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Abstract In the photothermal synergistic catalytic conversion of CO2 and H2O, the catalyst harnesses solar energy to accumulate heat, thereby elevating the reaction system’s temperature. The influence of this temperature effect on surface chemical reactions remains an underexplored area. Here the impact of temperature on the surface-level thermodynamic reactions and conversion of CO2 with H2O on oxide semiconductors at the atomic scale was investigated using first-principle calculations. 13 different metal oxides and 5 transition metal clusters were used to introduce surface functional sites on the TiO2 supporting catalyst. The potential metal oxide cocatalysts that could be most beneficial to the following conversion of CO2 by H2O were initially screened by calculating the degrees of promotion of CO2 adsorption and activation of surface H to provide protons. The proton donation and hydrogen evolution difficulty from H2O were further analyzed, identifying transition metal cocatalysts that promote direct CO2 hydrogenation. Upon introducing bifunctional sites to facilitate adsorption and reduction, the production of CH3OH and CH4 could be further enhanced through the facilitation of the proton donation process of H2O. The results of Gibbs free-energy calculations revealed that increasing temperature enhances the reaction thermodynamics for each C1 product formation at different surface sites to varying degrees. These findings offer valuable theoretical insights for designing and regulating active sites on oxide semiconductor surfaces for efficient photothermal catalytic CO2 reduction by H2O.

Abstract Purpose This study aimed to assess the relationship between A Body Shape Index (ABSI) and cognitive impairment among older adults in the United States. Methods This cross-sectional study analyzed cognitive function in 2,752 individuals aged 60 and older using data from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Cognitive assessments were conducted using the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). A Body Shape Index (ABSI) was calculated from waist circumference (WC), weight, and height. The relationship between ABSI and cognitive outcomes was examined through multifactorial linear regression, smooth curve fitting, and subgroup and interaction analyses. Results With complete data, 2752 persons 60 and older participated in the study. After adjusting for covariables, these results showed statistically significant negative relationships between ABSI, IRT, and DSST scores. The negative correlation between DSST and ABSI is more substantial in males than females. There is less of a negative link between ABSI, AFT, and DSST among drinkers who consume 12 or more drinks annually compared to those who consume less. Furthermore, compared to individuals without high blood pressure(HBP), those who suffered HBP showed a more significant negative connection between ABSI and AFT. Conclusion Lower cognitive function was linked to higher ABSI.

PurposeThis research aimed to assess the correlation between the Adjusted Body Shape Index (ABSI) and the presence of abdominal aortic calcification (AAC) among middle-aged and older American adults.MethodsEmploying a cross-sectional design, this study analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), focusing on 3077 participants aged 40 and above. AAC detection was conducted using dual-energy X-ray absorptiometry (DXA). ABSI was determined based on waist circumference (WC), weight, and height data. The association between ABSI and AAC was examined through multiple linear regression, smoothed curve analysis, threshold effect evaluation, subgroup analysis, and interaction testing.ResultsThe study encompassed 3077 individuals aged 40 and above. Findings indicated a noteworthy positive relationship between ABSI and AAC when adjusting various covariates. Analysis of threshold effects identified a K-point at 0.0908, showing no significant effect to its left but a significant effect to its right. Further, subgroup and interaction analyses highlighted the ABSI-AAC connection specifically within different age groups and among individuals with diabetes.ConclusionHigher ABSI was correlated with higher AAC score.

To understand the explosion characteristics of methane-lignite coal dust mixtures and the spatiotemporal evolution of the early flame flow field, explosion pressure, OH* emission spectra, and early flame schlieren images were captured in a 60L constant volume combustion bomb. Schlieren image velocimetry was used to obtain the instantaneous velocity distribution of the methane-coal dust flame front. The results indicate that adding coal dust causes a nonlinear increase in explosion pressure, particularly at low methane concentrations. At a 5 % methane concentration, adding coal dust can increase the maximum explosion pressure by up to 39 % (190 kPa). The trend of the OH* emission spectra corresponds with the maximum explosion pressure. A slight increase in coal dust significantly enhances the OH* emission spectra, especially at lower concentrations, potentially increasing it by nearly five times. However, at higher coal dust concentrations, the OH* emission spectra are significantly reduced. Additionally, within the considered concentration range (≤58.14 g/m³), larger turbulent integral length scales in initial conditions consistently result in the fastest flame acceleration. These findings provide experimental evidence for further exploration of the explosion mechanisms of methane-coal dust mixtures and the development of chemical reaction kinetic models.

Abstract Background Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. Methods In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3’ untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P

Abstract The phenomenon of stock price crash events (SPCs) has always attracted market attention, but existing research mainly focuses on its causes or determinants and rarely examines the consequences of SPCs. This study aims to fill this gap by examining the consequences of firm-specific stock price crash events (SPCs) on analyst forecast accuracy. Using the sample of analysts and listed companies from 2001 to 2020 and employing a difference-in-differences design, we find that after the company’s stock price crashed, the analyst forecast error decreased and the accuracy increased. For analysts who have not conducted site visits before SPC, and have no geographical advantages, this effect is more obvious, thus validating our hypothesis following analyst attention theory. Additional analysis shows that SPCs stimulate forecast accuracy more significantly for lowly-reputed analysts than for highly-reputed analysts. Channel analysis documents that, for the aforementioned group of analysts, the enhancement effect of SPCs on analyst forecasts is mediated by analyst effort increasing. This study adds to the evidence that SPCs bring positive externalities from the analyst perspective, that is, SPCs attract the attention of some analysts and improve their forecast accuracy. This study also enhances our understanding of analyst behavior under uncertainty, finally enriching the literature on the determinants of analyst forecast accuracy.

PurposeTo investigate the relationship between food insecurity and cognitive decline among elderly Americans.MethodsUtilizing NHANES 2011–2014 data, we examined cognitive function via the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST) and assessed food security through the US Food Security Survey Module. Multiple regression models were used to adjust for demographic and health variables.ResultsFood insecurity demonstrated a significant association with lower cognitive function scores. The effects of food insecurity on cognitive function were moderated by factors such as smoking and alcohol use, indicating a direct influence of food insecurity on cognitive decline.ConclusionThis study underscores the importance of food security for cognitive health in the elderly and advocates for targeted interventions to address nutritional disparities and enhance cognitive functioning in aging populations.

