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Linking outbreaks of Shigella spp. to specific foods is challenging due to poor selectivity of current enrichment media. We have previously shown that enrichment media, tailored to the genomically-predicted antimicrobial resistance (AMR) of Shiga toxigenic E. coli strains, enhances their isolation from foods. This study investigates the application of this approach for Shigella isolation. The AMR gene profiles of 21,908 published S. sonnei genomes indicated a high prevalence of genes conferring resistance to streptomycin (aadA, aph(3″)-Ib, aph(6)-Id, 92.8%), sulfonamides (sul1, sul2, 74.8%), and/or trimethoprim (dfrA, 96.2%). Genomic analysis and antibiotic susceptibility testing conducted with a panel of 17 outbreak-associated S. sonnei strains confirmed the correlation of AMR gene detection with resistance phenotypes. Supplementation of Shigella Broth (SB) with up to 400 µg/mL of trimethoprim or sulfadiazine did not suppress the growth of sensitive strains, whereas 100 µg/mL of streptomycin increased the selectivity of this broth. All three antibiotics increased the selectivity of modified Tryptone Soya Broth (mTSB). Based on these results, supplemented media formulations were developed and assessed by measuring the relative growth of S. sonnei in cultures coinoculated with a strain of bacteriocin-producing E. coli that is inhibitory to Shigella growth. S. sonnei was not recovered from cocultures grown in SB or mTSB without antibiotics. In contrast, media supplemented with streptomycin at 50 and 100 µg/mL, trimethoprim at 25 and 50 µg/mL, and sulfadiazine at 100 µg/mL increased the relative proportion of S. sonnei in postenrichment cultures. The enhanced recovery of resistant S. sonnei strains achieved in this study indicates that, in cases where genomic data are available for clinical S. sonnei isolates, customization of selective enrichment media based on AMR gene detection could be a valuable tool for supporting the investigation of foodborne shigellosis outbreaks.

Shigella spp. are Gram-negative gastrointestinal bacterial pathogens that cause bacillary dysentery or shigellosis in humans. Isolation of Shigella from outbreak-associated foods is often problematic due to the lack of selectivity of cultural enrichment broths. To facilitate Shigella recovery from foods, we have developed strain-specific enrichment media based on the genomically-predicted antimicrobial resistance (AMR) features of an outbreak-associated Shigella sonnei strain harboring resistance genes for streptomycin (STR) and trimethoprim (TMP). To assess performance of the method, baby carrots were artificially contaminated with the S. sonnei strain at low (2.4 CFU), medium (23.5 CFU), and high levels (235 CFU) along with 10-fold higher levels of a Shigella-inhibiting Escherichia coli strain. The target S. sonnei strain was successfully recovered from artificially-contaminated baby carrots when enriched in modified Tryptone Soya Broth (mTSB) supplemented with TMP, whereas Shigella was not recovered from Shigella broth (SB) or SB supplemented with STR. Quantitative PCR analysis indicated that supplementation of the enrichment broths with TMP or STR increased the relative proportion of S. sonnei in enrichment cultures, except at the lowest inoculation level for STR. Microbiome profiling of the baby carrot enrichment cultures conducted by 16S rRNA gene sequencing indicated that both SB-STR and mTSB-TMP repressed the growth of competing Enterobacteriaceae in the enrichment cultures, relative to SB without supplementation. Overall, improved Shigella recovery was achieved with the addition of the appropriate custom selective agent during cultural enrichments demonstrating that genomically informed custom selective enrichment of Shigella could be a valuable tool for supporting future foodborne shigellosis outbreak investigations.

Abstract Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). In parallel, the mice with myeloid Lamtor5 ablation developed SLE‐like manifestation. Impaired lysosomal function and aberrant activation of mTORC1 are evidenced in Lamtor5 deficient macrophages and PBMCs of SLE patients, accompanied by blunted autolysosomal pathway and undesirable inflammatory responses. Mechanistically, it is shown that Lamtor5 is physically associated with ATP6V1A, an essential subunit of vacuolar H+‐ATPase (v‐ATPase), and promoted the V0/V1 holoenzyme assembly to facilitate lysosome acidification. The binding of Lamtor5 to v‐ATPase affected the lysosomal tethering of Rag GTPase and weakened its interaction with mTORC1 for activation. Overall, Lamtor5 is identified as a critical factor for immune homeostasis by intergrading v‐ATPase activity, lysosome function, and mTOR pathway. The findings provide a potential therapeutic target for SLE and/or other autoimmune diseases.

