Atf7ip and Setdb1 interaction orchestrates the hematopoietic stem and progenitor cell state with diverse lineage differentiation.

Hematopoietic stem and progenitor cells (HSPCs) are a heterogeneous group of cells with expansion, differentiation, and repopulation capacities. How HSPCs orchestrate the stemness state with diverse lineage differentiation at steady condition or acute stress remains largely unknown. Here, we show that zebrafish mutants that are deficient in an epigenetic regulator Atf7ip or Setdb1 methyltransferase undergo excessive myeloid differentiation with impaired HSPC expansion, manifesting a decline in T cells and erythroid lineage. We find that Atf7ip regulates hematopoiesis through Setdb1-mediated H3K9me3 modification and chromatin remodeling. During hematopoiesis, the interaction of Atf7ip and Setdb1 triggers H3K9me3 depositions in hematopoietic regulatory genes including cebpß and cdkn1a, preventing HSPCs from loss of expansion and premature differentiation into myeloid lineage. Concomitantly, loss of Atf7ip or Setdb1 derepresses retrotransposons that instigate the viral sensor Mda5/Rig-I like receptor (RLR) signaling, leading to stress-driven myelopoiesis and inflammation. We find that ATF7IP or SETDB1 depletion represses human leukemic cell growth and induces myeloid differentiation with retrotransposon-triggered inflammation. These findings establish that Atf7ip/Setdb1-mediated H3K9me3 deposition constitutes a genome-wide checkpoint that impedes the myeloid potential and maintains HSPC stemness for diverse blood cell production, providing unique insights into potential intervention in hematological malignancy.

Resonant Tunneling-Enhanced Photoresponsivity in a Twisted Graphene van der Waals Heterostructure.

Leveraging its ultrahigh carrier mobility, zero-bandgap linear dispersion, and extremely short response time, graphene exhibits remarkable potential in ultrafast broad-band photodetection. Nonetheless, the inherently low responsivity of graphene photodetectors, due to the low photogenerated carrier density, significantly impedes the development of practical devices. In this study, we present an improved photoresponse within a graphene-hexagonal boron nitride-graphene vertical tunnel junction device, where the crystallographic orientation of the two graphene electrodes is aligned. Through meticulous device structure design and the adjustment of bias and gate voltages, we observe a 2 orders of magnitude increase in tunneling photocurrent, which is attributed to the momentum-conserving resonant electron tunneling. The enhanced external photoresponsivity is evident across a wide temperature and spectral range and achieves 0.7 A/W for visible light excitation. This characteristic, coupled with the device's negative differential conductance, suggests a novel avenue for highly efficient photodetection and high-frequency, logic-based optoelectronics using van der Waals heterostructures.

Antitumor Effect and Immunomodulatory Mechanism of "Oncolytic Extracellular Vesicles".

Enhancing the antitumor immune response and targeting ability of oncolytic viruses will improve the effect of tumor immunotherapy. Through infecting neural stem cells (NSCs) with a capsid dual-modified oncolytic adenovirus (CRAd), we obtained and characterized the "oncolytic extracellular vesicles" (CRAdEV) with improved targeted infection and tumor killing activity compared with CRAd. Both ex vivo and in vivo studies revealed that CRAdEV activated innate immune cells and importantly enhanced the immunomodulatory effect compared to CRAd. We found that CRAdEV effectively increased the number of DCs and activated CD4+ and CD8+ T cells, significantly increased the number and activation of B cells, and produced higher levels of tumor-specific antibodies, thus eliciting enhanced antitumor activity compared with CRAd in a B16 xenograft immunocompetent mice model. This study provides a novel approach to oncolytic adenovirus modification and demonstrates the potential of "oncolytic extracellular vesicles" in antitumor immunotherapy.

Molecular Mechanism of Adenovirus Late Protein L4-100K Chaperones the Trimerization of Hexon.

