Identification of new AAV vectors with enhanced blood-brain barrier penetration efficiency via organ-on-a-chip.

To overcome limitations in the generalizability and efficiency of current AAV vectors, in this current study, we constructed an AAV variant library by the insertion of random heptapeptide sequences in the receptor-binding domain of the AAV9 capsid gene. We then applied a recently developed organ-on-a-chip in vitro model of the human blood-brain barrier (BBB) to iteratively enrich for variants that efficiently cross the BBB and transduce astrocyte cells. Through multiple rounds of screening, we obtained two candidate AAV variants, AAV-M6 and AAV-M8, which showed significantly higher BBB penetration efficiency than AAV9 or AAV-PHP.eB. Quantitative PCR (qPCR) assay showed that AAV-M6 could accumulate to a 5 times higher titer, while AAV-M8 reached a 3 times higher titer, than AAV-PHP.eB in the neural chamber of the model. The transduction assay further verified that the AAV-M6 candidate vector was able to infect HA-1800 cells after crossing the BBB, suggesting it could potentially transduce brain parenchymal cells after crossing the hCMEC/D3 layer at higher efficiency than AAV-PHP.eB. Molecular simulations suggested that the human receptor proteins, LY6D and M6PR, could bind the AAV-M6 heptapeptide insertion with high affinity. This study provides two promising candidate AAV vectors and demonstrates the use of this in vitro BBB model for scalable, high-throughput screening of gene therapies. These tools can drive investigations of the mechanisms underlying BBB permeability and the cell-type specificity of virus vectors.

Millijoule Terahertz Radiation from Laser Wakefields in Nonuniform Plasmas.

We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.

Optimized LNS-FAID of LDPC codes: a hybrid precision decoding approach for 50G-PON.

Efficient error correction in high-speed communication networks, such as the 50G passive optical network (50G-PON), is paramount. This Letter focuses on optimizing a layered non-surjective finite alphabet iterative decoder (LNS-FAID) for 50G-PON, with an emphasis on high-throughput and low-power consumption. We propose using a distinct lookup table (LUT) for each iteration to enhance decoding performance and lower error floors. Additionally, we improve the 2-bit LNS-FAID architecture by adding operational states and a sign backtracking (SBT) strategy. This paper also introduces a hybrid precision model that merges 3-bit and 2-bit LNS-FAIDs, which balances error correction with computational efficiency. Our simulation results show that these approaches significantly improve the performance of the LDPC code in 50G-PON.

The significant contribution of comammox bacteria to nitrification in a constructed wetland revealed by DNA-based stable isotope probing.

The discovery of Comammox bacteria (CMX) has changed our traditional concept towards nitrification, yet its role in constructed wetlands (CWs) remains unclear. This study investigated the contributions of CMX and two canonical ammonia-oxidizing microorganisms, ammonia-oxidizing bacteria (AOB) and archaea to nitrification in four regions (sediment, shoreside, adjacent soil, and water) of a typical CW using DNA-based stable isotope probing. The results revealed that CMX not only widely occurred in sediment and shoreside zones with high abundance (5.08 × 104 and 6.57 × 104 copies g-1 soil, respectively), but also actively participated in ammonia oxidation, achieving ammonia oxidation rates of 1.43 and 2.00 times that of AOB in sediment and shoreside, respectively. Phylogenetic analysis indicated that N. nitrosa was the dominant and active CMX species. These findings uncovered the crucial role of CMX in nitrification of sediment and shoreside, providing a new insight into nitrogen cycle of constructed wetlands.

The driving factors and spatial evolution of industrial water pollution governance efficiency in the Yangtze River Delta urban agglomeration in China.

In order to explore the effective path to improve the efficiency of industrial water pollution governance efficiency (WGE), this study takes 27 prefecture-level cities in the Yangtze River Delta urban agglomeration in China as the research object, measures WGE through the improved SBM model, and tests the impact of WGE drivers using the spatial Durbin model (SDM). The study found that environmental pollution governance investment (EPGI) is positively correlated with WGE, and industrial agglomeration status (IAS) has inhibitory effects on the improvement of WGE. By testing IAS2, it was determined that the impact of IAS on WGE has a "U"-shaped relationship. The direct impact of EPGI on WGE is 0.5016, and the indirect impact on WGE is 0.6428; the direct impact of IAS on WGE is -0.3036, and the indirect impact on WGE is -0.5158. Among the other tested impact drivers, per capita GDP (PCG), industrial structure (IS), and level of technological innovation (TIL) are positively correlated with the dependent variable WGE, while energy consumption intensity (ECI), environmental regulation intensity (ERI), and degree of openness to foreign investment (FIR) are negatively correlated with the dependent variable WGE. In addition to the impact of the aforementioned main drivers, IAS and EPGI, these six drivers also largely influence and determine the final impact on WGE.

