Search

Abstract Clean hydrogen production requires large-scale deployment of water-electrolysis technologies, particularly proton-exchange-membrane water electrolyzers (PEMWEs). However, as iridium-based electrocatalysts remain the only practical option for PEMWEs, their low abundance will become a bottleneck for a sustainable hydrogen economy. Herein, we propose high-performing and durable ionomer-free porous transport electrodes (PTEs) with facile recycling features enabling Ir thrifting and reclamation. The ionomer-free porous transport electrodes offer a practical pathway to investigate the role of ionomer in the catalyst layer and, from microelectrode measurements, point to an ionomer poisoning effect for the oxygen evolution reaction. The ionomer-free porous transport electrodes demonstrate a voltage reduction of > 600 mV compared to conventional ionomer-coated porous transport electrodes at 1.8 A cm−2 and

The competing endogenous RNA (ceRNA)-based profiling has been extensively studied in carcinogenesis of lung adenocarcinoma (LUAD), while it has seldomly been applied to investigate the metastatic potential of LUAD. This study aims to examine the function and in-depth mechanism of GPR37-centered ceRNA network in LUAD. Cancer tissues and adjacent normal tissues from three LUAD patients were collected for high-throughput sequencing to screen for differentially expressed genes. A PPI network was constructed to screen the key gene GPR37, followed by analysis for the functions and pathways. Clinical data from LUAD patients were integrated with gene expression data in TCGA-LUAD dataset for survival analysis. Based on the miRNAs targeting_GPR37 and lncRNAs targeting_miRNAs, a lncRNA-miRNA-mRNA ceRNA network was established. GPR37 was up-regulated in LUAD tissue samples, and it may be a key gene involved in LUAD progression. GPR37 in LUAD was mainly enriched in the mitosis-related pathways. High GPR37 expression corresponded to poor prognosis in LUAD patients. Meanwhile, GPR37 could be used as an independent factor to predict the prognosis in LUAD patients. LncRNA DLEU1, up-regulated in LUAD tissue samples, may competitively bind to miR-4458 to up-regulate the expression of the miR-4458 downstream target GPR37. DLEU1 was associated with poor prognosis and tumor metastasis in LUAD patients. Altogether, our findings reveal a novel ceRNA network of DLEU1/miR-4458/GPR37 in LUAD growth and metastasis.

Background: Mitochondrial myopathy is a group of diseases caused by abnormal mitochondrial structure or function. The mitochondrial myopathy impacts muscles of the whole body and exhibits variable symptoms. Respiratory muscle deficits deteriorate pulmonary function in patients with severe pneumonia. Case presentation: We report the case of a male patient with severe pneumonia-induced respiratory failure. He was abnormally dependent invasive ventilator-assisted ventilation after his condition had improved. Then we found abnormal ventilator waveform and a decline in muscle strength of him. Mitochondrial myopathy was ultimately confirmed by muscle pathological biopsy and body fluid genetic testing. Vitamin B complex, coenzyme Q10, Neprinol AFD, l-arginine, and MITO-TONIC were used to improve mitochondrial function and muscle metabolism. After treatment, discomfort associated with chest tightness, fatigue, cough, and sputum disappeared, and the patient was discharged. Conclusion: This case presented an uncommon cause of difficult weaning and extubation—acute onset of mitochondrial myopathy. Muscle biopsy and genetic testing of body fluid are essential for diagnosing mitochondrial myopathy. The A3243G mutation in the MT-TL1 gene of mitochondrial DNA contributes to pathogenesis of this case.

The plant species Gelsemium elegans Benth. (GEB) promotes pig and sheep growth; however, little is known about its effects in chickens. In this study, a GEB extract (GEBE) was prepared, and its effects on the growth, slaughter, antioxidant performance, meat quality, serum biochemical indices, intestinal morphology, and microflora of yellow-feathered chickens were evaluated. In total, 600 chickens aged 15 days were randomly divided into four groups with five replicates each and fed a basal diet containing 0% (control), 0.25% (0.25 GEBE), 0.75% (0.75 GEBE), or 1.25% (1.25 GEBE) GEBE until 49 days of age. Chickens were then killed, and their meat, organs, and serum and cecal contents were collected. GEBE reduced the feed conversion ratio, particularly in the 0.75 and 1.25 GEBE groups. Furthermore, the GEBE diet improved meat tenderness and reduced the meat expressible moisture content and liver malondialdehyde content, indicating high meat quality. Whereas the 0.25 GEBE diet increased the level of Lactobacillus acidophilus in the cecum, the 0.75 GEBE diet decreased the Escherichia coli level therein. These findings demonstrate that GEBE may improve the meat quality and cecal microbiota of yellow-feathered chickens, providing a basis for identifying candidate alternatives to conventional antibiotics as growth promoting feed additives.

