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A preliminary study was conducted on the inactivation effects and mechanisms of spore inactivation of Aspergillus flavus and Aspergillus chevalieri spores, as well as the degradation of aflatoxins (AFs) and deoxynivalenol (DON) by ultraviolet combined with cold plasma. The results showed that ultraviolet combined with cold plasma could completely inactivate the two kinds of fungal spores and cause damage to cell membrane and nucleus when treated for 80 s. More than 70% of the two fungi carried by maize kernels were inactivated at 600 s. In terms of degradation of mycotoxins, the degradation rate of standard DON and aflatoxin B group exceeded 60% and 50% respectively at 600 s, and aflatoxin G group was less than 50%. However, toxins carried by maize kernels took longer time to degrade. The degradation rate of DON after 20 minutes of treatment was 36.41%, but the degradation rate of AFS did not exceed 30%. The use of ultraviolet combined with cold plasma treatment shows potential for the inactivation of fungal spores and the degradation of fungal toxins.

This study processed Jingxi rice 7233 into reasonably well milled (RWM, bran degree 2.8%, 4.9%) and well milled (WM, bran degree 1.4%) grades, and compared the processing characteristics, physicochemical properties, fatty acid composition, volatile composition and taste quality between the two grades. The results showed that the average rice yield and head rice yield of RWM were 1.3% and 1.8% higher than those of WM, respectively. The contents of total phenolic acids, water-soluble protein, unsaturated fatty acids, especially polyunsaturated fatty acids, in RWM rice were more than 1.5 times as high as those in RWM rice. The color difference between RWM and WM rice was greater than 2.0, which could be perceived with the naked eye. Totally 62 characteristic peaks were marked by gas chromatography-ion mobility spectrometry (GC-IMS), and 38 compounds were accurately identified. The contents of 58% of volatile components were significantly higher in RWM rice than in WM rice. The cooking time of RWM rice was significantly longer than that of WM rice, and the breakdown viscosity of starch and stickiness were significantly lower than those of WM rice. RWM rice has great advantages in paddy utilization rate, nutrition and health, but further research and optimization are needed in terms of appearance, smell and taste quality.

Abstract Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients’ prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co‐activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR‐3191‐5p. As a result, ADGRB1 prevents MDM2‐mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti‐tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.

Abstract Background Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. Methods In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. Results Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. Conclusions EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a large class of toxic contaminants. Nutrients are closely related to the ecological health of aquatic systems. Both have received widespread global attention. This study investigated the concentrations, compositions, and spatial distributions of PFAS and nutrients in surface water from two constructed wetlands and the nearby drinking water treatment plants (DWTPs). We explored the natural environmental factors and human activities that affect the composition and distribution of pollutants in wetlands and assessed the ability of the DWTPs to remove contaminants. Concentrations of ∑32PFAS varied from 153 to 405 ng/L. Hexafluoropropylene oxide trimer acid (HFPO-TA) was the predominant substance accounting for 45 % of ∑32PFAS concentrations. It might originate from the emissions of indirect sources of PFAS related manufacturers. The detection rate of 6:2 fluorotelomer carboxylic acid (6:2 FTCA) was 100 % with concentrations ranging from 0.915 to 19.7 ng/L 6:2 FTCA might come from the biotransformation of indirect sources in the air. Concentrations of total nitrogen (TN) and total phosphorus (TP) were from 1.47 to 3.54 mg/L, and non-detect (ND) to 0.323 mg/L, respectively. Constructed wetlands could effectively remove PFAS under nutrient stress, however, the removal of PFAS depends on the characteristics of specific compounds and their sources. The removal rates for PFAS and nutrients could be promoted through artificial dredging. But wetland bioremediation could have two opposing effects. On the one hand, plants can take up pollutants from water via roots, leading to pollutant removal and purification. On the other hand, plants may also absorb precursor intermediates from the air through leaves and release them into the water, leading to increased pollutant concentrations. Thirty-two emerging PFAS were identified by high resolution mass spectrum. The drinking water treatment process removed PFAS and nutrients below the drinking water quality standards of China, however, 9 non-target PFAS compounds were still found in tap water. These results provide case support and a theoretical basis for the pollution control and sustainable development of typical ecological wetlands used as drinking water sources.

