Heterogeneity of Lipid Metabolism and its Clinical and Immune Correlation in Lung Adenocarcinoma.

INTRODUCTION: The role of lipid metabolism in lung adenocarcinoma (LUAD) is not completely researched. Lipid metabolism reprogramming is a characteristic of malignancies and contributes to carcinogenesis and progression. The transcriptome and scRNA- seq data and clinical information were downloaded from the public databases. METHODS: Lipid metabolism pathways were collected from the MSigDB database, and molecular subtypes were classified based on lipid metabolism features via consensus clustering. The bidirectional crosstalk between immune cells and malignant cells was analyzed. Differences in lipid metabolism at the single-cell level and their correlation with the tumor microenvironment (TME) were also studied. LUAD patients were classified into two subtypes, showing distinct mutation and lipid metabolism features based on lipid metabolism characteristics. Meanwhile, significant differences in the overall survival, clinical characteristics, and immune landscape were observed between the two subtypes. We also found that clust1 had higher oxidative stress status. There were 116 differentially expressed genes between the two subtypes, which were significantly associated with cell cycle progression. We identified 4001 immune cells, including 483 malignant cells and 3518 normal cells, and found active intercellular communication and significant differences in lipid metabolism characteristics between the malignant cells and normal cells. Furthermore, several lipid metabolism pathways were found to be associated with TME factors, including hypoxia and angiogenesis. RESULT: The current findings indicated that lipid metabolism was involved in the development and cellular heterogeneity of LUAD and revealed widespread reprogramming across multiple cellular elements in the TME of LUAD. CONCLUSION: This characterization improved the current understanding of tumor biology and enabled the identification of novel targets for immunotherapy.

Photoredox Catalyzed [3 + 2]-Annulation Reaction of Pyridinium 1,4-Zwitterionic Thiolates with Alkenes: Synthesis of Dihydrothiophenes.

Pyridinium 1,4-zwitterionic thiolates are usually used to develop ionic annulation reactions. However, radical reactions were rare. We developed a photoredox catalyzed [3 + 2]-annulation reaction of pyridinium 1,4-zwitterionic thiolates with alkenes, disclosed the new reactivity of pyridinium 1,4-zwitterionic thiolate, and provided a new synthetic method for dihydrothiophene.

A semantic segmentation of the lung nodules using a shape attention-guided contextual residual network.

Objective. The early diagnosis of lung cancer depends on the precise segmentation of lung nodules. However, the variable size, uneven intensity, and blurred borders of lung nodules bring many challenges to the precise segmentation of lung nodules.Approach.We propose a shape attention-guided contextual residual network to address the difficult problem in lung nodule segmentation. Firstly, we establish a selective kernel convolution residual module to replace the original encoder and decoder. This module incorporates selective kernel convolution, which automatically selects convolutions with different receptive fields to acquire multi-scale spatial features. Secondly, we construct a multi-scale contextual attention module to assist the network in extracting multi-scale contextual features of local feature maps. Finally, we develop a shape attention-guided module to assist the network to restore details such as the boundary and shape of lung nodules during the upsampling phase.Main results.The proposed network is comprehensively analyzed using the publicly available LUNA16 data set, and an ablation experiment is designed to validate the effectiveness of each individual component. Ultimately, the dice similarity coefficient of the experimental results reaches 87.39% on the test set. Compared to other state-of-the-art segmentation methods, the proposed network achieves superior performance in lung nodule segmentation.Significance.Our proposed network improves the accuracy of lung nodule segmentation, which provides an important support for physicians to subsequently develop treatment plans.

Integrative stemness characteristics associated with prognosis and the immune microenvironment in lung adenocarcinoma.

