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Abstract Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.

Abstract Background Sexually transmitted infections (STIs) pose a significant global public health challenge. Early diagnosis and treatment reduce STI transmission, but rely on recognising symptoms and care-seeking behaviour of the individual. Digital health software that distinguishes STI skin conditions could improve health-seeking behaviour. We developed and evaluated a deep learning model to differentiate STIs from non-STIs based on clinical images and symptoms. Methods We used 4913 clinical images of genital lesions and metadata from the Melbourne Sexual Health Centre collected during 2010–2023. We developed two binary classification models to distinguish STIs from non-STIs: (1) a convolutional neural network (CNN) using images only and (2) an integrated model combining both CNN and fully connected neural network (FCN) using images and metadata. We evaluated the model performance by the area under the ROC curve (AUC) and assessed metadata contributions to the Image-only model. Results Our study included 1583 STI and 3330 non-STI images. Common STI diagnoses were syphilis (34.6%), genital warts (24.5%) and herpes (19.4%), while most non-STIs (80.3%) were conditions such as dermatitis, lichen sclerosis and balanitis. In both STI and non-STI groups, the most frequently observed groups were 25–34 years (48.6% and 38.2%, respectively) and heterosexual males (60.3% and 45.9%, respectively). The Image-only model showed a reasonable performance with an AUC of 0.859 (SD 0.013). The Image + Metadata model achieved a significantly higher AUC of 0.893 (SD 0.018) compared to the Image-only model (p

Abstract Freshwater scarcity and microplastics (MPs) pollution are two concerning and intertwined global challenges. In this work, we propose a “one stone kills two birds” strategy by employing an interfacial solar evaporation platform (ISEP) combined with a MPs adsorbent. This strategy aims to produce clean water and simultaneously enhance MPs removal. Unlike traditional predecessors, our ISEP generates condensed water free from MPs contamination. Additionally, the photothermally driven interfacial separation process significantly improves the MPs removal performance. We observed a removal ratio increase of up to 5.5 times compared to previously reported MPs adsorbents. Thus, our rationally-designed ISEP holds promising potential to not only mitigate the existing water scarcity issue but also remediate MPs pollution in natural water environments.

Abstract Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Abstract Cellulose fiber-based textiles are ubiquitous in daily life for their processability, biodegradability, and outstanding flexibility. Integrating cellulose textiles with functional coating materials can unlock their potential functionalities to engage diverse applications. Metal-organic frameworks (MOFs) are ideal candidate materials for such integration, thanks to their unique merits, such as large specific surface area, tunable pore size, and species diversity. However, achieving scalable fabrication of MOFs-textiles with high mechanical durability remains challenging. Here, we report a facile and scalable strategy for direct MOF growth on cotton fibers grafted via the diazonium chemistry. The as-prepared ZIF-67-Cotton textile (ZIF-67-CT) exhibits excellent ultraviolet (UV) resistance and organic contamination degradation via the peroxymonosulfate activation. The ZIF-67-CT is also used to encapsulate essential oils such as carvacrol to enable antibacterial activity against E. coli and S. aureus. Additionally, by directly tethering a hydrophobic molecular layer onto the MOF-coated surface, superhydrophobic ZIF-67-CT is achieved with excellent self-cleaning, antifouling, and oil-water separation performances. More importantly, the reported strategy is generic and applicable to other MOFs and cellulose fiber-based materials, and various large-scale multi-functional MOFs-textiles can be successfully manufactured, resulting in vast applications in wastewater purification, fragrance industry, and outdoor gears.

Paraquat (PQ), a commonly used herbicide, is a potent environmental neurotoxin associated with Parkinson’s disease (PD) and major depressive disorder (MDD). While the involvement of various brain cell types in the etiology of each disorder is well recognized, the specific cell subtypes implicated in the comorbidity of PD and MDD, especially under PQ neurotoxicity, remain poorly understood. In this study, we used single-cell RNA sequencing (scRNA-seq) to analyze brain tissues from mice with PQ-induced PD with MDD. By integrating genomic data with scRNA-seq profiles, we identified differences in cellular heterogeneity related to the pathogenesis of PD and MDD under PQ exposure. Our analysis of risk enrichment in genes with cell type-specific expression patterns revealed that astrocytes are predominantly linked to the comorbidity of PQ-induced PD and MDD. Furthermore, we identified a specific astrocyte subtype that plays a major role in the comorbidity-related changes observed in PQ-induced PD and MDD. This subtype appears to interact with and potentially transform into MDD-specific and PD-specific subtypes. Additionally, pathways related to chemical synaptic function and neuro-projection development were involved in all key stages of PD and MDD co-occurrence. We also identified RNF7 and MTCH2 as shared diagnostic hub genes for PD and MDD, which changed significantly in astrocytes following PQ exposure. These genes may serve as potential markers for astrocyte-specific prognostic diagnosis of PQ-induced PD with MDD. In summary, this study provides the first scRNA-seq profile of comorbidity in a PQ-exposed model. It highlights the heterogeneity of astrocytes in comorbidity and elucidates potential mechanisms underlying the co-occurrence of PD and MDD. These findings emphasize the need for further research into the pathogenesis of PD comorbid with MDD and offer novel insights into PQ neurotoxicity.

Abstract Solar desalination is a promising solution for alleviating water scarcity due to its low‐cost, environmentally friendly, and off‐grid capabilities. However, simultaneous salt rejection and heat localization remain challenging, as the rapid salt convection often results in considerable heat loss. Herein, this challenge is overcome via a facile design: i) isolating high‐temperature and high‐salt zones by rationally designing morning glory‐shaped wick structures and ii) bridging high‐salt zones and bulk water with low‐tortuosity macrochannels across low‐temperature surfaces. The salinity gradient in the macrochannels passively triggers convective flow, facilitating the rapid transfer of salt ions from the high‐salt zone to the bulk water. Meanwhile, the macrochannels are spatially isolated from the high‐temperature zone, preventing heat loss during salt convection and thereby achieving a high evaporation rate (≈3 kg m−2 h−1) and superior salt rejection even in highly concentrated real seawater. This work provides new insights into salt rejection strategies and advances practical applications for sustainable seawater desalination.

