Lung patterning: Is a distal-to-proximal gradient of cell allocation and fate decision a general paradigm?: A gradient of distal-to-proximal distribution and differentiation of tip progenitors produces distinct compartments in the lung.

Recent studies support a model in which the progeny of SOX9+ epithelial progenitors at the distal tip of lung branches undergo cell allocation and differentiation sequentially along the distal-to-proximal axis. Concomitant with the elongation and ramification of lung branches, the descendants of the distal SOX9+ progenitors are distributed proximally, express SOX2, and differentiate into cell types in the conducting airways. Amid subsequent sacculation, the distal SOX9+ progenitors generate alveolar epithelial cells to form alveoli. Sequential cell allocation and differentiation are integrated with the branching process to generate a functional branching organ. This review focuses on the roles of SOX9+ cells as precursors for new branches, as the source of various cell types in the conducting airways, and as progenitors of the alveolar epithelium. All of these processes are controlled by multiple signaling pathways. Many mouse mutants with defective lung branching contain underlying defects in one or more steps of cell allocation and differentiation of SOX9+ progenitors. This model provides a framework to understand the molecular basis of lung phenotypes and to elucidate the molecular mechanisms of lung patterning. It builds a foundation on which comparing and contrasting the mechanisms employed by different branching organs in diverse species can be made.

Wnt5a-Vangl1/2 signaling regulates the position and direction of lung branching through the cytoskeleton and focal adhesions.

Lung branching morphogenesis requires reciprocal interactions between the epithelium and mesenchyme. How the lung branches are generated at a defined location and projected toward a specific direction remains a major unresolved issue. In this study, we investigated the function of Wnt signaling in lung branching in mice. We discovered that Wnt5a in both the epithelium and the mesenchyme plays an essential role in controlling the position and direction of lung branching. The Wnt5a signal is mediated by Vangl1/2 to trigger a cascade of noncanonical or planar cell polarity (PCP) signaling. In response to noncanonical Wnt signaling, lung cells undergo cytoskeletal reorganization and change focal adhesions. Perturbed focal adhesions in lung explants are associated with defective branching. Moreover, we observed changes in the shape and orientation of the epithelial sheet and the underlying mesenchymal layer in regions of defective branching in the mutant lungs. Thus, PCP signaling helps define the position and orientation of the lung branches. We propose that mechanical force induced by noncanonical Wnt signaling mediates a coordinated alteration in the shape and orientation of a group of epithelial and mesenchymal cells. These results provide a new framework for understanding the molecular mechanisms by which a stereotypic branching pattern is generated.

Global entangling gates on arbitrary ion qubits.

Quantum computers can efficiently solve classically intractable problems, such as the factorization of a large number1 and the simulation of quantum many-body systems2,3. Universal quantum computation can be simplified by decomposing circuits into single- and two-qubit entangling gates4, but such decomposition is not necessarily efficient. It has been suggested that polynomial or exponential speedups can be obtained with global N-qubit (N greater than two) entangling gates5-9. Such global gates involve all-to-all connectivity, which emerges among trapped-ion qubits when using laser-driven collective motional modes10-14, and have been implemented for a single motional mode15,16. However, the single-mode approach is difficult to scale up because isolating single modes becomes challenging as the number of ions increases in a single crystal, and multi-mode schemes are scalable17,18 but limited to pairwise gates19-23. Here we propose and implement a scalable scheme for realizing global entangling gates on multiple 171Yb+ ion qubits by coupling to multiple motional modes through modulated laser fields. Because such global gates require decoupling multiple modes and balancing all pairwise coupling strengths during the gate, we develop a system with fully independent control capability on each ion14. To demonstrate the usefulness and flexibility of these global gates, we generate a Greenberger-Horne-Zeilinger state with up to four qubits using a single global operation. Our approach realizes global entangling gates as scalable building blocks for universal quantum computation, motivating future research in scalable global methods for quantum information processing.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.

FDA Review of Radiologic AI Algorithms: Process and Challenges.