BACKGROUND: To comprehensively analyze the stemness characteristics related to prognosis and the immune microenvironment in lung adenocarcinoma (LUAD). METHODS: The OCLR machine learning method was used to calculate the stemness index (mRNAsi) of the LUAD samples. DEGs common between the low mRNAsi, normal, and high mRNAsi groups were screened and the immune-stemness genes were obtained. Then the PPI network was created and enrichment analyses were performed. Moreover, different subtypes based on immune-stemness genes associated with prognosis were identified, and the relationships between LUAD stemness and TIME variables were systematically analyzed, followed by TMB analysis. RESULTS: Patients in the high mRNAsi groups with poor prognosis were screened along with 144 immune-stemness genes. IL-6, FPR2, and RLN3 showed a higher degree in the PPI network. A total of 26 immune-stemness genes associated with prognosis were screened. Two clusters were obtained (cluster 1 and cluster 2). Survival analysis revealed that patients in cluster 2 had a poor prognosis. A total of 12 immune cell subpopulations exhibited significant differences between cluster 1 and cluster 2 (P < 0.05). A total of 10 immune checkpoint genes exhibited significantly higher expression in cluster 1 (P < 0.05) than in cluster 2. Further, the TMB value in cluster 2 was higher than that in cluster 1 (P < 0.05). CONCLUSION: Immune-stemness genes, including L-6, FPR2, and RLN3, might play significant roles in LUAD development via cytokine-cytokine receptor interaction, neuroactive ligand‒receptor interaction, and the JAK‒STAT pathway. Immune-stemness genes were related to tumor-infiltrating immune cells, TMB, and expression of immune checkpoint gene.

Case report: A novel reciprocal ROS1-CD74 fusion in a NSCLC patient partially benefited from sequential tyrosine kinase inhibitors treatment.

Background: The clinical significance of majority oncogenic novel fusions is still unknown due to scarcity. Reciprocal ROS1 translocation is a rare form of ROS1 fusion and has not yet been clearly analyzed. Case presentation: A 44-year-old Chinese woman with a large dimension in the left lobe of the lung was admitted to the hospital with IVB lung adenocarcinoma. It was discovered that intron 28 of ROS1 and intron 6 of CD74 produced a unique reciprocal ROS1 rearrangement. In addition, the dual CD74-ROS1 fusions were discovered using the RNA next-generation sequencing (NGS) findings. Although benefiting from crizotinib and lorlatinib sequential treatment, the overall prognosis of the patient was relatively poor, whose progression-free survival was 4 and 5 months for crizotinib treatment and lorlatinib treatment, respectively. Conclusion: In summary, a novel ROS1-CD74 fusion identified by DNA NGS was translated into dual CD74-ROS1 transcripts. Furthermore, this patient with non-small cell lung cancer benefited from consecutive tyrosine kinase inhibitor therapy. Our discovery broadened the range of targetable ROS1 fusions and underlined the importance of sequential DNA and RNA sequencing in identifying uncommon but beneficial fusions, which eventually bring benefits to the patients.

Upregulation of CCT3 predicts poor prognosis and promotes cell proliferation via inhibition of ferroptosis and activation of AKT signaling in lung adenocarcinoma.

BACKGROUND: Chaperonin containing TCP1 subunit 3 (CCT3) acts as an oncogene in cancers, whereas its role and underlying mechanisms in lung adenocarcinoma (LUAD) are poorly understood. This study investigated the clinical relevance and function of CCT3 in LUAD. METHODS: Clinical relevance of CCT3 in LUAD and lung squamous cell carcinoma (LUSC) was analyzed based on TCGA database. qRT-PCR and Western blot were used to detect mRNA and protein expression, respectively. CCK8 and colony formation were performed to measure cell viability. PI and PI/Annexin V-FITC assay kit was used to determine cell cycle and cell death, respectively. Luciferase activity was performed to check whether CCT3 regulated slc7a11's transcription activity. Ferroptosis was determined by incubating the cells with ferroptosis and apoptosis inducer, their inhibitor and autophagy inhibitor, followed by cell viability examination. RESULTS: We found that CCT3 was overexpressed in LUAD and LUSC tissues. Overexpression of CCT3 predicted the poor prognosis of LUAD patients. Loss-of-function and gain-of-function experiments demonstrated that CCT3 promoted the proliferation and colony formation of LUAD cells. In addition, CCT3 promoted cell cycle progression and suppressed slc7a11-mediated cell ferroptosis, but not apoptosis. We also found that CCT3 activated AKT. MK2206 significantly reduced the viability of CCT3 overexpressed LUAD cells, while had smaller inhibitory effect on the proliferation of control cells, suggesting that CCT3 dictates the sensitivity of LUAD cells to AKT inhibition. CONCLUSION: Our study demonstrates that CCT3 contributes to the proliferation and growth of LUAD cells through inhibition of ferroptosis and activation of AKT.

Remanufacturability evaluation of end-of-life products considering technology, economy and environment: A review.

