Clonidine Patch for Tourette Syndrome With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). METHODS: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. RESULTS: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. CONCLUSION: Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.

Characteristic substance analysis and rapid detection of bacteria spores in cooked meat products by surface enhanced Raman scattering based on Ag@AuNP array substrate.

BACKGROUND: Bacterial spores are the main potential hazard in medium- and high-temperature sterilized meat products, and their germination and subsequent reproduction and metabolism can lead to food spoilage. Moreover, the spores of some species pose a health and safety threat to consumers. The rapid detection, prevention, and control of bacterial spores has always been a scientific problem and a major challenge for the medium and high-temperature meat industry. Early and sensitive identification of spores in meat products is a decisive factor in contributing to consumer health and safety. RESULTS: In this study, we developed a novel and stable Ag@AuNP array substrate by using a two-step synthesis approach and a liquid-interface self-assembly method that can directly detect bacterial spores in actual meat product samples without the need for additional in vitro bacterial culture. The results indicate that the Ag@AuNP array substrate exhibits high reproducibility and Raman enhancement effects (1.35 × 105). The differentiation in the Surface enhanced Raman scattering (SERS) spectra of five bacterial spores primarily arises from proteins in the spore coat and inner membrane, peptidoglycan of cortex, and Ca2⁺-DPA within the spore core. The correct recognition rate of linear discriminant analysis for spores in the meat product matrix can reach 100 %. The average recovery accuracy of the SERS quantitative model was at around 101.77 %, and the limit of detection can reach below 10 CFU/mL. SIGNIFICANCE: It provides a promising technological strategy for the characteristic substance analysis and timely monitoring of spores in meat products.

A New Species of Diploderma (Squamata, Agamidae) from the Valley of Dadu River in Sichuan Province, with a Redescription of Topotypes of D. splendidum from Hubei Province, China.

This study describes a novel species of Diploderma (Squamata, Agamidae) from the lower valley of the Dadu River of the Sichuan Province of Western China based on its distinct morphological features and molecular evidence. D. daduense sp. nov. can be distinguished from its congeners by its tympanum concealed; head mainly green-yellow, supplemented by black; skin folds under the nuchal and dorsal crest obviously present in adult males only, its vertebral crest discontinuous between nuchal and dorsal sections with a distinct gap; transverse gular fold present but not obvious in some individuals; gular spot absent in both sexes; dorsolateral stripes green-yellow anteriorly, cyan in the center and blurry off-white posteriorly in adult males, the upper edge of dorsolateral stripes strongly jagged in adult males; no radial stripes around the eyes; inner-lip coloration smoky-white, and the coloration of the tongue and oral cavity as a light-flesh color in life; bright green-yellow transverse stripes on dorsal body in males; black patches are evenly distributed along the vertebral line between the dorsolateral stripes from the neck to the base of the tail in males; beech-brown or gray-brown line along the vertebral line with heart-shaped or diamond-shaped black patches on the dorsal body in females; and supratemporals fewer than four on at least one side. The phylogenetic tree based on mitochondrial ND2 sequences indicates that D. daduense sp. nov. forms an independent clade with strong support 1/100 in ML bootstrap/Bayesian posterior probability and is the sister group to D. splendidum. At the inter-species level, the p-distance is at least 6.95%, further confirming that an independent species had been identified. Our work raises the number of species within the genus Diploderma to 47.

Biochar and Manure Co-Application Increases Rice Yield in Low Productive Acid Soil by Increasing Soil pH, Organic Carbon, and Nutrient Retention and Availability.