IntroductionSalt stress is a major environmental factor that constrains soybean growth, development, and productivity. Flavonoids are key secondary metabolites that play a crucial role in enhancing plant resistance to both biotic and abiotic stress. However, a comprehensive understanding of the regulatory mechanisms underlying flavonoid biosynthesis under salt stress in soybean is lacking.MethodsIn this study, an integrative analysis of soybean metabolome and transcriptome was conducted using two soybean lines, FQ03 (salt-sensitive, SS) and FQ07 (salt-tolerant, ST).ResultsA total of 650 significantly changed metabolites were identified in SS and ST after salt stress treatment. Among them, 151 flavonoids were categorized into nine classes, with flavones and flavonols being the predominant flavonoid types in soybean. Heatmap analysis showed higher contents of most flavonoid metabolites in ST than in SS under salt stress, and the total flavonoid content in ST was significantly higher than that in SS. In addition, transcriptome analysis revealed a higher number of differentially expressed genes (DEGs) in ST than in SS under salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways related to phenylpropanoid biosynthesis, isoflavonoid biosynthesis, flavonoid biosynthesis, as well as flavone and flavonol biosynthesis. Notably, 55 DEGs that were mapped to the flavonoid biosynthetic pathway were identified, with most showing higher expression levels in ST than in SS. Weighted gene correlation network analysis identified eight structural genes and six transcription factor genes as key regulators of flavonoid biosynthesis within the blue module. Furthermore, qRT-PCR results confirmed the accuracy of the transcriptomic data and reliability of the identified candidate genes.DiscussionThis study provides insights into the regulatory mechanisms underlying salt stress responses in soybean and highlights hub genes as potential targets for developing salt-tolerant soybean varieties.

Abstract This research explores the potential of multimodal fusion for the differential diagnosis of early-stage lung adenocarcinoma (LUAD) (tumor sizes < 2 cm). It combines liquid biopsy biomarkers, specifically extracellular vesicle long RNA (evlRNA) and the computed tomography (CT) attributes. The fusion model achieves an impressive area under receiver operating characteristic curve (AUC) of 91.9% for the four-classification of adenocarcinoma, along with a benign-malignant AUC of 94.8% (sensitivity: 89.1%, specificity: 94.3%). These outcomes outperform the diagnostic capabilities of the single-modal models and human experts. A comprehensive SHapley Additive exPlanations (SHAP) is provided to offer deep insights into model predictions. Our findings reveal the complementary interplay between evlRNA and image-based characteristics, underscoring the significance of integrating diverse modalities in diagnosing early-stage LUAD.

Abstract Background As a key regulatory enzyme in the glycolysis pathway, pyruvate kinase (PK) plays crucial roles in multiple physiological processes during plant growth and is also involved in the abiotic stress response. However, little information is known about PKs in soybean. Results In this study, we identified 27 PK family genes against the genome of soybean cultivar Zhonghuang13. They were classified into 2 subfamilies including PKc and PKp. 22 segmental duplicated gene pairs and 1 tandem duplicated gene pair were identified and all of them experienced a strong purifying selective pressure during evolution. Furthermore, the abiotic stresses (especially salt stress) and hormone responsive cis-elements were present in the promoters of GmPK genes, suggesting their potential roles in abiotic stress tolerance. By performing the qRT-PCR, 6 GmPK genes that continuously respond to both NaCl and ABA were identified. Subsequently, GmPK21, which represented the most significant change under NaCl treatment was chosen for further study. Its encoded protein GmPK21 was localized in the cytoplasm and plasma membrane. The transgenic Arabidopsis overexpressing GmPK21 exhibited weakened salinity tolerance. Conclusions This study provides genomic information of soybean PK genes and a molecular basis for mining salt tolerance function of PKs in the future.

Accurate assessment of water surface velocity (WSV) is essential for flood prevention, disaster mitigation, and erosion control within hydrological monitoring. Existing image-based velocimetry techniques largely depend on correlation principles, requiring users to input and adjust parameters to achieve reliable results, which poses challenges for users lacking relevant expertise. This study presents RivVideoFlow, a user-friendly, rapid, and precise method for WSV. RivVideoFlow combines two-dimensional and three-dimensional orthorectification based on Ground Control Points (GCPs) with a deep learning-based multi-frame optical flow estimation algorithm named VideoFlow, which integrates temporal cues. The orthorectification process employs a homography matrix to convert images from various angles into a top-down view, aligning the image coordinates with actual geographical coordinates. VideoFlow achieves superior accuracy and strong dataset generalization compared to two-frame RAFT models due to its more effective capture of flow velocity continuity over time, leading to enhanced stability in velocity measurements. The algorithm has been validated on a flood simulation experimental platform, in outdoor settings, and with synthetic river videos. Results demonstrate that RivVideoFlow can robustly estimate surface velocity under various camera perspectives, enabling continuous real-time dynamic measurement of the entire flow field. Moreover, RivVideoFlow has demonstrated superior performance in low, medium, and high flow velocity scenarios, especially in high-velocity conditions where it achieves high measurement precision. This method provides a more effective solution for hydrological monitoring.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Structured illumination microscopy (SIM) is a popular and powerful super-resolution (SR) technique in biomedical research. However, the conventional reconstruction algorithm for SIM heavily relies on the accurate prior knowledge of illumination patterns and signal-to-noise ratio (SNR) of raw images. To obtain high-quality SR images, several raw images need to be captured under high fluorescence level, which further restricts SIM’s temporal resolution and its applications. Deep learning (DL) is a data-driven technology that has been used to expand the limits of optical microscopy. In this study, we propose a deep neural network based on multi-level wavelet and attention mechanism (MWAM) for SIM. Our results show that the MWAM network can extract high-frequency information contained in SIM raw images and accurately integrate it into the output image, resulting in superior SR images compared to those generated using wide-field images as input data. We also demonstrate that the number of SIM raw images can be reduced to three, with one image in each illumination orientation, to achieve the optimal tradeoff between temporal and spatial resolution. Furthermore, our MWAM network exhibits superior reconstruction ability on low-SNR images compared to conventional SIM algorithms. We have also analyzed the adaptability of this network on other biological samples and successfully applied the pretrained model to other SIM systems.