Abstract Accumulation of vimentin is the core event in epithelial–mesenchymal transition (EMT). Post‐translational modifications have been widely reported to play crucial roles in imparting different properties and functions to vimentin. Here, a novel modification of vimentin, acetylated at Lys104 (vimentin‐K104Ac) is identified, which is stable in lung adenocarcinoma (LUAD) cells. Mechanistically, NACHT, LRR, and PYD domain‐containing protein 11 (NLRP11), a regulator of the inflammatory response, bind to vimentin and promote vimentin‐K104Ac expression, which is highly expressed in the early stages of LUAD and frequently appears in vimentin‐positive LUAD tissues. In addition, it is observed that an acetyltransferase, lysine acetyltransferase 7 (KAT7), which binds to NLRP11 and vimentin, directly mediates the acetylation of vimentin at Lys104 and that the cytoplasmic localization of KAT7 can be induced by NLRP11. Malignant promotion mediated by transfection with vimentin‐K104Q is noticeably greater than that mediated by transfection with vimentin‐WT. Further, suppressing the effects of NLRP11 and KAT7 on vimentin noticeably inhibited the malignant behavior of vimentin‐positive LUAD in vivo and in vitro. In summary, these findings have established a relationship between inflammation and EMT, which is reflected via KAT7‐mediated acetylation of vimentin at Lys104 dependent on NLRP11.

Berberine (BBR) has a long history of use in the treatment of Rheumatoid arthritis (RA) and is considered one of the most promising natural product for the treatment of RA. However, oral administration of berberine has low bioavailability and requires frequent administration, resulting in poor patient compliance. In this study, we developed a BBR-loaded phospholipid-based phase separation gel (BBR-PPSG) to achieve sustained drug release and long-term therapeutic effect. The stability of BBR-PPSG was verified and it was found that it can be stored for a long time. The pharmacokinetic study on rats and rabbits showed that BBR-PPSG not only achieved 1-month of sustained release, but also significantly increased the area under the curve (AUC) by nearly 9-fold and prolonged the half-life (t1/2) by 10-fold. By constructing rat and rabbit models of RA, we also proved that BBR-PPSG administration once a month effectively alleviated joint swelling, and significantly reduce TNF-α levels in AIA rats and OIA rabbits. Histopathological analysis of rabbit joint sections revealed that after intra-articular injection of BBR-PPSG, the synovial cell layer remained intact, while in the model group, the synovial cells were significantly reduced and exhibited necrosis. MicroCT data analysis showed that the values of Tb.N and Tb. Sp in the BBR-PPSG group were significantly better than those in the model group (p < 0.05). This study addressed the limitations of frequent administration of BBR by developing a phospholipid-based phase separation gel system for berberine delivery, achieving long-term sustained release. The BBR-PPSG demonstrated good biocompatibility, simple preparation and excellent stability, thus holding potential as a novel pharmaceutical formulation for RA treatment.

Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.

Abstract Background Alternative splicing (AS) plays important roles in transcriptome and proteome diversity. Its dysregulation has a close affiliation with oncogenic processes. This study aimed to evaluate AS-based biomarkers by machine learning algorithms for lung squamous cell carcinoma (LUSC) patients. Method The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database were utilized. After data composition balancing, Boruta feature selection and Spearman correlation analysis were used for differentially expressed AS events. Random forests and a nested fivefold cross-validation were applied for lymph node metastasis (LNM) classifier building. Random survival forest combined with Cox regression model was performed for a prognostic model, based on which a nomogram was developed. Functional enrichment analysis and Spearman correlation analysis were also conducted to explore underlying mechanisms. The expression of some switch-involved AS events along with parent genes was verified by qRT-PCR with 20 pairs of normal and LUSC tissues. Results We found 16 pairs of splicing events from same parent genes which were strongly related to the splicing switch (intrapair correlation coefficient = − 1). Next, we built a reliable LNM classifier based on 13 AS events as well as a nice prognostic model, in which switched AS events behaved prominently. The qRT-PCR presented consistent results with previous bioinformatics analysis, and some AS events like ITIH5-10715-AT and QKI-78404-AT showed remarkable detection efficiency for LUSC. Conclusion AS events, especially switched ones from the same parent genes, could provide new insights into the molecular diagnosis and therapeutic drug design of LUSC.

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthropathy with a high deformity rate. Despite numerous studies and clinical trials, no curative treatment is available for large weight-bearing joints. Intra-articular (IA) injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity. However, free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease. Herein, a phospholipids-based controlled-release gel was prepared for sustained IA delivery of celastrol (CEL) and the therapeutic efficiency was evaluated in a rheumatoid arthritis rabbit model. The CEL-loaded gel (CEL-gel) contained up to 70% phospholipids yet was easy to inject. After injecting into the joint cavity, CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent. In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel. A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution (CEL-sol). Furthermore, the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL. With good biocompatibility and biodegradability, CEL-gel might be a promising IA drug delivery system.

