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Abstract Background The diagnosis of peripheral isolated nodular lesions that are suspected as pulmonary tuberculosis (PTB) is challenging, which are not easily accessible via conventional bronchoscopy. This study evaluated the combined use of Xpert MTB/RIF assay and endobronchial ultrasonography with a guide sheath (EBUS-GS) for detecting MTB infection in peripheral lung bands, for early detection of PTB. Methods The clinical data of 232 patients with suspected peripheral nodular PTB who underwent EBUS-GS between June 2020 and October 2023 were retrospectively reviewed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of acid-fast bacilli smear, culture, Xpert MTB/RIF assay, and pathological examination were calculated. To assess diagnostic accuracy, the results of the four methods were directly compared with the final clinical diagnosis. Results In total, 146 and 86 patients were clinically diagnosed with peripheral nodular PTB and non-PTB, respectively. The sensitivity, specificity, PPV, NPV, and AUC values of combined Xpert MTB/RIF assay and EBUS-GS were 47.26%, 100.0%, 100.0%, 52.76%, and 0.74; those of acid-fast bacilli smear were 8.22%, 97.67%, 85.71%, 38.53%, and 0.53; those of culture were 31.51%, 100.0%, 100.0%, 46.24%, and 0.66; and those of pathological examination were 23.97%, 97.67%, 94.59%, 43.08%, and 0.61, respectively. Conclusion The diagnostic accuracy of the combined Xpert MTB/RIF assay and EBUS-GS was significantly better than that of other conventional tests. Hence, this novel technique can be routinely applied for diagnosing and managing peripheral nodular PTB.

Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14–1.18 per μg/m3 in the first trimester; 1.15, 1.12–1.17 in the second trimester; 1.06, 1.04–1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Objective To evaluate the effectiveness of a machine learning based on computed tomography (CT) radiomics to distinguish nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB).Methods In this retrospective analysis, medical records of 99 individuals afflicted with NTM-PD and 285 individuals with PTB in Zhejiang Chinese and Western Medicine Integrated Hospital were examined. Random numbers generated by a computer were utilized to stratify the study cohort, with 80% designated as the training cohort and 20% as the validation cohort. A total of 2153 radiomics features were extracted using Python (Pyradiomics package) to analyse the CT characteristics of the large disease areas. The identification of significant factors was conducted through the least absolute shrinkage and selection operator (LASSO) regression. The following four supervised learning classifier models were developed: random forest (RF), support vector machine (SVM), logistic regression (LR), and extreme gradient boosting (XGBoost). For assessment and comparison of the predictive performance among these models, receiver-operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were employed.Results The Student’s t-test, Levene test, and LASSO algorithm collectively selected 23 optimal features. ROC analysis was then conducted, with the respective AUC values of the XGBoost, LR, SVM, and RF models recorded to be 1, 0.9044, 0.8868, and 0.7982 in the training cohort. In the validation cohort, the respective AUC values of the XGBoost, LR, SVM, and RF models were 0.8358, 0.8085, 0.87739, and 0.7759. The DeLong test results noted the lack of remarkable variation across the models.Conclusion The CT radiomics features can help distinguish between NTM-PD and PTB. Among the four classifiers, SVM showed a stable performance in effectively identifying these two diseases.

Objective This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF).Design Single-centre retrospective study.Setting The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital.Participants We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023.Methods We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM.Results Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively.Conclusion The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.

Lilium davidii var. unicolor is an important edible Llilium species in China. In this study, we investigated the regulatory proteins and pathways affecting bulblet development through analyzing the proteomes among three developmental stages using the isobaric tags for relative and absolute quantitation proteomics approach. A total of 4,802 proteins were detected, 529, 735, and 637 proteins were differentially expressed between the 0 d vs 15 d, 15 d vs 30 d, 0 d vs 30 d stages, respectively. The Gene Otology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that the metabolic pathway, biosynthesis of secondary metabolites and microbial metabolism in diverse environments were the most enriched pathways, which may promote energy formation and protein synthesis processes. Starch and sucrose metabolism was vital to Lilium bulblets development, and energy needed was opposite in the early and later stage of lily bulblets development. Many proteins were significantly regulated, among them LdGASA was detected as being extremely differentially expressed. We cloned the full length of LdGASA, analyzed its expression profile during lily bulblet development, and constructed its overexpression vector and transformed into Arabidopsis thaliana. The results showed that the full length of LdGASA was 725 bp, and the CDS sequence was 336 bp, LdGASA was mainly expressed at the morphogenesis and development stages of bulblets, and reached the highest at the basic morphogenesis of bulblets (35 d), Arabidopsis thaliana transformation with LdGASA presented stronger growth. These results not only deepened our understanding of the bulblets proteome, but also uncovered new insights into lily bulblet enlargement.

Ethnopharmacological relevance: Tumour-derived extracellular vesicles (TEVs) have been confirmed to facilitate colorectal cancer (CRC) metastasis by remodelling the tumour microenvironment (TME). Drugs targeted TEVs is considered as a promising therapeutic strategy for cancer treatment. Traditional Chinese medicine (TCM) plays a vital role in improving the prognosis of CRC patients and eventually CRC patients with distant metastasis. Although the anti-tumour effects of active compounds from TCM prescriptions are observed widely, the molecular mechanisms remain unknown. Aim of the study: This study aims to investigate the effects of active compounds in our library of TCM on preventing CRC metastasis, and also explore the potential mechanisms from the perspective of TEVs. Materials and methods: The effects of active compounds on the proliferation of CRC cells were determined by CCK-8 assay. TEVs were extracted from MC38 cells by ultracentrifugation and characterized by electron microscopy, Nanosight NS300 and western blotting. The TEV particles were quantified by Nanosight NS300. The potential mechanism by which astragaloside IV (ASIV) reduced TEV secretion was determined by western blotting. RAW264.7 cells were cocultured with the conditioned medium (CM) of MC38 cells treated with or without ASIV, and the activation of tumour-associated macrophages (TAMs) was assessed by immunofluorescence and quantitative polymerase chain reaction (qPCR). The migration of CRC cells was measured by wound healing and Transwell assay. A spleen-to-liver metastasis model of colorectal cancer was used to confirm the efficiency of ASIV in vivo. Liver metastatic tumours of the mice were used for liver weight measures and H&E staining. Immunofluorescence was applied to observe the infiltration of TAMs, the expression of neutral sphingomyelinase 2 (nSMase2) and Rab27a. Results: By screening our TCM monomer library, we found that ASIV, which is mainly extracted from Radix Astragali, reduced the release of TEVs from CRC cells in a time- and concentration-dependent manner. Mechanistically, ASIV inhibited the production and secretion of TEVs by downregulating nSMase2 and Rab27a expression in CRC cells. CM from ASIV-treated CRC cells reshaped the polarization of TAMs by decreasing M2-type polarization, increasing M1-type polarization. Consequently, the repolarization of M2-type to M1-type macrophages led to reduced invasion and migration of CRC cells. Moreover, we confirmed that ASIV inhibited the liver metastasis of CRC, reduced M2-type macrophage infiltration and decreased the expression of nSMase2 and Rab27a in liver metastases. Conclusions: ASIV inhibited CRC metastasis by reducing EVs release and suppressing M2-type TAMs activation. All these findings reveal a new insight into the mechanisms of ASIV in preventing CRC progression and provide a promising approach for anti-tumour therapy.

Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.

Background: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. Objective: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. Methods: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. Results: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: −11.92%, −1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: −16.84%, −1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. Conclusion: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.

Background: Left bundle branch pacing (LBBP) is a physiological pacing that captures the main left bundle or its proximal branch. Electromechanical activation time (EMAT) is an acoustic cardiographic metric that provides a simple method for evaluating left ventricular (LV) synchrony. Prolonged EMAT reflects impaired LV electromechanical coupling. Objective: The purpose of this study was to explore whether EMAT can confirm that LBBP produces more satisfactory LV electromechanical synchronization than conventional right ventricular pacing modalities. Methods: Patients with standard pacing indications and narrow QRS duration were recruited for this study. Unipolar pacing under 3 different modalities—right ventricular apical pacing (RVAP), right ventricular high septal pacing (RVHSP), and LBBP—were successively performed in each patient. Pacing parameters, echocardiographic characteristics, and acoustic cardiographic parameters at different pacing modalities and during normal rhythm were collected. Results: A total of 55 patients were enrolled, and all had successful LBBP. Left ventricular activation time (LVAT) was significantly associated with EMAT, with LVAT vs EMAT correlation coefficient of 0.665 (P

Based on core observation, thin section examination, fluid inclusions analysis, carbon and oxygen isotopic composition analysis, and other approaches, the structural and burial evolution histories were investigated, and the diagenetic evolution process and genetic/development models were systematically discussed of the Upper Paleozoic Permian clastic rock reservoirs in the Bohai Bay Basin, East China. The Bohai Bay Basin underwent three stages of burial and two stages of uplifting in the Upper Paleozoic. Consequently, three stages of acid dissolution generated by the thermal evolution of kerogen, and two stages of meteoric freshwater leaching occurred. Dissolution in deeply buried, nearly closed diagenetic system was associated with the precipitation of authigenic clay and quartz, leading to a limited increase in storage space. Different structural uplifting–subsidence processes of tectonic zones resulted in varying diagenetic–reservoir-forming processes of the Permian clastic reservoirs. Three genetic models of reservoirs are recognized. The Model I reservoirs with pores formed in shallow strata and buried in shallow to medium strata underwent two stages of exposure to long-term open environment and two stages of meteoric freshwater leaching to enhance pores near the surface, and were shallowly buried in the late stage, exhibiting the dominance of secondary pores and the best physical properties. The Model II reservoirs with pores formed in shallow strata and preserved due to modification after deep burial experienced an early exposure-open to late burial-closed environment, where pore types were modified due to dissolution, exhibiting the dominance of numerous secondary solution pores in feldspar and the physical properties inferior to Model I. The Model III reservoirs with pores formed after being regulated after multiple periods of burial and dissolution experienced a dissolution of acidic fluids of organic origin under a near-closed to closed environment, exhibiting the dominance of intercrystalline micropores in kaolinite and the poorest physical properties. The target reservoirs lied in the waterflood area in the geological period of meteoric freshwater leaching, and are now the Model II deep reservoirs in the slope zone–depression zone. They are determined as favorable options for subsequent exploration.

Predicting construction costs often involves disadvantages, such as low prediction accuracy, poor promotion value and unfavorable efficiency, owing to the complex composition of construction projects, a large number of personnel, long working periods and high levels of uncertainty. To address these concerns, a prediction index system and a prediction model were developed. First, the factors influencing construction cost were first identified, a prediction index system including 14 secondary indexes was constructed and the methods of obtaining data were presented elaborately. A prediction model based on the Random Forest (RF) algorithm was then constructed. Bird Swarm Algorithm (BSA) was used to optimize RF parameters and thereby avoid the effect of the random selection of RF parameters on prediction accuracy. Finally, the engineering data of a construction company in Xinyu, China were selected as a case study. The case study showed that the maximum relative error of the proposed model was only 1.24%, which met the requirements of engineering practice. For the selected cases, the minimum prediction index system that met the requirement of prediction accuracy included 11 secondary indexes. Compared with classical metaheuristic optimization algorithms (Particle Swarm Optimization, Genetic Algorithms, Tabu Search, Simulated Annealing, Ant Colony Optimization, Differential Evolution and Artificial Fish School), BSA could more quickly determine the optimal combination of calculation parameters, on average. Compared with the classical and latest forecasting methods (Back Propagation Neural Network, Support Vector Machines, Stacked Auto-Encoders and Extreme Learning Machine), the proposed model exhibited higher forecasting accuracy and efficiency. The prediction model proposed in this study could better support the prediction of construction cost, and the prediction results provided a basis for optimizing the cost management of construction projects.

Scholars and engineers have increasingly focused on the safety of steel-structure buildings. An accurate analysis can substantially reduce the collapse probability of these buildings. This paper proposes a novel risk analysis model to assess the safety of steel-structure buildings. The vector entropy method and weight clustering were used to improve the controlled interval and memory (CIM) model. The proposed model has the advantages of a straightforward modeling approach, strong adaptability, and logical relationships. The new strategy improves the reliability and stability of the CIM model results when the maximum membership principle is not applicable. The Jiangxi Exhibition Center in China, which has a steel truss roof, is used as a case study. The results indicate a high safety risk of the project and the need for maintenance and repair. The improved CIM model has higher stability and adaptability for analyzing the safety risks of steel structure than the standard CIM model.

Aspergillus cristatus is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography–mass spectrometry (LC–MS) combined with multivariate analysis was performed to analyze the distribution and composition of A. cristatus under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC–MS metabolomics analysis revealed significant differences between three A. cristatus mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of A. cristatus mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that A. cristatus adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition.

Cutting edge preparation is a precision machining process that improves the surface quality of cutting tools through the relative movement of abrasives and the tool. Research on removing materials in drag finishing can be greatly beneficial to tool manufacturing. This paper proposes the hypothesis that both abrasive wear and erosion wear act on the surface of milling tools and discusses the material removal models for abrasive wear and erosion wear. The influence of immersion depth, abrasive velocity, abrasive radius, and abrasive density on the material removal rate in two material removal forms is compared and validated by discrete element simulations. The results show that immersion depth has a greater impact on abrasive wear, while abrasive properties have a greater impact on erosion wear. The correlation between simulation results and theoretical models demonstrates the sensitivity of the two forms of wear on this surface to parameter change differences. Dragging finishing was conducted to verify the effectiveness of the simulation, and the effects of immersion depth, dragging velocity, and abrasive properties on the edge radius and form factor (K value) were studied.

