[Research Progress of the Effect of Mediterranean Diet on the Correlation of Lung Cancer].

Lung cancer is one of the top 10 causes of death in the world today, and it is a great concern worldwide for its high mortality rate. Currently, the researchers are digging into various factors influencing the occurrence and development of lung cancer in order to increase the odds for curing lung cancer, improve the prognosis of lung cancer patients as well as reduce its morbidity. The Mediterranean diet (MD) is a special dietary structure that is based on eating vegetables, fruits, coarse grains, legumes and low-fat fish, which have anti-inflammatory, antioxidant and lipid-lowering effects. Recent studies have revealed that the MD may prevent lung cancer occurrence to some extent and inhibit its development. The purpose of this paper is to summarize and analytically discuss the effects of the MD on the oncogenesis and development of lung cancer through a review of the relevant literatures, thus to provide references for MD to prevent and treat lung cancer.
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Corrigendum: Heterologous vaccination with inactivated vaccine and mRNA vaccine augments antibodies against both spike and nucleocapsid proteins of SARS-CoV-2: a local study in Macao.

[This corrects the article DOI: 10.3389/fimmu.2023.1131985.].

Development of a Large-Range XY-Compliant Micropositioning Stage with Laser-Based Sensing and Active Disturbance Rejection Control.

This paper presents a novel design and control strategies for a parallel two degrees-of-freedom (DOF) flexure-based micropositioning stage for large-range manipulation applications. The motion-guiding beam utilizes a compound hybrid compliant prismatic joint (CHCPJ) composed of corrugated and leaf flexures, ensuring increased compliance in primary directions and optimal stress distribution with minimal longitudinal length. Additionally, a four-beam parallelogram compliant prismatic joint (4BPCPJ) is used to improve the motion decoupling performance by increasing the off-axis to primary stiffness ratio. The mechanism's output compliance and dynamic characteristics are analyzed using the compliance matrix method and Lagrange approach, respectively. The accuracy of the analysis is verified through finite element analysis (FEA) simulation. In order to examine the mechanism performance, a laser interferometer-based experimental setup is established. In addition, a linear active disturbance rejection control (LADRC) is developed to enhance the motion quality. Experimental results illustrate that the mechanism has the capability to provide a range of 2.5 mm and a resolution of 0.4 µm in both the X and Y axes. Furthermore, the developed stage has improved trajectory tracking and disturbance rejection capabilities.

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway.

Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.

Eriocitrin inhibits epithelial-mesenchymal transformation (EMT) in lung adenocarcinoma cells via triggering ferroptosis.

INTRODUCTION: Lung adenocarcinoma (LUAD) is the most prevalent pathological subtype of non-small cell lung cancer (NSCLC), characterized by a high propensity for relapse and metastasis due to epithelial-mesenchymal transition (EMT) of cancer cells. Ferroptosis, a newly discovered regulated cell death modality, is interconnected with the EMT process in certain cancers. Eriocitrin, a natural flavonoid compound, exerts anti-inflammatory and anticancer effects. OBJECTIVES: The aim of this study is to investigate the potential inhibitory effect of eriocitrin on lung adenocarcinoma metastasis and explore whether its underlying mechanism involves ferroptosis induction in cancer cells. METHODS: The CCK8 assay and wound healing assay and transwell were conducted to determine the cell viability and migration ability of A549 and H1299 cells, respectively. EMT process was assessed by western blot and RT-PCR to detect protein and mRNA levels of EMT markers. ROS and cell iron were measured to determine ferroptosis level. RESULTS: Eriocitrin treatment significantly inhibited cell viability and migration ability in a concentration-dependent manner. Furthermore, eriocitrin administration for 24 hours resulted in enhanced expression of E-cadherin, while downregulating vimentin, N-cadherin and snail expression, indicating marked repression of the EMT process. Additionally, eriocitrin significantly induced ferroptosis in A549 and H1299 cells, as evidenced by increased ROS levels, downregulation of Nrf-2, SLC7A11 and GPX4 expression, and enhanced cellular iron accumulation. Moreover, pretreatment with the ferroptosis inhibitor ferrostatin-1 effectively abrogated the inhibitory effects of eriocitrin on EMT. CONCLUSIONS: Our findings further support the anti-cancer properties of eriocitrin, as evidenced by its ability to inhibit the EMT process in LUAD cells, which is partially mediated through induction of ferroptosis in cancer cells.