Objective: The primary objective of this study was to scrutinise the disparities in the diversity, structure, and function of the oral microbiome among caries-free children from the Zhuang and Han ethnic groups with a focus on the influence of ethnically distinct oral health behaviours on the composition of the oral microbiota. Methods: A questionnaire survey was conducted to assess oral health behaviours and dental plaque samples were collected from 96 Zhuang and Han children aged 4–5 years living in Guangxi, southern China for high-throughput sequencing. PCR amplification was performed for sequencing of the V4 region of the 16S rDNA gene, and second-generation sequencing was performed using the Illumina MiSeq platform to compare and analyse the diversity, structure and function of the microbiota. Results: Single-factor analysis revealed significant differences between the Zhuang and Han ethnic groups regarding juice consumption, the frequency of consuming sugar-sweetened food or beverages before bedtime, the age that individuals started toothbrushing, the frequency of toothbrushing and the frequency of parental assistance with toothbrushing (p

Abstract DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.

Lung cancer is one of the most common cancers worldwide, and its mortality rate remains high. In addition to conventional surgery, radiotherapy, and chemotherapy, immunotherapy methods have been developed and used in recent years for the treatment of non-small cell lung cancer (NSCLC). However, only a small number of patients with NSCLC can benefit from immunotherapy strategies, and some patients even have hyperprogression after receiving immunotherapy. Therefore, precision immunotherapy requires effective biomarkers to guide it. In this paper, tissue samples, blood samples, intestinal microbiota, and other biomarkers are reviewed according to different sample sources. Blood samples, including TCR immune repertoire, Tregs cells, cytokines, lactate dehydrogenase, and other markers, are summarized and analyzed to provide reference for clinicians' diagnosis and treatment decisions.

Abstract Facial impressions contribute to evaluations of trustworthiness. Older adults are especially vulnerable to trust violations, incurring risks for deception and exploitation. Using the newly developed social Iowa Gambling Task (S-IGT), we examined age-group differences in the impact of facial trustworthiness on decision-making and learning. In the congruent condition (CS-IGT), advantageous decks were paired with trustworthy faces and disadvantageous decks with untrustworthy faces. In the incongruent condition (IS-IGT), this pairing was reversed. Younger (n = 143) and older (n = 129) participants completed either the standard Iowa Gambling Task (IGT), CS-IGT, or IS-IGT. Both age groups preferred trustworthy faces in their initial choices. Older adults performed worse than younger adults across all tasks over time. Further, compared to younger adults, older adults performed worse on the IS-IGT, suggesting that incongruent facial cues interfered with older adults’ performance, which aligns with reduced sensitivity to negative social reputations in aging. Multilevel modeling also indicated that age-group differences were most pronounced across all tasks in the last 40 trials. Together these findings suggest that differences between younger and older adults in experience-dependent decision-making are magnified in social contexts that involve a “wolf in sheep’s clothing,” which may reflect age-related difficulties in integrating incongruent information.

Mycotoxins are toxic, which can endanger health of animals and humans, causing a lot of economic losses to the food industry. Cold plasma is an emerging non-thermal technology featuring green and high efficiency, which can degrade mycotoxin in an effective way. To provide a theoretical reference for the application of cold plasma in the degradation of food mycotoxins, this paper first summarized the mycotoxins degradation mechanisms after cold plasma treatment. The key point is the structure of degradation products and possible degradation pathways of aflatoxin, deoxynivalenol, and zearalenone after cold plasma treatment under different discharge modes and treatment conditions. What’s more, the degradation effect of cold plasma on pure mycotoxins and mycotoxins on food matrix were reviewed. Finally, the safety and feasibility of cold plasma treatment was talked about from the perspective of toxicity, which was separated into structural, cellular and animal toxicity of the mycotoxin degradation products.

CRISPR-based screens have discovered novel functional genes involving in diverse tumor biology and elucidated the mechanisms of the cancer pathological states. Recently, with its randomness and unbiasedness, CRISPR screens have been used to discover effector genes with previously unknown roles for AML. Those novel targets are related to AML survival resembled cellular pathways mediating epigenetics, synthetic lethality, transcriptional regulation, mitochondrial and energy metabolism. Other genes that are crucial for pharmaceutical targeting and drug resistance have also been identified. With the rapid development of novel strategies, such as barcodes and multiplexed mosaic CRISPR perturbation, more potential therapeutic targets and mechanism in AML will be discovered. In this review, we present an overview of recent progresses in the development of CRISPR-based screens for the mechanism and target identification in AML and discuss the challenges and possible solutions in this rapidly growing field.

Abstract In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive “cold” tumor types into immuno-responsive “hot” ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.

Abstract Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We establish an uncertainty-inspired open set (UIOS) model, which is trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieves an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicts high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.