BackgroundMalnutrition often occurs in patients with colorectal cancer. This study aims to develop a predictive model based on GLIM criteria for patients with colorectal cancer who underwent radical surgery.MethodsFrom December 2015 to May 2021, patients with colorectal cancer who underwent radical surgery at our center were recruited for this study. We prospectively collected data on GLIM-defined malnutrition and other clinicopathological characteristics. Using Cox regeneration, we developed a novel nomogram for prognostic prediction, which was validated and compared to traditional nutritional factors for predictive accuracy.ResultsAmong the 983 patients enrolled in this study, malnutrition was identified in 233 (23.70%) patients. Multivariate analysis indicated that GLIM-defined malnutrition is the independent risk factor for overall survival (HR = 1.793, 95% CI = 1.390–2.313 for moderate malnutrition and HR = 3.485, 95% CI = 2.087–5.818 for severe malnutrition). The novel nomogram based on the GLIM criteria demonstrated a better performance than existing criteria, with AUC of 0.729, 0.703, and 0.683 for 1-year, 3-year, and 5-year OS, respectively, in the validation cohort. In addition, the risk score determined by this system exhibited significantly poorer short-term and long-term clinical outcomes in high-risk groups in both malnourished and well-nourished patients.ConclusionCombining handgrip strength, serum albumin level, and TNM stage would help improve the predictive effect of GLIM criteria for colorectal cancer patients post-radical surgery and benefit the individual prognostic prediction of colorectal cancer.

Abstract BackgroundVisual impairment (VI) is a prevalent global health issue, affecting over 2.2 billion people worldwide, with nearly half of the Chinese population aged 60 years and older being affected. Early detection of high-risk VI is essential for preventing irreversible vision loss among Chinese middle-aged and older adults. While machine learning (ML) algorithms exhibit significant predictive advantages, their application in predicting VI risk among the general middle-aged and older adult population in China remains limited. ObjectiveThis study aimed to predict VI and identify its determinants using ML algorithms. MethodsWe used 19,047 participants from 4 waves of the China Health and Retirement Longitudinal Study (CHARLS) that were conducted between 2011 and 2018. To envisage the prevalence of VI, we generated a geographical distribution map. Additionally, we constructed a model using indicators of a self-reported questionnaire, a physical examination, and blood biomarkers as predictors. Multiple ML algorithms, including gradient boosting machine, distributed random forest, the generalized linear model, deep learning, and stacked ensemble, were used for prediction. We plotted receiver operating characteristic and calibration curves to assess the predictive performance. Variable importance analysis was used to identify key predictors. ResultsAmong all participants, 33.9% (6449/19,047) had VI. Qinghai, Chongqing, Anhui, and Sichuan showed the highest VI rates, while Beijing and Xinjiang had the lowest. The generalized linear model, gradient boosting machine, and stacked ensemble achieved acceptable area under curve values of 0.706, 0.710, and 0.715, respectively, with the stacked ensemble performing best. Key predictors included hearing impairment, self-expectation of health status, pain, age, hand grip strength, depression, night sleep duration, high-density lipoprotein cholesterol, and arthritis or rheumatism. ConclusionsNearly one-third of middle-aged and older adults in China had VI. The prevalence of VI shows regional variations, but there are no distinct east-west or north-south distribution differences. ML algorithms demonstrate accurate predictive capabilities for VI. The combination of prediction models and variable importance analysis provides valuable insights for the early identification and intervention of VI among Chinese middle-aged and older adults.

Cigarette smoke (CS) is a prevalent chemical indoor air contaminant known to be the primary cause of EMT during airway remodeling in COPD. While some evidence indicates the involvement of SMAD4 in EMT across certain diseases, its specific role in CS-induced EMT in airway remodeling associated with COPD is not established. In our research, we observed a substantial upregulation in SMAD4 expression, O-GlcNAcylation and EMT in patients with COPD, as well as in vitro and in vivo COPD models induced by CS, than those of the controls. Downregulation of SMAD4 resulted in a reduction in CS-induced EMT in vitro and in vivo. As a post-translational modification of proteins, O-GlcNAcylation is dynamically controlled by the duo of enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA). We further discovered the enhancement of O-GlcNAcylation levels induced by CS was due to an elevated OGT expression, as the expression of OGA remained unchanged. Using an OGT inhibitor (OSMI-1) counteracted the effects of SMAD4 on EMT. Whereas, overexpressing OGT increased SMAD4 expression and promoted EMT. OGT-mediated SMAD4 O-GlcNAcylation shielded SMAD4 from proteasomal degradation by reducing its ubiquitination, thereby aiding in SMAD4 stabilization in response to EMT induced by CS. Overall, this research uncovers a fresh pathway for CS-induced EMT in the airway remodeling of COPD and offers valuable insights.

IntroductionMultiple myeloma (MM) is an incurable hematological malignancy with high chromosome instability and heavy dependence on the immunosuppressive bone marrow microenvironment. P53 mutations are adverse prognostic factors in MM; however, clinically, some patients without P53 mutations also exhibit aggressive disease progression. DNp73, an inhibitor of TP53 tumor suppressor family members, drives drug resistance and cancer progression in several solid malignancies. Nevertheless, the biological functions of DNp73 and the molecular mechanisms in myelomagenesis remain unclear.MethodsThe effects of DNp73 on proliferation and drug sensitivity were assessed using flow cytometry and xenograft models. To investigate the mechanisms of drug resistance, RNA-seq and ChIP-seq analyses were performed in MM cell lines, with validation by Western blot and RT-qPCR. Immunofluorescence and transwell assays were used to assess DNA damage and cell invasion in MM cells. Additionally, in vitro phagocytosis assays were conducted to confirm the role of DNp73 in immune evasion.ResultsOur study found that activation of NF-κB-p65 in multiple myeloma cells with different p53 mutation statuses upregulates DNp73 expression at the transcriptional level. Forced expression of DNp73 promoted aggressive proliferation and multidrug resistance in MM cells. Bulk RNA-seq analysis was conducted to assess the levels of MYCN, MYC, and CDK7. A ChIP-qPCR assay was used to reveal that DNp73 acts as a transcription factor regulating MYCN gene expression. Bulk RNA-seq analysis demonstrated increased levels of MYCN, MYC, and CDK7 with forced DNp73 expression in MM cells. A ChIP-qPCR assay revealed that DNp73 upregulates MYCN gene expression as a transcription factor. Additionally, DNp73 promoted immune evasion of MM cells by upregulating MYC target genes CD47 and PD-L1. Blockade of the CD47/SIRPα and PD-1/PD-L1 signaling pathways by the SIRPα-Fc fusion protein IMM01 and monoclonal antibody atezolizumab significantly restored the anti-MM activity of macrophages and T cells in the microenvironment, respectively.DiscussionIn summary, our study demonstrated for the first time that the p53 family member DNp73 remarkably induces proliferation, drug resistance, and immune escape of myeloma cells by directly targeting MYCN and regulating the MYC pathway. The oncogenic function of DNp73 is independent of p53 status in MM cells. These data contribute to a better understanding of the function of TP53 and its family members in tumorigenesis. Moreover, our study clarified that DNp73 overexpression not only promotes aggressive growth of tumor cells but, more importantly, promotes immune escape of MM cells through upregulation of immune checkpoints. DNp73 could serve as a biomarker for immunotherapy targeting PD-L1 and CD47 blockade in MM patients.