According to mounting evidence, long noncoding RNAs (lncRNAs) play a vital role in regulated cell death (RCD). A potential strategy for cancer therapy involves triggering ferroptosis, a novel form of RCD. Although it is thought to be an autophagy-dependent process, it is still unclear how the two processes interact. This study characterized a long intergenic noncoding RNA, LINC00551, expressed at a low level in lung adenocarcinoma (LUAD) and some other cancers. Overexpression of LINC00551 suppresses cell viability while promoting autophagy and RSL-3-induced ferroptosis in LUAD cells. LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes LUAD autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. This study provided an insight into the molecular mechanism regulating ferroptosis and highlighted LINC00551 as a potential therapeutic target for LUAD.

The intelligent tongue control system is of great significance for assisting the independent life of patients with a limb disability. In order to more accurately control the assisted living equipment of incompetent patients and solve the power-loss problem of the intelligent tongue control system, this research designs a non-invasive pressure sensor array for tongue touch signal detection in the oral cavity and proposes a tongue control system based on RSIC-V edge computing. The system converts the tongue touch pressure data into specific control instructions on the edge of the RSIC-V chip and transmits them to the receiver, thus reducing the transmission of data. This study takes control of the wheelchair motor as the test object. In the experiment, the speed response time test, the center click task, and the power consumption experiment are carried out, whose results show that the adaptive fuzzy PID control algorithm has good robustness in the system; when the DC motor with a given speed of 750 r/min reaches the steady state, its rise time is 0.108 s and the adjustment time is 0.59 s. The dynamic power consumption of the non-intrusive intraoral stand-alone tongue control system proposed in this paper is found to be 3.745 MW, which is 11.5% lower than the total power consumption of the sTD system.

In this paper， the types and expression characteristics of microRNAs related to cognitive impairment in schizophrenia patients were reviewed， so as to provide a reference for further research on the characteristics of cognitive impairment in schizophrenia patients， and to open up new ideas for further research on the molecular mechanism of cognitive impairment as well as subsequent precise treatment and prognosis evaluation.

Screening for early-stage lung cancer with low-dose computed tomography is recommended for high-risk populations; consequently, the incidence of pure ground-glass opacity (pGGO) is increasing. Ground-glass opacity (GGO) is considered the appearance of early lung cancer, and there remains an unmet clinical need to understand the pathology of small GGO (

Abstract Background Alternative splicing (AS) plays critical roles in generating protein diversity and complexity. Dysregulation of AS underlies the initiation and progression of tumors. Machine learning approaches have emerged as efficient tools to identify promising biomarkers. It is meaningful to explore pivotal AS events (ASEs) to deepen understanding and improve prognostic assessments of lung adenocarcinoma (LUAD) via machine learning algorithms. Method RNA sequencing data and AS data were extracted from The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database. Using several machine learning methods, we identified 24 pairs of LUAD-related ASEs implicated in splicing switches and a random forest-based classifiers for identifying lymph node metastasis (LNM) consisting of 12 ASEs. Furthermore, we identified key prognosis-related ASEs and established a 16-ASE-based prognostic model to predict overall survival for LUAD patients using Cox regression model, random survival forest analysis, and forward selection model. Bioinformatics analyses were also applied to identify underlying mechanisms and associated upstream splicing factors (SFs). Results Each pair of ASEs was spliced from the same parent gene, and exhibited perfect inverse intrapair correlation (correlation coefficient = − 1). The 12-ASE-based classifier showed robust ability to evaluate LNM status of LUAD patients with the area under the receiver operating characteristic (ROC) curve (AUC) more than 0.7 in fivefold cross-validation. The prognostic model performed well at 1, 3, 5, and 10 years in both the training cohort and internal test cohort. Univariate and multivariate Cox regression indicated the prognostic model could be used as an independent prognostic factor for patients with LUAD. Further analysis revealed correlations between the prognostic model and American Joint Committee on Cancer stage, T stage, N stage, and living status. The splicing network constructed of survival-related SFs and ASEs depicts regulatory relationships between them. Conclusion In summary, our study provides insight into LUAD researches and managements based on these AS biomarkers.

Abstract Abnormal DNA methylation persists throughout carcinogenesis and cancer development. Hence, gene promoter methylation may act as a prognostic tool and provide new potential therapeutic targets for patients with lung adenocarcinoma (LUAD). In this study, to explore prognostic methylation signature, data regarding DNA methylation and RNA‐seq, and clinical data of patients with LUAD from the Cancer Genome Atlas database (TCGA) were downloaded. After data preprocessing, the methylation data were divided into training (N = 405) and test sets (N = 62). Then, patients in the training set were assigned to five subgroups based on their different methylation levels using the consensus clustering method. We comprehensively analyzed the survival information, methylation levels, and clinical variables, including American Joint Committee on Cancer (AJCC) stage, tumor‐node‐metastasis (TNM) staging, age, smoking history, and gender of these five groups. Subsequently, we identified a 16‐CpG prognostic signature and constructed a prognostic model, which was verified in the test set. Further analyses showed stable prognostic performance in the stratified cohorts. In conclusion, the new predictive DNA methylation signature proposed in this study may be used as an independent biomarker to assess the overall survival of LUAD patients and provide bioinformatics information for development of targeted therapy.

