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Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linfócitos T CD4-Positivos , Quimiocina CXCL13 , Interferon Tipo I , Lúpus Eritematoso Sistêmico , Proteínas Proto-Oncogênicas c-jun , Receptores de Hidrocarboneto Arílico , Feminino , Humanos , Masculino , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Quimiocina CXCL13/metabolismo , Epigenômica , Perfilação da Expressão Gênica , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Interleucina 22/imunologia , Interleucina 22/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.
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Antifúngicos , Ácidos Cafeicos , Imidazóis , Antifúngicos/farmacologia , Antifúngicos/química , Imidazóis/química , Imidazóis/farmacologia , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Sais/química , Teoria Quântica , Modelos Moleculares , Testes de Sensibilidade Microbiana , Cristalografia por Raios X , Ligação de Hidrogênio , Eletricidade EstáticaRESUMO
Aqueous zinc-ion capacitors (AZICs) are considered potential energy storage devices thanks to their ultrahigh power density, high safety, and extended cycling life. Carbon-based materials widely used as cathodes in AZICs face challenges, such as inappropriate pore sizes, poor electrolyte-electrode wettability, and insufficient vacancy defects and active sites. These limitations hinder efficient energy storage capacity and long-term stability. To address these issues, the B and F co-doped hierarchical porous carbon cathode materials (BFPC) are constructed through a facile annealing treatment process. The BFPC-2//Zn device exhibited high capacities of 222.4 and 118.3 mAh g-1 at current densities of 0.2 and 10 A g-1, respectively. Notably, the BFPC-2//Zn device demonstrated long-term cycling stability with a high capacity retention of 96.9 % after 20,000 cycles at 10 A g-1. Additionally, the assembled BFPC-2 based AZICs displayed a maximum energy density of 175.8 Wh kg-1 and an ultrahigh power density of 17.3 kW kg-1. Mechanism studies revealed that the exceptional energy storage ability and charge-transfer process of the BFPC cathode are attributed to the synergistic effect of B and F heteroatoms and the coupling effect between vacancy defects and pore size. This work presents a novel design strategy by incorporating B and F active sites into hierarchical porous carbon materials, providing enhanced energy storage capabilities for practical application in AZICs.
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OBJECTIVE: To evaluate the effect of ginger with P6 acupressure in preventing and treating chemotherapy-induced nausea and vomiting (CINV) in cancer patients. METHOD: A total of 172 participants were randomly divided into the control, ginger, acupressure, and joint groups, who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from February and September 2022. The baseline characteristics, nausea, vomiting, and retching, benefit finding, functional living index-emesis, treatment satisfaction, and adverse reaction, were used in data collection. RESULTS: No significant difference was found in benefit finding and adverse reactions among the four groups (P > 0.05). Ginger significantly improved delayed CINV and function living index-nausea (P < 0.05) but had no significant effect on acute CINV, retching, and delayed vomiting, functional living index-emesis, and treatment satisfaction (P>0.05). Acute nausea and retching, delayed nausea, vomiting, and retching, functional living index-emesis, and treatment satisfaction were effectively improved in the acupressure and joint groups (P < 0.05). CONCLUSION: Ginger with P6 acupressure may contribute to improving CINV in patients undergoing chemotherapy.
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Acupressão , Antineoplásicos , Zingiber officinale , Humanos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle , Antineoplásicos/efeitos adversosRESUMO
BACKGROUND: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993). FINDINGS: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group. INTERPRETATION: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease. FUNDING: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Paclitaxel , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Método Duplo-Cego , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , China , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Resultado do Tratamento , Intervalo Livre de ProgressãoRESUMO
Dynamic 3D covalent organic frameworks (COFs) have shown concerted structural transformation and adaptive gas adsorption due to the conformational diversity of organic linkers. However, the isolation and observation of COF rotamers constitute undergoing challenges due to their comparable free energy and subtle rotational energy barrier. Here, we report the atomic-level observation and structural evolution of COF rotamers by cryo-3D electron diffraction and synchrotron powder X-ray diffraction. Specifically, we optimize the crystallinity and morphology of COF-320 to manifest its coherent dynamic responses upon adaptive inclusion of guest molecules. We observe a significant crystal expansion of 29 vol% upon hydration and a giant swelling with volume change up to 78 vol% upon solvation. We record the structural evolution from a non-porous contracted phase to two narrow-pore intermediate phases and the fully opened expanded phase using n-butane as a stabilizing probe at ambient conditions. We uncover the rotational freedom of biphenylene giving rise to significant conformational changes on the diimine motifs from synclinal to syn-periplanar and anticlinal rotamers. We illustrate the 10-fold increment of pore volumes and 100% enhancement of methane uptake capacity of COF-320 at 100 bar and 298 K. The present findings shed light on the design of smarter organic porous materials to maximize host-guest interaction and boost gas uptake capacity through progressive structural transformation.
