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Abstract Artificial intelligence applications in extreme environments place high demands on hardware robustness, power consumption, and speed. Recently, diffractive neural networks have demonstrated superb advantages in high-throughput light-speed reasoning. However, the robustness and lifetime of existing diffractive neural networks cannot be guaranteed, severely limiting their compactness and long-term inference accuracy. Here, we have developed a millimeter-scale and robust bilayer-integrated diffractive neural network chip with virtually unlimited lifetime for optical inference. The two diffractive layers with binary phase modulation were engraved on both sides of a quartz wafer. Optical inference of handwritten digital recognition was demonstrated. The results showed that the chip achieved 82% recognition accuracy for ten types of digits. Moreover, the chip demonstrated high-performance stability at high temperatures. The room-temperature lifetime was estimated to be 1.84×1023 trillion years. Our chip satisfies the requirements for diffractive neural network hardware with high robustness, making it suitable for use in extreme environments.

Sodium-glucose cotransporter 2 inhibitors are a class of glucose-lowering drugs known for robust cardiovascular protective properties. However, the side effects induced by Sodium-glucose cotransporter 2 inhibition limit application in cardiovascular medicine. Our prior research showed that thoughtful structural modifications can dissociate the anti-heart failure activity from glucose-lowering effects. Moreover, we showed that the glyceraldehyde derivative, JX22, developed by scaffold hopping from empagliflozin, exhibits a superior cardiomyocyte protective effect, albeit with increased cytotoxicity compared to empagliflozin. In the current study systematic structural modifications of JX22 were performed to enhance anti-heart failure efficacy and safety, while reducing glucose-lowering activity. Twenty glyceraldehyde-based derivatives were synthesized and compound 12 emerged as an optimal candidate by exhibiting an improved cytoprotective effect compared to JX22. Compound 12 significantly inhibited the activity of NHE1 on the myocardial membrane, thereby maintaining intracellular ion homeostasis. In vivo efficacy results demonstrated that compound 12 at 10 mg/kg significantly ameliorated cardiac dysfunction, myocardial fibrosis, and exercise tolerance in isoproterenol-induced heart failure mice without a glucose-lowering effect. Furthermore, compound 12 exhibited favorable safety profiles in single-dose toxicity and hERG inhibition tests, along with promising pharmacokinetic properties in mice. The current study not only underscores the potential of compound 12 for further investigation but also highlights the effectiveness of the scaffold hopping strategy.

In the long-term accumulation process, coal gangue can lead to severe consequences such as spontaneous combustion and explosions due to external factors. Additionally, the coal gangue that ignites spontaneously significantly pollutes the land and groundwater, causing serious risks to the health and safety of individuals living and working in the vicinity. Therefore, to mitigate the risk of spontaneous combustion resulting from the long-term accumulation of coal gangue, a monitoring system based on LoRa wireless communication technology is proposed to collect and monitor the internal temperature of coal gangue mountains in real time. In the laboratory, active temperature rise monitoring was conducted on the simulated coal gangue pile to effectively observe the range of temperature diffusion. Simultaneously, field tests were performed in the coal gangue mountain at the coal mine. The laboratory simulation and field test results demonstrate that the system can effectively monitor the internal temperature changes of the gangue mountain, particularly within the horizontal range of 0–0.2 m near the heat source and the vertical range of 0–0.3 m. In addition, the system test indicates that the maximum effective transmission distance for penetration between the main control station and the node is 8 m, while the distance between the nodes is 7.14 m. The system demonstrates strong feasibility for monitoring and providing early warnings regarding the internal temperature of the coal gangue mountain.