Abstract Background Bronchoscopy is applied broadly in the diagnosis and treatment of pulmonary diseases. Over the past few decades, an increasing number of studies about bronchoscopy have been published. However, little is known about their qualities and characteristics. Methods All of the databases in Web of Science (including the Web of Science Core Collection, BIOSIS Citation Index, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, and SciELO Citation Index) were utilized to identify articles published from 1990 to 2020. The top 100 most cited articles about bronchoscopy were selected for degree centrality analysis and analyses regarding publication time, total citation number, the citation density, time-related flux, first author, published journal, geographic origin, and research theme. Results The selected articles were published mainly in the 2000s and 1990s. Citations per article ranged from 731 to 196. The leading country was the USA, followed by the United Kingdom. The most frequently studied themes were bronchoalveolar lavage (BAL) fluid and biopsy. The degree centrality analysis connoted that “BAL, inflammation, diagnosis” had a high degree of centrality in the 1990s, while “diagnosis, BAL, biopsy, prospective” took centre stage in the 2000s. Conclusions The time, area, and theme distribution of the 100 most cited articles on bronchoscopy have been thoroughly analyzed. It is noticeable that researches based on BAL and endobronchial or transbronchial biopsies currently plays a major role.

Modern alkaline membrane fuel cells have generally shown very poor operational stability. Here, the authors combine operando neutron imaging and X-ray computed tomography to understand the root cause for this and then design new electrodes to enable high performance and operational stability.

Target-based point cloud registration methods are still widely used by many laser scanning professionals due to their direct and manipulable nature. However, placing and moving multiple targets such as spheres for registration is a time-consuming and tactical process. When the number of scans gets large, the time and labor costs will accumulate to a high level. In this paper, we propose a flexible registration method that requires the installation of only a low-cost cubical target: a die-like object. The method includes virtual coordinate system construction and two error compensation techniques, in which the non-orthogonality of the scanned facets, along with the unknown sizes of the dice are estimated based on projection geometry and cubical constraints so that three pairs of conjugate points can be accurately identified along the axes of the constructed coordinate systems for the registration. No scan overlap of the facet is needed. Two different low-cost dice (with a volume of 0.125 m3 and 0.027 m3) were used for verifying the proposed method, which shows that the proposed method delivers registration accuracy (with an RMSE discrepancy of less than 0.5 mm for check planes) comparable to the traditional sphere- based method using four to six spherical targets spanning the scene. Therefore, the proposed method is particularly useful for registering point clouds in harsh scanning environments with limited target-setting space and high chances of target interruption.

One of the most important needs for the future of low-cost fuel cells is the development of highly active platinum group metal (PGM)-free catalysts. For the oxygen reduction reaction, Fe–N–C materials have been widely studied in both acid and alkaline media. However, reported catalysts in the literature show quite different intrinsic activity and in-cell performance, despite similar synthesis routes and precursors. Here, two types of Fe–N–C are prepared from the same precursor and procedure – the main difference is how the precursor was handled prior to use. It is shown that in one case Fe overwhelmingly existed as highly active single-metal atoms in FeN4 coordination (preferred), while in the other case large Fe particles coexisting with few single metal atoms were obtained. As a result, there were drastic differences in the catalyst structure, activity, and especially in their performance in an operating anion exchange membrane fuel cell (AEMFC). Additionally, it is shown that catalyst layers created from single-atom-dominated Fe–N–C can have excellent performance and durability in an AEMFC using H2/O2 reacting gases, achieving a peak power density of 1.8 W cm−2 – comparable to similar AEMFCs with a Pt/C cathode – and being able to operate stably for more than 100 h. Finally, the Fe–N–C cathode was paired with a low-loading PtRu/C anode electrode to create AEMFCs (on H2/O2) with a total PGM loading of only 0.135 mg cm−2 (0.090 mgPt cm−2) that was able to achieve a very high specific power of 8.4 W mgPGM−1 (12.6 W mgPt−1).

Abstract Interfacial and bulk properties between the catalyst layer and the porous transport layer (PTL) restrict the iridium loading reduction for proton exchange membrane water electrolyzers (PEMWEs), by limiting their mass and charge transport. Using titanium fiber PTLs of varying thickness and porosity, the bulk and interface transport properties are investigated, correlating them to PEMWEs cell performance at ultra‐low Ir loadings of ≈0.05 mgIr cm−2. Electrochemical experiments, tomography, and modeling are combined to study the bulk and interfacial impacts of PTLs on PEMWE performance. It is found that the PEMWE performance is largely dependent on the PTL properties at ultra‐low Ir loadings; bulk structural properties are critical to determine the mass transport and Ohmic resistance of PEMWEs while the surface properties of PTLs are critical to govern the catalyst layer utilization and electrode kinetics. The PTL‐induced variation in kinetic and mass transport overpotential are on the order of ≈40 and 60 mV (at 80 A mgIr−1), respectively, while a nonnegligible 35 mV (at 3 A cm−2) difference in Ohmic overpotential. Thus at least 150 mV improvement in PEMWE performance can be achieved through PTL structural optimization without membrane thickness reduction or advent of new electrocatalysts.

