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1.
Nature ; 629(8012): 586-591, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720080

RESUMEN

Light-emitting diodes (LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiencies (EQEs) of more than 25% with narrowband emission1,2, but these LEDs have limited operating lifetimes. We posit that poor long-range ordering in perovskite QD films-variations in dot size, surface ligand density and dot-to-dot stacking-inhibits carrier injection, resulting in inferior operating stability because of the large bias required to produce emission in these LEDs. Here we report a chemical treatment to improve the long-range order of perovskite QD films: the diffraction intensity from the repeating QD units increases three-fold compared with that of controls. We achieve this using a synergistic dual-ligand approach: an iodide-rich agent (aniline hydroiodide) for anion exchange and a chemically reactive agent (bromotrimethylsilane) that produces a strong acid that in situ dissolves smaller QDs to regulate size and more effectively removes less conductive ligands to enable compact, uniform and defect-free films. These films exhibit high conductivity (4 × 10-4 S m-1), which is 2.5-fold higher than that of the control, and represents the highest conductivity recorded so far among perovskite QDs. The high conductivity ensures efficient charge transportation, enabling red perovskite QD-LEDs that generate a luminance of 1,000 cd m-2 at a record-low voltage of 2.8 V. The EQE at this luminance is more than 20%. Furthermore, the stability of the operating device is 100 times better than previous red perovskite LEDs at EQEs of more than 20%.


Asunto(s)
Compuestos de Calcio , Óxidos , Puntos Cuánticos , Titanio , Puntos Cuánticos/química , Titanio/química , Compuestos de Calcio/química , Óxidos/química , Conductividad Eléctrica , Ligandos , Luz , Semiconductores
2.
Adv Mater ; : e2403076, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733295

RESUMEN

The spotlight has shifted to near-infrared (NIR) luminescent materials emitting beyond 1000 nm, with growing interest due to their unique characteristics. The ability of NIR-II emission (1000-1700 nm) to penetrate deeply and transmit independently positions these NIR luminescent materials for applications in optical-communication devices, bioimaging, and photodetectors. The combination of rare earth metals/transition metals with a variety of matrix materials provides a new platform for creating new chemical and physical properties for materials science and device applications. In this review, the recent advancements in NIR emission activated by rare earth and transition metal ions are summarized and their role in applications spanning bioimaging, sensing, and optoelectronics is illustrated. It started with various synthesis techniques and explored how rare earths/transition metals can be skillfully incorporated into various matrixes, thereby endowing them with unique characteristics. The discussion to strategies of enhancing excitation absorption and emission efficiency, spotlighting innovations like dye sensitization and surface plasmon resonance effects is then extended. Subsequently, a significant focus is placed on functionalization strategies and their applications. Finally, a comprehensive analysis of the challenges and proposed strategies for rare earth/transition metal ion-doped near-infrared luminescent materials, summarizing the insights of each section is provided.

3.
Small ; : e2402371, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597692

RESUMEN

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation displays, but suffer from carrier imbalance arising from lower hole injection compared to electron injection. A defect engineering strategy is reported to tackle transport limitations in nickel oxide-based inorganic hole-injection layers (HILs) and find that hole injection is able to enhance in high-performance InP QLEDs using the newly designed material. Through optoelectronic simulations, how the electronic properties of NiOx affect hole injection efficiency into an InP QD layer, finding that efficient hole injection depends on lowering the hole injection barrier and enhancing the acceptor density of NiOx is explored. Li doping and oxygen enriching are identified as effective strategies to control intrinsic and extrinsic defects in NiOx, thereby increasing acceptor density, as evidenced by density functional theory calculations and experimental validation. With fine-tuned inorganic HIL, InP QLEDs exhibit a luminance of 45 200 cd m-2 and an external quantum efficiency of 19.9%, surpassing previous inorganic HIL-based QLEDs. This study provides a path to designing inorganic materials for more efficient and sustainable lighting and display technologies.