Remanufacturing has been regarded as an environmentally friendly way to dispose of End-of-Life (EOL) products to like-new condition, which can effectively save resources, energy and greatly prolong the service life of products. After entering the remanufacturing system, EOL products are disassembled into individual parts that may have different failure types and degrees, thus not all of them are suitable for remanufacturing. Remanufacturability needs to be conducted to determine the feasibility of remanufacturing. Due to the products' structural complexity and customer demand uncertainty, many factors need to be considered when evaluating the remanufacturing feasibility of waste products. In this article, we take three pillars of sustainable development as decision factors and make a comprehensive literature review on the technical performance indicator (TPI), economic cost indicator (ECI) and environmental benefits indicator (EBI) of remanufacturability to emphasize the importance of remanufacturability. The purpose of this literature review is to conduct critical review on the current literature and establish a contemporary understanding of the status of remanufacturability study by assessing the advantages and disadvantages of existing methods in this field. The research results demonstrated that there was relatively a lack of research on technical feasibility assessment, more on economic and environmental assessments. Most of remanufacturability assessment approaches are comprehensive, considering multiple factors. This article summarizes the limitations of previous evaluation methods, proposes the challenges and future development trends. It is concluded that design for remanufacturing, finding it will be one of the hot topics in the future remanufacturing research, which will provide valuable insights for academia and industry.

Comparative study on preoperative localization techniques using microcoil and hookwire by propensity score matching.

BACKGROUND: The purpose of this study was to compare the efficacy and safety of two preoperative pulmonary nodule localization techniques using microcoil and hookwire. METHODS: A total of 307 patients with 324 pulmonary nodules were included in the study from March 2012 to October 2016 in two medical centers. Baseline data, positioning operation data, success rate, complications, surgery and pathological results were statistically analyzed. Complications were used as the dependent variables, whereas others were used as covariates for the propensity score matching of the two groups. Statistical analyses were performed to compare the success rate and complication rate of the matched groups. RESULTS: There were 218 lesions in the microcoil group and 106 nodules in the hookwire group. There were no significant differences in gender, age and the location of nodules between the two groups. The diameters of the nodules were smaller (8.2 ± 3.5 mm vs. 10.7 ± 4.3 mm) and solid nodules were fewer (11.5% vs. 26.4%) in the microcoil group. The complication rate of the two groups was not statistically significant. After propensity score matching, 71 patients in each group were successfully matched. We found that the success rate was higher (97.2% vs. 94.4%) and the incidence of complications was lower (31% vs. 15.5%) in the microcoil group. CONCLUSIONS: Both techniques have been shown to be effective in preoperative localization of tiny pulmonary nodules. The method of microcoil localization has more advantages in clinical application. KEY POINTS: Comparison of the efficacy and safety of two methods in preoperative pulmonary nodule localization in order to determine the optimal method.

Innovative Solution for Grasping Forceps Support Suction to Facilitate Uniportal Video-Assisted Thoracoscopic Surgery.

Uniportal video-assisted thoracoscopic surgery has been limited to the use of very few instruments, which but at least include energy device, grasping forceps, and suction. The last two instruments must be temporarily replaced by each other in response to situation. This step prolongs operative duration and potentially impairs the surgical efficiency. We describe a novel instrument design of grasping forceps support suction. Its continuous suction can clear the smoke and blood simultaneously to keep the operative field dry and clean, minimize the requirement to exchange surgical devices, and allow for optimized surgical workflow.

Electrocoagulation of wastewater using aluminum, iron, and magnesium electrodes.

Primary influent from a municipal wastewater treatment plant was electrochemically treated with sacrificial aluminum, iron, and magnesium electrodes. The influence of sacrificial anodes on the removal of chemical oxygen demand, total nitrogen, total phosphorus, and orthophosphate during sedimentation was investigated. Nitrification kinetics were assessed on treated supernatant and biogas production was monitored on settled solids. Changes in alkalinity, conductivity, and pH were also recorded. Aluminum and iron electrodes provided high rates of orthophosphate removal (i.e., 6.8 mg-P/mmol-e). Aluminum and iron electrodes also provided similar treatment to equivalent doses of alum and ferric salts (i.e., 38-68% chemical oxygen demand, 10-13% total nitrogen, and 67-93% total phosphorus). The estimated stochiometric ratio of aluminum and iron dosed to orthophosphate removed was approximately 1.3:1 and 4.1:1, respectively. Magnesium electrodes, on the other hand, removed orthophosphate at rates 8-9 times slower than aluminum and iron (i.e., 0.9 mg-P/mmol-e). Magnesium had to be dosed at a ratio of 13.5:1 orthophosphate for phosphorus removal. Orthophosphate removal by magnesium electrodes was most likely limited by electrolysis reactions responsible for increases in pH (i.e., 0.52 pH units/mmol-e). Magnesium electrodes removed 49% chemical oxygen demand and 21% total nitrogen at the high molar ratios required for orthophosphate removal.

