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.

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.

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.

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.

Stereocontrolled Construction of 1-Vinylindanes via Intramolecular Cyclization of o-Cinnamyl Chalcones.

In this paper, a concise route for the synthesis of 1-vinylindanes is described, including (i) NaBH4-mediated reduction of o-cinnamyl chalcones and (ii) sequential BF3·OEt2-mediated intramolecular annulation of the resulting alkenols. The plausible mechanism is proposed and discussed herein. This protocol provides highly effective stereocontrolled cinnamyl-enone cross-coupling to construct three contiguous trans- trans stereocenters and one ( E)-configured alkenyl or styryl group.

mCPBA-Mediated Intramolecular Oxidative Annulation of ortho-Crotyl or Cinnamyl Arylaldehydes: Synthesis of Benzofused Five-, Six-, and Seven-Membered Oxacycles.

mCPBA-mediated intramolecular oxidative annulation of ortho-crotyl or cinnamyl arylaldehydes provides chroman, coumaran, isochroman, and tetrahydrobenzo[ c]oxepine under different reaction conditions. This research investigates the reaction conditions for facile and efficient transformation.

Comparative density functional theory-density functional tight binding study of fullerene derivatives: effects due to fullerene size, addends, and crystallinity on band structure, charge transport and optical properties.

We present a systematic comparative density functional theory-density functional tight binding study of multiple derivatives of C60 and C70 with different addends, in molecular as well as solid state. In particular, effects due to fullerene size, type and number of addends, and of crystallinity on band structure, charge transport, and optical properties are investigated. These are important, in particular, for rational selection of fullerene derivatives as acceptor and electron transport layers in organic as well as planar inverted perovskite solar cells. We find that by the choice of type and number of addends, one can modulate the LUMO within 0.4 eV. Changes in the HOMO can reach 0.7 eV. Substituting C70 for C60 results in destabilization of the HOMO by about 0.1 eV for indene and quinodimethane addends and by a less significant amount for PCBM addends. The effect of C70-C60 substitution on the LUMO is of similar magnitude. A more significant change in HOMO-LUMO energy is seen for the aryl addends. On the other hand, all C70 based molecules have strong visible absorption. For most addends, the crystal packing leads to a stabilization of both the LUMO and HOMO by about ∼0.2 and ∼0.1 eV, respectively, vs. single molecules. When using bis-addends, it is also possible to enhance the visible absorption. Electron and hole transport rates are computed to vary vastly depending on the addends chosen; specifically, we compute that indene and quimodimethane addends can enhance charge transport rates while the aryl addend is predicted to result in substantially smaller mobilities of electrons and holes, vs. PC60BM. Furthermore, the -CH2 and bisaddend addition can significantly enhance the charge transfer rates for the PCBM addend.

Distributed Information Compression for Target Tracking in Cluster-Based Wireless Sensor Networks.

Target tracking is a critical wireless sensor application, which involves signal and information processing technologies. In conventional target position estimation methods, an estimate is usually demonstrated by an average target position. In contrast, this work proposes a distributed information compression method to describe the measurement uncertainty of tracking problems in cluster-based wireless sensor networks. The leader-based information processing scheme is applied to perform target positioning and energy conservation. A two-level hierarchical network topology is adopted for energy-efficient target tracking with information compression. A Level 1 network architecture is a cluster-based network topology for managing network operations. A Level 2 network architecture is an event-based and leader-based topology, utilizing the concept of information compression to process the estimates of sensor nodes. The simulation results show that compared to conventional schemes, the proposed data processing scheme has a balanced system performance in terms of tracking accuracy, data size for transmission and energy consumption.

[Isolation of endophytic fungi from medicinal plant Brucea javanica and their microbial inhibition activity].

OBJECTIVE: To isolate and identify endophytic fungi from Brucea javanica, and to detect the antimicrobial activity of these strains. METHODS: Endophytic fungi were isolated by tissue inoculation culture and identified by conventional morphological characteristic method. Seven kinds of pathogenic fungi and three kinds of bacteria were used as targeting microbes to test microbial inhibition activities by agar plate antagonistic action and modified agar gel diffusion methods, respectively. RESULTS: A total of 83 endophytic fungi strains were isolated from the root, stem, leaf and fruit of Brucea javanica. 34 strains were obtained from the stem, 32 strains were obtained from the leaf, 15 strains were isolated from the root and 2 strains came from the fruit. These 73 strains which had been identified attribute to 5 orders, 6 families and 12 genera. For the isolated strains, 14 strains had antifungal activities against at least one pathogenic fungi, 9 strains showed antibacterial activities against one or more bacteria. Especially, the strain YJ-17 which belonged to Phomopsis genus showed the best inhibitory effect on the targeting microbes. CONCLUSION: The endophytic fungi from Brucea javanica show diversity and microbial inhibition activity, and are worthy for further study on plant disease controlling.

[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.
.

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.].

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.

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).

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.

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.

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.