Background: Emerging scientific evidence has shown that long non-coding RNAs (lncRNAs) exert critical roles in genomic instability (GI), which is considered a hallmark of cancer. To date, the prognostic value of GI-associated lncRNAs (GI-lncRNAs) remains largely unexplored in lung adenocarcinoma (LUAC). The aims of this study were to identify GI-lncRNAs associated with the survival of LUAC patients, and to develop a novel GI-lncRNA-based prognostic model (GI-lncRNA model) for LUAC.Methods: Clinicopathological data of LUAC patients, and their expression profiles of lncRNAs and somatic mutations were obtained from The Cancer Genome Atlas database. Pearson correlation analysis was conducted to identify the co-expressed mRNAs of GI-lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to determine the main biological function and molecular pathways of the differentially expressed GI-lncRNAs. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify GI-lncRNAs significantly related to overall survival (OS) for construction of the GI-lncRNA model. Kaplan–Meier survival analysis and receiver operating characteristic curve analysis were performed to evaluate the predictive accuracy. The performance of the newly developed GI-lncRNA model was compared with the recently published lncRNA-based prognostic index models.Results: A total of 19 GI-lncRNAs were found to be significantly associated with OS, of which 9 were identified by multivariate analysis to construct the GI-lncRNA model. Notably, the GI-lncRNA model showed a prognostic value independent of key clinical characteristics. Further performance evaluation indicated that the area under the curve (AUC) of the GI-lncRNA model was 0.771, which was greater than that of the TP53 mutation status and three existing lncRNA-based models in predicting the prognosis of patients with LUAC. In addition, the GI-lncRNA model was highly correlated with programed death ligand 1 (PD-L1) expression and tumor mutational burden in immunotherapy for LUAC.Conclusion: The GI-lncRNA model was established and its performance was found to be superior to existing lncRNA-based models. As such, the GI-lncRNA model holds promise as a more accurate prognostic tool for the prediction of prognosis and response to immunotherapy in patients with LUAC.

BackgroundLung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.MethodsWe analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.ResultsIL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.ConclusionThe IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.

Background Ferroptosis is a novel form of programmed cell death characterized by the excessive accumulation of intracellular iron and an increase in reactive oxygen species. Emerging studies have shown that ferroptosis plays a vital role in the progression of lung adenocarcinoma, but the effect of ferroptosis-related genes on prognosis has been poorly studied. The purpose of this study was to explore the prognostic value of ferroptosis-related genes. Methods Lung adenocarcinoma samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to establish a predictive signature for risk stratification. Kaplan–Meier (K–M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the signature. We further explored the potential correlation between the risk score model and tumor immune status. Results A 15-gene ferroptosis signature was constructed to classify patients into different risk groups. The overall survival (OS) of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The signature could predict OS independent of other risk factors. Single-sample gene set enrichment analysis (ssGSEA) identified the difference in immune status between the two groups. Patients in the high-risk group had stronger immune suppression, especially in the antigen presentation process. Conclusions The 15-gene ferroptosis signature identified in this study could be a potential biomarker for prognosis prediction in lung adenocarcinoma. Targeting ferroptosis might be a promising therapeutic alternative for lung adenocarcinoma.

The codling moth, Cydia pomonella, is one of the major pests of pome fruit (apples and pears) and walnuts. Here, the authors sequence and analyze its genome, providing insights on olfactory and detoxification processes that may underlie its worldwide expansion.

Grapholita molesta is one of the most serious pests in fruits orchards. Flight performance of male insects and fecundity of female insects are important quality control parameters when moths are mass-reared for use in environment-friendly control strategies such as the sterile insect technique (SIT). However, information about flight performance, fecundity, and ovary development of G. molesta at different ages is scarce. In this study, we used a flight mill information system to measure the flight ability of female and male adults of G. molesta at different ages, and evaluated fecundity and ovarian development of female adults at different ages. The results demonstrated that the flight parameters (cumulative flight distance, cumulative flight time, maximum flight distance and maximum flight duration) of female and male G. molesta varied with age. Six-day-old female moths and three-day-old male moths were the strongest fliers, whereas the fecundity of one-day and two-day-old female moths was significantly lower than that of three to seven-day-old females. Five-day-old females had the highest fecundity. Their ovaries demonstrated mature eggs in the lateral and middle oviducts as of the third day post-emergence. It is suggested that the optimal age for moths to be released in SIT programs is three days, and moths older three days can be used for mass-rearing in a factory.

The oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae) is one of the most severe fruit tree pests in China, causing huge economic losses to fruit production. So far, there are few detailed reports on the rearing protocols of G. molesta. In this study, we compared the longevity, 10-d fecundity, flight ability, and the activity of major energy metabolism enzymes in the flight muscles of G. molesta under three feeding regimes (supplement with sterile water, supplement with 10% honey solution and starvation) of the adult moths. The results showed that the longevity, 10-d fecundity, and flight parameters (cumulative flight distance and time, maximum flight distance and duration, and the average flight speed) of adult moths when supplemented with sterile water or honey solution were significantly higher than those of moths that were starved. There were no significant differences in the 10-d fecundity, flight parameters, and the activity of major energy metabolism enzymes of flight muscles between moths that were supplemented with sterile water or 10% honey solution. The flight muscles of G. molesta mainly used carbohydrates as an energy source when sterile water and honey solution were supplemented, and the moth mainly used lipids as an energy source under starvation. Considering the cost and potential for diet contamination during mass-rearing, supplying sterile water is considered a cost effective option for food substitution of adult G. molesta.

Aberrant N6-methyladenosine (m6A) RNA methylation regulatory genes and related gene alternative splicing (AS) could be used to predict the prognosis of non–small cell lung carcinoma. This study focused on 13 m6A regulatory genes (METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO, and ALKBH5) and expression profiles in TCGA-LUAD (n = 504) and TCGA-LUSC (n = 479) datasets from the Cancer Genome Atlas database. The data were downloaded and bioinformatically and statistically analyzed, including the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. There were 43,948 mRNA splicing events in lung adenocarcinoma (LUAD) and 46,020 in lung squamous cell carcinoma (LUSC), and the data suggested that m6A regulators could regulate mRNA splicing. Differential HNRNPC and RBM15 expression was associated with overall survival (OS) of LUAD and HNRNPC and METTL3 expression with the OS of LUSC patients. Furthermore, the non–small cell lung cancer prognosis-related AS events signature was constructed and divided patients into high- vs. low-risk groups using seven and 14 AS genes in LUAD and LUSC, respectively. The LUAD risk signature was associated with gender and T, N, and TNM stages, but the LUSC risk signature was not associated with any clinical features. In addition, the risk signature and TNM stage were independent prognostic predictors in LUAD and the risk signature and T stage were independent prognostic predictors in LUSC after the multivariate Cox regression and receiver operating characteristic analyses. In conclusion, this study revealed the AS prognostic signature in the prediction of LUAD and LUSC prognosis.

Background Esophageal carcinogenesis involves in alterations of DNA methylation and gene transcription. This study profiled genomic DNA methylome vs. gene expression using transcriptome data on esophageal adenocarcinoma (EAC) tissues from the online databases in order to identify methylation biomarkers in EAC early diagnosis. Materials and Methods The DNA methylome and transcriptome data were downloaded from the UCSC Xena, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases and then bioinformatically analyzed for the differentially methylated positions (DMPs) vs. gene expression between EAC and normal tissues. The highly methylated DMPs vs. reduced gene expression in EAC were selected and then stratified with those of the corresponding normal blood samples and other common human cancers to construct an EAC-specific diagnostic model. The usefulness of this model was further verified in other three GEO datasets of EAC tissues. Result A total of 841 DMPs were associated with expression of 320 genes, some of which were aberrantly methylated in EAC tissues. Further analysis showed that four (cg07589773, cg10474350, cg13011388 and cg15208375 mapped to gene IKZF1, HOXA7, EFS and TSHZ3, respectively) of these 841 DMPs could form and establish a diagnostic model after stratified them with the corresponding normal blood samples and other common human cancers. The data were further validated in other three GEO datasets on EAC tissues in early EAC diagnosis. Conclusion This study revealed a diagnostic model of four genes methylation to diagnose EAC early. Further study will confirm the usefulness of this model in a prospective EAC cases.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive tract, but its underlying molecular mechanisms are not known. We aim to identify the genes involved in ESCC carcinogenesis and discover potential prognostic markers using integrated bioinformatics analysis. Three pairs of ESCC tissues and paired normal tissues were sequenced by high-throughput RNA sequencing (RNA-seq). Integrated bioinformatics analysis was used to identify differentially expressed coding genes (DECGs) and differentially expressed long non-coding RNA (lncRNA) genes (DELGs). A protein–protein interaction (PPI) network of DECGs was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website and visualized with Cytoscape. Survival analysis was conducted by log-rank tests to identify “hub” genes with potential prognostic value, and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to assess expression of these genes in ESCC tissues. TranswellTM assays were employed to examine the migration ability of cells after knockdown of LINC01614 expression, followed by investigation of epithelial–mesenchymal transition (EMT) by western blotting (WB). A total of 106 upregulated genes and 42 downregulated genes were screened out from the ESCC data sets. Survival analysis showed two hub protein-coding genes with higher expression in module 1 of the PPI network (SPP1 and BGN) and another three upregulated lncRNAs (LINC01614, LINC01415, NKILA) that were associated with a poor prognosis. High expression of SPP1, BGN, LINC01614, and LINC01415 in tumor samples was validated further by RT-qPCR. In vitro experiments show that knockdown of LINC01614 expression could significantly inhibit the migration of ESCC cells by regulating EMT, which was confirmed by WB. These results indicate that BGN, SPP1, LINC01614, and LINC01415 might be critical genes in ESCC and potential prognostic biomarkers.

