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Abstract Advanced identification of the potential sliding surface of a slope and accurate early warning are crucial prerequisites for effective management of landslides and timely and prevention of catastrophic accidents. This study analyzes the statistical characteristics of landslide displacement evolution. Based on the normal distribution theory, random variables of displacement velocity and acceleration with random errors are introduced into the analysis of surface displacement information, and random variables of relative displacement with random errors are introduced into the analysis of deep displacement information. When the random variables do not follow the normal distribution, the warning time can be obtained. Therefore, an advanced landslide classification warning method is established. The analysis results showed that analysis results from the April 30 landslide project at an open pit mine indicate that the earliest warning time for landslide initiation is 2020/2/19, while the earliest warnings for acceleration occur on 2020/4/15 and the fast acceleration on 2020/4/25. These three-level warning times align with reality, and the inferred slip surface position corresponds to the actual weak layer range. The primary power source driving landslide originates from behind the sliding body which subsequently pushes rock mass along weak layers near the south wing, north wing, and front in succession. Research findings can enhance landslide warning accuracy, facilitate advance identification of sliding surface, provide scientific basis for open-pit slope engineering design, as well as mitigate casualties and property losses.

Abstract Background The aim of the study was to evaluate the prognostic value of postoperative folate receptor‐positive circulating tumor cell (FR + CTC) detection in patients with stage I–III invasive adenocarcinoma (IAC) treated with surgery. Methods Patients with lung adenocarcinoma (LUAD) who underwent surgical resection in Peking University Cancer Hospital and received postoperative FR + CTC analysis from July 2016 to January 2021 were retrospectively collected. Comparisons between or among groups were made using the Kruskal‐Wallis or Mann–Whitney U tests. Survival curves were estimated using the Kaplan–Meier method and compared using the log‐rank test. Cox proportional hazard regression analyses were performed to explore the factors predicting recurrence and survival. Results There were significant differences between the high and low groups in terms of age (p = 0.002), postoperative CA199 (p = 0.038), and postoperative SCC (p = 0.024). There were no significant differences in the other indicators (all p>0.05). N stage 1, N stage 2, and neoadjuvant therapy (NAT) were independent risk factors for disease recurrence and death; pleural invasion (PI), and nerve invasion were independent risk factors for death. The Kaplan–Meier curve showed a notable trend for a worse disease‐free survival (DFS) or overall survival (OS) for patients with high levels of FR + CTCs in our study, but none of these were statistically significant. Conclusion The detection of FR + CTCs postoperatively was an independent predictor of recurrence in patients treated for stage I–III IAC. Standardized detection methods and optimal time points for assessment should be established in future studies.

Abstract A novel type I arabinogalactan (AG‐I) polysaccharide (EPS) from Epiphyllum oxypetalum (DC.) Haw's flowers is hypothesized to possess immunomodulatory activity. This study investigated EPS's effects on immune functions and its potential mechanism for enhancing intestinal health in immunosuppressed mice. The results showed that supplementing EPS significantly alleviated immune organ damage, increased the thymus index (p

Abstract Social Media (SM) has become a popular medium for individuals to share their opinions on various topics, including politics, social issues, and daily affairs. During controversial events such as political elections, active users often proclaim their stance and try to persuade others to support them. However, disparities in participation levels can lead to misperceptions and cause analysts to misjudge the support for each side. For example, current models usually rely on content production and overlook a vast majority of civically engaged users who passively consume information. These “silent users” can significantly impact the democratic process despite being less vocal. Accounting for the stances of this silent majority is critical to improving our reliance on SM to understand and measure social phenomena. Thus, this study proposes and evaluates a new approach for silent users’ stance prediction based on collaborative filtering and Graph Convolutional Networks, which exploits multiple relationships between users and topics. Furthermore, our method allows us to describe users with different stances and online behaviors. We demonstrate its validity using real-world datasets from two related political events. Specifically, we examine user attitudes leading to the Chilean constitutional referendums in 2020 and 2022 through extensive Twitter datasets. In both datasets, our model outperforms the baselines by over 9% at the edge- and the user level. Thus, our method offers an improvement in effectively quantifying the support and creating a multidimensional understanding of social discussions on SM platforms, especially during polarizing events.

Abstract Background D-type cyclins (CYCD) regulate the cell cycle G1/S transition and are thus closely involved in cell cycle progression. However, little is known about their functions in rice. Results We identified 14 CYCD genes in the rice genome and confirmed the presence of characteristic cyclin domains in each. The expression of the OsCYCD genes in different tissues was investigated. Most OsCYCD genes were expressed at least in one of the analyzed tissues, with varying degrees of expression. Ten OsCYCD proteins could interact with both retinoblastoma-related protein (RBR) and A-type cyclin-dependent kinases (CDKA) forming holistic complexes, while OsCYCD3;1, OsCYCD6;1, and OsCYCD7;1 bound only one component, and OsCYCD4;2 bound to neither protein. Interestingly, all OsCYCD genes except OsCYCD7;1, were able to induce tobacco pavement cells to re-enter mitosis with different efficiencies. Transgenic rice plants overexpressing OsCYCD2;2, OsCYCD6;1, and OsCYCD7;1 (which induced cell division in tobacco with high-, low-, and zero-efficiency, respectively) were created. Higher levels of cell division were observed in both the stomatal lineage and epidermal cells of the OsCYCD2;2- and OsCYCD6;1-overexpressing plants, with lower levels seen in OsCYCD7;1-overexpressing plants. Conclusions The distinct expression patterns and varying effects on the cell cycle suggest different functions for the various OsCYCD proteins. Our findings will enhance understanding of the CYCD family in rice and provide a preliminary foundation for the future functional verification of these genes.