Abstract Machine learning with optical neural networks has featured unique advantages of the information processing including high speed, ultrawide bandwidths and low energy consumption because the optical dimensions (time, space, wavelength, and polarization) could be utilized to increase the degree of freedom. However, due to the lack of the capability to extract the information features in the orbital angular momentum (OAM) domain, the theoretically unlimited OAM states have never been exploited to represent the signal of the input/output nodes in the neural network model. Here, we demonstrate OAM-mediated machine learning with an all-optical convolutional neural network (CNN) based on Laguerre-Gaussian (LG) beam modes with diverse diffraction losses. The proposed CNN architecture is composed of a trainable OAM mode-dispersion impulse as a convolutional kernel for feature extraction, and deep-learning diffractive layers as a classifier. The resultant OAM mode-dispersion selectivity can be applied in information mode-feature encoding, leading to an accuracy as high as 97.2% for MNIST database through detecting the energy weighting coefficients of the encoded OAM modes, as well as a resistance to eavesdropping in point-to-point free-space transmission. Moreover, through extending the target encoded modes into multiplexed OAM states, we realize all-optical dimension reduction for anomaly detection with an accuracy of 85%. Our work provides a deep insight to the mechanism of machine learning with spatial modes basis, which can be further utilized to improve the performances of various machine-vision tasks by constructing the unsupervised learning-based auto-encoder.

Secret sharing is a promising technology for information encryption by splitting the secret information into different shares. However, the traditional scheme suffers from information leakage in decryption process since the amount of available information channels is limited. Herein, we propose and demonstrate an optical secret sharing framework based on the multi-dimensional multiplexing liquid crystal (LC) holograms. The LC holograms are used as spatially separated shares to carry secret images. The polarization of the incident light and the distance between different shares are served as secret keys, which can significantly improve the information security and capacity. Besides, the decryption condition is also restricted by the applied external voltage due to the variant diffraction efficiency, which further increases the information security. In implementation, an artificial neural network (ANN) model is developed to carefully design the phase distribution of each LC hologram. With the advantage of high security, high capacity and simple configuration, our optical secret sharing framework has great potentials in optical encryption and dynamic holographic display.

Abstract Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.

Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography–tandem mass spectrometry (LC–MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.

The orbital angular momentum (OAM) of light has been implemented as an information carrier in OAM holography. Holographic information can be multiplexed in theoretical unbounded OAM channels, promoting the applications of optically addressable dynamic display and high-security optical encryption. However, the frame-rate of the dynamic extraction of the information reconstruction process in OAM holography is physically determined by the switching speed of the incident OAM states, which is currently below 30 Hz limited by refreshing rate of the phase-modulation spatial light modulator (SLM). Here, based on a cross convolution with the spatial frequency of the OAM-multiplexing hologram, the spatial frequencies of an elaborately-designed amplitude distribution, namely amplitude decoding key, has been adopted for the extraction of three-dimensional holographic information encoded in a specific OAM information channel. We experimentally demonstrated a dynamic extraction frame rate of 100 Hz from an OAM multiplexing hologram with 10 information channels indicated by individual OAM values from –50 to 50. The new concept of cross convolution theorem can even provide the potential of parallel reproduction and distribution of information encoded in many OAM channels at various positions which boosts the capacity of information processing far beyond the traditional decoding methods. Thus, our results provide a holographic paradigm for high-speed 3D information processing, paving an unprecedented way to achieve the high-capacity short-range optical communication system.

Abstract Conjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to significantly inhibit the growth of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that fangchinoline suppressed the homologous recombination (HR)-directed DNA repair by binding with far upstream element binding protein 2 (FUBP2) and downregulating the expression of HR factors BRCA1 and RAD51. In vitro and in vivo antitumour experiments revealed that fangchinoline increased the efficacy of cisplatin by blocking HR factors and reduced the drug dose and toxicity. In conclusion, our work provides a promising therapeutic strategy for the treatment of CM that is worthy of extensive preclinical investigation.