Background: Copper transport proteins (SLC31A1, ATP7A, ATP7B) regulate copper levels in the body and may be involved in tumor development. However, their comprehensive expression and function across various cancers remain unclear. Methods: The expressions of copper transporters in 33 tumors and normal tissues were analyzed using TCGA, GTEx, CCLE, ULCAN, and HPA databases. Cox regression assessed their impact on patient survival. Gene alterations were explored using cBioPortal. Spearman correlation tests were performed to investigate the associations between copper transporters and tumor mutation burden (TMB), microsatellite instability (MSI), and infiltration of immune cells. Gene functions were analyzed using STRING and GeneMANIA databases. Drug sensitivity was assessed using GSCALite database. ATP7B expression in lung squamous cell carcinoma (LUSC) was validated by immunohistochemical staining. Results: Copper transporters exhibited variable expression patterns across various cancer types, indicating their potential dual role as either oncogenes or tumor suppressor genes, depending on the cancer type. Significant associations were found between these transporters and tumor stage, as well as prognosis in most tumors studied. Pathway analysis identified links between copper transporters and tumor-related pathways like apoptosis and RAS/MAPK. Copy number variation (CNV) analysis revealed varying degrees of gene amplification and deletion of copper transporters in most tumors. Copper transporters exhibited strong correlations with immune features, including TMB, MSI, and immune-infiltrating cells, suggesting their potential role in guiding immunotherapy. They were also associated with sensitivity to various chemotherapeutic and immunotherapeutic drugs. Immunohistochemical tests validated the correlation between elevated ATP7B level and worse progression-free survival (PFS) in LUSC. Conclusion: Copper transporters may serve as potential tumor markers and therapeutic targets.

BackgroundThe 2022 global outbreak of mpox has significantly impacted health facilities, and necessitated additional infection prevention and control measures and alterations to clinic processes. Early identification of suspected mpox cases will assist in mitigating these impacts. ObjectiveWe aimed to develop and evaluate an artificial intelligence (AI)–based tool to differentiate mpox lesion images from other skin lesions seen in a sexual health clinic. MethodsWe used a data set with 2200 images, that included mpox and non-mpox lesions images, collected from Melbourne Sexual Health Centre and web resources. We adopted deep learning approaches which involved 6 different deep learning architectures to train our AI models. We subsequently evaluated the performance of each model using a hold-out data set and an external validation data set to determine the optimal model for differentiating between mpox and non-mpox lesions. ResultsThe DenseNet-121 model outperformed other models with an overall area under the receiver operating characteristic curve (AUC) of 0.928, an accuracy of 0.848, a precision of 0.942, a recall of 0.742, and an F1-score of 0.834. Implementation of a region of interest approach significantly improved the performance of all models, with the AUC for the DenseNet-121 model increasing to 0.982. This approach resulted in an increase in the correct classification of mpox images from 79% (55/70) to 94% (66/70). The effectiveness of this approach was further validated by a visual analysis with gradient-weighted class activation mapping, demonstrating a reduction in false detection within the background of lesion images. On the external validation data set, ResNet-18 and DenseNet-121 achieved the highest performance. ResNet-18 achieved an AUC of 0.990 and an accuracy of 0.947, and DenseNet-121 achieved an AUC of 0.982 and an accuracy of 0.926. ConclusionsOur study demonstrated it was possible to use an AI-based image recognition algorithm to accurately differentiate between mpox and common skin lesions. Our findings provide a foundation for future investigations aimed at refining the algorithm and establishing the place of such technology in a sexual health clinic.

Summary: 4-Methylcytosine (4mC) and 6-methyladenine (6mA) are the most prevalent types of DNA modifications in prokaryotes. However, whether there is crosstalk between 4mC and 6mA remain unknown. Here, methylomes and transcriptomes of Geobacter sulfurreducens exposed to different intensities of extremely low frequency electromagnetic fields (ELF-EMF) were investigated. Results showed that the second adenine of all the 5′-GTACAG-3′ motif was modified to 6mA (M-6mA). For the other 6mA (O-6mA), the variation in their distance from the neighboring M-6mA increased with the intensity of ELF-EMF. Moreover, cytosine adjacent to O-6mA has a much higher probability of being modified to 4mC than cytosine adjacent to M-6mA, and the closer an unmodified cytosine is to 4mC, the higher the probability that the cytosine will be modified to 4mC. Furthermore, there was no significant correlation between DNA methylation and gene expression regulation. These results suggest a reference signal that goes from M-6mA to O-6mA to 4mC.

Abstract Image-based artificial intelligence (AI) systems stand as the major modality for evaluating ophthalmic conditions. However, most of the currently available AI systems are designed for experimental research using single-central datasets. Most of them fell short of application in real-world clinical settings. In this study, we collected a dataset of 1,099 fundus images in both normal and pathologic eyes from 483 premature infants for intelligent retinopathy of prematurity (ROP) system development and validation. Dataset diversity was visualized with a spatial scatter plot. Image classification was conducted by three annotators. To the best of our knowledge, this is one of the largest fundus datasets on ROP, and we believe it is conducive to the real-world application of AI systems.

Abstract This paper proposes an algorithm for the automatic assessment of programming exercises. The algorithm assigns assessment scores based on the program dependency graph structure and the program semantic similarity, but does not actually need to run the student’s program. By calculating the node similarity between the student’s program and the teacher’s reference programs in terms of structure and program semantics, a similarity matrix is generated and the optimal similarity node path of this matrix is identified. The proposed algorithm achieves improved computational efficiency, with a time complexity of $$O(n^2)$$ O ( n 2 ) for a graph with n nodes. The experimental results show that the assessment algorithm proposed in this paper is more reliable and accurate than several comparison algorithms, and can be used for scoring programming exercises in C/C++, Java, Python, and other languages.

Abstract Forest carbon sequestration capacity in China remains uncertain due to underrepresented tree demographic dynamics and overlooked of harvest impacts. In this study, we employ a process-based biogeochemical model to make projections by using national forest inventories, covering approximately 415,000 permanent plots, revealing an expansion in biomass carbon stock by 13.6 ± 1.5 Pg C from 2020 to 2100, with additional sink through augmentation of wood product pool (0.6-2.0 Pg C) and spatiotemporal optimization of forest management (2.3 ± 0.03 Pg C). We find that statistical model might cause large bias in long-term projection due to underrepresentation or neglect of wood harvest and forest demographic changes. Remarkably, disregarding the repercussions of harvesting on forest age can result in a premature shift in the timing of the carbon sink peak by 1–3 decades. Our findings emphasize the pressing necessity for the swift implementation of optimal forest management strategies for carbon sequestration enhancement.