Exploring the mechanism of aloe-emodin in the treatment of liver cancer through network pharmacology and cell experiments.

Objective: Aloe-emodin (AE) is an anthraquinone compound extracted from the rhizome of the natural plant rhubarb. Initially, it was shown that AE exerts an anti-inflammatory effect. Further studies revealed its antitumor activity against various types of cancer. However, the mechanisms underlying these properties remain unclear. Based on network pharmacology and molecular docking, this study investigated the molecular mechanism of AE in the treatment of hepatocellular carcinoma (HCC), and evaluated its therapeutic effect through in vitro experiments. Methods: CTD, Pharmmapper, SuperPred and TargetNet were the databases to obtain potential drug-related targets. DisGenet, GeneCards, OMIM and TTD were used to identify potential disease-related targets. Intersection genes for drugs and diseases were obtained through the Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of intersecting genes were conducted by the website of Bioinformatics. Intersection genes were introduced into STRING to construct a protein-protein interaction network, while the Cytoscape3.9.1 software was used to visualize and analyze the core targets. AutoDock4.2.6 was utilized to achieve molecular docking between drug and core targets. In vitro experiments investigated the therapeutic effects and related mechanisms of AE. Results: 63 overlapped genes were obtained and GO analysis generated 3,646 entries by these 63 intersecting genes. KEGG analysis mainly involved apoptosis, proteoglycans in cancer, TNF signaling pathway, TP53 signaling pathway, PI3K-AKT signaling pathway, etc. AKT1, EGFR, ESR1, TP53, and SRC have been identified as core targets because the binding energies of them between aloe-emodin were less than -5 kcal/Mol.The mRNA and protein expression, prognosis, mutation status, and immune infiltration related to core targets were further revealed. The involvement of AKT1 and EGFR, as well as the key target of the PI3K-AKT signaling pathway, indicated the importance of this signaling pathway in the treatment of HCC using AE. The results of the Cell Counting Kit-8 assay and flow analysis demonstrated the therapeutic effect of AE. The downregulation of EGFR, PI3KR1, AKT1, and BCL2 in mRNA expression and PI3KR1, AKT,p-AKT in protein expression confirmed our hypothesis. Conclusion: Based on network pharmacology and molecular docking, our study initially showed that AE exerted a therapeutic effect on HCC by modulating multiple signaling pathways. Various analyses confirmed the antiproliferative activity and pro-apoptotic effect of AE on HCC through the PI3K-AKT signaling pathway. This study revealed the therapeutic mechanism of AE in the treatment of HCC through a novel approach, providing a theoretical basis for the clinical application of AE.

The mechanism of vitamin D3 in preventing colorectal cancer through network pharmacology.

Objective: Colorectal cancer (CRC) is a common cancer that cannot be detected at an early stage and is a major challenge in oncology research. Studies have shown that vitamin D3 has some anti-cancer and preventive effects on colorectal cancer, but the exact anti-cancer mechanism is not clear. We applied the relevant research methods of network pharmacology to speculate and validate the possible potential pharmacological mechanisms of vitamin D3 for the prevention of colorectal cancer, and to provide more theoretical support for the clinical anticancer effects of vitamin D3. Methods: The relevant targets for vitamin D3 and CRC were obtained from the database of drug and disease targets, respectively. The target of vitamin D3 and the target of colorectal cancer were taken to intersect to obtain common targets. Then, the PPI network was constructed. In addition, the pathways of drug-disease interactions were predicted by GO and KEGG enrichment analysis. Finally, the obtained results were verified to ensure the reliability of the experiments. Results: 51 targets of vitamin D3 for the prevention of colorectal cancer were obtained. The 10 core targets were obtained from the PPI network. The 10 core targets include: ALB, SRC, MMP9, PPARG, HSP90AA1, IGF1, EGFR, MAPK1, MAP2K1 and IGF1R. The core targets were further validated by molecular docking and animal experiments. The results suggest that vitamin D3 plays a key role in the prevention of CRC through core targets, PI3K-Akt pathway, HIF-1 pathway, and FoxO pathway. Conclusion: This study will provide more theoretical support for vitamin D3 to reduce the incidence of CRC and is important to explore more pharmacological effects of vitamin D3.

