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Single-molecule magnets (SMMs) are a kind of nanosized magnetic materials that are capable of storing massive bytes of information. Strongly coupling the spin centers in a proper manner is a usual approach to promote the working temperature (or blocking temperature) for SMMs. Electron delocalized radicals have been widely employed to accomplish this job. Here, we show a new manner by using weak but multiple B–Hδ−⋯ Dy3+inverse hydrogen bonding (IHB) interactions to control the magnetic couplings in a series of dimeric dysprosiacaborane SMMs. This approach leads to a record high TB100sof 10 K among non-radical bridged dimeric SMMs, which is mainly ascribed to strong ferromagnetic coupling (4.38 cm−1) and the proper alignment of the magnetic principle axes of the adjacent dysprosium(III) ions. In verifying by theoretical calculations, these results demonstrate that IHB interactions can be used to construct strong axial ferromagnetic coupling and enhancing magnetic blocking temperature for SMMs.

Excellent oxygen barrier films were prepared by blending very small loadings (<1 wt%) of dihydroxyacetone (DHA), erythritol (ET) or xylitol (XT) in thermoplastic starch (TPS), and/or processing with supercritical carbon dioxide (scCO2) assistance. The minimum oxygen transmission rates (OTR) and all free-volume-hole characteristic (FVH) values of each scCO2-processed TPS/sugar alcohol film series are somewhat smaller than those of corresponding TPS/sugar alcohol film series without scCO2-assistance, and decrease with the decrease in sugar alcohol’s molecular weight. The minimum OTR values acquired for scCO2-processed TPS/DHA and TPS/ET blown films are only 3.6 and 4.3 cm3/m2·day·atm, respectively, which meet the demand of high oxygen barrier films having OTR ≦5 cm3/m2·day·atm. The longitudinal or transversal tensile strengths acquired for each scCO2-processed TPS/sugar alcohol series films are ∼30 % to ∼40 % higher than those of the TPS blown films. Dynamic mechanical relaxations of each TPS/sugar alcohol or scCO2-processed TPS/sugar alcohol film series reveal that the sugar alcohols are compatible with TPS, as their sugar alcohol contents are ≤ the corresponding compatibility values. The decreased OTR and FVH values acquired for TPS/sugar alcohol or scCO2-processed TPS/sugar alcohol films are most likely due to them being scCO2-processed or incorporated with smaller molecular weight of sugar alcohols.

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Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with a complex pathogenesis, which causes the lack of precise and personalized prevention, control, and treatment approaches in clinical practice. Traditional Chinese medicine (TCM) with multiple components acting on multiple targets plays a role in the prevention and treatment of COPD. After evaluating the treatment of cough, dyspnea, and lung distension based on syndrome differentiation in TCM, we summarized the commonly used TCM preparations for treating COPD. These preparations are mainly composed of medicines for clearing interior heat and releasing exterior, tonifying, activating blood and resolving stasis, resolving phlegm, relieving cough and breathlessness, and regulating Qi movement. Because all of them contain a variety of active ingredients such as flavonoids, terpenoids, and phenols, we analyzed the mechanisms of the classic prescriptions alone or in combination with other medicines or therapeutic methods. These mechanisms involve counteracting inflammation, oxidative stress, and fibrosis, inhibiting apoptosis, alleviating airway remodeling, and enhancing immunity. Meantime, we summarized the existing problems in the treatment of COPD by TCM. This review provides a scientific basis for the research and treatment of COPD in the future.

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

In the aerospace industry, the additive manufacturing of aluminum alloys has encountered significant challenges owing to fusion defects. In this work, the B2O3–NaF–SiO2fluxes are employed for the first time to improve the fusion defects and mechanical properties of butt-welded A7N01 alloy with unequal thickness under natural ageing. The finite element analysis (FEA) approach is used to account for the evolution mechanism of residual stresses. The simulated results indicate that the distribution and values of residual compressive stresses are improved, which contribute to the microhardness. After applying a coating-position optimization of the B2O3–NaF–SiO2fluxes, the fluxes plays a role in enhancing the welding current density and increasing the concentration of oxygen elements. The melt pool morphology and the fusion defect of the thicker side are ameliorated, resulting in a considerable increase in the yield strength and the tensile strength. Therefore, this paper establishes the viability of applying B2O3–NaF–SiO2fluxes for additive manufacturing of A7N01 aluminum alloys and provides new ideas for exploring the optimal active fluxes of other 7xxx series aluminum alloys.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with cognitive dysfunction as its major clinical symptom. However, there is no disease-modifying small molecular medicine to effectively slow down progression of the disease. Here, we show an optimized asparagine endopeptidase (AEP, also known as δ-secretase) inhibitor, #11 A, that displays an orderly in vivo pharmacokinetics/pharmacodynamics (PK/PD) relationship and robustly attenuates AD pathologies in a sporadic AD mouse model. #11 A is brain permeable with great oral bioavailability. It blocks AEP cleavage of APP and Tau dose-dependently, and significantly decreases Aβ40 and Aβ42 and p-Tau levels in APP/PS1 and Tau P301S mice after oral administration. Notably, #11 A strongly inhibits AEP and prevents mouse APP and Tau fragmentation by AEP, leading to reduction of mouse Aβ42 (mAβ42), mAβ40 and mouse p-Tau181 levels in Thy1-ApoE4/C/EBPβ transgenic mice in a dose-dependent manner. Repeated oral administration of #11 A substantially decreases mAβ aggregation as validated by Aβ PET assay, Tau pathology, neurodegeneration and brain volume reduction, resulting in alleviation of cognitive impairment. Therefore, our results support that #11 A is a disease-modifying preclinical candidate for pharmacologically treating AD.