Abstract Purpose This study assesses the metastasis rate of the key distal lymph nodes (KDLN) that are not routinely dissected in proximal gastrectomy, aiming to explore the oncological safety of proximal gastrectomy for upper gastric cancer who underwent neoadjuvant chemotherapy. Methods We analyzed a cohort of 150 patients with proximal locally advanced gastric cancer (cT3/4 before chemotherapy) from two high-volume cancer centers in China who received preoperative neoadjuvant chemotherapy (NAC) and total gastrectomy with lymph node dissection. Metastasis rate of the KDLN (No.5/6/12a) and the risk factors were analyzed. Results Key distal lymph node metastasis was detected in 10% (15/150) of patients, with a metastasis rate of 6% (9/150) in No. 5 lymph nodes, 6.7% (10/150) in No. 6 lymph nodes, and 2.7% (2/75) in No. 12a lymph nodes. The therapeutic value index of KDLN as one entity is 5.8. Tumor length showed no correlation with KDLN metastasis, while tumor regression grade (TRG) emerged as an independent risk factor (OR: 1.47; p-value: 0.04). Of those with TRG3 (no response to NAC), 80% (12/15) was found with KDLN metastasis. Conclusion For cT3/4 proximal locally advanced gastric cancer patients, the risk of KDLN metastasis remains notably high even after NAC. Therefore, proximal gastrectomy is not recommended; instead, total gastrectomy with thorough distal lymphadenectomy is the preferred surgical approach.

Ice cementation and ice-substrate adfreeze force are the primary contributors to the high bearing capacity of pile foundations in cold regions and the stability of frozen walls in areas subjected to artificial freezing. Given the significant temperature sensitivity of ice’s shear rheology, engineering structures in ice or ice-rich soils continue to deform even under constant external loads. A thorough understanding of shear creep and the long-term adfreeze force at the ice-substrate interface is essential for predicting the continuous deformation of these structures. However, research into the shear creep behavior at frozen interfaces has historically been constrained by the precision of temperature control in experimental settings and the complexity of load paths in shear testing devices. In this study, a temperature- and stress-control device for interface shear creep is assembled firstly, and multilevel loading-unloading creep tests on steel pipes embedded in layered frozen ice were conducted. Through the decoupling of deformation progression, the viscoelastic and viscoplastic shear behaviors at the steel-ice interface under various temperatures and shear stresses were characterized, the principle of sustainable interfacial shear creep along with its underlying physical mechanism were proposed. Subsequently, with the aid of a modified nonlinear Burger model, various interfacial shear creep parameters were derived. Results reveal that the interfacial generalized shear modulus continuously improves but with a gradually weakening degree until a point of accelerating creep is reached. Additionally, the long-term adfreeze force is found to be less than half of the short-term strength, which significantly decreases as the temperature approaches the water phase transition zone. Interestingly, the stress exponent associated with the interfacial steady creep rate is considerably smaller than that predicted by Glen’s law. This research provides a theoretical basis instrumental in the engineering design in cold regions and those structures employing artificial freezing techniques.

The red color of red pears is primarily attributed to the accumulation of anthocyanins, which are biosynthesized via the phenylalanine pathway. However, research into the regulation of these processes is currently limited. The study found that increasing the expression of the transcription factor PbMYB5-like resulted in increased expression of genes involved in anthocyanin, proanthocyanidin (PAs), and lignin biosynthesis, as well as anthocyanin accumulation in pear epidermis. The experiments demonstrated that PbMYB5-like interacts with bHLH3, resulting in the formation of the PbMYB5 like-bHLH3-WD40 complex, which regulates the expression of structural genes such as CCR, F5H, LAR, ANS, UFGT, and others. Furthermore, PbMYB5-like has been demonstrated to directly bind to the promoters of CHI, F3H, ANS, and UFGT genes, thereby regulating the synthesis of related metabolites. The findings of this study provide a foundation for understanding the mechanisms by which PbMYB5-like regulates pear skin color, which is a pivotal aspect in pear breeding and germplasm innovation.

Summary: Protospacer-adjacent motif (PAM) recognition licenses Cas nucleases for genome engineering applications, thereby restricting gene targeting to PAM-containing regions. Protein engineering has led to PAM-relaxed SpCas9 variants like SpG and SpRY. Given the evolved role of PAMs in facilitating target-searching kinetics, it remains unclear how these variants quickly locate their targets. We show that SpG and SpRY exhibit a preference for the seed region. To compensate for the relaxed PAM recognition, SpRY has evolved a sequence preference for the seed region through interactions with A61R and A1322R. Furthermore, SpCas9 exhibits a significant decrease in target search kinetics on high-PAM-density DNA, slowing down up to three orders of magnitude compared to low-PAM-density DNA, suggesting the necessity for sequence recognition even in PAM-relaxed variants. This underscores the importance of considering Cas9 target-searching kinetics in SpCas9 PAMless engineering, providing valuable insights for further PAMless Cas9 protein engineering efforts.

Background: This study reported the surgical details and outcomes in a case of totally robotic total gastrectomy (TRTG) using the da Vinci Xi robotic system, aiming to share surgical experience in difficult procedures during TRTG and add evidence supporting the feasibility and safety of TRTG. Methods: A 55-year-old male patient diagnosed with adenocarcinoma of gastroesophageal junction underwent TRTG via the da Vinci Xi robotic system in Sun Yat-sen University Cancer Center on January 10, 2024. The surgical details and perioperative outcomes were summarized. Results: With an estimated blood loss of 100 ​ml, the operation lasted 210 ​min, including an anastomosis time of 36 ​min. During a postoperative hospital stay of 7 days, the patient started liquid diet after the removal of gastric tube on the third day. There were no perioperative complications. Postoperative radiography demonstrated no evidence of anastomotic fistulas or luminal narrowing. The final pathology revealed a 4.5∗1.5 ​cm gastric adenocarcinoma with 10/61 positive lymph nodes. The pathological stage of this patient was pT3N3aM0 IIIB. Conclusions: This successful surgery reflected the effectiveness of minimally invasive surgery for total gastrectomy through a totally intracorporeal robotic approach. Future research is warranted to further validate the feasibility and safety of performing TRTG.

Abstract Marchiafava–Bignami disease (MBD) is an uncommon alcoholism‐related neuropsychiatric disorder, featured with symmetrical demyelination of part or whole corpus callosum (CC). Previous studies reported follow‐up neuroimaging changes with necrosis, cystic degeneration, and atrophy of the CC after the diagnosis of MBD, but it is unclear whether the white matter is damaged before MBD. We report a case of alcoholic MBD whose magnetic resonance imaging revealed structural lesions in the white matter before the typical demyelination of CC during MBD, which support the prior hypothesis that chronic hazardous drinking may initially lead to microstructure abnormalities of the white matter and CC through some possible mechanisms, then microstructure lesions in the CC, and white matter deterioration into extensive demyelination, that is MBD. In future clinical practice, when patients with chronic alcoholism seek treatment for neuropsychiatric disorders, they may need to undergo repeated MRI scans to reveal progressive neuroimaging features before and after MBD.

