Essential roles of the nucleolus during early embryonic development: a regulatory hub for chromatin organization.

The nucleolus is the most prominent liquid droplet-like membrane-less organelle in mammalian cells. Unlike the nucleolus in terminally differentiated somatic cells, those in totipotent cells, such as murine zygotes or two-cell embryos, have a unique nucleolar structure known as nucleolus precursor bodies (NPBs). Previously, it was widely accepted that NPBs in zygotes are simply passive repositories of materials that will be gradually used to construct a fully functional nucleolus after zygotic genome activation (ZGA). However, recent research studies have challenged this simplistic view and demonstrated that functions of the NPBs go beyond ribosome biogenesis. In this review, we provide a snapshot of the functions of NPBs in zygotes and early two-cell embryos in mice. We propose that these membrane-less organelles function as a regulatory hub for chromatin organization. On the one hand, NPBs provide the structural platform for centric and pericentric chromatin remodelling. On the other hand, the dynamic changes in nucleolar structure control the release of the pioneer factors (i.e. double homeobox (Dux)). It appears that during transition from totipotency to pluripotency, decline of totipotency and initiation of fully functional nucleolus formation are not independent events but are interconnected. Consequently, it is reasonable to hypothesize that dissecting more unknown functions of NPBs may shed more light on the enigmas of early embryonic development and may ultimately provide novel approaches to improve reprogramming efficiency.

Transmission of blaNDM in Enterobacteriaceae among animals, food and human.

Despite carbapenems not being used in animals, carbapenem-resistant Enterobacterales (CRE), particularly New Delhi metallo-ß-lactamase-producing CRE (NDM-CRE), are prevalent in livestock. Concurrently, the incidence of human infections caused by NDM-CRE is rising, particularly in children. Although a positive association between livestock production and human NDM-CRE infections at the national level was identified, the evidence of direct transmission of NDM originating from livestock to humans remains largely unknown. Here, we conducted a cross-sectional study in Chengdu, Sichuan Province, to examine the prevalence of NDM-CRE in chickens and pigs along the breeding-slaughtering-retail chains, in pork in cafeterias of schools, and in colonizations and infections from children's hospital and examined the correlation of NDM-CRE among animals, foods and humans. Overall, the blaNDM increases gradually along the chicken and pig breeding (4.70%/2.0%) -slaughtering (7.60%/22.40%) -retail (65.56%/34.26%) chains. The slaughterhouse has become a hotspot for cross-contamination and amplifier of blaNDM. Notably, 63.11% of pork from the school cafeteria was positive for blaNDM. The prevalence of blaNDM in intestinal and infection samples from children's hospitals was 21.68% and 19.80%, respectively. whole genome sequencing (WGS) analysis revealed the sporadic, not large-scale, clonal spread of NDM-CRE along the chicken and pig breeding-slaughtering-retail chain, with further spreading via IncX3-blaNDM plasmid within each stage of whole chains. Clonal transmission of NDM-CRE is predominant in children's hospitals. The IncX3-blaNDM plasmid was highly prevalent among animals and humans and accounted for 57.7% of Escherichia coli and 91.3% of Klebsiella pneumoniae. Attention should be directed towards the IncX3 plasmid to control the transmission of blaNDM between animals and humans.

Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Intelligent Detection and Odor Recognition of Cigarette Packaging Paper Boxes Based on a Homemade Electronic Nose.

The printing process of box packaging paper can generate volatile organic compounds, resulting in odors that impact product quality and health. An efficient, objective, and cost-effective detection method is urgently needed. We utilized a self-developed electronic nose system to test four different cigarette packaging paper samples. Employing multivariate statistical methods like Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Statistical Quality Control (SQC), and Similarity-based Independent Modeling of Class Analogy (SIMCA), we analyzed and processed the collected data. Comprehensive evaluation and quality control models were constructed to assess sample stability and distinguish odors. Results indicate that our electronic nose system rapidly detects odors and effectively performs quality control. By establishing models for quality stability control, we successfully identified samples with acceptable quality and those with odors. To further validate the system's performance and extend its applications, we collected two types of cigarette packaging paper samples with odor data. Using data augmentation techniques, we expanded the dataset and achieved an accuracy rate of 0.9938 through classification and discrimination. This highlights the significant potential of our self-developed electronic nose system in recognizing cigarette packaging paper odors and odorous samples.

Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.