Frequency conversion such as harmonic generation is a fundamental physical process in nonlinear optics. The conventional nonlinear optical systems suffer from bulky size and cumbersome phase-matching conditions due to the inherently weak nonlinear response of natural materials. Aiming at the manipulation of nonlinear frequency conversion at the nanoscale with favorable conversion efficiencies, recent research has shifted toward the integration of nonlinear functionality into nanophotonics. Compared with plasmonic nanostructures showing high dissipative losses and thermal heating, all-dielectric nanostructures have demonstrated many excellent properties, including low loss, high damage threshold, and controllable resonant electric and magnetic optical nonlinearity. In this review, we cover the recent advances in nonlinear nanophotonics, with special emphasis on third- and second-harmonic generation from all-dielectric nanoantennas and metasurfaces. We discuss the main theoretical concepts, the design principles, and the functionalities of third- and second-harmonic generation processes from dielectric nanostructures and provide an outlook on the future directions and developments of this research field.

Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting β-amyloid (Aβ) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD. Key words: Alzheimer's disease, Autophagy, Nitazoxanide, β-amyloid, Tau protein

Background: This meta-analysis aimed to assess the efficacy and safety of ginkgo terpene lactone preparations including ginkgo diterpene lactone meglumine injection, ginkgolide injection, and ginkgolide B injection for ischemic stroke (IS).Methods: We searched the randomized controlled trials (RCTs) with publication date earlier than 31 August 2021 in PubMed, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), Chinese Biomedical Literature Database (CBM), Wanfang Database, Embase, and the Cochrane Library. RevMan 5.3 software was applied to analyze the data and generate the forest plot and funnel plot. Meanwhile, publication bias was also assessed by Egger’s test with STATA 12 software.Results: A total of 28 RCTs were eligible for inclusion. Among them, 23 RCTs were used to evaluate the efficacy of ginkgo terpene lactone preparations as the main treatment intervention for IS. To be specific, ginkgo diterpene lactone meglumine injection was superior to control drug in improving clinical efficacy [RR = 1.18, 95% CI (1.12, 1.24), Z = 6.36, p < 0.001] and neurological function [MD = −1.42, 95% CI (−1.91, −0.93), Z = 5.66, p < 0.001]. However, the effectiveness of the ginkgolide B injection group was equivalent to that of the control group. Additionally, ginkgolide injection achieved better clinical efficacy [RR = 1.10, 95% CI (1.02, 1.18), Z = 2.36, p = 0.02], but the changes of neurological function deficit was not obviously different between two groups [MD = −0.43, 95% CI (−4.32, 3.46), Z = 0.22, p = 0.83]. Furthermore, meta-analysis of five trials on ginkgo diterpene lactone meglumine injection combined with recombinant tissue plasminogen activator (rt-PA) thrombolytic therapy for acute IS showed that combination therapy was better in improving clinical efficacy [OR = 1.91, 95% CI (1.13, 3.22), Z = 2.41, p = 0.02] and neurological function [MD = −3.31, 95% Cl (−3.64,−2.98), Z = 19.63, p < 0.001]. Importantly, no serious adverse drug reactions/adverse drug events (ADRs/ADEs) were reported.Conclusion: Ginkgo terpene lactone preparations have good therapeutic effects on patients with IS. For acute IS, ginkgo diterpene lactone meglumine injection can be used as a complementary therapy to improve the clinical efficacy of rt-PA.

Bidens plants are annuals or perennials of Asteraceae and usually used as medicinal materials in China. They are difficult to identify by using traditional identification methods because they have similar morphologies and chemical components. Universal DNA barcodes also cannot identify Bidens species effectively. This situation seriously hinders the development of medicinal Bidens plants. Therefore, developing an accurate and effective method for identifying medicinal Bidens plants is urgently needed. The present study aims to use phylogenomic approaches based on organelle genomes to address the confusing relationships of medicinal Bidens plants. Illumina sequencing was used to sequence 12 chloroplast and eight mitochondrial genomes of five species and one variety of Bidens. The complete organelle genomes were assembled, annotated and analysed. Phylogenetic trees were constructed on the basis of the organelle genomes and highly variable regions. The organelle genomes of these Bidens species had a conserved gene content and codon usage. The 12 chloroplast genomes of the Bidens species were 150,489 bp to 151,635 bp in length. The lengths of the eight mitochondrial genomes varied from each other. Bioinformatics analysis revealed the presence of 50–71 simple sequence repeats and 46–181 long repeats in the organelle genomes. By combining the results of mVISTA and nucleotide diversity analyses, seven candidate highly variable regions in the chloroplast genomes were screened for species identification and relationship studies. Comparison with the complete mitochondrial genomes and common protein-coding genes shared by each organelle genome revealed that the complete chloroplast genomes had the highest discriminatory power for Bidens species and thus could be used as a super barcode to authenticate Bidens species accurately. In addition, the screened highly variable region trnS-GGA-rps4 could be also used as a potential specific barcode to identify Bidens species.