A Food and Drug Administration (FDA)-cleared artificial intelligence (AI) algorithm misdiagnosed a finding as an intracranial hemorrhage in a patient, who was finally diagnosed with an ischemic stroke. This scenario highlights a notable failure mode of AI tools, emphasizing the importance of human-machine interaction. In this report, the authors summarize the review processes by the FDA for software as a medical device and the unique regulatory designs for radiologic AI/machine learning algorithms to ensure their safety in clinical practice. Then the challenges in maximizing the efficacy of these tools posed by their clinical implementation are discussed.

Identification and evaluation of an endophytic antagonistic yeast for the control of gray mold (Botrytis cinerea) in apple and mechanisms of action.

Gray mold, caused by Botrytis cinerea, is a prevalent postharvest disease of apple that limits their shelf life, resulting in significant economic losses. The use of antagonistic microorganisms has been shown to be an effective approach for managing postharvest diseases of fruit. In the present study, an endophytic yeast strain PGY-2 was isolated from apples and evaluated for its biocontrol efficacy against gray mold and its mechanisms of action. Results indicated that strain PGY-2, identified as Bullera alba, reduced the occurrence of gray mold on apples and significantly inhibited lesion development in pathogen-inoculated wounds. Gray mold control increased with the use of increasing concentrations of PGY-2, with the best disease control observed at 108 cells/mL. Notably, Bullera alba PGY-2 did not inhibit the growth of Botrytis cinerea in vitro indicating that the yeast antagonist did not produce antimicrobial compounds. The rapid colonization and stable population of PGY-2 in apple wounds at 4 °C and 25 °C confirmed its ability to compete with pathogens for nutrients and space. PGY-2 also had a strong ability to form a biofilm and enhanced the activity of multiple defense-related enzymes (POD, PPO, APX, SOD, PAL) in host tissues. Our study is the first time to report the use of Bullera alba PGY-2 as a biocontrol agent for postharvest diseases of apple and provide evidence that Bullera alba PGY-2 represents an endophytic antagonistic yeast with promising biocontrol potential and alternative to the use of synthetic, chemical fungicides for the control of postharvest gray mold in apples.

Effects of Ginseng on Cognitive Function: A Systematic Review and Meta-Analysis.

Ginseng is a kind of traditional Chinese medicine. It is widely believed that ginseng can improve cognitive function, but its clinical efficacy is still controversial. This study aimed to systematically evaluate the effects of ginseng on cognitive function improvement. This is a systematic review and meta-analysis of the randomized controlled trials (RCTs). Searching PubMed, Web of Science, the Cochrane Library, and Medline databases to collect RCTs of ginseng on the effects of human cognitive function. The time range is from the establishment of the database to December 2023. The main intervention in the trials was ginseng preparation. The Cochrane risk-of-bias tool 2.0 (RoB2.0) and Jadad scale were used to assess the risk of bias and evaluate the quality of the included articles. After data extraction, meta-analysis was performed using Stata 17.0 software. A total of 15 RCTs were included, and 671 patients were analyzed. The subjects included healthy people, patients of cognitive impairment, schizophrenia, hospitalized, and Alzheimer's disease. The intervention measures were mainly ginseng preparations. The meta-analysis results indicated that ginseng has a significant effect on memory improvement (SMD = 0.19, 95%CI: 0.02-0.36, p < 0.05), especially at high doses (SMD = 0.33, 95%CI: 0.04-0.61, p < 0.05). Ginseng did not have a positive effect on overall cognition, attention, and executive function (SMD = 0.06, 95%CI: -0.64-0.77, p = 0.86; SMD = 0.06, 95%CI: -0.12 to 0.23, p = 0.54; SMD = -0.03, 95%CI: -0.28 to 0.21, p = 0.79). Ginseng has some positive effects on cognitive improvement, especially on memory improvement. But in the future, more high-quality studies are needed to determine the effects of ginseng on cognitive function. Trial Registration: Prospero: CRD42024514231.