Background: Selective attention declines with age, due to age-related functional changes in dorsal anterior cingulate cortex (dACC). Real-time functional magnetic resonance imaging (rtfMRI) neurofeedback has been used in young adults to train volitional control of brain activity, including in dACC. Methods: For the first time, this study used rtfMRI neurofeedback to train 19 young and 27 older adults in volitional up- or down-regulation of bilateral dACC during a selective attention task. Results: Older participants in the up-regulation condition (experimental group) showed greater reward points and dACC BOLD signal across training sessions, reflective of neurofeedback training success; and faster reaction time and better response accuracy, suggesting behavioral benefits on selective attention. These effects were not observed for older participants in the down-regulation condition (inverse condition control group), supporting specificity of volitional dACC up-regulation training in older adults. These effects were, unexpectedly, also not observed for young participants in the up-regulation condition (age control group), perhaps due to a lack of motivation to continue the training. Conclusions: These findings provide promising first evidence of functional plasticity in dACC in late life via rtfMRI neurofeedback up-regulation training, enhancing selective attention, and demonstrate proof of concept of rtfMRI neurofeedback training in cognitive aging.

In recent years, with the implementation of grain safety engineering and high-quality grain engineering, grain storage enterprises have carried out research and application of multiple green grain storage technologies such as air conditioning temperature control, grain cooling temperature control and humidity control, internal circulation moisture and temperature control, controlled atmosphere, and comprehensive pest and mold prevention and control based on different regional climate conditions and the storage variety, storage scale, and enterprises processing. These efforts have effectively improved the level of grain storage safety guarantee in China. The safety of grain storage is closely related to moisture content. High moisture content in the grain may cause mold growth or even hotspots, which can endanger the safety of grain storage. On the other hand, low moisture may affect the quality of food consumption and processing. Thus, it is crucial to establish a scientifically and reasonably determined safe storage moisture content of grain under the premise of ensuring the safety of grain storage. This will effectively promote the “green warehousing improvement action” and help save grain to reduce losses. This paper focused on the research process of grain safe storage of moisture in China after more than a decade of research and expert argumentation, key indicators and detection methods that affect the safe storage of grain moisture have been determined, as well as the criteria for determining the safe storage of grain moisture content, in combination with the actual storage situation at home and abroad. Research on the safe storage of grain moisture content in conventional storage and temperature-controlled storage has been systematically carried out, and the relationships between grain moisture content and temperature have been established. The threshold for safe storage of grain moisture content in the region under the new situation has been proposed, which could provide technological support for the formulation of green grain storage related standards.

Advanced polymeric composites (APC) are important structural materials for realizing the lightweight of aerospace vehicles. However, unfavorable factors such as low manufacturing efficiency, high cost, and serious energy consumption hinder the further expansion of APC applications. Resistance implant welding (RIW) technology has the advantages of simple equipment, high welding efficiency, energy saving and environmental protection, and is suitable for the connection of large structural parts with curved surface. It can replace the traditional bonding process and promote APC structural parts to realize green manufacturing, re-manufacturing and recycling. The research progress of APC resistance implant welding process and its application technology were presented in this paper. The challenges faced by APC resistance implant welding technology were introduced. The research status of thermoplastic composite RIW, process parameter optimization for welding pressure and welding time, implant types, thermosetting composite RIW and the application technology of RIW in the manufacturing of large APC structural parts were summarized systematically. The existing problems of APC resistance implant welding were pointed out, which relate to material design, process optimization and fixture manufacturing. In the future, the research on RIW technology of TPC structure is expected to focus on the development of higher strength welding binder, the design of HE with new structure and the improvement of interface bonding strength between binder and HE to improve the bearing capacity of joints. The research on mechanical constitutive model, fatigue strength and service life of RIW joints will be strengthened; the research on welding equipment and fixtures for specific APC components will be carried out to promote RIW engineering to fill the gaps in this area in China.

Tunas are among the most economically important fish species and play critical roles in food composition and nutrition of humans. As apex predators, they also keep the marine ecosystem healthy and balanced. Both natural and human factors influence the status of this important marine resource and their habitats. There is a large cadre of studies on how tunas are of great significance to the exploitation and management of their fisheries, yet there are few summaries of this research. We aimed to quantitatively and qualitatively synthesize the global knowledge structure and emerging trends in tuna research using bibliometric software. References with ''Tuna'', ''Katsuwonus'', or ''Thunnus'' as the subject in the Web of Science Core Collection Database from 1995 to 2019 were visually analyzed using CiteSpace. Publication rate and output, active countries, institutions, authors, and co-cited references were performed. Results suggested that the number of international tuna research papers increased significantly between 2000 and 2010, as a considerable number of high-impact articles emerged during this period. Researchers paid more attention to 19 main topics during this period, notably ''overfishing'', ''bycatch'', ''climate change'', ''marine pollution'', and ''fish management'', which all posed potential risks and challenges to tuna survival. Future research should emphasize resolving these challenges and building international cooperation for the proper management of tuna populations.