Analysis for discharge within 2 days after thoracoscopic anatomic lung cancer surgery.

OBJECTIVES: The risk and beneficial factors of early discharge after thoracoscopic anatomic lung cancer surgery are unknown, and this study aims to investigate predictors and associated 30-day readmission for early discharge. METHODS: We performed a single-center retrospective analysis of 10,834 consecutive patients who underwent thoracoscopic anatomic lung cancer surgery. Two groups were determined based on discharge date: "discharged by postoperative Day 2" and "discharged after postoperative Day 2." Univariable and multivariable analysis were conducted to identify predictors for discharge. Using propensity score matching (PSM) to compare 30-day readmission rate between two cohorts. RESULTS: A total of 1911 patients were discharged by postoperative Day 2. Multivariable analysis identified older age (odds ratio (OR) = 1.014, p < 0.001), male sex (OR = 1.183, p = 0.003), larger tumor size (OR = 1.248, p < 0.001), pleural adhesions (OR = 1.638, p = 0.043), lymph nodes calcification (OR = 1.443, p = 0.009), advanced clinical T stage (vs. T < 2, OR = 1.470, p = 0.010), lobectomy resection (vs. segmentectomy resection, OR = 2.145, p < 0.001) and prolonged operative time (OR = 1.011, p < 0.001) as independent risk factors for discharge after postoperative Day 2. Three adjustable variables including higher FEV1 /FVC (OR = 0.989, p = 0.001), general anesthesia (GA) plus thoracic paravertebral blockade (vs. GA alone, OR = 0.823, p = 0.006) and uni-portal thoracoscopic surgery (vs. multi-portal, OR = 0.349, p < 0.001) were associated with a decreased likelihood of discharge after postoperative Day 2. Before and after a 1:1 PSM, discharged by postoperative Day 2 did not increase the risk of 30-day readmission compared to counterparts. CONCLUSIONS: Carefully selected patients can be safely discharged within 2 days after thoracoscopic anatomic lung cancer surgery. Three modifiable variables may be favorable for promoting discharge by postoperative Day 2.

Exploring the mechanism of curcumin in the treatment of colon cancer based on network pharmacology and molecular docking.

Objective: Curcumin is a plant polyphenol extracted from the Chinese herb turmeric. It was found that curcumin has good anti-cancer properties in a variety of cancers, but the exact mechanism is not clear. Based on the network pharmacology and molecular docking to deeply investigate the molecular mechanism of curcumin for the treatment of colon cancer, it provides a new research direction for the treatment of colon cancer. Methods: Curcumin-related targets were collected using PharmMapper, SwissTargetPrediction, Targetnet and SuperPred. Colon cancer related targets were obtained using OMIM, DisGeNET, GeneCards and GEO databases. Drug-disease intersection targets were obtained via Venny 2.1.0. GO and KEGG enrichment analysis of drug-disease common targets were performed using DAVID. Construct PPI network graphs of intersecting targets using STRING database as well as Cytoscape 3.9.0 and filter core targets. Molecular docking via AutoDockTools 1.5.7. The core targets were further analyzed by GEPIA, HPA, cBioPortal and TIMER databases. Results: A total of 73 potential targets of curcumin for the treatment of colon cancer were obtained. GO function enrichment analysis yielded 256 entries, including BP(Biological Progress):166, CC(celluar component):36 and MF(Molecular Function):54. The KEGG pathway enrichment analysis yielded 34 signaling pathways, mainly involved in Metabolic pathways, Nucleotide metabolism, Nitrogen metabolism, Drug metabolism - other enzymes, Pathways in cancer,PI3K-Akt signaling pathway, etc. CDK2, HSP90AA1, AURKB, CCNA2, TYMS, CHEK1, AURKA, DNMT1, TOP2A, and TK1 were identified as core targets by Cytoscape 3.9.0. Molecular docking results showed that the binding energies of curcumin to the core targets were all less than 0 kJ-mol-1, suggesting that curcumin binds spontaneously to the core targets. These results were further validated in terms of mRNA expression levels, protein expression levels and immune infiltration. Conclusion: Based on network pharmacology and molecular docking initially revealed that curcumin exerts its therapeutic effects on colon cancer with multi-target, multi-pathway. Curcumin may exert anticancer effects by binding to core targets. Curcumin may interfere with colon cancer cell proliferation and apoptosis by regulating signal transduction pathways such as PI3K-Akt signaling pathway,IL-17 signaling pathway, Cell cycle. This will deepen and enrich our understanding of the potential mechanism of curcumin against colon cancer and provide a theoretical basis for subsequent studies.

