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AIMS: While previous single-cell RNA sequencing (scRNA-seq) studies have attempted to dissect intracranial aneurysm (IA), the primary molecular mechanism for IA pathogenesis remains unknown. Here, we uncovered the alterations of cellular compositions, especially the transcriptome changes of vascular endothelial cells (ECs), in human IA. METHODS AND RESULTS: We performed scRNA-seq to compare the cell atlas of sporadic IA and the control artery. The transcriptomes of 43,462 cells were profiled for further analysis. In general, IA had increased immune cells (T/NK cells, B cells, myeloid cells, mast cells, neutrophils) and fewer vascular cells (ECs, vascular smooth muscle cells and fibroblasts). Based on the obtained high-quantity and high-quality EC data, we found genes associated with angiogenesis in ECs from IA patients. By EC-specific expression of candidate genes in vivo, we observed the involvement of angpt2a in causing cerebral vascular abnormality. Furthermore, an IA zebrafish model mimicking the main features of human IA was generated through targeting pdgfrb gene, and knockdown of angpt2a alleviated the vascular dilation in the IA zebrafish model. CONCLUSION: By performing a landscape view of the single-cell transcriptomes of IA and the control artery, we contribute to a deeper understanding of the cellular composition and the molecular changes of ECs in IA. The implication of angiogenic regulator ANGPT2 in IA formation and progression, provides a novel potential therapeutical target for IA interventions.
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This paper employs an innovative event study methodology to demonstrate the impact of climate change on the NASDAQ index from the unique perspective of extreme weather events. This is achieved through the application of the event study methodology to a total of 526 biological, climatic, geological, hydrological, and meteorological disasters of climate change occurring in the U.S. during the period of 2000-2019. The results of the study demonstrate that: â it can be generally observed that the five dimensions of climate change have a significant impact on stock returns. â¡ Empirical evidence indicates that the impact of different climate change dimensions on the return rate of stocks from NASDAQ stocks varies. In contrast, the biological and hydrological dimensions have a significantly negative impact on the return rate of stocks from the NASDAQ index, while the climate dimension has a significantly positive impact on the return rate of stocks from the NASDAQ index. ⢠From the perspective of time, the impact of the five dimensions of climate change on the stock yield exhibits certain non-linear characteristics. This can be observed in the phenomenon of shock reversal, which occurs before and after the event.
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High-performance thermal interface materials (TIMs) are highly desired for high-power electronic devices to accelerate heat dissipation. However, the inherent trade-off conflict between achieving high thermal conductivity and excellent compliance of filler-enhanced TIMs results in the unsatisfactory interfacial heat transfer efficiency of existing TIM solutions. Here, we report the graphene fiber (GF)-based elastic TIM with metal-level thermal conductivity via mechanical-electric dual-field synergistic alignment engineering. Compared with state-of-the-art carbon fiber (CF), GF features both superb high thermal conductivity of â¼1200 W m-1 K-1 and outstanding flexibility. Under dual-field synergistic alignment regulation, GFs are vertically aligned with excellent orientation (0.88) and high array density (33.5 mg cm-2), forming continuous thermally conductive pathways. Even at a low filler content of â¼17 wt %, GF-based TIM demonstrates extraordinarily high through-plane thermal conductivity of up to 82.4 W m-1 K-1, exceeding most CF-based TIMs and even comparable to commonly used soft indium foil. Benefiting from the low stiffness of GF, GF-based TIM shows a lower compressive modulus down to 0.57 MPa, an excellent resilience rate of 95% after compressive cycles, and diminished contact thermal resistance as low as 7.4 K mm2 W-1. Our results provide a superb paradigm for the directed assembly of thermally conductive and flexible GFs to achieve scalable and high-performance TIMs, overcoming the long-standing bottleneck of mechanical-thermal mismatch in TIM design.
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Indoor semivolatile organic compounds (SVOCs) pose a substantial threat to human health. However, identifying the sources of these emissions has been challenging owing to the scarcity of convenient and practical on-site methodologies. Herein, a novel method for source screening was proposed using aluminum silicate sampling strips to adsorb SVOCs from the surface air of indoor materials. The adsorbed SVOC levels indicate the emission intensity of these materials into indoor environments. Additionally, compact sampling strips can be readily fixed to any vertical surface using a static sticker, facilitating the characterization of various materials in practical settings. Laboratory-simulated experiments demonstrated the capability of the proposed method to differentiate between source and non-source materials within a 10-cm distance in the same space. In practical scenarios, the primary emission sources identified via this method exhibited a consistent correlation with the contents of the corresponding materials obtained from the traditional solvent-extraction method. As the adsorbed SVOCs were directly transferred to a GC-MS through thermal desorption instead of the solvent-extraction procedure, the proposed method demonstrated several-fold improvements in analytical sensitivity and efficiency. Using this versatile screening technique, some emerging and important SVOC species were identified within specific indoor materials. Eliminating these sources has been demonstrated as an effective approach to mitigate SVOC pollution. Overall, the proposed method offers a powerful tool for managing indoor pollutants and safeguarding human health.