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BACKGROUND AND PURPOSE: Psoriasis is a common autoimmune skin disease that significantly diminishes patients' quality of life. Interactions between primary afferents of the somatosensory system and the cutaneous immune system mediate the pathogenesis of psoriasis. This study aims to elucidate the molecular mechanisms of how primary sensory neurons regulate psoriasis formation. EXPERIMENTAL APPROACH: Skin and total RNA were extracted from wild-type (WT) and ASH1-like histone lysine methyltransferase (Ash1l+/- ) mice in both naive and imiquimod (IMQ)-induced psoriasis models. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence-activated cell sorting (FACS) were then performed. Microfluidic chamber coculture was used to investigate the interaction between somatosensory neurons and bone marrow dendritic cells (BMDCs) ex vivo. Whole-cell patch clamp recordings were used to evaluate neuronal excitability after Ash1L haploinsufficiency in primary sensory neurons. KEY RESULTS: The haploinsufficiency of ASH1L, a histone methyltransferase, in primary sensory neurons causes both neurite hyperinnervation and increased neuronal excitability, which promote miR-let-7b release from primary afferents in the skin in a neuronal activity-dependent manner. With a 'GUUGUGU' core sequence, miR-let-7b functions as an endogenous ligand of toll-like receptor 7 (TLR7) and stimulates the activation of dermal dendritic cells (DCs) and interleukin (IL)-23/IL-17 axis, ultimately exacerbating the symptoms of psoriasis. Thus, by limiting miR-let-7b release from primary afferents, ASH1L prevents dermal DC activation and ameliorates psoriasis. CONCLUSION AND IMPLICATIONS: Somatosensory neuron ASH1L modulates the cutaneous immune system by limiting neuronal activity-dependent release of miR-let-7b, which can directly activate dermal DCs via TLR7 and ultimately lead to aggravated psoriatic lesion.
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MicroRNAs , Psoríase , Humanos , Animais , Camundongos , Receptor 7 Toll-Like/genética , Qualidade de Vida , Psoríase/etiologia , Psoríase/patologia , Pele/patologia , MicroRNAs/genética , Neurônios/patologia , Modelos Animais de Doenças , Proteínas de Ligação a DNA , Histona-Lisina N-MetiltransferaseRESUMO
Singlet oxygen (1O2) has a very short half-life of 10-5 s; however, it is a strong oxidant that causes growth arrest and necrotic lesions on plants. Its signaling pathway remains largely unknown. The Arabidopsis flu (fluorescent) mutant accumulates a high level of 1O2 and shows drastic changes in nuclear gene expression. Only two plastid proteins, EX1 (executer 1) and EX2 (executer 2), have been identified in the singlet oxygen signaling. Here, we found that the transcription factor abscisic acid insensitive 4 (ABI4) binds the promoters of genes responsive to 1O2-signals. Inactivation of the ABI4 protein in the flu/abi4 double mutant was sufficient to compromise the changes of almost all 1O2-responsive-genes and rescued the lethal phenotype of flu grown under light/dark cycles, similar to the flu/ex1/ex2 triple mutant. In addition to cell death, we reported for the first time that 1O2 also induces cell wall thickening and stomatal development defect. Contrastingly, no apparent growth arrest was observed for the flu mutant under normal light/dim light cycles, but the cell wall thickening (doubled) and stomatal density reduction (by two-thirds) still occurred. These results offer a new idea for breeding stress tolerant plants.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Luz , Oxigênio Singlete/metabolismo , Transcriptoma , Estômatos de Plantas/metabolismoRESUMO
Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures: The primary end point was overall survival time from randomization. Results: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03745170.