Abstract Due to the diversity of climate and environment in China, the frequent occurrence of extreme rainfall events has brought great challenges to flood prevention. Water level measurement is one of the important research topics of flood prevention. Recently, the image‐based water level recognition method has become an important part of water level measurement research due to its advantages in easy installation, low cost, and zero need of manual reading. However, there are two mainly shortcomings of the existing image‐based water level recognition methods: (1) severely affected by light intensity and (2) low accuracy of water level recognition for stained water gauges. To solve these two problems, this paper proposes a water level recognition method in consideration of complex scenarios. This method first uses a semantic segmentation convolutional neural network to extract the water gauge mask, and then uses the YOLOv5 object detection network to extract the letter “E” on the water gauge. Based on the character sequence inspection strategy, the algorithm dynamically compensates for the missed detection of characters of stained water gauges. Through a large number of experiments, the proposed water level measurement method has good robustness in complex scenarios, meeting the needs of flash flood defense.

The spatial characteristics, pollution sources, and risks of soil heavy metals were analyzed on Hainan Island. The results showed that the heavily polluted points accounted for 0.56%, and the number of mildly and above polluted points accounted for 15.27%, respectively, which were mainly distributed in the northern part of the study area. The principal component analysis–absolute principal component score–multiple linear regression (APCS-MLR) and the positive matrix factorization (PMF) revealed four sources of heavy metals: agricultural pollution sources for cadmium, (Cd), industrial and mining pollution sources for arsenic, (As), transportation pollution sources for zinc and lead (Zn and Pb), and natural pollution sources for chromium, nickel, and copper (Cr, Ni, and Cu). The human health risk assessment indicated that the average non-carcinogenic risk (HI) for both adults and children was within the safe threshold (1, indicating a potential health risk above the safe threshold. Meanwhile, nearly 100% and 99.94% of the TCR values exceeded 1 × 10−4 for children and adults, indicating that Cr and Ni are priority heavy metals for control. The research results provide the necessary scientific basis for the prevention and control of heavy metals in agricultural soils.

Cadmium (Cd) is a harmful metal that seriously affects the male reproductive system, but the mechanism of how Cd exposure damages Sertoli cells is not fully understood. This study used TM4 cells to explore the mechanism of Cd damage to Sertoli cells. We found that Cd was concentration- and time-dependent on TM4 cell viability. Cd exposure increased intracellular reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH), and Interleukin-1β (IL-1β) release in TM4 cells, decreased mitochondrial function, and increased pyroptosis. N-acetylcysteine (NAC), MCC950 and BAY 11–7082 (BAY) alleviate the release of IL-1β and LDH induced by Cd. NAC reduced Cd induced increases in ROS, NLRP3, Caspase-1, Heme oxygenase-1(HO-1), superoxide dismutase (SOD2), and increased mitochondrial function. The activation of GSDMD is the main causes of pyroptosis, and NAC significantly inhibit its activation and formation. Our results suggest that Cd exposure induces a toxic mechanism of GSDMD-mediated pyroptosis in TM4 cells by increasing ROS levels and activating the inflammasome.

The fatigue crack growth behavior of 304L austenitic stainless steel (SS) in a 325 °C high-temperature and high-pressure water environment were investigated by a corrosion fatigue test system, by electron back scatter diffraction (EBSD), and by a transmission electron microscope (TEM). The experimental results indicated that the crack growth rate (CGR) of 304L SS increases with increasing the stress intensity factor, stress level, and fatigue frequency (f). Compared to dissolved hydrogen (DH) in a high-temperature water environment, dissolved oxygen (DO) significantly enhances the CGR by about an order of magnitude higher. The crack tip of 304L SS after the corrosion fatigue test under higher stress levels is sharper, with more secondary cracks on the fracture surface, while the crack tip under lower stress levels is blunter with relatively fewer secondary cracks. The oxidation behavior at the crack tip was analyzed under different loading and water chemistry conditions, and a related effect on the crack tip and CGR was clarified.

Karst aquifers are crucial for providing fresh water worldwide but are also incredibly sensitive to human impact and climate change. This study aims to reconstruct the historical water levels of karst springs, despite the lack of data. By combining collected data, we have created a detailed numerical model to understand the complex behavior of karst aquifers. Our research reveals significant drops in the water levels at Longtan Spring, mainly due to the overuse of groundwater and inadequate water recharge, which is critical for the success of the Springs Resurgence project. We have also mapped out historical groundwater levels and identified the necessary conditions to get the spring flowing again. The model proved to be reliable during its calibration from 2000 to 2007, with an average Nash–Sutcliffe efficiency coefficient of 0.52 for the monitoring wells. For the period from 1960 to 2019, our model showed a strong correlation coefficient of over 0.97 when compared with data from the GRACE satellite mission, demonstrating its high accuracy. The approach we have taken in this study provides a feasible way to figure out historical water levels in karst springs, which is vital for protecting these essential fresh water sources. This work will provide a strong basis for policies to restore the spring.

Ocean dynamic processes in the bottom boundary layer (BBL) are crucial for sedimentation, such as deposition and resuspension of marine sediments. In this study, we conducted in-situ tripod observations of the sediment ridge of a contourite drift in the northern South China Sea to understand the main dynamic processes affecting sedimentation on the contourite drifts. It was found that the diurnal tidal current was the strongest current at the study site, thus acting as the main dynamic affecting sedimentation processes. Periodic events of elevated suspended sediment concentration (SSC) were observed, some of which occurred only within 15 m above the seafloor and were termed near-bottom high SSC events, while others covered the entire range of the observed water column and were termed full-depth high SSC events. In-situ sediment resuspension at the sediment ridge is not an important factor affecting the formation of high SSC events. Rather, these high SSC events were mainly caused by lateral transport of sediments from the main body of the contourite drift by the northwestward diurnal tidal currents. The seafloor sediments at the main drift body are resuspened owing to the near-critical reflection of diurnal tidal currents on the slope topography of the drift. During periods when diurnal tidal currents were weak, locally generated internal waves could also induce burst-like full-depth high SSC events. This study highlights the diurnal tidal current as the main dynamic regulating the sedimentary processes of the contourite drifts in regions where the near-critical reflection prone to occur, implying the complexity of sediment dynamics of contourite drifts.