Systematic analysis of histone acetylation regulators across human cancers.

BACKGROUND: Histone acetylation (HA) is an important and common epigenetic pathway, which could be hijacked by tumor cells during carcinogenesis and cancer progression. However, the important role of HA across human cancers remains elusive. METHODS: In this study, we performed a comprehensive analysis at multiple levels, aiming to systematically describe the molecular characteristics and clinical relevance of HA regulators in more than 10000 tumor samples representing 33 cancer types. RESULTS: We found a highly heterogeneous genetic alteration landscape of HA regulators across different human cancer types. CNV alteration may be one of the major mechanisms leading to the expression perturbations in HA regulators. Furthermore, expression perturbations of HA regulators correlated with the activity of multiple hallmark oncogenic pathways. HA regulators were found to be potentially useful for the prognostic stratification of kidney renal clear cell carcinoma (KIRC). Additionally, we identified HDAC3 as a potential oncogene in lung adenocarcinoma (LUAD). CONCLUSION: Overall, our results highlights the importance of HA regulators in cancer development, which may contribute to the development of clinical strategies for cancer treatment.

Heterologous vaccination with inactivated vaccine and mRNA vaccine augments antibodies against both spike and nucleocapsid proteins of SARS-CoV-2: a local study in Macao.

The mRNA vaccines (RVs) can reduce the severity and mortality of severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, almost only the inactivated vaccines (IVs) but no RVs had been used in mainland China until most recently, and the relaxing of its anti-pandemic strategies in December 2022 increased concerns about new outbreaks. In comparison, many of the citizens in Macao Special Administrative Region of China received three doses of IV (3IV) or RV (3RV), or 2 doses of IV plus one booster of RV (2IV+1RV). By the end of 2022, we recruited 147 participants with various vaccinations in Macao and detected antibodies (Abs) against the spike (S) protein and nucleocapsid (N) protein of the virus as well as neutralizing antibodies (NAb) in their serum. We observed that the level of anti-S Ab or NAb was similarly high with both 3RV and 2IV+1RV but lower with 3IV. In contrast, the level of anti-N Ab was the highest with 3IV like that in convalescents, intermediate with 2IV+1RV, and the lowest with 3RV. Whereas no significant differences in the basal levels of cytokines related to T-cell activation were observed among the various vaccination groups before and after the boosters. No vaccinees reported severe adverse events. Since Macao took one of the most stringent non-pharmaceutical interventions in the world, this study possesses much higher confidence in the vaccination results than many other studies from highly infected regions. Our findings suggest that the heterologous vaccination 2IV+1RV outperforms the homologous vaccinations 3IV and 3RV as it induces not only anti-S Ab (to the level as with 3RV) but also anti-N antibodies (via the IV). It combines the advantages of both RV (to block the viral entry) and IV (to also intervene the subsequent pathological processes such as intracellular viral replication and interference with the signal transduction and hence the biological functions of host cells).

Uridine Alleviates Sepsis-Induced Acute Lung Injury by Inhibiting Ferroptosis of Macrophage.