Over the past decade, orbital angular momentum has garnered considerable interest in the field of plasmonics owing to the emergence of surface-confined vortices, known as plasmonic vortices. Significant progress has been made in the generation and manipulation of plasmonic vortices, which broadly unveil the natures of plasmonic spin–orbit coupling and provide accessible means for light–matter interactions. However, traditional characterizations in the frequency domain miss some detailed information on the plasmonic vortex evolution process. Herein, an exotic spin–orbit coupling phenomenon is demonstrated. More specifically, we theoretically investigated and experimentally verified a temporally deuterogenic vortex mode, which can be observed only in the time domain and interferes destructively in the intensity field. The spatiotemporal evolution of this concomitant vortex can be tailored with different designs and incident beams. This work extends the fundamental understanding of plasmonic spin–orbit coupling and provides a unique optical force manipulation strategy, which may fuel plasmonic research and applications in the near future.

Megalurothrips usitatus (Bagnall) feeds on the young tissues of plants, causing wilting and deformity of leaves as well as damage to flowers and fruits, thereby seriously affecting plant yield. Due to its small size and difficulty of control, the species is one of the most important pests in the legume family. To clarify the occurrence and damage pattern of M. usitatus on field crops, a study was conducted using eight different crops as experimental materials, and an age-stage, two-sex life table was constructed. The population density of M. usitatus was the highest on cowpeas (Vigna unguiculata L. Walp.), followed by green beans (Phaseolus vulgaris L.) and Vigna cylindrica (Vigna unguiculata subsp. cylindrica (L.) Verdc.) in terms of net reproductive rate and the intrinsic rate of increase. In terms of reproductive capacity, cowpeas and V. cylindrica were more suitable for M. usitatus growth and reproduction, followed by green beans. M. usitatus could develop into adults on courgettes (Cucurbita pepo L.), wax gourds (Benincasa hispida Thunb. Cogn.), Momordica charantia (Momordica charantia L.), and soybeans (Glycine max L. Merr.) but had difficulty reproducing on those plants. Cucumber (Cucumis sativus L.) was the least suitable for the survival of M. usitatus. Population parameter analysis showed that the cowpea was the most suitable host plant for M. usitatus, followed by green beans and V. cylindrica. M. usitatus had difficulty reproducing on courgette, wax gourd, M. charantia, and soybeans, and feeding on cucumbers inhibited M. usitatus development and reproduction.

Amidoxime-functionalized hydrogels are one of most promising adsorbents for high-efficiency uranium (U) extraction from seawater, but bioadhesion on their surface seriously decreases their adsorption efficiency and largely shortens their service life. Herein, a semi-interpenetrating zwitterion–poly(amidoxime) (ZW-PAO) hydrogel was explored through introducing a PAO polymer into a poly [3-(dimethyl 4-vinylbenzyl amino) propyl sulfonate] (PDVBAP) polyzwitterionic (PZW) network via ultraviolet (UV) polymerization. Owing to the anti-polyelectrolyte effect of the PZW network, this ZW-PAO hydrogel can provide excellent super-hydrophilicity in seawater for high-efficiency U-adsorption from seawater. Furthermore, the ZW-PAO hydrogel had outstanding anti-biofouling performance for both highly enhanced U-adsorption and a relatively long working life in natural seawater. As a result, during only 25 days in seawater (without filtering bacteria), the U-uptake amount of this ZW-PAO hydrogel can reach 9.38 mg/g and its average rate can reach 0.375 mg/(g∙day), which is excellent among reported adsorbents. This work has explored a promising hydrogel for high-efficiency U-recovery from natural seawater and will inspire new strategy for U-adsorbing materials.