Background The highest rate of cancer-related deaths worldwide is from lung adenocarcinoma (LUAD) annually. Metabolism was associated with tumorigenesis and cancer development. Metabolic-related genes may be important biomarkers and metabolic therapeutic targets for LUAD. Materials and Methods In this study, the gleaned cohort included LUAD RNA-SEQ data from the Cancer Genome Atlas (TCGA) and corresponding clinical data (n = 445). The training cohort was utilized to model construction, and data from the Gene Expression Omnibus (GEO, GSE30219 cohort, n = 83; GEO, GSE72094, n = 393) were regarded as a testing cohort and utilized for validation. First, we used a lasso-penalized Cox regression analysis to build a new metabolic-related signature for predicting the prognosis of LUAD patients. Next, we verified the metabolic gene model by survival analysis, C-index, receiver operating characteristic (ROC) analysis. Univariate and multivariate Cox regression analyses were utilized to verify the gene signature as an independent prognostic factor. Finally, we constructed a nomogram and performed gene set enrichment analysis to facilitate subsequent clinical applications and molecular mechanism analysis. Result Patients with higher risk scores showed significantly associated with poorer survival. We also verified the signature can work as an independent prognostic factor for LUAD survival. The nomogram showed better clinical application performance for LUAD patient prognostic prediction. Finally, KEGG and GO pathways enrichment analyses suggested several especially enriched pathways, which may be helpful for us investigative the underlying mechanisms.

Bridge defects are important indicator for the bridge safety assessment. Considering the cost and inefficiency of the traditional method, the UAV system applied for bridge crack inspection is a better choice. Therefore, we have configured a bridge inspection UAV system with SLR camera, laser rangefinder. First, we have carried an evaluation experiment to determine the distance range of stable imaging for planning the safer bridge inspection route based on the special UAV system. Then, the crack recognition method combining neural network and support vector machine is used to locate and extract the bridge cracks, and then, the actual cracks are calculated according to the optical principle. Finally, a case study of the Xiangjiang-River bridge inspection is carried out to verify the feasibility of bridge defects recognition based on this UAV system, achieving above 90% in the crack width recognition, which provides a better platform for bridge inspection.

Abstract Background Induction chemotherapy has been shown to improve survival of patients with stage III A/N2 (T1–3, N2, M0) non-small cell lung cancer (NSCLC), followed by resection, but the benefits of neoadjuvant radiotherapy still remain controversial. Methods PubMed, Embase, and Cochrane library databases were searched for relevant randomized controlled trials (RCTs) comparing the outcomes of induction chemoradiotherapy over induction chemotherapy, in patients with resectable stage IIIA/N2 NSCLC. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects model, and heterogeneity was assessed using I2 test. Publication bias was examined by funnel plots analysis. Results A total of three RCTs met the inclusion criteria of our meta-analysis. The pooled results demonstrated that, in comparison to induction chemotherapy, induction chemoradiotherapy has a significant benefit in tumor response, mediastinal downstaging, and pathological complete response of mediastinal lymph nodes. In addition, no more peri-intervention mortality was detected in patients from chemoradiotherapy group, and a higher number of patients from this group had R0 resection. However, our results did not show any difference between overall survival and progression-free survival after 2, 4, and 6 years of follow-ups, in patients undergoing radiation therapy vs. induction chemotherapy. Conclusion Preoperative chemoradiotherapy, as compared to induction chemotherapy alone, is associated with similar peri-intervention mortality, a greater tumor response, mediastinal nodule downstaging, and rate of R0 resection, but does not improve survival of resectable stage IIIA/N2 NSCLC patients.

In the modern radar signal environment, hybrid modulation signals are increasingly used in many systems. This study focuses on the Time Difference Of Arrival (TDOA) estimation problem of FSK-BPSK hybrid modulation signals. The method combines the characteristic of modulated signal and utilizes the sum of simple correlation functions of sub-pulses to elicit the complex correlation function of the entire pulse signal. Finally, a correlation function fitting algorithm is used to estimate the exact TDOA. Experimental results indicate an obvious improvement in the accuracy and noise immunity of the method, and the method is appropriate for the TDOA estimation of low-bandwidth hybrid modulation signals.