Cadmium (Cd) is a toxic heavy metal commonly found in nature and an endocrine disrupting chemical (EDC). Previous studies found that Cd can damage several organs, including the kidneys, bones, cardiovascular system and reproductive system. However, the effect of paternal Cd exposure on the offspring is unclear. In this study, 1 mg/kg of cadmium chloride (CdCl2) was injected intraperitoneally every other day in 8-week-old C57BL/6 J male mice to study the effects on their female offspring. Our results showed an increase in body weight, water intake and food intake in F1 female mice from the Cd-exposed group. The development of secondary follicles and antral follicles in the ovaries of Cd-treated was inhibited. Serum estradiol (E2) was found to be decreased. Further analysis revealed significant downregulation of StAR, P450scc, 17β-HSD, CYP17A1 and CYP19A1, which are related to E2 synthesis. Serum total cholesterol was increased and free cholesterol was reduced. Total cholesterol in ovarian tissue was decreased. qRT-PCR and Western blot analysis revealed a decrease in the mRNA and protein expression of HMGCR, LDLR, and ABCA1, which are associated with cholesterol homeostasis. Oil red O staining indicated that lipid droplets (LDs) were accumulated in ovarian tissues, while the expression of ATGL and HSL proteins associated with lipid droplet degradation was significantly downregulated. In juvenile female mice, ultrastructural alterations of mitochondria in the ovaries were observed by transmission electron microscopy (TEM). In adult female mice, the expression of proteins associated with mitochondrial dynamics (DRP1 and MFN2) was significantly reduced in the ovaries. Overall, our study suggests that paternal Cd exposure inhibits follicular development, and affects serum E2 synthesis by impairing cholesterol homeostasis and affecting mitochondrial function.

Abstract Long non-coding RNAs (lncRNAs) play a vital role in regulating adipogenesis. However, the associated regulatory mechanisms have yet to be described in detail in pig. In this study, we demonstrate a critical role for lncMYOZ2 in adipogenesis from porcine preadipocytes. Specifically, lncMYOZ2 was more abundant in the adipose tissue of Mashen (fat-type) pigs than for Large White (lean-type) pigs, and knockdown of this lncRNA significantly inhibited the differentiation of porcine preadipocytes into adipocytes. Mechanistically, we used RNA pull-down and RIP assays to establish that lncMYOZ2 interacts with adenosylhomocysteinase (AHCY). Moreover, lncMYOZ2 knockdown increased promoter methylation of the target gene MYOZ2 and lowered its expression. Finally, we describe a positive regulatory role for MYOZ2 in adipogenesis. Collectively, these findings establish lncMYOZ2 as an important epigenetic regulator of adipogenesis via the aforementioned AHCY/MYOZ2 pathway, and provide insights into the role of lncRNAs in porcine adipose development.

Abstract Background Small cell lung cancer (SCLC) is the most malignant and common form of neuroendocrine lung cancer with pure (P‐SCLC) and combined subtypes (C‐SCLC). However, little is known about the differences between these two groups and in this study we aimed to provide a more comprehensive insight into SCLC. Methods Data from 580 postoperative patients with pathologically confirmed SCLC in Shanghai Chest Hospital from January 2010 to December 2020 were collected retrospectively. The clinical characteristics and prognosis were analyzed. Results A total of 357 P‐SCLC patients and 223 C‐SCLC patients were included. The results indicated that P‐SCLC appeared to have a higher proportion of being located in the middle lobe than C‐SCLC. The incidences of P‐SCLC in patients with visceral pleural invasion (VPI) and in stage II were higher than C‐SCLC, while C‐SCLC was more likely to be accompanied by higher incidences of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) rearrangement, and higher levels of CEA, SCCA and CYFRA21‐1 than P‐SCLC. The most common were SCLC combined with large cell neuroendocrine components among 223 C‐SCLCs. Survival analysis confirmed a more favorable disease‐free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.024) in patients with P‐SCLCs compared with C‐SCLCs. Histological type, tumor location, pN stage, adjuvant chemotherapy, serum NSE and CA125 levels were independent risk factors for survival rate in SCLC. In addition, adjuvant chemotherapy was beneficial in improving stage I P‐SCLC and C‐SCLC DFS and OS rates, and similar results were not seen in adjuvant radiation therapy. Conclusions Patients with C‐SCLC have a poorer prognosis than P‐SCLC patients. We determined that large cell neuroendocrine carcinoma was the most common additional component of C‐SCLC, and patients with this component appeared to have a longer DFS and OS than other combined components.

Increasing attention has been paid to the regulation of electromagnetic parameters by reasonable micromorphological design and proper composition to realize high-performance electromagnetic wave absorbers. Herein, a unique hierarchical SiC nanowire-reinforced SiC aerogel decorated with Ni-capped carbon nanotubes (SiCnw@SiC-Ni@CNT) was constructed. The effective synergism between the combination of multiphase magnetic/dielectric materials and the introduction of specific 3D hierarchical microstructures is beneficial for the apparent improvement of multiple dielectric/magnetic losses, electromagnetic scattering effects, and impedance matching capabilities, exhibiting remarkable tunable microwave absorption performance. Accordingly, a strong microwave absorption intensity (RLmin) at 10.24 GHz of −47.75 dB with a loading of 20 wt% and an ultrawide effective absorption bandwidth (EAB, RL

Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.

Background: microRNAs (miRNAs) are closely associated with the pathogenesis of various diseases, but the relationship between miRNAs and myocardial ischemia-reperfusion (I/R) injury remains unclear. Therefore, we aimed to explore the role and function of miRNAs and identify target genes regulating I/R. Methods: We established a hypoxia/reoxygenation (H/R) model to detect differentially expressed miRNAs using high-throughput sequencing in rat myocardial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the potential functions and signaling pathways of target genes. Results: We identified 113 differentially expressed miRNAs, comprising 76 and 37 upregulated and downregulated genes, respectively. Database predictions suggested that miR-200a-3p may act through the ferroptosis pathway, and we assessed the expression of miR-200a-3p, iron ions, and ferroptosis markers. The expression of miR-200a-3p significantly increased in the H/R group, along with increased production of reactive oxygen species (ROS) and iron ions. When the expression of miR-200a-3p was inhibited, iron ions and ROS levels decreased significantly. Western blotting showed that transferrin receptor (TFRC) and Acyl-coA synthetase long-chain family member 4 (ACSL4) levels were decreased and Glutathione peroxidase 4 (GPX4) expression was increased. Conclusions: These findings offer a novel perspective on I/R regulation, and the specific mechanisms underlying the actions of miR-200a-3p merit further investigation.