One-step fabrication of nanosized LiFePO4/expanded graphite composites with a particle growth inhibitor and enhanced electrochemical performance of aqueous Li-ion capacitors.

It is reported that olivine-type lithium iron phosphate (LFP) for Li-ion batteries is one of the most widely utilized cathode materials, but its high-power applications are limited due to its intrinsically poor ion transfer rate and conductivity. Therefore, it is highly desired to fabricate LFP Li-ion capacitors (LICs) with high power performance and excellent cyclic reversibility, especially in safe, low cost and environmentally friendly aqueous electrolytes. Here, we fabricate LFP/expanded graphite (EG) nanocomposites by a one-step process, in which polyethylene glycol (PEG) is used as the particle growth inhibitor combined with vacuum infiltration of the LFP precursor into EG as a conductive sub-phase, and further investigate their high-power performance in aqueous LICs. Embedding spherical LFP nanoparticles with well-controlled size and agglomeration into the pores of EG and wrapping LFP nanoparticles by EG films contribute to the rapid electron and ion diffusion in LFP/EG composites, resulting in excellent cyclic reversibility and rate performance of LFP/EG composites. The aqueous LFP/EG//active carbon (AC) LICs were assembled in LiNO3 electrolytes with LFP/EG composites and AC as the positive and negative electrodes, respectively. The optimal LIC shows a power density of 2367.9 W kg-1 at an energy density of 6.5 W h kg-1, dramatically favorable rate characteristics and excellent cycle life with 82.1% capacitance retention of its primary capacitance at 2 A g-1 after 6000 cycles, markedly higher than those of the commercial LFP LIC. The presented aqueous LFP/EG//AC LICs with excellent electrochemical performance are expected to have broad high-power appliances that are cost-sensitive and highly secure.

Identification of genes associated with matrix metalloproteinases in invasive lung adenocarcinoma.

The aim of the present study was to identify genes with similar function to that of matrix metalloproteinases (MMPs) in invasive lung adenocarcinoma (AC) and to screen the transcription factors that regulate MMPs. The gene expression dataset GSE2514, including 20 invasive lung AC samples and 19 adjacent normal lung samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Genes with similar function to MMPs were identified by K-means clustering. Their correlations with MMPs were validated using Pearson correlation analysis. The expression of MMPs in lung cancer and normal tissues was evaluated by western blot analysis. Protein-protein interaction (PPI) network and transcriptional regulatory network analyses were performed with Retrieval of Interacting Genes and Database for Annotation, Visualization and Integrated Discovery, respectively. As a result, 269 DEGs were identified between invasive lung AC samples and normal lung samples, including 78 upregulated and 191 downregulated genes. Four MMPs (MMP1, MMP7, MMP9 and MMP12), which were upregulated in lung AC, were clustered into one group with other genes, including NAD(P)H quinone oxidoreductase 1, claudin 3 (CLDN3), S100 calcium-binding protein P, serine protease inhibitor Kazal type 1, collagen type XI α 1 chain, periostin and desmoplakin (DSP), following cluster analysis. Pearson correlation analysis further confirmed correlations between MMP9-CLDN3, MMP9-DSP and MMP12-DSP. PPI network analysis also indicated multiple interactions between MMPs-associated genes. Furthermore, MMPs were commonly regulated by CCAAT/enhancer binding protein α transcription factor. These findings may provide further insight into the mechanisms of MMPs in invasive lung AC.

Epoxy composites with functionalized molybdenum disulfide nanoplatelet additives.