In recent years, overuse of chemical fertilization has led to soil acidification and decreased rice yield productivity in southern China. Biochar and manure co-application remediation may have positive effects on rice yield and improve acid paddy soil fertility. This study was conducted to understand the effects of co-application of wood biochar and pig manure on rice yield and acid paddy soil quality (0-40 cm soil layers) in a 5-year field experiment. The experiment consisted of six treatments: no biochar and no fertilizer (CK); biochar only (BC); mineral fertilizer (N); mineral fertilizer combined with biochar (N + BC); manure (25% manure N replacing fertilizer N) combined with mineral fertilizer (MN); and manure combined with mineral fertilizer and biochar (MN + BC). Total nitrogen application for each treatment was the same at 270 kg nitrogen ha-1y-1, and 30 t ha-1 biochar was added to the soil only in the first year. After five years, compared with N treatments, N + BC, MN, and MN + BC treatments increased the rice yield rate to 2.8%, 4.3%, and 6.3%, respectively, by improving soil organic matter, total nitrogen, and available phosphate under a 0-40 cm soil layer. MN + BC had the strongest resistance to soil acidification among all the treatments. The interaction between fertilizers and biochar application was significant (p < 0.05) in rice yield, soil electrical conductivity (10-20 cm), and soil available phosphate (20-40 cm). Principal component analysis indicated that the effect of manure on soil property was stronger than that of biochar in the 0-40 cm soil layer. The overall rice yield and soil fertility decreased in the order of biochar + mineral fertilizer + manure > mineral fertilizer + manure > biochar + mineral fertilizer > mineral fertilizer > biochar > control. These results suggest that biochar and manure co-application is a long-term viable strategy for improving acid soil productivity due to its improvements in soil pH, organic carbon, nutrient retention, and availability.

Aberrant Enhanced NLRP3 Inflammasomes and Cell Pyroptosis in the Brains of Prion-Infected Rodent Models Are Largely Associated with the Proliferative Astrocytes.

Neuroinflammation is a common pathological feature in a number of neurodegenerative diseases, which is mediated primarily by the activated glial cells. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome-associated neuroinflammatory response is mostly considered. To investigate the situation of the NLRP3-related inflammation in prion disease, we assessed the levels of the main components of NLRP3 inflammasome and its downstream biomarkers in the scrapie-infected rodent brain tissues. The results showed that the transcriptional and expressional levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein (ASC) in the brains of scrapie-infected rodents were significantly increased at terminal stage. The increased NLPR3 overlapped morphologically well with the proliferated GFAP-positive astrocytes, but little with microglia and neurons. Using the brain samples collected at the different time-points after infection, we found the NLRP3 signals increased in a time-dependent manner, which were coincidental with the increase of GFAP. Two main downstream cytokines, IL-1ß and IL-18, were also upregulated in the brains of prion-infected mice. Moreover, the gasdermin D (GSDMD) levels, particularly the levels of GSDMD-NT, in the prion-infected brain tissues were remarkably increased, indicating activation of cell pyroptosis. The GSDMD not only co-localized well with the astrocytes but also with neurons at terminal stage, also showing a time-dependent increase after infection. Those data indicate that NLRP3 inflammasomes were remarkably activated in the infected brains, which is largely mediated by the proliferated astrocytes. Both astrocytes and neurons probably undergo a pyroptosis process, which may help the astrocytes to release inflammatory factors and contribute to neuron death during prion infection.

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia.

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

The Comparative Genomics of Botryosphaeriaceae Suggests Gene Families of Botryosphaeria dothidea Related to Pathogenicity on Chinese Hickory Tree.