Abstract Objective To compare the computed tomography (CT) images of patients with locally advanced gastric cancer (GC) before and after neoadjuvant chemotherapy (NAC) in order to identify CT features that could predict pathological response to NAC. Methods We included patients with locally advanced GC who underwent gastrectomy after NAC from September 2016 to September 2021. We retrieved and collected the patients’ clinicopathological characteristics and CT images before and after NAC. We analyzed CT features that could differentiate responders from non-responders and established a logistic regression equation based on these features. Results We included 97 patients (69 [71.1%] men; median [range] age, 60 [26–75] years) in this study, including 66 (68.0%) responders and 31 (32.0%) non-responders. No clinicopathological variable prior to treatment was significantly associated with pathological response. Out of 16 features, three features (ratio of tumor thickness reduction, ratio of reduction of primary tumor attenuation in arterial phase, and ratio of reduction of largest lymph node attenuation in venous phase) on logistic regression analysis were used to establish a regression equation that demonstrated good discrimination performance in predicting pathological response (area under receiver operating characteristic curve 0.955; 95% CI, 0.911–0.998). Conclusion Logistic regression equation based on three CT features can help predict the pathological response of patients with locally advanced GC to NAC.

Abstract Objective Most patients with Marchiafava–Bignami disease (MBD) had unfavorable prognosis, with disability or death. We aimed to determine the risk factors of early unfavorable prognosis of MBD, and to develop a predictive nomogram for early unfavorable prognosis of MBD. Methods MBD patients admitted to our hospital between 1 January 2013 and 31 December 2021 were included. Unfavorable prognosis was defined as mRS score ≥3, the independent risk factors for unfavorable prognosis of MBD with the odds ratio (OR) and 95% confidential interval (CI) acquired by multiple logistic regression were included in development of the predictive nomogram for early unfavorable prognosis of MBD, and the area under curve (AUC) of the receiver operating characteristic curve was calculated. The published case reports of MBD were used as the external validation group to verify the predictive ability of the nomogram. Results Independent risk factors for early unfavorable prognosis of MBD included Glasgow Coma Scale score (OR = 0.636, 95% CI = 0.506–0.800, p = 0.004) and pneumonia (OR = 2.317, 95% CI = 1.003–5.352, p = 0.049). The AUC of the nomogram was 0.852. Ninety‐four case reports, a total of 100 cases of MBD were included as the external validation group, its AUC was 0.840. The online dynamic nomogram for early unfavorable prognosis of MBD was constructed. Interpretation It is confirmed by external validation that the nomogram has a preferable predictive ability and clinical efficacy, and the dynamic online predictive nomogram is helpful for physicians to quickly assess the prognosis of MBD.

The development of sponge cities advocates for sustainable urban rainwater management, effectively alleviating urban flood disasters, reducing non-point-source pollution, and promoting the recycling of rainwater resources. Low-Impact Development (LID) serves as a key strategy in this context, providing essential support for urban rainwater control and pollution reduction. To investigate the runoff control effects of LID measures and to reveal the relationship between facility runoff control performance and installation scale, this study focuses on a sponge community in Beijing. A SWMM model was constructed to analyze the rainwater flood control and pollutant load reduction effects of different LID facilities, including bio-retention cells, green roofs, and permeable pavements. Using evaluation indicators such as surface runoff, node overflow, and pollutant control rates, this study examined how facility performance varies with installation scale under different rainfall conditions. The combination scheme of LID equipment optimal configuration is designed by using multiple criteria decision analysis (MCDA) and cost–benefit theory. The results indicate significant differences in performance among the various LID facilities across different rainfall scenarios. Specifically, the optimal installation proportion for runoff and overflow control of permeable pavements were found to be between 30% and 70%. Green roofs demonstrate superior performance in handling extreme rainfall events, while bio-retention cells exhibit significant effectiveness in controlling Total Suspended Solids (TSSs). Through comprehensive performance evaluation, this study identified the optimal combination scale under a 3-year rainfall recurrence interval as 30% permeable pavements, 20% green roof, and 60% bio-retention cells. This combination effectively leverages the strengths of each facility, ensuring system stability and efficiency while also demonstrating optimal management efficiency in cost–benefit analyses. The findings of this research provide valuable insights for future urban water management and infrastructure development.

IntroductionThe ancient ivories unearthed from the Sanxingdui Ruins site are valuable cultural relics, however, the microbial biodeterioration on ivories during temporary cold storage poses a great threat to their later long-term preservation.MethodsHere, the combination of high-throughput sequencing and biochemical assays was applied for the in-depth investigation of the key deteriorative microorganisms colonizing on the ivories and the tracing of their origin, as well as the assessment of the ethanol disinfection impact on the microbial communities on ivories.ResultsIt was observed that the surfaces of ivories were scattered by the fungal patches of white, dark grey, and hedge green colors during cold storage. The high-throughput sequencing results showed that the genera Mortierella (38.51%), Ilyonectria (14.43%), Penicillium (1.15%), and Aspergillus (1.09%) were the dominant fungi, while Pseudomonas (22.63%), Sphingopyxis (3.06%), and Perlucidibaca (2.92%) were the dominant bacteria on ivories. The isolated Aspergillus A-2 resulted in the highest amount of calcium releasing from the degradation of hydroxyapatite (HAP), the main component of ivory, by the organic acids produced, including oxalic acid and citric acid. The fast expectation-maximization for microbial source tracking (FEAST) analysis revealed that the majority of the fungi (57.45%) and bacteria (71.84%) colonizing on the ivories were derived from the soils surrounding ivories in the sacrifice pits, indicating soils as the primary source for the spoilage microbes growing on ivories. The dominant strains could degrade cellulose, the key components of wet cotton towels commonly applied on ivories for moisture maintenance, aiding the spoilage microbes colonizing on ivories. Notably, the ivory disinfection with 75% ethanol during the cleansing significantly decreased the relative abundance of the dominant genera of Ilyonectria, Aspergillus, and Pseudomonas, with Mortierella becoming the dominant one on ivories.DiscussionTogether, the fungi, particularly Aspergillus and Penicillium, played a significant role in the microbial biodeterioration of unearthed ancient ivories by producing the organic acids. These results may improve the control of the microbial biodeterioration and develop more efficient strategies for the long-time conservation of unearthed ancient ivories and other cultural relics.

