aspergillus fungi for further improving phenolic productivity via biological elicitation. Aspergillus oryzae CGMCC 3.951 (AO 3.951) was found to be the optimal fungus that could achieve the maximum increment of CSA (10.73-fold increase) in 42-day-old PPHRCs under the inoculum size of mycelia 0.50% and cocultivation time 36 h. More precisely, the contents of CSA in hairy roots and culture media after fungal elicitation increased by 9.87- and 62.18-fold over control, respectively. Meanwhile, the contents of flavonoid glycosides decreased, while aglycone yields increased upon AO 3.951 elicitation. Moreover, AO 3.951 could trigger the oxidative stress and pathogen defense response thus activating the expression of biosynthesis- and ABC transporter-related genes, which contributed to the intracellular accumulation and extracellular secretion of phenolic compounds (especially CSA) in PPHRCs. And PAL2, 4CL2, STS1, and I3'H were likely to be the potential key enzyme genes regulating the biosynthesis of CSA, and ABCB11X1-1, ABCB11, and ABCG24X2 were closely related to the transmembrane transport of CSA. Overall, the cocultivation approach could make PPHRCs more commercially attractive for the production of high-value phenolic compounds such as CSA and flavonoid aglycones in nutraceutical/medicinal fields. And the elucidation of crucial biosynthesis and transport genes was important for systematic metabolic engineering aimed at increasing CSA productivity. KEY POINTS: • Cocultivation of PPHRCs and live fungi was to enhance CSA production and secretion. • PPHRCs augmented CSA productivity 10.73-fold when cocultured with AO 3.951 mycelia. • Several biosynthesis and transport genes related to CSA production were clarified.

Modelling women's team line-ups based on effectiveness and quality.

Understanding how different player rotations may impact team performance allows basketball coaches to select effective line-ups for specific tactical scenarios. The study aimed to i) assess how different line-ups or player combinations impact a team's game performance; ii) explore the variations in line-up utilization among different national women's basketball teams; and iii) examine how the offensive efficiency of each line-up evolves during the game. Data from 3,387 ball possessions in 23 international women's basketball games were collected across four major competitions over six years. Offensive and defensive ratings, along with other features, were calculated. Then, a Markov chain model distinguished overperforming and underperforming line-ups of Chinese women's basketball team, determining long-term probabilities for each rating level. The results indicated that i) the most dominant offensive line-up of the Chinese women's basketball team, is PG-G-SF-PF-C, while G-G-F-PF-PF had the highest defensive rating; and ii) US and Australian women's basketball teams favour using line-ups with three guards, while the Chinese women's basketball team heavily relies on centre players. These results offer valuable insights for coaches regarding the performance of different line-ups in FIBA Female Basketball Competitions, optimizing line-up performance and aiding talent selection and recruitment at the international level.

Semi-supervised Long-tail Endoscopic Image Classification.

Objective To explore the semi-supervised learning (SSL) algorithm for long-tail endoscopic image classification with limited annotations. Method We explored semi-supervised long-tail endoscopic image classification in HyperKvasir, the largest gastrointestinal public dataset with 23 diverse classes. Semi-supervised learning algorithm FixMatch was applied based on consistency regularization and pseudo-labeling. After splitting the training dataset and the test dataset at a ratio of 4:1, we sampled 20%, 50%, and 100% labeled training data to test the classification with limited annotations. Results The classification performance was evaluated by micro-average and macro-average evaluation metrics, with the Mathews correlation coefficient (MCC) as the overall evaluation. SSL algorithm improved the classification performance, with MCC increasing from 0.8761 to 0.8850, from 0.8983 to 0.8994, and from 0.9075 to 0.9095 with 20%, 50%, and 100% ratio of labeled training data, respectively. With a 20% ratio of labeled training data, SSL improved both the micro-average and macro-average classification performance; while for the ratio of 50% and 100%, SSL improved the micro-average performance but hurt macro-average performance. Through analyzing the confusion matrix and labeling bias in each class, we found that the pseudo-based SSL algorithm exacerbated the classifier's preference for the head class, resulting in improved performance in the head class and degenerated performance in the tail class. Conclusion SSL can improve the classification performance for semi-supervised long-tail endoscopic image classification, especially when the labeled data is extremely limited, which may benefit the building of assisted diagnosis systems for low-volume hospitals. However, the pseudo-labeling strategy may amplify the effect of class imbalance, which hurts the classification performance for the tail class.

