Inorganic micro light-emitting diodes (micro-LEDs) based on III-V compound semiconductors have been widely studied for self-emissive displays. From chips to applications, integration technology plays an indispensable role in micro-LED displays. For example, large-scale display relies on the integration of discrete device dies to achieve extended micro-LED array, and full color display requires integration of red, green, and blue micro-LED units on the same substrate. Moreover, the integration with transistors or complementary metal-oxide-semiconductor circuits are necessary to control and drive the micro-LED display system. In this review article, we summarized the 3 main integration technologies for micro-LED displays, which are called transfer integration, bonding integration, and growth integration. An overview of the characteristics of these 3 integration technologies is presented, while various strategies and challenges of integrated micro-LED display system are discussed.

Stress granules (SGs) are membraneless cytoplasmic condensates that dynamically assemble in response to various stressors and reversibly disassemble after stimulus removal; however, the mechanisms underlying SG dynamics and their physiological roles in germ cell development are elusive. Here, we show that SERBP1 (SERPINE1 mRNA binding protein 1) is a universal SG component and conserved regulator of SG clearance in somatic and male germ cells. SERBP1 interacts with the SG core component G3BP1 and 26S proteasome proteins PSMD10 and PSMA3 and recruits them to SGs. In the absence of SERBP1, reduced 20S proteasome activity, mislocalized valosin containing protein (VCP) and Fas associated factor family member 2 (FAF2), and diminished K63-linked polyubiquitination of G3BP1 during the SG recovery period were observed. Interestingly, the depletion of SERBP1 in testicular cells in vivo causes increased germ cell apoptosis upon scrotal heat stress. Accordingly, we propose that a SERBP1-mediated mechanism regulates 26S proteasome activity and G3BP1 ubiquitination to facilitate SG clearance in both somatic and germ cell lines.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality, and the efficacy of monotherapy for TNBC is still disappointing. Here, we developed a novel combination therapy for TNBC based on a multifunctional nanohollow carbon sphere. This intelligent material contains a superadsorbed silicon dioxide sphere, sufficient loading space, a nanoscale hole on its surface, a robust shell, and an outer bilayer, and it could load both programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) small-molecule immune checkpoints and small-molecule photosensitizers with excellent loading contents, protect these small molecules during the systemic circulation, and achieve accumulation of them in tumor sites after systemic administration followed by the application of laser irradiation, thereby realizing dual attack of photodynamic therapy and immunotherapy on tumors. Importantly, we integrated the fasting-mimicking diet condition that can further enhance the cellular uptake efficiency of nanoparticles in tumor cells and amplify the immune responses, further enhancing the therapeutic effect. Thus, a novel combination therapy “PD-1/PD-L1 immune checkpoint blockade + photodynamic therapy + fasting-mimicking diet”was developed with the aid of our materials, which eventually achieved a marked therapeutic effect in 4T1-tumor-bearing mice. The concept can also be applied to the clinical treatment of human TNBC with guiding significance in the future.

The real-world vaccine protection rates (VPRs) against the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection are critical in formulating future vaccination strategies against the virus. Based on a varying coefficient stochastic epidemic model, we obtain 7 countries’ real-world VPRs using daily epidemiological and vaccination data, and find that the VPRs improved with more vaccine doses. The average VPR of the full vaccination was 82% (SE: 4%) and 61% (SE: 3%) in the pre-Delta and Delta-dominated periods, respectively. The Omicron variant reduced the average VPR of the full vaccination to 39% (SE: 2%). However, the booster dose restored the VPR to 63% (SE: 1%) which was significantly above the 50% threshold in the Omicron-dominated period. Scenario analyses show that the existing vaccination strategies have significantly delayed and reduced the timing and the magnitude of the infection peaks, respectively, and doubling the existing booster coverage would lead to 29% fewer confirmed cases and 17% fewer deaths in the 7 countries compared to the outcomes at the existing booster taking rates. These call for higher full vaccine and booster coverage for all countries.