The location of visceral pleural invasion in stage IB patients with non-small cell lung cancer: Comparison and prognosis.

OBJECTIVES: Recently, early-stage lung cancer has been drawing more attention, especially in screening and treatment. Visceral pleural invasion in stage IB cancer is considered as risk factor for poor prognosis. Herein, we aimed to study the distinction between the different locations of visceral pleural invasion. METHODS: In this retrospective cohort study, we summarized 58,242 patient cases that underwent surgery from 2015 to 2018 at Shanghai Chest Hospital. Of those patients, 389 met the inclusion criteria. Patients with PL3 pleural invasion were excluded. The patients were dichotomized into the interlobar pleural and peripheral pleural groups. The outcomes measured were overall survival (OS) and recurrence-free survival (RFS) rates. RESULTS: According to the initial analysis, the baseline characteristics of the two groups were largely balanced. In multivariate Cox analyses, we found that the location of visceral pleural invasion was not a risk factor for prognosis in the overall population (RFS: P = 0.726, OS: P = 0.599). However, we discovered that relative to patients with peripheral pleura invasion, those with interlobar pleura invasion, PL1 invasion, lesions with greater than 3 cm solid components, and those who underwent segmentectomy had a compromised prognosis. Additionally, tumors larger than 3 cm in size with interlobar pleura invasion showed poor prognosis in patients who underwent postoperative chemotherapy. CONCLUSIONS: In most cases, the location of tumor invasion did not worsen the postoperative prognosis of stage IB non-small cell lung cancer patients with visceral pleural invasion. However, interlobar pleural invasion still had some potential risks compared to that of peripheral pleural invasion.

Vitamin D3 promotes gastric cancer cell autophagy by mediating p53/AMPK/mTOR signaling.

Objective: Vitamin D3 has the general properties of a lipid-soluble vitamin, but is also an active steroid hormone that can regulate the proliferation, apoptosis and differentiation of many tumor cells, and exerts anticancer activity against numerous malignancies. However, the mechanism underlying the effects of vitamin D3 on tumors is not fully understood. Here, we used network pharmacology and in vitro experimental approaches to explore the mechanism of vitamin D3 activity in the context of gastric cancer. Methods: The Targetnet, SuperPred, SwissTargetPrediction, and PharmMapper databases were screened for potential drug-related targets, while we used data from the PharmGKB, Drugbank, OMIM, DisGeNET, CTD, and GeneCards databases to identify potential targets associated with gastric cancer. Disease-drug crossover genes were obtained by constructing Venn diagrams. Gene ontology and Kyoto Encyclopedia of Genomes (KEGG) enrichment analyses of crossover genes were conducted and STRING was used to generate protein interaction networks and identify core targets. CCK-8 experiments were performed and apoptosis detected to assess the effect of vitamin D3 on gastric cancer cells. Western blotting was applied to detect p53/AMPK/mTOR signaling, as well as autophagy-, cell cycle-, and apoptosis-related proteins. Results: A total of 485 targets of vitamin D3 activity were obtained and 1200 gastric cancer disease-related targets discovered. Further, 60 potential targets for vitamin D3 in gastric cancer treatment were identified. KEGG analysis indicated that potential targets were mainly involved in the cell cycle, HIF-1 signaling, and the AMPK pathway, among other pathways. These findings were validated using cellular experiments, which demonstrated that the viability of AGS and SGC-7901 cells was impeded by vitamin D3. Further, vitamin D3 promoted apoptosis and inhibited the cell cycle in those cell lines, as well as activating the p53/AMPK/mTOR pathway, which promotes autophagy and inhibits tumor development. Conclusion: Our network pharmacological analyses provide preliminarily data supporting a role for vitamin D3 in promoting autophagy and apoptosis in gastric cancer cells, and in activating the p53/AMPK/mTOR pathway, which inhibits gastric cancer cell proliferation. Our findings demonstrate the molecular mechanism underlying the effect of vitamin D3 in cure of gastric cancer.

Advances in the study of nicotinamide adenine dinucleotide phosphate oxidase in myocardial remodeling.