Background and objectivesPrevious observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn’s disease (CD) and ulcerative colitis (UC) as IBD subtypes.Materials and methodsA large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach.ResultsThe IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively).ConclusionThis MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

Abstract Background Prolonged treatment of HER2+ breast cancer with lapatinib (LAP) causes cellular senescence and acquired drug resistance, which often associating with poor prognosis for patients. We aim to explore the correlation between cellular senescence and LAP resistance in HER2+ breast cancer, screen for molecular marker of reversible senescence, and construct targeted nanobubbles for ultrasound molecular imaging to dynamically evaluate LAP resistance. Methods and Results In this study, we established a new cellular model of reversible cellular senescence using LAP and HER2+ breast cancer cells and found that reversible senescence contributed to LAP resistance in HER2+ breast cancer. Then, we identified ecto‐5′‐nucleotidase (NT5E) as a marker of reversible senescence in HER2+ breast cancer. Based on this, we constructed NT5E‐targeted nanobubbles (NT5E‐FITC‐NBs) as a new molecular imaging modality which could both target reversible senescent cells and be used for ultrasound imaging. NT5E‐FITC‐NBs showed excellent physical and imaging characteristics. As an ultrasound contrast agent, NT5E‐FITC‐NBs could accurately identify reversible senescent cells both in vitro and in vivo. Conclusions Our data demonstrate that cellular senescence‐based ultrasound‐targeted imaging can identify reversible senescence and evaluate LAP resistance effectively in HER2+ breast cancer cells, which has the potential to improve cancer treatment outcomes by altering therapeutic strategies ahead of aggressive recurrences.

Abstract Permafrost degradation due to climate warming is severely reducing slope stability by increasing soil pore water pressure and decreasing shear strength. Retrogressive thaw slumps (RTSs) are among the most dynamic landforms in permafrost areas, which can result in the instability of landscape and ecosystem. However, the spatiotemporal characteristics of surface deformation of RTSs are still unclear, and the potentials of deformation properties in mapping large-scale RTSs need to be further assessed. In this study, we applied a multi-temporal Interferometric Synthetic Aperture Radar (MT-InSAR) method to map the spatiotemporal variations in surface deformation of RTSs in the Beiluhe region of the Tibetan Plateau by using 112 scenes of Sentinel-1 SAR data acquired from 2017 to 2021. The deformation rates of RTSs ranged from − 35 to 20 mm/year, and three typical motion stages were inferred by analyzing the deformation variation trend of the headwall of RTSs: stable, abrupt thaw, and linear subsidence. A total of 375 RTSs were identified in the Mati Hill region by combining InSAR-based deformation results with visual interpretation of optical remote sensing images. Among them, 76 RTSs were newly developed, and 26% more than the inventory derived from the optical images alone. This study demonstrated that the combination of InSAR-derived deformation with optical images has significant potential for detecting RTSs with high accuracy and efficiency at the regional scale.

The three-axis parallel motion platform (TAPMP) with a common stator has low motion inertia, enabling highly precise and high-speed motion over a large range of strokes. The primary challenge faced by the TAPMP lies in the mutual pulling exerted between the common stator motors during motion. The driving forces generated by the motors are closely associated with their synchronization motion, a connection often overlooked in the design of existing controllers. To address this issue, this paper presents a novel synchronization controller with dynamics compensation (SC–DC) to achieve motion synchronization between the three motors, ultimately enhancing the platform’s tracking accuracy in task space. In this SC–DC method, the synchronization error of the common stator motors is introduced to represent the synchronized motion relationship between adjacent motors, and a dynamic feedforward control is adopted to compensate for the motor’s driving force. The stability of the proposed controller is analyzed using Lyapunov theory, demonstrating the convergence of both the tracking error and synchronization error. Trajectory tracking simulations and experimental studies are conducted on the TAPMP. The results show that, compared to the augmented proportional-derivative controller with dynamic compensation, the proposed controller significantly reduces both the MAE of the tracking error and synchronization error on the q1 motor by 71.88% and 73.02%, respectively, demonstrating its performance advantages in trajectory tracking and synchronization.

The increased global incidence of chronic metabolic diseases, a vital threat to human health and a burden on our healthcare systems, includes a series of clinical metabolic syndromes such as obesity, diabetes, hypertension, and dyslipidemia. One of the well-known probiotic microorganisms, Lactiplantibacillus plantarum plays an important role in promoting human health, including inhibiting the occurrence and development of a variety of chronic metabolic diseases. The present study provides an overview of the preventive and therapeutic effects of L. plantarum on diabetes, obesity, non-alcoholic fatty liver disease, kidney stone disease, and cardiovascular diseases in animal models and human clinical trials. Ingesting L. plantarum demonstrated its ability to reduce inflammatory and oxidative stress levels by regulating the production of cytokines and short-chain fatty acids (SCFAs), the activity of antioxidant enzymes, and the balance of intestinal microbial communities to alleviate the symptoms of chronic metabolic diseases. Furthermore, updated applications and technologies of L. plantarum in food and biopharmaceutical industries are also discussed. Understanding the characteristics and functions of L. plantarum will guide the development of related probiotic products and explore the modulatory benefit of L. plantarum supplementations on the prevention and treatment of multiple chronic metabolic diseases.

Objective A mini-invasive and good-compliance program is critical to broaden colorectal cancer (CRC) screening and reduce CRC-related mortality. Blood testing combined with imaging examination has been proved to be feasible on screen for multicancer and guide intervention. The study aims to construct a machine learning-assisted detection platform with available multi-targets for CRC and colorectal adenoma (CRA) screening. Methods This was a retrospective study that the blood test data from 204 CRCs, 384 CRAs, and 229 healthy controls was extracted. The classified models were constructed with 4 machine learning (ML) algorithms including support vector machine (SVM), random forest (RF), decision tree (DT), and eXtreme Gradient Boosting (XGB) based on the candidate biomarkers. The importance index was used by SHapely Adaptive exPlanations (SHAP) analysis to identify the dominant characteristics. The performance of classified models was evaluated. The most dominating features from the proposed panel were developed by logistic regression (LR) for identification CRC from control. Results The candidate biomarkers consisted of 26 multi-targets panel including CEA, AFP, and so on. Among the 4 models, the SVM classifier for CRA yields the best predictive performance (the area under the receiver operating curve, AUC: .925, sensitivity: .904, and specificity: .771). As for CRC classification, the RF model with 26 candidate biomarkers provided the best predictive parameters (AUC: .941, sensitivity: .902, and specificity: .912). Compared with CEA and CA199, the predictive performance was significantly improved. The streamlined model with 6 biomarkers for CRC also obtained a good performance (AUC: .946, sensitivity: .885, and specificity: .913). Conclusions The predictive models consisting of 26 multi-targets panel would be used as a non-invasive, economical, and effective risk stratification platform, which was expected to be applied for auxiliary screening of CRA and CRC in clinical practice.