Fiscal decentralization, leader localization, and reduction of pollution and carbon emissions -empirical evidence from China's fiscal "province-managing-county" reform.

The fiscal system plays an important role in the government's environmental governance efforts. There is currently no consensus on how fiscal structure adjustments impact pollution and carbon reduction. This paper uses China's fiscal "province-managing-county" reform (FPMCR) implemented in 2004 as a quasi-natural experiment, utilizing panel data from 1670 counties in China from 2000 to 2020 to investigate the impact of fiscal decentralization on reduction pollution and carbon emissions (RPCE), as well as its underlying mechanisms. The results show that (1) from 2000 to 2020, China's RPCE shows an overall trend of fluctuating increase, with its value turning positive after 2013. China's RPCE exhibits a spatial pattern characterized by "lower in the north, higher in the south; higher in the east, lower in the west". (2) After implementing FPMCR, the RPCE levels in reformed counties decreased by -1.44%, showing that reformed county-level governments prioritize economic development over environmental protection. (3) The mechanism analysis found that after implementing FPMCR, reformed counties experienced a 9.16% increase in nighttime light intensity (NLI), and a 3.99% and 4.34% increase in the number of large-scale industrial enterprises (NLIE) and industrial agglomeration (IA), respectively. This suggests that FPMCR leads to radical urbanization and rapid industrialization in counties, which is detrimental to the improvement of RPCE levels. (4) The spatial heterogeneity analysis found that FPMCR's impact coefficient on RPCE levels in the eastern regions is -1.96%, while in the western regions it is -1.16%. This indicates that reformed counties in the eastern regions are more likely to invest expanded fiscal resources in economic development projects, leading to a decrease in RPCE levels. (5) The temporal heterogeneity analysis found that after the promulgation of the "Three-Year Action Plan to Win the Blue Sky Defense Battle" in 2018, the adverse impact of FPMCR on RPCE is completely reversed, leading to a 1.76% increase in RPCE levels. (6) Further analysis reveals that localizing leaders can slow down the promotion of county-level urbanization and industrialization by the FPMCR, benefiting the improvement of RPCE levels. In other words, "the outsider monk will not recite scriptures as well as a local one". This study has clarified the causal relationship and underlying mechanisms between fiscal decentralization and environmental governance, providing reliable theoretical support for optimizing grassroots fiscal systems and reducing environmental pollution in other transitional economies. It enriches the field of environmental economics related to fiscal decentralization.

Oriented Assembled Prussian Blue Analogue Framework for Confined Catalytic Decomposition of Ammonium Perchlorate.

The design of highly dispersed active sites of hollow materials and unique contact behavior with the components to be catalyzed provide infinite possibilities for exploring the limits of catalyst capacity. In this study, the synthesis strategy of highly open 3-dimensional frame structure Prussian blue analogues (CoFe-PBA) was explored through structure self-transformation, which was jointly guided by template mediated epitaxial growth, restricted assembly and directional assembly. Additionally, good application prospect of CoFe-PBA as combustion catalyst was discussed. The results show that unexpected thermal decomposition behavior can be achieved by limiting AP(ammonium perchlorate) to the framework of CoFe-PBA. The high temperature decomposition stage of AP can be advanced to 283.6 °C and the weight loss rate can reach 390.03% min-1 . In-situ monitoring shows that CoFe-PBA can accelerate the formation of NO and NO2 . The calculation of reaction kinetics proved that catalytic process was realized by increasing the nucleation factor. On this basis, the catalytic mechanism of CoFe-PBA on the thermal decomposition of AP was discussed, and the possible interaction process between AP and CoFe-PBA during heating was proposed. At the same time, another interesting functional behavior to prevent AP from caking was discussed.

MATE transporter GFD1 cooperates with sugar transporters, mediates carbohydrate partitioning and controls grain-filling duration, grain size and number in rice.

