Search

N6‐methyladenosine (m6A) modification, installed by METTL3‐METTL14 complex, is abundant and critical in eukaryotic mRNA. However, its role in oral mucosal immunity remains ambiguous. Periodontitis is a special but prevalent infectious disease characterized as hyperinflammation of oral mucosa and bone resorption. Here, it is reported that genetic deletion of Mettl3 alleviates periodontal destruction via suppressing NLRP3 inflammasome activation. Mechanistically, the stability of TNFAIP3 (also known as A20) transcript is significantly attenuated upon m6A modification. When silencing METTL3, accumulated TNFAIP3 functioning as a ubiquitin‐editing enzyme facilitates the ubiquitination of NEK7 [NIMA (never in mitosis gene a)‐related kinase 7], and subsequently impairs NLRP3 inflammasome assembly. Furtherly, Coptisine chloride, a natural small‐molecule, is discovered as a novel METTL3 inhibitor and performs therapeutic effect on periodontitis. The study unveils a previously unknown pathogenic mechanism of METTL3‐mediated m6A modifications in periodontitis and indicates METTL3 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Subtropical evergreen broad‐leaved forest (EBLF) is the predominant vegetation type in eastern China. However, the majority of the region it covers in eastern China was an arid area during the Paleogene. The temporal history and essential factors involved in the evolution of subtropical EBLFs in eastern China remain enigmatic. Here we report on the niche evolution of Quercus section Cyclobalanopsis, which appeared in south China and Japan during the Eocene and became a dominant component of subtropical EBLFs since the Miocene in eastern Asia, using integrative analysis of occurrences, climate data and a dated phylogeny of 35 species in Cyclobalanopsis. Species within clades Cyclobalanoides, Lamellosa, and Helferiana mainly exist in the Himalaya–Hengduan region, adapting to a plateau climate, while species within the other clades mainly live in eastern China under the control of the East Asian monsoon. Reconstructed history showed that significant divergence of climatic tolerance in Cyclobalanopsis began around 19 million years ago (Ma) in the early Miocene. Simultaneously, disparities in precipitation of wettest/warmest quarter and annual precipitation were markedly enhanced in Cyclobalanopsis, especially in the recent eastern clades. During the Miocene, the marked radiation of Cyclobalanopsis and many other dominant taxa of subtropical EBLFs strongly suggest the rapid formation and expansion of subtropical EBLFs in eastern China. Our research highlights that the intensification of the East Asian monsoon and subsequent occupation of new niches by the ancient clades already present in the south may have jointly promoted the formation of subtropical EBLFs in eastern China since the early Miocene. [ABSTRACT FROM AUTHOR]

Multi‐dimensional force sensing that combines intensity, location, area and the like could gather a wealth of information from mechanical stimuli. Developing materials with force‐induced optical and electrical dual responses would provide unique opportunities to multi‐dimensional force sensing, with electrical signals quantifying the force amplitude and the luminescence output providing spatial distribution of force. However, the reliance on external power supply and high‐energy excitation source brings significant challenges to the applicability of multi‐dimensional force sensors. Here we reported the mechanical energy‐driven and sunlight‐activated materials with force‐induced dual responses, and investigated the underlying mechanisms of self‐sustainable force sensing. Theoretical analysis and experimental data unraveled that trap‐controlled luminescence and interfacial electron transfer play a major role in force‐induced optical and electrical output. These materials were manufactured into pressure sensor with renewable dual‐mode output for quantifying and visualization of pressures by electrical and optical output, respectively, without power supply and high‐energy irradiation. The quantification of tactile sensation and stimuli localization of mice highlighted the multi‐dimensional sensing ability of the sensor. Overall, this self‐powered pressure sensor with multimodal output provides more modalities of force sensing, poised to change the way that intelligent devices sense with the world. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody‐based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual‐domain‐engineered anti‐hepatitis B virus (HBV) therapeutic antibody 73‐DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV‐tolerant mice, administration of a single dose of 73‐DY at 2 mg kg−1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL−1 and suppress HBsAg to < 100 IU mL−1 for two weeks, demonstrating a dose‐lowering advantage of at least tenfold. Furthermore, 10 mg kg−1 of 73‐DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73‐DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long‐term immunotherapy with reverse chimeric 73‐DY facilitated the restoration of anti‐HBV immune responses. This study provides a foundation for the development of next‐generation antibody‐based CHB therapies. [ABSTRACT FROM AUTHOR]

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface‐enhanced Raman spectroscopy (SERS) is a non‐invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost‐effective identification of closely associated S. enterica serovars. [ABSTRACT FROM AUTHOR]

Objective: Recombinant humanized type III collagen (rhCol III) is a highly adhesive biomaterial composed of 16 adhesion‐related tandem repeats refined from human type III collagen. Here, we aimed to investigate the effect of rhCol III on oral ulcers and reveal the underlying mechanism. Methods: Acid‐induced oral ulcers were induced on the murine tongue, and rhCol III or saline drops were administered. The effect of rhCol III on oral ulcers was assessed using gross and histological analyses. The effects on the proliferation, migration, and adhesion of human oral keratinocytes were investigated in vitro. The underlying mechanism was explored using RNA sequencing. Results: Administration of rhCol III accelerated the lesion closure of oral ulcers, reduced the release of inflammatory factors, and alleviated pain. rhCol III promoted the proliferation, migration, and adhesion of human oral keratinocytes in vitro. Mechanistically, the enrichment of genes associated with the Notch signaling pathway was upregulated after rhCol III treatment. Conclusion: rhCol III promoted the healing of oral ulcers, showing promising therapeutic potential in oral clinics. [ABSTRACT FROM AUTHOR]

Background: Lung Large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive, high‐grade neuroendocrine carcinoma with a poor prognosis, mainly seen in elderly men. To date, we have found no studies on predictive models for LCNEC. Methods: We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database of confirmed LCNEC from 2010 to 2018. Univariate and multivariate Cox proportional risk regression analyses were used to identify independent risk factors, and then we constructed a novel nomogram and assessed the predictive effectiveness by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: A total of 2546 patients with LCNEC were included, excluding those diagnosed with autopsy or death certificate, tumor, lymph node, metastasis (TNM) stage, tumor grade deficiency, etc., and finally, a total of 743 cases were included in the study. After univariate and multivariate analyses, we concluded that the independent risk factors were N stage, intrapulmonary metastasis, bone metastasis, brain metastasis, and surgical intervention. The results of ROC curves, calibration curves, and DCA in the training and validation groups confirmed that the nomogram could accurately predict the prognosis. Conclusions: The nomogram obtained from our study is expected to be a useful tool for personalized prognostic prediction of LCNEC patients, which may help in clinical decision‐making. [ABSTRACT FROM AUTHOR]

The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti‐neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV‐LAV) against KC. The findings clearly demonstrate that PRV‐LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV‐LAV was confirmed in both a subcutaneous tumor‐bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA‐seq analysis and flow cytometry revealed that PRV‐LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV‐LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV‐LAV with anti‐PD‐1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV‐LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients. [ABSTRACT FROM AUTHOR]

Viruses rely completely on host translational machinery to produce the proteins encoded by their genes. Controlling translation initiation is important for gaining translational advantage in conflicts between the host and virus. The eukaryotic translation initiation factor 4E (eIF4E) has been reported to be hijacked by potyviruses for virus multiplication. The role of translation regulation in defence and anti‐defence between plants and viruses is not well understood. We report that the transcript level of eIF6 was markedly increased in turnip mosaic virus (TuMV)‐infected Nicotiana benthamiana. TuMV infection was impaired by overexpression of N. benthamiana eIF6 (NbeIF6) either transiently expressed in leaves or stably expressed in transgenic plants. Polysome profile assays showed that overexpression of NbeIF6 caused the accumulation of 40S and 60S ribosomal subunits, the reduction of polysomes, and also compromised TuMV UTR‐mediated translation, indicating a defence role for upregulated NbeIF6 during TuMV infection. However, the polysome profile in TuMV‐infected leaves was not identical to that in leaves overexpressing NbeIF6. Further analysis showed that TuMV NIb protein, the RNA‐dependent RNA polymerase, interacted with NbeIF6 and interfered with its effect on the ribosomal subunits, suggesting that NIb might have a counterdefence role. The results propose a possible regulatory mechanism at the translation level during plant–virus interaction. [ABSTRACT FROM AUTHOR]

The electrical resistivity tomography (ERT) method is often challenged by the presence of reinforced concrete (RC) in urban and industrial environments, because the embedded metallic wire mesh can severely distort the distribution of subsurface currents. We investigate one typical scenario in real applications, in which an RC floor overlays the natural topsoil or rock. Our synthetic forward simulations show that the embedded wire mesh behaves like a local good conductor in data of small source‐receiver separations and acts like an equal‐potential object that keeps the potential from decaying at large source‐receiver separations. Routine ERT inversions that ignore the RC cannot work properly because the thin and highly conductive wire mesh may be manifested as large uninterpretable low‐resistivity anomalies in the imaging results. Two remedies are adopted to improve the ERT resolution in such cases. First, we find a top layer with high conductivity in our model to adequately represent the wire mesh; then, we initiate the inversion with the top‐layer model as the starting and reference model. This warm‐start approach overcomes the difficulty of recovering the large conductivity contrast between metallic objects and regular earth materials. Second, underground electrodes are added to the survey array, so more information from depth can be obtained to fight against the dominance of current channelling in the wire mesh. Finally, our strategies are used to invert a real ERT dataset from an indoor manufacturing plant, where RC covers the entire floor of the building and electrodes are in contact with the soil through open holes in the floor. Our simulation and field data inversion verify our findings and demonstrate the effectiveness of our solutions in improving the resolution of ERT when the survey is carried out over RC floor in urban and industrial environments. [ABSTRACT FROM AUTHOR]

This note presents an exact analytical solution of Fredlund–Hasan consolidation for unsaturated soils under an arbitrary loading using the mode superposition method. Air pressure and water pressure are expressed in a series of products of Eigen functions with respect to depth and normal coordinates with respect to time, respectively. A pressure function substitutes for the related homogeneous problem. Eigen functions can be first obtained based on two pairs of drainage condition. Then, the nonhomogeneous governing equations of unsaturated soils under constant loading, exponential loading, and sine loading are considered. After matrix algebraic manipulation, the normal coordinates can be obtained based on the initial conditions that compose the final solutions of the Fredlund–Hasan unsaturated consolidation. This solution can avoid inconvenient Laplace transform and inverse Laplace transform. Through comparisons with a classic example, the validation of the proposed analytical solution is verified against other analytical solutions and the finite difference method solutions. [ABSTRACT FROM AUTHOR]

Membrane lipids play essential roles in regulating physiological properties in higher plants and algae. Monogalactosyldiacylglycerol (MGDG) is a major thylakoid membrane lipid, and it is an important source of polyunsaturated fatty acids for cells, plays a key role in the biogenesis of plastids, and maintains the function of the photosynthetic machinery. Several studies have indicated that the knockdown of MGDG synthase results in membrane lipid remodeling, albino seedlings, and changes in photosynthetic performance. However, the effects of MGDG synthase (MGD) inhibitors on lipids in macroalgae have not yet been clarified. Here, we characterized the effects of MGD inhibitors (ortho‐phenanthroline and N‐ethylmaleimide) on the composition of the fatty acids observed in MGDG and digalactosyldiacylglycerol (DGDG) in Gracilariopsis lemaneiformis using electrospray ionization–mass spectrometry. The most abundant MGDG species contained 16:0/18:1 (sn‐1/sn‐2) fatty acids, and the most dominant DGDG species contained 20:5/16:0 (sn‐1/sn‐2) fatty acids. Measurements of photosynthetic pigments and photosynthetic parameters revealed that photosynthesis of G. lemaneiformis was impaired. Principal component analysis and Spearman's correlation analysis revealed interactions between specific MGDG structural composition patterns and key metabolites involved in photosynthesis, indicating that 20:4/16:0 (sn‐1/sn‐2) MGDG and 16:0/18:1 (sn‐1/sn‐2) MGDG affect the structure and function of phycobilisomes and thus the color of G. lemaneiformis. Three genes (GlMGD1, GlMGD2, and GlMGD3) were cloned and identified. The addition of N‐ethylmaleimide to G. lemaneiformis did not affect the abundance of GlMGD mRNA, and the abundance of transcripts was significantly decreased by ortho‐phenanthroline. [ABSTRACT FROM AUTHOR]

A core issue inherent to decision‐making and path‐planning tasks is managing the uncertainties in the motion of dynamic obstacles. Therefore, this article proposes a new decision‐making and path‐planning framework, based on game theory, that considers the multistate future actions of surrounding vehicles. First, multistate future actions of neighboring vehicles, whose driving styles vary, are estimated and fed into a decision‐making module for risk assessment. Then, based on the Stackelberg game theory, the ego vehicle and the rear object vehicle are modeled as two players in the game, and their optimal decisions are obtained. In addition, the path‐planning model incorporates a potential‐field model that utilizes several potential functions to explain the varied styles and physical limitations of the surrounding vehicles. Finally, the trajectory of the ego vehicle is obtained through model predictive control that is based on the outputs of the decision‐making and constructed potential‐field models. The results of simulation experiments that used designed scenarios demonstrate that the proposed method effectively manages various social interactions and generates safe and appropriate trajectories for autonomous vehicles. In addition, the simulation results demonstrate that considering multistate trajectories caused the decision‐making and path‐planning modules to be appropriate for unpredictable environmental conditions. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the effects of Traditional Chinese medicine, Periplaneta americana extract (PAE), on osteoblast differentiation of human alveolar bone marrow‐derived mesenchymal stem cells (hABMMSCs). Materials and Methods: Human alveolar bone marrow‐derived mesenchymal stem cells were treated with different concentrations of PAE. Cell Counting Kit‐8 (CCK‐8) assay and transwell migration assay were conducted to evaluate cell proliferation and migration, respectively. Alkaline phosphatase (ALP) staining, ALP activity assay, and Alizarin red S staining were performed to detect osteogenesis in hABMMSCs. In addition, real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot (WB) assay were performed to evaluate expression levels of osteogenic markers. Finally, RNA sequencing analysis and WB were carried out to elucidate the underlying mechanism. Results: A total of 0.1 mg/ml PAE promoted cell proliferation and migration. PAE also increased ALP activity and mineralized nodule formation of hABMMSCs. In addition, PAE upregulated the expression of osteogenesis‐related genes (RUNX2, COL1A1, and BGLAP). RNA‐sequencing analysis revealed that PAE activated the focal adhesion signaling pathway. Treatment with Defactinib, an inhibitor of FAK, attenuated the effects induced by PAE. Conclusions: PAE could enhance osteoblast differentiation of hABMMSCs through focal adhesion signaling pathway, suggesting a therapeutic potential for the alveolar bone defect. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: With the advantages of high sensitivity, rapid response, label‐free, and simple operation, field effect transistor biosensors have shown promising application prospects in large‐scale pathogen screening. However, in practical biological fluids with relatively high ionic strength, such as saliva and serum, the Debye screening effect will weaken the interaction between FET biosensors and target bio‐molecules, thereby affecting the sensing sensitivity and accuracy. Herein, an interfacial polymer‐engineered field effect transistor (IPE FET) biosensor was developed for the efficient identification of SARS‐CoV‐2 N antigens in saliva samples. The inclusion of a polymer layer shortens the distance between target molecules and the electrode interface, which effectively overcomes the limitation of Debye screening. The constructed IPE FET biosensors exhibit high sensitivity and anti‐fouling capability, achieving efficient detection of SARS‐CoV‐2 N antigen in saliva within 5 min with a detection limit of 4.6 fg·mL−1. In a cohort of 35 simulated throat swab samples of SARS‐CoV‐2 N antigen, IPE FET exhibits an identification accuracy of up to 97.1%, with predictive sensitivity and specificity of 96.0% and 100.0%, respectively. The excellent performance of IPE FET not only provides a strategy to design efficient detection platforms but also suggests a pathway to realize rapid and scalable epidemic screening. [ABSTRACT FROM AUTHOR]

Monitoring microbial metabolism is vital for revealing the mechanism of disease related to microbial metabolism and providing guidance for biomanufacturing processes optimization. However, it remains a grand challenge to offer real‐time insights into microbial metabolism owing to the complex and dynamic process. In this paper, the recent advances and prospects of optical biosensors including the organic, genetic coding and inorganic optical biosensors are briefly described for real‐time monitoring of dynamic microbial metabolism. This paper points out that challenges remain in microbial heterogeneity. We believe that this work will inspire the application of developing new methods for single cell real‐time analysis. [ABSTRACT FROM AUTHOR]

Mass pathogen screening is critical to preventing the outbreaks and spread of infectious diseases. The large‐scale epidemic of COVID‐19 and the rapid mutation of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus have put forward new requirements for virus detection and identification techniques. Here, we report a CRISPR‐based Amplification‐free Viral RNA Electrical Detection platform (CAVRED) for the rapid detection and identification of SARS‐CoV‐2 variants. A series of CRISPR RNA assays were designed to amplify the CRISPR‐Cas system's ability to discriminate between mutant and wild RNA genomes with a single‐nucleotide difference. The identified viral RNA information was converted into readable electrical signals through field‐effect transistor biosensors for the achievement of highly sensitive detection of single‐base mutations. CAVRED can detect the SARS‐CoV‐2 virus genome as low as 1 cp μL−1 within 20 mins without amplification, and this value is comparable to the detection limit of real‐time quantitative polymerase chain reaction. Based on the excellent RNA mutation detection ability, an 8‐in‐1 CAVRED array was constructed and realized the rapid identification of 40 simulated throat swab samples of SARS‐CoV‐2 variants with a 95.0 % accuracy. The advantages of accuracy, sensitivity, and fast speed of CAVRED promise its application in rapid and large‐scale epidemic screening. [ABSTRACT FROM AUTHOR]

With specific structures and unique features, biological ion channel proteins play crucial roles in many life processes of living organisms. Inspired by the biological ion channel proteins, researchers have developed a variety of artificial nanochannels to explore the mechanisms of selective ion transport and achieve applications in molecular filters, biosensors, and energy conversion devices. The ion transport behavior in nanochannels is mainly governed by the interaction between ions and the nanochannels interface. Herein, the structures, fabrication methods, and ion transport properties of biomimetic solid‐state ion nanochannels are reviewed, with emphasis on the transport performance and mechanism of nanochannels. In addition, the current challenges faced and the future outlooks of these solid‐sate ion nanochannels for practical applications are discussed. [ABSTRACT FROM AUTHOR]

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR‐MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR‐MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR‐MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7‐dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re‐modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS‐CoV‐2 and all tested variants. [ABSTRACT FROM AUTHOR]

Lipoxin A4 (LXA4) has been identified as the braking signal of inflammation, but the specific role of LXA4 in regulating the regenerative potential of periodontal ligament stem cells (PDLSCs) remains unclear. The aim of this study was to investigate whether and, if so, how LXA4 improves the osteogenic differentiation of PDLSCs in a lipopolysaccharide (LPS)‐induced inflammatory environment. We detected the effects of LXA4 on the osteogenic differentiation of PDLSCs in vitro and explored the bone regenerative potential of LXA4‐treated inflammatory PDLSCs in vivo using a calvarial critical sized defect model in male rats. RNA sequencing, real‐time PCR and western blot were performed to elucidate the relevant potential mechanisms. Results showed that LXA4 promoted the proliferation, migration and osteogenic differentiation of PDLSCs in vitro, and effectively improved the impaired osteogenic capacity of PDLSCs induced by LPS both in vitro and in vivo. Mechanistically, LXA4 significantly promoted the PI3K/AKT phosphorylation under inflammatory conditions. Additionally, LY294002 (a PI3K inhibitor) blocked the effect of LXA4, suggesting that the PI3K/AKT pathway is a key signaling pathway that mediates the effect of LXA4 on the osteogenesis of inflammatory PDLSCs. These findings indicate LXA4 may be a promising strategy for periodontal regeneration using inflammatory PDLSCs. [ABSTRACT FROM AUTHOR]

Sepsis is a dysregulation of the immune response to pathogens and has high morbidity and mortality worldwide. However, the unclear mapping and course of dysregulated immune cells currently hinders the development of advanced therapeutic strategies to treat sepsis. Here, evidence is provided using single‐cell RNA sequencing from peripheral blood mononuclear cells in sepsis that pathogens attacking monocytes/macrophages disrupt their immune function. The results reveal an enormous decline in monocytes/macrophages in sepsis and chart the evolution of their impaired phagocytosis (Pha) capabilities. Inspired by these findings, nanoparticles, named "Alpha‐MOFs," are developed that target dysfunctional monocytes/macrophages to actively (A) lift (L) Pha by the release of lysosome‐sensitive ions from a mineralized metal–organic framework (MOF). Alpha‐MOFs have good stability and biosafety in peripheral blood and efficiently targeted monocytes/macrophages. They also release calcium and zinc ions into monocyte/macrophage lysosomes to promote the Pha and degradation of bacteria. Taken together, these results suggest that Alpha‐MOFs rescue monocytes/macrophages dysfunction and effectively improve their survival rate during sepsis. [ABSTRACT FROM AUTHOR]

Objectives: Periplaneta americana extract (PAE) is proven to be promising in treating fever, wound healing, liver fibrosis, and cardiovascular disease. However, the role of PAE in skeletal disorders remains unclear. This study investigated whether PAE regulates osteoclastic differentiation in vitro via the culture using RAW264.7 cells and bone marrow derived macrophages (BMDMs). Materials and Methods: RAW264.7 cells and BMDMs were cultured and induced for osteoclastic differentiation supplementing with different concentrations of PAE (0, 0.1, 1, and 10 mg/mL). Cell counting kit‐8 (CCK‐8) assay was used to detect the cytotoxicity and cell proliferation. TRAP staining, actin ring staining, real‐time quantitative PCR (RT‐qPCR), and bone resorption activity test were performed to detect osteoclastic differentiation. RT‐qPCR and enzyme‐linked immunosorbent assay (ELISA) were conducted to assay the expression and secretion of inflammatory factors. RNA sequencing (RNA‐seq) and western blot analysis were carried out to uncover the underlying mechanism. Results: CCK‐8 results showed that 10 mg/mL and a lower concentration of PAE did not affect cell proliferation. RT‐qPCR analysis verified that PAE down‐regulated the osteoclastic genes Nfatc1, Ctsk, and Acp5 in macrophages. Moreover, PAE restrained the differentiation, formation, and function of osteoclasts. Besides, RT‐qPCR and ELISA assays showed that PAE decreased inflammatory genes expression and reduced the secretion of inflammatory factors, including IL1β, IL6, and TNFα. Subsequent RNA‐seq analysis identified possible genes and signaling pathways of PAE‐mediated osteoclastogenesis suppression. Conclusions: Our study indicates that PAE has inhibitive effects on osteoclastogenesis and may be a potential therapeutic alternative for bone diseases. [ABSTRACT FROM AUTHOR]

The plasticity of Schwann cells (SCs) following nerve injury is a critical feature in the regeneration of peripheral nerves as well as surrounding tissues. Here, we show a pivotal role of Schwann cell‐derived cells in alveolar bone regeneration through the specific ablation of proteolipid protein 1 (Plp)‐expressing cells and the transplantation of teased nerve fibers and associated cells. With inducible Plp specific genetic tracing, we observe that Plp+ cells migrate into wounded alveolar defect and dedifferentiate into repair SCs. Notably, these cells barely transdifferentiate into osteogenic cell lineage in both SCs tracing model and transplant model, but secret factors to enhance the proliferation of alveolar skeletal stem cells (aSSCs). As to the mechanism, this effect is associated with the upregulation of extracellular matrix (ECM) receptors and receptor tyrosine kinases (RTKs) signaling and the downstream extracellular signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK) pathway and the phosphoinositide 3‐kinase–protein kinase B (PI3K‐Akt) pathway. Collectively, our data demonstrate that SCs dedifferentiate after neighboring alveolar bone injury and contribute to bone regeneration mainly by a paracrine function. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

With the widespread application of digital impression techniques in prosthetic dentistry, accurate intraoral scan mounting, and virtual articulator parameters setting as per patients' anatomic structures are essential for treatment planning and restoration fabrication, especially for complex rehabilitation cases; meanwhile, marginal fit checking, occlusal adjustment, and porcelain layering of restorations are also crucial procedures in all cases in which the analog procedure to mount maxillary arches on a mechanical articulator is still required. This technique article presents an indirect digital approach that can first achieve virtual intraoral scan mounting and sagittal condylar inclination value setting of an Artex virtual articulator based on bony structures provided by a single cone beam computed tomography scan. It then facilitates the transfer of virtually mounted intraoral scans from the virtual articulator to the matched Artex mechanical articulator by relating a digitally scanned mounting plate of the Artex mechanical articulator to the virtual articulator, printing the intraoral scan and mounting plate scan assembly, and then mounting the printed casts on the mechanical articulator based on the printed mounting plate. This technique eliminates the conventional facebow transfer and protrusive bite registration procedures and offers a straightforward approach for the seamless integration of virtual environments and analog workflows into clinical practice. It aids in the design of restorations that are harmonious with the mandibular movements and reduces chairside adjustment time. [ABSTRACT FROM AUTHOR]

Microbial cell factories reinvigorate current industries by producing complex fine chemicals at low costs. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is the main reducing power to drive the biosynthetic pathways in microorganisms. However, insufficient intrinsic NADPH limits the productivity of microorganisms. Here, we report that supplying microorganisms with long‐lived electrons from persistent phosphor mesoporous Al2O3 (meso‐Al2O3) can elevate the NADPH level to facilitate efficient fine chemical production. The defects in meso‐Al2O3 were demonstrated to be highly efficient in prolonging electrons' lifetime. The long‐lived electrons in meso‐Al2O3 can pass the material–microorganism interface and power the biosynthetic pathways of E. coli to produce jet fuel farnesene. This work represents a reliable strategy to design photo‐biosynthesis systems to improve the productivity of microorganisms with solar energy. [ABSTRACT FROM AUTHOR]

The generation, manipulation, and detection of polarized light are the foundations of spin optoelectronics. Polarized light has a wide range of applications in new‐generation information transmission, storage, and quantum communications. Hybrid organic–inorganic halide perovskites have attracted extensive attention recently because of their strong spin–orbit coupling, Rashba splitting, spin‐dependent optical selection, and have been regarded as promising candidates for application in spin optoelectronic devices. Herein, the authors report the successful synthesis of 2D layered lead halide perovskites (PEA)2PbI4 (PEI) doped with magnetic metal Co2+ and the observation of strong circularly polarized photoluminescence and photoresponse. The introduction of magnetic metals in perovskites can induce an analogous Zeeman effect in the system, which can increase its energy degeneracy, giving rise to an imbalanced population of electronic spin states, thereby enhancing the spin polarization in doped samples. Thus, a maximum circularly polarized PL of 35% is observed at room temperature. Moreover, the achieved Co2+‐doped (PEA)2PbI4 also exhibits a selective photoresponse with circularly polarized light (CPL) emission, and an outstanding anisotropy factor of 0.41 for photocurrent is achieved. The experimental results lay the foundation for the controlled synthesis of magnetically doped perovskites as well as applications for direct CPL detection in spin optoelectronics. [ABSTRACT FROM AUTHOR]

Organic‐free perovskite solar cells (PSCs) have been of rising interest due to their remarkable resistance toward long‐term thermal stress. Nevertheless, the inorganic perovskite films usually suffer from poor crystallization and high‐density defects in bulk and near/at the interfaces, which leads to significant charge recombination loss and hence inferior device performance. Herein, it is demonstrated that high‐quality CsPbI2Br perovskite films could be prepared by using 2D non‐layered materials as additives, such as In2S3 nanoflakes (Nano‐In2S3) with well‐matched lattices and unsaturated dangling bonds on the surface. In addition, it is found that the introduction of Nano‐In2S3 results in not only defect passivation but also remarkable quasi‐Fermi level splitting across the perovskite film due to its gradient doping behavior, thereby enhancing the built‐in electric field in the inverted PSCs. As a result, the optimal devices based on Nano‐In2S3:CsPbI2Br absorber and all‐inorganic interfacial layers deliver a champion power conversion efficiency of 15.17% along with excellent ambient and thermal stabilities, superior to those of the pristine devices and comparable to the best organic‐free PSCs. A novel strategy for highly efficient and stable organic‐free photovoltaics by using 2D non‐layered materials as multifunctional additives is demonstrated. [ABSTRACT FROM AUTHOR]

Monitoring microbial metabolism is vital for biomanufacturing processes optimization. However, it remains a grand challenge to offer insight into microbial metabolism due to particularly complex and dynamic processes. Here, we report an electron‐sensing probe Zn2GeO4:Mn@Fe3+ for real‐time and dynamic monitoring of Fe(III) respiration metabolism. The quenched persistent luminescence of Zn2GeO4:Mn@Fe3+ is recovered when Fe3+ accepted electrons from the dynamic Fe(III) respiration metabolism, enabling the real‐time monitoring of microbial metabolism. The probe shows the capability to verify the role of related biomolecules in microbial Fe(III) respiration metabolism, to track the dynamic Fe(III) respiration metabolic response to environmental stress and microbial co‐culture interactions. Furthermore, the Zn2GeO4:Mn@Fe3+ probe provides guidance for improving biosynthesis efficiency by monitoring Fe redox recycling in microbial co‐culture. [ABSTRACT FROM AUTHOR]

Regulation of cellular oxidative stress plays a critical role in revealing the molecular mechanisms of cellular activities and thus is a potential strategy for tumor treatment. Optical methods have been employed for intelligent regulation of oxidative stress in tumor regions. However, long‐time continuous irradiation inevitably causes damage to normal tissues. Herein, a ferrocene‐containing nucleic acid‐based energy‐storage nanoagent was designed to achieve the continuous photo‐regulation of cellular oxidative stress in the dark. Specifically, the photoenergy stored in the agent could convert effectively and accelerate Fenton‐like reaction continuously, augmenting cellular oxidative stress. This nanoagent could also silence oxidative damage repair genes to further amplify oxidative stress. This strategy not only provides oxidative stress regulation for studying the molecular mechanisms of biological activities, but also offers a promising step toward tumor microenvironment modulation. [ABSTRACT FROM AUTHOR]

In some digital signature schemes, the signer needs to maintain a dynamic state while signing messages. These are called stateful signature schemes. Although stateful signature schemes are commonly used as cryptographic primitives, they do not fit the standard definition of a signature scheme in cryptography. In this work, formal and general definitions for stateful signature schemes are given. In the definitions of security notions, various scenarios are considered where the adversaries have different levels of control over the signing oracle in terms of messages and states. After that, generic constructions of stateful signature schemes with different security levels are provided. In addition, some black‐box constructions of stateful signature schemes that can be instantiated by primitives under any assumptions are given. Note that the constructions in this work are proven to be secure in standard models. [ABSTRACT FROM AUTHOR]

Customized cast orientations and parameter settings of the virtual articulator according to the patient's condyles are indispensable parts of today's digital workflows in prosthodontics. This article describes a digital technique to align the intraoral scans to a virtual articulator by using a facial scanner to locate the patient's cutaneous landmarks of the arbitrary hinge axis and the reference plane, and to customize the sagittal condylar inclination of the virtual articulator through a digital protrusive interocclusal record and a dental computer‐aided design software program. It enables individual cast orientations and virtual articulator parameter settings without conventional facebow transferring and bite registration procedures and can be easily integrated with most virtual articulator systems on the market to allow clinicians and technicians to work in a complete digital workflow and facilitate customized treatment planning and dental prosthesis fabrication. [ABSTRACT FROM AUTHOR]

Persistent luminescence is an optical phenomenon where solid phosphors can store photoenergy in defects and release the energy by luminescence after stopping excitation. Due to the intriguing optical characteristics, the defect luminescence based persistent phosphors have attracted enormous attention in recent decades, especially in biomedical fields such as biosensing and bioimaging. Persistent luminescence nanoparticles (PLNPs) can effectively avoid the autofluorescence interference from complex samples or tissues, leading to significantly improved sensitivity in biological analysis. In this review, we summarized the methods to control the optical performance of PLNPs from the perspectives of controlled synthesis and defect regulation, and emphasized the close relationship between their optical performance and applications. We further provided a summary about a series of PLNPs nanoprobes designed by our group for biosensing and bioimaging. Our efforts, summarized in this review, will not only open a window for manipulating luminescence in PLNPs, but also further promote the application of PLNPs in biomedicine. What is the most favorite and original chemistry developed in your research group? Synthesis and bioapplications of persistent phosphors. How do you get into this specific field? Could you please share some experiences with our readers? I got into chemistry related to biomedicine during my graduate student period. The research situation of luminescent nanomaterials in China has a strong effect on me, inspiring me to pursuit new luminescent nanomaterials and their applications. We need have interest and concentrate on our research with passion. We are encouraged to work hard. What is the most important personality for scientific research? Curiosity and hard‐working. What are your hobbies? What's your favorite book(s)? Shopping and reading books. My favorite books are novels, such as "The Three‐Body Problem". How do you keep balance between research and family? I have two boys and it takes me much time to take care of them. I need to elevate my work efficiency and work hard. I also buy household service to save time. Who influences you mostly in your life? My father. He loves reading and writing. I know one need to have passion on something under my father's influence. [ABSTRACT FROM AUTHOR]

Chloroplasts play crucial roles in plant defence against viral infection. We now report that chloroplast NADH dehydrogenase‐like (NDH) complex M subunit gene (NdhM) was first up‐regulated and then down‐regulated in turnip mosaic virus (TuMV)‐infected N. benthamiana. NbNdhM‐silenced plants were more susceptible to TuMV, whereas overexpression of NbNdhM inhibited TuMV accumulation. Overexpression of NbNdhM significantly induced the clustering of chloroplasts around the nuclei and disturbing this clustering facilitated TuMV infection, suggesting that the clustering mediated by NbNdhM is a defence against TuMV. It was then shown that NbNdhM interacted with TuMV VPg, and that the NdhMs of different plant species interacted with the proteins of different viruses, implying that NdhM may be a common target of viruses. In the presence of TuMV VPg, NbNdhM, which is normally localized in the nucleus, chloroplasts, cell periphery and chloroplast stromules, colocalized with VPg at the nucleus and nucleolus, with significantly increased nuclear accumulation, while NbNdhM‐mediated chloroplast clustering was significantly impaired. This study therefore indicates that NbNdhM has a defensive role in TuMV infection probably by inducing the perinuclear clustering of chloroplasts, and that the localization of NbNdhM is altered by its interaction with TuMV VPg in a way that promotes virus infection. Chloroplasts have been reported to play a vital role in plant defense against viruses. Increasing evidence indicates that the perinuclear clustering of chloroplasts is a defense response against pathogens. Here, we found that the chloroplast NADH dehydrogenase‐like complex M subunit (NdhM) induced the clustering of chloroplasts around the nuclei and disturbing this clustering facilitated turnip mosaic virus (TuMV) infection. Interestingly, to counteract it, TuMV VPg protein interacted with NbNdhM and redirected it into the nucleus and nucleolus, thereby impairing NdhM‐induced perinuclear chloroplast clustering to promote virus infection. The results provide a better insight into the complicated virus‐chloroplast interaction that occurs during TuMV infection. [ABSTRACT FROM AUTHOR]

A full‐scale wastewater treatment plant in China experienced unintentional anammox bacterial enrichment on biofilm carriers placed in the anaerobic and anoxic zones of an anaerobic/anoxic/oxic process under ambient temperatures and without bioaugmentation. Here, we show that microaerophilic conditions resulting from air scouring needed for biofilm carrier suspension in the anaerobic/anoxic zones can support a robust nitritation/anammox process. Results from an in situ on/off air scouring test showed that air scouring strongly induced both ammonia and total inorganic nitrogen removal in the anaerobic/anoxic zones. Ammonium concentration in the anaerobic and anoxic tanks remained constant or even slightly increased when air scouring was off, indicating that air scouring made a noticeable difference in nitrogen profiles in the anaerobic/anoxic zones. Various batch tests further indicated that partial denitrification is not likely to generate nitrite for anammox bacteria. Robust nitritation, and anammox on the carriers, can occur at low dissolved oxygen conditions, as measured in the full‐scale facility. The observations show that mainstream deammonification without sidestream bioaugmentation at moderate temperature is feasible and further optimization by a more dedicated design can result in improved nitrogen removal in cases when chemical oxygen demand is limited in mainstream wastewater treatment. Practitioner points: Microaerophilic conditions in a full‐scale IFAS reactor caused mainstream anammox in moderate temperate area.Robust nitritation, and anammox on the carriers, can occur at low dissolved oxygen conditions in anaerobic/anoxic tanks with air scouring.Anammox can function well with conventional nitrification and denitrification process at mainstream conditions for stable nitrogen removal. [ABSTRACT FROM AUTHOR]