The root of Bupleurum marginatum var. stenophyllum (H. Wolff) Shan & Yin Li (Apiaceae), a new substitution for the popular Chinese medicinal material, Bupleuri Radix (Chai hu), is not easily distinguishable via traditional methods. The complete chloroplast genome sequence of B. marginatum var. stenophyllum was characterized using next-generation sequencing and the de novo assembly method. The complete genome was 155,576 bp in length and contained two inverted repeat (IR) regions of 26,311 bp, a large single-copy (LSC) region of 85,351 bp, and a small single-copy (SSC) region of 17,603 bp. It encoded 113 unique genes consisting of 79 protein-coding genes (PCGs), 30 transfer RNA genes, and four ribosomal RNA genes. Importantly, three genes (petB, petD and rps16) with small exon, and one trans-splicing gene (rps12) were correctly annotated. The overall GC content of the B. marginatum var. stenophyllum chloroplast genome is 37.7%. The phylogenetic analyses indicated that B. marginatum var. stenophyllum was closely related to B. marginatum. Moreover, many genetic information sites were available for distinguishing B. marginatum var. stenophyllum from the official ‘Chai hu’ plant sources, B. scorzonerifolium Willd. and B. chinense DC.

With the widespread use of traditional medicine around the world, the safety and efficacy of traditional herbal patent medicine have become an increasing concern to the public. However, it is difficult to supervise the authenticity of herbal materials in mixed herbal products according to the current quality standards, especially for traditional herbal patent medicine, with a distinct variance in the dosage of herbal materials. This study utilized the shotgun metabarcoding approach to analyze the biological ingredients of Fuke Desheng Wan (FKDSW), which is an effective traditional herbal product for the treatment of dysmenorrhea. Six herbal materials were collected, and a lab-made mock FKDSW sample was produced to establish a method for the authentication assessment of biological ingredients in traditional herbal patent medicine based on shotgun metabarcoding. Furthermore, four commercial FKDSW samples were collected to verify the practicality of the shotgun metabarcoding approach. Then, a total of 52.16 Gb raw data for 174 million paired-end reads was generated using the Illumina NovaSeq sequencing platform. Meanwhile, 228, 23, and 14 operational taxonomic units (OTUs) were obtained for the ITS2, matK, and rbcL regions, respectively, after bioinformatic analysis. Moreover, no differences were evident between the assembly sequences obtained via shotgun metabarcoding and their corresponding reference sequences of the same species obtained via Sanger sequencing, except for part of the ITS2 and matK assembly sequences of Paeonia lactiflora Pall., Saussurea costus (Falc.) Lipsch. and Bupleurum chinense DC. with 1–6 different bases. The identification results showed that all six prescribed ingredients were successfully detected and that the non-authentic ingredient of Bupleuri Radix (Chaihu, Bupleurum chinense DC. or Bupleurum scorzonerifolium Willd.) was found in all the commercial samples, namely Bupleurum falcatum L. Here, 25 weed species representing 16 genera of ten families were detected. Moreover, 26 fungal genera belonging to 17 families were found in both lab-made and commercial FKDSW samples. This study demonstrated that the shotgun metabarcoding approach could overcome the biased PCR amplification and authenticate the biological ingredients of traditional herbal patent medicine with a distinct variance in the dosage of the herbal materials. Therefore, this provides an appropriate evaluation method for improving the safety and efficacy of traditional herbal patent medicine.