Assembly of the adenovirus capsid protein hexon depends on the assistance of the molecular chaperone L4-100K. However, the chaperone mechanisms remain unclear. In this study, we found that L4-100K was involved in the hexon translation process and could prevent hexon degradation by the proteasome in cotransfected human cells. Two nonadjacent domains, 84-133 and 656-697, at the N-terminal and C-terminal regions of human adenovirus type 5 L4-100K, respectively, were found to be crucial and cooperatively responsible for hexon trimer expression and assembly. These two chaperone-related domains were conserved in the sequence of L4-100K and in the function of hexon assembly across different adenovirus serotypes. Different degrees of cross-activity of hexon trimerization with different serotypes were detected in subgroups B, C, and D, which were proven to be controlled by the interaction between the C-terminal chaperone-related domain of L4-100K and hypervariable regions (HVR) of hexon. Additionally, HVR-chimeric hexon mutants were successfully assembled with the assistance of the 1-697 mutant. Structural analysis of 656-697 by nuclear magnetic resonance and structural prediction of L4-100K using Robetta showed that the two conserved domains are mainly composed of α-helices and are located on the surface of the highly folded core region. Our research provides a more complete understanding of hexon assembly and guidance for the development of hexon-chimeric adenovirus vectors that will be safer, smarter, and more efficient. IMPORTANCE Adenovirus vectors have been widely used in clinical trials of vaccines and gene therapy, although some deficiencies remain. Chimeric modification of the hexon was expected to improve the potency of preexisting immune evasion and targeting, but in many cases, viral packaging is prevented by the inability of the chimeric hexon to assemble correctly. So far, few studies have examined the mechanisms of hexon trimer assembly. Here, we show how the chaperone protein L4-100K contributes to the assembly of the adenovirus capsid protein hexon, and these data will provide a guide for novel adenovirus vector design and development, as we desired.

Identification of transcriptionally-active human papillomavirus integrants through nanopore sequencing reveals viable targets for gene therapy against cervical cancer.

Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.

Single-pixel imaging based on self-supervised conditional mask classifier-free guidance.

Reconstructing high-quality images at a low measurement rate is a pivotal objective of Single-Pixel Imaging (SPI). Currently, deep learning methods achieve this by optimizing the loss between the target image and the original image, thereby constraining the potential of low measurement values. We employ conditional probability to ameliorate this, introducing the classifier-free guidance model (CFG) for enhanced reconstruction. We propose a self-supervised conditional masked classifier-free guidance (SCM-CFG) for single-pixel reconstruction. At a 10% measurement rate, SCM-CFG efficiently completed the training task, achieving an average peak signal-to-noise ratio (PSNR) of 26.17 dB on the MNIST dataset. This surpasses other methods of photon imaging and computational ghost imaging. It demonstrates remarkable generalization performance. Moreover, thanks to the outstanding design of the conditional mask in this paper, it can significantly enhance the accuracy of reconstructed images through overlay. SCM-CFG achieved a notable improvement of an average of 7.3 dB in overlay processing, in contrast to only a 1 dB improvement in computational ghost imaging. Subsequent physical experiments validated the effectiveness of SCM-CFG.

Supramolecular Interactions Induce Dynamics in Metal-Organic Layers to Selectively Separate Acetylene from Carbon Dioxide.

We report the synthesis and structural characterization of a 2D metal-organic framework with AB-packing layers, [Co2(pybz)2(CH3COO)2]·DMF (Co2, pybz= 4-(4-pyridyl)benzoate), containing a stable (4,4)-grid network fabricated by paddle-wheel nodes, ditopic pybz, and acetate ligands. After removal of the guest, the layer structure is retained but reorganized into an ABCD packing mode in the activated phase (Co2a). Consequently, the intralayer square windows (7.2 × 5.0 Å2) close, while the interlayer separation is decreased slightly from 3.69 to 3.45 Å, leaving a narrow gap. Importantly, the dangling methyl group of the acetate with H-bonds to the adjacent layers and also the well-distributed π-π interactions between the aromatic rings of neighboring layers facilitate the structural stability. These weak supramolecular interactions further allow for favorable dynamic exfoliation of the layers, which promotes efficient adsorption of C2H2 (41.6 cm3 g-1) over CO2 with an adsorption ratio of 6.3 (0.5 bar, 298 K). The effective separation performance of equimolar C2H2/CO2 was verified by cycling breakthrough experiments and was even tolerable to moisture (R.H = 52%). DFT calculations, in situ PXRD, and PDF characterization reveal that the favorable retention of C2H2 rather than that of CO2 is due to its H-bond formation with the paddle-wheel oxygen atoms that triggers the increase in interlayer separation during C2H2 adsorption.