Gastrointestinal (GI) tumor is a serious disease with high mortality rates and morbidity rates worldwide. Chemotherapy is a key treatment for GI, however, systematic side effects and inevitable drug resistance complicate the situation. In the process of therapy, P-glycoprotein (P-gp) could remove chemotherapy drugs from cells, thus causing multi-drug resistance. Chemodynamic therapy (CDT) utilizing Fenton chemistry has been used for cancer therapy, along with various combination therapies. The reactive oxygen species produced by CDT could inhibit P-gp’s efflux pump function, which reduce chemoagents excretion and reverse drug resistance. In the present study, we developed novel nanocrystals (Cu2O@Pt NCs) to overcome drug resistance by reducing mitochondria-derived ATP through chemo/CDT in GI cancer. Furthermore, in vivo results in tumor-bearing mice demonstrated that treatment with Cu2O@Pt NCs with CDT and chemotherapy could achieve the most effective antitumor therapeutic effect with the least amounts of adverse effects. As a result, Cu2O@Pt NCs could provide a promising strategy for chemo/CDT-synergistic therapy.

Meteorological satellites can provide more details of cloud, which can be used to analyze the development process of convective cloud in the rainstorm events. To investigate the "21·7" extreme heavy rainfall in Henan Province, satellite cloud image characteristics, the development and evolution process of precipitation clouds, macro structure and microphysical features are deeply analyzed by FY-4A satellite data, FY-3D satellite data, and ERA5 reanalysis data. Particularly, FY-4A satellite data are used to study the cloud microphysical features of this event for the first time. The boundary position and intensity of the water vapor dark area of continental high are relatively stable from 18 July to 22 July in 2021, and the subtropical high continues to extend westward. The stable saddle field is conductive to the long-term development and maintenance of the low vortex cloud system over Henan Province. Two streams of water vapor locate at the north central part of Henan Province, which is favorable for the occurrence of rainstorm at Zhengzhou on 20 July. The reorganization and adjustment of the convective system are due to the consolidation and development of several convective clouds over Henan Province on 20 July. From 1400 BT to 1600 BT, the boundary of cold cloud is over Zhengzhou, where the brightness temperature gradient value is large, indicating that the convection is in its development stage. Furthermore, the cloud optical thickness increases from 1200 BT to 1400 BT, and still maintains a large value at 1500 BT. It indicates that this period is critical for a large number of liquid particles to merge. The time when the cloud optical thickness reaches peak value is prior to that of the precipitation. The increasing trend and value of cloud optical thickness have great significance for the magnitude and occurrence time of heavy rainfall. The relations between cloud top temperature and particle effective radius(T-re relations) are analyzed by FY-4A data. The results show that the rain zone over Henan Province is the deepest at 1600 BT 20 July, and the effective radius of cloud particles at different heights maintain at 20-25 μm. It indicates that the updraft in the cloud is strong, which is conductive to the occurrence of heavy rainfall.

The growth of fungi on rice grains during storage will affect rice quality. In severe cases, these fungi will produce mycotoxins and cause food safety issues. It is the premise of effective prevention and control of deleterious fungi to determine the fungal community composition of rice grains during storage and accurately identify the dominant species, which is of great significance in ensuring the quality safety and food safety of rice grains. In this study, we used the methods of traditional microbial separation culture to investigate the fungal communities of stored rice grains from warehouses of different regions. In combination with the sequence of ex-types and authentic strains, we used morphological observations and multigene phylogenetic analysis to accurately identify the dominant fungal species of stored rice grains in China. The dominant species were A. flavus, A. niger and A. montevidensis (A. amstelodami) in Southern China and A. proliferans and A. montevidensis in Northern China. The detailed identification process and related data of the predominant fungal species on the stored rice grains in the North and South China were expounded in this paper, which has provided a reference for the accurate identification of deleterious fungi in grains.