Lactic acid bacteria are widespread in nature, with rich species diversity, and are widely used in the food, feed and clinical medicine. Currently, the majority of probiotics are lactic acid bacteria. Recently, the whole-genome sequencing is booming, which has greatly promoted the development and application of LAB. Based on the whole genome information of lactic acid bacteria, it can systematically and comprehensively understand the metabolic characteristics, potential probiotic functions and application directions of strains, and can more accurately explore the inheritance, evolution and classification of lactic acid bacteria. The safety evaluation procedure of lactic acid bacteria requires searching whether there are genes related to drug resistance, virulence, and pathogen at the genome level, and determining whether the related genes can be transferred horizontally. It can efficiently and completely determine the genetic stability of lactic acid bacteria in the process of industrial application, using whole-genome sequencing technology to compare the differences of genomes of different generations strains. Reconstruction of the genome-scale metabolic network model can predict the behavior of organisms under specific conditions and systematically guide metabolic engineering of microbial. This article reviews the application status of whole-genome sequencing in metabolic characteristics, genetic, evolution, safety and stability of lactic acid bacteria, aiming to provide theoretical support for the genome of lactic acid bacteria.

Abstract Background Circulating tumour DNA (ctDNA)-based sequencing might provide a simple test for the stratified model of non-small cell lung cancer (NSCLC). Here, we aimed to assess the ctDNA sequencing-based tumour mutation index (TMI) model for screening responders (from non-responders) among NSCLC patients who received monotherapy with docetaxel or atezolizumab. Methods We performed a retrospective analysis of the POPLAR (NCT01903993) and OAK (NCT02008227) trials. We identified three biomarkers, blood tumour mutation burden (bTMB), sensitive blood tumour mutation burden (sbTMB) and unfavourable mutation score (UMS), of the ctDNA profiles. After integrating the advantages and disadvantages of the three independent biomarkers, we developed the TMI model and identified NSCLC patients who may benefit from monotherapy with docetaxel or atezolizumab in terms of overall survival (OS). Results The TMI model as a stratified biomarker for docetaxel responders provided a median OS duration of 5.55 months longer than non-responders in the OAK cohort, with a significantly decreased hazard ratio (HR). Moreover, atezolizumab responders had a 10.21-month OS advantage over atezolizumab non-responders in the OAK cohort via TMI stratification, and the HR was also decreased significantly. The TMI demonstrated effectiveness for stratifying responders in the POPLAR cohort. Importantly, we found that the TMI model could screen additional responders upon combining the cohorts from the POPLAR and OAK trials after adjustment. Conclusion In the present study, we provide a novel TMI model for screening responders (from non-responders) among NSCLC patients who received the 2nd-line monotherapy with docetaxel or atezolizumab. We believe that the biomarker TMI will potentially be effective for the clinical treatment of NSCLC in the future.

IntroductionPlatinum-based chemotherapy is still the standard of care for Epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) patients after developing EGFR-TKI resistance. However, no study focusing on the role of immuno checkpoint inhibitor (ICI) based treatments for EGFR mutated NSCLC patients who carried programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50% progressed after EGFR-TKI therapy. In this study, we retrospectively investigated the outcomes of ICI-based treatments for EGFR mutated NSCLC patients carried PD-L1 TPS≥50% after developing EGFR-TKI resistance and to explore the population that may benefited from ICI-based treatment.MethodsWe retrospectively collected data of advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation at Shanghai Chest Hospital between January 2018 and June 2021. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of this study.ResultsA total of 146 patients were included. Up to June 20th, 2022, median follow-up was 36.7 months (IQR, 12.5-44.2 months). Among the population, 66 patients (45.2%) received chemotherapy, the remaning (54.8%) received ICI-based treatment, including 56 patients(70.0%) received ICI combined with chemotherapy (IC) and 24 patients (30.0%) received ICI monotherapy (IM). In IC group,31 patients received ICI combined with chemotherapy,19 patients received ICI combined with antiangiogenic therapy and remaing received ICI combined with chemotherapy and antiangiogenic therapy. Survival analysis shown that patients who received ICI-based treatment had better progress-free survival (PFS) and overall survival (OS) compared with those treated with other therapy (median PFS, 10.0 vs. 4.0 months, P

Abstract Background Local consolidative therapy (LCT) has emerged as a treatment option in patients with oligometastatic non‐small cell lung cancer (NSCLC) undergoing chemotherapy or targeted therapy. However, the current literature lacks evidence as to whether LCT improves survival in NSCLC patients receiving immunotherapy. Our study aimed to assess whether LCT combined with pembrolizumab ± chemotherapy could improve the survival of patients with synchronous oligometastatic NSCLC. Methods Patients with NSCLC, without EGFR or ALK genetic aberrations, who were treated with first‐line pembrolizumab ± chemotherapy, were included in the study. Survival analysis of the LCT and non‐LCT groups was compared. Results A total of 231 patients were included in the study. The median follow‐up time was 15.24 months. Median progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 12.00 and 23.43 months, respectively. Of the 231 patients included, 76 patients received LCT combined with pembrolizumab ± chemotherapy (LCT group) while 155 patients received pembrolizumab ± chemotherapy alone (non‐LCT group). Of note, the PFS of the LCT and non‐LCT groups was 13.97 and 10.08 months (p = 0.016), respectively. The OS were 30.67 and 21.97 months (p = 0.011), respectively. The PFS and OS were significantly improved with LCT for patients with brain or lung metastases but not bone metastases. No significant increase in treatment‐related toxicity was observed in the LCT group. Conclusions The present study shows that LCT to metastatic sites is an option for consideration in patients with synchronous oligometastatic NSCLC during first‐line pembrolizumab treatment, with significantly improved PFS and OS compared with systemic treatment alone.

Abstract Background Epidermal growth factor receptor (EGFR) mutations were frequently found with concomitant genetic alterations in lung adenocarcinoma (LUAD). This study aimed to investigate the profile of concomitant alterations of EGFR‐mutant LUAD ≤3 cm in size and its prognostic effect on recurrence. Methods From January 2018 to December 2018, patients with resected LUAD ≤3 cm in size in Shanghai Chest Hospital were identified. All patients underwent capture‐based targeted next‐generation sequencing (NGS) with a panel of 68 lung cancer‐related genes and were found with EGFR mutation. Clinicopathological and molecular characteristics and recurrence‐free survival (RFS) were analyzed. Results A total of 637 patients were enrolled in this study. The top three frequent co‐mutational genes were TP53 (179 of 637, 28.1%), PIK3CA (27 of 637, 4.2%), and ATM (22 of 637, 3.5%). The most common amplified genes were EGFR (37 of 637, 5.8%), followed by CDK4 (37 of 637, 5.8%) and MYC (12 of 637, 2.0%). Only TP53 mutation and EGFR amplification were adverse prognostic factors for RFS (all p