Quorum sensing-induced transition from colloidal waves to Turing-like patterns in chemorepulsive active colloids.

The study of active systems, especially in the presence of a chemical background field, is garnering significant attention. Traditionally, the self-propelled velocity of active colloids was assumed to be constant, independent of the local density of colloids. In this work, we introduce a chemotactic active system that features quorum sensing (QS), wherein particles act as chemorepellents. Interestingly, these particles lose their activity in regions of high local particle density. Our findings reveal that QS leads to a transition from an oscillatory colloidal wave to a Turing-like pattern, with the observation of an intermediate state. With the variation of the sensing threshold, both the mean oscillation frequency of the system and the number of clusters exhibit non-monotonic dependence. Furthermore, the QS-induced pattern differs markedly from systems without QS, primarily due to the competitive interplay between diffusion and chemotaxis. The dynamics of this phenomenon are explained using a coarse-grained mean field model.

Different metal (Mn, Fe, Co, Ni, and Zr) decorated Cu/CeO2 catalysts for efficient CO oxidation in a rich CO2/H2 atmosphere.

In this work, CuM/CeO2 (M = Mn, Fe, Co, Ni, and Zr) catalysts with a low Cu content of 1 wt% were purposely designed and prepared using the co-impregnation method. The samples were characterized using various techniques (TG-DTA, XRD, N2-adsorption/desorption measurements, H2-TPR, XPS and Raman spectroscopy) and CO preferential oxidation (CO-Prox) under H2/CO2-rich conditions was performed. The results have shown that enhanced catalytic performance was achieved upon the introduction of Mn, Co and Ni, and little impact was observed with Zr doping, but Fe showed a negative effect, as compared with the Cu/CeO2 catalyst. Characterization data revealed that the M doping strongly changed the surface composition, revealing the decreased Cu/Ce ratios on the surface, which could be accounted for by the formation of more M/Cu-O-Ce solid solution, or strong Cu-M interactions. When Mn was used, the obtained CuMn/CeO2 catalyst revealed the highest concentration of the oxygen vacancies and Ce3+ ions, which could be correlated well with its superior catalytic performance. Compared with the Cu/CeO2 catalyst, the CO conversion rate increased by 24.7% at a low temperature of 90 °C over the CuMn/CeO2 catalyst. At 130 °C, the maximum CO conversion was 94.7% and the CO2 selectivity was 78.9%. Conversely, the Fe doped Cu/CeO2 catalyst demonstrated the poorest catalytic activity, which was due to the blockage effect of Fe species on Cu showing a high Fe/Cu ratio of 1.9 on the surface.

The XCL1-Mediated DNA Vaccine Targeting Type 1 Conventional Dendritic Cells Combined with Gemcitabine and Anti-PD1 Antibody Induces Potent Antitumor Immunity in a Mouse Lung Cancer Model.