Soluble uric acid induces myocardial damage through activating the NLRP3 inflammasome.

Uric acid crystal is known to activate the NLRP3 inflammasome and to cause tissue damages, which can result in many diseases, such as gout, chronic renal injury and myocardial damage. Meanwhile, soluble uric acid (sUA), before forming crystals, is also related to these diseases. This study was carried out to investigate whether sUA could also activate NLRP3 inflammasome in cardiomyocytes and to analyse the mechanisms. The cardiomyocyte activity was monitored, along with the levels of mature IL-1ß and caspase-1 from H9c2 cells following sUA stimulus. We found that sUA was able to activate NLRP3 inflammasome, which was responsible for H9c2 cell apoptosis induced by sUA. By elevating TLR6 levels and then activating NF-κB/p65 signal pathway, sUA promoted NLRP3, pro-caspase 1 and pro-IL-1ß production and provided the first signal of NLRP3 inflammasome activation. Meanwhile, ROS production regulated by UCP2 levels also contributed to NLRP3 inflammasome assembly and subsequent caspase 1 activation and mature IL-1ß secretion. In addition, the tlr6 knockdown rats suffering from hyperuricemia showed the lower level of IL-1ß and an ameliorative cardiac function. These findings suggest that sUA activates NLRP3 inflammasome in cardiomyocytes and they may provide one therapeutic strategy for myocardial damage induced by sUA.

Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation.

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1ß secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1ß secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1ß secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.

Exercise Prevents Upregulation of RyRs-BKCa Coupling in Cerebral Arterial Smooth Muscle Cells From Spontaneously Hypertensive Rats.

OBJECTIVE: Regular exercise is an effective nonpharmacological means of preventing and controlling hypertension. However, the molecular mechanisms underlying its effects remain undetermined. The hypothesis that hypertension increases the functional coupling of large-conductance Ca(2+)-activated K(+) (BKCa) channels with ryanodine receptors in spontaneously hypertensive rats (SHR) as a compensatory response to an increase in intracellular Ca(2+) concentration in cerebral artery smooth muscle cells was assessed here. It was further hypothesized that exercise training would prevent this increase in functional coupling. APPROACH AND RESULTS: SHR and Wistar-Kyoto (WKY) rats were randomly assigned to sedentary groups (SHR-SED and WKY-SED) and exercise training groups (SHR-EX and WKY-EX). Cerebral artery smooth muscle cells displayed spontaneous transient outward currents at membrane potentials more positive than -40 mV. The amplitude of spontaneous transient outward currents together with the spontaneous Ca(2+) sparks in isolated cerebral artery smooth muscle cells was significantly higher in SHR-SED than in WKY-SED. Moreover, hypertension displayed increased whole-cell BKCa, voltage-gated Ca(2+) channel, but decreased KV currents in cerebral artery smooth muscle cells. In SHRs, the activity of the single BKCa channel increased markedly, and the protein expression of BKCa (ß1, but not α-subunit) also increased, but KV1.2 decreased significantly. Exercise training ameliorated all of these functional and molecular alterations in hypertensive rats. CONCLUSIONS: These data indicate that hypertension leads to enhanced functional coupling of ryanodine receptors-BKCa to buffer pressure-induced constriction of cerebral arteries, which attributes not only to an upregulation of BKCa ß1-subunit function but also to an increase of Ca(2+) release from ryanodine receptors. However, regular aerobic exercise efficiently prevents augmented coupling and so alleviates the pathological compensation and restores cerebral arterial function.

Pyrazolone-quinazolone hybrids: a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization. Most of the new compounds displayed potent inhibitory activity against the recombinant human HPPD in nanomolar range. Compounds 3h and 3u were identified as the most potent candidates with Ki values of around 10 nM against human HPPD, about three-fold more potent than NTBC. Molecular modeling indicated that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contributed greatly to the high potency of these inhibitors. Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation.