More than half of the world's food is provided by cereals, as humans obtain >60% of daily calories from grains. Producing more carbohydrates is always the final target of crop cultivation. The carbohydrate partitioning pathway directly affects grain yield, but the molecular mechanisms and biological functions are poorly understood, including rice (Oryza sativa L.), one of the most important food sources. Here, we reported a prolonged grain filling duration mutant 1 (gfd1), exhibiting a long grain-filling duration, less grain number per panicle and bigger grain size without changing grain weight. Map-based cloning and molecular biological analyses revealed that GFD1 encoded a MATE transporter and expressed high in vascular tissues of the stem, spikelet hulls and rachilla, but low in the leaf, controlling carbohydrate partitioning in the stem and grain but not in the leaf. GFD1 protein was partially localized on the plasma membrane and in the Golgi apparatus, and was finally verified to interact with two sugar transporters, OsSWEET4 and OsSUT2. Genetic analyses showed that GFD1 might control grain-filling duration through OsSWEET4, adjust grain size with OsSUT2 and synergistically modulate grain number per panicle with both OsSUT2 and OsSWEET4. Together, our work proved that the three transporters, which are all initially classified in the major facilitator superfamily family, could control starch storage in both the primary sink (grain) and temporary sink (stem), and affect carbohydrate partitioning in the whole plant through physical interaction, giving a new vision of sugar transporter interactome and providing a tool for rice yield improvement.

Applications of Induced Pluripotent Stem Cell-Derived Glia in Brain Disease Research and Treatment.

Glia are integral components of neural networks and are crucial in both physiological functions and pathological processes of the brain. Many brain diseases involve glial abnormalities, including inflammatory changes, mitochondrial damage, calcium signaling disturbance, hemichannel opening, and loss of glutamate transporters. Induced pluripotent stem cell (iPSC)-derived glia provide opportunities to study the contributions of glia in human brain diseases. These cells have been used for human disease modeling as well as generating new therapies. This chapter introduces glial involvement in brain diseases, then summarizes different methods of generating iPSC-derived glia disease models of these cells. Finally, strategies for treating disease using iPSC-derived glia are discussed. The goal of this chapter is to provide an overview and shed light on the applications of iPSC-derived glia in brain disease research and treatment.

Evaluation of growth status of children with non-syndromic oral clefts.

To assess the growth status of children with non-syndromic oral clefts (NSOC) and explore potential influencing factors. The data of NSOC children aged ≤5 years hospitalized between December 2018 and June 2020 were retrieved and evaluated, including their height, weight, NSOC subtypes and demographic characteristics before reparative surgeries. The growth status of the children was assessed using height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ) and weight-for-height Z-score (WHZ). In total, 504 NSOC children (271 females & 233 males) were included. The proportion of stunting (HAZ <-2), underweight (WAZ <-2) and wasting (WHZ <-2) was 4.96%, 5.16% and 3.97%, respectively. In addition, we observed that HAZ and WAZ decreased with increasing age (both p < 0.01). Moreover, non-syndromic cleft palate only (NSCP) and non-syndromic cleft lip and palate (NSCLP) were associated with lower HAZ and WAZ compared with non-syndromic cleft lip only (NSCL) (all p < 0.01), while NSCLP was associated with a lower WHZ compared with NSCL (p < 0.01). The growth retardation and low weight rate of NSOC children under 5 years old were higher than the national average level and differed by the age of NSOC children and disease subtypes. Further improvements are warranted to promote the growth status of the NSOC-affected children.

Renormalization of Transverse-Momentum-Dependent Parton Distribution on the Lattice.

To calculate the transverse-momentum-dependent parton distribution functions (TMDPDFs) from lattice QCD, an important goal yet to be realized, it is crucial to establish a viable nonperturbative renormalization approach for linear divergences in the corresponding Euclidean quasi-TMDPDF correlators in large-momentum effective theory. We perform a first systematic study of the renormalization property of the quasi-TMDPDFs by calculating the relevant matrix elements in a pion state at five lattice spacings ranging from 0.03 fm to 0.12 fm. We demonstrate that the square root of the Wilson loop combined with the short distance hadron matrix element provides a successful method to remove all ultraviolet divergences of the quasi-TMD operator, and thus provides the necessary justification to perform a continuum limit calculation of TMDPDFs. In contrast, the popular regularization independent momentum subtraction renormalization (RI/MOM) scheme fails to eliminate all linear divergences.