Abstract The “hotness” or “coldness” of the tumors are determined by the information of the cancer cells themselves, tumor immune characteristics, tumor microenvironment, and signaling mechanisms, which are key factors affecting cancer patients’ clinical efficacy. The switch mechanism of “hotness” and “coldness” and its corresponding pathological characteristics and treatment strategies are the frontier and hot spot of tumor treatment. How to distinguish the “hotness” or “coldness” effectively and clarify the causes, microenvironment state, and characteristics are very important for the tumor response and efficacy treatments. Starting from the concept of hot and cold tumor, this review systematically summarized the molecular characteristics, influencing factors, and therapeutic strategies of “hot and cold tumors,” and analyzed the immunophenotypes, the tumor microenvironment, the signaling pathways, and the molecular markers that contribute to “hot and cold tumors” in details. Different therapeutic strategies for “cold and hot tumors” based on clinical efficacy were analyzed with drug targets and proteins for “cold and hot tumors.” Furthermore, this review combines the therapeutic strategies of different “hot and cold tumors” with traditional medicine and modern medicine, to provide a basis and guidance for clinical decision‐making of cancer treatment.

Platelet-derived extracellular vesicles (P-EVs), as the most abundant vesicles in blood, have been proven to play cardinal roles in cardiovascular injury. RNAs (especially miRNAs) carried by P-EVs can be transferred to the receptor, which plays a critical role in regulating vascular endothelial function. PM2.5 is one of the most well-known risk factors that cause cardiovascular disease. Therefore, the objective of the current study was to explore whether exposure to PM2.5 would alter the gene expression profile of P-EVs, and to further elucidate the role of RNAs (especially miRNAs) carried by P-EVs in cardiovascular injury induced by PM2.5 exposure. P-EVs were isolated from the platelet-rich plasma which was exposed and unexposed to PM2.5, and the differentially expressed target genes were evaluated using whole-transcriptome gene sequencing. Rats were treated with P-EVs under different exposure conditions (a protein concentration of 50 µg/mL) and an equal volume of normal saline. The pathological damage of the thoracic aorta and cardiac tissue was evaluated and the coagulation function of the rats was detected. The differentially expressed genes were shown to be mainly concentrated in inflammation, angiogenesis, and apoptosis-related pathways. Moreover, P-EVs extracted from PM2.5-exposed plasma had the potential to trigger an inflammatory response, impair vascular endothelial function, disrupt the normal coagulation process, and promote a prothrombotic state. Our study indicated that PM2.5 induces cardiovascular injury in rats by interfering with the gene expression of P-EVs. It will provide new targets for studying the mechanism involved in PM2.5-induced cardiovascular injury.

The non-Hermitian skin effect comprises of boundary localised eigenmodes and has been realised in a range of 1D systems such as photonics and metamaterials. Here, the authors achieve the same effect in a quantum many-body setting using ultra-cold gases and, by tuning the strength of the spin orbit coupling, realise a non-trivial band topology.

Bohai Bay Basin is one of the main exploitation areas of continental shale oil resources in China.Qikou Sag, located in the hinterland of the basin, is one of the typical oil and gas rich depressions in Bohai Bay Basin.This paper selects the organic rich shale in the Lower First Member of Shahejie Formation in Qikou Sag as the research object, and comprehensively uses geochemical logging technology and hydrocarbon generation and expulsion simulation technology to describe the shale sedimentary characteristics and comprehensive evaluation of shale oil potential in the Lower First Member of Shahejie Formation in Qikou Sag.The results show that the Lower First Member of Shahejie Formation in Qikou Sag was deposited in the reduction strong reduction environment with high water salinity, rich nutrients, hot and humid climate, suitable for biological mass reproduction and high productivity.Combined with the hydrocarbon generation and expulsion simulation experiment results, the Lower First Member of Shahejie Formation shale in the study area has strong hydrocarbon generation capacity, high hydrocarbon generation efficiency and low oil discharge rate.Most of the generated crude oil is still left in the shale, which has good exploration potential.The Lower First Member of Shahejie Formation shale in the study area contains an appropriate amount of carbonate minerals, which improves the reservoir conditions during diagenesis and provides a good reservoir site for shale oil.The occurrence of transgression in the southwest margin of Qikou Sag affects the enrichment of organic matter in the Lower First Member of Shahejie Formation from the aspects of sedimentary environment, paleoproductivity and its impact on diagenesis.The enrichment of organic matter, high hydrocarbon generation intensity and good reservoir conditions control the large-area distribution of shale oil in the Lower First Member of Shahejie Formation.Shale oil reservoirs in the Lower First Member of Shahejie Formation in the study area can be divided into carbonate rocks and mixed sedimentary rocks.After synthesizing the oil-bearing characteristics of the two reservoirs, it is found that the mineral content and brittleness index of carbonate rocks have a great impact on shale oil-bearing properties.In the process of further exploration, oil reservoirs can be found in the wide and gentle slope area conducive to the formation of structural fractures and the area with high degree of dolomitization in the study area.The favorable exploration intervals are dolomite, dolomitic shale and calcareous shale with developed pores and micro fractures.The research results provide guidance for the exploration and development of shale oil in Qikou Sag.

Objectives: The aim of this study was to assess the role of nanopore sequencing using respiratory specimens in the early diagnosis of pulmonary tuberculosis (PTB) and simultaneously compare it head-to-head with Mycobacterium tuberculosis (MTB) culture, and Xpert MTB/rifampin (RIF). Methods: The clinical data of 164 patients with suspected PTB were retrospectively reviewed to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the acid-fast bacilli (AFB) smear, MTB culture, Xpert MTB/RIF, and nanopore sequencing and assess their diagnostic accuracy compared with culture combined with clinical diagnosis. Results: The overall sensitivity, specificity, PPV, NPV, and AUC of the AFB smear were 27.6%, 87.5%, 84.2%, 33.3%, and 0.58, respectively; for MTB culture, these values were 57.8%, 100.0%, 100.0%, 49.5%, and 0.79, respectively; for Xpert MTB/RIF, these values were 62.9%, 97.9%, 98.7%, 52.2%, and 0.80, respectively; and for nanopore sequencing, these values were 94.8%, 97.9%, 99.1%, 88.7%, and 0.96, respectively. Conclusion: The diagnostic accuracy of nanopore sequencing was excellent in terms of PTB diagnosis and was considerably better than that of the Xpert MTB/RIF and MTB culture. Nanopore sequencing could be an effective alternative to Xpert MTB/RIF for the initial detection of PTB to improve the accuracy of PTB diagnosis.