With the advent of cancer immunotherapy, there is a growing interest in vaccine development as a means to activate the cellular immune system against cancer. Despite the promise of DNA vaccines in this regard, their effectiveness is hindered by poor immunogenicity, leading to modest therapeutic outcomes across various cancers. The role of Type 1 conventional dendritic cells (cDC1), capable of cross-presenting vaccine antigens to activate CD8+T cells, emerges as crucial for the antitumor function of DNA vaccines. To address the limitations of DNA vaccines, a promising approach involves targeting antigens to cDC1 through the fusion of XCL1, a ligand specific to the receptor XCR1 on the surface of cDC1. Here, female C57BL/6 mice were selected for tumor inoculation and immunotherapy. Additionally, recognizing the complexity of cancer, this study explored the use of combination therapies, particularly the combination of cDC1-targeted DNA vaccine with the chemotherapy drug Gemcitabine (Gem) and the anti-PD1 antibody in a mouse lung cancer model. The study's findings indicate that fusion antigens with XCL1 effectively enhance both the immunogenicity and antitumor effects of DNA vaccines. Moreover, the combination of the cDC1-targeted DNA vaccine with Gemcitabine and anti-PD1 antibody in the mouse lung cancer model demonstrates an improved antitumor effect, leading to the prolonged survival of mice. In conclusion, this research provides important support for the clinical investigation of cDC1-targeting DNA vaccines in combination with other therapies.

Crown Ether Electrolyte Induced Li2O2 Amorphization for Low Polarization and Long Lifespan Li-O2 Batteries.

Lithium-oxygen batteries possess an extremely high theoretical energy density, rendering them a prime candidate for next-generation secondary batteries. However, they still face multiple problems such as huge charge polarization and poor life, which lay a significant gap between laboratory research and commercial applications. In this work, we adopt 15-crown-5 ether (C15) as solvent to regulate the generation of discharge products in lithium-oxygen batteries. The coronal structure endows C15 with strong affinity to Li+, firmly stabilizes the intermediate LiO2 and discharge product Li2O2. Thus, the crystalline Li2O2 is amorphized into easily decomposable amorphous products. The lithium-oxygen batteries assembled with 0.5 M C15 electrolyte show an increased discharge capacity from 4.0 mAh cm-2 to 5.7 mAh cm-2 and a low charge overpotential of 0.88 V during the whole lifespan at 0.05 mA cm-2. The batteries with 1 M C15 electrolyte can cycle stably for 140 cycles. Furthermore, the amorphous characteristic of Li2O2 product is preserved when matched with redox mediators such as LiI, with the charge polarization further decreasing to 0.74 V over a cycle life of 190 cycles. This provides new possibilities for electrolyte design to promote Li2O2 amorphization and reduce charge overpotential in lithium-oxygen batteries.

The Synthesis of Three-Dimensional Hexagonal Boron Nitride as the Reinforcing Phase of Polymer-Based Electrolyte for All-Solid-State Li Metal Batteries.

Powdery hexagonal boron nitride (h-BN), as an important material for electrochemical energy storage, has been typically synthesized in bulk and one/two-dimensional (1/2D) nanostructured morphologies. However, until now, no method has been developed to synthesize powdery three-dimensional (3D) h-BN. This work introduces a novel NaCl-glucose-assisted strategy to synthesize micron-sized 3D h-BN with a honeycomb-like structure and its proposed formation mechanism. We propose that NaCl acts as the template of 3D structure and promotes the nitridation reaction by adsorbing NH3 . Glucose facilitates the homogeneous coating of boric acid onto the NaCl surface via functionalizing the NaCl surface. During the nitridation reaction, boron oxides (BO4 and BO3 ) form from a dehydration reaction of boric acid, which is then reduced to O2 -B-N and O-B-N2 intermediates before finally being reduced to BN3 by NH3 . When incorporated into polyethylene oxide-based electrolytes for Li metal batteries, 5 wt % of 3D h-BN significantly enhances ionic conductivity and mechanical strength. Consequently, this composite electrolyte demonstrates superior electrochemical stability. It delivers 300 h of stable cycles in the Li//Li cell at 0.1 mA cm-2 and retains 89 % of discharge capacity (138.9 mAh g-1 ) after 100 cycles at 1 C in the LFP//Li full cell.

Dominant Negative Mutants of Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) Disrupt Core-Binding Factor Beta-Vif Interaction.

Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 family members (APOBEC3s) are host restriction factors that inhibit viral replication. Viral infectivity factor (Vif), a human immunodeficiency virus type 1 (HIV-1) accessory protein, mediates the degradation of APOBEC3s by forming the Vif-E3 complex, in which core-binding factor beta (CBFß) is an essential molecular chaperone. Here, we screened nonfunctional Vif mutants with high affinity for CBFß to inhibit HIV-1 in a dominant negative manner. We applied the yeast surface display technology to express Vif random mutant libraries, and mutants showing high CBFß affinity were screened using flow cytometry. Most of the screened Vif mutants containing random mutations of different frequencies were able to rescue APOBEC3G (A3G). In the subsequent screening, three of the mutants restricted HIV-1, recovered G-to-A hypermutation, and rescued APOBEC3s. Among them, Vif-6M showed a cross-protection effect toward APOBEC3C, APOBEC3F, and African green monkey A3G. Stable expression of Vif-6M in T lymphocytes inhibited the viral replication in newly HIV-1-infected cells and the chronically infected cell line H9/HXB2. Furthermore, the expression of Vif-6M provided a survival advantage to T lymphocytes infected with HIV-1. These results suggest that dominant negative Vif mutants acting on the Vif-CBFß target potently restrict HIV-1. IMPORTANCE Antiviral therapy cannot eliminate HIV and exhibits disadvantages such as drug resistance and toxicity. Therefore, novel strategies for inhibiting viral replication in patients with HIV are urgently needed. APOBEC3s in host cells are able to inhibit viral replication but are antagonized by HIV-1 Vif-mediated degradation. Therefore, we screened nonfunctional Vif mutants with high affinity for CBFß to compete with the wild-type Vif (wtVif) as a potential strategy to assist with HIV-1 treatment. Most screened mutants rescued the expression of A3G in the presence of wtVif, especially Vif-6M, which could protect various APOBEC3s and improve the incorporation of A3G into HIV-1 particles. Transduction of Vif-6M into T lymphocytes inhibited the replication of the newly infected virus and the chronically infected virus. These data suggest that Vif mutants targeting the Vif-CBFß interaction may be promising in the development of a new AIDS therapeutic strategy.

Caged Luciferase Inhibitor-Based Bioluminescence Switching Strategy Enables Efficient Detection of Serum APN Activity and the Identification of Its Roles in Metastasis of Non-Small Cell Lung Cancer.

Bioluminogenic probes emerged as powerful tools for imaging and analysis of various bioanalyses, but traditional approaches would be limited to the low sensitivity during determine the low activity of protease in clinical specimens. Herein, we proposed a caged luciferase inhibitor-based bioluminescence-switching strategy (CLIBS) by using a cleavable luciferase inhibitor to modulate the activity of luciferase reporter to amplify the detective signals, which led to the enhancement of detection sensitivity, and enabled the determination of circulating Aminopeptidase N (APN) activity in thousands of times diluted serum. By applying the CLIBS to serum samples in non-small cell lung cancer (NSCLC) patients from two clinical cohorts, we revealed that, for the first time, higher circulating APN activities but not its concentration, were associated with more NSCLC metastasis or higher metastasis stages by subsequent clinical analysis, and can serve as an independent factor for forecasting NSCLC patients' risk of metastasis.

Probing the photocurrent in two-dimensional titanium disulfide.

Generating photocurrent in a condensed matter system involves the excitation, relaxation, and transportation of charge carriers. As such, it is viewed a potent method for probing the dynamics of non-equilibrium carriers and the electronic band structure of solid state materials. In this research, we analyze the photoresponse of the mechanically exfoliated titanium disulfide (TiS2), a transition metal dichalcogenide whose classification as either a semimetal or a semiconductor has been the subject of debate for years. The scanning photocurrent microscopy and the temperature-dependent photoresponse characterization expose the appearance of a photovoltaic current primarily from the metal/TiS2junction in an unbiased sample, while negative photoconductivity due to the bolometric effect is observed in the conductive TiS2channel. The optoelectronic experimental results, combined with electrical transport characterization and angle-resolved photoemission spectroscopy measurements, indicate that the TiS2employed in this study is likely a heavily-doped semiconductor. Our findings unveil the photocurrent generation mechanism of two dimensional TiS2, highlighting its prospective optoelectronic applications in the future.

Dynamics of polymer chains confined to a periodic cylinder: molecular dynamics simulation vs. Lifson-Jackson formula.

The dynamics of polymer chains confined to a periodic cylinder is explored using molecular dynamics simulation and theoretical analysis. The cylinder is divided into two cavities in one periodicity: one cavity consists of a channel of length L1 and diameter D1 and another cavity is a channel of length L2 and diameter D2. For L1 = L2 = L/2, the diffusion coefficient D of a single confined polymer chain decreases rapidly with increase in periodicities L. For a fixed periodicity with L = L1 + L2 = constant, the diffusion coefficient D of a single confined polymer chain shows strong dependence on L1 (or L2). Moreover, for a multi-chain system with L1 = L2, the diffusion coefficient D shows strong non-monotonic dependence on the chain monomer density ρ, and the confined polymer chains diffuse fastest for ρ = 0.068, in which there are three polymer chains in two periodicities as well as two opposing effects: one is that the excluded volume effect between polymer chains can reduce the free energy barrier, and another is that when the chain monomer density ρ increases further, the entanglement effect increases, which leads to that the diffusion coefficient D decreases as ρ increases. Finally, we found that the diffusion coefficient D has a similar oscillation relationship with the ratio of R/L for different chain lengths N and different periodicity L, and the oscillation amplitude decreases gradually as R/L increases; here R is the mean end-to-end distance of a single confined polymer chain, i.e., . From the view of free energy potential, both the width of the free energy potential well and the height of the free energy potential barrier govern simultaneously the diffusion behavior of confined polymer chains. According to the mean force potential (PMF) based on the weighted histogram analysis method (WHAM), we found that our results agree very well with the theoretical analysis using the Lifson-Jackson formula. Our investigation may help us understand the dynamics of particles in a periodic medium, which is one of the interesting problems in many different fields of science, such as physics, chemistry and biology.

Mechanistic insight into humic acid-enhanced sonophotocatalytic removal of 17ß-estradiol: Formation and contribution of reactive intermediates.

In this study, humic acid (HA) enhanced 17ß-estradiol (17ß-E2) degradation by Er3+-CdS/MoS2 (ECMS) was investigated under ultrasonic and light conditions. The degradation reaction rate of 17ß-E2 was increased from (14.414 ± 0.315) × 10-3 min-1 to (122.677 ± 1.729) × 10-3 min-1 within 90 min sonophotocatalytic (SPC) reaction with the addition of HA. The results of quenching coupled with chemical probe experiments indicated that more reactive intermediates (RIs) including reactive oxygen species (ROSs) and triplet-excited states were generated in the HA-enhanced sonophotocatalytic system. The triplet-excited states of humic acid (3HA*), hydroxyl radical (•OH), and superoxide radical (•O2-) were the dominant RIs for 17ß-E2 elimination. In addition, the energy- and electron-transfer process via coexisting HA also account for 12.86% and 29.24% contributions, respectively. The quantum yields of RIs in the SPC-ECMS-HA system followed the order of 3HA* > H2O2 > 1O2 > â€¢O2-> •OH. Moreover, the spectral and fluorescence characteristics of HA were further analyzed during the sonophotocatalytic reaction process. The study expanded new insights into the comprehension of the effects of omnipresent coexisting HA and RIs formation for the removal of 17ß-E2 during the sonophotocatalytic process.

Longitudinal study of multidimensional factors influencing maternal and offspring health outcomes: a study protocol.

