Atomic Bose-Einstein condensate in twisted-bilayer optical lattices.

Observation of strong correlations and superconductivity in twisted-bilayer graphene1-4 has stimulated tremendous interest in fundamental and applied physics5-8. In this system, the superposition of two twisted honeycomb lattices, generating a moiré pattern, is the key to the observed flat electronic bands, slow electron velocity and large density of states9-12. Extension of the twisted-bilayer system to new configurations is highly desired, which can provide exciting prospects to investigate twistronics beyond bilayer graphene. Here we demonstrate a quantum simulation of superfluid to Mott insulator transition in twisted-bilayer square lattices based on atomic Bose-Einstein condensates loaded into spin-dependent optical lattices. The lattices are made of two sets of laser beams that independently address atoms in different spin states, which form the synthetic dimension accommodating the two layers. The interlayer coupling is highly controllable by a microwave field, which enables the occurrence of a lowest flat band and new correlated phases in the strong coupling limit. We directly observe the spatial moiré pattern and the momentum diffraction, which confirm the presence of two forms of superfluid and a modified superfluid to insulator transition in twisted-bilayer lattices. Our scheme is generic and can be applied to different lattice geometries and for both boson and fermion systems. This opens up a new direction for exploring moiré physics in ultracold atoms with highly controllable optical lattices.

Recognition of Highly Branched N-Glycans of the Porcine Whipworm by the Immune System.

Glycans are key to host-pathogen interactions, whereby recognition by the host and immunomodulation by the pathogen can be mediated by carbohydrate binding proteins, such as lectins of the innate immune system, and their glycoconjugate ligands. Previous studies have shown that excretory-secretory products of the porcine nematode parasite Trichuris suis exert immunomodulatory effects in a glycan-dependent manner. To better understand the mechanisms of these interactions, we prepared N-glycans from T. suis and both analyzed their structures and used them to generate a natural glycan microarray. With this array, we explored the interactions of glycans with C-type lectins, C-reactive protein, and sera from T. suis-infected pigs. Glycans containing LacdiNAc and phosphorylcholine-modified glycans were associated with the highest binding by most of these proteins. In-depth analysis revealed not only fucosylated LacdiNAc motifs with and without phosphorylcholine moieties but phosphorylcholine-modified mannose and N-acetylhexosamine-substituted fucose residues, in the context of maximally tetraantennary N-glycan scaffolds. Furthermore, O-glycans also contained fucosylated motifs. In summary, the glycans of T. suis are recognized by both the innate and adaptive immune systems and also exhibit species-specific features distinguishing its glycome from those of other nematodes.

Historic dog furs unravel the origin and artificial selection of modern Nordic Lapphund and Elkhound dog breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100-200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features.

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.

Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents.

BACKGROUND: During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs. METHODS: Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro. RESULTS: PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis. CONCLUSIONS: This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds.

Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3)1 and the disease-causing protein may target the latter for autophagic clearance. Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurable neurodegenerative disorder2. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington's disease. We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract3. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds.

Switching of brain networks across different cerebral perfusion states: insights from EEG dynamic microstate analyses.

The alteration of neural interactions across different cerebral perfusion states remains unclear. This study aimed to fulfill this gap by examining the longitudinal brain dynamic information interactions before and after cerebral reperfusion. Electroencephalogram in eyes-closed state at baseline and postoperative 7-d and 3-month follow-ups (moyamoya disease: 20, health controls: 23) were recorded. Dynamic network analyses were focused on the features and networks of electroencephalogram microstates across different microstates and perfusion states. Considering the microstate features, the parameters were disturbed of microstate B, C, and D but preserved of microstate A. The transition probabilities of microstates A-B and B-D were increased to play a complementary role across different perfusion states. Moreover, the microstate variability was decreased, but was significantly improved after cerebral reperfusion. Regarding microstate networks, the functional connectivity strengths were declined, mainly within frontal, parietal, and occipital lobes and between parietal and occipital lobes in different perfusion states, but were ameliorated after cerebral reperfusion. This study elucidates how dynamic interaction patterns of brain neurons change after cerebral reperfusion, which allows for the observation of brain network transitions across various perfusion states in a live clinical setting through direct intervention.

Pkd2 Deficiency in Embryonic Aqp2 + Progenitor Cells Is Sufficient to Cause Severe Polycystic Kidney Disease.