Total dissolved gas supersaturation (TDGS) caused by high dam discharge may threaten the survival of fish downstream. This study investigated the TDGS of Dadu River in the first 3 years (2016–2018) after the operation of Dagangshan hydropower station. The effect of TDGS on endemic fish was also evaluated for the first time in this study. Schizothoracin prenanti, Schizothorax davidi and Leptobotia elongata, which are endangered and endemic species in the Dadu River, were selected to evaluate the adverse effects of supersaturation on fish. We found that the supersaturation level varied from 115% to 127% in 2016, from 111% to 121% in 2017, and from 103% to 112% in 2018. The average water levels in these 3 years were 2.99, 2.34 and 1.14 m, respectively. The mortality of fish was positively correlated with TDGS and negatively correlated with water depth. The mortality of juvenile fish was highest in 2016, and increased TDGS had a greater contribution to fish mortality than the other factors. The highest mortality of adults occurred in 2017, and inadequate water depth was an important factor that caused fish mortality. The lowest mortality of both adults and juveniles occurred in 2018, and gas bubble disease in fish was almost never found. Even at shallow water depths, low TDGS (103%–112%) did not cause fish mortality. [ABSTRACT FROM AUTHOR]

Facet‐selective nanostructures in living systems usually exhibit outstanding optical and enzymatic properties, playing important roles in photonics, matter exchange, and biocatalysis. Bioinspired construction of facet‐selective nanostructures offers great opportunities for sophisticated nanomaterials, but remains a formidable task. We have developed a macromolecule‐mediated strategy for the assembly of upconversion nanoparticles (UCNPs)/two‐dimensional metal–organic frameworks (2DMOFs) heterostructures with facet selectivity. Both experimental and theoretical results demonstrate that polyvinylpyrrolidone (PVP) can be utilized as an interface‐selective mediator to further promote the facet‐selective assembly of MOFs onto the surface of UCNPs. The UCNPs/2DMOFs nanostructures with facet selectivity display specific optical properties and show great advantages in anti‐counterfeiting. Our demonstration of UCNPs/2DMOFs provides a vivid example for the controlled fabrication of facet‐selective nanostructures and can promote the development of advanced functional materials for applications in biosensing, energy conversion, and information assurance. [ABSTRACT FROM AUTHOR]

Objectives: Oestrogen deficiency is an aetiological factor of postmenopausal osteoporosis (PMO), which not only decreases bone density in vertebrae and long bone but also aggravates inflammatory alveolar bone loss. Recent evidence has suggested the critical role of gut microbiota in osteoimmunology and its influence on bone metabolisms. The present study aimed to evaluate the therapeutic effects of probiotics on alveolar bone loss under oestrogen‐deficient condition. Materials and Methods: Inflammatory alveolar bone loss was established in ovariectomized (OVX) rats, and rats were daily intragastrically administered with probiotics until sacrifice. Gut microbiota composition, intestinal permeability, systemic immune status and alveolar bone loss were assessed to reveal the underlying correlation between gut microbiota and bone metabolisms. Results: We found administration of probiotics significantly prevented inflammatory alveolar bone resorption in OVX rats. By enriching butyrate‐producing genera and enhancing gut butyrate production, probiotics improved intestinal barrier and decreased gut permeability in the OVX rats. Furthermore, the oestrogen deprivation‐induced inflammatory responses were suppressed in probiotics‐treated OVX rats, as reflected by reduced serum levels of inflammatory cytokines and a balanced distribution of CD4+IL‐17A+ Th17 cells and CD4+CD25+Foxp3+ Treg cells in the bone marrow. Conclusions: This study demonstrated that probiotics can effectively attenuate alveolar bone loss by modulating gut microbiota and further regulating osteoimmune response and thus represent a promising adjuvant in the treatment of alveolar bone loss under oestrogen deficiency. [ABSTRACT FROM AUTHOR]

Spontaneous anammox bacteria enrichment at mainstream conditions was reported in a full‐scale Wastewater Treatment Plant (WWTP) in a temperate zone of China. The mainstream anammox was observed after WWTP process retrofit, which constructed a hybrid sludge retention time (SRT) system by providing moving carriers in the anaerobic/anoxic tank and was initially designed to enhance the denitrification process in a conventional anaerobic/anoxic/oxic process. The hybrid SRT system achieved 86.0 ± 4.6% total nitrogen (TN) removal via combined mainstream anammox and conventional denitrification. Autotrophic denitrification via mainstream anammox was confirmed by various shreds of evidence including high‐throughput sequencing, specific anammox activity test, and 15N isotopic tracing. Long‐term anammox bacteria existence in the biofilm of the carrier in anoxic zones was detected in a much higher relative abundance compared with other spots. The contribution of anammox activity to TN removal was estimated at around 20%–30%. The reasons leading to spontaneous anammox enrichment were mainly attributed to the carriers for slow‐growing bacteria growth and dissolved oxygen gradient in the anoxic tank (caused by intermittent aeration) for nitrite production. The insights of this full‐scale case study provide important perspectives for future mainstream anammox application, and also the design of an energy‐neutral WWTP process. Practitioner points: Spontaneous mainstream anammox in a full‐scale WWTP after its retrofit in a temperate zone of China was reported.Anammox bacteria enrichment and long‐term stability on moving carriers at mainstream conditions was achieved by modified hybrid SRT system.The hybrid SRT system achieve stable nitrogen removal even in cold winter and high BOD/N situation by combining mainstream anammox with conventional denitrification.Long term full‐scale operation demonstrated excellent nitrogen removal with about 20%–30% contribution of mainstream anammox.This full‐scale case study provided perspectives for future optimizing mainstream anammox application, and also energy‐neutral WWTP process design. [ABSTRACT FROM AUTHOR]