Background: Mesenchymal stem cells are capable of self-renewal and multi-lineage differentiation. They are used extensively to treat several diseases. Traditionally, mesenchymal stem cells are cultured in serum-containing media, typically supplemented with fetal bovine serum (FBS). However, the variability of FBS is likely to skew experimental results. Although serum-free media used to expand mesenchymal stem cells has facilitated remarkable achievements, immunomodulation of these cells in under serum-free conditions is poorly understood. We hypothesized that mesenchymal stem cells expanded in serum-free media will retain powerful immunoregulatory functions in vitro and in vivo. Design and Methods: Immunosuppressive activity and the immunomodulatory cytokines produced by mesenchymal stem cells in serum-free media were characterized in vitro. Immunomodulation by serum-free mesenchymal stem cell expansion in monocrotaline-induced pulmonary hypertension was explored in vivo. Results: Similar to cells in serum-containing media, mesenchymal stem cells expanded in serum-free media inhibited proliferation and apoptosis of CD4+T cells. They also exhibited strong immunosuppressive activities and secreted high levels of immunomodulatory cytokines such as PGE2, IDO1, COX2, IL-6, and IL-1β, but not HGF. On the other hand, growth of mesenchymal stem cells in serum-free media attenuated pulmonary vascular remodeling and inhibited mRNA expression of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-1β, and IL-18. Conclusions: Mesenchymal stem cells in serum-free media maintained powerful immunomodulatory function in vitro and in vivo; serum-free media may replace serum-containing media for basic research and clinical applications.

This paper reports the successful construction of novel polymerizable ionic liquid microemulsions and the in situ synthesis of poly(ionic liquid) adsorbents for the removal of Zn2+ from aqueous solution. Dynamic light-scattering data were used to confirm the polymerization media and to illustrate the effect of the crosslinker dosage on the droplet size of the microemulsion. FTIR and thermal analysis were employed to confirm the successful preparation of the designed polymers and characterize their thermostability and glass transition-temperature value. The optimization of the adsorption process indicates that the initial concentration of Zn2+, pH, adsorbent dosage and contact time affected the adsorption performance of poly(ionic liquid)s toward Zn2+. Furthermore, our research revealed that the adsorption process can be effectively described by the pseudo second-order kinetic model and the Freundlich isotherm model.

Chirality has been a property of central importance in physics, chemistry and biology for more than a century. Recently, electrons were found to become spin polarized after transmitting through chiral molecules, crystals, and their hybrids. This phenomenon, called chirality-induced spin selectivity (CISS), presents broad application potentials and far-reaching fundamental implications involving intricate interplays among structural chirality, topological states, and electronic spin and orbitals. However, the microscopic picture of how chiral geometry influences electronic spin remains elusive, given the negligible spin-orbit coupling (SOC) in organic molecules. In this work, we address this issue via a direct comparison of magnetoconductance (MC) measurements on magnetic semiconductor-based chiral molecular spin valves with normal metal electrodes of contrasting SOC strengths. The experiment reveals that a heavy-metal electrode provides SOC to convert the orbital polarization induced by the chiral molecular structure to spin polarization. Our results illustrate the essential role of SOC in the metal electrode for the CISS spin valve effect. A tunneling model with a magnetochiral modulation of the potential barrier is shown to quantitatively account for the unusual transport behavior.

NADPH-cytochrome P450 reductase (CPR) plays an important role in the cytochrome P450 (CYP)-mediated metabolism of endogenous and exogenous substrates. CPR has been found to be associated with insecticide metabolism and resistance in many insects. However, information regarding CPR in the bird cherry-oat aphid, Rhopalosiphum padi, is unavailable. In the current study, a full-length cDNA (2,476 bp) of CPR (RpCPR) encoding 681 amino acids was cloned from R. padi. Nucleotide sequence and deduced amino acid sequence analysis showed that RpCPR exhibits characteristics of classical CPRs and shares high identities with those of other insects, especially with the pea aphid, Acyrthosiphon pisum. The mRNA of RpCPR was expressed at all developmental stages, with the highest expression level found in the second instar and the lowest in adult. Expression levels of RpCPR in isoprocarb-resistant and imidacloprid-resistant strains were 3.74- and 3.53-fold higher, respectively, than that of a susceptible strain. RpCPR expression could also be induced by low concentrations (LC30) of isoprocarb and imidacloprid. Moreover, we sequenced the open reading frame (ORF) of RpCPR from 167 field samples collected in 11 geographical populations. Three hundred and thirty-four SNPs were detected, of which, 65 were found in more than two individuals. One hundred and ninety-four missense mutations were present in the amino acid sequence, of which, the P484S mutant had an allele frequency of 35.1%. The present results suggest that RpCPR may play an important role in the P450-mediated insecticide resistance of R. padi to isoprocarb and imidacloprid and possibly other insecticides. Meanwhile, RpCPRmaintains high genetic diversity in natural individuals, which provides the possibility of studying potential correlations between variants and certain special physiological characters.