Developing efficient catalysts to degrade pollutants in water is a very important way to alleviate water pollution. However, it is crucial but challenging to broaden the functions of conventional photocatalysts and improve their environmental adaptability. In this paper, Bi(Er3+/Yb3+)OBr/polyacrylonitrile (BOB-EY/PAN) composite fibers with a swallowed-embedded structure assembled with nanopetal-rich microflowers were designed and fabricated, integrating photocatalytic and temperature-monitoring functions simultaneously. Their unique structure brings a large specific surface area, and the doping of rare earth ions improves the separation efficiency of electron–hole pairs, which enhances the photocatalytic efficiency and endows the fibers with a temperature-monitoring function at the same time. Under simulated sunlight irradiation, the nanofibers show a maximum degradation efficiency of 99.2% for tetracycline hydrochloride (TC) with a degradation constant of Kas high as 0.078 min–1. Based on the fluorescence intensity ratio (FIR), the two thermally coupled levels of Er3+in the nanofibers, 2H11/2and 4S3/2, provide real-time temperature feedback, displaying a maximum relative sensitivity as high as 0.0215 K–1at 303 K. Dual-functional BOB-EY/PAN composite nanofibers show great potential for industrial wastewater disposition, providing solutions for wastewater purification in special scenarios.

Artificial intelligence (AI) has demonstrated outstanding performance in some perfect- and imperfect-information games, such as Go, Atari, and Texas Hold'em. Even though AI is successful in these games with small action spaces, it does not play well in large-scale multiplayer, imperfect-information games like DouDiZhu. DouZero, a DouDizhu AI system, has recently been proposed and beaten all the existing DouDizhu AI programs. This article introduces minimum split pruning (MSP) and a single Q-network to accelerate the training of DouZero, called MDou. Our experiments show that MDou improved through self-play using limited computational ability (only a 4-core CPU and 1 GPU) and less learning time (30 days), while achieving comparable performance to DouZero.

Edge vision devices face real 3-D scenes with lighting fluctuations. They require a vision chip capable of acquiring 2-D/3-D vision with a high dynamic range and performing real-time intelligent in situ processing, while maintaining low end-to-end latency. Aimed at this versatile edge vision, this article presents a bio-inspired full-spiking vision chip that consists of a single-photon-avalanche-diode (SPAD) image sensor and a spiking vision processor monolithically. To decrease latency while realizing versatile functions, we build a bio-inspired full spiking vision on chip by directly coupling spike-like SPAD imaging with a neuroinspired spike-computing paradigm. By modeling this spiking visual flow, we theoretically demonstrate direct coupling and derive a spike preprocessing method for dim-vision enhancement. The SPAD image sensor equipped with a configurable exposure gating scheme can realize three modes: 2-D, 3-D depth, and dim-vision imaging. The spiking vision processor contains a parallel processing element (PE) array and can be reconfigured as a preprocessor or a spiking neural network (SNN) processor. A prototype chip integrated with a $128 \,\, \times \,\, 128$ SPAD image sensor with a reconfigurable spiking vision processor (256 PEs) was implemented in a 0.18- $\mu \text{m}$ CMOS technology. The chip experimentally demonstrates three imaging modes, 99.30% classification accuracy on the MNIST dataset with 2-D vision, only 3.9% accuracy loss under 0.02 lux with dim-vision, 1.68 cm obstacle detection error with 3-D depth vision, and a 3.58 $\mu \text{s}$ latency for light adaptation. The chip realizes a 100 dB dynamic range, 100 000 spiking maps per second (SMps), and 81.92 GSOPS at an 80-MHz clock.

Israel was the first country to launch COVID-19 boosters, in late July 2021, with strong public health messaging. The booster campaign reversed rising infection rates from the Delta variant and reduced hospitalizations and deaths. The US booster rollout was slower, and public health messaging was mixed. We used the Israeli experience to ask the counterfactual question: How many lives could the US have saved if it had authorized boosters sooner? We estimated that through June 30, 2022, if the US had moved at Israel’s speed and booster take-up percentages, it would have saved 29,000 lives. US regulatory caution, in the middle of a pandemic, thus had a large, avoidable cost. Yet the US booster rollout still avoided 42,000 deaths. Moving more slowly to approve boosters, as some advocated, would have cost many additional lives.