Quantitative data analysis in single-molecule localization microscopy (SMLM) is crucial for studying cellular functions at the biomolecular level. In the past decade, several quantitative methods were developed for analyzing SMLM data; however, imaging artifacts in SMLM experiments reduce the accuracy of these methods, and these methods were seldom designed as user-friendly tools. Researchers are now trying to overcome these difficulties by developing easy-to-use SMLM data analysis software for certain image analysis tasks. But, this kind of software did not pay sufficient attention to the impact of imaging artifacts on the analysis accuracy, and usually contained only one type of analysis task. Therefore, users are still facing difficulties when they want to have the combined use of different types of analysis methods according to the characteristics of their data and their own needs. In this paper, we report an ImageJ plug-in called DecodeSTORM, which not only has a simple GUI for human–computer interaction, but also combines artifact correction with several quantitative analysis methods. DecodeSTORM includes format conversion, channel registration, artifact correction (drift correction and localization filtering), quantitative analysis (segmentation and clustering, spatial distribution statistics and colocalization) and visualization. Importantly, these data analysis methods can be combined freely, thus improving the accuracy of quantitative analysis and allowing users to have an optimal combination of methods. We believe DecodeSTORM is a user-friendly and powerful ImageJ plug-in, which provides an easy and accurate data analysis tool for adventurous biologists who are looking for new imaging tools for studying important questions in cell biology.

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow–derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane–localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport–independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.

Abstract Experimental Advanced Superconducting Tokamak (EAST) was built to demonstrate high-power, long-pulse operations under fusion-relevant conditions, with major radius R = 1.9 m, minor radius a = 0.5 m, and design pulse length up to 1000s. It has an ITER-like D-shaped cross-section with two symmetric divertors at the top and bottom, accommodating both single null and double null divertor configurations. EAST construction was started in 2000, and its first plasma was successfully obtained in 2006. In the past 15 years, plasma-facing components, plasma heating, diagnostics, and other systems have been upgraded step by step to meet its mission on exploring of the scientific and technological bases for fusion reactors and studying the physics and engineering technology issues with long pulse steady-state operation. An advanced steady-state plasma operation scenario has been developed, and plasma parameters were greatly improved. Meanwhile, front physics on the magnetic confinement plasmas have been systemically investigated and lots of fruitful results were realized, covering transport and confinement, MHD stabilities, pedestal physics, divertor and scrap-off layer (SOL) physics, and energetic particle physics. This brief review of EAST on engineering upgrading, stand-steady operation scenario development, and plasma physics investigation would be useful for the reference on construction and operation of a superconducting tokamak, such as ITER and future fusion reactor.

The high dimensionality of ion mobility (IM)-resolved metabolomics data presents a great challenge to data processing. Here, authors develop a mass spectrum-oriented bottom-up assembly algorithm and the end-to-end computational framework Met4DX for IM-resolved metabolomics.

In order to study the characteristics of P-wave velocity and resistivity of loess with different moisture contents, low-field nuclear magnetic resonance, resistivity, and P-wave velocity tests were carried out on loess samples with 11 different moisture contents. The test results show that under the condition of the same dry density, the water in loess exists in two forms: bound water and free water. With the increase in moisture content, the water porosity of loess increases, the proportion of free water increases, and the resistivity gradually decreases and then tends to be stable, showing a power function relationship with moisture content. When the moisture content is less than 20%, the P-wave velocity decreases with the increase in the moisture content. In comparison, when the moisture content is greater than 20%, the wave velocity increases with the increase in the moisture content. A modified relation between wave velocity and moisture content and saturation is put forward, and the relationship expression between wave velocity and resistivity of loess is established. Finally, the reliability is verified by experimental data. The research results have a certain guiding significance for real-time monitoring of loess moisture content and engineering stability analysis in the loess area.

Abstract Background The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. Patients and Methods Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. Results Multivariate analysis showed that the surgical procedure (P

This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods. Porcine placenta was subjected to the analysis for its bioactive substances, and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract (PPE) and freeze-dried porcine placenta powder at high (PPH) and low (PPL) dosage. Results showed that porcine placenta contained placental peptides and 15 free amino acids, and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard. Mice model experiment revealed that compared with the control, the PPH treatment significantly improved the spleen index (P < 0.05) by increasing the phagocytic rate of macrophages from 20 % to 60 % and the conversion rate of T lymphocytes from 8 % to 60 %. The qPCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2 (IL-2) and IFN-γ, especially the former, by almost 8 times in the spleens of male mice, while inhibited Th2 cytokines of IL-4 and IL-10. This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.

Unknown metabolite annotation is a grand challenge in untargeted metabolomics. Here, the authors develop knowledge-guided multi-layer networking (KGMN) to enable global metabolite annotation from knowns to unknowns in untargeted metabolomics.

Tumour microenvironment has been linked with immunotherapy response in gastric cancer. Here, the authors use CT-based radiomics to predict neutrophils-to-lymphocyte ratio and response to immunotherapy.

Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high β _P has been significantly extended ( H _98y2 > 1.3, β _P ∼ 4.0, β _N ∼ 2.4 and n _e / n _GW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q _95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (

Stable-isotope tracing allows quantifying metabolic activity by measuring isotopically labeled metabolites, but its metabolome coverage has been limited. Here, the authors develop a global isotope tracing approach with metabolome-wide coverage and use it to characterize metabolic activities in aging Drosophila.