The durability of the resin–dentin bonding interface is a key issue in clinical esthetic dentistry. Inspired by the extraordinary bioadhesive properties of marine mussels in a wet environment, we designed and synthetized N-2-(3,4-dihydroxylphenyl) acrylamide (DAA) according to the functional domain of mussel adhesive proteins. DAA’s properties of collagen cross-linking, collagenase inhibition, inducing collagen mineralization in vitro, and as a novel prime monomer for clinical dentin adhesion use, its optimal parameters, and effect on the adhesive longevity and the bonding interface’s integrity and mineralization, were evaluated in vitro and in vivo. The results showed that oxide DAA can inhibit the activity of collagenase and cross collagen fibers to improve the anti-enzymatic hydrolysis of collagen fibers and induce intrafibrillar and interfibrillar collagen mineralization. As a primer used in the etch-rinse tooth adhesive system, oxide DAA can improve the durability and integrity of the bonding interface by anti-degradation and mineralization of the exposed collagen matrix. Oxidized DAA (OX-DAA) is a promising primer for improving dentin durability; using 5% OX-DAA ethanol solution and treating the etched dentin surface for 30 s is the optimal choice when used as a primer in the etch-rinse tooth adhesive system.

Efficient regulation of thermal radiation is an effective way to conserve energy consumption of buildings. Because windows are the least energy-efficient part of buildings, their thermal radiation regulation is highly demanded, especially in the changing environment, but is still a challenge. Here, by employing a kirigami structure, we design a variable-angle thermal reflector as a transparent envelope of windows for their thermal radiation modulation. The envelope can be easily switched between heating and cooling modes by loading different pre-stresses, which endow the envelope windows with the ability of temperature regulation, and the interior temperature of a building model can be reduced by ~3.3 °C under cooling mode and increased by ~3.9 °C under heating mode in the outdoor test. The improved thermal management of windows by the adaptive envelope provides an extra heating, ventilation, and air-conditioning energy savings percentage of 13% to 29% per year for buildings located in different climate zones around the world, making the kirigami envelope windows a promising way for energy-saving utilization.

Akkermansia muciniphila (A. muciniphila) has drawn much attention as an important gut microbe strain in recent years. A. muciniphila can influence the occurrence and development of diseases of the endocrine, nervous, digestive, musculoskeletal, and respiratory systems and other diseases. It can also improve immunotherapy for some cancers. A. muciniphila is expected to become a new probiotic in addition to Lactobacillus and Bifidobacterium. An increase in A. muciniphila abundance through direct or indirect A. muciniphila supplementation may inhibit or even reverse disease progression. However, some contrary findings are found in type 2 diabetes mellitus and neurodegenerative diseases, where increased A. muciniphila abundance may aggravate the diseases. To enable a more comprehensive understanding of the role of A. muciniphila in diseases, we summarize the relevant information on A. muciniphila in different systemic diseases and introduce regulators of A. muciniphila abundance to promote the clinical transformation of A. muciniphila research.

Oncolytic viruses (OVs) as one promising antitumor methods have made important contributions to tumor immunotherapy, which arouse increasing attention. They provide the dual mechanisms including direct killing effect toward tumor cells and immune activation for elevating antitumor responses, which have been proved in many preclinical studies. Especially, natural or genetically modified viruses as clinical immune preparations have emerged as a new promising approach objective to oncology treatment. The approval of talimogene laherparepvec (T-VEC) by the U.S. Food and Drug Administration (FDA) for the therapy of advanced melanoma could be considered as a milestone achievement in the clinical translation of OV. In this review, we first discussed the antitumor mechanisms of OVs with an emphasis on targeting, replication, and propagation. We further outlined the state of the art of current OVs in tumor and underlined the activated biological effects especially including immunity. More significantly, the enhanced immune responses based on OVs were systematically discussed from different perspectives such as combination with immunotherapy, genetic engineering of OVs, integration with nanobiotechnology or nanoparticles, and antiviral response counteraction, where their principles were shed light on. The development of OVs in the clinics was also highlighted to analyze the actuality and concerns of different OV applications in clinical trials. At last, the future perspectives and challenges of OVs as an already widely accepted treatment means were discussed. This review will provide a systematic review and deep insight into OV development and also offer new opportunities and guidance pathways to drive the further clinical translation.

Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less known. We here report that lysine acetyltransferase 2A (KAT2A) as an illustrative instance of HATs can selectively utilize acetyl-CoA, propionyl-CoA, butyryl-CoA, and succinyl-CoA to directly deposit 18 histone acylation hallmarks in nucleosome. By analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, succinyl-CoA, and glutaryl-CoA, we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by KAT2A. This study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes, which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells.

Industry 4.0 is a digital paradigm that refers to the integration of cutting-edge computing and digital technologies into global industries because of which the state of manufacturing, communication, and control of smart industries has changed altogether. Industry 4.0 has been profoundly influenced by some major disruptive technologies such as the Internet of Things (IoT), smart sensors, machine learning and artificial intelligence, cloud computing, big data analytics, advanced robotics, augmented reality, 3D printing, and smart adaptive communication. In this review paper, we discuss physical layer-based solutions with a focus on high reliability and seamless connectivity for Industry 4.0 and beyond applications. First, we present a harmonized review of the industrial revolution journey, industrial communication infrastructure, key performance requirements, and potential sub-6-GHz frequency bands. Then, based on that, we present a comprehensive review of intelligent tunable dynamic antenna systems at sub-6 GHz as key enablers for next-generation smart industrial applications. State-of-the-art smart antenna techniques such as agile pattern reconfigurability using electrical components, machine learning- and artificial intelligence-based agile beam-scanning antennas, and beam-steerable dynamic metasurface antennas are thoroughly reviewed and emphasized. We unfolded the exciting prospects of reconfigurable dynamic antennas for intelligent and reliable connectivity in application scenarios of Industry 4.0 and beyond such as Industrial IoT and smart manufacturing.

Repelling liquid drops from engineering surfaces has attracted great attention in a variety of applications. To achieve efficient liquid shedding, delicate surface textures are often introduced to sustain air pockets at the liquid–solid interface. However, those surfaces are prone to suffer from mechanical failure, which may bring reliability issues and thus limits their applications. Here, inspired by the aerodynamic Leidenfrost effect, we present that impacting drops are directionally repelled from smooth surfaces supplied with an exogenous air layer. Our theoretical analysis reveals that the synchronized nonwetting and oblique bouncing behavior is attributed to the aerodynamic force arising from the air layer. The versatility and practicability of our approach allow for drop repellency without the aid of any surface wettability treatment and also avoid the consideration of mechanical stability issues, which thereby provides a promising candidate for the applications that necessitate liquid shedding, e.g., resolve the problem of tiny raindrop adhesion on the automobile side window during driving.

Metal halide perovskites have advanced greatly in both light-emitting diodes (LEDs) and photovoltaics (PVs) through delicate device engineering. The optimization strategies of perovskite LEDs and PVs have been demonstrated to be quite different. Here, we show that this dissimilarity in device fabrications can be well understood based on the analysis of carrier dynamics in LEDs and PVs.

Amphiphilic copolymers can self-assemble into nano-objects in aqueous solution. However, the self-assembly process is usually performed in a diluted solution (<1 wt%), which greatly limits scale-up production and further biomedical applications. With recent development of controlled polymerization techniques, polymerization-induced self-assembly (PISA) has emerged as an efficient approach for facile fabrication of nano-sized structures with a high concentration as high as 50 wt%. In this review, after the introduction, various polymerization method-mediated PISAs that include nitroxide-mediated polymerization-mediated PISA (NMP-PISA), reversible addition-fragmentation chain transfer polymerization-mediated PISA (RAFT-PISA), atom transfer radical polymerization-mediated PISA (ATRP-PISA), and ring-opening polymerization-mediated PISA (ROP-PISA) are discussed carefully. Afterward, recent biomedical applications of PISA are illustrated from the following aspects, i.e., bioimaging, disease treatment, biocatalysis, and antimicrobial. In the end, current achievements and future perspectives of PISA are given. It is envisioned that PISA strategy can bring great chance for future design and construction of functional nano-vehicles.