4.
J Hazard Mater ; 471: 134410, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38677121

RESUMEN

Heavy metal (HM) pollution in agricultural soils has arisen sharply in recent years. However, the impact of main factors on available HMs concentrations in agricultural soils of the three main industries (smelting, chemical and mining industry) is unclear. Herein, soil properties (pH, cation exchange capacity (CEC) and texture (sand, slit, clay)), total and available concentrations were concluded based on the results of 165 research papers from 2000 to 2023 in Web of Science database. In the three industries, the correlation and redundancy analysis were used to study the correlation between main factors and available concentrations, and quantitatively analyzed the contribution of each factor to available concentrations with gradient boosting decision tree model. The results showed that different factors had varying degrees of impact on available metals in the three main industries, and the importance of same factors varied in each industry, as for soil pH, it was most important for available Pb and Zn in the chemical industry, but the total concentrations were most important in the smelting and mining industry. There was no significant correlation between total and available concentrations. Soil properties involved in this paper (especially soil pH) were negatively correlated with available concentrations. This study provides effective guidance for the formulation of soil pollution control and risk assessment standards based on industry classification in the three major industrial impact areas.

5.
Sci Rep ; 14(1): 7473, 2024 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553555

RESUMEN

Orexin signaling plays a facilitatory role in respiration. Abnormalities in orexin levels correlate with disordered breathing patterns and impaired central respiratory chemoreception. Nucleus tractus solitarii (NTS) neurons expressing the transcription factor Phox2b contribute to the chemoreceptive regulation of respiration. However, the extent to which orexinergic signaling modulates respiratory activity in these Phox2b-expressing NTS neurons remains unclear. In the present study, the injection of orexin A into the NTS significantly increased the firing rate of the phrenic nerve. Further analysis using fluorescence in situ hybridization and immunohistochemistry revealed that orexin 1 receptors (OX1Rs) were primarily located in the ventrolateral subdivision of the NTS and expressed in 25% of Phox2b-expressing neurons. Additionally, electrophysiological recordings showed that exposure to orexin A increased the spontaneous firing rate of Phox2b-expressing neurons. Immunostaining experiments with cFos revealed that the OX1R-residing Phox2b-expressing neurons were activated by an 8% CO2 stimulus. Crucially, OX1R knockdown in these NTS neurons notably blunted the ventilatory response to 8% CO2, alongside an increase in sigh-related apneas. In conclusion, orexinergic signaling in the NTS facilitates breathing through the activation of OX1Rs, which induces the depolarization of Phox2b-expressing neurons. OX1Rs are essential for the involvement of Phox2b-expressing NTS neurons in the hypercapnic ventilatory response.


Asunto(s)
Dióxido de Carbono , Núcleo Solitario , Núcleo Solitario/metabolismo , Orexinas/metabolismo , Hibridación Fluorescente in Situ , Respiración
6.
J Control Release ; 368: 650-662, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38490374

RESUMEN

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.


Asunto(s)
Glioblastoma , Nanopartículas , Neoplasias , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/terapia , Fototerapia/métodos , Encéfalo , Barrera Hematoencefálica , Colorantes , Nanomedicina Teranóstica/métodos , Nanopartículas/uso terapéutico , Línea Celular Tumoral
7.
Nano Lett ; 24(9): 2765-2772, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38393855

RESUMEN

Alloying lanthanide ions (Yb3+) into perovskite quantum dots (Yb3+:CsPb(Cl1-xBrx)3) is an effective method to achieve efficient near-infrared (NIR) luminescence (>950 nm). Increasing the Yb3+ alloying ratio in the perovskite matrix enhances the luminescence intensity of Yb3+ emission at 990 nm. However, high Yb3+ alloying (>15%) results in vacancy-induced inferior material stability. In this work, we developed a polarity-mediated antisolvent manipulation strategy to resolve the incompatibility between a high Yb3+ alloying ratio and inferior stability of Yb3+:CsPb(Cl1-xBrx)3. Precise control of solution polarity enables increased uniformity of the perovskite matrix with fewer trap densities. Employing this strategy, we obtain Yb3+:CsPb(Cl1-xBrx)3 with the highest Yb3+ alloying ratio of 30.2% and a 2-fold higher electroluminescence intensity at 990 nm. We lever the engineered Yb3+:CsPb(Cl1-xBrx)3 to fabricate NIR-LEDs, achieving a peak external quantum efficiency (EQE) of 8.5% at 990 nm: this represents the highest among perovskite NIR-LEDs with an emission wavelength above 950 nm.