BACKGROUND: Reducing preventable adverse maternal and offspring outcomes is a global priority. The causes of adverse maternal and fetal outcomes are complex with multidimensional influencing factors. In addition, the Covid-19 epidemic has had a significant psychological and physical impact on people. China is now stepping into the post-epidemic era. We are curious about the psychological and physical situation of maternity in China at this stage. Therefore, we plan to initiate a prospective longitudinal study to investigate the multidimensional influences and mechanisms that affect maternal and offspring health. METHOD: We will recruit eligible pregnant women at Renmin Hospital of Hubei Province, China. The expected sample size is 1490. We will assess socio-demographics, Covid-19 related information, social capital, sleep, mental health and medical records, including clinical examination and biochemical tests. Eligible pregnant women will be enrolled in the study with less than 14 weeks of gestation. Participants will receive a total of nine follow-up visits between mid-pregnancy and one year postpartum. The offspring will be followed up at birth, 6 weeks, 3 months, 6 months and one year. In addition, a qualitative study will be conducted to understand the underlying causes that affect maternal and offspring health outcomes. DISCUSSION: This is the first longitudinal study of maternity in Wuhan, Hubei Province which integrates physical, psychological and social capital dimensions. Wuhan is the first city to be affected by Covid-19 in China. As China moves into the post-epidemic era, this study will provide us with a better understanding of the long-term impact of the epidemic on maternal and offspring health outcomes. We will implement a range of rigorous measures to enhance participants' retention rate and ensure the quality of data. The study will provide empirical results for maternal health in the post-epidemic era.

Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer's disease.

BACKGROUND: Progressive neuronal death is the key pathological feature of Alzheimer's disease (AD). However, the molecular mechanisms underlying the neuronal death in AD patients have not been fully elucidated. Necroptosis reportedly activates and induces neuronal death in patients with Alzheimer's disease (AD); however, the main mediators and mechanisms underlying necroptosis induction in AD remain elusive. METHODS: The function of hyperphosphorylated tau (pTau) in inducing necroptosis in neuronal cell was examined using Western blotting, RT-PCR and flow cytometry. Tau-induced inflammation was identified via RNA sequencing and transwell assay. Pharmacological methods and CRISPR-Cas9 technology were used to verify the role of necrosome proteins in pTau-stimulated neuronal death and inflammation. TauP301S model mice were treated with Nec-1 s to evaluate the role of necroptosis in tau pathology. RESULTS: Hyperphosphorylated tau could induce necroptosis in neuronal cells by promoting the formation of the RIPK1/RIPK3/MLKL necrosome. In addition, pTau significantly stimulated cell-autonomous overexpression of cytokines and chemokines via the intracellular nuclear factor kappa B (NF-κB) signaling pathway. Importantly, the RIPK1/RIPK3/MLKL axis was essential for the pTau-mediated NF-κB activation and cytokine storm. Furthermore, necroptosis stimulation, NF-κB activation, and cytokine induction have been detected in TauP301S mice and blocking necroptosis markedly ameliorated behavioral defects and excessive neuroinflammation in AD mice. CONCLUSIONS: Our study, for the first time, revealed that pTau contributes to neuronal death by inducing necroptosis and inflammation, mediated by activating the RIPK1/RIPK3/MLKL and NF-κB pathways, thereby delineating the hierarchical molecular network of neuronal necroptosis induction in AD.

Recent advances in polysaccharide-based edible coatings for preservation of fruits and vegetables: A review.

Harvested fruits and vegetables are prone to decay and quality deterioration during storage. Although traditional packaging and chemical treatments are effective, they are harmful to the environment and human health. Hence, higher requirements for food preservation technology are increasingly proposed. Nontoxic, renewable, degradable, and edible packaging for fruits and vegetables has become a research hotspot in recent years. Chitosan, alginate, cellulose, pectin, starch, and other polysaccharides as coating materials have been widely used. Compared with traditional plastic packaging and chemical treatment, these coatings exhibited a better preservation effect and higher safety. In this paper, the preservation mechanism of fruits and vegetables by edible coatings treatment was described, and the research on edible coatings used in fruits and vegetables was summarized. The effects polysaccharide-based edible coatings on physicochemical quality and antimicrobial effect of fruits and vegetables were reviewed.