SIGNIFICANCE STATEMENT: Autosomal dominant polycystic kidney disease (ADPKD) is a devastating disorder caused by mutations in polycystin 1 ( PKD1 ) and polycystin 2 ( PKD2 ). Currently, the mechanism for renal cyst formation remains unclear. Here, we provide convincing and conclusive data in mice demonstrating that Pkd2 deletion in embryonic Aqp2 + progenitor cells (AP), but not in neonate or adult Aqp2 + cells, is sufficient to cause severe polycystic kidney disease (PKD) with progressive loss of intercalated cells and complete elimination of α -intercalated cells, accurately recapitulating a newly identified cellular phenotype of patients with ADPKD. Hence, Pkd2 is a new potential regulator critical for balanced AP differentiation into, proliferation, and/or maintenance of various cell types, particularly α -intercalated cells. The Pkd2 conditional knockout mice developed in this study are valuable tools for further studies on collecting duct development and early steps in cyst formation. The finding that Pkd2 loss triggers the loss of intercalated cells is a suitable topic for further mechanistic studies. BACKGROUND: Most cases of autosomal dominant polycystic kidney disease (ADPKD) are caused by mutations in PKD1 or PKD2. Currently, the mechanism for renal cyst formation remains unclear. Aqp2 + progenitor cells (AP) (re)generate ≥5 cell types, including principal cells and intercalated cells in the late distal convoluted tubules (DCT2), connecting tubules, and collecting ducts. METHODS: Here, we tested whether Pkd2 deletion in AP and their derivatives at different developmental stages is sufficient to induce PKD. Aqp2Cre Pkd2f/f ( Pkd2AC ) mice were generated to disrupt Pkd2 in embryonic AP. Aqp2ECE/+Pkd2f/f ( Pkd2ECE ) mice were tamoxifen-inducted at P1 or P60 to inactivate Pkd2 in neonate or adult AP and their derivatives, respectively. All induced mice were sacrificed at P300. Immunofluorescence staining was performed to categorize and quantify cyst-lining cell types. Four other PKD mouse models and patients with ADPKD were similarly analyzed. RESULTS: Pkd2 was highly expressed in all connecting tubules/collecting duct cell types and weakly in all other tubular segments. Pkd2AC mice had obvious cysts by P6 and developed severe PKD and died by P17. The kidneys had reduced intercalated cells and increased transitional cells. Transitional cells were negative for principal cell and intercalated cell markers examined. A complete loss of α -intercalated cells occurred by P12. Cysts extended from the distal renal segments to DCT1 and possibly to the loop of Henle, but not to the proximal tubules. The induced Pkd2ECE mice developed mild PKD. Cystic α -intercalated cells were found in the other PKD models. AQP2 + cells were found in cysts of only 13/27 ADPKD samples, which had the same cellular phenotype as Pkd2AC mice. CONCLUSIONS: Hence, Pkd2 deletion in embryonic AP, but unlikely in neonate or adult Aqp2 + cells (principal cells and AP), was sufficient to cause severe PKD with progressive elimination of α -intercalated cells, recapitulating a newly identified cellular phenotype of patients with ADPKD. We proposed that Pkd2 is critical for balanced AP differentiation into, proliferation, and/or maintenance of cystic intercalated cells, particularly α -intercalated cells.

Sustained Secretion of CCL21 via an Implantable Cell Reservoir Hydrogel Enhances the Systemic Antitumor Effect of Radiotherapy.

The combination of radiotherapy (RT) and immunotherapy shows promise in improving the clinical treatment of solid tumors; however, it faces challenges of low response rates and systemic toxicity. Herein, an implantable alginate/collagen hydrogel encapsulating C-C motif ligand 21 (CCL21)-expressing dendritic cells (CCL21-DCs@gel) was developed to potentiate the systemic antitumor effects of RT. The hydrogel functioned as a suitable reservoir for in vivo culture and proliferation of CCL21-DCs, thereby enabling sustained CCL21 release. The local CCL21 gradient induced by CCL21-DCs@gel significantly enhanced the efficacy of RT in suppressing primary tumor growth and inhibiting distant metastasis across several mouse models. Furthermore, the combination of RT with CCL21-DCs@gel provided complete prophylactic protection to mice. Mechanistic investigations revealed that CCL21-DCs@gel potentiated RT by promoting tumor lymphangiogenesis and attracting immune cell infiltration into the tumor. Collectively, these results suggest that CCL21-DCs@gel is a promising adjunct to RT for effectively eradicating tumors and preventing tumor recurrence.

High Performance Nacre Fibers by Engineering Interfacial Entanglement.

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.

Microglial HO-1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co-located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG-mediated autophagy and HO-1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf-A1 or HO-1 inhibitor ZnPP protected against hemin-induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG-mediated autophagy and HO-1 signalling pathway. Knock-down of FoxO3a inhibited autophagy and prevented hemin-induced ferroptosis dependent of HO-1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO-1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro-inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis-induced striatum injury in the autologous blood-induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG-mediated autophagy and HO-1 play an important role in microglial activation and ferroptosis-induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.