The exploitation of offshore wind resources is a crucial step towards a clean energy future. It requires an advanced approach for high-resolution wind resource evaluations. We explored the suitability of the Sentinel-1 Level-2 OCN ocean wind field (OWI) product for offshore wind resource assessments. The SAR data were compared to in situ observations and three reanalysis products: the global reanalysis ERA5 and two regional reanalyses CARRA and NORA3. This case study matches 238 scenes from 2022 for the Goliat station, an oil platform located 85 km northwest of Hammerfest in the Barents Sea, where a new offshore wind park has been proposed. The analysis showed that despite their unique limitations in spatial and temporal resolutions, all data sources have similar statistical properties (RMSE, correlation coefficient, and standard deviation). The Weibull parameters characterizing the wind speed distributions showed strong similarities between the Sentinel-1 and all reanalysis data. The Weibull parameters of the in situ measurements showed an underestimation of wind speed compared to all other sources. Comparing the full reanalysis datasets with the subsets matching the SAR scenes, only slight changes in Weibull parameters were found, indicating that, despite its low temporal resolution, the Sentinel-1 Level 2 OWI product can compete with the more commonly used reanalysis products in the estimation of offshore wind resources. Its high spatial resolution, which is unmatched by other methods, renders it especially valuable in offshore areas close to complex coastlines and in resolving weather events at a smaller scale.

Abstract Background Milk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas. Objectives To evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months. Methods In a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months. Results Infants (n = 375) completed the study with average dropout of

As the main factors affecting stable and high production and the production regularity of lacustrine shale oil are unclear, the theoretical understandings, key exploration and development technologies, development effect and production regularity of lacustrine shale oil have been analyzed and summarized based on 700 m cores taken systematically from Paleogene Kong 2 Member of 4 wells in Cangdong sag, over 100 000 analysis data and formation testing data. Three theoretical understandings on shale oil enrichment and high production have been reached: (1) High-quality shale with “three highs and one low” is the material base for shale oil enrichment. (2) Medium—slightly high thermal evolution degree is the favorable condition for shale oil enrichment. (3) Laminar felsic shale is the optimal shale layer for oil enrichment in semi-deep lake facies. Key exploration and development technologies such as shale oil enrichment layer and area evaluation and prediction, horizontal well pattern layout, shale oil reservoir fracturing, optimization of shale oil production regime have been established to support high and stable shale oil production. Under the guidance of these theoretical understandings and technologies, shale oil in Cangdong sag has achieved high and stable production, and 4 of them had the highest production of over 100 tons a day during formation testing. In particular, Well GY5-1-1L had a daily oil production of 208 m3. By April, 2022, the 28 wells combined have a stable oil production of 300–350 tons a day, and have produced 17.8×104 t of oil cumulatively. It is found that the shale oil production of horizontal well declines exponentially in natural flow stage, and declines in step pattern and then tends stable in the artificial lift stage. Proportion of light hydrocarbons in produced shale oil is in positive correlation with daily oil production and decreases regularly during production test.

With the detection of nano-plastics (NPs) in daily essentials and drinking water, the potential harm of NPs to human health has become the focus of global attention. Studies have shown that long term exposure to NPs can lead to disorders of glucose and lipid metabolism in organisms, while the effects of short term exposure are rarely reported. Moreover, environmental factors cause the aging of NPs, and it is unclear whether this has an effect on their toxicity. In this study, we use 100 nm polystyrene (PS) NPs and ultraviolet (UV) aging PS (aPS) NPs to gavage mice for 7 days at an exposure dose of 50 mg/kg/day. To evaluate the effects of exposure on mice hepatic glucose lipid metabolism, we performed blood biochemical, pathological and metabolomic analyses. The results showed that exposure to PS NPs and aPS NPs increased serum glucose, disrupted serum lipoprotein levels, and up-regulated the expression levels of phosphatidylinositol 3-kinase (PI3K)/ phosphoprotein kinase B (p-AKT)/Glucose transporter 4 (GLUT4) proteins in the glucose metabolism pathway. The expression levels of key proteins sterol regulatory element binding protein-1 (SREBP-1)/peroxisome proliferator-activated receptor-γ (PPARγ)/adipose triglyceride lipase (ATGL) in the lipid metabolism signaling pathway were significantly increased. These findings suggest that short term exposure to PS NPs and aPS NPs induces glycolipid metabolism disturbance in mice, which may subsequently awaken the mice to self-regulate the serum levels of various lipoproteins and the expression of related key proteins. Compared with PS NPs, the aPS NPs interfered more strongly with glucose metabolism, and the corresponding self-regulation in mice was also more obvious. These findings not only provide a basis for environmental factors to increase the health risk of NPs but also provided a reference for the selection of test substances for further studies on the toxicity of NPs.

Abstract Background Quantum dots (QDs) have gained increased attention for their extensive biomedical and electronic products applications. Due to the high priority of QDs in contacting the circulatory system, understanding the hemocompatibility of QDs is one of the most important aspects for their biosafety evaluation. Thus far, the effect of QDs on coagulation balance haven’t been fully understood, and limited studies also have yet elucidated the potential mechanism from the perspective of interaction of QDs with coagulation-related proteins. Results QDs induced the derangement of coagulation balance by prolonging the activated partial thromboplastin time and prothrombin time as well as changing the expression levels of coagulation and fibrinolytic factors. The contact of QDs with PTM (prothrombin), PLG (plasminogen) and FIB (fibrinogen) which are primary coagulation-related proteins in the coagulation and fibrinolysis systems formed QDs-protein conjugates through hydrogen-bonding and hydrophobic interaction. The affinity of proteins with QDs followed the order of PTM > PLG > FIB, and was larger with CdTe/ZnS QDs than CdTe QDs. Binding with QDs not only induced static fluorescence quenching of PTM, PLG and FIB, but also altered their conformational structures. The binding of QDs to the active sites of PTM, PLG and FIB may promote the activation of proteins, thus interfering the hemostasis and fibrinolysis processes. Conclusions The interactions of QDs with PTM, PLG and FIB may be key contributors for interference of coagulation balance, that is helpful to achieve a reliable and comprehensive evaluation on the potential biological influence of QDs from the molecular level.

A negative tectonic area refers to the relatively lower tectonic area from slope to deep depression in a basin. The theoretical understanding of oil and gas accumulation in the negative tectonic area is based on three accumulation models of "lithologic and stratigraphic reservoirs in the area of sag, lacustrine shale oil in deep depression, and coalbed methane in syncline area". Integrating with previous studies on reservoirs in negative tectonic area, a systematic knowledge system of oil and gas accumulation mechanisms and distribution laws in negative tectonic areas has been formed. The key points are as follows: (1) From the center to the margin of basin, oil and gas reservoirs are distributed in a circular order in the transverse direction, and enrich radially along dominant petroleum migration pathways in the longitudinal direction. (2) Due to different tectonic backgrounds, the sedimentary characteristics, hydrocarbon accumulation conditions, accumulation mechanism and distribution laws of negative tectonic area are greatly different from those of the positive tectonic area. (3) In deep depression and low slope, in situ hydrocarbon accumulation is dominant, and unconventional oil and gas distribution ring (inner ring) is formed. On medium and high slopes, passing oil and gas are captured, and lithologic and stratigraphic oil and gas distribution ring (central ring) is formed. While in positive tectonic area, oil and gas accumulate in high locations, and tectonic oil and gas distribution ring (outer ring) is developed. (4) An exploration idea based on the theory of oil and gas accumulation in negative tectonic area was proposed as follows. The target area should be integrately considered and exploration should be carried out from ring to ring. Migration pathways must be reguarded as a clue to seize oil and gas targets. The theory of oil and gas accumulation in negative tectonic area has effectively guided the discovery of a large number of subtle and unconventional oil and gas reservoirs in the slopes and deep sags of Jizhong and Huanghua depressions, and enriched the modern theory of oil and gas accumulation. It has an important practical guiding value for the exploration of deep complex subtle reservoirs and unconventional reservoirs in the negative tectonic area of basins.