IntroductionThe gut-brain axis has been widely recognized in autism spectrum disorder (ASD), and probiotics are considered to potentially benefit the rescuing of autism-like behaviors. As a probiotic strain, Lactiplantibacillus plantarumN-1(LPN-1) was utilized to investigate its effects on gut microbiota and autism-like behaviors in ASD mice constructed by maternal immune activation (MIA).MethodsAdult offspring of MIA mice were given LPN-1 at the dosage of 2 × 109 CFU/g for 4 weeks before subject to the behavior and gut microbiota evaluation.ResultsThe behavioral tests showed that LPN-1 intervention was able to rescue autism-like behaviors in mice, including anxiety and depression. In which the LPN-1 treatment group increased the time spent interacting with strangers in the three-chamber test, their activity time and distance in the central area increased in the open field test, and their immobility time decreased when hanging their tails. Moreover, the supplementation of LPN-1 reversed the intestinal flora structure of ASD mice by enhancing the relative abundance of the pivotal microorganisms of Allobaculum and Oscillospira, while reducing those harmful ones like Sutterella at the genus level.DiscussionThese results suggested that LPN-1 supplementation may improve autism-like behaviors, possibly via regulating the gut microbiota.

Introduction: The embankment in the permafrost zone of the Qinghai–Tibet Railway (QTR) faces the problem of permafrost degradation, especially in the warm and ice-rich permafrost areas. The settlement deformation of the embankment is more serious in these areas.Methods: This study systematically investigates the settlement deformation characteristics during 16 operational years of three types of typical roadbed structures. The traditional embankment (TE), U-shaped crushed-rock embankment (UCRE), and crushed-rock revetment embankment (CRRE) are the roadbed structures. The long-term monitoring ground temperature and deformation data of the embankment section along the QTR in warm permafrost areas from 2005 to 2020 are utilized in analysis.Results and Discussion: This study focuses on the influence law of the roadbed structure form, shady–sunny slope effect, and temperature field change on the settlement of the roadbed. The results indicated that the two types of the crushed-rock embankment (CRE) of the long-term cumulative settlement are less than 50% of the cumulative settlement of the TE, and the impact on controlling the settlement is significant. The annual settlements of the three types of embankment structures are related to the artificial permafrost table (APT) and influenced by cyclical climate change at the regional scale. The annual growth rate of the settlement at the left and right shoulders of the UCRE as a result of the effect of the shady–sunny slope does not vary considerably as the number of operational years increases. The impact of the shady–sunny slope on the CRRE for the various settlements before 2008 was negligible. After 2008, the thermal disturbance to the embankment temperature field induced by the preconstruction and the effect of shady–sunny slopes decreased gradually as the number of operational years increased. In some years of operation, a thawed interlayer in the TE and CRRE greatly affected the embankment settlement acceleration. The settlement growth rate of the TE is related to the decline of the artificial permafrost table (APT). During the operational years, there was no thawed interlayer in the UCRE. The development of the settlement rate is unaffected by the temperature field for either the left or right embankment shoulder.

Abstract Clarifying the shear creep characteristics of rock and scientifically analyzing its creep deformation law is the key to solving the problem of safe construction and long-term stability analysis of the open-pit coal slope rock mass. Shear creep tests were carried out on mudstone from an open-pit coal mine in Eastern Mongolia to reveal the creep characteristics of mudstone under different normal and shear stresses. Based on the classical Nishihara model, a new composite six-element nonlinear shear creep damage model is established by introducing nonlinear elastomers. Using the least square method, model verification and parameter identification are carried out on the variable test data. At the same time, the influence law of the model parameters on the rock creep deformation is analyzed according to the theoretical curve. The study results showed that the nonlinear shear creeps damage model could better describe the creep characteristics of rock different normal stress and shear stress levels, significantly the non-linear both the strain and time of attenuation creep and accelerated creep. The creep characteristics of the accelerated creep stage described by this model are better than those described by the classical Nishihara model. The model curve is consistent with the changing trend of the experimental data, and the degree of agreement is very high. The correlation coefficients are all above 0.98, which verifies the accuracy and rationality of the model. The influence law of creep parameters is analyzed. The parameters b and c increase nonlinearly with creep. The increase of λ accelerates the process of rock attenuation creep stage; the increase of η 10 slows down the progress of rock decay creep stage; with the increase of α, the deformation and creep rate of rock in accelerated creep stage gradually increase. When η 2 increases, the deformation in the acceleration stage decreases gradually. The research results can provide important theoretical support for the safe construction and long-term stability analysis of open-pit coal slope rock masses.

Water control dikes, as an important infrastructure for national economic and social development, play an important supporting and guaranteeing role in flood control, irrigation, power generation, water supply, tourism, and other aspects. Jiangxi is a major province in water conservancy, with dense rivers and lakes, and it owns tens of thousands of water control dikes of various types. Most of the water control dikes exhibit structural aging, continuous medical risks, and reduced benefits, which urgently require efficient maintenance and standardized management. Management is a complex task, and the level of management directly affects the functional efficiency and service life of dikes. In view of these issues, this study takes dikes as essential and typical water conservancy engineering objects and analyzes the evaluation criteria of safe production and the demands of engineering management. It establishes an evaluation index system suitable for normalized management. The Analytic Hierarchy Process (AHP) model is utilized to determine indicator weights, and a neural network water conservancy engineering evaluation algorithm is constructed to match the evaluation model. Finally, an improved algorithm for the GA (genetic algorithm)-BP (backpropagation) neural network is proposed, incorporating additional momentum factors and considering adaptive learning rates. The developed model is validated through a case study in Jiangxi, China, and the results demonstrate its accuracy and comprehensiveness in reflecting the actual situation. This research is relevant to designers, contractors, and governments seeking solutions to achieve standardized management in water control dikes.

Cattleyak, the interspecies hybrid from cattle (males) and yak (females), displays a faster growth rate and higher feeding efficiency than yak with usually one-year shorter raising cycle. This study aimed to assess the carcass characteristics and meat quality attributes of cattleyak by compared to yak at a similar bodyweight. Results showed that cattleyak exhibited an elevated dressing percentage (58.33%) and a significantly higher content of healthy fatty acids, including eicosapentaenoic acid (5.64%) and docosahexaenoic acid (0.46%) (P < 0.05). Compared to yak meat, the tenderness of cattleyak meat was significantly enhanced (P < 0.05), with the lower Warner-Bratzler shear force (59.53 N) and hardness value (580.92 g), as well as the significant reduction of more than 20% of muscle fiber diameter (P < 0.05). Additionally, myofibrillar proteins in cattleyak, including desmin, tropomyosin, and troponin-T, degraded faster than those in yak (P < 0.05), indicating their role in tenderization improvement in cattleyak. These findings suggest that, in comparison to yaks of the similar bodyweight, cattleyaks with less than one year of the raising cycle have improved meat quality and economic efficiency.

