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This paper presents a new end-to-end signal classification method using the signed cumulative distribution transform (SCDT). We adopt a transport generative model to define the classification problem. We then make use of mathematical properties of the SCDT to render the problem easier in transform domain, and solve for the class of an unknown sample using a nearest local subspace (NLS) search algorithm in SCDT domain. Experiments show that the proposed method provides high accuracy classification results while being computationally cheap, data efficient, and robust to out-of-distribution samples with respect to the existing end-to-end classification methods. The implementation of the proposed method in Python language is integrated as a part of the software package PyTransKit [1].

Synchronized intestinal electrical stimulation (SIES), in which intestinal electrical stimulation (IES) is delivered in synchronization with the intrinsic slow wave of small intestine, was previously reported to be more potent in accelerating small intestine transit than IES delivered at fixed frequency and phase. We hypothesized that SIES is more potent in suppressing postprandial blood glucose by enhancing the release of glucagon-like peptide-1 (GLP-1) and insulin.

In order to improve the mental health level of college students, a data mining based mental health education strategy for college students is proposed. Firstly, analyse the characteristics of data mining and its potential value in mental health education. Secondly, after denoising the mental health data of college students using wavelet transform, data mining methods are used to identify the psychological crisis status of college students. Finally, based on the psychological crisis status of college students, measures for mental health education are proposed from the following aspects: building a psychological counselling platform, launching psychological health promotion activities, establishing a psychological support network, strengthening academic guidance and stress management. The example analysis results show that after the application of the strategy in this article, the psychological health scores of college students have been effectively improved, with an average score of 93.5 points.

To determine pathological changes of meibomian glands (MGs) after transient exposure of the rat eyelid margin to alkali solution.

Ga-based liquid metal stretchable conductors have recently gained interest in flexible electronic devices such as electrodes, antennas, and sensors. It is essential to maintain electrical stability under strain or cyclic strain for reliable data acquisition and exhibit tough interfacial bonding between liquid metal and polymers to prevent performance loss and device failure. Herein, a highly stable conductor with superior electrical stability and tough interface bonding is introduced by casting curable polymers and a peeling-activated process from liquid metal particles. Based on the compensating effect of liquid metal, similar to the recharge relationship of water between rivers and lakes in nature, the conductor is not only strain-insensitive (ΔR/R0< 10% for 100% strain) but also immune to cyclic deformation (ΔR/R0< 7% with 5000 stretching cycles at 50% strain). Embedding liquid metal within the elastomer to create stretchable conductors effectively improves interfacial adhesion properties (the fluid–solid interfacial adhesion force increases from 0.48 to 0.62 mN/mm2). The constructed tough interface could even withstand sonication treatment. Finally, by combining strategies in material design and fabrication, an integrated array composed of vertical interconnect access and robust electrodes is fabricated, which simultaneously holds tough interfacial bonding with the upper and lower layers.

Cu-based catalysts have been widely studied for the electrochemical CO2reduction reaction (CO2RR) to yield high-value-added products with two or more carbons (C2+products). The rational design of Cu-based catalysts is critical to improve the selectivity and energy efficiency of the CO2RR-to-C2+process. Herein, we review recent advances in Cu-based catalysts with surface modification for four crucial factors in CO2RR-to-C2+based on briefly analyzing the reaction mechanisms: (1) surface hydrophobization to inhibit the hydrogen evolution reaction;(2) introduction of CO2-capture materials, halide-ion doping, and Cuδ+/Cu0synergy to promote CO2adsorption and activation (3) bifunctional catalysts and locally enhanced electric-thermal fields for modulating CO generation and adsorption; and (4) development of confinement structures and heterostructures, addition of oxidation states or defects, and use of single-atoms with different coordination environments to promote carbon–carbon coupling. In particular, the relationships between the surface properties of Cu-based catalysts and improved activity and C2+selectivity in CO2RR are discussed, along with strategies for enhancing the stability of the catalyst. Furthermore, the current challenges and potential strategies for future CO2RR-to-C2+research are discussed in this review.

The anti-oxidative characteristic and immunosuppressive microenvironment contribute to a high resistance of tumor to many treatments. In this work, a glutathione (GSH)-responsive metal-coordinated oxidative stress amplifier (designated as CuPA) is fabricated to suppress tumor growth through elevating the cellular level of reactive oxygen species (ROS) and eliminating M2 macrophages. Among which, cooper ion (Cu2+) is capable of coordinating with thioredoxin (Trx) inhibitor of PX-12 and signal transducer and activator of transcription 6 (STAT6) inhibitor of AS1517499 with the assistance of distearoyl phosphoethanolamine-PEG2000(DSPE-PEG2000), which can extensively increase the stability to enhance drug delivery in vitroand in vivo. Furthermore, CuPA can upregulate intracellular ROS to cause tumor cell death through restraining Trx and degrading GSH. Also, CuPA-mediated STAT6 inhibition results in the elimination of M2 macrophage to reverse the immunosuppressive tumor microenvironment. Finally, the elevated oxidative stress and increased immune activation amplify the synergistic antitumor effect without causing obvious side effect. This work provides a new sight for synergistic tumor suppression through chemo-immunotherapy in consideration of the complex resistant tumor microenvironment.