Uridine metabolism is extensively reported to be involved in combating oxidative stress. Redox-imbalance-mediated ferroptosis plays a pivotal role in sepsis-induced acute lung injury (ALI). This study aims to explore the role of uridine metabolism in sepsis-induced ALI and the regulatory mechanism of uridine in ferroptosis. The Gene Expression Omnibus (GEO) datasets including lung tissues in lipopolysaccharides (LPS) -induced ALI model or human blood sample of sepsis were collected. In vivo and vitro, LPS was injected into mice or administered to THP-1 cells to generate sepsis or inflammatory models. We identified that uridine phosphorylase 1 (UPP1) was upregulated in lung tissues and septic blood samples and uridine significantly alleviated lung injury, inflammation, tissue iron level and lipid peroxidation. Nonetheless, the expression of ferroptosis biomarkers, including SLC7A11, GPX4 and HO-1, were upregulated, while lipid synthesis gene (ACSL4) expression was greatly restricted by uridine supplementation. Moreover, pretreatment of ferroptosis inducer (Erastin or Era) weakened while inhibitor (Ferrostatin-1 or Fer-1) strengthened the protective effects of uridine. Mechanistically, uridine inhibited macrophage ferroptosis by activating Nrf2 signaling pathway. In conclusion, uridine metabolism dysregulation is a novel accelerator for sepsis-induced ALI and uridine supplementation may offer a potential avenue for ameliorating sepsis-induced ALI by suppressing ferroptosis.

Comprehensive analysis reveals the potential value of inflammatory response genes in the prognosis, immunity, and drug sensitivity of lung adenocarcinoma.

BACKGROUND: Although the relationship between inflammatory response and tumor has been gradually recognized, the potential implications of of inflammatory response genes in lung adenocarcinoma (LUAD) remains poorly investigated. METHODS: RNA sequencing and clinical data were obtained from multiple independent datasets (GSE29013, GSE30219, GSE31210, GSE37745, GSE42127, GSE50081, GSE68465, GSE72094, TCGA and GTEx). Unsupervised clustering analysis was used to identify different tumor subtypes, and LASSO and Cox regression analysis were applied to construct a novel scoring tool. We employed multiple algorithms (ssGSEA, CIBERSORT, MCP counter, and ESTIMATE) to better characterize the LUAD tumor microenvironment (TME) and immune landscapes. GSVA and Metascape analysis were performed to investigate the biological processes and pathway activity. Furthermore, 'pRRophetic' R package was used to evaluate the half inhibitory concentration (IC50) of each sample to infer drug sensitivity. RESULTS: We identified three distinct tumor subtypes, which were related to different clinical outcomes, biological pathways, and immune characteristics. A scoring tool called inflammatory response gene score (IRGS) was established and well validated in multiple independent cohorts, which could well divide patients into two subgroups with significantly different prognosis. High IRGS patients, characterized by increased genomic variants and mutation burden, presented a worse prognosis, and might show a more favorable response to immunotherapy and chemotherapy. Additionally, based on the cross-talk between TNM stage, IRGS and patients clinical outcomes, we redefined the LUAD stage, which was called 'IRGS-Stage'. The novel staging system could distinguish patients with different prognosis, with better predictive ability than the conventional TNM staging. CONCLUSIONS: Inflammatory response genes present important potential value in the prognosis, immunity and drug sensitivity of LUAD. The proposed IRGS and IRGS-Stage may be promising biomarkers for estimating clinical outcomes in LUAD patients.

Puerarin: A protective drug against ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) is a pathological process that occurs in numerous organs throughout the human body and is frequently associated with severe cellular damage and death. Puerarin is an isoflavone compound extracted from the root of Pueraria lobata and has pharmacological effects such as dilating cerebral vessels and anti-free radical generation in cerebral ischemic tissues. With the deepening of experimental research and clinical research on puerarin, it has been found that puerarin has a protective effect on ischemia-reperfusion injury (IRI) of the heart, brain, spinal cord, lung, intestine and other organs. In summary, puerarin has a vast range of pharmacological effects and significant protective effects, and it also has obvious advantages in the clinical protection of patients with organ IRI. With the deepening of experimental pharmacological research and clinical research, it is expected to be an effective drug for IRI treatment. In this review, we summarize the current knowledge of the protective effect of puerarin on I/R organ injury and its possible underlying molecular mechanisms.