Updated global epidemiology atlas of human prion diseases.

Introduction: Human prion disease (PrD), a group of fatal and transmissible neurodegenerative diseases, consists of Creutzfeldt-Jakob disease (CJD), kuru, fatal familial insomnia (FFI), Gerstmann-Sträussler-Scheinker disease (GSS), and variably protease-sensitive prionopathy (VPSPr). The emergence of bovine spongiform encephalopathy (BSE) in cattle and variant CJD (vCJD) has greatly threatened public health, both in humans and animals. Since the 1990's, dozens of countries and territories have conducted PrD surveillance programs. Methods: In this study, the case numbers and alternative trends of different types of PrD globally and in various countries or territories from 1993 to 2020 were collected and analyzed based on the data from the websites of the international and national PrD surveillance programs, as well as from relevant publications. Results: The total numbers of the reported PrD and sporadic CJD (sCJD) cases in 34 countries with accessible annual case numbers were 27,872 and 24,623, respectively. The top seven countries in PrD cases were the USA (n = 5,156), France (n = 3,276), Germany (n = 3,212), Italy (n = 2,995), China (n = 2,662), the UK (n = 2,521), Spain (n = 1,657), and Canada (n = 1,311). The annual PrD case numbers and mortalities, either globally or in the countries, showed an increased trend in the past 27 years. Genetic PrD cases accounted for 10.83% of all reported PrD cases; however, the trend varied largely among the different countries and territories. There have been 485 iatrogenic CJD (iCJD) cases and 232 vCJD cases reported worldwide. Discussion: The majority of the countries with PrD surveillance programs were high- and upper-middle-income countries. However, most low- and lower-middle-income countries in the world did not conduct PrD surveillance or even report PrD cases, indicating that the number of human PrD cases worldwide is markedly undervalued. Active international PrD surveillance for both humans and animals is still vital to eliminate the threat of prion disease from a public health perspective.

Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases.

Background and purpose: Calmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs. Methods: A total of 103 CSF samples from patients diagnosed with T188K-gCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzyme-linked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors. Results: The positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in PRNP, as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients. Conclusion: Western blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF.

Treatment of Ulcerative Colitis by Cationic Liposome Delivered NLRP3 siRNA.

Purpose: The abnormal activation of NLRP3 inflammasome is related to the occurrence and development of ulcerative colitis (UC). However, the ideal drug and delivery system remain important factors limiting the targeting of NLRP3 inflammasome in UC therapy. Gene therapy by delivering siRNA is effective in treating various diseases. Therefore, delivering siNLRP3 using an ideal vector for UC treatment is necessary. Materials and Methods: Nanoparticles delivering siNLRP3 were developed based on cationic liposome (CLP/siNLRP3). Their ability to inhibit NLRP3 inflammasome activation was monitored using Western blot (WB) and Enzyme-linked Immunosorbent Assay (ELISA). The ASC oligomerization in LPS-primed peritoneal macrophages (PMs) was detected by WB and immunofluorescence. Moreover, we assessed the role of CLP/siNLRP3 on dextran sodium sulfate (DSS)-induced UC by examining NLRP3 levels, pro-inflammatory cytokines expression, and disease-associated index (DAI). Flow cytometry (FCM) was used to detect the contents of macrophages and T cells. Finally, we assessed the safety of CLP/siNLRP3. Results: The prepared CLP was spherical, with a small particle size (94 nm) and low permeability. The CLP could efficiently protect siNLRP3 from degradation and then deliver siNLRP3 into PMs, inhibiting NLRP3 inflammasome activation. Also, the CLP/siNLRP3 could inhibit the secretion of mature IL-1ß and IL-18 from PMs, thereby achieving a favorable anti-inflammation effect. In vivo, CLP/siNLRP3 could effectively alleviate intestinal injury in UC mice, which was attributed to down-regulating levels of IL-1ß and IL-18, inhibiting infiltration of macrophages and other immune cells, and the polarization of M1 macrophages. Finally, pathological testing of tissue sections and blood biochemical tests showed no significant toxic effects of CLP/siNLRP3. Conclusion: We introduced a prospective approach for the efficient delivery of siRNA in vitro and in vivo with high safety and stability, which was found to have great potential in treating NLRP3-driven diseases in an RNA-silencing manner.