Small extracellular vesicle (sEV) is an emerging source of potential biomarkers of Alzheimer's disease (AD), but the role of microRNAs (miRNAs) in sEV is not well understood. In this study, we conducted a comprehensive analysis of sEV-derived miRNAs in AD using small RNA sequencing and coexpression network analysis. We examined a total of 158 samples, including 48 from AD patients, 48 from patients with mild cognitive impairment (MCI), and 62 from healthy controls. We identified an miRNA network module (M1) that was strongly linked to neural function and showed the strongest association with AD diagnosis and cognitive impairment. The expression of miRNAs in the module was decreased in both AD and MCI patients compared to controls. Conservation analysis revealed that M1 was highly preserved in the healthy control group but dysfunctional in the AD and MCI groups, suggesting that changes in the expression of miRNAs in this module may be an early response to cognitive decline prior to the appearance of AD pathology. We further validated the expression levels of the hub miRNAs in M1 in an independent population. The functional enrichment analysis showed that 4 hub miRNAs might interact with a GDF11-centered network and play a critical role in the neuropathology of AD. In summary, our study provides new insights into the role of sEV-derived miRNAs in AD and suggests that M1 miRNAs may serve as potential biomarkers for the early diagnosis and monitoring of AD.

A corrected group contribution (CGC)–molecule contribution (MC)–Bayesian neural network (BNN) protocol for accurate prediction of absorption spectra is presented. Upon combination of BNN with CGC methods, the full absorption spectra of various molecules are afforded accurately and efficiently—by using only a small dataset for training. Here, with a small training sample (<100), accurate prediction of maximum wavelength for single molecules is afforded with the first stage of the protocol; by contrast, previously reported machine learning (ML) methods require >1,000 samples to ensure the accuracy of prediction. Furthermore, with <500 samples, the mean square error in the prediction of full ultraviolet spectra reaches <2%; for comparison, ML models with molecular SMILES for training require a much larger dataset (>2,000) to achieve comparable accuracy. Moreover, by employing an MC method designed specifically for CGC that properly interprets the mixing rule, the spectra of mixtures are obtained with high accuracy. The logical origins of the good performance of the protocol are discussed in detail. Considering that such a constituent contribution protocol combines chemical principles and data-driven tools, most likely, it will be proven efficient to solve molecular-property-relevant problems in wider fields.

Miniature robots show great potential in exploring narrow and confined spaces to perform various tasks, but many applications are limited by the dependence of these robots on electrical or pneumatic tethers to power supplies outboard. Developing an onboard actuator that is small in size and powerful enough to carry all the components onboard is a major challenge to eliminate the need for a tether. Bistability can trigger a dramatic energy release during switching between the 2 stable states, thus providing a promising way to overcome the intrinsic limitation of insufficient power of small actuators. In this work, the antagonistic action between torsional deflection and bending deflection in a lamina emergent torsional joint is utilized to achieve bistability, yielding a buckling-free bistable design. The unique configuration of this bistable design enables integrating of a single bending electroactive artificial muscle in the structure to form a compact, self-switching bistable actuator. A low-voltage ionic polymer–metal composites artificial muscle is employed, yielding a bistable actuator capable of generating an instantaneous angular velocity exceeding 300 °/s by a 3.75-V voltage. Two untethered robotic demonstrations using the bistable actuator are presented, including a crawling robot (gross weight of 2.7 g, including actuator, battery, and on-board circuit) that can generate a maximum instantaneous velocity of 40 mm/s and a swimming robot equipped with a pair of origami-inspired paddles that swims breaststroke. The low-voltage bistable actuator shows potential for achieving autonomous motion of various fully untethered miniature robots.

Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence (ECL) immunoassays, but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development. In this study, we synthesized a series of gold nanoparticles (AuNPs)/reduced graphene oxide (Au/rGO) composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine) ruthenium(II) (Ru(bpy)₃²⁺)’s multisignal luminescence. With the increase in the diameter of AuNPs (3 to 30 nm), their ability to promote Ru(bpy)₃²⁺’s anodic ECL was first impaired and then strengthened, and cathodic ECL was first enhanced and then weakened. Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)₃²⁺’s cathodic and anodic luminescence, respectively. Notably, the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)₃²⁺ co-reactants. Moreover, we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)₃²⁺’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution. This method avoids signal cross talk between luminophores and their respective co-reactants, which achieved a good linear range of 10⁻⁷ to 10⁻¹ ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen. This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)₃²⁺, broadening its application in biomaterial detection. Furthermore, the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)₃²⁺ could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)₃²⁺ luminescence enhancers or applications of Au/rGOs to other luminophores. This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.