Second-stage cesarean delivery and preterm birth in subsequent pregnancy: A large multi-institutional cohort study.

OBJECTIVE: To estimate the risk of preterm birth associated with mode of delivery in a previous pregnancy. PATIENTS AND METHODS: This was a multicenter retrospective cohort study. Women who had two consecutive deliveries in the participating hospitals between January 2012 and January 2022 were included in this study. They were divided into three groups according to the mode of delivery in a previous pregnancy: vaginal birth (group A), cesarean section before the second stage of labor (group B), and second stage cesarean section (group C). Data were extracted from the medical records. The primary outcome was the risk of spontaneous preterm birth in the subsequent pregnancy. The secondary outcomes were the risk of early spontaneous preterm birth (< 34 weeks) and the medically indicated preterm birth in the subsequent pregnancy. The logistic regression was employed to estimate odds and adjust for confounders. RESULTS: 18,253 women were included. Among them, 10,951 women were in group A, 5111 women in group B, and 2191 women in group C. The rates of spontaneous preterm birth in groups A, B, and C were 5.5%, 7.3%, and 15.1%, respectively. The rates of early spontaneous preterm birth in groups A, B, and C were 2.3%, 3.4%, and 8.2%, respectively. When compared with vaginal birth, second-stage cesarean section significantly increased the risk of spontaneous preterm birth (aOR, 3.23; 95% CI, 2.02-5.17; P = 0.003) and early spontaneous preterm birth (aOR, 3.59; 95% CI, 2.01-5.19; P <0.001) in the subsequent pregnancy. The rates of medically indicated preterm birth in groups A, B, and C were 2.3%, 2.8%, and 2.2%, respectively. There was no statistical difference across the three groups. CONCLUSION: History of cesarean section at full dilation is independently associated with an increased risk of spontaneous preterm birth in the subsequent pregnancy.

Oncological Safety of Diagnostic Hysteroscopy for Apparent Early-Stage Type II Endometrial Cancer: A Multicenter Retrospective Cohort Study.

Objective: To study the oncological safety of diagnostic hysteroscopy for women with apparent early-stage type II endometrial cancer. Patients and Methods: A total of 429 women with presumed early-stage type II endometrial cancer were included. The 5-year disease-free survival (DFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients diagnosed by Dilation & Curettage (D&C) or diagnostic hysteroscopy. The Cox proportional hazards regression model was employed to adjust for potential confounding factors. Results: 160 cases underwent D&C and 269 cases were diagnosed by diagnostic hysteroscopy. The 5-year DFS rate was 72.17% in the diagnostic hysteroscopy group and 76.16% in the D&C group, diagnostic hysteroscopy was not associated with deteriorated 5-year DFS rate (HR 1.25, 95% CI 0.84-1.86, P=0.281). The 5-year OS rate was 67.23% in the diagnostic hysteroscopy group and 70.71% in the D&C group, diagnostic hysteroscopy did not increase the risk of all-cause death (HR 1.11, 95% CI 0.78-1.57, P=0.573). Multivariable analysis showed that the method of endometrial sampling was not independently associated with DFS (aHR 1.38, 95% CI 0.92-2.07, P=0.122) and OS (aHR 1.23, 95% CI 0.85-1.77, P=0.272). Conclusion: For apparent early-stage type II endometrial cancer, endometrial sampling by diagnostic hysteroscopy was as safe as D&C.

Identification of an inflammatory response signature associated with prognostic stratification and drug sensitivity in lung adenocarcinoma.