Interleukin (IL) 21 is a pleiotropic cytokine that plays an important role in regulating innate and adaptive immune responses. In fish, the biological functions and cell source of IL-21 remain largely unknown. In this study, we performed qRT-PCR, Western blotting and immunofluorescent microscopy to examine the expression of IL-21 at the mRNA and protein levels. We found that il21 expression was induced in the primary head kidney leukocytes of grass carp (Ctenopharyngodon idella) by heat-inactivated Aeromonas hydrophila (A. hydrophila) and LPS and in tissues after infection with A. hydrophila. Recombinant IL-21 protein produced in the CHO-S cells was effective in elevating the expression of antibacterial genes, including β-defensin and lysozyme, and, interestingly, inhibited the NF-κB signaling pathway. Furthermore, we investigated the response of the IL-21 expressing cells to A. hydrophila infection. Immunofluorescent assay showed that IL-21 protein was detected in the CD3γ/δ T cells and was markedly accumulated in the anterior, middle and posterior intestine. Collectively, the results indicate that IL-21 plays an important role in regulating the intestinal inflammation induced by bacterial infection in grass carp.

Compared with the traditional antenna array, the time-modulated array can increase the flexibility of the array by adding time switches. However, due to the introduction of time switches, the time-modulated array antenna is more sensitive to random errors than the traditional array. Besides random errors caused by unavoidable factors such as array deformation and defects of processing and assembly in the traditional array, time-modulation parameter errors will be introduced by time switches. As errors in the traditional array can degrade the performance of the array, time-modulation parameter errors can lower the performance of the array pattern as well, which will lift the side-lobe and increase the dynamic range of the side-lobe. Aiming at the time-modulation parameter errors in the time-modulated array, an anti-error robust pattern synthesis algorithm (AERPS) based on the convex optimization (CVX) is proposed in this paper. In the algorithm, the optimization model for the pattern synthesis of the time-modulated array is established and analyzed. Then the model is divided into two sub-models of the center frequency and the first sideband, and the convex optimization solution is first performed on the center frequency model. After the center frequency model is solved, the convex optimization solution is used to solve the first-order sideband model to obtain the final results. The simulation results of the time-modulated array in this paper show that the algorithm can reduce the average value and the dynamic range of the normalized side-lobe level, thus verifying the effectiveness and the robustness of the algorithm.

Cantharellus cibarius, an ectomycorrhizal fungus belonging to the Basidiomycetes, has significant medicinal and edible value, economic importance, and ecological benefits. However, C. cibarius remains incapable of artificial cultivation, which is thought to be due to the presence of bacteria. Therefore, much research has focused on the relationship between C. cibarius and bacteria, but rare bacteria are frequently overlooked, and symbiotic pattern and assembly mechanism of the bacterial community associated with C. cibarius remain unknown. In this study, the assembly mechanism and driving factors of both abundant and rare bacterial communities of C. cibarius were revealed by the null model. The symbiotic pattern of the bacterial community was examined using a co-occurrence network. Metabolic functions and phenotypes of the abundant and rare bacteria were compared using METAGENassist2, and the impacts of abiotic variables on the diversity of abundant and rare bacteria were examined using partial least squares path modeling. In the fruiting body and mycosphere of C. cibarius, there was a higher proportion of specialist bacteria compared with generalist bacteria. Dispersal limitation dominated the assembly of abundant and rare bacterial communities in the fruiting body and mycosphere. However, pH, 1-octen-3-ol, and total phosphorus of the fruiting body were the main driving factors of bacterial community assembly in the fruiting body, while available nitrogen and total phosphorus of the soil affected the assembly process of the bacterial community in the mycosphere. Furthermore, bacterial co-occurrence patterns in the mycosphere may be more complex compared with those in the fruiting body. Unlike the specific potential functions of abundant bacteria, rare bacteria may provide supplementary or unique metabolic pathways (such as sulfite oxidizer and sulfur reducer) to enhance the ecological function of C. cibarius. Notably, while volatile organic compounds can reduce mycosphere bacterial diversity, they can increase fruiting body bacterial diversity. Findings from this study further, our understanding of C. cibarius-associated microbial ecology.

Background: Metal exposure were assumed to be closely related with declined renal function, but the conclusions were controversial. We employed diverse statistical models and assessed the association between metal mixture exposure and mild renal impairment. Methods: A total of 13 plasma metals were measured in 896 general population from Southern China. Subjects with estimated glomerular filtration rate within 60–89 ml/min/1.73 m2 and urinary albumin-creatinine ratio

Cadmium（Cd） is a heavy metal that is harmful to human health. Early studies have shown that cadmium can damage testicular structure, affecting testosterone synthesis and spermatogenesis. However, the effect of paternal Cd exposure on the reproductive system of offspring remains unclear. In this study, male 8-week C57BL/6 J mice were used as research objects, and Cd was injected intraperitoneally every other day at a dose of 1 mg/kg for 5 weeks, after which the effect on the reproductive system of offspring male mice was studied. Our results showed that the body weight of the offspring male mice increased faster, with increases of the testicular and epididymis indices under Cd exposure. At the same time, the serum testosterone and free cholesterol decreased, total cholesterol increased, and the sperm concentration decreased. Further qRT-PCR and western blot analyses showed that the expressions of StAR, P450scc, 3β-HSD and 17β-HSD, which are related to testosterone synthesis, was significantly downregulated. Additionally, ATGL, LDLR and SR-BI, which are related to the intracellular cholesterol pool were downregulated, leading to the reduction of the cholesterol pool and the accumulation of lipid droplets. Oil red O and BODIPY staining revealed an increase in the abundance of lipid droplets in testicular tissue of newborn and adult mice. Prediction of tsRNA target genes in the sperm of parents and testicular transcriptome of newborn mice showed that the differentially expressed genes were associated with catabolism of fatty acids, cholesterol and ion channels, while the mitochondrial and lysosome functions of testicular tissue of adult offspring mice were decreased. Overall, our results suggest that paternal Cd exposure reduced the intracellular cholesterol pool of testicular of offspring, affected testosterone synthesis and reproductive system development.