Health-Promoting Phenolic Compound Accumulation, Antioxidant Response, Endogenous Salicylic Acid Generation, and Biosynthesis Gene Expression in Germinated Pigeon Pea Seeds Treated with UV-B Radiation.

Germinated pigeon pea seeds (GPPSs) are good dietary supplements with satisfactory nutritional and medicinal values. In this study, UV-B treatment was used to promote the accumulation of health-promoting phenolic compounds (10 flavonoids and 1 stilbene) in GPPS. The total yield of 11 phenolic compounds (235 839.76 ± 17 118.24 ng/g DW) significantly improved (2.53-fold increase) in GPPSs exposed to UV-B radiation (3 W/m2) for 8 h, whereas free amino acid and reducing sugar contents exhibited a decreasing tendency during UV-B exposure. Meanwhile, the positive response in the antioxidant activities of enzymes and nonenzymatic extracts was noticed in UV-B-treated GPPSs. Moreover, UV-B radiation could cause tissue damages in hypocotyls and cotyledons of the GPPSs and enhance the generation of endogenous salicylic acid, thus activating the expression of biosynthesis genes (especially CHS and STS1). Overall, the simple UV-B supplementation strategy makes GPPSs more attractive as functional foods/nutraceuticals in diet for promoting human health.

Functional movement screen dataset collected with two Azure Kinect depth sensors.

This paper presents a dataset for vision-based autonomous Functional Movement Screen (FMS) collected from 45 human subjects of different ages (18-59 years old) executing the following movements: deep squat, hurdle step, in-line lunge, shoulder mobility, active straight raise, trunk stability push-up and rotary stability. Specifically, shoulder mobility was performed only once by different subjects, while the other movements were repeated for three episodes each. Each episode was saved as one record and was annotated from 0 to 3 by three FMS experts. The main strength of our database is twofold. One is the multimodal data provided, including color images, depth images, quaternions, 3D human skeleton joints and 2D pixel trajectories of 32 joints. The other is the multiview data collected from the two synchronized Azure Kinect sensors in front of and on the side of the subjects. Finally, our dataset contains a total of 1812 recordings, with 3624 episodes. The size of the dataset is 190 GB. This dataset provides the opportunity for automatic action quality evaluation of FMS.

Polysaccharide from Echinacea purpurea plant ameliorates oxidative stress-induced liver injury by promoting Parkin-dependent autophagy.

BACKGROUND: Acetaminophen (APAP) overdose represents one of the most common drug-induced liver injuries (DILI) worldwide. Oxidative damage to the hepatocytes and their resultant autophagy are the key components in the APAP-induced DILI. Echinacea purpurea polysaccharide (EPPS), the component extracted from the root of Echinacea purpurea (L.) Moench, shows various biological functions including immunoregulation and antioxidant activity. PURPOSE: This study aimed to elucidate the protective effect of EPPS against APAP-induced DILI and the underlying mechanisms. RESULTS: EPPS attenuates APAP overdose induced DILI in mice and ameliorates inflammation and oxidative stress in mice with APAP overdose-induced DILI. Furthermore, EPPS protected the hepatocytes against APAP-induced liver injury by suppressing apoptosis. EPPS ameliorates APAP-induced DILI via an autophagy-dependent mechanism in vivo and increases autophagy with a reduction in oxidative stress and inflammation in vitro. Parkin knockdown prevents the autophagic-dependent manner of EPPS effects in APAP-treated hepatocytes. CONCLUSIONS: EPPS exhibited a strong hepatoprotective effect against APAP-induced DILI and was correlated with reduction of autophagy-dependent oxidant response, inflammation, and apoptosis. Moreover, the findings indicated that EPPS exerts its hepatoprotective effect against APAP mainly via Parkin-dependent autophagy, and the use of EPPS can serve as a promising novel therapeutic strategy for APAP-induced DILI.

miR-30a-5p suppresses lung squamous cell carcinoma via ATG5 - mediated autophagy.