AbstractObjective The main purpose of this systematic review and meta-analysis was to investigate the diagnostic value of ultrasound elastography in the evaluation of polycystic ovary syndrome (PCOS).Methods A comprehensive and methodical investigation was carried out in the databases of PubMed, EMBASE, Cochrane, Scopus, Web of Science, and China National Knowledge Infrastructure, covering the entire duration of these databases until October 18, 2023. The primary purpose of this research was to evaluate and contrast ovarian tissue elasticity in people with and without PCOS. The elasticity of ovarian tissue was quantified using standardized mean difference (SMD).Results A total of eight studies were ultimately selected for systematic evaluation and meta-analysis. Five studies used shear wave elastography (SWE) as a diagnostic tool, and it was discovered that women with PCOS had higher levels of ovarian shear wave elasticity than their healthy counterparts. The SMD was determined to be 1.86 kilopascal (95% CI: 1.27 to 2.44). Three studies were conducted using strain elastography (SE) to compare the ovarian strain ratio of patients with PCOS to that of a healthy control group. The SMD for the PCOS group was 2.07 (95% CI: 1.79 to 2.34), which indicated that the ovarian strain ratio was significantly higher in that group.Conclusion This systematic review and meta-analysis found that women with PCOS had stiffer ovarian tissue than women without the disorder. Ultrasound elastography may provide clinicians with value beyond 2D ultrasound in the diagnosis of PCOS.

Abstract Dynamic covalent polymers (DCPs) that strike a balance between high performance and rapid reconfiguration have been a challenging task. For this purpose, a solution is proposed in the form of a new dynamic covalent supramolecular motif—guanidine urea structure (GUAs). GUAs contain complex and diverse chemical structures as well as unique bonding characteristics, allowing guanidine urea supramolecular polymers to demonstrate advanced physical properties. Noncovalent interaction aggregates (NIAs) have been confirmed to form in GUA‐DCPs through multistage H‐bonding and π‐π stacking, resulting in an extremely high Young's modulus of 14 GPa, suggesting remarkable mechanical strength. Additionally, guanamine urea linkages in GUAs, a new type of dynamic covalent bond, provide resins with excellent malleability and reprocessability. Guanamine urea metathesis is validated using small molecule model compounds, and the temperature dependent infrared and rheological behavior of GUA‐DCPs following the dissociative exchange mechanism. Moreover, the inherent photodynamic antibacterial properties are extensively verified by antibacterial experiments. Even after undergoing three reprocessing cycles, the antibacterial rate of GUA‐DCPs remains above 99% after 24 h, highlighting their long‐lasting antibacterial effectiveness. GUA‐DCPs with dynamic nature, tuneable composition, and unique combination of properties make them promising candidates for various technological advancements.

Abstrct: Background: Aging is the primary risk factor for the onset of Alzheimer's disease (AD). Inflamma-aging is a major feature in the process of aging, and the chronic neuroinflammation caused by inflamma-aging is closely related to AD. As the main participant of neuroinflammation, the polarization of microglia (MG) could influence the development of neuroinflammation. Objective: This study aims to observe the impact of YHD on microglia (MG) polarization and neuroinflammation to delay the onset and progression of AD. Methods: In vivo experiment, four-month senescence accelerated mouse prone 8 (SAMP8) were used as the model group, the SAMR1 mice of the same age were used as the control group. In YHD group, 6.24 g/kg YHD was intragastrically administrated continuously for 12 weeks, and Ibuprofen 0.026 g/kg in positive control group. Morris Water Maze test was used to evaluate the learning and memory ability, Nissl's staining and immunofluorescence double staining for neuron damage and MG M1/M2 polarization, Enzyme-Linked Immunosorbent Assay (ELISA) for neuroinflammation biomarkers in hippocampus, Western blot for key protein expression of TREM2/NF-κB signaling pathway. In vitro experiments, 10 μM/l Aβ1-42 induced BV-2 cell model was used to re-verify the effect of YHD regulating MG polarization to reduce neuroinflammation. Also, TREM2 small interfering RNA (siRNA) was used to clarify the key target of YHD. Results: YHD could improve the learning and memory ability of SAMP8 mice evaluated by the Morris Water Maze test. Like Ibuprofen, YHD could regulate the M1/M2 polarization of MG and the levels of neuroinflammatory markers TNF-α and IL-10 in hippocampus, and relieve neuroinflammation and neuron loss. In addition, YHD could also regulate the expression of PU.1, TREM2, p–NF–κB P65 in the TREM2/NF-κB signaling pathway. Further in vitro experiments, we found that YHD had a significant regulatory effect on Aβ1-42-induced BV-2 cell polarization, and it could significantly increase PU.1, TREM2, decrease p–NF–κB P65, p-IKKβ, TNF-α, IL-6, IL-1β. At the same time, using siRNA to inhibit TREM2, it proved that TREM2 was a key target for YHD to promote Aβ1-42-induced BV-2 cell M2 polarization to reduce neuroinflammation. Conclusions: YHD could regulate the TREM2/NF-κB signaling pathway through TREM2, thereby to adjust MG polarization and reduce AD-related neuroinflammation.

Extant studies have empirically tested the main two behavior responses following ostracism: prosocial or antisocial. Few studies have investigated the relationship between ostracism and social withdrawal. According to the temporal need-threat model and the self-verification theory, the present study aimed to examine the influence mechanism of ostracism on social withdrawal, especially the mediating role of self-esteem and the moderating role of rejection sensitivity. A total of 1,315 Chinese high school students (52.6% female) completed a written questionnaire. Results showed that ostracism was positively correlated with social withdrawal. Ostracism not only directly predicted social withdrawal, but also indirectly affected social withdrawal by threatening adolescents’ self-esteem. High rejection sensitivity may help aggravate adolescents’ self-esteem threaten perceive from ostracism. Adolescents with high rejection sensitivity felt a greater threat to self-esteem when ostracized. Findings suggest a new direction for understanding individuals’ responses to ostracism.

This study investigated the impact of seasonal environmental factors on microorganisms and flavor compounds during acetic acid fermentation (AAF) of Zhenjiang aromatic vinegar (ZAV). Environmental factors were monitored throughout the fermentation process, which spanned multiple seasons. Methods such as headspace solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), high performance liquid chromatography (HPLC), and high-throughput sequencing were employed to examine how these environmental factors influenced the flavor profile and microbial community of ZAV. The findings suggested that ZAV brewed in autumn had the strongest flavor and sweetness. The key microorganisms responsible for the flavor of ZAV included Lactobacillus acetotolerans, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, Acetobacter pasteurianus. Moreover, correlation analysis showed that room temperature had a significant impact on the composition of the microbial community, along with other key seasonal environmental factors like total acid, pH, reducing sugar, and humidity. These results provide a theoretical foundation for regulating core microorganisms and environmental factors during fermentation, enhancing ZAV quality.