8.
BMC Infect Dis ; 24(1): 263, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408969

RESUMEN

BACKGROUND: In this retrospective study, we aimed to evaluate the factors associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children aged under 2 years who were admitted to the Children's Hospital of Hebei between June 2018 and January 2019. METHODS: Sputum samples positive for RSV via multiplex PCR were subtyped using real-time PCR. Data collected included risk factors for disease severity, demographics, microbiology, and outcomes. RESULTS: Of the 82 children with RSV bronchiolitis, 79 were treated and discharged with improvement, while 3 died. All three patients had underlying medical conditions, including complex congenital heart disease and severe combined immunodeficiency. Further, disease severity was associated with preexisting underlying disease, fever duration, and bacterial co-infection, but not with the RSV subtype. CONCLUSIONS: Our findings suggest that an appropriate therapeutic regimen should include the detection of bacterial co-infections and the identification of underlying diseases for the effective management of severe RSV bronchiolitis.


Asunto(s)
Infecciones Bacterianas , Bronquiolitis , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Niño , Humanos , Lactante , Estudios Retrospectivos , Hospitalización
9.
Nat Commun ; 15(1): 1134, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326370

RESUMEN

Preharvest sprouting (PHS) is a deleterious phenotype that occurs frequently in rice-growing regions where the temperature and precipitation are high. It negatively affects yield, quality, and downstream grain processing. Seed dormancy is a trait related to PHS. Longer seed dormancy is preferred for rice production as it can prevent PHS. Here, we map QTLs associated with rice seed dormancy and clone Seed Dormancy 3.1 (SDR3.1) underlying one major QTL. SDR3.1 encodes a mediator of OsbZIP46 deactivation and degradation (MODD). We show that SDR3.1 negatively regulates seed dormancy by inhibiting the transcriptional activity of ABIs. In addition, we reveal two critical amino acids of SDR3.1 that are critical for the differences in seed dormancy between the Xian/indica and Geng/japonica cultivars. Further, SDR3.1 has been artificially selected during rice domestication. We propose a two-line model for the process of rice seed dormancy domestication from wild rice to modern cultivars. We believe the candidate gene and germplasm studied in this study would be beneficial for the genetic improvement of rice seed dormancy.


Asunto(s)
Oryza , Latencia en las Plantas , Latencia en las Plantas/genética , Mapeo Cromosómico , Oryza/genética , Sitios de Carácter Cuantitativo/genética , Fenotipo , Semillas/genética
10.
Sci Rep ; 14(1): 3292, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38332112

RESUMEN

Natural gas distributed energy is recognized as a pivotal means to enhance energy efficiency and mitigate carbon dioxide emissions through localized energy cascading. Positioned as a key option for advancing the Sustainable Development Goals, this system optimizes energy utilization near end-users. While maximizing energy efficiency, it is imperative to address potential environmental challenges. A thorough, comprehensive environmental assessment, facilitated by the life cycle assessment method, proves instrumental in meeting this standard. Employing this method enables an intuitive grasp of the environmental strengths and weaknesses inherent in natural gas distributed energy within the power structure. This insight serves as a foundation for informed project decision-making, fostering the growth of the industry. We selected six environmental impact assessment categories based on the CML 2001 method, and conducted the life cycle analysis across four stages. China's inaugural natural gas distributed energy demonstration project was chosen as a model case, and an environmental impact assessment inventory was established, utilizing survey data and literature for comprehensive data collection and analysis. Results from case testing yield environmental impact assessment outcomes, with a specific sensitivity analysis for stages with notable environmental impact factors. The study underscores that the operation phase has the highest environmental impact, comprising 78.37% of the total combined environmental impact, followed by the fuel production phase. Comparative analyses with coal-fired and conventional natural gas power generation, based on dimensionless literature data, reveal that abiotic resources depletion potential is the primary contributor to the environmental impact of 1 kWh of electricity product, constituting 52.76% of the total impact value, followed by global warming potential. Concrete strategies have been outlined for decision-making in both the operational and planning phases of natural gas distributed energy projects. The strengthening of policies is pinpointed towards grid connection and scale expansion.