As a typical layered inorganic analogue of graphene, molybdenum disulfide (MoS2) has gained intensive attention and become a research hotspot due to its unique two dimensional nanostructure and excellent properties. The enhancement in the thermal and mechanical properties of polymer/inorganic nanosheet composites depends strongly on their interfacial interaction. In this study, we exfoliated bulk MoS2 into nanosheets which were subsequently functionalized using 3-mercaptopropyltriethoxysilane. The functionalized MoS2 (f-MoS2) were dispersed in epoxy polymers at loading fractions of up to 1% by weight via ultrasonication and three roll mills. We characterized the tensile, fracture and adhesive properties of the composite and show that f-MoS2 nanoplatelets are highly effective at enhancing the mechanical properties of the epoxy at very low nanofiller loading fractions (0.1-0.7% by weight). Our results show the potential of functionalized 2D sheets of transition metal dichalcogenides as reinforcing additives in polymeric composites. The results indicate that the glass transition temperature increases significantly for the lower weight fraction composites, from 135 °C for the baseline (unfilled) epoxy to 146 °C at 0.7% f-MoS2 loading. The apparent shear strength at 120 °C increases significantly for the lower weight fraction composites, from 13.8 MPa for the baseline (unfilled) epoxy to 24.9 MPa at 0.7% f-MoS2 loading.

Chirality-Discriminated Conductivity of Metal-Amino Acid Biocoordination Polymer Nanowires.

Biocoordination polymer (BCP) nanowires are successfully constructed through self-assembly of chiral cysteine amino acids and Cd cations in solution. The varied chirality of cysteine is explored to demonstrate the difference of BCP nanowires in both morphology and structure. More interestingly and surprisingly, the electrical property measurement reveals that, although all Cd(II)/cysteine BCP nanowires behave as semiconductors, the conductivity of the Cd(II)/dl-cysteine nanowires is 4 times higher than that of the Cd(II)/l-cysteine or Cd(II)/d-cysteine ones. The origin of such chirality-discriminated characteristics registered in BCP nanowires is further elucidated by theoretical calculation. These findings demonstrate that the morphology, structure, and property of BCP nanostructures could be tuned by the chirality of the bridging ligands, which will shed light on the comprehension of chirality transcription as well as construction of chirality-regulated functional materials.

Hearing characteristics of cephalopods: modeling and environmental impact study.

Cephalopods (octopus, squid and cuttlefish) are some of the most intriguing molluscs, and they represent economically important commercial marine species for fisheries. Previous studies have shown that cephalopods are sensitive to underwater particle motion, especially at low frequencies in the order of 10 Hz. The present paper deals with quantitative modeling of the statocyst system in three cephalopod species: Octopus vulgaris, Sepia officinalis and Loligo vulgaris. The octopus's macula/statolith organ was modeled as a 2nd-order dynamic oscillator using parameter values estimated from scanning electron micrograph images. The modeling results agree reasonably well with experimental data (acceleration threshold) in the three cephalopod species. Insights made from quantitative modeling and simulating the particle motion sensing mechanism of cephalopods elucidated their underwater particle motion detection capabilities. Sensitivity to emerging environmental issues, such as low frequency noise caused by near-shore wind farms and increasing levels of carbon dioxide in the ocean, and sensitivity to sounds produced by impending landslides were investigated in octopus using the model.

[Freezing-thawing damages plasma membrane integrity of goat spermatozoa].

OBJECTIVE: To evaluate the plasma membrane integrity and morphology of fresh and frozen goat spermatozoa. METHODS: The ejaculates of three male goats were obtained by the artificial vagina method of collection and the rates of sperm abnormality and acrosome integrity were detected after freezing-thawing processing. The plasma membrane integrity of the fresh and frozen-thawed goat spermatozoa was evaluated with a combination of fluorescent probes, carboxyfluorescein diacetate and propidium iodide. RESULTS: The freezing-thawing process significantly influenced the viability and integrity of the spermatozoa ([74.43 +/- 13.78]% vs. [46.25 +/- 2.69]%; [64.26 +/- 7.03]% vs. [6.27 +/- 2.90]%, P < 0.01). The results showed differences in acrosome integrity rate between the fresh and frozen samples ([80.77 +/- 10.70]% vs. [58.42 +/- 18.05]% , P < 0.05). CONCLUSION: The freezing-thawing process significantly reduces sperm viability and acrosome integrity and seriously damages the plasma membrane integrity.