Squid is traded globally as an important food resource. However, the occurrence of carcinogenic halogenated polycyclic aromatic hydrocarbons (HPAHs) in squid and the risk of their transfer through trade is little understood or recognized. Here, we comprehensively evaluated the occurrence and risk transfer by quantifying the congener-specific concentrations of HPAHs in 121 squid samples collected from the Pacific, Atlantic and Indian oceans. This was the first time that nine of the 36 target chlorinated and brominated PAH congeners had been detected in squid. The HPAHs exhibited growth-dilution effects in the squid. The lipid content of squid was the most significant factor influencing HPAH bioaccumulation, while differences in squid growth and local ocean contamination influenced by geographical distribution also affected HPAH bioaccumulation. The redistribution and risk transfers of HPAHs in squid as a food could be affected by international trading. The cancer risks from squid consumption in China and Mexico were increased by 50 % and 30 %, respectively, because of international squid trading.

ObjectiveTo infer the relationship between bisphenol A （BPA） exposure and adverse health effects in humans， the human epidemiological data of BPA was evaluated by the weight of evidence approach.MethodsBased on the weight of evidence approach， the human epidemiological research articles on BPA published between 2013 and 2020 were systematically searched， screened and classified. The selected articles were evaluated following the guidelines of evaluating the relevance and reliability of toxicological data developed by the China National Center for Food Safety Risk Assessment. The hazard assessment was performed based on different endpoints.ResultsA total of 188 papers were obtained screening from 134 897 records， of which 68 papers were evaluated as “A/B” or “B” in terms of relevance， and the rest were evaluated as “C”. Only the studies with the relevance evaluation grade of “A/B” or “B” were evaluated for reliability， of which 6 studies were evaluated as “high” reliability and 62 studies were evaluated as “medium” reliability. The endpoints of toxicological effects should include metabolic， reproductive and developmental， neurological， immunological and cardiovascular effects. However， the effect indicators across studies lacked consistency due to study population， exposure duration and indicator design.ConclusionBased on the available evidence of human epidemiological data， the relationship between BPA exposure and adverse health effects in humans is not yet clear.

Through comprehensively applying geological and geophysical data, as well as core and thin section observation, the characteristics of reservoirs and fractures in the second member of the Xujiahe Formation (hereinafter referred to as Xu2 Member) in the Yuanba area, northern Sichuan Basin, were studied. Combined with the analysis of the main controlling factors of production capacity, the types and characteristics of the sweet spots in the tight sandstone gas reservoir were determined. The evaluation standards and geological models of the sweet spots were established. The results are as follows: (1) There are bedding-parallel fracture-, fault-induced fracture-, and pore-dominated sweet spots in the tight sandstone gas reservoirs of the Xu2 Member. (2) The bedding parallel fracture-dominated sweet spots have developed in quartz sandstones with well-developed horizontal fractures and micro-fractures. They are characterized by high permeability and high gas output during production tests. This kind of sweet spots is thin and shows a limited distribution. Their logging responses show extremely low gamma-ray (GR) values and medium-high AC values. Moreover, the bedding parallel fracture-dominated sweet spots can be mapped using seismic methods. (3) The fault-induced fracture-dominated sweet spots have well-developed medium- and high-angle shear fractures. Their logging responses show an increase in peaks of AC values and total hydrocarbon content and a decrease in resistivity. Seismically, the areas with well-developed fault-induced fracture-dominated sweet spots can be effectively mapped using the properties such as seismic entropy and maximum likelihood. (4) The pore-dominated sweet spots are developed in medium-grained feldspathic litharenites with good reservoir properties. They are thick and widely distributed. (5) These three types of sweet spots are mainly determined by sedimentation, diagenesis, and tectonism. The bedding parallel fracture-dominated sweet spots are distributed in beach-bar quartz sandstones on the top of the 1st sand layer group in the Xu2 Member, which develops in a shore-shallow lake environment. The fault-induced fracture-dominated sweet spots mainly occur near faults. They are increasingly developed in areas closer to faults. The pore-dominated sweet spots are primarily distributed in the 2nd and 3rd sand layer groups, which lie in the development areas of distributary channels near provenances at western Yuanba area. Based on the geological and seismic data, a comprehensive evaluation standard for these three types of sweet spots of the tight sandstone reservoirs in the Xu2 Member has been established, which, on the one hand, lays the foundation for the development and evaluation of the gas reservoir, and on the other hand, deepens the understanding of sweet spot in the tight sandstone gas reservoirs.