Abstract The present study aimed to reveal the amount per application of facial sheet masks and its influencing factors in Chinese population to form the base for an accurate exposure assessment. A total of 175 healthy subjects aged 18 years or older were recruited and divided into two subgroups: one group of 35 subjects were asked to apply same mask for 5, 10, 15, 20, 25, and 30 min respectively, and the other 140 subjects were instructed to apply one of four types of facial sheet masks presented in the market for 15 min. Furthermore, phenoxyethanol and methylparaben were measured to reflect actual exposure to chemicals. The sharp increase in the relative exposure to phenoxyethanol (CAS NO.122-99-6) and methylparaben at 25 min and longer suggests applying facial sheet masks for longer than 20 min may drive the exposure to hazardous chemicals to increase significantly. The 90th percentile of amount per application for plant-cellulose, bamboo charcoal fiber, bio-cellulose, and binchotan charcoal fiber-based masks was 5.753, 5.371, 5.017, and 4.821 g respectively. In addition, men and subjects with sebaceous skin demonstrated lower amount per application compared to women and subjects with dry skin, respectively. Finally, our data showed that the larger the contacting area between face and mask, the more amount per application. We concluded that the appropriate time of application should be less than 20 min. And mask fabrics, gender, sebum content, and contacting area could significantly impact the risk assessment of facial sheet masks. Our data for the first time provides insights into a realistic risk assessment of facial sheet masks in Chinese population.

Abstract Cancer occurs in a complex tissue environment, and its progression depends largely on the tumour microenvironment (TME). The TME has a highly complex and comprehensive system accompanied by dynamic changes and special biological characteristics, such as hypoxia, nutrient deficiency, inflammation, immunosuppression and cytokine production. In addition, a large number of cancer-associated biomolecules and signalling pathways are involved in the above bioprocesses. This paper reviews our understanding of the TME and describes its biological and molecular characterization in different stages of cancer development. Furthermore, we discuss in detail the intervention strategies for the critical points of the TME, including chemotherapy, targeted therapy, immunotherapy, natural products from traditional Chinese medicine, combined drug therapy, etc., providing a scientific basis for cancer therapy from the perspective of key molecular targets in the TME.

Background Phosphorus (P) is abundant in soils, including organic and inorganic forms. Nevertheless, most of P compounds cannot be absorbed and used by plants. Aspergillus niger v. Tiegh is a strain that can efficiently degrade P compounds in soils. Methods In this study, A. niger xj strain was mutated using Atmospheric Room Temperature Plasma (ARTP) technology and the strains were screened by Mo-Sb Colorimetry with strong P-solubilizing abilities. Results Compared with the A. niger xj strain, setting the treatment time of mutagenesis to 120 s, four positive mutant strains marked as xj 90–32, xj120–12, xj120–31, and xj180–22 had higher P-solubilizing rates by 50.3%, 57.5%, 55.9%, and 61.4%, respectively. Among them, the xj120–12 is a highly efficient P solubilizing and growth-promoting strain with good application prospects. The growth characteristics such as plant height, root length, and dry and fresh biomass of peanut (Arachis hypogaea L.) increased by 33.5%, 43.8%, 43.4%, and 33.6%, respectively. Besides available P, the chlorophyll and soluble protein contents also vary degrees of increase in the P-solubilizing mutant strains. Conclusions The results showed that the ARTP mutagenesis technology can improve the P solubilization abilities of the A. niger mutant strains and make the biomass of peanut plants was enhanced of mutant strains.

Based on detailed core description and systematic joint test data, enrichment laws of continental shale oil have been examined deeply. Key technologies such as the identification and quantitative evaluation method for sweet spot, precise design and tracking of horizontal well trajectory, and the low-cost horizontal well volume fracturing technology of the whole process “slick water + quartz sand” for continental shale oil have been formed. The research results show that the enrichment of pure continental shale oil of the Paleogene Kong 2 Member in Cangdong Sag is controlled by predominant fabric facies and cross-over effect of retained hydrocarbons jointly; and there are four modes of shale oil enrichment, i.e. laminar felsic, laminar mixed, thin-layer limy dolomitic, and thick-layer limy dolomitic shales. The identification and evaluation method for shale oil sweet spots can predict sweet spots accurately. The precise trajectory design for sweet spot layer and tracking-trajectory optimization while drilling by considering geological and engineering factors have been proved effective by field application, with drilling rate of sweet spots reaching 100% and drilling rate of type I sweet spots reaching over 75%. The whole process “slick water + quartz sand” low cost volume fracturing has been proved effective in creating multi-stage fracture network in the horizontal section, and improved productivity greatly. It can lower the comprehensive engineering cost by 26.4%.

Compared with marine facies shale strata, lacustrine shale strata are more complicated in geological conditions, and thus more difficult to explore and develop. To realize economic exploration and development of lacustrine shale oil, the geological regularities of accumulation and high yield of retained movable petroleum in shale should be understood first. In this work, taking the shale strata of Kong 2 Member and Sha 3 Member in the Paleogene of Huanghua depression in the Bohai Bay Basin as examples, based on the previous joint analysis results of over ten thousand core samples and the latest oil testing, production test and geochemical data of more than 30 horizontal wells, accumulation conditions and models of retained movable petroleum in lacustrine shale were studied comprehensively. The study shows that at moderate organic matter abundance (with TOC from 2% to 4%), shale strata have the best match between oil content and brittleness, and thus are rich in oil and good in fracability. Moderate ancient lake basin size and moderate sediment supply intensity are the internal factors leading to best coupling of organic matter abundance and brittle mineral content in the shale formation. Moderate thermal evolution maturity of Ro of 0.7%–1.0% (at burial depth of 3200 to 4300 m) is the interval where oil generation from thermal evolution and oil adsorption by kerogen in shale layers match best, and retained movable petroleum is high in proportion. Moderate diagenetic evolution stage (3200 to 4300 m in the middle diagenetic stage A) is conducive to the formation of a large number of dissolved pores and organic matter pores, which provide storage space for shale oil enrichment. Moderate development degree of natural fractures (without damaging the shale oil roof and floor sealing conditions) is conducive to the storage, seepage and preservation of shale oil. The research results have overthrown the general understanding that high organic matter abundance, high maturity, and high development degree of natural fractures are conducive to shale oil enrichment, and have guided the comprehensive evaluation of shale oil and gas sweet spots and well deployment in the second member of the Kongdian Formation in the Cangdong sag and the Shahejie Formation in the Qikou sag. Industrial development of the shale oil in Kong 2 Member of the Cangdong sag has made major breakthrough, and important signs of shale oil have been found in Sha 3 Member of the Qikou sag, demonstrating huge exploration potential of lacustrine shale oil.