Continuous Flow System for Highly Efficient and Durable Photocatalytic Oxidative Coupling of Methane.

Photocatalytic oxidative coupling of methane (OCM) into value-added industrial chemicals offers an appealing green technique for achieving sustainable development, whereas it encounters double bottlenecks in relatively low methane conversion rate and severe overoxidation. Herein, we engineer a continuous gas flow system to achieve efficient photocatalytic OCM while suppressing overoxidation by synergizing the moderate active oxygen species, surface plasmon-mediated polarization, and multipoint gas intake flow reactor. Particularly, a remarkable CH4 conversion rate of 218.2 µmol h-1 with an excellent selectivity of ∼90% toward C2+ hydrocarbons and a remarkable stability over 240 h is achieved over a designed Au/TiO2 photocatalyst in our continuous gas flow system with a homemade three-dimensional (3D) printed flow reactor. This work provides an informative concept to engineer a high-performance flow system for photocatalytic OCM by synergizing the design of the reactor and photocatalyst to synchronously regulate the mass transfer, activation of reactants, and inhibition of overoxidation.

Click Conjugation of Zwitterionic Peptide with DNA Strand: An Efficient Antifouling Strategy for Versatile Photoelectrochemical Aptasensor.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate. This intriguing conjugate exploited the BZP domain to create an antifouling biointerface, while the cDNA component facilitated subsequent hybridization with probe DNA (pDNA). To advance the development of the aptasensor, an upgraded PDA/HOF-101/ZnO ternary photoelectrode was designed as the signal converter for the modification of the BZP-cDNA conjugate, while a bipyridinium (MCEPy) molecule with strong electron-withdrawing properties was labeled at the front end of the pDNA to form the pDNA-MCEPy signal probe. Targeting the model of mucin-1, a remarkable enhancement in the photocurrent signal was achieved through exonuclease-I-aided target recycling. Such an engineered zwitterionic peptide-DNA conjugate surpasses the limitations imposed by conventional peptide-based sensing modes, exhibiting unique advantages such as versatility in design and capability for signal amplification.

Highly Light-Harvesting MOF-on-MOF Heterostructure: Cascading Functionality to Flexible Photogating of Organic Photoelectrochemical Transistor and Bienzyme Cascade Detection.

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.

Intelligent Cell Profiling and Precision Release: Multimolecular Marker-Activated Transmembrane DNA Computing Nanosystem.

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

Cytological characteristics of blueberry fruit development.

Using the blueberry cultivar "Powderblue" after pollination, fruits at different developmental stages were collected for study. The transverse and longitudinal diameters, individual fruit weight, and fruit water content were measured during their development. Employing tissue sectioning and microscopy techniques, we systematically studied the morphological features and anatomical structures of the fruits and seeds at various developmental stages, aiming to elucidate the cytological patterns during blueberry fruit development. The results of our study revealed that the "Powderblue" blueberry fruit growth and development followed a double "S" curve. Mature "Powderblue" blueberries were blue-black in color, elliptical in shape, with five locules, an inferior ovary, and an average fruit weight of 1.73 ± 0.17 g, and a moisture content of 78.865 ± 0.9%. Blueberry fruit flesh cells were densely arranged with no apparent intercellular spaces, and mesocarp cells accounted for 52.06 ± 7.4% of fruit cells. In the early fruit development stages, the fruit flesh cells were rapidly dividing, significantly increasing in number but without greatly affecting the fruit's morphological characteristics. During the later stages of fruit development, the expansion of the fruit flesh cells became prominent, resulting in a noticeable increase in the fruit's dimensions. Except for the epidermal cells, cells in all fruit tissues showed varying degrees of rupture as fruit development progressed, with the extent of cell rupture increasing, becoming increasingly apparent as the fruit gradually softened. Additionally, numerous brachysclereids (stone cells) appeared in the fruit flesh cells. Stone cells are mostly present individually in the fruit flesh tissue, while in the placental tissue, they often group together. The "Powderblue" blueberry seeds were light brown, 4.13 ± 0.42 mm long, 2.2 ± 0.14 mm wide, with each fruit containing 50-60 seeds. The "Powderblue" seeds mainly consisted of the seed coat, endosperm, and embryo. The embryo was located at the chalazal end in the center of the endosperm and was spatially separated. The endosperm, occupying the vast majority of the seed volume, comprised both the chalazal and outer endosperm, and the endosperm developed and matured before the embryo. As the seed developed, the seed coat was gradually lignified and consisted of palisade-like stone cells externally and epidermal layer cells internally.