Abstract Individuals encounter varying environmental exposures throughout their lifetimes. Some exposures such as smoking are readily observed and have high personal recall; others are more indirect or sporadic and might only be inferred from long occupational histories or lifestyles. We evaluated the utility of using lifetime-long self-reported exposures for identifying differential methylation in an amyotrophic lateral sclerosis cases-control cohort of 855 individuals. Individuals submitted paper-based surveys on exposure and occupational histories as well as whole blood samples. Genome-wide DNA methylation levels were quantified using the Illumina Infinium Human Methylation450 array. We analyzed 15 environmental exposures using the OSCA software linear and MOA models, where we regressed exposures individually by methylation adjusted for batch effects and disease status as well as predicted scores for age, sex, cell count, and smoking status. We also regressed on the first principal components on clustered environmental exposures to detect DNA methylation changes associated with a more generalised definition of environmental exposure. Five DNA methylation probes across three environmental exposures (cadmium, mercury and metalwork) were significantly associated using the MOA models and seven through the linear models, with one additionally across a principal component representing chemical exposures. Methylome-wide significance for four of these markers was driven by extreme hyper/hypo-methylation in small numbers of individuals. The results indicate the potential for using self-reported exposure histories in detecting DNA methylation changes in response to the environment, but also highlight the confounded nature of environmental exposure in cohort studies.

Abstract. Background:. Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC. Methods:. The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN). Results:. A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P = 0.011) and N3b status (OR = 1.752, P = 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1–2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16–29: 8.6% vs. 10.4%, ELN30–44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1–2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16–29: 8.6% vs. 7.9%, ELN30–44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1–2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16–29: 3.6 vs. 4.6, ELN30–44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN. Conclusions:. DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.

Although the Triassic Xujiahe Formation in Yuanba area of northern Sichuan has a large amount of resources, the proportion of proved reserves to the amount of resources is low. Production of most of the pilot production wells is high at the initial stage, but it declines rapidly, mainly due to tight rock properties and strong heterogeneity of Xujiahe Formation. Thus, it is important to investigate the distribution of high-quality reservoirs. The Member 3 of Xujiahe Formation develops sandstone interbedded with mudstone, and its lateral thickness of different sandstone groups varies greatly, so it is a challenge to identify appropriate time windows for seismic attribute analysis, thus, so the prediction effect of the glutenite in the Member 3 of Xujiahe Formation. In this study, through analysis of core data and logging facies, single-well sedimentary microfacies subdivision is carried out. Single-well lithological interpretation is also studied with application of lithological identification technique. Then, lithological associations and its seismic responses at the top and bottom interfaces of each sandstone group in the Member 3 of Xujiahe Formation are well investigated, The lithological association with the glutenite above and the mudstone below the stratigraphic interface respectively, corresponds to a trough in seismic profiles; in this case, when extracting the seismic attributes of sandstone groups above the stratigraphic interface, only the difference of between drilling horizons and seismic horizons needs to be considered. The lithological association with the mudstone above and glutenite below the stratigraphic interface respectively, corresponds to a peak in seismic profiles; in this case, when extracting the seismic attributes of sandstone groups above the stratigraphic interface, influence of which should be eliminated; thus, a method of time window determination for seismic attribute extraction is established. Among amplitude, frequency, and phase attributes, the total peak energy has the good correlation with thickness of the glutenite at well sites and it also can reflect the distribution of distributary channels well. The results show that belt-like glutenite in each sandstone group in the Member 3 of Xujiahe Formation extends in a NW-SE direction and thins out toward the southeast, and the distribution of glutenite has certain inheritance in the longitudinal direction, the glutenite in the third sandstone group in the Member 3 of Xujiahe Formation (TX33) and the first sandstone group in the Member 3 of Xujiahe Formation (TX31) are both developed.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.MethodsWe retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.ResultsOverall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].ConclusionsLaparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.