The precise characterization of cellular differentiation potency remains an open question, which is fundamentally important for deciphering the dynamics mechanism related to cell fate transition. We quantitatively evaluated the differentiation potency of different stem cells based on the Hopfield neural network (HNN). The results emphasized that cellular differentiation potency can be approximated by Hopfield energy values. We then profiled the Waddington energy landscape of embryogenesis and cell reprogramming processes. The energy landscape at single-cell resolution further confirmed that cell fate decision is progressively specified in a continuous process. Moreover, the transition of cells from one steady state to another in embryogenesis and cell reprogramming processes was dynamically simulated on the energy ladder. These two processes can be metaphorized as the motion of descending and ascending ladders, respectively. We further deciphered the dynamics of the gene regulatory network (GRN) for driving cell fate transition. Our study proposes a new energy indicator to quantitatively characterize cellular differentiation potency without prior knowledge, facilitating the further exploration of the potential mechanism of cellular plasticity.

Periodontal lesions are common and frustrating diseases that impact life quality. Efforts in this aspect aim at developing local drug delivery systems with better efficacy and less toxicity. Herein, inspired by the sting separation behavior of bees, we conduct novel reactive oxygen species (ROS)-responsive detachable microneedles (MNs) that carry antibiotic metronidazole (Met) for controllable periodontal drug delivery and periodontitis treatment. Benefiting from the needle-base separation ability, such MNs can penetrate through the healthy gingival to reach the gingival sulcus's bottom while offering minimal impact to oral function. Besides, as the drug-encapsulated cores were protected by poly (lactic-co-glycolic acid) (PLGA) shells in MNs, the surrounding normal gingival tissue is not affected by Met, resulting in excellent local biosafety. Additionally, with the ROS-responsive PLGA-thioketal-polyethylene glycol MN tips, they can be unlocked to release Met directly around the pathogen under the high ROS in the periodontitis sulcus, bringing about improved therapeutic effects. Based on these characteristics, the proposed bioinspired MNs show good therapeutic results in treating a rat model with periodontitis, implying their potential in periodontal disease.

Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the brain. However, it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life events. We used tissue clearing techniques, immunostaining, light-sheet whole-brain imaging, confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain parenchyma. Chronic unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful events. Western blotting and coimmunoprecipitation were used to provide mechanistic insights. We demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex, cerebellum, hippocampus, midbrain, and brainstem. Furthermore, we showed that deep brain lymphatic vessels can be regulated by stressful life events. Chronic stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the amygdala. No changes were observed in prefrontal cortex, lateral habenula, or dorsal raphe nucleus. Chronic corticosterone treatment reduced lymphatic endothelial cell markers in the hippocampus. Mechanistically, chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization mechanisms. Our results provide new insights into the characteristic features of deep brain lymphatic vessels, as well as their regulation by stressful life events.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 (Cdk5) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca²⁺-activated K⁺ channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5^f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

Soft pneumatic actuators (SPAs) have attracted enormous attention in the growing field of robotics. Among different SPAs, composite reinforced actuators (CRAs) are widely used because of their simple structure and high controllability. However, multistep molding, a time-consuming method, is still the predominant fabrication method. Here, we propose a multimaterial embedded printing method (ME3P) to fabricate CRAs. In comparison with other 3-dimensional printing methods, our method improves fabrication flexibility greatly. Via the design and fabrication of the reinforced composites’ patterns and different geometries of the soft body, we demonstrate actuators with programmable responses (elongation, contraction, twisting, bending, and helical and omnidirectional bending). Finite element analysis is employed for the prediction of pneumatic responses and the inverse design of actuators based on specific actuation needs. Lastly, we use tube-crawling robots as a model system to demonstrate our ability to fabricate complex soft robots for practical applications. This work demonstrates the versatility of ME3P for the future manufacturing of CRA-based soft robots.