A promising research area in nanomaterials is the use of superatomic clusters as building blocks for creating novel molecules or materials with tailored properties. However, assembling these superatoms into functional materials is challenging, and a thorough understanding of this process is still lacking. In this study, we introduce a new concept called the “superatomic family,” which refers to superatoms that share similar valence electron structures but differ in size. We demonstrate this concept with the synthesized [Au6{Ni3(CO)6}4]2− cluster and the designed [Au16{Ni6(CO)10}4]2− and [Au31{Ni10(CO)15}4]5− clusters. These serve as analogs to simple hydrocarbons, such as methane (CH4), silicon hydride (SiH4), and germanium hydride (GeH4). In these supermolecular structures, the central cores of Au6, Au16, and Au31 exhibit the formation of superatomic SP3 hybridized orbitals, which influence the molecular shape and bonding. Moreover, we explored superatomic bonding involving SP3–SP3 hybridized cores, representing a single superatomic bond between members of the superatomic family, analogous to CH3–SiH3 bonds. By integrating the concept of group superatoms into the Lewis structure framework, we present a powerful approach for predicting and engineering cluster properties, thus opening a vast landscape of nanomaterial design possibilities.

Abstract Water evaporation–induced electricity generators (WEGs) are regarded as one of the most promising solutions for addressing the increasingly severe environmental pollution and energy crisis. Owing to the potential carbon emission in the preparation process of WEGs, whether WEG represents a clean electricity generation technology is open to question. Here, a brand‐new strategy is proposed for manufacturing negative carbon emission WEG (CWEG). In this strategy, the microalgae film is used as the electricity generation interface of WEG, which achieves a stable open‐circuit voltage (Voc) of 0.25 V and a short‐circuit current (Isc) of 3.3 µA. Since microalgae can capture carbon dioxide during its growing process, CWEG holds great promise to generate electricity without carbon emissions in the full life cycle compared with other WEGs. To the best of the author's knowledge, this is the first work using microalgae films to fabricate WEG. Therefore, it is believed that this work not only provides a new direction for designing high‐efficiency and eco‐friendly WEG but also offers an innovative approach to the resource utilization of microalgae.

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment.

Objective: To investigate the effects of excessive light exposure during gestation on intrauterine development and early growth of neonates in rats. Methods: Pregnant rats were randomly allocated to three groups: the constant light exposure group, non-light exposure group and control group. Blood samples were collected from the tail vein to analyze melatonin and cortisol levels. Weight, daily food and water consumption were recorded. Uterine weight, placental weight and placental diameter were measured on gestational day 19. Natural birth and neonate growth were also monitored. The expression of NR1D1(nuclear receptor subfamily 1 group D member 1) in offspring’s SCN (suprachiasmatic nuclei), liver and adipose tissue was measured. Expression of NR1D1, MT1(melatonin 1 A receptor) and 11β-HSD2 (placental 11β-hydroxysteroid dehydrogenase type 2) in placenta was also measured. Finally, the expression of MT1 and 11β-HSD2 in NR1D1 siRNA transfected JEG-3 cells was evaluated. Results: There were no significant differences in maternal weight gain, pregnancy duration, uterine weight, placental body weight, placental diameter, fetal number among three groups. There were no significant differences in weights or lengths of offspring at birth. Compared to other two groups, constant light exposure group showed significantly more rapid growth of offspring in 21st day post-birth. The expression of NR1D1 in SCN, liver and adipose tissues of offspring was not significantly different among three groups. The maternal serum melatonin and cortisol levels of the constant light exposure group were lower and higher than other two groups, respectively. The expressions of NR1D1, MT1 and 11β-HSD2 were all decreased in placenta of the constant light exposure group. The expression of MT1 and 11β-HSD2 in JEG-3 cells were decreased after NR1D1 siRNA transfection. Conclusion: Excessive light exposure during pregnancy results in elevated cortisol and reduced melatonin exposure to fetuses in uterus, potentially contributing to an accelerated early growth of offspring in rats.

The merging of neural radiance fields with generative adversarial networks (GANs) can synthesize novel views of objects from latent code (noise). However, the challenge for generative neural radiance fields (NERFs) is that a single multiple layer perceptron (MLP) network represents a scene or object, and the shape and appearance of the generated object are unpredictable, owing to the randomness of latent code. In this paper, we propose a stylized generative radiance field (SGRF) to produce 3D-aware images with explicit control. To achieve this goal, we manipulated the input and output of the MLP in the model to entangle and disentangle label codes into/from the latent code, and incorporated an extra discriminator to differentiate between the class and color mode of the generated object. Based on the labels provided, the model could generate images of prohibited items varying in class, pose, scale, and color mode, thereby significantly increasing the quantity and diversity of images in the dataset. Through a systematic analysis of the results, the method was demonstrated to be effective in improving the detection performance of deep learning algorithms during security screening.

Abstract Background Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. Case presentation A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. Conclusion To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

Abstract Background PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherapeutics can accumulate in tumor tissues due to enhanced permeability and retention (EPR) effects. In this study, a novel nanotherapeutic for cancer immunotherapy was implemented with albumin nanoparticles functionalized by both PD-1 and PD-L1 aptamers. Results Albumin nanoparticles (NP) were functionalized with either PD-1 aptamers (PD1-NP), PD-L1 aptamers (PDL1-NP), or both types of aptamers (PD1-NP-PDL1). Average sizes of PD1-NP, PDL1-NP, and PD1-NP-PDL1 were 141.8 nm, 141.8 nm, and 164.2 nm, respectively. PD1-NP had good affinity for activated T cells that expresses PD-1. Similarly, PDL1-NP could bind with MDA-MB-231 or CT26 tumor cells that express PD-L1. Moreover, the bispecific PD1-NP-PDL1 could bind with both the activated T cells and the PD-L1-expressing tumor cells, and tether the two type of cells together. Functionally, aptamer-modified nanoparticles exhibited stronger immune-stimulating effects vs. free aptamers. Specifically, PD1-NP or PDL1-NP induced stronger lymphocyte-mediated cytotoxicity against PD-L1-expressing tumor cells in vitro vs. free PD-1 or PD-L1 aptamers. Animal studies also showed that PD1-NP or PDL1-NP significantly improved antitumor efficacy against CT26 colon cancer in vivo vs. free PD-1 or PD-L1 aptamers. Importantly, the bispecific PD1-NP-PDL1 further boosted the in vivo antitumor efficacy compared with PD1-NP or PDL1-NP, without raising systemic toxicity. Conclusion The results suggest that the bispecific PD1-NP-PDL1 is a promising nanotherapeutic to improve the efficacy of PD-1/PD-L1 blockade, and may have application potential in colon cancer treatment.