Human activities have increased the possibility of simultaneous warming and drought, which will lead to different carbon (C) allocation and water use strategies in plants. However, there is no conclusive information from previous studies. To explore C and water balance strategies of plants in response to warming and drought, we designed a 4-year experiment that included control (CT), warming (W, with a 5°C increase in temperature), drought (D, with a 50% decrease in precipitation), and warming and drought conditions (WD) to investigate the non-structural carbohydrate (NSC), C and nitrogen (N) stoichiometry, and intrinsic water use efficiency (iWUE) of leaves, roots, and litter of Cunninghamia lanceolata, a major tree species in southern China. We found that W significantly increased NSC and starch in the leaves, and increased NSC and soluble sugar is one of the components of NSC in the roots. D significantly increased leaves’ NSC and starch, and increased litter soluble sugar. The NSC of the WD did not change significantly, but the soluble sugar was significantly reduced. The iWUE of leaves increased under D, and surprisingly, W and D significantly increased the iWUE of litter. The iWUE was positively correlated with NSC and soluble sugar. In addition, D significantly increased N at the roots and litter, resulting in a significant decrease in the C/N ratio. The principal component analysis showed that NSC, iWUE, N, and C/N ratio can be used as identifying indicators for C. lanceolata in both warming and drought periods. This study stated that under warming or drought, C. lanceolata would decline in growth to maintain high NSC levels and reduce water loss. Leaves would store starch to improve the resiliency of the aboveground parts, and the roots would increase soluble sugar and N accumulation to conserve water and to help C sequestration in the underground part. At the same time, defoliation was potentially beneficial for maintaining C and water balance. However, when combined with warming and drought, C. lanceolata growth will be limited by C, resulting in decreased NSC. This study provides a new insight into the coping strategies of plants in adapting to warming and drought environments.

Summary: Neutrophil swarming is an emergent host defense mechanism triggered by targets larger than a single neutrophil’s capacity to phagocytose. Swarming synergizes neutrophil functions, including chemotaxis, phagocytosis, and reactive oxygen species (ROS) production, and coordinates their deployment by many interacting neutrophils. The potent inflammatory lipid mediator leukotriene B4 (LTB4) has been established as central to orchestrating neutrophil activities during swarming. However, the details regarding how this eicosanoid choreographs the neutrophils involved in swarming are not well explained. Here we leverage microfluidics, genetically deficient mouse cells, and targeted metabolipidomic analysis to demonstrate that transcellular biosynthesis occurs among neutrophils to generate LTB4. Furthermore, transcellular biosynthesis is an entirely sufficient means of generating LTB4 for the purposes of orchestrating neutrophil swarming. These results further our understanding of how neutrophils coordinate their activities during swarming, which will be critical in the design of eventual therapies that can harness the power of swarming behavior.

Paddy plants provide staple food for 3 billion people worldwide. This study explores the environmental fate and behavior of a high-volume production emerging contaminants chlorinated paraffins (CPs) in the paddy ecosystem. Very-short-, short-, medium-, and long-chain CPs (vSCCPs, SCCPs, MCCPs, and LCCPs, respectively) were analyzed in specific tissue of paddy plants at four main growth stages and soils from the Yangtze River Delta, China throughout a full rice growing season. The total CP concentrations in the paddy roots, stalks, leaves, panicles, hulls, rice, and soils ranged from 181 to 1.74 × 103, 21.7–383, 19.6–585, 108–332, 245–470, 59.6–130, and 99.6–400 ng/g dry weight, respectively. The distribution profile indicated the translocation of SCCPs and MCCPs from soils to paddy tissue, highlighting their elevated bioaccumulative potential. The evolution of CP level/mass/pattern during the whole growth cycle suggested atmospheric CPs deposition on leaves and hulls, as well as stalk-rice transfer. CSOIL plant uptake model well predicted the level, distribution pattern, and bioconcentration factors (BCFs) of SCCPs and MCCPs in paddy shoot and recognized the soil-air-shoot pathway as the major contributor. Moreover, risk evaluation indicated that MCCPs intake and subsequent risks dominated the total exposure to CPs via rice ingestion. This is the first report on the occurrence, fate and risk assessment of all CPs classes in paddy ecosystems, and the results underline the potential health effects caused by the in-use MCCPs via rice ingestion.

The amygdala has been shown to be responsive to face trustworthiness. While older adults typically give higher face trustworthiness ratings than young adults, a direct link between amygdala response and age-related differences in face trustworthiness evaluation has not yet been confirmed. Additionally, there is a possible modulatory role of the neuropeptide oxytocin in face trustworthiness evaluation, but the results are mixed and effects unexplored in aging. To address these research gaps, young, and older adults were randomly assigned to oxytocin or placebo self-administration via a nasal spray before rating faces on trustworthiness while undergoing functional magnetic resonance imaging. There was no overall age-group difference in face trustworthiness ratings, but older compared to young participants gave higher trustworthiness ratings to ambivalently untrustworthy-looking faces. In both age groups, lower face trustworthiness ratings were associated with higher left amygdala activity. A comparable negative linear association was observed in right amygdala but only among young participants. Also, in the right amygdala, lower and higher, compared to moderate, face trustworthiness ratings were associated with greater right amygdala activity (i.e., positive quadratic (U-shaped) association) for both age groups. Neither the behavioral nor the brain effects were modulated by a single dose of intranasal oxytocin administration, however. These results suggest dampened response to faces with lower trustworthiness among older compared to young adults, supporting the notion of reduced sensitivity to cues of untrustworthiness in aging. The findings also extend evidence of an age-related positivity effect to the evaluation of face trustworthiness.