To solve the problems of low information collection accuracy, recall and evaluation accuracy in traditional methods, an evaluation method of online learning effectiveness for college students based on social network data mining is proposed. A web crawler architecture is utilised to mine social network data and collect information on university student network learning. Linear regression models are employed to filter indicator data and establish an index system for evaluating learning effectiveness. The weights of indicators are determined using the analytic hierarchy process, and fuzzy evaluation vectors are obtained by combining membership degree functions. An evaluation model is constructed using fuzzy evaluation vectors and fuzzy judgement method, and evaluation indicator data are input into the model to obtain scores for learning effectiveness. Experimental results demonstrate that the maximum accuracy of information collection for the proposed method is 98.1%, the maximum recall rate is 97.9%, the mean precision is 97.67%.

Yield performances of wheat (Triticum aestivumL.) cultivars are decided by the combined effects of key phenotypes. However, it is unclear which phenotypes are the key phenotypes that determine yield. We conducted a two‐site multicultivar test in Henan and Anhui in China during the 2016‒2017 wheat growing season. The objectives were to assess the relationships between grain yield and other related phenotypes and reveal the key phenotypes related to grain yield. Grain yield and nineteen phenotypes were assessed in a field trial consisting of 28 wheat cultivars. Multivariate statistical analysis methods (e.g., principal component analysis, partial least squares model, structural equation model) were used to reveal the relationships between grain yield and other related phenotypes. Wheat phenotypes changed as a result of the differences in environment (site) and genotype (cultivar). Eleven phenotypes were identified as the key phenotypes closely related to grain yield: biomass, harvest index, spike density, leaf nitrate reductase, net photosynthetic rate, canopy temperature, leaf chlorophyll, leaf area index, stomatal conductance, carboxylation efficiency, and transpiration rate. For analyzing the mechanisms of yield differences, multiple related phenotypes (rather than a single phenotype) should be considered. Relationships between wheat grain yield and nineteen phenotypes were analyzed with the data of 28 cultivars.The yield rankings of 28 wheat cultivars changed little between the two sites.Eleven phenotypes were identified as the key phenotypes closely related to wheat grain yield in the study.Nine phenotypes had great indirect effects on grain yield.Biomass and harvest index were the two most important phenotypes in deciding grain yield.

The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region.

The development of nanotheranostics for precision imaging-guided regulated cell death-mediated synergistic tumor therapy is still challenging. Herein, a novel multifunctional nanotheranostic agent, iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated hydrophobic gold nanocages (AuNCs) and hydrophilic epigallocatechin gallate (EGCG) (PAuE) is developed for multispectral optoacoustic tomography (MSOT)-guided photothermal therapy (PTT) and chemotherapy. The portions of necroptotic and apoptotic tumor cells were 52.9 and 5.4%, respectively, at 6 h post-incubation after the AuNC-induced mild PTT treatment, whereas they became 14.0 and 46.1% after 24 h, suggesting that the switch of the cell death pathway is a time-dependent process. Mild PTT facilitated the release of EGCG which induces the downregulation of hypoxia-inducible factor-1 (HIF-1α) expression to enhance apoptosis at a later stage, realizing a remarkable tumor growth inhibition in vivo. Moreover, RNA sequence analyses provided insights into the significant changes in genes related to the cross-talk between necroptosis and apoptosis pathways via PAuE upon laser irradiation. In addition, the biodistribution and metabolic pathways of PAuE have been successfully revealed by 3D MSOT. Taken together, this strategy of first combination of EGCG and AuNC-based photothermal agent via triggering necroptosis/apoptosis to downregulate HIF-1α expression in a tumor environment provides a new insight into anti-cancer therapy.

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2and are dysregulated in multiple human neurological disorders3–5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6–8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.

Many researchers have contributed to the assembly of zeolitic nanosheets and nanocrystallites into three-dimensional (3D) networks as it can remarkably improve the catalytic and/or adsorptive performances of zeolites. However, the applications of these synthesized materials are seriously limited because of low hydrothermal stability. A highly interesting strategy, but a great challenge, is the alignment of well-crystallized zeolite crystals into desirable architectures. Here, well-crystallized silicalite-1 crystals are assembled like toy Lego bricks into one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) architectures, and the assembly mechanism is investigated by combining elaborate experiments, in situ spectroscopy, and theoretical calculations. A 1D architecture was formed by stacking crystals along the baxis with the assistance of ethanol that is selectively adsorbed on (100) and (001) crystal facets. Such adsorption increases the condensation energy barriers along aand caxes, but facilitates the condensation between (010) facets. The assembly of the crystals into well-arrayed 2D architectures is achieved using both ethanol and benzaldehyde because of their preferable adsorption on the (001) facet. When an amphiphilic copolymer (P123) was further added in the gel along with the substitution of ethanol by 1-propanol, a 3D network was fabricated by the agglomeration and self-pillaring of the 2D Lego bricks possibly with P123 aggregates as the substrate matrix. Excitingly, upon alignment of crystals into 2D architectures, the adsorptive selectivity of 1-butanol (2 wt %) to water of silicalite-1 increases by 45.3 times, while into 3D networks, the catalytic activity for the Beckmann rearrangement of cyclohexanone oxime elevates by 79% along with a great enhancement of catalytic stability.

Constipation and opioid‐induced constipation (OIC) are common with limited treatment options. We investigated whether a noninvasive method of auricular vagal nerve stimulation (aVNS) could be used for treating OIC and explored its potential mechanisms and neural pathways in a rodent model of OIC. Sprague–Dawley were chronically implanted with one pair of auricular electrodes for aVNS. Sixteen rats were treated with loperamide for a week while another 16 rats received bilateral vagotomy, then randomly treated with aVNS or sham‐aVNS for a week. In addition, eight normal rats were implanted with a polyethylene catheter in the proximal colon for assessing whole colon transit. 1) The number of fecal pellets and water content in feces increased after aVNS, compared with sham‐aVNS. 2) aVNS accelerated colon transit and whole gut transit, compared with sham‐aVNS. 3) In colon tissues, aVNS increased the protein expression of choline acetyltransferase, glial cell line‐derived neurotrophic factor and the c‐kit expression in myenteric interstitial cells of Cajal but decreased the protein expression of neural nitric oxide synthase (p< 0.05 for all, vs. sham‐VNS). 4) The prokinetic effects of aVNS were abolished by both subdiaphragmatic vagotomy and atropine. 5) aVNS increased the c‐fos expression in both nucleus tractus solitarius and dorsal motor nucleus of vagus, and increased vagal efferent activity (p< 0.05, vs. sham‐VNS). aVNS improves OIC by enhancing colon motility and restoring enteric neural functions mediated via the central and vagal efferent pathway.

Introduction: OC26, an ortho-aryl chalcone compound, shows excellent antitumor activity in vitro and vivo. However, the pharmacokinetic characteristics of OC26 have not been comprehensively reported. It is essential to investigate the correlation of pharmacological response. Objective: To further explore OC26, this study aims to develop an ultra-performance liquid chromatography- tandem mass spectrometric (UPLC-MS/MS) method to reveal the pharmacokinetics and distribution characteristics in rats of OC26. Methods: An UPLC-MS/MS method was developed to detect OC26 in plasma and various tissues. The protein precipitation method was applied to process the biological samples. After intravenous injection 12.5mg/kg of OC26 in rats, plasma and tissue samples were collected from rats and the method was applied to investigate pharmacokinetic and distribution characteristics of OC26. Results: Calibration curve samples of OC26 concentration range from 20 to 2000 ng/mL with the goodness of fit (r2> 0.99). The precisions for the method were within 12.3%, while the accuracies for the method were within ±11% (bias). The matrix effect had no influence on the accuracy and precision of the method. After intravenous injection 12.5mg/kg of OC26 in rats, OC26 was rapidly eliminated (t1/2=31.39±7.87min, MRT0→∞=15.03±2.55min) from rat plasma and widely distributed (Vd=4.83±0.96L/kg) in tissues. The highest concentration of OC26 was detected in the brain in which peak content (~8962.78ng/g at 15min) was over 5-fold higher than that of in other tissues, which prompted new potential targets in the brain. Besides, lung and heart also detected quite a high level of OC26. Benefited from quick elimination in the collected tissues and plasma, long-term accumulation was not observed as chronic toxicity might be less. Conclusion: This UPLC-MS/MS method was successfully applied to detect OC26 and provide a theoretical basis for the further study of OC26.

Immunotherapeutic effect is restricted by the nonimmunogenic tumor phenotype and immunosuppression behaviors of tumor‐associated macrophages (TAMs). In this work, a drug self‐assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor‐associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration, and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the nonimmunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior antitumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management. A drug self‐assembly based on Chlorin e6 and BLZ945 is developed to improve the drug stability and delivery efficiency, which can enhance photodynamic immunotherapy through tumor immunogenic induction and tumor‐associated macrophage depletion. The self‐assembled drug delivery system not only promotes the primary tumor eradication but also improves immunosuppression microenvironments to activate abscopal effect for distant tumor suppression.

Iterative slice-matching procedures are efficient schemes for transferring a source measure to a target measure, especially in high dimensions. These schemes have been successfully used in applications such as color transfer and shape retrieval, and are guaranteed to converge under regularity assumptions. In this paper, we explore approximation properties related to a single step of such iterative schemes by examining an associated slice-matching operator, depending on a source measure, a target measure, and slicing directions. In particular, we demonstrate an invariance property with respect to the source measure, an equivariance property with respect to the target measure, and Lipschitz continuity concerning the slicing directions. We furthermore establish error bounds corresponding to approximating the target measure by one step of the slice-matching scheme and characterize situations in which the slice-matching operator recovers the optimal transport map between two measures. We also investigate connections to affine registration problems with respect to (sliced) Wasserstein distances. These connections can be also be viewed as extensions to the invariance and equivariance properties of the slice-matching operator and illustrate the extent to which slice-matching schemes incorporate affine effects.

Corneal neovascularization (CNV) compromises corneal avascularity and visual acuity. Current clinical visualization approaches are subjective and unable to provide molecular information. Photoacoustic (PA) imaging offers an objective and non-invasive way for angiogenesis investigation through hemodynamic and oxygen saturation level (sO_2) quantification. Here, we demonstrate the utility of PA and slit lamp microscope for in vivo rat CNV model. PA images revealed untreated corneas exhibited higher sO_2 level than treatment groups. The PA results complement with the color image obtained with slit lamp. These data suggest PA could offer an objective and non-invasive method for monitoring CNV progression and treatment outcome through the sO_2 quantification.

Electroacupuncture (EA) is effective in treating visceral pain associated with functional dyspepsia (FD). The aim of this study was to explore the effect of chronic EA (CEA) on gastric hypersensitivity and the involvement of sympathetic nervous system in a rodent model of FD. Gastric hypersensitivity in adulthood was induced by iodoacetamide (IA) in neonatal rats. The IA‐treated rats were randomized to receive no treatment (control), sham‐CEA, CEA, or adrenergic antagonists, for one week. Gastric sensitivity to graded gastric distensions was then assessed by electromyogram (EMG) analysis. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) to derive the low‐frequency (LF, sympathetic activity) and high‐frequency (HF, mainly vagal activity) components expressed as percentage of total spectral power. Blood was collected for the measurement of corticosterone (CORT) and norepinephrine (NE). 1) CEA, but not sham‐CEA, reduced the EMG response to graded gastric distension in IA‐treated control rats at 40 mmHg (128 ± 6% vs. 171 ± 15%, p= 0.009), 60 mmHg (204 ± 14% vs. 271 ± 24%, p= 0.010) and 80 mmHg (269 ± 19% vs. 364 ± 33%, p= 0.025), respectively. 2) CEA, but not sham CEA, increased HF component (0.61 ± 0.02 vs. 0.46 ± 0.04 in IA‐treated rats, p= 0.003) and decreased LF component (0.39 ± 0.02 vs. 0.54 ± 0.04, p= 0.003). 3) Adrenergic antagonists reduced the EMG response to graded gastric distension. 4) CEA significantly reduced plasma CORT and NE in IA‐treated rats. EA ameliorates gastric hypersensitivity in IA‐treated rats and the effect may be related to the improved sympathovagal balance and the decrease of stress hormones.

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4variants. Forty‐two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full‐field electroretinography (objective function), were performed. Next‐generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5–52)/29.5 (12–72) years, and the median visual acuity in the right/left eye was 1.30 (0.15–2.28)/1.30 (0.15–2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty‐eight pathogenic/likely pathogenic ABCA4variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype–phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well‐characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype–phenotype association was similarly represented.

Objectives Female obesity may be improved by the consumption of a high-polyphenolic-rich diet. Lycium ruthenicumMurray is a renowned edible plant, the fruit of which is abundant in anthocyanins and exhibits many biological activities. This study aimed to investigate the potential impact of anthocyanins derived from Lycium ruthenicumMurray (ACN) intervention on improving obesity by regulating the gut microbiota and bile acids (BAs) metabolism in high-fat diet (HFD)-induced female mice.Methods A total of 32 C57BL/6J female mice were divided into four distinct groups: the Ctrl group (fed a normal diet), Ctrl + ACN group (fed a normal diet plus 8 mg/mL extract of ACN), HFD group (fed a high-fat diet), and HFD + ACN group (fed a HFD plus 8 mg/mL extract of ACN).Results The findings showed that ACN significantly reduced the body weight, periovarian adipose mass, and adipocyte diameter, ameliorated lipid accumulation in the liver, and lowered the serum total cholesterol and low-density lipoprotein (LDL-C) levels in HFD-induced female mice. In addition, ACN exhibited a reversal of gut microbial dysbiosis in HFD-fed female mice, such as by enhancing the quantity of Lactobacillusand Allobaculumand reducing the abundance of Blautiaand Faecalibaculum. Moreover, the results of fecal BAs showed that ACN led to a decrease in the ratio of primary to secondary BAs, mainly attributed to decreased levels of primary BAs, including CA, CDCA, αMCA, and HCA in HFD-induced female mice. Further analysis revealed that ACN may exert its anti-obesity effect by increasing the relative abundance of Lactobacillus_ jonsoniiand Lactobacillus_reuteriwithin the gut and subsequently affecting the metabolism of fecal HDCA and GUDCA.Conclusion These results indicated that ACN effectively inhibits HFD-induced obesity in female mice by regulating gut microbiota-related BA metabolism.

Objective: To study Ermiaosan in the treatment of UC by using network pharmacology and molecular docking, and to provide references for experiments and clinical application for treating UC with dampness-heat syndrome. Methods: The main active chemical components of Ermiaosan were screened out through TCMSP, the targets of components were obtained from TCMSP, the SwissTargetPrediction, TTD and the DrugBank database, and these targets genes were retrieved by UniProt database, the disease genes were obtained from TTD and Genecard database. String tool was used to constructed the PPI network, to built these components and their corresponding targets, Cytoscape software was applied to merge the networks and screen out the core network. And Bioinformatic analysis was performed using the OECloud tools to explore the enrichment analyses of GO and KEGG. Molecular docking was applied to check the affinity between the components and selected targets. Results: Forty-six main active components were predicted from Ermiaosan, and 408 intersection genes were screened from drug-disease genes. The enrichment included PI3K–Akt, TNF and HIF-1 signaling pathway, and the networks analysis showed that Ermiaosan acted on seven key targets AKT1, TNF, IL6,TP53, VEGFA, IL1B and CTNNB1 to play roles in treating UC. Molecular docking showed that top 3 chemical components could bind stably with these targets. Conclusion: Ermiaosan can relieve dampness-heat syndrome of UC, the possible potential mechanism might be related to the targets AKT1, TNF, IL6,TP53, VEGFA, IL1B and CTNNB1 linked with TNF, PI3K-Akt, and HIF-1 signaling pathway, it will provide meaningful references for further study in experiments and clinical investigations.

This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population.

Clinical high‐frequency spinal cord stimulation (hfSCS) (>250 Hz) applied at subperception amplitudes reduces leg and low back pain. This study investigates, via labeling for c‐fos—a marker of neural activation, whether 500 Hz hfSCS applied at amplitudes above and below the dorsal column (DC) compound action potential (CAP) threshold excites dorsal horn neurons. DC CAP thresholds in rats were determined by applying single biphasic pulses of SCS to T12–T13segments using pulse widths of 40 or 200 μsec via a ball electrode placed over the left DC and increasing amplitude until a short latency CAP was observed on the L5DC and sciatic nerve. The result of this comparison allowed us to substitute sciatic nerve CAP for DC CAP. SCS at T12–T13was applied continuously for two hours using: sham or hfSCS at 500 Hz SCS, 40 μsec pulse width, and 50, 70, 90, or 140% CAP threshold. Spinal cord slices from T11–L1were immunolabeled for c‐fos, and the number of c‐fos‐positive cells was quantified. 500 Hz hfSCS applied at 90 and 140% CAP threshold produced substantial (≥6 c‐fos + neurons on average per slice per segment) c‐fos expression in more segments between T11and L1than did sham stimulation (p< 0.025, 90% CAP; p< 0.001, 140% CAP, Fisher's Exact Tests) and resulted in more c‐fos‐positive neurons on average per slice per segment ipsilateral to than contralateral to the SCS electrode at 70, 90, and 140% CAP threshold (p< 0.01, Wilcoxon Signed Rank Tests). The finding of enhanced c‐fos expression in the ipsilateral superficial dorsal horn provides evidence for activation/modulation of neuronal circuitry associated with subperception hfSCS.

There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region.

Oxidative therapies receive a limited antitumor efficiency due to the insufficient reactive oxygen species (ROS) levels at focal sites and the evolvement of antioxidant defense systems. Herein, we develop an albumin-based nanomedicine to co-deliver chlorin e6 (Ce6) and COH-SR4 (CS), which can simultaneously enhance the yield and lethality of intracellular ROS for amplified photodynamic therapy (PDT). In which, CS acts as both an activator of AMP-activated protein kinase (AMPK) and an inhibitor of glutathione S-transferases (GSTs). Benefiting from it, the prepared HSA-Ce6@COH-SR4 (HCCS) enables positive feedback uptake by promoting AMPK phosphorylation, leading to rapid and extensive tumor accumulation of drugs. As a result, HCCS obviously increases the ROS production to elevate intracellular oxidative stress. Furthermore, HCCS can inhibit GSTs to disturb the antioxidant defense system of tumor cells, intensifying the oxidative damage of ROS. Ultimately, the PDT of HCCS is significantly strengthened by improving the ROS yield and lethality, which greatly declines the proliferation of breast cancer in vivo. This study may open a window in the development of drug co-delivery system for enhanced oxidative therapy of tumors.

Spinal cord stimulation (SCS) at both conventional and higher frequencies may effectively reduce pain, but optimal parameters need to be established. This study investigated how SCS at different frequencies and pulse widths acutely modulates nociceptive activity of wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in rats at a stimulus amplitude that influences both local circuits and dorsal column fibers. L2–L3and L6–S2spinal segments were exposed for SCS and spinal neuronal recordings, respectively. Responses to pinch of a hindpaw were recorded before and after SCS (40 or 200 µsec pulse width at 50, 500, 1 kHz and 10 kHz, amplitude: 90% of motor threshold) for 5 or 20 min. Pinch responses were tested within 30 s after SCS ceased (first pinch) and at ∼4 min intervals until response recovery. 1) SCS for 5 min suppressed averaged first pinch responses, except for 40 µsec/50 Hz. 2) Only SCS with 40 µs/1 kHz suppressed more spinal neurons than 200 µsec/50 Hz. 3) All SCS parameters at 5 min increased pinch responses for a small population of cells, with the incidence being greater for WDR than for HT neurons. 4) SCS at 1 kHz (40 or 200 µsec) for 20 min reduced the response to the second pinch as compared with baseline responses. In addition, no neurons exhibited increased pinch responses. Compared with a typical low frequency SCS (200 µs/50 Hz) or high‐frequency SCS at 10 kHz, at an amplitude designed to influence both local spinal circuits and dorsal column fiber tracts, 1 kHz SCS suppressed nociceptive responses of more spinal neurons and/or demonstrated longer persisting suppressive effects. SCS at 1 kHz surpassed both low‐frequency (50 Hz) and high‐frequency (10 kHz) SCS application in this normal animal model.

Acupuncture or electroacupuncture (EA) has been applied for treating chemotherapy‐induced emesis with limited success. The aims of this study were to investigate the anti‐emetic effect of EA and to explore underlying anti‐emetic mechanisms. Rats were chronically implanted with a pair of stainless steel leads at acupoint pericardium 6 (PC6). Effects of EA with different parameters on cisplatin‐induced nausea were assessed by pica (intake of kaolin, a surrogate of nausea in species without vomiting reflex). C‐fos expressions in the area postrema (AP) and nucleus tractus solitarii (NTS) were analyzed. Subdiaphragmatic vagotomy was used to study involvement of the vagal pathway. 1) EA at 20 Hz/0.6 msec reduced kaolin intake in the first and second days after cisplatin injection compared with the sham‐EA group (first day: 1.0 ± 0.2 vs. 1.9 ± 0.3 g, p= 0.017; second day: 0.4 ± 0.2 vs.1.1 ± 0.3 g, p= 0.010). However, EA at 10 Hz/1.2 msec was ineffective on both days. 2) Subdiaphragmatic vagotomy significantly reduced cisplatin‐induced kaolin intake (1.1 ± 0.3 vs. 2.2 ± 0.3 g, p= 0.014) and also blocked the inhibitory effect of EA on kaolin intake in the first day. 3) Cisplatin significantly increased the expression of c‐fos in the NTS and AP. Vagotomy greatly reduced c‐fos expression in both NTS and AP. EA reduced the cisplatin‐induced c‐fos expression in the AP but not the NTS. EA at PC6 with appropriate parameters has an inhibitory effect on cisplatin‐induced nausea. The anti‐emetic effect of the EA is centrally medicated involving the AP via the vagal pathway as well as the potential effect on AP by reducing the release of hormones.

The dehydrogenation and conversion of methanol into 1,1-dimethoxymethane (DMM) was achieved over noble metal-free photocatalyst CdS/Ni2P under visible light. This photocatalytic process for methanol-to-H2and DMM conversion is efficient and atom economic, with an optimal rate and selectivity of DMM of 188.42 mmol g−1h−1and 82.93%, respectively. This work supplies a new green approach for the direct efficient conversion of methanol into DMM and provides a promising avenue for sustainable bio-methanol applications.

The catalytic role of various acid sites located at the straight channel, sinusoidal channel and intersection cavity on ZSM-5 zeolite in the carbonylation of methanol and dimethyl ether (DME) was investigated through combined DFT-D calculation and micro-kinetic analysis. The results indicate that the formation of acetate takes priority in the straight channel, whereas the acid sites in the intersection cavity may induce the conversion of methanol and DME into unexpected by-products that lead to the rapid deactivation of the ZSM-5 catalyst. The catalytic behavior of various acid sites in carbonylation is strongly influenced by their local environment and the surrounding framework structure which determine the space confinement and electrostatic stabilization effects. Meanwhile, DME as feedstock shows a higher carbonylation activity than methanol in the straight channel, producing preferably methyl acetate. As a result, the catalytic activity and product selectivity of ZSM-5 in carbonylation can be finely tuned through purposely regulating the location of acid sites. Moreover, the carbonylation reaction rate can be further elevated through incorporating Cu into the ZSM-5 zeolites, especially mononuclear copper (Cu) species, due to the strong electrostatic interaction between the nucleophilic CH3+–CO intermediate and electrophilic Cu sites. This work helps to clarify the catalytic role of various acid sites on ZSM-5, as well as the nature of active Cu species in the carbonylation reaction, which is of great benefit to the design of efficient zeolite catalysts for the carbonylation process.

Stress is considered an independent factor causing and aggravating gastrointestinal symptoms, including visceral pain. The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on stress‐induced gastric hypersensitivity in rats treated with neonatal iodoacetamide mimicking human functional dyspepsia (FD). Neonatal rats were treated with gavage of 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily for six days starting on tenth day after birth. The control group was given 0.2 mL of 2% sucrose. When the rats were eight weeks old, acute restraint stress was performed on them for 90 min. EA at ST36 (ZuSanLi) was performed during the acute stress or 30 min after the stress. Adrenoceptor blocking drugs (propranolol and phentolamine) were injected intraperitoneally 30 min before acute restraint stress to explore possible sympathetic mechanisms. Visceral‐motor responses to gastric distention were assessed by electromyogram (EMG). 1) Stress‐induced gastric hypersensitivity was significantly more severe in the FD rats, compared to the control rats. It was blocked by the adrenoceptor antagonists. 2) EA inhibited stress‐induced gastric hypersensitivity; the preventive effect of EA (given during stress) was more remarkable than the curative effect (given after stress). Stress resulted in a higher sympathovagal ratio and this was suppressed by EA. Rats treated with neonatal iodoacetamide mimicking FD are more vulnerable to stress. Stress‐induced gastric hypersensitivity can be prevented or suppressed by EA at ST36 via the restoration of sympathovagal balance.

Chainlike zeolites are advantageous to various applications as a catalyst or an adsorbent with specific selectivity; however, it is often very difficult to get desired morphology due to the complexity of zeolite synthesis process. In this work, appropriate parameters for the synthesis of perfect chainlike ZSM-5 zeolites were well determined, which illustrates that the chain length can be controlled by the composition of synthesis mixture, the amount of residual alcohol in the synthesis system, and the crystallization time. Moreover, the mechanism of chainlike crystal growth was investigated by analyzing the surface species during the synthesis process, with the help of density functional theory (DFT) calculation. The results indicate that the formation of disk crystals with proper dimension and flat surface having abundant hydroxyl groups is crucial to the growth of chainlike ZSM-5 crystals; the condensation of Si–OH groups on the (010) facet is energetically more favorable than that on other facets, leading to the growth of MFI crystals along the b-orientation. Through finely tuning the multifarious synthesis parameters, chainlike ZSM-5 zeolites with controllable length in b-orientation are obtained without using any other extra organic additives except the necessary template agent such as tetrapropylammonium hydroxide (TPAOH). Owing to the increased tortuosity of pore channels in the chainlike ZSM-5, the difference between p-xylene and o/m-xylenes in their adsorption behavior and diffusivity is greatly enhanced. These results help to clarify the formation mechanism of zeolites with chainlike morphology and then bring forward an effective approach to get zeolite materials with specific properties in adsorption and catalysis.

Transforming growth factor-β (TGF-β) belongs to a group of pleiotropic cytokines that are involved in a variety of biological processes, such as inflammation and immune reactions, cellular phenotype transition, extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition. TGF-β is widely distributed throughout the body, including the nervous system. Following injury to the nervous system, TGF-β regulates the behavior of neurons and glial cells and thus mediates the regenerative process. In the current article, we reviewed the production, activation, as well as the signaling pathway of TGF-β. We also described altered expression patterns of TGF-β in the nervous system after nerve injury and the regulatory effects of TGF-β on nerve repair and regeneration in many aspects, including inflammation and immune response, phenotypic modulation of neural cells, neurite outgrowth, scar formation, and modulation of neurotrophic factors. The diverse biological actions of TGF-β suggest that it may become a potential therapeutic target for the treatment of nerve injury and regeneration.

Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs (ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering. The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

A series of ZSM-11 zeolites was synthesized by adding different amounts of boron to a synthesis gel for the purpose of improving its catalytic performance for conversion of methanol to olefins (MTO). It was found that boron has marginal effects on the crystal structure, texture properties and acid site strength of ZSM-11, but it significantly increases its catalytic stability and hydride transfer activity that results in an increase in the amounts of aromatics and alkanes in products. DFT calculations revealed that aluminum and boron atoms competitively enter the ZSM-11 framework. In combination with 27Al MAS NMR, GC-MS, m-xylene isomerization and Co2+-exchanged ZSM-11 diffuse reflectance UV-vis spectroscopy results, it can be deduced that incorporation of boron compels some aluminum atoms to shift towards the intersection T sites, which can greatly alleviate the coking process although it allows the formation of more bulky molecules. This shows that the MTO catalytic performance of ZSM-11 can be largely adjusted by changing the amount of incorporated boron through regulation of aluminum or acid site locations in the framework.

This study investigates advertising aimed at children and the food environment in children’s programs broadcast on the China Central Television network. The study documented how foods were shown in television advertisements and editorial content. Findings show that children were exposed to a large number of unhealthy food advertisements. In addition, the advertising appeals used in the television advertisements were similar to those used in Western countries. As part of the socialization process, the television advertisements may have a negative influence on children’s health in China.

MicroRNAs (miRNAs, miRs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level. We have previously identified a group of novel miRNAs in proximal sciatic nerve after sciatic nerve transection by Solexa sequencing, and miR-sc3 is a member of the group. In this study, we aimed to investigate the effects of miR-sc3 on phenotypic modulation of Schwann cells (SCs). miR-sc3 was highly expressed in the injured nerve after sciatic nerve transection. An increased and decreased expression of miR-sc3 promoted and reduced the proliferation and migration of primary SCs, respectively. miR-sc3 directly targeted astrotactin 1 (Astn1) and led to translational suppression of Astn1. There was an inverse association between the time-dependent expressions of miR-sc3 and Astn1 in proximal sciatic nerve after sciatic nerve transection. Overall, miR-sc3 affected SC proliferation and migration by targeting Astn1, thus playing the regulatory role in peripheral nerve regeneration.

Photodynamic therapy (PDT) is applied as a robust therapeutic option for tumor, which exhibits some advantages of unique selectivity and irreversible damage to tumor cells. Among which, photosensitizer (PS), appropriate laser irradiation and oxygen (O2) are three essential components for PDT, but the hypoxic tumor microenvironment (TME) restricts the O2supply in tumor tissues. Even worse, tumor metastasis and drug resistance frequently happen under hypoxic condition, which further deteriorate the antitumor effect of PDT. To enhance the PDT efficiency, critical attention has been received by relieving tumor hypoxia, and innovative strategies on this topic continue to emerge. Traditionally, the O2supplement strategy is considered as a direct and effective strategy to relieve TME, whereas it is confronted with great challenges for continuous O2supply. Recently, O2-independent PDT provides a brand new strategy to enhance the antitumor efficiency, which can avoid the influence of TME. In addition, PDT can synergize with other antitumor strategies, such as chemotherapy, immunotherapy, photothermal therapy (PTT) and starvation therapy, to remedy the inadequate PDT effect under hypoxia conditions. In this paper, we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor, which were classified into O2-dependent PDT, O2-independent PDT and synergistic therapy. Furthermore, the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

Synergistic therapy strategy and prognostic monitoring of glioblastoma’s immune response to treatment are crucial to optimize patient care and advance clinical outcomes. However, current systemic temozolomide (TMZ) chemotherapy and imaging methods for in vivotracing of immune responses are inadequate. Herein, we report an all-in-one theranostic nanoprobe (PEG/αCD25-Cy7/TMZ) for precise chemotherapy and real-time immune response tracing of glioblastoma by photoacoustic-fluorescence imaging. The nanoprobe was loaded with TMZ and targeted regulatory T lymphocyte optical dye αCD25-Cy7 encapsulated by glutathione-responsive DSPE-SS-PEG2000. The results showed that the targeted efficiency of the nanoprobe to regulatory T lymphocytes is up to 92.3%. The activation of PEG/αCD25-Cy7/TMZ by glutathione enhanced the precise delivery of TMZ to the tumor microenvironment for local chemotherapy and monitored glioblastoma’s boundary by photoacoustic-fluorescence imaging. Immunotherapy with indoleamine 2,3-dioxygenase inhibitors after chemotherapy could promote immunological responses and reduce regulatory T lymphocyte infiltration, which could improve the survival rate. Photoacoustic imaging has in real-time and noninvasively depicted the dynamic process of immune response on a micrometer scale, showing that the infiltration of regulatory T lymphocytes after chemotherapy was up-regulated and would down-regulate after IDO inhibitor treatment. This all-in-one theranostic strategy is a promising method for precisely delivering TMZ and long-term dynamically tracing regulatory T lymphocytes to evaluate the immune response in situfor accurate tumor chemo-immunotherapy.

The molecular diversity of glia in the human hippocampus and their temporal dynamics over the lifespan remain largely unknown. Here, we performed single-nucleus RNA sequencing to generate a transcriptome atlas of the human hippocampus across the postnatal lifespan. Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identified subpopulations with distinct molecular signatures and revealed their association with specific physiological functions, age-dependent changes in abundance, and disease relevance. We further characterized spatiotemporal heterogeneity of GFAP-enriched astrocyte subpopulations in the hippocampal formation using immunohistology. Leveraging glial subpopulation classifications as a reference map, we revealed the diversity of glia differentiated from human pluripotent stem cells and identified dysregulated genes and pathological processes in specific glial subpopulations in Alzheimer’s disease (AD). Together, our study significantly extends our understanding of human glial diversity, population dynamics across the postnatal lifespan, and dysregulation in AD and provides a reference atlas for stem-cell-based glial differentiation.