Abstract Background Although pertussis cases globally have been controlled through the Expanded Programme on Immunization (EPI), the incidence of pertussis has increased significantly in recent years, with a “resurgence” of pertussis occurring in developed countries with high immunization coverage. Attracted by its fast-developing economy, the population of Shenzhen has reached 14 million and has become one of the top five largest cities by population size in China. The incidence of pertussis here was about 2.02/100,000, far exceeding that of the whole province and the whole country (both

Studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in regulating virus infection, host immune response, and other biological processes. Although some lncRNAs have been reported to be involved in antiviral immunity, many lncRNAs have unknown functions in interactions between the host and various viruses, especially influenza A virus (IAV). Herein, we demonstrate that the expression of lncRNA LINC02574 can be induced by IAV infection. Treatment with viral genomic RNA, poly (I:C), or interferons (IFNs) significantly stimulated LINC02574 expression, while RIG-I knockdown and IFNAR1 knockout significantly decreased LINC02574 expression after viral infection or IFN treatment. In addition, inhibition of LINC02574 expression in A549 cells enhanced IAV replication, while overexpression of LINC02574 inhibited viral production. Interestingly, knockdown of LINC02574 attenuated the expression of type I and type III IFNs and multiple ISGs, as well as the activation of STAT1 triggered by IAV infection. Moreover, LINC02574 deficiency impaired the expression of RIG-I, TLR3, and MDA5, and decreased the phosphorylation level of IRF3. In conclusion, the RIG-I-dependent interferon signaling pathway can induce LINC02574 expression. Moreover, the data reveal that LINC02574 inhibits IAV replication by positively regulating the innate immune response.

This study aimed to address the problems of low detection accuracy and inaccurate positioning of small-object detection in remote sensing images. An improved architecture based on the Swin Transformer and YOLOv5 is proposed. First, Complete-IOU (CIOU) was introduced to improve the K-means clustering algorithm, and then an anchor of appropriate size for the dataset was generated. Second, a modified CSPDarknet53 structure combined with Swin Transformer was proposed to retain sufficient global context information and extract more differentiated features through multi-head self-attention. Regarding the path-aggregation neck, a simple and efficient weighted bidirectional feature pyramid network was proposed for effective cross-scale feature fusion. In addition, extra prediction head and new feature fusion layers were added for small objects. Finally, Coordinate Attention (CA) was introduced to the YOLOv5 network to improve the accuracy of small-object features in remote sensing images. Moreover, the effectiveness of the proposed method was demonstrated by several kinds of experiments on the DOTA (Dataset for Object detection in Aerial images). The mean average precision on the DOTA dataset reached 74.7%. Compared with YOLOv5, the proposed method improved the mean average precision (mAP) by 8.9%, which can achieve a higher accuracy of small-object detection in remote sensing images.

Clapping-wing micro air vehicles (CWMAVs) face many control problems due to their lightweight design and susceptibility to disturbances. This study proposes a radial basis function (RBF) model-based adaptive model predictive control (AMPC) for trajectory tracking to solve the control problem in the presence of internal uncertainties and external disturbances. First, a method for calculating the desired attitude is given. Second, a control optimization model is used by adjusting future control inputs to minimize the difference between the future and desired outputs. Third, a nonlinear predictive linearization is used to transform the nonlinear optimization model into a quadratic programming problem. Two observers are introduced to estimate the internal uncertainties and the external disturbances. Finally, the control assignment method is combined with the trajectory tracking method to obtain the design variables of actuators (flapping frequency, pitch angle, and yaw angle). Validation studies were performed to verify the effectiveness and accuracy in the presence of constant and time-dependent disturbances. The comparison of RAMPC with classical methods shows that RAMPC has better control performance with smaller errors. The proposed RAMPC framework can be well used for CWMAV control and provides an excellent basis for accurate navigation and autonomous obstacle avoidance.

Abstract Epidermal growth factor receptor (EGFR) is a key oncogene in lung adenocarcinoma (LUAD). Resistance to EGFR tyrosine kinase inhibitors is a major obstacle for EGFR-mutant LUAD patients. Our gene chip array, quantitative polymerase chain reaction validation, and shRNA-based high-content screening identified the Akt kinase lanthionine synthetase C-like protein 2 (LANCL2) as a pro-proliferative gene in the EGFR-mutant LUAD cell line PC9. Therefore, we investigated whether LANCL2 plays a role in promoting cell proliferation and drug resistance in EGFR-mutant LUAD. In silico clinical correlation analysis using the Cancer Genome Atlas Lung Adenocarcinoma dataset revealed a positive correlation between LANCL2 and EGFR expression and an inverse relationship between LANCL2 gain-of-function and survival in LUAD patients. The EGFR-mutant LUAD cell lines PC9 and HCC827 displayed higher LANCL2 expression than the non-EGFR-mutant cell line A549. In addition, LANCL2 was downregulated following gefitinib+pemetrexed combination therapy in PC9 cells. LANCL2 knockdown reduced proliferation and enhanced apoptosis in PC9, HCC827, and A549 cells in vitro and suppressed murine PC9 xenograft tumor growth in vivo. Notably, LANCL2 overexpression rescued these effects and promoted gefitinib + pemetrexed resistance in PC9 and HCC827 cells. Pathway analysis and co-immunoprecipitation followed by mass spectrometry of differentially-expressed genes in LANCL2 knockdown cells revealed enrichment of several cancer signaling pathways. In addition, Filamin A and glutathione S-transferase Mu 3 were identified as two novel protein interactors of LANCL2. In conclusion, LANCL2 promotes tumorigenic proliferation, suppresses apoptosis, and promotes gefitinib+pemetrexed resistance in EGFR-mutant LUAD cells. Based on the positive association between LANCL2, EGFR, and downstream Akt signaling, LANCL2 may be a promising new therapeutic target for EGFR-mutant LUAD.

Abstract For pre-operative osteoarthritis (OA) patients with varus knee, previous studies showed inconsistent results. Therefore, we conducted this study to better identify the association of Hospital for Special Surgery (HSS) score and mechanical alignment. 44 patients (51 knees) with constitutional varus knee caused by combined deformities (LDFA (lateral distal femoral angle) > 90°and MPTA (medial proximal tibial angle)

Abstract Background Angiogenic placental growth factor (PlGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PlGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms. Methods PlGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) for 24 h. PlGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PlGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed. Results Hypoxia treatment led to up-regulation of PlGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis in H358 and H1975 cells, which were obviously reversed by knocking down PlGF. In tumors, PlGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PlGF overexpression markedly strengthened cell proliferation, which was inhibited by β-catenin knockdown. Consistently, XAV939, inhibitor of Wnt/β-catenin pathway, also inhibited PlGF-induced cell proliferation, glycolysis, and β-catenin expression in PC9 cells. Conclusion PlGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.

With the rapid development of urbanization, land transfer has become a significant part of urban development. This article builds a comprehensive evaluation system to quantify the new-type urbanization level of urban agglomeration in the middle reaches of the Yangtze River from 2006 to 2017. To explore the relationship between the two more clearly, the spatial econometric model and the threshold panel model are used to explore how land transfer affects new-type urbanization. The results show that: the level of new-type urbanization is characterized by fluctuating increases, but that the regional differences show an expanding trend. The Moran’s I of the new-type urbanization fluctuates at approximately 0.120, showing positive spatial correlation. The estimation results of the spatial Durbin model (SDM) indicate that the coefficient of land transfer and its spatial lag coefficient are 0.040 and 0.006 respectively, indicating that it has positive impacts on new-type urbanization. The results of the threshold panel model show that there is a significant nonlinear relationship between land transfer and new-type urbanization. The impacts of land transfer on the level of new urbanization will change in both positive and negative directions with changes in government intervention.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer with heterogeneous outcomes and diverse therapeutic responses. However, the understanding of the potential mechanism behind LUAD initiation and progression remains limited. Increasing evidence shows the clinical significance of the interaction between immune and hypoxia in tumor microenvironment. To mine reliable prognostic signatures related to both immune and hypoxia and provide a more comprehensive landscape of the hypoxia-immune genome map, we investigated the hypoxia-immune-related alteration at the multi-omics level (gene expression, somatic mutation, and DNA methylation). Multiple strategies including lasso regression and multivariate Cox proportional hazards regression were used to screen the signatures with clinical significance and establish an incorporated prognosis prediction model with robust discriminative power on survival status on both the training and test datasets. Finally, combing all the samples, we constructed a robust model comprising 19 signatures for the prognosis prediction of LUAD patients. The results of our study provide a comprehensive landscape of hypoxia-immune related genetic alterations and provide a robust prognosis predictor for LUAD patients.

Abstract Background It has previously been demonstrated that surgically resected small‐cell lung cancer (SCLC) patients could benefit from prophylactic cranial irradiation (PCI). However, PCI in patients without lymph node involvement remains controversial. This study includes a larger sample size to evaluate the benefit of PCI therapy in this specific population. Methods The records of surgically resected SCLC patients without lymph node involvement (N0M0) in Shanghai Chest Hospital were retrospectively reviewed. Results Between January 2006 and May 2017, a total of 146 cases of surgically resected SCLC without lymph node involvement were included. A total of 46 patients received PCI therapy and 100 patients received no therapy. During the observation period, 12.0% (12/100) of the patients who did not receive PCI therapy developed brain metastases while 10.9% (5/46) of patients who received PCI therapy developed brain metastases. With regard to time to recurrence, no significant difference was observed among the groups (P = 0.798). Moreover, there was no significant difference in either the overall survival benefit (hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.49–1.45, P = 0.532) or disease‐free survival rate (HR = 0.95, 95% CI: 0.52–1.75, P = 0.864). Conclusions The evidence obtained does not support PCI therapy in the management of surgically resected SCLC with no lymph node involvement. Key points Prophylactic cranial irradiation (PCI) remains controversial for resected small‐cell lung cancer (SCLC) without lymph node involvement. In this study, the results indicated that PCI does not reduce the risk of cerebral recurrence of resected p‐T1‐2N0M0 SCLC. This is the largest sample size study focused on PCI in resected p‐T1‐2N0M0 SCLC. Future revised versions of the guidelines should address this issue.

ObjectiveSeveral trials have shown that pembrolizumab plus chemotherapy was more effective in patients with advanced non-small-cell lung cancer (NSCLC) than chemotherapy monotherapy. However, whether pembrolizumab plus chemotherapy is still a better choice for first-line treatment in elderly patients (≥75 years old) remain unknown. We retrospectively compared the efficacy and safety of these two treatments in elderly patients.Patients and MethodsWe collected data of 136 elderly patients with advanced NSCLC who were treated with pembrolizumab plus chemotherapy or chemotherapy monotherapy in our hospital from 2018 to 2020. We compared the progression-free survival (PFS) and overall survival (OS) of patients and analyzed which subgroups might benefit more significantly from pembrolizumab plus chemotherapy.ResultsIn total population, pembrolizumab plus chemotherapy showed superior PFS and OS than chemotherapy monotherapy (PFS: 12.50 months vs. 5.30 months, P

Objective: Obesity caused by a high-fat diet (HFD) will expand adipose tissue and cause chronic low-grade systemic inflammation, leading to osteoporosis. Folic acid (FA) is a water-soluble vitamin that plays an essential role in regulating blood lipids and antioxidants. However, the effects and underlying mechanisms of FA in osteoporosis induced by an HFD remain poorly understood. This study aimed to investigate the effect of FA on bone health by using HFD-induced osteoporosis mice.Materials and Methods: Mice were fed a normal diet, HFD or an HFD supplemented with FA (20 μg/ml in drinking water) for 16 weeks. Throughout the 16 weeks study period, the rats were weighed once every week. GTT, ITT and lipid indexes were detected to evaluate the effects of FA on lipid metabolism in the HFD-fed mice. Morphological and structural changes of the femur and tibial bone were observed using micro-CT, HE staining and bone conversion parameters. The expression of MDA, SOD and inflammatory factors were detected to evaluate the effects of FA on oxidative stress and inflammatory response in the HFD-fed mice. Quantitative real-time PCR and Western blot (WB) were used to investigate the AMPK signaling pathway.Results: After the intervention of FA, the body fat rate of obese mice was reduced, and related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation were alleviated. In correlation with those modifications, FA attenuated bone loss and improved bone microarchitecture, accompanied the number of osteoclasts and adipocytes decreased. Furthermore, FA promoted the phosphorylation of AMPK, thereby promoting the expression of Carnitine palmitoyltransferase 1 (CPT1), nuclear factor erythroid-2 related factor 2 (Nrf2) and antioxidant enzymes.Conclusion: These findings suggest that FA may modulate lipid metabolism and oxidative stress responses activating the AMPK signaling pathway, thereby alleviating HFD-induced osteoporosis. The results from our study provide experimental evidence to prevent HFD-induced osteoporosis.