This paper proposes an effective hardware accelerator for 2D $8\times 8$ discrete cosine transform (DCT) and inverse discrete cosine transform (IDCT) using an improved Loeffler architecture. The accelerator optimizes the data stream of the Loeffler 8-point 1D DCT/IDCT according to the characteristics of image and video processing. An 8-stage pipeline structure greatly improves the processing speed by reasonably dividing the number of clock cycles and simplifying the arithmetic operations in each cycle. The multiplication-free approximation of the DCT coefficients is implemented through adders and shifters, combined with both fixed-point and canonic signed digit (CSD) coding. In particular, the proposed fast parallel transposed matrix architecture achieves the function of row-column coefficient conversion with lower circuit complexity. The FPGA implementation of the proposed architecture uses a Virtex-7 XC7VX330T device, running at 288 MHz with a throughput of 558 M Pixel/sec, and a Full HD real-time frame rate of up to 269 fps. Only 33 cycles are required to complete the $8\times 8$ blocks of 2D DCT/IDCT, which can be used as a high-performance hardware accelerator for image and video compression encoding.

In areas with large differences between day and night temperature, the freeze-thaw cycle and frost heaving force in rock mass generate cracks within the rock, which seriously threatens the stability and safety of geotechnical engineering structures and surrounding buildings. This problem can be solved by developing a reasonable model that accurately represents the rock creep behavior. In this study, we developed a nonlinear viscoelastic-plastic creep damage model by introducing material parameters and a damage factor while connecting an elastomer, a viscosity elastomer, a Kelvin element, and a viscoelastic-plastic element in series. One- and three-dimensional creep equations were derived, and triaxial creep data were used to determine the model parameters and to validate the model. The results showed that the nonlinear viscoelastic-plastic creep damage model can accurately describe rock deformation in three creep stages under freeze-thaw cycles. In addition, the model can describe the time-dependent strain in the third stage. Parameters G1, G2, and η20' decrease exponentially with the increase in the number of freeze-thaw cycles while parameter λ increases exponentially. These results provide a theoretical basis for studying the deformation behavior and long-term stability of geotechnical engineering structures in areas with large diurnal temperature differences.

Abstract Lymph node (LN) metastasis is known as one of the most important prognostic factors for early gastric cancer (EGC) patients. Patients without LNM normally have better prognosis. However, there is no evaluation criteria to accurately assess the possibility of LN metastasis. Therefore, this study aims to establish an effective nomogram for prognosis prediction. In this study, 285 EGC patients from January 2010 to December 2015 were enrolled. Pearson’s Chi-Square (χ 2) test (including continuity correction when appropriate) and logistics regression analyses was used to identify the risk factors for LN metastasis. The independent risk factors identified were then incorporated in a nomogram model. The predictive accuracy and discriminative ability of the nomogram were evaluated by receiver operating characteristic curve (ROC) and calibration curve. LN metastasis occurred in 59 (20.7%) EGC patients. And most of these patients were submucosal cancers (48/59). Chi-square test indicated lymphovascular emboli, carbohydrate antigen 19-9 (CA19-9), ulcer, tumor size, tumor infiltration and histological grade were the risk factors, and multivariate logistics analyses confirmed all these six factors were independent risk factors of LN metastasis, which were selected to construct the nomogram. The nomogram proved well calibrated and had good discriminative ability (C-index value: 0.842). The proposed nomogram could result in more-accurate risk prediction for EGC patients.

This study was conducted to increase the enzymatic activity of Bacillus licheniformis XS-4, which was isolated from the traditional fermented mash of Xianshi soy sauce. The mutation was induced by atmospheric and room-temperature plasma (ARTP), and a mutant strain, mut80, was obtained. mut80 exhibited significant increases in protease and amylase activity by 90.54% and 143.10%, respectively, and the enhanced enzymatic activities were stably maintained after 20 consecutive incubations. Re-sequencing analysis of mut80 revealed that the mutation sites were located in 1518447(AT-T) and 4253106(G-A) in its genome, which was involved in the metabolic pathways of amino acids. The expression of the protease synthetic gene (aprX) increased 1.54 times, while that of the amylase gene (amyA) increased 11.26 times, as confirmed via RT-qPCR. Using ARTP mutagenesis, the present study proposes a highly efficient microbial resource with enhanced protease and amylase activity provided by B. licheniformis, which can potentially be used to improve the efficiency of traditional soy sauce fermentation.

Sterol lipids are crucial for maintaining proper brain function. Here, the authors combine ion mobility-mass spectrometry and machine learning to assemble a sterol lipid library and characterize differences in sterol lipids across ten brain regions and two age groups in mice.

Duchenne muscular dystrophy is characterized by structural degeneration of muscle, which is exacerbated by localized functional ischemia due to loss of nitric oxide synthase-induced vasodilation. Treatment strategies aimed at increasing vascular perfusion have been proposed. Toward this end, we have developed monoclonal antibodies (mAbs) that bind to the vascular endothelial growth factor (VEGF) receptor VEGFR-1 (Flt-1) and its soluble splice variant isoform (sFlt-1) leading to increased levels of free VEGF and proangiogenic signaling. The lead chimeric mAb, 21B3, had high affinity and specificity for both human and mouse sFlt-1 and inhibited VEGF binding to sFlt-1 in a competitive manner. Proof-of-concept studies in the mdx mouse model of Duchenne muscular dystrophy showed that intravenous administration of 21B3 led to elevated VEGF levels, increased vascularization and blood flow to muscles, and decreased fibrosis after 6–12 weeks of treatment. Greater muscle strength was also observed after 4 weeks of treatment. A humanized form of the mAb, 27H6, was engineered and demonstrated a comparable pharmacologic effect. Overall, administration of anti-Flt-1 mAbs in mdx mice inhibited the VEGF:Flt-1 interaction, promoted angiogenesis, and improved muscle function. These studies suggest a potential therapeutic benefit of Flt-1 inhibition for patients with Duchenne muscular dystrophy.