Propose: Autophagy plays a complicated role in cancer progression. This study aims at assessing the function of ATG5-induced autophagy in progression of lung squamous cell carcinoma and its upstream mechanism. METHOD: TCGA database of lung squamous cell carcinoma was analyzed to explore the differentially expressed miRNAs and mRNAs and relative prognosis. RT-PCR and Western blot were performed to evaluate autophagy relative gene expression level in human lung squamous cell carcinoma cell Lines. Autophagy flux was observed using transmission electron microscopy and immunofluorescence. Meanwhile, binding relationship of potential target miRNA and mRNAs were also confirmed using Dual-luciferase reporter gene assay. Lung metastatic model was established to evaluated the effect of targeting protein and miRNA. RESULT: High level expression of ATG5 was detected in LUSC patients. Relative experiments confirmed that ATG5 silencing could decrease the autophagy flux in LUSC. In addition, our research revealed that there is a binding sites between hsa-mir-30a-5p and 3'-UTR of ATG5. Mimic miR-30a-5p suppresses ATG5-mediated autophagy in lung squamous cell carcinoma cells. The in vivo experiments confirmed that miR-30a-5p could attenuate lung squamous cell carcinoma progression through the autophagy pathway. CONCLUSION: Accordingly, the in vivo and in vitro study in our research have demonstrated that miR-30a-5p inhibits lung squamous cell carcinoma progression via ATG5-mediated autophagy.

The D-dimer level predicts the prognosis in patients with lung cancer: a systematic review and meta-analysis.

OBJECTIVE: Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan-Meier survival curves. The publication bias was examined by Egger's test. RESULTS: Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542-1.969, P < 0.001) and PFS (HR = 1.385, 95%CI:1.169-1.641, P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis. CONCLUSION: This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer.

Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme.

Extracellular traps released by neutrophils (NETs) are essential for the clearance of Pseudomonas aeruginosa. Alkaline protease (AprA) secreted by P. aeruginosa negatively correlates with clinical improvement. Moreover, anti-AprA in patients with cystic fibrosis (CF) can help identify patients with aggressive forms of chronic infection. However, the mechanism underlying the clinical outcomes remains unclear. We demonstrated that aprA deficiency in P. aeruginosa decreased the bacterial burden and reduced lung infection. AprA degraded NET components in vitro and in vivo but did not affect NET formation. Importantly, antibodies induced by AprA acted as an agonist and directly enhanced the degrading activities of AprA. Moreover, antisera from patients with P. aeruginosa infection exhibited antibody-dependent enhancement (ADE) similar to that of the antibodies we prepared. Our further investigations showed that the interaction between AprA and the specific antibodies might make the enzyme active sites better exposed, and subsequently enhance the recognition of substrates and accelerate the degradation. Our findings revealed that AprA secreted by P. aeruginosa may aggravate infection by destroying formed NETs, an effect that was further enhanced by its antibodies.

Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

OBJECTIVE: It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype. METHODS: Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses. RESULTS: Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20-2.21) and OS (HR 1.53, 95% CI 1.19-1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45-2.85) and OS (HR 2.26, 95% CI 1.46-3.52) were also poor in the subgroup of patients with the presence of an MP component. CONCLUSIONS: Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.

[Progress in Survival Prognosis of Segmentectomy for 
Early-stage Non-small Cell Lung Cancer].

Surgery is currently the most appropriate treatment for early-stage non-small cell lung cancer (NSCLC). Increasing unilateral or bilateral multiple primary lung cancer being found, segmentectomy has attracted wide attention for its unique advantages in the treatment for such tumors. Ground glass opacity dominant early-stage NSCLC is associated with a good prognosis and can be cured by segmentectomy, however, the treatment of solid-dominant NSCLC remains controversial owing to the invasive nature. With the in-depth study on the lymph node metastasis pathway, radiological characteristics and molecular biology of NSCLC, a large part of solid nodules with certain characteristics can also be cured by segmentectomy. This paper reviews the research status and progress about the indication of segmentectomy.
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