Myocardial remodeling is a key pathophysiological basis of heart failure, which seriously threatens human health and causes a severe economic burden worldwide. During chronic stress, the heart undergoes myocardial remodeling, mainly manifested by cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, chamber enlargement, and cardiac dysfunction. The NADPH oxidase family (NOXs) are multisubunit transmembrane enzyme complexes involved in the generation of redox signals. Studies have shown that NOXs are highly expressed in the heart and are involved in the pathological development process of myocardial remodeling, which influences the development of heart failure. This review summarizes the progress of research on the pathophysiological processes related to the regulation of myocardial remodeling by NOXs, suggesting that NOXs-dependent regulatory mechanisms of myocardial remodeling are promising new therapeutic targets for the treatment of heart failure.

LY6E protein facilitates adeno-associated virus crossing in a biomimetic chip model of the human blood-brain barrier.

The blood-brain barrier (BBB) controls chemical access to the brain and maintains fluid homeostasis, but in vitro models accurately simulating the physiological characteristics of the BBB are lacking. Here, we describe a simple and reproducible biomimetic chip-based model of the human BBB. In this bilayer co-culture, astrocytes and brain microvascular endothelial cells (BMECs) are respectively seeded in upper and lower chambers separated by a semi-permeable membrane, with fluid shear force provided by a precision tilt shaker. Evaluation of barrier crossing by fluorescein sodium, 40 kDa or 70 kDa FITC-dextran, or adeno-associated virus (AAV) particles demonstrates that this bilayer model provides similar or greater barrier function than Transwell assays. Comparison of AAV serotypes indicated that AAV-PHP.eB can cross the human BBB in vitro, and at higher efficiency than AAV9. Additionally, RNAi knockdown and virus capsid protein binding assays show that AAV-PHP.eB delivery is facilitated by receptor protein lymphocyte antigen-6E (LY6E) in humans. This in vitro model system uses a miniaturized chip to enable high-throughput investigations of AAV crossing efficiency in the BBB, and provides strong initial evidence that human LY6E mediates AAV-PHP.eB crossing the BBB.

CRC-Aided Adaptive BP Decoding of PAC Codes.

Although long polar codes with successive cancellation decoding can asymptotically achieve channel capacity, the performance of short blocklength polar codes is far from optimal. Recently, Arikan proposed employing a convolutional pre-transformation before the polarization network, called polarization-adjusted convolutional (PAC) codes. In this paper, we focus on improving the performance of short PAC codes concatenated with a cyclic redundancy check (CRC) outer code, CRC-PAC codes, since error detection capability is essential in practical applications, such as the polar coding scheme for the control channel. We propose an enhanced adaptive belief propagation (ABP) decoding algorithm with the assistance of CRC bits for PAC codes. We also derive joint parity-check matrices of CRC-PAC codes suitable for iterative BP decoding. The proposed CRC-aided ABP (CA-ABP) decoding can effectively improve error performance when partial CRC bits are used in the decoding. Meanwhile, the error detection ability can still be guaranteed by the remaining CRC bits and adaptive decoding parameters. Moreover, compared with the conventional CRC-aided list (CA-List) decoding, our proposed scheme can significantly reduce computational complexity, to achieve a better trade-off between the performance and complexity for short PAC codes.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease.

Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Methods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.

The outcomes of margin status after sleeve lobectomy for patients of non-small cell lung cancer.

BACKGROUND: Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy. METHODS: In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence-free survival (RFS). We performed a subgroup analysis to further our investigation. RESULTS: After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence-free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status. CONCLUSION: In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status.

Reconstruction of the trachea and carina: Surgical reconstruction, autologous tissue transplantation, allograft transplantation, and bioengineering.

There have been significant advancements in medical techniques in the present epoch, with the emergence of some novel operative substitutes. However, the treatment of tracheal defects still faces tremendous challenges and there is, as yet, no consensus on tracheal and carinal reconstruction. In addition, surgical outcomes vary in different individuals, which results in an ambiguous future for tracheal surgery. Although transplantation was once an effective and promising method, it is limited by a shortage of donors and immune rejection. The development of bioengineering has provided an alternative for the treatment of tracheal defects, but this discipline is full of ethical controversy and hindered by limited cognition in this area. Meanwhile, progression of this technique is blocked by a deficiency in ideal materials. The trachea together with the carina is still the last unpaired organ in thoracic surgery and propososal of a favorable scheme to remove this dilemma is urgently required. In this review, four main tracheal reconstruction methods, especially surgical techniques, are evaluated, and a thorough interpretation conducted.