This study aims to compare the effects of three calcium compounds on the workability, setting time and mechanical properties of red mud (RM)–blast furnace slag (BFS)-based geopolymers. The crystalline phase, hydration process and microstructure of RM-BFS-based geopolymers were characterized by X-ray diffraction (XRD), heat evolution, X-ray photoelectron spectroscopy (XPS), and scanning electron microscope (SEM) tests. The results showed that an appropriate amount of calcium compounds can improve the flowability and compressive strength of the geopolymers, but the excessiveness causes a decrease in strength due to rapid hardening. Other than calcium carbonate, both calcium oxide and calcium chloride played important roles in accelerating the setting times of RM-BFS-based geopolymers. The acceleration in the setting times of geopolymers could be attributed to the calcium hydroxide produced by the dissolution of the calcium compounds, which also provides nucleation sites for the geopolymerization reaction. This study gives new insights into the effect of calcium on the setting times and mechanical properties of geopolymers in the geopolymerization process.

Abstract Human astroviruses (HAstV) are etiologic agents of acute gastroenteritis that most often afflict young children and elderly adults. Most studies of HAstV have focused on epidemiology. In this study, we collected 10 stool samples from a diarrhea outbreak from a diarrhea sentinel surveillance hospital in Beijing. Samples were evaluated immediately using parallel multiplex RT-qPCR and nanopore sequencing, and were then amplified by designed primers and Sanger sequencing to obtain whole genome sequences. Six isolates were categorized as HAstV-5 and subjected to whole genome analysis to characterize their genetic variation and evolution. Full genome analysis revealed low genetic variation (99.38–100% identity) among isolates. Phylogenetic analysis showed that all isolates were closely related to domestic strains Yu/1-CHN and 2013/Fuzhou/85. The recombination breakpoint of the six isolates was located at 2741 bp in the overlap region of ORF1a and ORF1b, similar to those of Yu/1-CHN and 2013/Fuzhou/85. Overall, our study highlights the combined use of RT-qPCR and sequencing as an important tool in rapid diagnosis and acquisition of whole genome sequences of HAstV.

Abstract Background Hydrocephalus is a frequent complication of tuberculous meningitis (TBM), and ventriculoperitoneal shunt (VPS) has been shown to improve short-term prognosis for patients with TBM-associated hydrocephalus. However, questions remain about long-term prognosis and shunt-related complications. This study aims to provide a comprehensive assessment of both long-term prognosis and shunt-related complications in patients with TBM-induced hydrocephalus who have undergone VPS treatment. Methods This retrospective study analyzed the clinical data of TBM patients with hydrocephalus treated with VPS at Peking Union Medical College Hospital between December 1999 and February 2023. Both short-term outcomes at discharge and long-term outcomes during follow-up were examined. Prognosis and shunt-related complications were assessed using the modified Rankin Scale (mRS) and the Activity of Daily Living (ADL) score to evaluate neurological function and autonomic living ability, respectively. Results A total of 14 patients with TBM-associated hydrocephalus were included in this study. Of these, 92.9% (13/14) exhibited favorable short-term outcomes, while 57.1% (8/14) showed positive long-term outcomes. Initial results indicated 6 complete recoveries (CR), 7 partial recoveries (PR), and 1 treatment failure. No catheter-related complications were observed initially. Long-term results included 4 CRs, 4 PRs, and 6 treatment failures. A variety of shunt surgery-related complications were noted, including three instances of catheter obstruction, one of incision infection, one of catheter-related infection, one of acute cerebral infarction, and one of transient peritoneal irritation accompanied by diarrhea. Conclusions VPS appears to be an effective and well-tolerated treatment for TBM-associated hydrocephalus, efficiently alleviating acute intracranial hypertension. Nonetheless, continuous long-term monitoring and proactive management are essential to mitigate the risk of catheter-related complications.

Abstract Background This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area. Methods We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1β, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software. Results A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1β: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6–9). Conclusions This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS. PROSPERO registration number CRD42022368744.