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Adenocarcinoma , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Junção Esofagogástrica , Neoplasias Gástricas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Imunoglobulina G/imunologia , Método Duplo-Cego , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversosRESUMO
Chlorophyll a (Chla) and diatom community structure are two indicators of lake water quality. In this study, we investigated the environmental parameters, chlorophyll a, and diatom community of four small urban lakes in Kunming (Beitan, Beihu, Nanhu and Longtan lakes in the campus of Yunnan Normal University) between March 2017 and December 2019. The results showed that the concentrations of total nitrogen (TN), total phosphorus (TP), and Chla in the four lakes showed significant seasonal fluctuation. The Chla concentration in Nanhu Lake, which had the highest nutrient level among the four lakes, was significantly higher than that in the other three lakes and largely affected by TN. In comparison, water temperature significantly contributed to the increases in Chla concentration in the other three lakes. Water temperature and TN were significantly correlated with Chla across the four lakes. Diatom assemblages in Beitan, Nanhu, and Longtan lakes were dominated by planktonic diatoms, and benthic diatoms were dominant in the shallowest lake Beihu, suggesting that water depth significantly affected the proportion of planktonic diatoms and dominant taxa. Water depth, TN, TP, transparency, and water temperature affected the spatio-temporal changes of diatom community structure, with water temperature as the major factor in causing the seasonal variation in diatom community, and TN and TP as the major drivers for community variation among lakes within the same season.
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Diatomáceas , Humanos , Clorofila A , Lagos/química , Clorofila/análise , Monitoramento Ambiental , China , Fósforo/análise , Nitrogênio/análise , EutrofizaçãoRESUMO
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are biologically active substances secreted by MSCs into the extracellular matrix that play an immunomodulatory role in skin damage repair. To investigate the mechanism of MSC-EVs in reducing inflammation, promoting angiogenesis, promoting the proliferation and migration of epithelial cells and fibroblasts, and extracellular matrix remodeling during wound healing, we focused on the effects of EVs on multiple cell types at various stages of skin injury. A literature review was conducted to explore related research on the influence of MSC-EVs on the types of cells involved in wound healing. MSC-EVs show a strong regulatory ability on immune cells involved in the regulation of inflammation, including macrophages, neutrophils, and T cells, and other cells involved in tissue proliferation and remodeling, such as fibroblasts, keratinocytes, and endothelial cells, during wound healing in in vitro and in vivo experiments, which substantially promoted the understanding of wound healing in the field of trauma medicine. MSC-EVs have potential applications in combating poor skin wound healing. Elucidating the mechanism of action of EVs in the wound-healing process would greatly advance the understanding of therapeutic wound healing.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Células Endoteliais , Inflamação , Cicatrização , RegeneraçãoRESUMO
KEY MESSAGE: Ethylene formation via methionine reacting with trichloroisocyanuric acid under FeSO4 condition in a non-enzymatical manner provides one economically and efficiently novel ethylene-forming approach in planta. Rice seed germination can be stimulated by trichloroisocyanuric acid (TCICA). However, the molecular basis of TCICA in stimulating rice seed germination remains unclear. In this study, the molecular mechanism on how TCICA stimulated rice seed germination was examined via comparative transcriptome. Results showed that clustering of transcripts of TCICA-treated seeds, water-treated seeds, and dry seeds was clearly separated. Twenty-two and three hundred differentially expressed genes were identified as TCICA treatment responsive genes and TCICA treatment potentially responsive genes, respectively. Two and one TCICA treatment responsive genes were involved in ethylene signal transduction and iron homeostasis, respectively. Seventeen of the three hundred TCICA treatment potentially responsive genes were significantly annotated to iron ion binding. Meanwhile, level of methionine (ethylene precursor) showed a 73.9% decrease in response to TCICA treatment. Ethylene was then proved to produce via methionine reacting with TCICA under FeSO4 condition in vitro. Revealing ethylene formation by TCICA not only may bring novel insights into crosstalk between ethylene and other phytohormones during rice seed germination, but also may provide one economically and efficiently novel approach to producing ethylene in planta independently of the ethylene biosynthesis in plants and thereby may broaden its applications in investigational and applied purposes.