Abstract Background Graves’ disease and anti-GQ1b antibody syndrome are both autoimmune diseases, and there have been few reports on whether there is a correlation between the two. In this study, we present the case of a woman who was diagnosed with Graves’ disease and anti-GQ1b antibody syndrome in succession. Case presentation The chief complaints of this patient were limb weakness and blurred vision. Graves’ disease was diagnosed by examination of thyroid function and thyroid autoantibodies, but the clinical symptoms were not relieved after antihyperthyroidism treatment. Finally, it was found that Graves’ disease was complicated by anti-GQ1b antibody syndrome, and the symptoms were relieved after treatment with glucocorticoids and intravenous immunoglobulin. We also explored the possible mechanism of these diseases through a literature review. Conclusions We report a rare case of the cooccurrence of Graves’ disease and anti-GQ1b antibody syndrome. Immune dysregulation might be the pathogenesis of the association, but there is no precise supporting evidence, and more research is needed.

Centimeter-scale magmatic enclaves are abundant in peralkaline felsic volcanic rocks in the Sanshui Basin. Their lithology is mainly syenite and syenitic porphyry, and they mainly comprise alkali feldspar and amphibole, which is similar to the mineral assemblage of the host trachyte and comendite. The SiO2 content in the syenitic enclaves is ~63 wt%, which is similar to that of the host trachyte but lower than that of the comendite. Thermobarometric calculations showed that the syenitic enclaves crystallized at similar temperature and pressure conditions as their host trachyte. The results of mass-balance modeling and MCS modeling indicate that the syenitic enclaves likely experienced an approximately 74% fractional crystallization from the basaltic parental magma. Combined with the similar mineral assemblages and geochemical characteristics of the host trachyte, we think that the enclaves resulted from the in situ crystallization of trachytic magma in the shallow crust and that they had a cogenetic origin with their host volcanic rocks, which means that they were likely to derived from the identical magma chamber which was formed from different batches of magma mixing/mingling. The recharge and mixing of basaltic magma triggered the eruption of trachytic magma eruption. The syenitic crust may have been disaggregated by the ascending trachytic magma and brought to the surface as syenitic enclaves. The syenitic enclaves in volcanic rocks provide unique information on the magmatism of the shallow crust as evidence of magma mixing/mingling.

Ingestion of food toxins such as aflatoxin B1 (AFB1) during pregnancy may impair fetal neurodevelopment. However, animal model results may not be accurate due to the species’ differences, and testing on humans is ethically impermissible. Here, we developed an in vitro human maternal–fetal multicellular model composed of a human hepatic compartment, a bilayer placental barrier, and a human fetal central nervous system compartment using neural stem cells (NSCs) to investigate the effect of AFB1 on fetal-side NSCs. AFB1 passed through the HepG2 hepatocellular carcinoma cells to mimic the maternal metabolic effects. Importantly, even at the limited concentration (0.0641 ± 0.0046 μM) of AFB1, close to the national safety level standard of China (GB-2761-2011), the mixture of AFB1 crossing the placental barrier induced NSC apoptosis. The level of reactive oxygen species in NSCs was significantly elevated and the cell membrane was damaged, causing the release of intracellular lactate dehydrogenase (p < 0.05). The comet experiment and γ-H2AX immunofluorescence assay showed that AFB1 caused significant DNA damage to NSCs (p < 0.05). This study provided a new model for the toxicological evaluation of the effect of food mycotoxin exposure during pregnancy on fetal neurodevelopment.

Probiotics have gained tremendous attention as an alternative to antibiotics, while synbiotics may exhibit a greater growth promoting effect than their counterpart probiotics due to the prebiotics’ promotion on the growth and reproduction of probiotics. The objective of this study was to investigate the influence of Lactiplantibacillus plantarum N-1 and its synbiotic with oligomeric isomaltose on the growth performance and meat quality of Hu sheep. Hu sheep (0–3 days old) were fed with water, probiotics of N-1, or synbiotics (N-1 and oligomeric isomaltose) daily in three pens for 60 days and regularly evaluated to measure growth performance and collect serum (five lambs per group). Longissimus thoracis (LT) and biceps brachii (BB) muscle tissues were collected for the analysis of pH value, color, texture, nutrients, mineral elements, amino acids, volatile compounds, and antioxidant capacity. The results showed that dietary supplementation of N-1 tended to improve growth performance and meat quality of Hu sheep, while the synergism of N-1 with oligomeric isomaltose significantly improved their growth performance and meat quality (p < 0.05). Both the dietary supplementation of N-1 and synbiotics (p < 0.05) increased the body weight and body size of Hu sheep. Synbiotic treatment reduced serum cholesterol and improved LT fat content by increasing the transcription level of fatty acid synthase to enhance fat deposition in LT, as determined via RT-qPCR analysis. Moreover, synbiotics increased zinc content and improved LT tenderness by decreasing shear force and significantly increased the levels of certain essential (Thr, Phe, and Met) and non-essential (Asp, Ser, and Tyr) amino acids of LT (p < 0.05). Additionally, synbiotics inhibited the production of carbonyl groups and TBARS in LT and thus maintained antioxidant stability. In conclusion, it is recommended that the use of synbiotics in livestock breeding be promoted to improve sheep production and meat quality.

Single molecule localization microscopy (SMLM) enables the analysis and quantification of protein complexes at the nanoscale. Using clustering analysis methods, quantitative information about protein complexes (for example, the size, density, number, and the distribution of nearest neighbors) can be extracted from coordinate-based SMLM data. However, since a final super-resolution image in SMLM is usually reconstructed from point clouds that contain millions of localizations, current popular clustering methods are not fast enough to enable daily quantification on such a big dataset. Here, we provide a fast and accurate clustering analysis method called FACAM, which is modified from the Alpha Shape method (a point dataset analysis method used in many fields). By taking advantage of parallel computation, FACAM is able to process millions of localizations in less than an hour, which is at least 10 times faster than the popular DBSCAN method. Furthermore, FACAM adaptively determines the segmentation threshold, and thus overcomes the problem of user-defined parameters. Using simulation and experimental datasets, we verified the advantages of FACAM over other reported clustering methods (including Ripley’s H, DBSCAN, and ClusterViSu).