Aberrant Notch signaling profoundly affects cancer progression. Especially the Notch3 receptor was found to be dysregulated in cancer, where its expression is correlated with worse clinicopathological features and poor prognosis. The activation of Notch3 signaling is closely related to the activation of cancer stem cells (CSCs), a small subpopulation in cancer that is responsible for cancer progression. In addition, Notch3 signaling also contributes to tumor chemoresistance against several drugs, including doxorubicin, platinum, taxane, epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) and gemcitabine, through complex mechanisms. In this review, we mainly focus on discussing the molecular mechanisms by which Notch3 modulates cancer stemness and chemoresistance, as well as other cancer behaviors including metastasis and angiogenesis. What’s more, we propose potential treatment strategies to block Notch3 signaling, such as non-coding RNAs, antibodies and antibody-drug conjugates, providing a comprehensive reference for research on precise targeted cancer therapy.

As one of the high-incidence diseases in the world, pharyngitis seriously affects the lives of those with the condition. Qingguo Wan is a herbal medicine used for treating pharyngitis, and its quality evaluation is currently only accomplished via traditional identification. However, precise identification becomes challenging with fake products on the market or fungal contamination during the production process. This study used the Illumina NovaSeq platform for targeting the ITS2, psbA-trnH, matK, and rbcL sequences to survey the species composition of lab-made and commercial samples. The results showed that a total of 34.56 Gb of raw data that was obtained represented more than 0.23 billion reads. After assembly, annotation, and operational taxonomic unit clustering, 103, 12, 10, and 12 OTUs were obtained, which belonged to the ITS2, psbA-trnH, matK, and rbcL sequences of the mock lab-made and commercial samples. The analytical results indicated that the sequences of all the prescription ingredients were successfully obtained in the two lab-made samples. The positive control medicinal Panax quinquefolius L. sequence was obtained in HSZY175, while Scutellaria baicalensis Georgi, Lonicera japonica Thunb. Menispermum dauricum DC. and Paeonia lactiflora Pall. were detected in the three commercial samples. The detection results of the other four herbs in different fragments were not all the same. In addition, a total of 28 fungi OTUs, representing 19 families and 20 genera, were obtained from both the commercial and mock lab-made samples. Aspergillus, Cladosporium, and Penicillium dominated among the 20 genera. This study demonstrated that the shotgun metabarcoding method is a powerful tool for the molecular identification of the biological ingredients in Qingguo Wan. It can be used to effectively supplement traditional methods while providing a new technique for the quality evaluation of Qingguo Wan.

The energy consumption of a vehicle is closely related to the resistance it receives, and it is of great significance to study the drag reduction of a vehicle to promote energy conservation and emissions reductions. Boundary layer control drag reduction is mainly achieved by controlling the coherent structure in turbulence and reducing its burst intensity and frequency. It can be divided into an active control drag reduction and passive control drag reduction. In passive drag reduction, the advantages of the surface groove drag reduction are relatively obvious. In this paper, the large eddy simulation method is used to study the boundary layer flow with triangular groove and rectangular groove plates along the flow direction under subsonic flow, and to explore the influence of a surface micro-groove structure on the boundary layer flow. The simulation results show that the fluid inside the groove can be blocked by the triangular groove which can keep the low-velocity fluid at the bottom of the groove, and that it can increase the thickness of the viscous bottom layer as well as reduce the velocity gradient at the wall. The spanwise stress component of the Reynolds stress in the triangular groove boundary layer and the burst of turbulence on the wall are inhibited, and the spanwise flow in the boundary layer is blocked. In the subsonic range, about 10% shear force can be reduced because there are secondary vortices induced by the upper flow vortices at the top of the groove wall, and these secondary vortices can restrain the rising of the low-speed strip in the groove and reduce the burst of turbulence. The rectangular groove creates a weak blocking effect on the fluid inside the groove, which can only inhibit spanwise pulsation under subsonic speed. The wall shear stress cannot be reduced when the flow velocity is low, and it even increases.

Abstract Background Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. Methods CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. Results Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. Conclusions Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.