Highly Flexible and Superelastic Graphene Nanofibrous Aerogels for Intelligent Sign Language.

Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels. The mechanical robustness is demonstrated to be derived from the trans-scale porous structure, which is composed of hyperbolic micropores and porous nanofibers to enable the large elastic deformation capability. It is further revealed that flexible and superelastic GNFAs exhibit high sensitivity and ultrastability as an electrical sensors to detect tension and flexion deformation. As proof, The GNFA sensor is implemented onto a human finger and achieves the intelligent recognition of sign language with high accuracy by multi-layer artificial neural network. This study proposes a highly flexible and elastic graphene aerogel for wearable human-machine interfaces in sensor technology.

Tailoring the Molecular Planarity of Perylene Diimide-Based Third Component toward Efficient Ternary Organic Solar Cells.

Incorporating a third component into binary organic solar cells (b-OSCs) has provided a potential platform to boost power conversion efficiency (PCEs). However, gaining control over the non-equilibrium blend morphology via the molecular design of the perylene diimide (PDI)-based third component toward efficient ternary organic solar cells (t-OSCs) still remains challenging. Herein, two novel PDI derivatives are developed with tailored molecular planarity, namely ufBTz-2PDI and fBTz-2PDI, as the third component for t-OSCs. Notably, after performing a cyclization reaction, the twisted ufBTz-2PDI with an amorphous character transferred to the highly planar fBTz-2PDI followed by a semi-crystalline character. When incorporating the semi-crystalline fBTz-2PDI into the D18:L8-BO system, the resultant t-OSC achieved an impressive PCE of 18.56%, surpassing the 17.88% attained in b-OSCs. In comparison, the addition of amorphous ufBTz-2PDI into the binary system facilitates additional charge trap sites and results in a deteriorative PCE of 14.37%. Additionally, The third component fBTz-2PDI possesses a good generality in optimizing the PCEs of several b-OSCs systems are demonstrated. The results not only provided a novel A-DA'D-A motif for further designing efficient third component but also demonstrated the crucial role of modulated crystallinity of the PDI-based third component in optimizing PCEs of t-OSCs.

UHRF1 Deficiency Inhibits Alphaherpesvirus through Inducing RIG-I-IRF3-Mediated Interferon Production.

Type I interferon (IFN-I) response plays a prominent role in innate immunity, which is frequently modulated during viral infection. Here, we report DNA methylation regulator UHRF1 as a potent negative regulator of IFN-I induction during alphaherpesvirus infection, whereas the viruses in turn regulates the transcriptional expression of UHRF1. Knockdown of UHRF1 in cells significantly increases interferon-ß (IFN-ß)-mediated gene transcription and viral inhibition against herpes simplex virus 1 (HSV1) and pseudorabies virus (PRV). Mechanistically, UHRF1 deficiency promotes IFN-I production by triggering dsRNA-sensing receptor RIG-I and activating IRF3 phosphorylation. Knockdown of UHRF1 in cells upregulates the accumulation of double-stranded RNA (dsRNA), including host endogenous retroviral sequence (ERV) transcripts, while the treatment of RNase III, known to specifically digest dsRNA, prevents IFN-ß induction by siUHRF1. Furthermore, the double-knockdown assay of UHRF1 and DNA methyltransferase DNMT1 suggests that siUHRF1-mediated DNA demethylation may play an important role in dsRNA accumulation and subsequently IFN induction. These findings establish the essential role of UHRF1 in IFN-I-induced antiviral immunity and reveal UHRF1 as a potential antivrial target. IMPORTANCE Alphaherpesviruses can establish lifelong infections and cause many diseases in humans and animals, which rely partly on their interaction with IFN-mediated innate immune response. Using alphaherpesviruses PRV and HSV-1 as models, we identified an essential role of DNA methylation regulator UHRF1 in IFN-mediated immunity against virus replication, which unravels a novel mechanism employed by epigenetic factor to control IFN-mediated antiviral immune response and highlight UHRF1, which might be a potential target for antiviral drug development.

Focal plane coincidence method for a multi-view telecentric 3D imaging system.

Multi-view microscopic fringe projection systems, which use high-resolution telecentric lenses and the Scheimpflug condition, face challenges in coinciding focal planes accurately, resulting in inconsistent measurements between views. In this Letter, we developed a sharpness evaluation function based on the total power of the line-spread function, which was subsequently used to generate a full-field sharpness distribution map. Then we employed the correlation between the sharpness map and orientation of the focal plane to precisely coincide the focal planes. Experimental results validate the proposed method and demonstrate its improved consistency in 3D reconstruction.