CO2 sequestration in microbial electrolytic cell-anaerobic digestion system combined with mineral carbonation for sludge hydrolysate treatment.

The combination of microbial electrolytic cells and anaerobic digestion (MEC-AD) became an efficient method to improve CO2 capture for waste sludge treatment. By adding CaCl2 and wollastonite, the CO2 sequestration effect with mineral carbonation under 0 V and 0.8 V was studied. The results showed that applied voltage could increase dissolved chemical oxygen demand (SCOD) degradation efficiency and biogas yield effectively. In addition, wollastonite and CaCl2 exhibited different CO2 sequestration performances due to different Ca2+ release characteristics. Wollastonite appeared to have a better CO2 sequestration effect and provided a wide margin of pH change, but CaCl2 released Ca2+ directly and decreased the pH of the MEC-AD system. The results showed methane yield reached 137.31 and 163.50 mL/g SCOD degraded and CO2 content of biogas is only 12.40 % and 2.22 % under 0.8 V with CaCl2 and wollastonite addition, respectively. Finally, the contribution of chemical CO2 sequestration by mineral carbonation and biological CO2 sequestration by hydrogenotrophic methanogenesis was clarified with CaCl2 addition. The chemical and biological CO2 sequestration percentages were 46.79 % and 53.21 % under 0.8 V, respectively. With the increased applied voltage, the contribution of chemical CO2 sequestration rose accordingly. The findings in this study are of great significance for further comprehending the mechanism of calcium addition on CO2 sequestration in the MEC-AD system and providing guidance for the later engineering application.

Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer.

Mitochondriopathy inspired adenosine triphosphate (ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration (IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites, leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages. Briefly, the reported transformable nucleopeptide (NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei, which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines (T24, EJ and RT-112) revealed that the half-maximal inhibitory concentration (IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6.

Helicobacter pylori (H. pylori, Hp) has been designated a class I carcinogen and is closely associated with severe gastric diseases. During colonization in the gastric mucosa, H. pylori develops immune escape by inducing host immune tolerance. The gastric epithelium acts as the first line of defense against H. pylori, with Toll-like receptors (TLRs) in gastric epithelial cells being sensitive to H. pylori components and subsequently activating the innate immune system. However, the mechanism of immune tolerance induced by H. pylori through the TLR signalling pathway has not been fully elucidated. In this research, we detected the expression of TLRs and inflammatory cytokines in GES-1 cells upon sustained exposure to H. pylori or H. pylori lysate from 1 to 30 generations and in Mongolian gerbils infected with H. pylori for 5 to 90 weeks. We found that the levels of TLR6 and inflammatory cytokines first increased and then dropped during the course of H. pylori treatment in vitro and in vivo. The restoration of TLR6 potentiated the expression of IL-1ß and IL-8 in GES-1 cells, which recruited neutrophils and reduced the colonization of H. pylori in the gastric mucosa of gerbils. Mechanistically, we found that persistent infection with H. pylori reduces the sensitivity of TLR6 to bacterial components and regulates the expression of inflammatory cytokines in GES-1 cells through TLR6/JNK signaling. The TLR6 agonist obviously alleviated inflammation in vitro and in vivo. Promising results suggest that TLR6 may be a potential candidate immunotherapy drug for H. pylori infection.

Digital PCR-based GRHL2 methylation testing in acute myeloid leukemia: diagnosis, prognosis and monitoring.

Background: Acute myeloid leukemia (AML) is a challenging disease with high rates of recurrence. The role of the cancer-related gene GRHL2 in AML has not been widely studied. Methods: Peripheral blood samples were collected from 73 AML patients and 68 healthy controls. Droplet digital PCR was used to detect GRHL2 methylation levels to explore the value of GRHL2 methylation in the diagnosis, treatment response and prognosis of AML. Result: GRHL2 methylation was significantly increased in AML patients (p < 0.01), with high diagnostic accuracy (area under the curve: 0.848; p < 0.001). GRHL2 methylation was correlated with chemotherapy response (p < 0.05) and is an independent prognostic factor for AML (p < 0.05). Conclusion: GRHL2 methylation is expected to serve as a biomarker for diagnosing AML patients and predicting prognosis.

Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway.

BACKGROUND: Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets. METHODS: Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC­1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-ß-galactosidase (SA-ß-Gal) staining. RESULTS: Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs. CONCLUSION: APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.

An evaluation model for in-situ bioremediation technology of petroleum hydrocarbon contaminated soil.

Considering the interference of the complexity of underground environment to the bioremediation scheme, an evaluation model for bioremediation technology in the soil source area of oil contaminated sites was established. On the basis of traditional CDE model, a compartment model was coupled to express the adsorption and degradation process, and the spatial expression of biodegradation was enriched through environment-dependent factors. The visualization of the model was achieved based on COMSOL Multiphysics software platform. Two sets of indoor sandbox experiments on natural attenuation and bioaugmentation were carried out for 120 days to verify the prediction function of the model. The results showed that bioaugmentation greatly improved the remediation effect. Petroleum hydrocarbons with different occurrence states exhibited different spatial distributions under the influence of environmental factors. The prediction accuracy evaluation results of total petroleum hydrocarbons, bio available hydrocarbons and non extractable hydrocarbons showed excellent fitting degree, and the model had a good prediction function for petroleum hydrocarbon in soil under different bioremediation scenarios. This model can be used to screen bioremediation technical schemes, prevent pollution and assess risk of petroleum hydrocarbon contaminated sites.

Strain-modulated Ru-O Covalency in Ru-Sn Oxide Enabling Efficient and Stable Water Oxidation in Acidic Solution.

RuO2 is one of the benchmark electrocatalysts used as the anode material in proton exchange membrane water electrolyser. However, its long-term stability is compromised due to the participation of lattice oxygen and metal dissolution during oxygen evolution reaction (OER). In this work, weakened covalency of Ru-O bond was tailored by introducing tensile strain to RuO6 octahedrons in a binary Ru-Sn oxide matrix, prohibiting the participation of lattice oxygen and the dissolution of Ru, thereby significantly improving the long-term stability. Moreover, the tensile strain also optimized the adsorption energy of intermediates and boosted the OER activity. Remarkably, the RuSnOx electrocatalyst exhibited excellent OER activity in 0.1 M HClO4 and required merely 184 mV overpotential at a current density of 10 mA cm-2 . Moreover, it delivered a current density of 10 mA cm-2 for at least 150 h with negligible potential increase. This work exemplifies an effective strategy for engineering Ru-based catalysts with extraordinary performance toward water splitting.

A Study on the Surface Quality and Damage Properties of Single-Crystal Silicon Using Different Post-Treatment Processes.

Detecting subsurface defects in optical components has always been challenging. This study utilizes laser scattering and photothermal weak absorption techniques to detect surface and subsurface nano-damage precursors of single-crystal silicon components. Based on laser scattering and photothermal weak absorption techniques, we successfully establish the relationship between damage precursors and laser damage resistance. The photothermal absorption level is used as an important parameter to measure the damage resistance threshold of optical elements. Single-crystal silicon elements are processed and post-processed optimally. This research employs dry etching and wet etching techniques to effectively eliminate damage precursors from optical components. Additionally, detection techniques are utilized to comprehensively characterize these components, resulting in the successful identification of optimal damage precursor removal methods for various polishing types of single-crystal silicon components. Consequently, this method efficiently enhances the damage thresholds of optical components.

Long-term impact of nano zero-valent iron on methanogenic activity, microbial community structure, and transcription activity in anaerobic wastewater treatment system.

Nano zero-valent iron (NZVI) is commonly used in industrial wastewater treatment. However, its long-term impact mechanisms of metabolization in anaerobic systems are not well understood. This study investigated the effects of long-term and continuous addition of NZVI on methanogenic activity, microbial community, and transcription activity. The results demonstrated that low levels of NZVI (1000 mg/L) induced inhibition of methanogenesis after 80 days, while high levels of NZVI (5000 mg/L) immediately led to a sharp decrease of cumulative methane production and chemical oxygen demand removal, which arrived at a steady state (14.4 % of control and 17 %) after 30 days. NZVI adversely affected cell viability, adenosine triphosphate production, and fatty acid evolution of cell membranes played a crucial role in resisting chronic NZVI toxicity. Moreover, high NZVI levels hindered the transcription of key enzymes CoM and mcrA, while low NZVI levels maintained its high CoM and mcrA activity, but down-regulated the transcription of cdh and hdr. Besides, amino-utilizing bacteria was reduced under the high NZVI concentration, while low NZVI changed dominant genus with potential protein hydrolysis function from Candidatus Cloacamonas to Sedimentibacter. These results provide a guideline for proper NZVI utilization in wastewater treatment.

Deubiquitinating enzyme PSMD7 promotes bladder cancer development: Involvement of RAB1A stabilization.

BACKGROUND: Proteasome 26S subunit, non-ATPase 7 (PSMD7) is a deubiquitinating enzyme that is involved in the stability of ubiquitinated proteins and participates in the development of multiple types of cancer. The roles of PSMD7 and its potential mechanisms in bladder cancer (BC) remain elusive. METHODS: In this study, we identified that PSMD7 was overexpressed in BC tissues based on gene expression omnibus (GEO) database and TNMplot web. To investigate the functional role of PSMD7, two BC cell lines, T24 and 5637, were selected. The cells were transfected with vectors containing short hairpin RNAs against PSMD7 or plasmids containing full-length PSMD7 to knockdown or overexpress PSMD7. RESULTS: Our results revealed that silencing PSMD7 inhibited cell proliferation, cycle progression, migration, invasion, and promoted cell apoptosis, whereas PSMD7 overexpression led to the opposite effects in the BC cells. Mechanically, PSMD7 influenced the protein expression but not the mRNA expression of the Ras-related protein Rab-1 A (RAB1A). PSMD7 combined with RAB1A and negatively regulated its ubiquitination, indicating that PSMD7 enhanced the stability of RAB1A through post-transcriptional modification. Moreover, the rescue experiment demonstrated that RAB1A was an important downstream effector molecule of PSMD7. Besides, the negative regulation of silencing PSMD7 on tumor growth was confirmed in mice. CONCLUSIONS: Our study substantiated a novel mechanism by which PSMD7 stabilized RAB1A to accelerate the progression of BC.

Human neural stem cells.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications.

Human midbrain dopaminergic progenitors.

Human midbrain dopaminergic progenitors (mDAPs) are one of the most representative cell types in both basic research and clinical applications. However, there are still many challenges for the preparation and quality control of mDAPs, such as the lack of standards. Therefore, the establishment of critical quality attributes and technical specifications for mDAPs is largely needed. "Human midbrain dopaminergic progenitor" jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human mDAPs in China. This standard specifies the technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for human mDAPs, which is applicable to the quality control for human mDAPs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will facilitate the institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human mDAPs for clinical development and therapeutic applications.

AdvMIL: Adversarial multiple instance learning for the survival analysis on whole-slide images.

The survival analysis on histological whole-slide images (WSIs) is one of the most important means to estimate patient prognosis. Although many weakly-supervised deep learning models have been developed for gigapixel WSIs, their potential is generally restricted by classical survival analysis rules and fully-supervised learning requirements. As a result, these models provide patients only with a completely-certain point estimation of time-to-event, and they could only learn from the labeled WSI data currently at a small scale. To tackle these problems, we propose a novel adversarial multiple instance learning (AdvMIL) framework. This framework is based on adversarial time-to-event modeling, and integrates the multiple instance learning (MIL) that is much necessary for WSI representation learning. It is a plug-and-play one, so that most existing MIL-based end-to-end methods can be easily upgraded by applying this framework, gaining the improved abilities of survival distribution estimation and semi-supervised learning. Our extensive experiments show that AdvMIL not only could often bring performance improvement to mainstream WSI survival analysis methods at a relatively low computational cost, but also enables these methods to effectively utilize unlabeled data via semi-supervised learning. Moreover, it is observed that AdvMIL could help improving the robustness of models against patch occlusion and two representative image noises. The proposed AdvMIL framework could promote the research of survival analysis in computational pathology with its novel adversarial MIL paradigm.

A hybrid attention network with convolutional neural network and transformer for underwater image restoration.

The analysis and communication of underwater images are often impeded by various elements such as blur, color cast, and noise. Existing restoration methods only address specific degradation factors and struggle with complex degraded images. Furthermore, traditional convolutional neural network (CNN) based approaches may only restore local color while ignoring global features. The proposed hybrid attention network combining CNN and Transformer focuses on addressing these issues. CNN captures local features and the Transformer uses multi-head self-attention to model global relationships. The network also incorporates degraded channel attention and supervised attention mechanisms to refine relevant features and correlations. The proposed method fared better than existing methods in a variety of qualitative criteria when evaluated against the public EUVP dataset of underwater images.