11.
Animals (Basel) ; 14(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38338053

RESUMEN

Through a 30-day experiment, this study investigated the effects of five photoperiods (0L:24D, 6L:18D, 12L:12D, 18L:6D, and 24L:0D) on the survival, enzyme activity, body color, and growth-related gene expression of redclaw crayfish (Cherax quadricarinatus) juveniles. The results showed that C. quadricarinatus juveniles under 18L:6D and 24L:0D photoperiods exhibited the highest survival rate, which was significantly higher than the survival rates of juveniles under the other three photoperiods (p < 0.05). However, the 0L:24D group had the highest final body weight and weight gain rate, significantly surpassing those of the 12L:12D, 18L:6D, and 24L:0D groups (p < 0.05). Regarding enzyme activity and hormone levels, juveniles under the 18L:6D photoperiod exhibited relatively higher activity of superoxide dismutase (SOD), acid phosphatase (ACP), and lysozyme (LZM) enzymes than those under other photoperiods, but their levels of melatonin and cortisol were relatively low. In addition, the 24L:0D group showed the highest malondialdehyde (MDA) content. Analysis of gene expression levels revealed that retinoid X receptor (RXR) and α-amylase (α-AMY) genes in C. quadricarinatus juveniles exhibited significantly higher expression levels under the 18L:6D photoperiod than those under the other four photoperiods (p < 0.05). With increasing daylight exposure, the body color of C. quadricarinatus changed from pale blue to yellow-brown. In summary, C. quadricarinatus juveniles achieved high survival rates, good growth performance, strong antioxidant stress response, and immune defense capabilities under an 18 h photoperiod. Therefore, in the industrial seedling cultivation of redclaw crayfish, it is recommended to provide 18 h of daily light. Further, the study demonstrated the ability to manipulate the body color of C. quadricarinatus through controlled artificial photoperiods. These findings provide essential technical parameters needed for the industrial cultivation of C. quadricarinatus juveniles.

12.
Animals (Basel) ; 14(3)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38338122

RESUMEN

The Asian yellow pond turtle (Mauremys mutica) is widely traded in China, and its artificial breeding has now become a major industry. However, the insufficient offspring supply and reproductive decline of farmed turtles make the wild turtles more vulnerable. The present study was mainly designed to quantify the fecundity of M. mutica and attempt to screen for good reproductive performance in females. The genetic variability of the population and its genetic structure were also analysed. The parent-offspring relationships of all offspring in four consecutive years were confirmed using sixteen microsatellite loci. The genetic variability between the parents and offspring was low, and offspring of different years also showed little variability. We summarised the reproductive results of all females and counted the annual number of offspring and the variation in the number of offspring. The females were then divided into three types (stable, undulating and levelling off) according to the continuity. We selected seven females with good reproductive ability, which provided 16.94% of the annual contributions, while there were two females that had no offspring in four years. We also analysed the possible reasons for this difference and the importance of carrying out a family survey. This research can provide the basis and materials for the creation of a good reproductive group and the study of the reproductive biology of turtles in M. mutica aquaculture.

13.
Innovation (Camb) ; 5(2): 100561, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38379784

RESUMEN

Helicobacter pylori infection is associated with the risk of gastrointestinal (GI) cancers; however, its impact on immunotherapy for GI cancers remains uncertain. In this study, we included 10,122 patients who underwent 13C-urea breath tests. Among 636 patients with Epstein-Barr virus-negative microsatellite-stable gastric cancer (GC) who were treated with anti-PD-1/PD-L1 therapy, H. pylori-positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with H. pylori-negative patients (6.97 months versus 5.03 months, p < 0.001, hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95, p = 0.015). Moreover, the H. pylori-positive group demonstrated a trend of 4 months longer median immune-related overall survival (irOS) than the H. pylori-negative group. H. pylori-positive GC displayed higher densities of PD-L1+ cells and nonexhausted CD8+ T cells, indicative of a "hot" tumor microenvironment. Transcriptomic analysis revealed that H. pylori-positive GC shared molecular characteristics similar to those of immunotherapy-sensitive GC. However, H. pylori-positive patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal adenocarcinoma and esophageal squamous cell carcinoma (ESCC) had shorter irPFS compared with H. pylori-negative patients (16.13 months versus not reached, p = 0.042, HR 2.26, 95% CI 1.13-4.50, p = 0.021 and 5.57 months versus 6.97 months, p = 0.029, HR 1.59, 95% CI 1.14-2.23, p = 0.006, respectively). The difference in irOS between H. pylori-positive and -negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients. We also identified a trend of shorter irPFS and irOS in H. pylori-positive liver cancer and pancreatic cancer patients. In summary, our findings supported that H. pylori infection is a beneficial factor for GC immunotherapy by shaping hot tumor microenvironments. However, in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients, H. pylori adversely affects the efficacy of immunotherapy.