Increasing evidence has confirmed the close connection between inflammatory response and tumorigenesis. However, the relationship between inflammatory response genes (IRGs) and the prognosis of lung adenocarcinoma (LUAD) as well as the response to drug therapy remains poorly investigated. Here, we comprehensively analyzed IRGs RNA expression profiling and clinical features of over 2000 LUAD patients from 12 public datasets. The Cox regression method and LASSO analysis were combined to develop a novel IRG signature for risk stratification and drug efficacy prediction in LUAD patients. Enriched pathways, tumor microenvironment (TME), genomic and somatic mutation landscape in different subgroups were evaluated and compared with each other. This established IRG signature including 11 IRGs (ADM, GPC3, IL7R, NMI, NMURI, PSEN1, PTPRE, PVR, SEMA4D, SERPINE1, SPHK1), could well categorize patients into significantly different prognostic subgroups, and have better predictive in independently assessing survival as compared to a single clinical factor. High IRG scores (IRGS) patients might benefit more from immunotherapy and chemotherapy. Comprehensive analysis uncovered significant differences in enriched pathways, TME, genomic and somatic mutation landscape between the two subgroups. Additionally, integrating the IRGS and TNM stage, a reliable prognostic nomogram was developed to optimize survival prediction, and validated in an independent external dataset for clinical application. Take together, the proposed IRG signature in this study is a promising biomarker for risk stratification and drug efficacy prediction in LUAD patients. This study may be meaningful for explaining the responses of clinical therapeutic drugs and providing new strategies for administrating sufferer of LUAD.

The microbiological diagnostic performance of metagenomic next-generation sequencing in patients with sepsis.

BACKGROUND: In this study, we aimed to perform a comprehensive analysis on the metagenomic next-generation sequencing for the etiological diagnosis of septic patients, and further to establish optimal read values for detecting common pathogens. METHODS: In this single-center retrospective study, septic patients who underwent pathogen detection by both microbial culture and metagenomic next-generation sequencing in the intensive care unit of the Second People's Hospital of Shenzhen from June 24, 2015, to October 20, 2019, were included. RESULTS: A total of 193 patients with 305 detected specimens were included in the final analysis. The results of metagenomic next-generation sequencing showed significantly higher positive rates in samples from disparate loci, including blood, bronchoalveolar lavage fluid, and cerebrospinal fluid, as well as in the determination of various pathogens. The optimal diagnostic reads were 2893, 1825.5, and 892.5 for Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively. CONCLUSIONS: The metagenomic next-generation sequencing is capable of identifying multiple pathogens in specimens from septic patients, and shows significantly higher positive rates than culture-based diagnostics. The optimal diagnostic reads for frequently detected microbes might be useful for the clinical application of metagenomic next-generation sequencing in terms of timely and accurately determining etiological pathogens for suspected and confirmed cases of sepsis due to well-performed data interpretation.

On the Sensing and Calibration of Residual Stresses Measurements in the Incremental Hole-Drilling Method.

The current study presents three calibration approaches for the hole-drilling method (HDM). A total of 72 finite element models and 144 simulations were established to calibrate the measurements of the strain sensors. The first approach assumed the stresses acted on the boundaries of the drilled hole and thus analyzed the surrounding displacements field. The second analysis considered the loads on the outer surfaces of the specimen while measuring the strains' differences between the model with and without the drilled hole. The third approach was more comprehensive as it considered the mechanical and thermal effects of the drilling operations. The proposed approaches were applied to two different materials (AISI 1045 and CFRP). The steel specimens were machined using a CNC lathe while the composite laminates were manufactured using the robotic fiber placement (RFP) process. Subsequently, the residual stresses (RSs) were measured using the HDM. The obtained data were compared with X-ray diffraction measurements for validation. The results showed better estimation of the RSs when utilizing the third approach and clear underestimation of the stresses using the second approach. A divergence in RSs values between the three approaches was also detected when measuring the stresses in the internal layers of the composite laminates.

Using a Partially Evaporating Cycle to Improve the Volume Ratio Problem of the Trilateral Flash Cycle for Low-Grade Heat Recovery.