Abstract Background Altitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m. Methods The incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge. Results There was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year. Conclusions At altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe. Trial registration The study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

Multiple myeloma (MM) remains an incurable hematological malignancy. Despite tremendous advances in the treatment, about 10% of patients still have very poor outcomes with median overall survival less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to the rapid disease progression and provide novel therapeutic selection for these ultra-high-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients with survival of less than two years (EM24). Notably, an enrichment of LILRB4high pre-matured plasma-cell cluster was observed in the patients in EM24 compared to patients with durable remission. This cluster exhibited aggressive proliferation and drug-resistance phenotype. High-level LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/refractory MM patients. The ATAC-seq analysis identified that high chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of MDSCs, and further rescued T cell dysfunction in MM microenvironment. The more infiltration of myeloid-derived suppressive cells (MDSCs) was observed in EM24 patients as well. Therefore, we innovatively generated a TCR-based chimeric antigen receptor (CAR) T cell, LILRB4-STAR-T. Cytotoxicity experiment demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSCs function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T cell immunotherapy is promising against tumor cells and immunosuppressive tumor microenvironment in MM.

IntroductionThe starter used in solid-state fermentation (SSF) vinegar, known as seed Pei is a microbial inoculant from the previous batch that is utilized during the acetic acid fermentation stage. The seed Pei, which has a notable impact on vinegar fermentation and flavor, is under-researched with comparative studies on microorganisms.MethodsHerein metagenomics was employed to reveal the microbes and their potential metabolic functions of four seed Pei from three regions in China.ResultsThe predominant microbial taxa in all four starters were bacteria, followed by viruses, eukaryotes, and archaea, with Lactobacillus sp. or Acetobacter sp. as main functional taxa. The seed Pei used in Shanxi aged vinegar (SAV) and Sichuan bran vinegar (SBV) exhibited a higher similarity in microbial composition and distribution of functional genes, while those used in two Zhenjiang aromatic vinegar (ZAV) differed significantly. Redundancy analysis (RDA) of physicochemical factors and microbial communities indicated that moisture content, pH, and reducing sugar content are significant factors influencing microbial distribution. Moreover, seven metagenome-assembled genomes (MAGs) that could potentially represent novel species were identified.ConclusionsThere are distinctions in the microbiome and functional genes among different seed Pei. The vinegar starters were rich in genes related to carbohydrate metabolism. This research provides a new perspective on formulating vinegar fermentation starters and developing commercial fermentation agents for vinegar production.

Gestational cadmium exposure increases the risk of preeclampsia. Placenta mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative real-time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced mitophagy. Mitophagy marker LC3BII/I and P62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and P62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and P62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and P62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta mitophagy through downregulation of thyroid hormone receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.

Introduction Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) often coexist and increase risk for developing liver fibrosis and diabetes complications if no effective measures are taken. Dietary intervention is known to be able to achieve diabetes remission, while evidence regarding the long-term effect on liver fat is limited for comorbidity management of type 2 diabetes and NAFLD. This study aims to investigate the long-term effect of a Chinese Medical Nutrition Therapy (CMNT) diet accompanied by intermittent energy restriction on reducing liver fat and glycated haemoglobin (HbA1c) in patients with type 2 diabetes and NAFLD.Methods and analysis This is a multicentre two-armed parallel randomised controlled trial study. 120 participants with type 2 diabetes and NAFLD will be recruited from the physical examination centres of multiple hospitals in China. Participants will be randomly allocated 1:1 to either the CMNT group or the usual care group. The CMNT group will be instructed to consume the provided specific meal replacement Chinese medicinal foods consisting of 6 cycles of 5 consecutive days followed by 10 days of regular food intake. The usual care group will be given standard dietary advice. Primary outcomes are changes in the controlled attenuation parameter value by transient elastography and HbA1c level. Secondary outcomes include differences in anthropometrics, clinical blood markers, questionnaires, gut microbiota and metabolomics. Further follow-up will be performed at 6 months, 1 year and 2 years.Ethics and dissemination The study protocol was approved by the Biomedical Research Ethics Committee of Hunan Agricultural University (BRECHAU20200235).The results will be disseminated via relevant peer-reviewed publications and conference presentations.Trial registration number NCT05439226.

BackgroundTalaromycosis is a serious opportunistic infectious disease caused by Talaromyces marneffei, which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death.Case presentationBoth patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for T. marneffei. T. marneffei was detected in the blood culture of case 2, with infection of Candida parapsilosis and Pneumocystis jirovecii. Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy.ConclusionTalaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.

There are two cultivated and weedy types of Perilla crop (TCWTPC), and they are widely distributed and cultivated in East Asia, especially in South Korea and Japan. The objective of this study is to create simple sequence repeat (SSR) markers linked to morphological traits that show differences between accessions of the TCWTPC using recently designed SSR primer sets in Perilla crop. Genetic diversity within 52 accessions of the TCWTPC, gathered from South Korea, was assessed using 28 novel Perilla SSR primer sets. Based on the assessment, a collection of 28 Perilla SSR primer sets were shown to exhibit polymorphism and yielded a total of 142 alleles across the 52 accessions of the TCWTPC. Through inspection of a phylogenetic tree and population structure, the 52 accessions of the TCWTPC were classified into three major groups. Although most accessions of the TCWTPC were relatively clearly distinguished, SSR markers failed to distinguish several accessions belonging to the two weedy types of the Perilla crop. By using an association mapping analysis (AMA) of the 28 Perilla SSR markers and seven morphological characteristics in the 52 TCWTPC accessions, we detected that three of the Perilla SSR markers (KNUPF134, KNUPF137, KNUPF149) were associated with plant and seed characteristics. The novel SSR primer sets developed in Perilla crop should be useful in AMA for assessing genetic diversity and relationships between and within TCWTPC accessions, and this information will be helpful for genetic mapping in breeding programs for Perilla crop.

The construction and application of underground ponding goaf in coal mine provide important guarantee for underground production and mining and surface industrial water. The mine pays more attention to the safe operation performance of artificial waterproof sealing. For providing reliable monitoring scheme and safety evaluation technical means, taking 3# waterproof sealing wall in 31205 ponding goaf of Shigetai Coal Mine as the research object, the monitoring scheme for surface strain gauge, borehole stress gauge and osmometer is designed, and the surface strain gauge B1, B3 and borehole stress gauge LY are used as the input matrix, and the osmometer LS1 is used as the output matrix. The GRNN model (generalized neural network) is introduced, and the network training and data prediction evaluation are conducted using the ten fold cross validation method and cycle iteration logic. The best smoothing factor is 0.2, and 97% of the absolute error of seepage pressure prediction results under this condition is less than 0.01; at the same time, compared with BP neural network model, GRNN model is superior to BP model. PNN model (probabilistic neural network) is introduced to verify the classification of 100 data in 10 grades of GRNN model classification evaluation results, and the accuracy of evaluation samples is 96.7%. The results show that GRNN model can accurately predict the seepage pressure monitoring data, and the accuracy of GRNN model is higher than that of BP model; the evaluation grade predicted by GRNN model can still be effectively evaluated and verified by using PNN model.