Expression profiles and prognostic values of BolA family members in ovarian cancer.

BACKGROUND: The BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. However, there was less known about its role in ovarian cancer. METHODS: In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BolA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan-Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of BOLA proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying BolA family members' involvement in OC by using gene set enrichment analysis. RESULTS: The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than in normal ovarian tissues. Dysregulated mRNA expressions of three BolA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BolA family members in ovarian cancer. GO analysis indicated that BolA family members might regulate the function of metal ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BolA family members were mainly associated with oxidative phosphorylation, proteasome, protein export, and glutathione metabolism in ovarian cancer. CONCLUSION: In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for ovarian cancer.

A microfluidic-integrated lateral flow recombinase polymerase amplification (MI-IF-RPA) assay for rapid COVID-19 detection.

The COVID-19 pandemic, caused by SARS-CoV-2, currently poses an urgent global medical crisis for which there remains a lack of affordable point-of-care testing (POCT). In particular, resource-limited areas need simple and easily disseminated testing solutions to manage the outbreak. In this work, a microfluidic-integrated lateral flow recombinase polymerase amplification (MI-IF-RPA) assay was developed for rapid and sensitive detection of SARS-CoV-2, which integrates the reverse transcription recombinase polymerase amplification (RT-RPA) and a universal lateral flow (LF) dipstick detection system into a single microfluidic chip. The single-chamber RT-RPA reaction components are mixed with running buffer, and then delivered to the LF detection strips for biotin- and FAM-labelled amplified analyte sequences, which can provide easily interpreted positive or negative results. Testing requires only a simple nucleic acid extraction and loading, then incubation to obtain results, approximately 30 minutes in total. SARS-CoV-2 armored RNA particles were used to validate the MI-IF-RPA system, which showed a limit of detection of 1 copy per µL, or 30 copies per sample. Chip performance was further evaluated using clinically diagnosed cases of COVID-19 and revealed a sensitivity of 97% and specificity of 100%, highly comparable to current reverse transcription-polymerase chain reaction (RT-PCR)-based diagnostic assays. This MI-IF-RPA assay is portable and comprises affordable materials, enabling mass production and decreased risk of contamination. Without the need for specialized instrumentation and training, MI-IF-RPA assay can be used as a complement to RT-PCR for low-cost COVID-19 screening in resource-limited areas.

Co-culturing polarized M2 Thp-1-derived macrophages enhance stemness of lung adenocarcinoma A549 cells.

BACKGROUND: The tumor microenvironment (TME) is highly associated with cancer stem cells, and affects tumor initiation, progression, and metastasis. This study aimed to explore the underlying molecular mechanism of induction of A549 cancer cell stemness by THP-1-derived macrophages. METHOD: The Hedgehog inhibitor (Vismodegib), Notch inhibitor Gamma Secretase Inhibitor (GSI), and Signal Transducer and Activator of Transcription 3 (STAT3) inhibitor Cucurbitacin I (JSI-124) were added separately into the co-culture system of A549 cancer cell with THP-1-derived macrophages. Cell Counting Kit-8 (CCK-8) assay and the Cell-IQ continuous surveillance system were used to examine the cell growth and morphological changes of A549 cells. The messenger ribonucleic acid (mRNA) and protein expression levels of stem cell markers were respectively analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, and the activity of Acetaldehyde dehydrogenase (ALDH) enzyme was assessed by flow cytometry analysis. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR assays were performed to evaluate the activation and differentiation of macrophages. RESULTS: Results showed that the proliferation and stemness of A549 cells were significantly enhanced by co-culturing with THP-1-derived macrophages. The expression levels of Transforming growth factor-ß (TGF-ß) and Interleukin-6 (IL-6) in macrophages were notably increased after co-culturing with A549 cells. Meanwhile, co-culturing with A549 cells induced the polarization of macrophages towards the M2 phenotype. Moreover, the inhibitors could reduce the proliferation and stemness of the co-culture system, and decrease the expression of TGF-ß and IL-6. CONCLUSIONS: These results suggested that co-culturing A549 cells with THP-1-derived macrophages could induce the stemness of A549 cells via multiple pro-tumorigenic pathways. Thus, inhibition of the interaction between macrophages and lung cancer stem cells may be a viable target for lung cancer treatment in the future.