Seeking new strategies to tune the intrinsic defect and optimize the thermoelectric performance via no or less use of external doped elements (i.e., plain optimization) is an important method to realize the sustainable development of thermoelectric materials. Meanwhile, creating dislocation defects in oxide systems is quite challenging because the rigid and stiff ionic/covalent bonds can hardly tolerate the large strain energy associated with dislocations. Herein, taking BiCuSeO oxide as an example, the present work reports a successful construction of dense lattice dislocations in BiCuSeO by self-doping of Se at the O site (i.e., Se_O self-substitution), and achieves plain optimization of the thermoelectric properties with only external Pb doping. Owing to the self-substitution-induced large lattice distortion and the potential reinforcement effect by Pb doping, high-density (about 3.0 × 10¹⁴ m⁻²) dislocations form in the grains, which enhances the scattering strength of mid-frequency phonon and results in a substantial low lattice thermal conductivity of 0.38 W m⁻¹ K⁻¹ at 823 K in Pb-doped BiCuSeO. Meanwhile, Pb_Bi doping and Cu vacancy markedly improve the electrical conductivity while maintaining a competitively high Seebeck coefficient, thereby contributing to a highest power factor of 942 μW m⁻¹ K⁻². Finally, a remarkably enhanced zT value of 1.32 is obtained at 823 K in Bi_0.94Pb_0.06Cu_0.97Se_1.05O_0.95 with almost compositional plainification. The high-density dislocation structure reported in this work will also provide a good inspiration for the design and construction of dislocations in other oxide systems.

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD–platelet interaction was partially dependent on the β3 integrin as binding was significantly reduced in β3^−/− mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbβ3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbβ3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

Natural killer (NK) cells, as key immune cells, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut microbiota community affects the efficacy of anti-PD1 immunotherapy and that remodeling the gut microbiota is a promising strategy to enhance anti-PD1 immunotherapy responsiveness in advanced melanoma patients; however, the details of the mechanism remain elusive. In this study, we found that Eubacterium rectale was significantly enriched in melanoma patients who responded to anti-PD1 immunotherapy and that a high E. rectale abundance was related to longer survival in melanoma patients. Furthermore, administration of E. rectale remarkably improved the efficacy of anti-PD1 therapy and increased the overall survival of tumor-bearing mice; moreover, application of E. rectale led to a significant accumulation of NK cells in the tumor microenvironment. Interestingly, conditioned medium isolated from an E. rectale culture system dramatically enhanced NK cell function. Gas chromatography–mass spectrometry/ultrahigh performance liquid chromatography–tandem mass spectrometry-based metabolomic analysis showed that l-serine production was significantly decreased in the E. rectale group; moreover, administration of an l-serine synthesis inhibitor dramatically increased NK cell activation, which enhanced anti-PD1 immunotherapy effects. Mechanistically, supplementation with l-serine or application of an l-serine synthesis inhibitor affected NK cell activation through Fos/Fosl. In summary, our findings reveal the role of bacteria-modulated serine metabolic signaling in NK cell activation and provide a novel therapeutic strategy to improve the efficacy of anti-PD1 immunotherapy in melanoma.

Microneedles (MNs) have drawn rising attention owing to their merits of convenience, noninvasiveness, flexible applicability, painless microchannels with boosted metabolism, and precisely tailored multifunction control. MNs can be modified to serve as novel transdermal drug delivery, which conventionally confront with the penetration barrier caused by skin stratum corneum. The micrometer-sized needles create channels through stratum corneum, enabling efficient drug delivery to the dermis for gratifying efficacy. Then, incorporating photosensitizer or photothermal agents into MNs can conduct photodynamic or photothermal therapy, respectively. Besides, health monitoring and medical detection by MN sensors can extract information from skin interstitial fluid and other biochemical/electronic signals. Here, this review discloses a novel monitoring, diagnostic, and therapeutic pattern by MNs, with elaborate discussion about the classified formation of MNs together with various applications and inherent mechanism. Hereby, multifunction development and outlook from biomedical/nanotechnology/photoelectric/devices/informatics to multidisciplinary applications are provided. Programmable intelligent MNs enable logic encoding of diverse monitoring and treatment pathways to extract signals, optimize the therapy efficacy, real-time monitoring, remote control, and drug screening, and take instant treatment.