Abstract Background Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. Methods Here, we used C57BL/6 J Apc Min/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Results We report herein, YYFZBJS treatment blocked tumor initiation and progression in Apc Min/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal’s natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation’ expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in Apc Min/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin. Conclusions In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract Graphical abstract

To better understand the micropore characteristics of lacustrine shale and develop quantitative methods for characterizing lacustrine shale, the reservoir space types, structures and spatial distribution patterns of effective pores in the shale of Member 2 of Kongdian Formation in Cangdong sag are studied using cores, thin sections, scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), nuclear magnetic resonance (NMR), whole-rock X-ray diffraction (XRD) data, etc. Various shale porosity calculation methods are evaluated. The study results show that the reservoir spaces of the shale mainly include three types, i.e., matrix pores, organic pores and fractures. Flaky pore throats formed by dissolution-induced pores and mould pores can improve the pore connectivity. NMR effective porosity of the shale varies from 0.59% to 4.42% with an average of 2.38%, accounting for 49.54% of the total NMR porosity and 34.53% of the gas porosity. The shale is divided into the unimodal-type felsic shale, bimodal-type felsic shale, carbonate shale and mixed shale. The different lithologies exhibit linear correlations among NMR, gas and effective porosities. The shale has effective porosity of 0.56%–4.53% with an average of 2.12%. Furthermore, the shale reservoir is divided into four classes: Class I reservoir with effective porosities of more than 2.5%; Class II1 reservoir with effective porosity of 2.0%–2.5%; Class II2 reservoir with effective porosity of 1.5%–2%; and Class III reservoir with effective porosity of less than 1.5%.

Based on core, logging, lab test and seismic data, sedimentary characteristics and pattern of marine hyperpycnal flow, the distribution rules of hyperpycnal flow reservoir, prediction method of favorable hyperpycnal flow reservoir zones, hydrocarbon accumulation model in hyperpycnal flow reservoir in D block of Bay of Bengal were investigated, and the favorable exploration zone and well sites were predicted. Pliocene in D block has typical hyperpycnal flow sediment, which is a set of fine-medium sandstone held between thick layers of marine mudstone and features a series of reverse grading unit and normal grading unit pairs. The hyperpycnal flow sediment appears as heavily jagged box shape, bell shape and tongue shape facies on log curves with linear gradient, and corresponds to multiple phases of deep channels on the seismic section and high sinuous channel on stratal slices. The sedimentary bodies formed by a single phase hyperpycnal flow which include five types of microfacies, namely, supply channel (valley), channel complex, branch channel, levee and sheet sand. The hyperpycnal flow sediments appear in multiple branches, multiple generations and stages in space, forming high-quality reservoirs in strips on the plane and superposition vertically, with fairly good physical properties. The channel complex sandstone, with large thickness, coarse particle size and good physical properties, is the most favorable exploration facies. Based on the guidance of the sedimentary model, distribution of the channel complex microfacies was delineated in detail by seismic reflection structure analysis, spectrum waveform characteristic analysis, slice and attribute fusion, and combined with the structural feature analysis, the favorable drilling zone was sorted out, effectively guiding the exploration deployment of the block. Key words: Bay of Bengal, Rakhine Basin, Pliocene, gravity flow, hyperpycnal flow, sedimentary pattern, reservoir, oil and gas exploration

Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

Objective. Because the response of evaporating light scattering detector (ELSD) being in a nonlinear mode, there is no consensus on the method of calculating its relative correction factors (RCF), which limits the application of the quantitative analysis for multi-components by a single marker (QAMS) with LC-ELSD. Methods. Using eight fructooligosaccharides of Morinda officinalis as a case study, the nystose (GF3) as a single standard was adopted to develop a QAMS method to simultaneously determine the other seven fructooligosaccharides with HILIC-HPLC-ELSD method. Six calculation methods of RCF were investigated to select the most reasonable method. The relative error of content between the QAMS and the external standard method (ESM) obtained from 30 batches of samples was used as an indicator to evaluate the six methods. Finally, a chemometrics analysis was performed to find the differential components among MO and its three processing products. Results. It was first reported that only one calculation method was scientific for calculating RCF for the LC-ELSD method. The RCFs of GF3 to the other seven fructooligosaccharides (GF1–GF8) were obtained as 0.86, 0.91, 0.93, 1.05, 1.15, 1.12, and 1.18, respectively. The QAMS of eight fructooligosaccharides of Morinda officinalis was validated with good linearity (R2 > 0.9998) and accepted the accuracy of 95–105% (RSD

Wind energy, an important component of clean energy, is highly dictated by the disposable wind speed within the working regime of wind turbines (typically between 3 and 25 m s ^−1 at the hub height). Following a continuous reduction (‘stilling’) of global annual mean surface wind speed (SWS) since the 1960s, recently, researchers have reported a ‘reversal’ since 2011. However, little attention has been paid to the evolution of the effective wind speed for wind turbines. Since wind speed at hub height increases with SWS through power law, we focus on the wind speed frequency variations at various ranges of SWS through hourly in-situ observations and quantify their contributions to the average SWS changes over 1981–2021. We found that during the stilling period (here 1981–2010), the strong SWS (⩾ 5.0 m s ^−1 , the 80th of global SWS) with decreasing frequency contributed 220.37% to the continuous weakening of mean SWS. During the reversal period of SWS (here 2011–2021), slight wind (0 m s ^−1 < SWS < 2.9 m s ^−1 ) contributed 64.07% to a strengthening of SWS. The strengthened strong wind (⩾ 5.0 m s ^−1 ) contributed 73.38% to the trend change of SWS from decrease to increase in 2010. Based on the synthetic capacity factor series calculated by considering commercial wind turbines (General Electric GE 2.5-120 model with rated power 2.5 MW) at the locations of the meteorological stations, the frequency changes resulted in a reduction of wind power energy (−10.02 TWh yr ^−1 , p < 0.001) from 1981 to 2010 and relatively weak recovery (2.67 TWh yr ^−1 , p < 0.05) during 2011–2021.