Growing evidence supports a role of the neuropeptide oxytocin in promoting social cognition and prosocial behavior, possibly via modulation of the salience of social information. The effect of intranasal oxytocin administration on the salience network, however, is not well understood, including in the aging brain. To address this research gap, 42 young (22.52 ± 3.02 years; 24 in the oxytocin group) and 43 older (71.12 ± 5.25 years; 21 in the oxytocin group) participants were randomized to either self-administer intranasal oxytocin or placebo prior to resting-state functional imaging. The salience network was identified using independent component analysis (ICA). Independent t-tests showed that individuals in the oxytocin compared to the placebo group had lower within-network resting-state functional connectivity, both for left amygdala (MNI coordinates: x = -18, y = 0, z = -15; corrected p < 0.05) within a more ventral salience network and for right insula (MNI coordinates: x = 39, y = 6, z = -6; corrected p < 0.05) within a more dorsal salience network. Age moderation analysis furthermore demonstrated that the oxytocin-reduced functional connectivity between the ventral salience network and the left amygdala was only present in older participants. These findings suggest a modulatory role of exogenous oxytocin on resting-state functional connectivity within the salience network and support age-differential effects of acute intranasal oxytocin administration on this network.

Psychiatric research encompasses diverse methodologies to understand the complex interplay between neurochemistry and behavior in mental health disorders. Despite significant advancements in pharmacological interventions, there remains a critical gap in understanding the precise functional changes underlying psychiatric conditions and the mechanisms of action of therapeutic agents. Genetically encoded sensors have emerged as powerful tools to address these challenges by enabling real-time monitoring of neurochemical dynamics in specific neuronal populations. This prospective explores the utility of neurotransmitter binding genetically encoded sensors in uncovering the nature of neuronal dysregulation underpinning mental illness, assessing the impact of pharmaceutical interventions, and facilitating the discovery of novel treatments.

We recorded dopamine release signals in centromedial and centrolateral sectors of the striatum as mice learned consecutive versions of visual cue-outcome conditioning tasks. Dopamine release responses differed for the centromedial and centrolateral sites. In neither sector could these be accounted for by classic reinforcement learning alone as classically applied to the activity of nigral dopamine-containing neurons. Medially, cue responses ranged from initial sharp peaks to modulated plateau responses; outcome (reward) responses during cue conditioning were minimal or, initially, negative. At centrolateral sites, by contrast, strong, transient dopamine release responses occurred at both cue and outcome. Prolonged, plateau release responses to cues emerged in both regions when discriminative behavioral responses became required. At most sites, we found no evidence for a transition from outcome signaling to cue signaling, a hallmark of temporal difference reinforcement learning as applied to midbrain dopaminergic neuronal activity. These findings delineate a reshaping of striatal dopamine release activity during learning and suggest that current views of reward prediction error encoding need review to accommodate distinct learning-related spatial and temporal patterns of striatal dopamine release in the dorsal striatum.

BackgroundAntibodies against programmed death 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) have recently shown promising results in gastric cancer (GC). However, clinicians still lack predictive biomarkers for the efficacy of anti-PD-1 therapy; thus, we investigated the expression of PD-L1 in GC and further assessed its clinical relevance with other clinicopathological features.MethodsWe retrospectively collected clinical data on 968 consecutive GC cases from Nanfang Hospital between November 2018 and August 2021. Discrepancy in the combined positive score (CPS) of PD-L1 protein expression between gastric mucosa biopsy and postoperative pathology were investigated. Correlations between CPS and clinicopathological parameters were determined using chi-squared test, multiple logistic aggression analysis, and linear regression analysis.ResultsAmong the 968 consecutive GC patients, 199 who did not receive preoperative chemotherapy or immunotherapy were tested for CPS both in gastric mucosa biopsy and postoperative pathology, and the results showed that the CPS of gastric mucosa biopsy was significantly lower than that of postoperative pathology [mean ± SD: 5.5 ± 9.4 vs. 13.3 ± 17.4; M(IQR): 2(5) vs. 5(12), p

Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.