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Poluição do Ar em Ambientes Fechados , Monitoramento Ambiental , Compostos Orgânicos Voláteis , Poluição do Ar em Ambientes Fechados/análise , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Poluentes Atmosféricos/análise , HumanosRESUMO
BACKGROUND: Gastric cancer is one of the most common tumors worldwide, and most patients are deprived of treatment options when diagnosed at advanced stages. PRDM14 has carcinogenic potential in breast and non-small cell lung cancer. however, its role in gastric cancer has not been elucidated. METHODS: We aimed to elucidate the expression of PRDM14 using pan-cancer analysis. We monitored the expression of PRDM14 in cells and patients using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. We observed that cell phenotypes and regulatory genes were influenced by PRDM14 by silencing PRDM14. We evaluated and validated the value of the PRDM14-derived prognostic model. Finally, we predicted the relationship between PRDM14 and small-molecule drug responses using the Connectivity Map and The Genomics of Drug Sensitivity in Cancer databases. RESULTS: PRDM14 was significantly overexpressed in gastric cancer, which identified in cell lines and patients' tissues. Silencing the expression of PRDM14 resulted in apoptosis promotion, cell cycle arrest, and inhibition of the growth and migration of GC cells. Functional analysis revealed that PRDM14 acts in epigenetic regulation and modulates multiple DNA methyltransferases or transcription factors. The PRDM14-derived differentially expressed gene prognostic model was validated to reliably predict the patient prognosis. Nomograms (age, sex, and PRDM14-risk score) were used to quantify the probability of survival. PRDM14 was positively correlated with sensitivity to small-molecule drugs such as TPCA-1, PF-56,227, mirin, and linsitinib. CONCLUSIONS: Collectively, our findings suggest that PRDM14 is a positive regulator of gastric cancer progression. Therefore, it may be a potential therapeutic target for gastric cancer.
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Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas , Fatores de Transcrição , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Prognóstico , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Feminino , Masculino , Nomogramas , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Epigênese GenéticaRESUMO
RNA modification, especially RNA methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all RNA modifications. It plays a significant role in RNA metabolism, affecting RNA processing, stability, and translation, thereby modulating gene expression and cell functions essential for proliferation, survival, and metastasis. Increasing studies have revealed the disruption in RNA metabolism mediated by RNA methylation has been implicated in various aspects of cancer progression, particularly in metabolic reprogramming and immunity. This disruption of RNA methylation has profound implications for tumor growth, metastasis, and therapy response. Herein, we elucidate the fundamental characteristics of RNA methylation and their impact on RNA metabolism and gene expression. We highlight the intricate relationship between RNA methylation, cancer metabolic reprogramming, and immunity, using the well-characterized phenomenon of cancer metabolic reprogramming as a framework to discuss RNA methylation's specific roles and mechanisms in cancer progression. Furthermore, we explore the potential of targeting RNA methylation regulators as a novel approach for cancer therapy. By underscoring the complex mechanisms by which RNA methylation contributes to cancer progression, this review provides a foundation for developing new prognostic markers and therapeutic strategies aimed at modulating RNA methylation in cancer treatment.
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The chemistry of ozone (O3) on indoor surfaces leads to secondary pollution, aggravating the air quality in indoor environments. Here, we assess the heterogeneous chemistry of gaseous O3 with glass plates after being 1 month in two different kitchens where Chinese and Western styles of cooking were applied, respectively. The uptake coefficients of O3 on the authentic glass plates were measured in the dark and under UV light irradiation typical for indoor environments (320 nm < λ < 400 nm) at different relative humidities. The gas-phase product compounds formed upon reactions of O3 with the glass plates were evaluated in real time by a proton-transfer-reaction quadrupole-interface time-of-flight mass spectrometer. We observed typical aldehydes formed by the O3 reactions with the unsaturated fatty acid constituents of cooking oils. The formation of decanal, 6-methyl-5-hepten-2-one (6-MHO), and 4-oxopentanal (4-OPA) was also observed. The employed dynamic mass balance model shows that the estimated mixing ratios of hexanal, octanal, nonanal, decanal, undecanal, 6-MHO, and 4-OPA due to O3 chemistry with authentic grime-coated kitchen glass surfaces are higher in the kitchen where Chinese food was cooked compared to that where Western food was cooked. These results show that O3 chemistry on greasy glass surfaces leads to enhanced VOC levels in indoor environments.