The study of lithofacies identification and its distribution characterizations of shales is essential for the geological evaluation of shale oil exploration and development. In this study, core description, optical microscope, total organic carbon (TOC) content, whole-rock X-ray diffraction (XRD), Rock-Eval pyrolysis, X-ray fluorescence (XRF), scanning electron microscope (SEM), and well logging data were used in the qualitative analyses of the geochemical and mineralogical characteristics of shales. Since the work of detailed lithofacies identification is still lacking in the previous studies, based on TOC, sedimentary structure, and ternary diagram of siliceous minerals, carbonate minerals, and clay minerals, eight predominant lithofacies were identified in the shale of the second member of the Kongdian Formation (Ek2): ① low to moderate organic matter content (referred to as “low to moderate TOC”) massive calcareous mudstone (C-1); ② low to moderate TOC laminated calcareous mudstone (C-2); ③ low to moderate TOC layered mixed calcareous mudstone (C-3); ④ moderate to high organic matter content (referred to as “moderate to high TOC”) laminated calcareous siliceous mudstone (S-1); ⑤ moderate to high TOC massive mixed siliceous mudstone (S-2); ⑥ moderate to high TOC laminated clayey siliceous mudstone (S-3); ⑦ low to moderate TOC massive mixed mudstone (M-1); ⑧ moderate to high TOC layered calcareous/siliceous mixed mudstone (M-2). The favorability of lithofacies was investigated based on TOC, pyrolysis parameters, pore structures, and specific mineral contents. S-1 was currently considered as the most favorable lithofacies with excellent hydrocarbon potential, high amount of free hydrocarbon, and abundant organic pores; S-2, S-3, and M-2 were considered as favorable lithofacies, while C-1 and M-1 were ranked as the least-promising lithofacies in the research area. The lateral distribution of the shale is quite different, and Ek23 contains the most favorable lithofacies for shale oil exploration.

Based on seismic and logging data, taking the downthrow fault nose of Binhai fault in Qikou Sag as the object of study, we analyzed fault characteristics, sand body distribution, fault-sand combinations and hydrocarbon accumulation to reveal the hydrocarbon enrichment law in the fault-rich area of fault depression lake basin. The results show that the Binhai Cenozoic fault nose is characterized by east-west zoning, the main part of the western fault segment is simple in structure, whereas the broom-shaped faults in the eastern segment are complex in structure, including several groups of faults. The difference of fault evolution controls the spatial distribution of sand bodies. The sand bodies are in continuous large pieces in the downthrow fault trough belt along the Gangdong Fault in the middle segment of the fault nose, forming consequent fault-sand combination; whereas the fault activity period of the eastern part of the fault nose was later, and the sand bodies controlled by paleogeomorphology are distributed in multi-phase north-south finger-shaped pattern, forming vertical fault-sand combination pattern matching with the fault. The configuration between faults and sand bodies, and oil sources and caprocks determine the vertical conductivity, plane distribution and vertical distribution of oil and gas. Two oil and gas accumulation modes, i.e. single main fault hydrocarbon supply–fault sand consequent matching–oil accumulation in multi-layers stereoscopically and fault system transportation–fault sand vertical matching–oil accumulation in banded overlapping layers occur in the middle and eastern segments of the fault nose respectively, and they control the difference of oil and gas distribution and enrichment degree in the Binhai fault nose. Key words: Bohai Bay Basin, Qikou Sag, Binhai fault nose, sandstone development mechanism, fault-sand combination, oil and gas accumulation, reservoir control mechanism

Abstract Background Our previous work demonstrated that lncRNA-MALAT1 was overexpressed in recurrent colorectal cancer (CRC) and metastatic sites in post-surgical patients. However, the upstream regulatory mechanism of MALAT1 is not well-defined. Histone demethylase JMJD2C holds great potential of epigenetic regulating mechanism in tumor diseases, especially the moderating effect on the promoter activity of targeted genes associated closely with tumor development. Therefore, we herein investigated whether JMJD2C could epigeneticly regulate the promoter activity of MALAT1 and the downstream β-catenin signaling pathway, thereby affecting the metastatic abilities of CRC cells. Methods JMJD2C expressions in human CRC samples were detected by real-time PCR and immunohistochemistry staining. Gene silencing and overexpressing efficiencies of JMJD2C were confirmed by real-time PCR and western blot. The migration of CRC cells in vitro were tested by transwell and wound healing assays. The protein expression and cellular localization of JMJD2C and β-catenin were characterized by immunofluorescence staining and western blot. The histone methylation level of MALAT1 promoter region (H3K9me3 and H3K36me3) was tested by ChIP-PCR assays. The promoter activity of MALAT1 was detected by luciferase reporter assay. The expressions of MALAT1 and the downstream β-catenin signaling pathway related genes in CRC cells were detected by real-time PCR and western blot, respectively. The nude mice tail vein metastasis model was established to observe the effect of JMJD2C on the lung metastasis of CRC cells in vivo. Results Our present results indicated that histone demethylase JMJD2C was overexpressed in matched CRC tumor tissues of primary and metastatic foci, and CRC patients with lower JMJD2C expression in primary tumors had better prognosis with longer OS (Overall Survival). The following biological function observation suggested that JMJD2C promoted CRC metastasis in vitro and in vivo. Further molecular mechanism investigation demonstrated that JMJD2C protein translocated into the nuclear, lowered the histone methylation level of MALAT1 promoter in the sites of H3K9me3 and H3K36me3, up-regulated the expression of MALAT1, and enhanced the β-catenin signaling pathway in CRC cells. Conclusion Our data demonstrated that JMJD2C could enhance the metastatic abilities of CRC cells in vitro and in vivo by regulating the histone methylation level of MALAT1 promoter, thereby up-regulating the expression of MALAT1 and enhancing the activity of β-catenin signaling pathway, providing that JMJD2C might be a novel therapeutic target for CRC metastasis.

In recent years, several wells in the Qibei and Wumaying buried hills of Dagang Oilfield tapped oil in the Carboniferous–Permian and Ordovician strata. This major breakthrough reveals that the deep Paleozoic in the Bohai Bay is a new petroleum system. Through re-evaluating the Paleozoic source rock, reservoir-cap combinations and traps, it is found the oil and gas mainly come from Carboniferous–Permian source rock. The study shows that the Paleozoic strata are well preserved in the central-south Huanghua Depression and developed two kinds of reservoirs, Upper Paleozoic clastic rock and Lower Paleozoic carbonate rock, which form favorable source-reservoir assemblages with Carboniferous–Permian coal measure source rock. The Carboniferous–Permian coal-bearing source rock is rich in organic matters, which are mainly composed of type II2 and III kerogens, and minor II1 kerogen in partial areas. Multi-stage tectonic movements resulted in two stages of hydrocarbon generation of the source rocks. The period from the deposition of Kongdian Formation to now is the second stage of hydrocarbon generation. The matching between large-scale oil and gas charging, favorable reservoir-cap combinations and stable structure determines the enrichment of oil and gas. According to the new comprehensive evaluation of Paleozoic petroleum system, the primary oil and gas resources of the Paleozoic in the Bohai Bay Basin are over 1×1012 m3. The exploration breakthrough in Paleozoic petroleum system, especially Carboniferous–Permian petroleum system in Huanghua Depression is inspirational for oil and gas exploration in similar provinces of Bohai Bay Basin. Key words: Paleozoic, primary oil reservoirs, secondary hydrocarbon generation, oil and gas source, Huanghua Depression, Bohai Bay Basin