Trunk canker poses a major threat to the production of Chinese hickory tree (Carya cathayensis Sarg.), which is primarily determined by Botryosphaeriaceae. In our previous work, we identified Botryosphaeria dothidea as the predominant pathogen of this disease. However, it is still unclear about corresponding gene families and mechanisms associated with B. dothidea's pathogenicity on Chinese hickory tree. Here, we present a comparative analysis of high-quality genome assemblies of Botryosphaeria dothidea and other isolated pathogens, showing highly syntenic relationships between B. dothidea and its closely related species and the conservative evolution of the Botryosphaeriaceae family. Higher GC contents were found in the genomes of B. dothidea and three other isolated pathogens (Botryshaeria cortices, Botryshaeria fabicerciana, and Botryshaeria qingyuanensis) compared to Macrophomina phaseolina, Neofusicoccum parvum, Diplodia corticola, and Lasiodiplodia theobromae. An investigation of genes specific to or expanded in B. dothidea revealed that one secreted glucanase, one orsellinic acid biosynthesis enzyme, and two MFS transporters positively regulated B. dothidea's pathogenicity. We also observed an overrepresentation of viral integrase like gene and heterokaryon incompatibility proteins in the B. dothidea's genome. In addition, we observed one LRR-domain-containing protein and two Sec-domain-containing proteins (Sec_1 and Sec_7) that underwent positive selection. This study will help to understand B. dothidea's pathogenicity and potential influence on the infection of Chinese hickory, which will help in the development of disease control and ensure the security of Chinese hickory production.

A PCR-independent approach for mtDNA enrichment and next-generation sequencing: comprehensive evaluation and clinical application.

BACKGROUND: Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing). RESULTS: By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases. CONCLUSIONS: Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.

B1 inhomogeneity corrected CEST MRI based on direct saturation removed omega plot model at 5T.

PURPOSE: CEST can image macromolecules/compounds via detecting chemical exchange between labile protons and bulk water. B1 field inhomogeneity impairs CEST quantification. Conventional B1 inhomogeneity correction methods depend on interpolation algorithms, B1 choices, acquisition number or calibration curves, making reliable correction challenging. This study proposed a novel B1 inhomogeneity correction method based on a direct saturation (DS) removed omega plot model. METHODS: Four healthy volunteers underwent B1 field mapping and CEST imaging under four nominal B1 levels of 0.75, 1.0, 1.5, and 2.0 µT at 5T. DS was resolved using a multi-pool Lorentzian model and removed from respective Z spectrum. Residual spectral signals were used to construct the omega plot as a linear function of 1/ B 1 2 $$ {B}_1^2 $$ , from which corrected signals at nominal B1 levels were calculated. Routine asymmetry analysis was conducted to quantify amide proton transfer (APT) effect. Its distribution across white matter was compared before and after B1 inhomogeneity correction and also with the conventional interpolation approach. RESULTS: B1 inhomogeneity yielded conspicuous artifact on APT images. Such artifact was mitigated by the proposed method. Homogeneous APT maps were shown with SD consistently smaller than that before B1 inhomogeneity correction and the interpolation method. Moreover, B1 inhomogeneity correction from two and four CEST acquisitions yielded similar results, superior over the interpolation method that derived inconsistent APT contrasts among different B1 choices. CONCLUSION: The proposed method enables reliable B1 inhomogeneity correction from at least two CEST acquisitions, providing an effective way to improve quantitative CEST MRI.

Genetic Background of Blood ß-Hydroxybutyrate Acid Concentrations in Early-Lactating Holstein Dairy Cows Based on Genome-Wide Association Analyses.

Ketosis is a common metabolic disorder in the early lactation of dairy cows. It is typically diagnosed by measuring the concentration of ß-hydroxybutyrate (BHB) in the blood. This study aimed to estimate the genetic parameters of blood BHB and conducted a genome-wide association study (GWAS) based on the estimated breeding value. Phenotypic data were collected from December 2019 to August 2023, comprising blood BHB concentrations in 45,617 Holstein cows during the three weeks post-calving across seven dairy farms. Genotypic data were obtained using the Neogen Geneseek Genomic Profiler (GGP) Bovine 100 K SNP Chip and GGP Bovine SNP50 v3 (Illumina Inc., San Diego, CA, USA) for genotyping. The estimated heritability and repeatability values for blood BHB levels were 0.167 and 0.175, respectively. The GWAS result detected a total of ten genome-wide significant associations with blood BHB. Significant SNPs were distributed in Bos taurus autosomes (BTA) 2, 6, 9, 11, 13, and 23, with 48 annotated candidate genes. These potential genes included those associated with insulin regulation, such as INSIG2, and those linked to fatty acid metabolism, such as HADHB, HADHA, and PANK2. Enrichment analysis of the candidate genes for blood BHB revealed the molecular functions and biological processes involved in fatty acid and lipid metabolism in dairy cattle. The identification of novel genomic regions in this study contributes to the characterization of key genes and pathways that elucidate susceptibility to ketosis in dairy cattle.

Revealing the mechanisms of semantic satiation with deep learning models.

The phenomenon of semantic satiation, which refers to the loss of meaning of a word or phrase after being repeated many times, is a well-known psychological phenomenon. However, the microscopic neural computational principles responsible for these mechanisms remain unknown. In this study, we use a deep learning model of continuous coupled neural networks to investigate the mechanism underlying semantic satiation and precisely describe this process with neuronal components. Our results suggest that, from a mesoscopic perspective, semantic satiation may be a bottom-up process. Unlike existing macroscopic psychological studies that suggest that semantic satiation is a top-down process, our simulations use a similar experimental paradigm as classical psychology experiments and observe similar results. Satiation of semantic objectives, similar to the learning process of our network model used for object recognition, relies on continuous learning and switching between objects. The underlying neural coupling strengthens or weakens satiation. Taken together, both neural and network mechanisms play a role in controlling semantic satiation.

Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Connectional-style-guided contextual representation learning for brain disease diagnosis.

Structural magnetic resonance imaging (sMRI) has shown great clinical value and has been widely used in deep learning (DL) based computer-aided brain disease diagnosis. Previous DL-based approaches focused on local shapes and textures in brain sMRI that may be significant only within a particular domain. The learned representations are likely to contain spurious information and have poor generalization ability in other diseases and datasets. To facilitate capturing meaningful and robust features, it is necessary to first comprehensively understand the intrinsic pattern of the brain that is not restricted within a single data/task domain. Considering that the brain is a complex connectome of interlinked neurons, the connectional properties in the brain have strong biological significance, which is shared across multiple domains and covers most pathological information. In this work, we propose a connectional style contextual representation learning model (CS-CRL) to capture the intrinsic pattern of the brain, used for multiple brain disease diagnosis. Specifically, it has a vision transformer (ViT) encoder and leverages mask reconstruction as the proxy task and Gram matrices to guide the representation of connectional information. It facilitates the capture of global context and the aggregation of features with biological plausibility. The results indicate that CS-CRL achieves superior accuracy in multiple brain disease diagnosis tasks across six datasets and three diseases and outperforms state-of-the-art models. Furthermore, we demonstrate that CS-CRL captures more brain-network-like properties, and better aggregates features, is easier to optimize, and is more robust to noise, which explains its superiority in theory.

DPP: deep phase prior for parallel imaging with wave encoding.

Objective.In Magnetic Resonance (MR) parallel imaging with virtual channel-expanded Wave encoding, limitations are imposed on the ability to comprehensively and accurately characterize the background phase. These limitations are primarily attributed to the calibration process relying solely on center low-frequency Auto-Calibration Signals (ACS) data for calibration.Approach.To tackle the challenge of accurately estimating the background phase in wave encoding, a novel deep neural network model guided by deep phase priors is proposed with integrated virtual conjugate coil (VCC) extension. Concretely, within the proposed framework, the background phase is implicitly characterized by employing a carefully designed decoder convolutional neural network, leveraging the inherent characteristics of phase smoothness and compact support in the transformed domain. Furthermore, the proposed model with wave encoding benefits from additional priors, which incorporate transmission sparsity of the latent image and coil sensitivity smoothness.Main results.Ablation experiments were conducted to ascertain the proposed method's capability to implicitly represent CSM and the background phase. Subsequently, the superiority of the proposed method is demonstrated through confidence comparisons with competing methods, employing 4-fold and 5-fold acceleration experiments. In achieving 4-fold and 5-fold acceleration, the optimal quantitative metrics (PSNR/SSIM/NMSE) are 44.1359 dB/0.9863/0.0008 (4-fold) and 41.2074/0.9846/0.0017 (5-fold), respectively. Furthermore, the generalizability of the proposed method is further validated by conducting acceleration experiments with T1, T2, T2*, and various undersampling patterns. In addition, the DPP delivered much better performance than the conventional methods by exploring accelerated phase-sensitive SWI imaging. In SWI accelerated imaging, it also surpasses the optimal competing method in terms of (PSNR/SSIM/NMSE) with 0.096%/0.009%/0.0017%.Significance.The proposed method enables precise characterization of the background phase in the integrated VCC and wave encoding framework, supported via theoretical analysis and empirical findings. Our code is available at:https://github.com/sober235/DPP.

Triterpenoids and triterpenoid saponins from Vitex negundo and their anti-inflammatory activities.

Seven undescribed polyoxygenated ursane-type triterpenoids (vitnegundins A-G), three undescribed triterpenoid saponins (vitnegundins H-J), and 17 known ones were isolated from an EtOH extract of the aerial parts of Vitex negundo L. The structures of the undescribed compounds were established by extensive spectroscopic analysis. The absolute configurations of vitnegundins A, B, and E were determined by single-crystal X-ray diffraction data. Vitnegundins B-D are pentacyclic triterpenoids possessing rare cis-fused C/D rings and vitnegundins C-H represent undescribed ursane-type triterpenoids with 12,19-epoxy moiety. In the biological activity assay, vitnegundin A, vitnegundin E, and swinhoeic acid displayed inhibitory effects against LPS-induced NO release in BV-2 microglial cells, with IC50 values of 11.8, 44.2, and 19.6 µM, respectively.

N-Cinnamoylpyrrole-derived alkaloids from the genus Piper as promising agents for ischemic stroke by targeting eEF1A1.

BACKGROUND: Ischemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile. PURPOSE: The present research aimed to explore the antineuroinflammatory and antioxidative stress effects of N-cinnamoylpyrrole-derived alkaloids isolated from the genus Piper and to explain the effects and mechanism on IS. METHODS: N-cinnamoylpyrrole-derived alkaloids were isolated from Piper boehmeriaefolium var. tonkinense and Piper sarmentosum and identified by various chromatographic methods. Lipopolysaccharide (LPS)-induced BV-2 microglia and a mouse model intracerebroventricularly injected with LPS were used to evaluate the antineuroinflammatory and antioxidative stress effects. Oxygen‒glucose deprivation/reperfusion (OGD/R) and transient middle cerebral artery occlusion (tMCAO) models were used to evaluate the effect of PB-1 on IS. To elucidate the fundamental mechanism, the functional target of PB-1 was identified by affinity-based protein profiling (ABPP) strategy and verified by cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and circular dichroism (CD) analyses. The effect of PB-1 on the NF-κB and NRF2 signaling pathways was subsequently evaluated via western blotting and immunofluorescence staining. RESULTS: The results showed that N-cinnamoylpyrrole-derived alkaloids significantly affected neuroinflammation and oxidative stress. The representative compound, PB-1 not only inhibited neuroinflammation and oxidative stress induced by LPS or OGD/R insult, but also alleviated cerebral ischemic injury induced by tMCAO. Further molecular mechanism research found that PB-1 promoted antineuroinflammatory and antioxidative stress activities via the NF-κB and NRF2 signaling pathways by targeting eEF1A1. CONCLUSION: Our research initially unveiled that the therapeutic impact of PB-1 on cerebral ischemic injury might rely on its ability to target eEF1A1, leading to antineuroinflammatory and antioxidative stress effects. The novel discovery highlights eEF1A1 as a potential target for IS treatment and shows that PB-1, as a lead compound that targets eEF1A1, may be a promising therapeutic agent for IS.

High-performance multi-junction cascade 1.3†µm quantum dot vertical cavity surface-emitting laser.

A high-performance 5-junction cascade quantum dot (QD) vertical cavity surface-emitting laser (VCSEL) with 1.3 µm wavelength was designed. The characteristics of the QD as active regions and tunnel junctions are combined to effectively increase output power. The photoelectric characteristics of single-junction, 3-junction cascade, and 5-junction cascade QD VCSELs are compared at continuous-wave conditions. Results indicate that the threshold current gradually decreases, and the output power and slope efficiency exponential increase with the increase of the number of active regions. The peak power conversion efficiency of 58.4% is achieved for the 5-junction cascade individual QD VCSEL emitter with 10 µm oxide aperture. The maximum slope efficiency of the device is 6.27 W/A, which is approximately six times than that of the single-junction QD VCSEL. The output power of the 5-junction cascade QD VCSEL reaches 188.13 mW at injection current 30 mA. High-performance multi-junction cascade 1.3-µm QD VCSEL provides data and theoretical support for the preparation of epitaxial materials.

Amendment of straw with decomposing inoculants benefits the ecosystem carbon budget and carbon footprint in a subtropical wheat cropping field.

The incorporation of straw with decomposing inoculants into soils has been widely recommended to sustain agricultural productivity. However, comprehensive analyses assessing the effects of straw combined with decomposing inoculants on greenhouse gas (GHG) emissions, net primary production (NPP), the net ecosystem carbon budget (NECB), and the carbon footprint (CF) in farmland ecosystems are scant. Here, we carried out a 2-year field study in a wheat cropping system with six treatments: rice straw (S), a straw-decomposing Bacillus subtilis inoculant (K), a straw-decomposing Aspergillus oryzae inoculant (Q), a combination of straw and Bacillus subtilis inoculant (SK), a combination of straw and Aspergillus oryzae inoculant (SQ), and a control with no rice straw or decomposing inoculant (Control). We found that all the treatments resulted in a positive NECB ranging between 838 and 5065 kg C ha-1. Relative to the Control, the S treatment increased CO2 emissions by 16%, while considerably enhancing the NECB by 349%. This difference might be attributed to the straw C input and an increase in plant productivity (NPP, 30%). More importantly, in comparison to that in S, the NECB in SK and SQ significantly increased by 27-35% due to the positive response of NPP to the decomposing inoculants. Although the combination of straw and decomposing inoculants yielded a 3% increase in indirect GHG emissions, it also exhibited the lowest CF (0.18 kg CO2-eq kg-1 of grain). This result was attributed to the synergistic effects of straw and decomposing inoculants, which reduced direct N2O emissions and increased wheat productivity. Overall, the findings of the present study suggested that the combined amendment of straw and decomposing inoculants is an environmentally sustainable management practice in wheat cropping systems that can generate win-win scenarios through improvements in soil C stock, crop productivity, and GHG mitigation.

Emergence, Pattern, and Frequency of Spontaneous Waves in Spreading Epithelial Monolayers.

A striking phenomenon of collective cell motion is that they can exhibit a spontaneously emerging wave during epithelia expansions. However, the fundamental mechanism, governing the emergence and its crucial characteristics (e.g., the eigenfrequency and the pattern), remains an enigma. By introducing a mechanochemical feedback loop, we develop a highly efficient discrete vertex model to investigate the spatiotemporal evolution of spreading epithelia. We find both numerically and analytically that expanding cell monolayers display a power-law dependence of wave frequency on the local heterogeneities (i.e., cell density) with a scaling exponent of -1/2. Moreover, our study demonstrates the quantitative capability of the proposed model in capturing distinct X-, W-, and V-mode wave patterns. We unveil that the phase transition between these modes is governed by the distribution of active self-propulsion forces. Our work provides an avenue for rigorous quantitative investigations into the collective motion and pattern formation of cell groups.