This study examined the trilateral flash cycle characteristics (TFC) and partially evaporating cycle (PEC) using a low-grade heat source at 80 °C. The evaporation temperature and mass flow rate of the working fluids and the expander inlet's quality were optimized through pinch point observation. This can help advance methods in determining the best design points and their operating conditions. The results indicated the partially evaporating cycle could solve the high-volume ratio problem without sacrificing the net power and thermal efficiency performance. When the system operation's saturation temperature decreased by 10 °C, the net power, thermal efficiency, and volume ratio of the trilateral flash cycle system decreased by approximately 20%. Conversely, with the same operational conditions, the net power and thermal efficiency of the partially evaporating cycle system decreased by only approximately 3%; however, the volume ratio decreased by more than 50%. When the system operating temperature was under 63 °C, each fluid's volume ratio could decrease to approximately 5. The problem of high excessive expansion would be solved from the features of the partially evaporating cycle, and it will keep the ideal power generation efficiency and improve expander manufacturing.

Deep-Learning-Based Power Generation Forecasting of Thermal Energy Conversion.

ORC is a heat to power solution to convert low-grade thermal energy into electricity with relative low cost and adequate efficiency. The working of ORC relies on the liquid-vapor phase changes of certain organic fluid under different temperature and pressure. ORC is a well-established technology utilized in industry to recover industrial waste heat to electricity. However, the frequently varied temperature, pressure, and flow may raise difficulty to maintain a steady power generation from ORC. It is important to develop an effective prediction methodology for power generation in a stable grid system. This study proposes a methodology based on deep learning neural network to the predict power generation from ORC by 12 h in advance. The deep learning neural network is derived from long short-term memory network (LSTM), a type of recurrent neural network (RNN). A case study was conducted through analysis of ORC data from steel company. Different time series methodology including ARIMA and MLP were compared with LSTM in this study and shows the error rate decreased by 24% from LSTM. The proposed methodology can be used to effectively optimize the system warning threshold configuration for the early detection of abnormalities in power generators and a novel approach for early diagnosis in conventional industries.

Comparative clinical outcomes of Tecnis toric IOL implantation in femtosecond laser-assisted cataract surgery and conventional phacoemulsification surgery.

AIM: To compare the short-term visual outcomes, residual refractive cylinder, and rotation stability after Tecnis toric intraocular lens (IOL) implantation during femtosecond laser-assisted cataract surgery (Femto phaco) and conventional phacoemulsification surgery (Conventional phaco). METHODS: In a prospective cohort study, Conventional phaco and Femto phaco (anterior capsulotomy and lens fragmentation by a femtosecond laser) with Tecnis toric IOL implantation were performed in 40 eyes from 36 patients and 37 eyes from 33 patients, respectively. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refraction were assessed during 1d, 1wk, and 1mo follow-ups. The orientation of the Tecnis Toric IOL was evaluated during 1wk and 1mo follow-ups. RESULTS: There were no significant differences in UDCA or CDVA between two groups at 1mo postoperatively, though relatively more subjects had UDVA values of 20/25 or better in Femto phaco group than in the Conventional group (P>0.05). A lower but not significantly lower rate of having more than 5° of IOL rotation was observed in Femto phaco group at the 1-month follow-up, while a significant lower rate of residual astigmatism of ≤1 D was observed in Femto phaco group. CONCLUSION: The Femto phaco group has significantly more subjects with the residual astigmatism of ≤1 D, but there are no significant differences in rotation stability and visual outcomes as compared with the Conventional phaco group after the application of the Tecnis toric IOL in this cohort.

In(OTf)3-catalyzed intramolecular hydroarylation of α-phenylallyl ß-ketosulfones - synthesis of sulfonyl 1-benzosuberones and 1-tetralones.

In(OTf)3-catalyzed intramolecular hydroarylation of α-phenylallyl ß-ketosulfones provides sulfonyl 1-benzosuberones and 1-tetralones in moderate to good yields in refluxing (CH2Cl)2 under open-vessel and easy-operation reaction conditions. A plausible mechanism is proposed and discussed. This highly regioselective protocol provides an atom-economic ring-closure route.