Abstract Introduction The use of the neodymium:yttrium–aluminum-garnet (Nd:YAG) laser to treat malignant glaucoma (MG) has been described in the literature since the 1980s. However, the technique has been reported to have a short-term effect, with a notable relapse rate. In the present study, we report the efficacy and durability of a modified Nd:YAG laser treatment methodology for treatment of pseudophakic or aphakic MG. Methods Patients with chronic angle-closure glaucoma and deemed at high risk of developing post-operative MG received prophylactic peripheral iridectomy during their conventional operation beginning in 2017. When the diagnosis of pseudophakic or aphakic MG was confirmed, a thorough Nd:YAG laser capsulo/zonulo-hyaloido-vitreolysis (CZHV) was performed through iridectomy, along with standardized pre- and post-laser medications. This retrospective case series includes 14 eyes of 11 patients with MG who had surgical preset iridectomy and modified Nd:YAG laser CZHV between 2017 and 2022. Outcome measures included resolution and recurrence of MG and incidence of treatment complications. Results The mean follow-up was 27.1 ± 15.0 months (range, 12–48). Long-term resolution of MG was obtained in all included eyes at the end of the follow-up. Six eyes (42.9%) achieved long-term resolution with a single Nd:YAG laser intervention. Eight eyes (57.1%) achieved long-term resolution following two to three laser interventions, with two eyes (14.3%) experiencing recurrence. There was no complication during the follow-up. At the final visit, a significant reduction (P = 0.0001) in the mean intraocular pressure (IOP) was observed (13.1 ± 2.8 mmHg) compared to presentation (21.4 ± 6.3 mmHg). Conclusion The modified Nd:YAG laser treatment methodology is a minimally invasive option to manage pseudophakic or aphakic MG with sustained effectiveness. Reduced inflammatory reactions due to prophylactic peripheral iridectomy, rapid diagnosis, and timely treatment initiation have all contributed to the favorable outcomes associated with this modified treatment methodology.

Abstract Background It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. Methods Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. Results Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRβ, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRβ. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. Conclusion Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.

Abstract Transcription factors (TFs) and long noncoding RNAs (lncRNAs) contribute to gastric cancer (GC). However, the roles of TFs and lncRNAs in the invasion and metastasis of GC remain largely unknown. Here, we observed that the transcription factor VAX2 is significantly upregulated in GC cells and tissues and acts as an oncogene. Moreover, high VAX2 expression is associated with the advancement of tumors in GC. In terms of functionality, the enforced expression of VAX2 promotes the proliferation and metastasis of GC cells. Mechanistically, VAX2 specifically interacts with the LINC01189 promoter and represses LINC01189 transcription. Furthermore, LINC01189 exhibits significant downregulation in GC and functions as a suppressor gene. Functionally, it inhibits migratory and invasive abilities in GC cells. In the context of GC metastasis, VAX2 plays a role in modulating it by trans-repressing the expression of LINC01189. Additionally, LINC01189 binds to hnRNPF to enhance hnRNPF degradation through ubiquitination. The cooperation between LINC01189 and hnRNPF regulates GC cell invasion and migration. In addition, both VAX2 and hnRNPF are highly expressed, while LINC01189 is expressed in at low levels in GC tissues compared to normal gastric tissues. Our study suggests that VAX2 expression facilitates, while LINC01189 expression suppresses, metastasis and that the VAX2-LINC01189-hnRNPF axis plays a contributory role in GC development.

Abstract Various miRNAs have been shown to participate in the tumor progression and development of colorectal cancer (CRC). However, the role of miR-3913-5p in CRC are yet to be clearly defined. In the present study, we determine that miR-3913-5p is downregulated in CRC cell lines and CRC tissues. Exogenous miR-3913-5p expression weakens the CRC cells growth, migration and invasion. Mechanistically, miR-3913-5p directly targets the 3’UTR of CREB5. Overexpression of CREB5 reverses the suppression of CRC cells proliferation, migration and invasion induced by miR-3913-5p. Furthermore, ATF2 negatively regulates the transcription of miR-3913-5p by binding to its promoter. CREB5 can cooperate with ATF2. CREB5 is required for ATF2 in regulating miR-3913-5p. Finally, inverse correlations can be found between the expressions of miR-3913-5p and CREB5 or ATF2 in CRC tissues. Thus, a plausible mechanism of ATF2/miR-3913-5p/CREB5 axis regulating CRC progression is elucidated. Our findings suggest that miR-3913-5p functions as a tumor suppressor in CRC. ATF2/miR-3913-5p/CREB5 axis might be a potential therapeutic target against CRC progression.

Highlights Micro–nano water film enhanced interfacial solar evaporator enables a high evaporation rate of 2.18 kg m−2 h−1 under 1 sun. An outdoor device with an enhanced condensation design demonstrates a high water production rate of 15.9–19.4 kg kW−1 h−1 m−2. A multi-objective predictive model is established to assess outdoor water production performance.

Background: Arsenic is a toxic metalloid that can cause acute and chronic adverse health problems. Unfortunately, rice, the primary staple food for more than half of the world’s population, is generally regarded as a typical arsenic-accumulating crop plant. Evidence indicates that arsenic stress can influence the growth and development of the rice plant, and lead to high concentrations of arsenic in rice grain. But the underlying mechanisms remain unclear. Methods: In the present research, the possible molecules and pathways involved in rice roots in response to arsenic stress were explored using bioinformatics methods. Datasets that involving arsenic-treated rice root and the “study type” that was restricted to “Expression profiling by array” were selected and downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the arsenic-treated group and the control group were obtained using the online web tool GEO2R. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to investigate the functions of DEGs. The protein-protein interactions (PPI) network and the molecular complex detection algorithm (MCODE) of DEGs were analyzed using STRING and Cystoscope, respectively. Important nodes and hub genes in the PPI network were predicted and explored using the Cytoscape-cytoHubba plug-in. Results: Two datasets, GSE25206 and GSE71492, were downloaded from Gene Expression Omnibus (GEO) database. Eighty common DEGs from the two datasets, including sixty-three up-regulated and seventeen down-regulated genes, were then selected. After functional enrichment analysis, these common DEGs were enriched mainly in 10 GO items, including glutathione transferase activity, glutathione metabolic process, toxin catabolic process, and 7 KEGG pathways related to metabolism. After PPI network and MCODE analysis, 49 nodes from the DEGs PPI network were identified, filtering two significant modules. Next, the Cytoscape-cytoHubba plug-in was used to predict important nodes and hub genes. Finally, five genes [Os01g0644000, PRDX6 (Os07g0638400), PRX112 (Os07g0677300), ENO1(Os06g0136600), LOGL9 (Os09g0547500)] were verified and could serve as the best candidates associated with rice root in response to arsenic stress. Conclusions: In summary, we elucidated the potential pathways and genes in rice root in response to arsenic stress through a comprehensive bioinformatics analysis.