14.
J Org Chem ; 89(5): 3453-3470, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38335461

RESUMEN

In the present study, we successfully developed an efficient thiocyanation of carbonyl compounds by using low-toxicity and inexpensive ammonium thiocyanate as the thiocyanate source under visible light in air (O2) at room temperature. This unified strategy is very facile for thiocyanation of various carbonyl compound derivatives (ß-keto esters, ß-keto amides, pyrazo-5-ones, isoxazol-5-ones, etc.). More importantly, the reaction proceeded smoothly without the addition of a photocatalyst and strong oxidant, ultimately minimizing the production of chemical waste. Furthermore, this green and sustainable synthetic chemistry can be used in the late-stage functionalization (LSF) of biorelevant compounds, which offers unique opportunities to achieve smooth and clean thiocyanation of drugs under mild reaction conditions.

15.
J Org Chem ; 89(5): 3304-3308, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38356371

RESUMEN

A protocol for the construction of an angular tricyclic benzofuran skeleton based on the C-H activation strategy has been established. Different phthalide lactones on this skeleton can be easily assembled with various side chains by using C-H activation with aldehydes and subsequent reduction. This skeleton provides a versatile and crucial motif for the total synthesis of naturally occurring angular tricyclic benzofurans and their derivatives. Based on this protocol, the improved total syntheses of daldinin A and annullatin D were achieved in yields of 17.3 and 7.6%, respectively.

16.
EClinicalMedicine ; 68: 102415, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38235421

RESUMEN

Background: Although the antibody-drug conjugates (ADCs) have significantly improved the survival outcomes of patients with human epidermal receptor 2 (HER2)-expressing gastric or gastroesophageal junction (G/GEJ) cancer, the efficacy of ADC used as a single agent is limited. Therefore, it is necessary to investigate effective and safe combination regimens. Preclinical data indicated a synergetic antitumour effect of RC48 and programmed cell death protein 1 (PD-1) inhibitors. We aimed to evaluate the safety and efficacy of RC48 plus toripalimab in patients with HER2-expressing G/GEJ cancer and other solid tumours. Methods: This was a open-label, multicentre, phase 1 trial performed at three hospitals in China. Eligible patients had advanced G/GEJ cancer or other solid tumours with HER2 IHC≥1 or ISH positivity and were refractory to at least one line of treatment, or standard treatment was intolerable or unavailable for these patients. This study followed a "3 + 3" design with predefined RC48 dosages of 2.0 mg/kg and 2.5 mg/kg plus toripalimab 3 mg/kg, once every 2 weeks (q2w). The primary objectives were to evaluate the safety and determine the recommended phase II dose (RP2D), and the secondary objectives included assessing the pharmacokinetics (PK) and preliminary efficacy. This study was registered with ClinicalTrials.gov, NCT04280341. Findings: Between July 13, 2020 and August 30, 2022, 56 patients, including 30 patients with G/GEJ cancer and 26 patients with other solid tumours, were enrolled and received RC48 plus toripalimab (n = 7 for RC48 2.0 mg/kg, toripalimab 3 mg/kg, q2w; n = 49 for RC48 2.5 mg/kg, toripalimab 3 mg/kg, q2w). No dose-limiting toxic effects occurred. The RP2D was declared as RC48 2.5 mg/kg plus toripalimab 3 mg/kg, q2w. The most common grade 3 adverse events were a decreased neutrophil count (n = 13), and a decreased white blood cell count (n = 7). The efficacy assessment was completed for 52 patients. Among patients with G/GEJ cancer (n = 30), the confirmed objective response rate (ORR) was 43% (12/28, 95% CI 25, 63), median progression-free survival (PFS) was 6.2 months (95% CI 4.0, 6.9), median overall survival (OS) was 16.8 months (95% CI 7.2, NE). The ORR of patients with G/GEJ cancer receiving RP2D (n = 24) reached 50% (11/22, 95% CI 28, 72), with median PFS of 5.1 months (95% CI 1.4, 7.3) and median OS of 14.0 months (95% CI 6.3, NE). Among patients with G/GEJ cancer who received RP2D, a clinical benefit was observed in both HER2-positive and low HER2 expressing populations, with an ORR of 56% (5/9, 95% CI 21, 86) vs. 46% (6/13, 95% CI 19, 75), median PFS of 7.8 months (95% CI 0.9, NE) vs. 5.1 months (95% CI 1.2, 6.9), median OS of NE months (95% CI 4.3, NE) vs. 14.0 months (95% CI 5.1, NE), respectively. Antitumour activity was also observed for other solid tumours, including breast cancer (5/13) and endometrial carcinoma (1/1). Interpretation: Our findings suggested that RC48 plus toripalimab had a manageable safety profile and showed encouraging efficacy in pretreated patients with HER2-positive and low HER2-expressing G/GEJ cancer. The findings of our phase 1 clinical trial support further investigation of HER2-targeted ADC plus immunotherapy in HER2-expressing G/GEJ cancer and pancancer treatment in the future. Funding: Beijing Municipal Medical Research Institutes, Beijing Medical Research Institute (Z200015).