Previous studies on how to prolong the relaxation times of single-molecule magnets (SMMs) focus on mitigating the quantum tunneling effect. However, recent progress shows that Raman relaxation is more critical. Yet, the study of the Raman process turns out to be a barren zone for molecular systems and requires further exploration.

Adoptive chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have shown promise in treating various cancers. However, limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications. Here, we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein (FITC) single-chain variable fragment (scFv) to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors. We next genetically engineer human pluripotent stem cells (hPSCs) with optimized CARs and differentiate them into functional dual CAR-NK cells. The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3 (pSTAT3) and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptor β-chain (ΔIL-2Rβ) and STAT3-binding tyrosine-X-X-glutamine (YXXQ) motif. Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells. Collectively, our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.

Polyradicals, i.e., multispin organic molecules, are playing important roles in radical-based material applications for their spin–spin interaction. A dynamic covalently bonded multispin molecule may endow materials with added function such as memory and switching. However, such a species has yet to be reported. We here report the synthesis, characterization, and crystal structure of a dynamic triradical species. It is generated by the self-assembly of two molecules through a Lewis acid coupled electron transfer. The crystalline species is spin-frustrated without Jahn–Teller distortion at low temperature, while it dissociates back to diamagnetic starting material in solution at high temperature. The reversible process is tracked by variable-temperature NMR, EPR, and UV–vis–NIR spectroscopy. Isolation, property study, and dynamic bonding investigation on such a species lay the foundation for the design of functional polyradicals with potential application as memory or switching devices.

Hematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias, and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has recently been reported to affect hematopoiesis. However, there is currently limited empirical evidence explaining the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed a significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Furthermore, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated the FoxO signaling pathway, and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota composition and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.

Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein (HDL) particles. Here, we showed that the POAG risk allele near ABCA1attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells (RGCs) by using an artificial intelligence (AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing (scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1−/−retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1−/−mice using atorvastatin reduced the cholesterol level in the retina, thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1−/−retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.

Ship detection is essential in ship rescue and marine traffic safety. However, high-speed real-time ship detection has become problematic in practical applications. In this brief, we propose a high-performance ship detection system utilizing the co-design of algorithm and hardware. First, the proposed Coarse-to-Fine Classification and Segmentation algorithm contains a two-stage convolutional neural network. It quickly locates the Region of Interest (RoI) and then accurately locates the ship’s position in the RoI without low-parallelism non-maximum suppression (NMS) post-processing. Second, we proposed a Hierarchical Parallel Vision Processor, including a pixel-parallel processing unit, a patch-parallel processing unit, and a global micro-processing unit, ensuring high-speed processing with different parallelism. Finally, we designed a high-speed real-time ship detection system. The experimental results show that our ship detection system based on the frequency of 100Mhz on Arria 10 FPGA can achieve a speed of 4778FPS, which is beneficial in practical applications.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34+cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34+HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.

A quartz sub-mirror was figure-corrected in a parallel removal process for the first time. An Reactive Ion Figuring (RIF) process with a simple and universal masking method was demonstrated, and the 350-mm quartz sub-mirror was figure-corrected from the initial figure error of ~23 nm RMS to the final figure error of ~8 nm RMS in total effective figuring time of ~52 minutes after 4 iterations, which exhibited the actual potential of RIF on the figure-correction of quartz optical elements and the possibility on applying RIF to meet the requirement of mass production for sub-mirrors of transmissive diffractive segmented telescopes.

Here we use a pseudoallyl ligand, N,N′-chelating amidinate (Am), together with pentamethylcyclopentadienyl (Cp*) to give two dysprosium(III) single-molecule magnets (SMMs): [{(AmiPr)DyCp*(μ-Cl)}2] and [AmdippDyCp*(Cl)(μ-Cl)Li(THF)3] with distinct energy barriers (Ueff) of 97 and 472 K, respectively. The latter Ueffvalue is similar to the homoleptic Cp*-based Dy-SMM.

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting “cold” to “hot” tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.

Two primitive metal-organic frameworks (MOFs), NiL1and NiL2, based on Ni8O6-cluster and ditopic pyrazolate linkers, L1(with rigid alkyne arms) and L2(with flexible alkyne chains), were prepared. The proton conductivities of these MOFs in pristine form and imidazole-encapsulated forms, Im@NiL1and Im@NiL2, were measured and compared. Upon introduction of imidazole molecules, the proton conductivity could be increased by 3 to 5 orders of magnitude and reached as high as 1.72 × 10−2S/cm (at 98% RH and 80 °C). Also, whether imidazole molecules were introduced or not, Ni8O6-based MOFs with L2in general gave better proton conductivity than those with L1signifying that flexible side arms indeed assist proton conduction probably viaestablishment of efficient proton-conducting channels along with formation of highly ordered domains of water/imidazole molecules within the network cavities. Beyond the active Ni8O6-cluster, tuning flexibility of linker pendants serves as an alternative approach to regulate/modulate the proton conductivity of MOFs.