Objective To evaluate the effects of acupuncture on physical function, depression and quality of life in stroke patients. Methods A systematic search of the publicly available databases such as the Cochrane Library, PubMed, Embase, China Knowledge Network (CNKI), Wan Fang Data, VIP Database (VIP) and China Biomedical Literature Database (CBM) was conducted, and randomized controlled trials on the use of acupuncture in stroke patients from its inception to April 10, 2023 were included for the Meta analysis. Results Thirteen studies were included. The results showed that acupuncture could promoted recovery of limb function ［MD=6. 86, 95%CI (5. 63, 8. 08), P＜0. 01］, improved depressive symptoms common in post-stroke patients ［MD=-6. 95, 95%CI (-9. 32, -4. 57), P＜0. 01］, and improved patients' quality of life ［SMD=1. 83, 95%CI (1. 63, 2. 04), P＜0. 01］. Conclusion Acupuncture can not only promote the recovery of limb function, but also improve depressive symptoms common in post-stroke patients and enhance their quality of life. (目的 评价针灸对卒中患者肢体功能、抑郁症状和生活质量的干预效果。方法 系统检索the Cochrane Library、Pub Med、Embase、中国知网(CNKI)、万方数据库(Wan Fang Data)、维普数据库(VIP)和中国生物医学文献数据库(CBM)从建库至2023年4月10日公开发表的关于针灸应用于卒中患者的随机对照试验。结果 最终纳入13篇文献。结果表明, 针灸在促进患者肢体功能的恢复［MD=6. 86, 95%CI(5. 63, 8. 08), P＜0. 01］, 改善卒中后患者常见的抑郁症状［MD=-6. 95, 95%CI(-9. 32, -4. 57), P＜0. 01］, 提升患者生活质量［SMD=1. 83, 95%CI(1. 63, 2. 04), P＜0. 01］方面优于对照组。结论 针灸不仅可以促进患者肢体功能的恢复, 而且可以改善卒中后患者常见的抑郁症状, 提升患者生活质量。)

Flower endophytic fungi play a major role in plant reproduction, stress resistance, and growth and development. However, little is known about how artificial cultivation affects the endophytic fungal community found in the tepals of rare horticultural plants. In this research, we used high-throughput sequencing technology combined with bioinformatics analysis to reveal the endophytic fungal community of tepals in Lirianthe delavayi and the effects of artificial cultivation on the community composition and function of these plants, using tepals of L. delavayi from wild habitat, cultivated campus habitat, and cultivated field habitat as research objects. The results showed that the variety of endophytic fungi in the tepals of L. delavayi was abundant, with a total of 907 Amplicon sequencing variants (ASVs) obtained from all the samples, which were further classified into 4 phyla, 23 classes, 51 orders, 97 families, 156 genera, and 214 species. We also found that artificial cultivation had a significant impact on the community composition of endophytic fungi. Although there was no significant difference at the phylum level, with Ascomycota and Basidiomycota being the main phyla, there were significant differences in dominant and unique genera. Artificial cultivation has led to the addition of new pathogenic fungal genera, such as Phaeosphaeria, Botryosphaeria, and Paraconiothyrium, increasing the risk of disease in L. delavayi. In addition, the abundance of the endophytic fungus Rhodotorula, which is typical in plant reproductive organs, decreased. Artificial cultivation also altered the metabolic pathways of endophytic fungi, decreasing their ability to resist pests and diseases and reducing their ability to reproduce. A comparison of endophytic fungi in tepals and leaves revealed significant differences in community composition and changes in the endophytic diversity caused by artificial cultivation. To summarize, our results indicate that endophytic fungi in the tepals of L. delavayi mainly consist of pathogenic and saprophytic fungi. Simultaneously, artificial cultivation introduces a great number of pathogenic fungi that alter the metabolic pathways associated with plant resistance to disease and pests, as well as reproduction, which can increase the risk of plant disease and reduce plant reproductive capacity. Our study provides an important reference for the conservation and breeding of rare horticultural plants.

Piezoelectric materials, which exhibit a charge distribution across the surfaces in reaction to mechanical strain, find significant utility in actuation and sensing applications. Apart from actuation applications like acoustic devices, motors, and vibration damping, an emerging domain for ultrasonic actuators lies in additive manufacturing processes. Ultrasonic waves applied during solidification aim to modulate grain structure and minimize defects. This research focuses on a fixture designed to facilitate and optimize ultrasonic wave propagation through the build plate in laser powder bed fusion additive manufacturing by utilizing a piezoelectric transducer. Three implementations of piezoelectric transducers were evaluated based on their out-of-plane ultrasonic velocity transmissions. It was determined that a thin plate adhered to the surface of the piezoelectric transducer yielded the most favorable outcomes for implementation, achieving 100% transmission of velocity and energy. Preliminary analysis of melt pool morphology and defects in single-track laser scanning experiments demonstrated the impact of ultrasound on solidification, hinting at a novel approach to enhancing the printability of alloys in laser powder bed fusion additive manufacturing processes. The optimal fixture and the explored transducing efficiency could further guide advanced ultrasound testing to enable in situ defect and texture detection during the additive manufacturing processes.

The rubber blends for rubber roller were prepared with natural rubber, styrene-butadiene rubber and trans-1,4-poly(butadiene-co-isoprene) rubber, the effects of trans-1,4-poly(butadiene-co-isoprene) rubber amount on the compatibility, curing characteristics, mechanical properties, wear resistance and aging resistance of the blends were investigated. The results showed that as the trans-1,4-poly(butadiene-co-isoprene) rubber amount increased from 0 to 20 phr (mass), the crosslinking density of the blend increased gradually and curing time shortened, tensile strength increased gradually, hardness increased slightly, compression permanent set showed a downward trend, and wear resistance improved. The compatibility of the three rubbers was good, and the dispersion of filler and aging resistance of the blending rubber were improved.

Abstract Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

Abstract Background Single-cell RNA sequencing (scRNA-seq) enables the high-throughput profiling of gene expression at the single-cell level. However, overwhelming dropouts within data may obscure meaningful biological signals. Various imputation methods have recently been developed to address this problem. Therefore, it is important to perform a systematic evaluation of different imputation algorithms. Results In this study, we evaluated 11 of the most recent imputation methods on 12 real biological datasets from immunological studies and 4 simulated datasets. The performance of these methods was compared, based on numerical recovery, cell clustering and marker gene analysis. Most of the methods brought some benefits on numerical recovery. To some extent, the performance of imputation methods varied among protocols. In the cell clustering analysis, no method performed consistently well across all datasets. Some methods performed poorly on real datasets but excellent on simulated datasets. Surprisingly and importantly, some methods had a negative effect on cell clustering. In marker gene analysis, some methods identified potentially novel cell subsets. However, not all of the marker genes were successfully imputed in gene expression, suggesting that imputation challenges remain. Conclusions In summary, different imputation methods showed different effects on different datasets, suggesting that imputation may have dataset specificity. Our study reveals the benefits and limitations of various imputation methods and provides a data-driven guidance for scRNA-seq data analysis.

Designing and developing photocatalysts with excellent performance in order to achieve efficient hydrogen production is an important strategy for addressing future energy and environmental challenges. Traditional single-phase photocatalytic materials either have a large bandgap and low visible light response or experience rapid recombination of the photogenerated carriers with low quantum efficiency, seriously hindering their photocatalytic applications. To solve these issues, an important solution is to construct well-matched heterojunctions with highly efficient charge separation capabilities. To this end, an in situ sulfurization reaction was adopted after the deposition of Bi3+ supramolecular complex on a layered supramolecular precursor of tubular carbon nitride (TCN). X-ray diffraction (XRD) patterns confirmed that the as-prepared sample has a good crystalline structure without any other impurities, while high-resolution transmission electron microscopy (HR-TEM) revealed that the heterojunction possesses a 2D structure with a layer of nano-array on its surface. Combined Fourier-transform infrared (FT-IR) spectra and energy-dispersive X-ray spectroscopy (EDX) revealed the interfacial interactions. Owing to the formation of the Z-scheme heterojunction, the visible light adsorption and the separation efficiency of the photo-generated carriers are both obviously enhanced, leaving the high energy electrons and high oxidative holes to participate in the photocatalytic reactions. As a result, the photocatalytic hydrogen evolution rate of Bi2S3-TCN achieves 65.2 μmol g-1·h-1. This proposed green and environmentally benign route can also be applied to construct other sulfides with 2D TCN, providing some important information for the design and optimization of novel carbon-nitride-based semiconductors.

Sinomenine (SIN), an alkaloid extracted from the Chinese herbal medicine Sinomenium acutum, has great potential in anti-inflammatory, immune regulation, analgesic and sedative, and is already a clinical drug for the treatment of rheumatoid arthritis in China. Our previous studies show SIN inhibits inflammation by regulating ɑ7nAChR, a key receptor of cholinergic anti-inflammatory pathway (CAP), which plays an important role in regulating peripheral and central nervous system inflammation. Growing evidence supports the cholinergic dysregulation and inflammatory responses play the key role in the pathogenesis of AD. The intervention effects of SIN on AD by regulating CAP and homeostasis in brain and gut were analyzed for the first time in the present study using scopolamine-induced AD model mice. Behavioral tests were used to assess the cognitive performance. The neurons loss, cholinergic function, inflammation responses, biological barrier function in the mouse brain and intestinal tissues were evaluated through a variety of techniques, and the gut microbiota was detected using 16SrRNA sequencing. The results showed that SIN significantly inhibited the cognitive decline, dysregulation of cholinergic system, peripheral and central inflammation, biological barrier damage as well as intestinal flora disturbance caused by SCOP in mice. More importantly, SIN effectively regulated CAP to suppress the activation of TLR4/NF-κB and protect the homeostasis in brain and gut to alleviate cognitive impairment.

Chronic granulomatous disease (CGD) is a rare X-linked recessive primary immunodeficiency disease (PID). Herein, a human induced pluripotent stem cell (iPSC) line was generated from the peripheral blood mononuclear cells (PBMCs) of a CGD patient with a mutation (c.785_786delTT) in the CYBB gene. These iPSCs showed the expression of pluripotency markers, the ability to differentiate into three germ layers. They offer a promising technique for studying the pathogenesis and conducting drug screening for CGD patients.

Artificial intelligence of things systems equipped with flexible sensors can autonomously and intelligently detect the condition of the surroundings. However, current intelligent monitoring systems always rely on an external computer with the capability of machine learning rather than integrating it into the sensing device. The computer-assisted intelligent system is hampered by energy inefficiencies, privacy issues, and bandwidth restrictions. Here, a flexible, large-scale sensing array with the capability of low-power in-sensor intelligence based on a compression hypervector encoder is proposed for real-time recognition. The system with in-sensor intelligence can accommodate different individuals and learn new postures without additional computer processing. Both the communication bandwidth requirement and energy consumption of this system are significantly reduced by 1,024 and 500 times, respectively. The capability for in-sensor inference and learning eliminates the necessity to transmit raw data externally, thereby effectively addressing privacy concerns. Furthermore, the system possesses a rapid recognition speed (a few hundred milliseconds) and a high recognition accuracy (about 99%), comparing with support vector machine and other hyperdimensional computing methods. The research holds marked potential for applications in the integration of artificial intelligence of things and flexible electronics.

Aerodynamic modeling and control law design methods are crucial foundational technologies that enable efficient maneuvering flight of aircraft. Hence, this study focuses on how to construct the aerodynamic model and design control law using machine learning, as well as their differences from classical methods. To conduct this, a modified NACA0012 airfoil with a tail functioning as an elevator is employed as the geometry model. Through the utilization of the rigid dynamic grid method and overlapping grid technology, the pitch of the airfoil and the deflection of the elevator are efficient to execute. Firstly, the pitching moment coefficient is sampled through both steady and unsteady computations. Then, multivariate nonlinear regression (MNR) models and artificial neural network (ANN) models are established based on steady and unsteady sampling data, respectively. Additionally, the obtained model is evaluated using open-loop control laws. Based on the evaluation, the proportional-integral-derivative (PID) control algorithm is used to design the airfoil pitching control law using the MNR model. Meanwhile, deep reinforcement learning (DRL) is used to design the pitching control law using the ANN model. Finally, the PID and DRL controllers are implemented in a CFD environment for airfoil pitching control to verify their effectiveness in application scenarios. The results suggest that models based on both steady and unsteady data can reflect dynamic aerodynamic characteristics. However, using unsteady computation for data sampling significantly reduces time consumption compared to steady computation. Furthermore, the model constructed by ANN may have unexpected excellent characteristics. Both the PID and DRL control laws, designed based on the models, perfectly complete the control process in the CFD environment. This study provides valuable insights for the implementation of controllable maneuvering flight in aircraft.

Abstract Albeit nanozymes‐based tumor catalytic therapy (NCT) relies on endogenous chemical reactions that could achieve tumor microenvironment (TME)‐specialized reactive oxygen species (ROS) production, the unsatisfactory catalytic activity of nanozymes accompanied by complex TME poses a barrier to the therapeutic effect of NCT. Herein, a one‐step in situ synthesis strategy is reported to construct ternary Ru/TiO2−x@TiCN heterojunctions through oxidative conversion of TiCN nanosheets (NSs) to TiO2−x NSs and reductive deposition of Ru3+ to Ru nanoparticles. The narrow bandgap and existence of heterojunctions enhance the ultrasound‐activated ROS generation of Ru/TiO2−x@TiCN because of the accelerated electron transfer and inhibits electron–hole pair recombination. The augmented ROS production efficiency is achieved by Ru/TiO2−x@TiCN with triple enzyme‐like activities, which amplifies the ROS levels in a cascade manner through the catalytic decomposition of endogenous H2O2 to relieve hypoxia and heterojunction‐mediated NCT, as well as depletion of overexpressed glutathione. The satisfactory therapeutic effects of Ru/TiO2−x@TiCN heterojunctions are achieved through synergetic sonodynamic therapy and NCT, which achieve the complete elimination of tumors without recurrence. This strategy highlights the potential of in situ synthesis of semiconductor heterojunctions as enhanced sonosensitizers and nanozymes for efficient tumor therapy.

Multi-dimensional vibration isolation platforms often use parallel mechanisms to achieve multi-dimensional vibration isolation control. However, due to the high stiffness of the parallel mechanism, its own natural frequency is high, and it has good performance when applied to high-frequency vibration isolation, but it is hard to achieve low-frequency vibration isolation. This paper aims at the problem that the actual polishing and grinding equipment is often subjected to axial and circumferential low-frequency disturbances during operation, a novel C/2-(2-RRR) RR two-degree-of-freedom (2-DOF) translational-rotation low-frequency vibration isolation platform is proposed based on the singular configuration of planar 2-RRR mechanism. The coupling dynamic model of the vibration isolation platform is established, and the amplitude-frequency curve and force transmissibility curve are analyzed. The simulation analysis and prototype experiment are carried out by using the independent external excitation in both translational and rotational directions, and the corresponding linear system is compared to verify the effectiveness of the low-frequency vibration isolation of the two-degree-of-freedom vibration isolation platform.

IntroductionA series of significant ecological construction projects in the southern hilly region have brought about substantial changes to the ecological status and comprehensive zoning of the region. Hunan Province, with its strategic significance, was chosen as a representative research subject in the southern hilly region.MethodsWe conducted a dynamic evaluation of the ecological status change and comprehensive zoning of Hunan Province from a structure–function perspective by applying the transfer matrix, Theil-Sen, Mann-Kendall, and ecosystem service trade-offs or synergies methods. The research goal was to integrate and harmonize structural complexity and functional diversification, providing valuable insights for optimizing both ecological background and territorial background.ResultsThe main results are as follows: (1) The structural changes of ecosystems were mainly concentrated in settlement and Cropland ecosystems. While the area of bulti-up ecosystems has increased significantly, from 1.34% in 2000 to 2.72% in 2020. Cropland ecosystems marking a decrease of 1.39%, with a continued conversion of Cropland into construction land ecosystems. (2) Ecosystem function changes have introduced instability. Over time, NPP exhibited an oscillating trend of increase followed by a decrease. Spatially, there was a sharp decline in peripheral building land, and the regions of declining NPP displayed a lateral U-shaped distribution. (3) The overall trend in ecosystem service changes was positive. Quantitatively, GP and CS experienced an ascending-then-decreasing pattern, while HQ showed a weak decline and WY increased annually. At the county scale, there was noticeable spatial heterogeneity. Human socio-economic activities and environmental protection policies exert a significant impact on the ecological conditions within the study area. (4) Regarding the national territory space function partition, urban functional zones have primarily catered to residential functions and were mainly distributed in the Changsha-Zhuzhou-Xiangtan area.DiscussionEcological functional zones were mainly centered on ecological functions, and most were located in the mountainous areas of western and southern Hunan Province. The agricultural function areas were mainly to serve production functions and were mainly located in the Dongting Lake Plain, the nearshore plain of the mainstream and tributary systems of the rivers of Xiang, Zi, Yuan, and Li. In general, the changes in ecosystem structure and function in the study area reflect changes in ecological conditions. In the future, ecosystem diversity, stability, and sustainability should be improved from an integrated structure–function perspective.