In fermented foods, acetic acid bacteria (AAB), kinds of bacteria with a long history of utilization, contribute to safety, nutritional, and sensory properties primarily through acetic acid fermentation. AAB are commonly found in various fermented foods such as vinegar, sour beer, fermented cocoa and coffee beans, kefir beverages, kombucha, and sourdough. They interact and cooperate with a variety of microorganisms, resulting in the formation of diverse metabolites and the production of fermented foods with distinct flavors. Understanding the interactions between AAB and other microbes is crucial for effectively controlling and utilizing AAB in fermentation processes. However, these microbial interactions are influenced by factors such as strain type, nutritional conditions, ecological niches, and fermentation duration. In this review, we examine the relationships and research methodologies of microbial interactions and interaction studies between AAB and yeasts, lactic acid bacteria (LAB), and bacilli in different food fermentation processes involving these microorganisms. The objective of this review is to identify key interaction models involving AAB and other microorganisms. The insights gained will provide scientific guidance for the effective utilization of AAB as functional microorganisms in food fermentation processes.

The rotating annular flume has been widely adopted to generate quasi-steady and uniform flow, thus serving for the investigation of sediment motion characteristics. This complex flow structure is significantly associated with the rotational speed ratio. The present study aims to explore the optimal speed ratio based on the OpenFOAM simulation. In this paper, the physical properties of a rotating annular flume with different speed ratios are investigated and analyzed in terms of bottom shear stress, turbulent velocity ratio, cross-sectional secondary flow, and vector field by interFoam, a built-in solver of the open-source CFD program OpenFOAM. The RNG k-epsilon model has been adopted to solve multiphase flow problems. The results demonstrate that the optimal speed ratio differs with the specific evaluation criterion. Given the uniform distribution of bottom shear stress, the turbulence velocity ratio, and the minimum secondary flow as the evaluation criteria, the corresponding optimal speed ratios are determined as 1.2, 1.7, and 1.7, respectively. The conclusion is generally consistent with the results derived by other scholars. Computational fluid dynamics programs have been proven as practical tools for investigating complex hydrodynamic characteristics. The present study shares useful insights into the optimal rotational speed ratio of a rotating annular flume. The OpenFOAM-based numerical model will provide guidance for experimental research using rotating annular flumes.

The replacement of common urea with controlled-release nitrogen fertilizer can improve rice yield and quality, but the effect of controlled-release nitrogen fertilizer on rice yield and quality at different release stages is still unclear. In this experiment, two nitrogen application rates (240 kg/ha and 300 kg/ha) and five different nutrient release characteristics (urea and coated urea with controlled release periods of 30, 50, 70 and 90 days, respectively) were set up to explore the effects of nitrogen application rate, release characteristics and their interactions on rice yield, quality, starch structure, and physicochemical properties. The results showed that, compared with other controlled-release nitrogenous fertilizers, application of controlled-release nitrogenous fertilizers for 30 days and 90 days could increase rice yield (14.17% to 20.83%), and application of controlled-release nitrogenous fertilizers for 70 days and 90 days had the highest comprehensive evaluation of rice quality. The decrease of amylose content and the increase of protein content significantly improved the eating and nutritional quality of rice by changing the structure and physicochemical properties of starch particles. The results showed that in the comprehensive evaluation system based on rice yield and quality, under the condition of 300 kg/ha, controlled-release nitrogen treatment with a controlled release period of 90 days had the highest comprehensive score, which could increase rice yield and improve grain quality.

The post-deployment challenges in developing and upgrading blockchain smart contracts necessitate a high level of accuracy in their development and business logic. However, current methodologies for verifying the business logic of smart contracts frequently fail to address their alignment with end-user business requirements. This paper introduces a two-step language transformation process to bridge this gap. Initially, we establish a transformation rule from the Business Process Model and Notation (BPMN) to Prolog, enabling the translation of business processes into a Prolog representation. This step not only validates the business process logic but also ensures it meets user specifications. Subsequently, we introduce a transformation rule from the BPMN to Go, which facilitates the transformation of the BPMN model, once validated, into a Go language smart contract. To enhance usability, we have engineered a dedicated tool that streamlines this transformation process. We present a case study involving a banking loan process to exemplify the utility of our tool in creating BPMN diagrams, conducting requirement and syntax validations, and effecting the transformation to Go smart contracts. The case study and empirical results suggest that our methodology and the accompanying tool mitigate the complexities inherent in smart contract development. They also ensure the fidelity of business logic to user demands, thereby promoting the broader adoption of blockchain smart contract technology.

The two-part tariff (TPT) policy is implemented as an important initiative to accelerate the marketization of the pumped storage industry and promote its high-quality development. However, it is not clear exactly how the TPT policy affects the productivity of the pumped storage industry. Using the EBM-GML method and the DID model, this paper measures the total factor productivity of the pumped storage industry and explores the impact of the Two-Part Tariff (TPT) policy on its total factor productivity. Based on the samples of 16 provinces in China from 2004 to 2020, we find the following: (1) At present, the total factor productivity of China’s pumped storage industry is still at a low level. (2) TPT policy can promote the improvement of total factor productivity, which was strongly supported by the robustness test. Innovation incentive is one of the main mechanisms. (3) The impact of TPT policy on total factor productivity has obvious regional heterogeneity. By geographic location, the TPT policy has little effect on the pumped storage industry’s TFP in the eastern region, but it exerts a significant positive role in the central region. By energy affluence, TPT policy effect is stronger in provinces with low energy dependence. By environmental governance, the role of this policy is more obvious in provinces with low environmental regulation but developed green financial market. Finally, some corresponding policy implications have been put forward.

MicroRNAs (MiRNAs) carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment. Our study aimed at identifying the expression profile of exosomal miRNAs (exo-miRNAs) in the serum of multiple myeloma (MM) patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis. Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing. Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted. CytoHubba was applied to identify the hub miRNAs and core target genes. The LASSO Cox regression model was used to develop the prognostic model, and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients. The top six hub differentially expressed serum exo-miRNAs were identified. 513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset. Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing, cellular response to stress, and deubiquitination. 13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients, which is associated with the immune microenvironment of MM patients. Our study comprehensively investigated the exo-miRNA profiles in MM patients. A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.