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Oryza , Oryza/genética , Oryza/metabolismo , Germinação/genética , Perfilação da Expressão Gênica , Etilenos/farmacologia , Etilenos/metabolismo , Sementes/metabolismo , Transcriptoma/genética , Metionina/genética , Metionina/metabolismo , Ferro/metabolismo , Regulação da Expressão Gênica de Plantas , Ácido Abscísico/metabolismoRESUMO
BACKGROUND: Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China. METHODS: Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders. RESULTS: During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HRâ=â0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively. CONCLUSIONS: High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.
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Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.
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Emerging aqueous zinc-ion hybrid capacitors (AZICs) are considered a promising energy storage because of their superior electrochemical performance. The pore structure, suitable heteroatom content, and graphitization degree (GD) of carbon-based cathodes significantly influence the electrochemical performance of AZICs. The N, S dual-doped porous graphitic carbon materials (LC-750) with the combined characteristics of high GD (1.11) and large specific surface area (1678.38 m2 g-1) are successfully developed by a facile "killing two birds with one stone" strategy using K3Fe(C2O4)3·3H2O as the activating and graphitizing agent, and waste sponge (WS) and coal tar pitch (CTP) as the heteroatom and carbon resource, respectively. Results show that the LC-750 cathode displays high capacities of 185.3 and 95.2 mAh g-1 at 0.2 and 10 A g-1. Specifically, the assembled LC-750//Zn capacitor can offer a maximal energy density of 119.5 Wh kg-1, a power density of 20.3 kW kg-1, and a capacity retention of 87.8% after 15,000 cycles at 10 A g-1. Density functional theory simulations demonstrate that N and S dual-doping can promote the adsorption kinetics of Zn ions. This design strategy is a feasible and cost-effective method for the preparation of dual heteroatom-doped graphitic carbon electrodes, which enables recycling of WS and CTP into high-valued products.
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Correction for 'Supramolecular self-assembly of amantadine hydrochloride with ferulic acid via dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal' by Ling-Yang Wang et al., Analyst, 2021, 146, 3988-3999, https://doi.org/10.1039/D1AN00478F.
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Three-dimensional covalent organic frameworks (3D COFs) have been of great interest due to their inherent numerous open sites and pore confinement effect. However, it has remained challenging to build 3D frameworks via interdigitation (also known as inclined interpenetration) by generating an entangled network formed by multiple 2D layers inclined with respect to each other. Herein, we report the first case of constructing a 3D COF, termed COF-904, through interdigitating 2D hcb nets, which was formed via [3+2] imine condensation reactions by the use of 1,3,5-triformylbenzene and 2,3,5,6-tetramethyl-1,4-phenylenediamine. The single-crystal structure of COF-904 is solved, and the locations of all non-hydrogen atoms are determined by 3D electron diffraction with a resolution up to 0.8 Å. These results not only broaden the strategy for achieving 3D COFs via interdigitation but also demonstrate that structurally complex extended frameworks can arise from simple molecules.
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Plum is an important stone fruit in China, but the fruit is easily perishable and susceptible to infection by pathogens. Traditionally, synthetic fungicides are used to control diseases. However, the side effects of fungicides should not be ignored. Cysteine, generally recognized as safe (GRAS) amino acid, has been reported to play roles in the plant abiotic stress response, but little is known about the role of cysteine to control postharvest diseases in fruits. Therefore, this study was designed to investigate the effect of L-cysteine treatment on control of postharvest brown rot in artificially inoculated plum fruits and the possible biocontrol mechanisms involved. Postharvest plum fruits were inoculated with 1, 10, 100 and 1000 mg L-1 L-cysteine. 100 mg L-1 L-cysteine treatment effectively controlled brown rot in artificially inoculated plum fruits by inducing resistance. Furthermore, 100 mg L-1 L-cysteine treatment increased the activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH), enhanced the content of NADPH of the pentose phosphate pathway, as well as improved the contents of H2O2 and some amino acids in the artificially inoculated plum fruits. 100 mg L-1 L-cysteine treatment also elevated the antioxidant content (AsA, GSH) and the antioxidant enzymes activities (APX, GR, MDAR, DHAR) of the ascorbate-glutathione (AsA-GSH) pathway. The protective effects of L-cysteine treatment on postharvest plum fruits likely be due to activating some defense-related responses of the fruit against infection. L-cysteine treatment is a safe promising method for controlling postharvest brown rot in plum fruits.