Fabrication of cell plastics composed only of unicellular green alga Chlamydomonas reinhardtii as a raw material.

Cell plastics in this study were fabricated with only unicellular green alga Chlamydomonas reinhardtii as raw materials. The sizes of cell-major axis as structures were 8.4 ± 1.2 µm, and the aspect ratios of those were 1.2 ± 0.1, showing homogeneous particle size. After optimizing extraction condition of intracellular contents, cell plastics were fabricated with the cells as ingredient components and the intracellular contents as matrix components. Those cell plastics were observed with scanning electron microscopy, displaying the smooth surfaces of the cell plastics at a low magnification level. However, the surface, especially exposed surface, were rough at high magnification level. Tensile strength test revealed that increasing the ratio of intracellular contents in the cell plastics until 21% led enhancing mechanical properties of Young's modulus and tensile strength; however, 25% of intracellular contents displayed decreases of those properties. As the optimal point, the cell plastic (21%), which contained 21% (w/w) of intracellular contents in cell plastics, showed 764 ± 100 MPa and 8.6 ± 5.2 MPa of Young's modulus and tensile strength. The cell plastics showed few plastic region and soon fractured, indicating the possibility that cells and intracellular contents could be electrostatically connected. Additionally, cells were shown as a negative charge and displayed the possibility to contribute electrically cell-gathering with intracellular ionic components. Therefore, cells and intracellular contents containing ionic metabolites could be electrostatically connected for giving the mechanical strength to cell plastics. In this study, we successfully demonstrated fabricating cell plastics with only cells for the first time and also showed the high possibility of conjugating each cell with the intracellular contents. KEY POINTS: • Cell plastics are fabricated with unicellular green algal cell directly. • Unicellular cells required to be conjugated for the fabrication with matrix. • Cells were conjugated with intracellular contents for cell-plastic fabrication.

LncRNA CBR3-AS1 predicts a poor prognosis and promotes cervical cancer progression through the miR-3163/LASP1 pathway.

LncRNA carbonyl reductase antisense RNA 1 (CBR3-AS1) is increased in cervical cancer and predicts poor prognosis. This study aims to investigate the underlying mechanism of lncRNA CBR3-AS1 in cervical cancer. LncRNA CBR3-AS1 and LASP1 expressions were significantly elevated in cervical cancer tissue and cells, whereas miR-3163 expression was significantly decreased in cervical cancer tissue and cells. High lncRNA CBR3-AS1 expression and LASP1 expression showed a lower overall survival rate, whereas high miR-3163 expression showed a higher overall survival rate. Correlation between clinicopathological parameters of cervical cancer patients and lncRNA CBR3-AS1, miR-3163, LASP1 expressions indicated that the expressions of lncRNA CBR3-AS1, miR-3163, and LASP1 were closely related with distant metastasis and lymphatic metastasis of cervical cancer. LncRNA CBR3-AS1 knockdown suppressed cervical cancer cell viability and inhibited cancer stem cell-like properties. Besides, we identified that lncRNA CBR3-AS1 interacted with miR-3163, and miR-3163 targeted to LASP1. Moreover, the correlation between lncRNA CBR3-AS1 and miR-3163, as well as the correlation between miR-3163 and LASP1 was confirmed. Finally, lncRNA CBR3-AS1 knockdown inhibited tumor growth and suppressed cancer stem cell-like properties of cervical cancer in vivo. Taken together, high expression of lncRNA CBR3-AS1 predicts poor prognosis in cervical cancer, and the lncRNA CBR3-AS1/miR-3163/LASP1 pathway plays a vital function in the modulation of cervical cancer cell proliferation and cancer stem cell-like properties.

Crosstalk between the Circadian Clock and Histone Methylation.

The circadian clock and histone modifications could form a feedback loop in Arabidopsis; whether a similar regulatory mechanism exists in rice is still unknown. Previously, we reported that SDG724 and OsLHY are two rice heading date regulators in rice. SDG724 encodes a histone H3K36 methyltransferase, and OsLHY is a vital circadian rhythm transcription factor. Both could be involved in transcription regulatory mechanisms and could affect gene expression in various pathways. To explore the crosstalk between the circadian clock and histone methylation in rice, we studied the relationship between OsLHY and SDG724 via the transcriptome analysis of their single and double mutants, oslhy, sdg724, and oslhysdg724. Screening of overlapped DEGs and KEGG pathways between OsLHY and SDG724 revealed that they could control many overlapped pathways indirectly. Furthermore, we identified three candidate targets (OsGI, OsCCT38, and OsPRR95) of OsLHY and one candidate target (OsCRY1a) of SDG724 in the clock pathway. Our results showed a regulatory relationship between OsLHY and SDG724, which paved the way for revealing the interaction between the circadian clock and histone H3K36 methylation.

Dual function of clock component OsLHY sets critical day length for photoperiodic flowering in rice.

Circadian clock, an endogenous time-setting mechanism, allows plants to adapt to unstable photoperiod conditions and induces flowering with proper timing. In Arabidopsis, the central clock oscillator was formed by a series of interlocked transcriptional feedback loops, but little is known in rice so far. By MutMap technique, we identified the candidate gene OsLHY from a later flowering mutant lem1 and further confirmed it through genetic complementation, RNA interference knockdown, and CRISPR/Cas9-knockout. Global transcriptome profiling and expression analyses revealed that OsLHY might be a vital circadian rhythm component. Interestingly, oslhy flowered later under ≥12 h day length but headed earlier under ≤11 h day length. qRT-PCR results exhibited that OsLHY might function through OsGI-Hd1 pathway. Subsequent one-hybrid assays in yeast, DNA affinity purification qPCR, and electrophoretic mobility shift assays confirmed OsLHY could directly bind to the CBS element in OsGI promoter. Moreover, the critical day length (CDL) for function reversal of OsLHY in oslhy (11-12 h) was prolonged in the double mutant oslhy osgi (about 13.5 h), indicating that the CDL set by OsLHY was OsGI dependent. Additionally, the dual function of OsLHY entirely relied on Hd1, as the double mutant oslhy hd1 showed the same heading date with hd1 under about 11.5, 13.5, and 14 h day lengths. Together, OsLHY could fine-tune the CDL by directly regulating OsGI, and Hd1 acts as the final effector of CDL downstream of OsLHY. Our study illustrates a new regulatory mechanism between the circadian clock and photoperiodic flowering.

US3 Kinase-Mediated Phosphorylation of Tegument Protein VP8 Plays a Critical Role in the Cellular Localization of VP8 and Its Effect on the Lipid Metabolism of Bovine Herpesvirus 1-Infected Cells.

Bovine herpesvirus 1 (BoHV-1) infects bovine species, causing respiratory infections, genital disorders and abortions. VP8 is the most abundant tegument protein of BoHV-1 and is critical for virus replication in cattle. In this study, the cellular transport of VP8 in BoHV-1-infected cells and its ability to alter the cellular lipid metabolism were investigated. A viral kinase, US3, was found to be involved in regulating these processes. In the early stages of infection VP8 was localized in the nucleus. Subsequently, presumably after completion of its role in the nucleus, VP8 was translocated to the cytoplasm. When US3 was deleted or the essential US3 phosphorylation site of VP8 was mutated in BoHV-1, the majority of VP8 was localized in the nuclei of infected cells. This suggests that phosphorylation by US3 may be critical for cytoplasmic localization of VP8. Eventually, the cytoplasmic VP8 was accumulated in the cis-Golgi apparatus but not in the trans-Golgi network, implying that VP8 was not involved in virion transport toward and budding from the cell membrane. VP8 caused lipid droplet (LD) formation in the nuclei of transfected cells and increased cellular cholesterol levels. Lipid droplets were not found in the nuclei of BoHV-1-infected cells when VP8 was cytoplasmic in the presence of US3. However, when US3 was deleted or phosphorylation residues in VP8 were mutated, nuclear VP8 and LDs appeared in BoHV-1-infected cells. The total cholesterol level was increased in BoHV-1-infected cells but not in ΔUL47-BoHV-1-infected cells, further supporting a role for VP8 in altering the cellular lipid metabolism during infection.IMPORTANCE Nuclear localization signals (NLSs) and nuclear export signals (NESs) are important elements directing VP8 to the desired locations in the BoHV-1-infected cell. In this study, a critical regulator that switches the nuclear and cytoplasmic localization of VP8 in BoHV-1-infected cells was identified. BoHV-1 used viral kinase US3 to regulate the cellular localization of VP8. Early during BoHV-1 infection VP8 was localized in the nucleus, where it performs various functions; once US3 was expressed, phosphorylated VP8 was cytoplasmic and ultimately accumulated in the cis-Golgi apparatus, presumably to be incorporated into virions. The Golgi localization of VP8 was only observed in virus-infected cells and not in US3-cotransfected cells, suggesting that this is mediated by other viral factors. Interestingly, VP8 was shown to cause increased cholesterol levels, which is a novel function for VP8 and a potential strategy to supply lipid for viral replication.

Atomic and electronic reconstruction at the van der Waals interface in twisted bilayer graphene.

Control of the interlayer twist angle in two-dimensional van der Waals (vdW) heterostructures enables one to engineer a quasiperiodic moiré superlattice of tunable length scale1-8. In twisted bilayer graphene, the simple moiré superlattice band description suggests that the electronic bandwidth can be tuned to be comparable to the vdW interlayer interaction at a 'magic angle'9, exhibiting strongly correlated behaviour. However, the vdW interlayer interaction can also cause significant structural reconstruction at the interface by favouring interlayer commensurability, which competes with the intralayer lattice distortion10-16. Here we report atomic-scale reconstruction in twisted bilayer graphene and its effect on the electronic structure. We find a gradual transition from an incommensurate moiré structure to an array of commensurate domains with soliton boundaries as we decrease the twist angle across the characteristic crossover angle, θc ≈ 1°. In the solitonic regime (θ < θc) where the atomic and electronic reconstruction become significant, a simple moiré band description breaks down and the secondary Dirac bands appear. On applying a transverse electric field, we observe electronic transport along the network of one-dimensional topological channels that surround the alternating triangular gapped domains. Atomic and electronic reconstruction at the vdW interface provide a new pathway to engineer the system with continuous tunability.

Thermo-Sensitive Dual-Functional Nanospheres with Enhanced Lubrication and Drug Delivery for the Treatment of Osteoarthritis.

Osteoarthritis is a typical degenerative joint disease related to a lubrication deficiency of articular cartilage, which is characterized by increased friction at the joint surface and severe inflammation of the joint capsule. Consequently, therapies combining lubrication restoration and drug intervention are regarded as a promising strategy for the treatment of osteoarthritis. In the present study, thermo-sensitive dual-functional nanospheres, poly[N-isopropylacrylamide-2-methacryloyloxyethyl phosphorylcholine] (PNIPAM-PMPC), are developed through emulsion polymerization. The PNIPAM-PMPC nanospheres could enhance lubrication based on the hydration lubrication mechanism by forming a tenacious hydration layer surrounding the zwitterionic headgroups, and achieve local drug delivery by encapsulating the anti-inflammatory drug diclofenac sodium. The lubrication and drug release tests showed improved lubrication and thermo-sensitive drug release of the nanospheres. The in vitro test using cytokines-treated chondrocytes indicated that the PNIPAM-PMPC nanospheres were biocompatible and upregulated anabolic genes and simultaneously downregulated catabolic genes of the articular cartilage. In summary, the developed PNIPAM-PMPC nanospheres, with the property of enhanced lubrication and local drug delivery, can be an effective nanomedicine for the treatment of osteoarthritis.