Summary: We show that an imaginary magnetic field (IMF), which can be generated in non-Hermitian systems with spin-dependent dissipations, can greatly enhance the s-wave pairing and superfluidity of spin-1/2 fermions, in distinct contrast to the effect of a real magnetic field. The enhancement can be attributed to the increased coupling constant in low-energy space and the reduced spin gap in forming singlet pairs. We have demonstrated this effect in a number of different fermion systems with and without spin-orbit coupling, using both the two-body exact solution and many-body mean-field theory. Our results suggest an alternative route toward strong fermion superfluid with high superfluid transition temperature. : Cold Atom; Superconductivity; Theoretical Physics Subject Areas: Cold Atom, Superconductivity, Theoretical Physics

In order to identify the effect of the particle size of sediment media on the nucleation of gas hydrate (hereinafter referred to as hydrate), we conducted gas hydrate nucleation kinetics experiments on six types of sediment media by using the high-pressure visualized reactor to measure the nucleation induction time of hydrates in sediment media with different particle sizes, based on the size of hydrate-bearing sediments in the Shenhu sea area of the South China Sea. Besides, the nucleation pattern of hydrates in sediment media was analyzed using the probability distribution function. Then, considering the effect of capillarity on the liquid-gas interfacial tension in the pores of sediments, a theoretical model for the pore radius of sediment-nucleation induction time of hydrates was established based on the Kashchiev model in combination with the Arrhenius equation. Finally, the calculation results of the theoretical model were compared with the experimental results. The following results were obtained. First, sediment media with larger particle sizes can help effectively shorten the nucleation induction time of hydrate and increase the concentration degree of induction time. Second, it is deduced from the theoretical model formula that, due to the interfacial tension of pores in the sediment, the nucleation induction time of hydrate increases and then decreases with the increase of sediment particle size, and there is a critical particle size. Third, there is a non-positive correlation between the sediment particle size and the change of hydrate formation difficulty. Within a certain range, the hydrate formation difficulty decreases gradually with the increase of sediment particle size. The research results provide a technical support for the exploration of marine gas hydrate deposits. Keywords: Gas hydrate, Nucleation induction time, Sediment, Particle size, Pore, Capillarity, Induction time, Laboratory experiment

Based on the merged 3D seismic data, well logging, formation testing, analysis and testing data, the structural evolution, sedimentary reservoirs, thermal evolution of source rocks were investigated of Paleogene Kongdian Formation in the trough area of Cangdong sag, Bohai Bay Basin. A conventional-unconventional hydrocarbon accumulation pattern in the trough area of rifted basin was revealed. The reservoir forming elements in the trough area of Cangdong sag have a zonation feature in terms of reservoirs and source rocks. There are two types of reservoir forming models, primary trough and reformed trough. The formation and evolution of trough controlled the orderly distribution of conventional oil to unconventional oil in the trough. Particularly, structural reservoirs occur in the upper part of the trough, stratigraphic-lithologic reservoirs are likely to form in the delta front deposits at the outer ring of trough, the middle ring transitional belt is the favorable site for tight oil reservoirs, while the fine grain deposits zone in the inner ring is shale oil and gas exploration area. The study has pointed out the new domains and directions for searching reserves in the secondary exploration of mature oilfields. Key words: rifted basin, trough hydrocarbon accumulation, stratigraphic-lithologic reservoir, shale oil, orderly accumulation, Bohai Bay Basin, Cangdong sag, Paleogene Kongdian Formation

Recurrence and metastasis seriously affects the prognosis of patients with tumors, and the epithelial-to-mesenchymal transition (EMT) plays a key role in promoting tumor invasion and metastasis. Previous studies have showed that β-arrestin1 acted as a tumor-promoting factor in multiple types of tumor. However, the exact role and mechanism of β-arrestin1 in colorectal cancer (CRC) progression remains to be elucidated. Our research aimed to explore the potential mechanism underlying the role of β-arrestin1 in CRC metastasis. The expression of β-arrestin1 was investigated in both primary and metastatic CRC tissues using the GSE41258 database, and it was revealed that CRC patients with liver/lung metastasis had a higher expression level of β-arrestin1, and the expression level of β-arrestin1 was inversely correlated with the prognosis of CRC patients. Further in vitro mechanism studies indicated that β-arrestin1 had the ability to promote the migration of CRC cells through regulating the EMT process by activating Wingless/integration-1 (Wnt)/β-catenin signaling pathways. Blocking Wnt/β-catenin signaling with inhibitor ICG001 decreased the promoting effect of β-arrestin1 on EMT in CRC. In vivo imaging experiments further demonstrated the promoting effect of β-arrestin1 on the lung metastasis of CRC cells by tail vein injection in mice. The results of this paper suggest that β-arrestin1 promotes EMT via Wnt/β-catenin signaling pathway in CRC metastasis, and provides a novel therapeutic target for CRC metastasis.

BackgroundChemotherapy is the standard adjuvant treatment for colon cancer. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting.MethodsIn this parallel-group study, patients who had undergone curative resection for stage III colon cancer were randomly assigned to receive adjuvant chemotherapy (FOLFOX q2w for 6 months, or CapeOx q3w for 6 months) plus PRM1201 (chemo+PRM1201 group) or adjuvant chemotherapy plus placebo (chemo+placebo group). The primary endpoint was disease-free survival (DFS), and the secondary endpoints were quality of life (QOL) and toxicity.ResultsA total of 370 patients were randomly assigned to chemotherapy plus PRM1201 group (n = 184) and chemotherapy plus placebo group (n = 186). Up to October 30, 2019, 96 events of recurrence, metastasis, or death had been reported, of which 38 events were in the group of chemotherapy plus PRM1201 and 58 events in the chemo+placebo group. The 3-year DFS rate was 77.1 and 68.6% in the chemo+PRM1201 and chemo+placebo group, respectively (hazard ratio [HR], 0.63; 95% CI, 0.42 to 0.94). The QOL of patients in the chemo+PRM1201 group were significantly improved in terms of global quality of life, physical functioning, role functioning, emotional functioning, fatigue, and appetite loss. The incidence of grade 3 or 4 treatment-related adverse event (TRAEs) were similar between the two arms.ConclusionsChemotherapy in combination with PRM1201 improved the adjuvant treatment of colon cancer. PRM1201 can be recommended as an effective option in clinical practice.Clinical Trial RegistrationChinese Clinical Trials Registry, identifier ChiCTR-IOR-16007719.

Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number of studies indicate that epithelial-to-mesenchymal transition (EMT) plays an important role in CRC metastasis, and our previous studies demonstrate that β-arrestin1could regulate EMT in CRC partly through β-catenin signaling pathway. In this work, we investigate whether Tan IIA could regulate EMT in CRC through β-arrestin1-mediated β-catenin signaling pathway both in vivo and in vitro. Our results showed that Tan IIA inhibited lung metastases of CRC cells in vivo and extended the survival time of mice with CRC. In vitro, Tan IIA increased the expression of E-cadherin, decreased the expression of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression of β-arrestin1 expression, resulting in the increase of GSK-3β expression, reduction of β-catenin nuclear localization, thereby decreased the activity of β-catenin signaling pathway. Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC.