Fabrication of multi-functional molecular tunnelling junctions by click chemistry.

Continuous advancement in molecular electronics demands increasing functionality and diversity of integrated molecular junctions; however, single-functional molecular junctions fail to meet these requirements. In this article, we propose the use of a widely applicable and efficient click reaction on the surface to modify self-assembled monolayers (SAMs) to achieve multifunctional molecular tunnelling junctions, current rectification and memristance, on a single chip. This approach has allowed us to meet the growing demand for versatility and functionality in molecular electronic devices.

OBOX regulates mouse zygotic genome activation and early development.

Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition1,2. However, the identity of transcription factors that underlie mammalian ZGA in vivo remains elusive. Here we show that OBOX, a PRD-like homeobox domain transcription factor family (OBOX1-OBOX8)3-5, are key regulators of mouse ZGA. Mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 had a two-cell to four-cell arrest, accompanied by impaired ZGA. The Obox knockout defects could be rescued by restoring either maternal and zygotic OBOX, which suggests that maternal and zygotic OBOX redundantly support embryonic development. Chromatin-binding analysis showed that Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated the 'preconfiguration' of RNA polymerase II, as the polymerase relocated from the initial one-cell binding targets to ZGA gene promoters and distal enhancers. Impaired polymerase II preconfiguration in Obox mutants was accompanied by defective ZGA and chromatin accessibility transition, as well as aberrant activation of one-cell polymerase II targets. Finally, ectopic expression of OBOX activated ZGA genes and MERVL repeats in mouse embryonic stem cells. These data thus demonstrate that OBOX regulates mouse ZGA and early embryogenesis.

Single-cell landscape analysis reveals systematic senescence in mammalian Down syndrome.

BACKGROUND: Down syndrome (DS), which is characterized by various malfunctions, is the most common chromosomal disorder. As the DS population continues to grow and most of those with DS live beyond puberty, early-onset health problems have become apparent. However, the cellular landscape and molecular alterations have not been thoroughly studied. METHODS: This study utilized single-cell resolution techniques to examine DS in humans and mice, spanning seven distinct organs. A total of 71 934 mouse and 98 207 human cells were analyzed to uncover the molecular alterations occurring in different cell types and organs related to DS, specifically starting from the fetal stage. Additionally, SA-ß-Gal staining, western blot, and histological study were employed to verify the alterations. RESULTS: In this study, we firstly established the transcriptomic profile of the mammalian DS, deciphering the cellular map and molecular mechanism. Our analysis indicated that DS cells across various types and organs experienced senescence stresses from as early as the fetal stage. This was marked by elevated SA-ß-Gal activity, overexpression of cell cycle inhibitors, augmented inflammatory responses, and a loss of cellular identity. Furthermore, we found evidence of mitochondrial disturbance, an increase in ribosomal protein transcription, and heightened apoptosis in fetal DS cells. This investigation also unearthed a regulatory network driven by an HSA21 gene, which leads to genome-wide expression changes. CONCLUSION: The findings from this study offer significant insights into the molecular alterations that occur in DS, shedding light on the pathological processes underlying this disorder. These results can potentially guide future research and treatment development for DS.

A Study on the Fatigue Performance and Corrosion Resistance of 304/45 Bimetallic Composite Bolts.

This paper utilized a hot-rolling process to produce composite rods and subsequently manufactured 304/45 composite bolts through the process of drawing and thread rolling. The study focused on examining the microstructure, fatigue performance, and corrosion resistance of these composite bolts. Additionally, the impacts of quenching and tempering on the fatigue performance of the composite bolts were explored and compared to the performance of 304 stainless steel (SS) bolts and Grade 6.8 35K carbon steel (CS) bolts. The results indicate that the SS cladding of the cold-worked 304/45 composite (304/45-CW) bolts was primarily strengthened by the cold deformation mechanism, which resulted in high microhardness, averaging 474 HV. At a maximum surface bending stress of 300 MPa, the fatigue cycles of the 304/45-CW reached 342,600 cycles at a 63.2% failure probability, which was significantly higher than that of commercial 35K CS bolts. The S-N fatigue curves showed that the fatigue strength of the 304/45-CW bolts was approximately 240 MPa, but the fatigue strength of the quenched and tempered 304/45 composite (304/45-QT) bolts decreased significantly to 85 MPa, due to the loss of the cold deformation strengthening effect. The corrosion resistance of the SS cladding of the 304/45-CW bolts was impressive and remained largely unaffected by carbon element diffusion.

A composite energy harvester based on human reciprocating motion.

In this paper, a piezoelectric electromagnetic composite energy harvester is studied. The device consists of a mechanical spring, upper and lower base, magnet coil, etc. The upper and lower bases are connected by struts and mechanical springs and secured by end caps. The device moves up and down under the vibration of the external environment. As the upper base moves downward, the circular excitation magnet moves downward, and the piezoelectric magnet is deformed under a non-contact magnetic force. Traditional energy harvesters have the problems of a single form of power generation and inefficient energy collection. This paper proposes a piezoelectric electromagnetic composite energy harvester to improve energy efficiency. Through theoretical analysis, the power generation trends of rectangular, circular, and electric coils are obtained. Simulation analysis yields the maximum displacement of the rectangular and circular piezoelectric sheets. The device uses piezoelectric power generation and electromagnetic power generation to achieve compound power generation, improve the output voltage and output power, and can provide power supply to more electronic components. By introducing the nonlinear magnetic action, the mechanical collision and wear of the piezoelectric elements during the work are avoided, so that the service life and service life of the equipment is extended. The experimental results show that the highest output voltage of the device is 13.28 V when the circular magnets mutually repel rectangular mass magnets and the tip magnet of the piezoelectric element is 0.6 mm from the sleeve. The external resistance is 1000 Ω, and the maximum power output of the device is 5.5 mW.

Construction of a cross-species cell landscape at single-cell level.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.

How many cell types are there in nature? How do they change during the life cycle? These are two fundamental questions that researchers have been trying to understand in the area of biology. In this study, single-cell mRNA sequencing data were used to profile over 2.6 million individual cells from mice, zebrafish and Drosophila at different life stages, 1.3 million of which were newly collected. The comprehensive datasets allow investigators to construct a cross-species cell landscape that helps to reveal the conservation and diversity of cell taxonomies at genetic and regulatory levels. The resources in this study are assembled into a publicly available website at http://bis.zju.edu.cn/cellatlas/.

The Age of Mobility: Can Equalization of Public Health Services Alleviate the Poverty of Migrant Workers?

Migrants workers are important participants in and contributors to economic and social construction, but they still face the reality of being marginalized. Based on data from the China Migrants Dynamic Survey in 2018, this paper systematically investigated the impact of public health services on the multidimensional poverty of migrant workers. The research found that, first, the current mean of the multidimensional poverty deprivation value of migrant workers is 0.1806, which is one dimension of poverty that exists on average. In addition, migrant workers do not have high access to public health services. The proportions of migrant workers who have not established residents' health files and who have not received public health education are 74.22% and 29.92%, respectively. Second, public health services can significantly alleviate the multidimensional poverty of migrant workers. After mitigating the potential endogeneity problem by the IV-2SLS method and conducting robustness tests by the PSM method, the conclusion is still robust. Further research found that the impact of public health services on the multidimensional poverty alleviation of migrant workers is heterogeneous. The improvement of public health services has the greatest effect on the multidimensional poverty alleviation of the new generation of migrant female workers in the western region. The research in this paper helps to examine and clarify the policy significance of public health services for the multidimensional poverty alleviation of migrant workers and provides empirical evidence for the use of public health services to tackle the poverty problem.

Plasmon enhanced light-matter interaction of rice-like nanorods by a cube-plate nanocavity.

Plasmonic nanocavity is widely used for enhancing light-matter interaction. Here, an efficient plasmonic nanocavity of the cube-plate system is constructed for the fluorescence enhancement of rice-like CdSe/CdS nanorods (NRs) with tunable emission wavelength. Over ten thousand times fluorescence enhancement is achieved with the assistance of the plasmonic nanocavity. Additionally, a small splitting effect is observed in both photoluminescence and scattering spectra of the NRs in the nanocavity owing to the intermediate coupling effect between the NRs and plasmonic nanocavity, which provides a potential application for optical signal enhancement and strong light-matter interaction.

Correction: Plasmon enhanced light-matter interaction of rice-like nanorods by a cube-plate nanocavity.

[This corrects the article DOI: 10.1039/D1NA00777G.].

Two new lactam derivatives from a Sphagneticola trilobata derived fungus Penicillium rubens PQJ-2.

A new bicyclic lactam derivatives penicilactam B (1) and a new monocyclic amide penicillamide D (2), along with four known compounds (3-6), were isolated from the fermentation broth of the derived fungus Penicillium rubens PQJ-2. Their structures and stereochemistry were elucidated by comprehensive spectroscopic analyses and quantum ECD calculations. All the compounds were evaluated for their antibacterial activities against Staphylococcus aureus subsp, Candida albicans, Escherichia coli and insecticidal activity against Helicoverpa armigera Hubner. Compounds 1-3 exhibited modest insecticidal activity against H. armigera Hubner.

Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development.

Waddington's epigenetic landscape is a metaphor frequently used to illustrate cell differentiation. Recent advances in single-cell genomics are altering our understanding of the Waddington landscape, yet the molecular mechanisms of cell-fate decisions remain poorly understood. We constructed a cell landscape of mouse lineage differentiation during development at the single-cell level and described both lineage-common and lineage-specific regulatory programs during cell-type maturation. We also found lineage-common regulatory programs that are broadly active during the development of invertebrates and vertebrates. In particular, we identified Xbp1 as an evolutionarily conserved regulator of cell-fate determinations across different species. We demonstrated that Xbp1 transcriptional regulation is important for the stabilization of the gene-regulatory networks for a wide range of mouse cell types. Our results offer genetic and molecular insights into cellular gene-regulatory programs and will serve as a basis for further advancing the understanding of cell-fate decisions.

Microglia-derived TNF-α inhibiting GABAergic neurons in the anterior lateral bed nucleus of the stria terminalis precipitates visceral hypersensitivity induced by colorectal distension in rats.

Irritable bowel syndrome (IBS) is a common and debilitating gastrointestinal disorder that is exacerbated by stress and characterized by abdominal pain. Although microglia in the CNS have been implicated as an important mediator of the stress response, the role of microglia and microglia-GABAergic neuron interactions in the limbic area, most notably BNST, in the development of colorectal hypersensitivity has not been determined. We established a neonatal colorectal distension-induced chronic visceral hyperalgesia model in rats. The results showed that the frequency of spontaneous discharges of alBNST GABAergic neurons and the expression of GAD65/67 were significantly decreased in rats with chronic visceral pain. Moreover, ablation of BNST GABAergic neurons significantly reduced the visceral pain threshold in normal rats. Meanwhile, the number of M1 proinflammatory microglia and the expression of the M1 proinflammatory microglia-derived cytokines IL-6 and TNF-α were increased in the alBNST of rats with chronic visceral pain. Furthermore, alBNST infusion of the microglial inhibitor minocycline or IL-6 and TNF-α neutralizing antibodies significantly increased the visceral pain threshold. The decreased frequency of spontaneous discharges of alBNST GABAergic neurons in rats with chronic visceral pain was mimicked by a bath perfusion of TNF-α, but not IL-6, and was abolished by a perfusion of the microglial inhibitor minocycline. In addition, the alBNST infusion of the microglial inhibitor minocycline upregulated the expression of GAD65/67. Moreover, ablation of BNST GABAergic neurons significantly decreased the visceral pain threshold in normal rats, which was not reversed by a subsequent infusion of the microglial inhibitor minocycline. Our findings revealed this microglia-GABAergic neuron circuit in the alBNST, and this microglia-driven disinhibitory mechanism is essential for brain and gut dysfunction in stressful condition, providing a novel potential target for treating patients with IBS presenting visceral pain that is worsened during episodes of stress.

Parametric analysis of the output performance of a valveless piezoelectric pump with a bullhorn-shaped structure.

In response to the serious problem of backflow in valveless piezoelectric pumps, this paper proposes a valveless piezoelectric pump with a bullhorn-shaped structure. In this paper, we analyze the flow guide by using the "tail flow space pressure comparison method" and "fluid unit dynamic analysis method," revealing the working principle of the flow guide in the valveless piezoelectric pump. The effects of the height, sharp angle, and filter angle of the bullhorn-shaped structure on the output flow were investigated separately by the experiment. The experimental results show that the output flow rate is best when the height of the bullhorn structure is 2 mm, the choke of the bullhorn-shaped structure is 2, and the sharp angle and fillet angle are 180°. The output flow rate of this valveless piezoelectric pump can reach 170.6 ml/min at a drive voltage of 210 V and a drive frequency of 45 Hz, indicating that the valveless piezoelectric pump has good pumping capability and can effectively alleviate the backflow phenomenon. This study offers some valuable insights into improving its performance and practical application.

Porous solid carbon source-supported denitrification in simulated mariculture wastewater.

A porous solid carbon source was prepared by semen litchi (SL), poly(vinyl alcohol) (PVA) and sodium alginate (SA) in aqueous. The effect of SL content on the structures and denitrification performance of the porous solid carbon source in simulated mariculture wastewater was investigated. The SL/PVA/SA beads showed a network structure with a wide range of macropores. Compared with blank beads, the SL/PVA/SA beads showed an increased rough surface and whole distribution on the surface with the increase of SL. In addition, SL/PVA/SA beads have more uniform pore size, but the porosity of SL/PVA/SA beads was decreased with the increase of SL. The porosity of the beads was 83.24%, 74.24%, 71.48% and 71.29% for blank beads and SL/PVA/SA beads contained 30%, 40% and 50% SL, when it was used as a solid carbon source for denitrification. Owing to their good porosity and biocompatibility, SL/PVA/SA beads had shorter acclimation time. Nitrate removal rate could reach up to 100% after two days of adaptation. After the exhaustion of carbon sources, nitrate removal rate less than 50% occurred at the 9th, 10th and 11th day for SL/PVA/SA beads that contained 30%, 40% and 50% SL, respectively. The beads that contained 50% SL exhibited longer lifetime during the denitrification reaction and denitrification rate could reach 243.5 ± 7.08 mg N (L d)-1. It could be used as an economical and effective carbon source for denitrification in mariculture wastewater.

A single-cell survey of cellular hierarchy in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. METHODS: Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. RESULTS: From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic "cancer attractor" that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. CONCLUSIONS: We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.

Causal Inference Machine Learning Leads Original Experimental Discovery in CdSe/CdS Core/Shell Nanoparticles.

The synthesis of CdSe/CdS core/shell nanoparticles was revisited with the help of a causal inference machine learning framework. The tadpole morphology with 1-2 tails was experimentally discovered. The causal inference model revealed the causality between the oleic acid (OA), octadecylphosphonic acid (ODPA) ligands, and the detailed tail shape of the tadpole morphology. Further, with the identified causality, a neural network was provided to predict and directly lead to the original experimental discovery of new tadpole-shaped structures. An entropy-driven nucleation theory was developed to understand both the ligand and temperature dependent experimental data and the causal inference from the machine learning framework. This work provided a vivid example of how the artificial intelligence technology, including machine learning, could benefit the materials science research for the discovery.

The role of SOCS3 in the hypothalamic paraventricular nucleus in rat model of inflammatory pain.

BACKGROUND: Inflammatory molecular signals are modulated by a variety of intracellular transduction pathways, the activation of which may induce and amplify the spread of inflammatory response. Suppresser of cytokine signaling 3 (SOCS3) is an established negative feedback regulation transcription factor associated with tumor, diabetes mellitus, inflammation and anaphylaxis. Herein, we investigated whether SOCS3 in the paraventricular nucleus (PVN) can attenuate pro-inflammatory responses, and thereby relieve the inflammatory pain. METHODS: Adeno-associated virus (AAV) overexpressing SOCS3 was pre-injected into the PVN. Three weeks later, rat model of chronic inflammatory pain was established via subcutaneous injection of complete Freund's adjuvant (CFA) into the plantar center of hind paws. The therapeutic effect of SOCS3 was tested by the measurement of thermal and mechanical allodynia. In mechanistic study, the protein level of SOCS3 was evaluated by Western blotting, and the expression of c-fos and Iba-1 were assessed by immunofluorescent staining. RESULTS: Inflammatory pain was associated with upregulated interleukin 6 (IL-6) and SOCS3 in PVN in the acute phase. Thermal hyperalgesia can be relieved by intra-PVN injection of IL-6 neutralizing antibody (NA). Meanwhile, the upregulated c-fos and microglial activation was reversed. Furthermore, SOCS3 expression in PVN was downregulated in the chronic phase. Intra-PVN injection of AAV overexpressing SOCS3 suppressed the activation of neurons and attenuated thermal hyperalgesia and mechanical allodynia. CONCLUSION: Inhibition of IL-6 signaling attenuated inflammatory hyperalgesia in the acute phase. SOCS3 overexpression in the PVN attenuated inflammatory pain in the chronic phase via suppression of neuronal activation.

Construction of a human cell landscape at single-cell level.

Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems1. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.

Adsorption behaviour and mechanism of the PFOS substitute OBS (sodium p-perfluorous nonenoxybenzene sulfonate) on activated carbon.

Perfluorooctane sulfonate (PFOS) was listed as a persistent organic pollutant by the Stockholm Convention. As a typical alternative to PFOS, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has recently been detected in the aquatic environment which has caused great concern. For the first time, the adsorption behaviour and mechanism of OBS on activated carbon (AC) with different physical and chemical properties were investigated. Decreasing the particle size of AC can accelerate its adsorption for OBS, while AC with too small particle size was not conducive to its adsorption capacity due to the destruction of its pore structure during the mechanical crushing process. Intra-particle diffusion had a lesser effect on the adsorption rate of AC with smaller particle size, higher hydrophilicity and larger pore size. Reactivation of AC by KOH can greatly enlarge their pore size and surface area, greatly increasing their adsorption capacities. The adsorption capacity of two kinds of R-GAC exceeded 0.35 mmol g-1, significantly higher than that of other ACs. However, increasing the hydrophilicity of AC would decrease their adsorption capacities. Further investigation indicated that a larger pore size and smaller particle size can greatly enhance the adsorptive removal of OBS on AC in systems with other coexisting PFASs and organic matter due to the reduction of the pore-blocking effect. The spent AC can be successfully regenerated by methanol, and it can be partly regenerated by hot water and NaOH solution. The percentage of regeneration for the spent AC was 70.4% with 90°C water temperature and up to 95% when 5% NaOH was added into the regeneration solution. These findings are very important for developing efficient adsorbents for the removal of these newly emerging PFASs from wastewater and understanding their interfacial behaviour.