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Poluição do Ar em Ambientes Fechados , Culinária , Vidro , Ozônio , Compostos Orgânicos Voláteis , Ozônio/química , Vidro/química , Poluentes AtmosféricosRESUMO
The brachial plexus injury (BPI) is one of the most severe types of peripheral nerve injuries, often caused by upper limb traction injury. In clinic, the surgery is widely used to treat the BPI. However, surgery may need to be performed multiple times at different stages, which carries risks and brings heavy economic burden. In non-surgical treatment, splinting, local injection of corticosteroids, and oral corticosteroids can achieve significant short-term benefits, but they are prone to recurrence and may cause complications of mechanical or chemical nerve damage. In this report, we present a case of a 46-year-old female patient with BPI. The patient had difficulty in raising, flexing and extending of the left upper limb, and accompanied with the soreness and pain of neck and shoulder. After 3 months of EA treatment, a significant reduction in the inner diameter of the left C5 to C7 root at the outlet of brachial plexus nerve was detected by musculoskeletal ultrasound, and the soreness and pain in the left neck and shoulder were significantly reduced. The soreness and pain in the left neck and shoulder did not recur for 2 years. Case summary: The patient is a 46-year-old female with BPI. She experienced difficult in lifting, flexing and extending of the left upper limb, which accompanied by soreness and pain in the left neck and shoulder. After 3 months of EA treatment, the patient's pain and limb's movement disorder was improved. After 2 years of follow-up, the patient's left neck and shoulder showed no further pain. Conclusion: EA has shown satisfied efficacy in BPI, improving limb restrictions and relieving pain in patients for at least 2 years.
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Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. Here, we identify a neuroprotective role for NG2 glia against prion toxicity. NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia enhanced the biosynthesis of prostaglandin E2 (PGE2) by microglia, which augmented prion neurotoxicity through binding to the EP4 receptor. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.
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Dinoprostona , Microglia , Neuroglia , Neurônios , Doenças Priônicas , Transdução de Sinais , Animais , Microglia/metabolismo , Dinoprostona/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neuroglia/metabolismo , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Camundongos Endogâmicos C57BL , Antígenos/metabolismo , Proteoglicanas/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Príons/metabolismo , Príons/toxicidade , Cerebelo/metabolismo , Cerebelo/patologiaRESUMO
Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels. The mechanical robustness is demonstrated to be derived from the trans-scale porous structure, which is composed of hyperbolic micropores and porous nanofibers to enable the large elastic deformation capability. It is further revealed that flexible and superelastic GNFAs exhibit high sensitivity and ultrastability as an electrical sensors to detect tension and flexion deformation. As proof, The GNFA sensor is implemented onto a human finger and achieves the intelligent recognition of sign language with high accuracy by multi-layer artificial neural network. This study proposes a highly flexible and elastic graphene aerogel for wearable human-machine interfaces in sensor technology.
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OBJECTIVE: Craniocervical junction arteriovenous fistulas (CCJ-AVFs) are complex vascular shunts that present a challenge for treatment. The aim of this study was to compare the clinical outcomes of microsurgery and endovascular embolization for CCJ-AVFs and to determine whether the treatment approach affected the obliteration rate and neurological improvement. METHODS: The authors conducted a retrospective analysis of 64 patients who had undergone microsurgery or endovascular embolization for CCJ-AVF at one of two neurosurgical centers from January 2014 to February 2022. Additionally, a pooled analysis of 68 patients from 38 studies was performed. Baseline characteristics, angioarchitectural features, and clinical outcomes were compared between two treatment groups. A subgroup analysis of CCJ-AVFs with carotid artery (CA) feeders was also performed. RESULTS: In the multicenter cohort, the complete obliteration rate was 95.1% with microsurgery, 81.8% with embolization via the CA, and 50.0% with embolization via the vertebral artery (VA). After adjusting for baseline and confounding features, the occlusion rate was significantly lower in the VA embolization group (adjusted OR 41.06, 95% CI 2.37-711.9, p = 0.01). No new-onset infarctions occurred in the microsurgical group, whereas 1 patient each in the CA and VA embolization groups experienced posttreatment infarction. Microsurgery demonstrated a neurological improvement rate similar to that in the CA embolization group (65.9% vs 63.6%, respectively). In the subgroup analysis of CCJ-AVF with CA feeders in the multicenter cohort, the occlusion rate and neurological improvement in the CA embolization group were comparable to those in the microsurgery group. The subgroup analysis in the pooled analysis revealed complete obliteration rates of 100.0% in the microsurgical group, 88.9% in the CA embolization group, and 66.7% in the VA embolization group. CONCLUSIONS: This study supports microsurgery as the best treatment modality for CCJ-AVFs, exhibiting the highest rates of complete obliteration. Conversely, embolization via the VA can result in a lower occlusion rate and less neurological improvement. In CCJ-AVFs with CA feeders, embolization via the CA can be a safe and effective alternative to microsurgery.
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Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.
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Background: For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial. Objectives: The present study was conducted to evaluate the efficacy and explore new treatment strategies of TBP for patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer in the era of cancer immunotherapy. Design: Retrospective analysis. Methods: Patients with HER2-positive advanced or metastatic gastric cancer who have failed first-line treatment based on trastuzumab-targeted therapy from June 2019 to December 2020 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival curves of patients were estimated by the Kaplan-Meier method and compared using the log-rank test. Results: In all, 30 patients received TBP with chemotherapy, immunotherapy, or anti-angiogenic therapy, and the other 26 patients received treatment of physician's choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0 [95% confidence interval (CI) = 3.8-8.2] and 3.5 (95% CI = 2.2-4.8) months, respectively (p = 0.038), and the median OS was 12.3 (95% CI = 10.4-14.2) and 9.0 (95% CI = 6.6-11.4) months (p = 0.008). The patients who received TBP treatment had more favorable PFS and OS than the non-TBP population. In the TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR (40.0% versus 16.7%), DCR (90.0% versus 50.0%), and showed a significant improvement in PFS (7.0 versus 1.9 m) compared to TBP with chemotherapy alone. Subgroup analysis suggested that patients with male, HER2 positive with immunohistochemistry score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The incidence of Grade 3-4 adverse events in the TBP and non-TBP groups was 43.3% and 38.5%. Conclusion: The continuous use of TBP improves PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well-tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy. Trial registration: This study is a retrospective study, which does not require clinical registration.
The value of TBP in trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer Patients with human epidermal growth factor receptor-2 (HER2) positive advanced or metastatic gastric cancer who have failed from first-line treatment based on trastuzumab targeted therapy from June 2019 to December 2020 were retrospectively analyzed. 30 patients received TBP with chemotherapy, immunotherapy or anti-angiogenic therapy, and the other 26 patients received treatment of physician's choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0(95% CIâ=â3.8-8.2) and 3.5 (95% CIâ=â2.2-4.8) months, respectively (Pâ=â0.038), and the median OS was 12.3 (95% CIâ=â10.4-14.2) and 9.0 (95% CIâ=â6.6-11.4) months (Pâ=â0.008). In TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR, DCR and showed a significant improvement in PFS compared to TBP with chemotherapy-alone (pâ=â0.024). Subgroup analysis suggested that patients with male, HER2-positive with IHC score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The continuous use of TBP does not increase the incidence of adverse events (AEs). The continuous use of TBP improve PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy further enhanced the clinical benefit and provide new treatment strategy.
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Flat membranes ubiquitously transform into mysterious complex shapes in nature and artificial worlds. Behind the complexity, clear determinative deformation modes have been continuously found to serve as basic application rules but remain unfulfilled. Here, we decipher two elemental deformation modes of thin membranes, spontaneous scrolling and folding as passing through shrinking channels. We validate that these two modes rule the deformation of membranes of a wide thickness range from micrometer to atomic scale. Their occurrence and the determinative fold number quantitatively correlate with the Föppl-von Kármán number and shrinkage ratio. The unveiled determinative deformation modes can guide fabricating foldable designer microrobots and delicate structures of two-dimensional sheets and provide another mechanical principle beyond genetic determinism in biological morphogens.
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Background: Severe delayed diarrhea and hematological toxicity limit the use of irinotecan. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a critical enzyme in irinotecan metabolism. The study aims to investigate the safety and efficacy of irinotecan under the guidance of the pre-treatment UGT1A1 genotype in the second-line treatment of gastric cancer. Methods: This study involved 110 patients. Irinotecan was injected intravenously every 3 weeks, and the dose of irinotecan was determined by polymorphism of the UGT1A1 gene, which was divided into three groups (125â mg/m2: GG type; 100â mg/m2: GA type; 75â mg/m2: AA type). The primary end point was overall survival (OS), the secondary end points were progression-free survival (PFS) and safety. Results: One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Among 107 patients, there were no significant differences in PFS (4.8â m vs 4.9â m vs 4.4â m; p = 0.5249) and OS (9.3â m vs 9.3â m vs NA; p = 0.6821) among patients with GG/GA/AA subtypes after dose adjustment. For the patient with homozygosity mutation, treatment was switched to paclitaxel. There were no significant differences in PFS and OS among patients with different alleles or after dose adjustment (p > 0.05). There was a significant difference in the risk of delayed diarrhea (p = 0.000), leukopenia (p = 0.003) and neutropenia (p = 0.000) in patients with different UGT1A1*6 genotypes, while no difference in patients with different UGT1A1*28 genotypes. Additionally, grade 3/4 diarrhea, neutropenia, and leukopenia were significantly more common in AA genotype patients compared to GG (2%, 19%, 24%) or GA (23%, 31%, 31%) genotype patients. Conclusion: Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.
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Antineoplásicos Fitogênicos , Neutropenia , Neoplasias Gástricas , Humanos , Antineoplásicos Fitogênicos/uso terapêutico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Genótipo , Glucuronosiltransferase/genética , Irinotecano/efeitos adversos , Neutropenia/induzido quimicamente , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genéticaRESUMO
Pectin has been extensively studied in animal immunity, and exogenous pectin as a food additive can provide protection against inflammatory bowel disease. However, the utility of pectin to improve immunity in plants is still unstudied. Here, we found exogenous application of pectin triggered stomatal closure in Arabidopsis in a dose- and time-dependent manner. Additionally, pectin activated peroxidase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to produce reactive oxygen species (ROS), which subsequently increased cytoplasmic Ca2+ concentration ([Ca2+ ]cyt ) and was followed by nitric oxide (NO) production, leading to stomatal closure in an abscisic acid (ABA) and salicylic acid (SA) signalling-dependent mechanism. Furthermore, pectin enhanced the disease resistance to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) with mitogen-activated protein kinases (MPKs) MPK3/6 activated and upregulated expression of defence-responsive genes in Arabidopsis. These results suggested that exogenous pectin-induced stomatal closure was associated with ROS and NO production regulated by ABA and SA signalling, contributing to defence against Pst DC3000 in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Pectinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estômatos de Plantas/genética , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismoRESUMO
PURPOSE: More than 90% of patients with diabetes worldwide are type 2 diabetes (T2D), which is caused by insulin resistance or impaired producing insulin by pancreatic ß cells. T2D and its complications, mainly large cardiovascular (LCV) and kidney (Ne) complications, are the major cause of death in diabetes patients. Recently, the dysregulation of peripheral T cell immune homeostasis was found in most T2D patients. However, the characteristics of T-cell receptors (TCR) remain largely unexplored in T2D patients. PATIENTS AND METHODS: Here we investigated the TCR repertoire using high-throughput sequencing in peripheral blood collected from T2D patient with (8 LCV and 7 Ne) or without complications. RESULTS: Our analysis of TCR repertoires in peripheral blood samples showed that TCR profiles in T2D patients with complications tended to be single and specific compared to controls, according to the characteristics of TCR repertoire in V-J combination number, diversity, principal component analysis (PCA) and differential genes. And we identified some differentially expressed V-J gene segments and amino acid clonotypes, which had the potential to contribute to distinguishing T2D patient with or without complications. As the progression of the disease, we found that the profiling of TCR repertoire was also differential between T2D patients with LVD and Ne complications base on this pilot analysis. CONCLUSION: This study demonstrated the protentional unique property of TCR repertoire in peripheral blood of T2D patient with and without complications, or T2D patients with LVD and Ne complications, which provided the possibility for future improvements in immune-related diagnosis and therapy for T2D complications.
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Diabetes Mellitus Tipo 2 , Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T/genética , Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Receptores de Antígenos de Linfócitos T alfa-beta/genéticaRESUMO
Macroscopic fibres assembled from two-dimensional (2D) nanosheets are new and impressing type of fibre materials besides those from one-dimensional (1D) polymers, such as graphene fibres. However, the preparation and property-enhancing technologies of these fibres follow those from 1D polymers by improving the orientation along the fibre axis, leading to non-optimized microstructures and low integrated performances. Here, we show a concept of bidirectionally promoting the assembly order, making graphene fibres achieve synergistically improved mechanical and thermal properties. Concentric arrangement of graphene oxide sheets in the cross-section and alignment along fibre axis are realized by multiple shear-flow fields, which bidirectionally promotes the sheet-order of graphene sheets in solid fibres, generates densified and crystalline graphitic structures, and produces graphene fibres with ultrahigh modulus (901 GPa) and thermal conductivity (1660 W m-1 K-1). We believe that the concept would enhance both scientific and technological cognition of the assembly process of 2D nanosheets.
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Human occupants themselves constitute an important source of volatile organic compounds (VOCs) in indoor environments through breath and dermal emissions. In order to quantify VOC emissions from occupants under real-world settings, previous indoor observational studies often determined emission factors (i.e., average emission rates per person). However, the values obtained across these studies exhibited large variability, and the causes of this variability still need to be understood. Herein we report 10-day real-time VOC measurements in a university student office, using a proton transfer reaction-quadrupole interface-time-of-flight mass spectrometer. A method was developed to identify VOCs of primary human origin and to quantify the corresponding emission factors, accounting for the dynamically changing occupancy level and ventilation rate in the assessed office. We found that the emission factors of many dermally emitted VOCs strongly increased as the ozone concentration increased from <3 to 10-15 ppb. These VOCs include geranyl acetone, 6-methyl-5-hepten-2-one (6-MHO), and C10-C12 saturated aldehydes, which align with characteristic first-generation ozonolysis products of skin oil. The strongest increase occurred for 6-MHO, from 113 to 337 µg/h/p. In comparison, acetone and isoprene, which are primarily emitted from human breath, varied little with the ozone level. In light of this finding, we conducted an integrated analysis of emission factors reported in the literature for two frequently reported species, namely, 6-MHO and decanal. Ozone concentration alone can explain 94-97% of the variation in their emission factors across previous studies, and the best-estimated ozone dependence obtained using the literature data is consistent with those obtained in the current study. These results suggest that the ozone concentration is a key factor regulating emission factors of many dermally emitted VOCs in real indoor environments, which has to be considered when reporting or using the emission factors.
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BACKGROUND: Novel ADC drugs provide a new therapeutic strategy for gastric cancer.The present study aimed to analyze the clinical efficacy and drug toxicities of disitamab vedotin (RC48) plus immune checkpoint inhibitors(ICIs) and RC48 as third-line therapies and beyond for advanced and metastatic gastric cancer patients. METHODS: This was an observational multicenter real-world study.From August 2021 to January 2022,patients with HER2-positive or HER2-low advanced and metastatic gastric cancer and failed from two or more lines of prior therapy were enrolled and treated with RC48 plus ICIs or RC48. In this study, progression free survival(PFS) was the primary end point. Other evaluation indicators were objective response rate(ORR),disease control rate(DCR),overall survival(OS) and drug toxicities. RESULTS: 45 patients were enrolled,of which 25 patients received RC48 plus ICIs,20 patients received RC48.Patients who received RC48 plus ICIs obtained better ORR (36.0% vs. 10.0%, P = 0.044) and DCR (80.0% vs. 50.0%, P = 0.034) compared with RC48,and simultaneously,the median PFS in RC48 plus ICIs group were superior to RC48 group(6.2 m vs. 3.9 m).The median OS was not reached.No statistically differences were found between HER2-positive and HER2-low group with respect to ORR (27.3% vs. 16.7%, P = 0.464),DCR (66.7% vs. 66.7%, P = 1.000),median PFS(5.7 m vs. 4.3 m, P = 0.299).The most common adverse events (AEs) were decreased white blood count,decreased neutrophil count,fatigue,hypoaesthesia and alopecia.Grade 3-4 AEs occurred in 7(35.0%) patients of RC48 group and 10(40.0%) patients of RC48 plus ICIs group,respectively. CONCLUSION: Compared with RC48 monotherapy, ICIs plus RC48 demonstrated superior third-line and beyond therapeutic efficacy for HER2-positive or HER2-low advanced and metastatic gastric cancer patients with manageable safety.