17.
J Inflamm Res ; 17: 253-277, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38229690

RESUMEN

Purpose: Chronic rhinosinusitis is a prevalent condition in the field of otorhinolaryngology; however, its pathogenesis remains to be elucidated. The immunological defense of the nasal mucosa is significantly influenced by dendritic cells (DCs). We identified specific biological indicators linked to DCs and explored their significance in cases of chronic rhinosinusitis with nasal polyps (CRSwNP). Patients and Methods: We categorized cells using single-cell RNA (scRNA) sequencing, and combined transcriptome sequencing was used to identify potential candidate genes for CRSwNP. We selected three biomarkers based on two algorithms and performed enrichment and immune correlation analyses. Biomarkers were verified using training and validation sets, receiver operating characteristic curves, immunohistochemistry, and quantitative real-time reverse-transcription PCR (qRT-PCR). Variations in biomarker expression were validated using pseudotime analysis. The networks of competing transcription factor (TF)-mRNA and competing endogenous RNA (ceRNA) were established, and the protein drugs associated with these biomarkers were predicted. Results: Both scRNA-seq and transcriptome data showed that DCs immune infiltration was higher in the CRSwNP group than in the control group. Three DC-related biomarkers (NR4A1, CLEC4G, and CD163) were identified. In CRSwNP, NR4A1 expression decreased, whereas CLEC4G and CD163 expression increased. All biomarkers were shown to be involved in immunological and metabolic pathways by enrichment analysis. These biomarkers were associated with γδ T cells, effector memory CD4 + T cells, regulatory T cells, and immature DCs. According to pseudotime analysis, NR4A1 and CD163 expression decreased from high to low, whereas CLEC4G expression remained low. Conclusion: We screened and identified potential DC-associated biomarkers of CRSwNP progression by integrating scRNA-seq with whole transcriptome sequencing. We analyzed the biological pathways in which they were involved, explored their molecular regulatory mechanisms and related drugs, and constructed ceRNA, TF-mRNA, and biomarker-drug networks to identify new CRSwNP treatment targets, laying the groundwork for the clinical management of CRSwNP.

18.
Rice (N Y) ; 17(1): 8, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38228921

RESUMEN

As the source of isoprenoid precursors, the plastidial methylerythritol phosphate (MEP) pathway plays an essential role in plant development. Here, we report a novel rice (Oryza sativa L.) mutant ygl3 (yellow-green leaf3) that exhibits yellow-green leaves and lower photosynthetic efficiency compared to the wild type due to abnormal chloroplast ultrastructure and reduced chlorophyll content. Map-based cloning showed that YGL3, one of the major genes involved in the MEP pathway, encodes 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, which is localized in the thylakoid membrane. A single base substitution in ygl3 plants resulted in lower 4-hydroxy-3-methylbut-2-enyl diphosphate reductase activity and lower contents of isopentenyl diphosphate (IPP) compared to the wild type. The transcript levels of genes involved in the syntheses of chlorophyll and thylakoid membrane proteins were significantly reduced in the ygl3 mutant compared to the wild type. The phytochrome interacting factor-like gene OsPIL11 regulated chlorophyll synthesis during the de-etiolation process by directly binding to the promoter of YGL3 to activate its expression. The findings provides a theoretical basis for understanding the molecular mechanisms by which the MEP pathway regulate chloroplast development in rice.

19.
Sci Rep ; 14(1): 2270, 2024 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280891

RESUMEN

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nasal mucosa, and epithelial-mesenchymal transition (EMT) is thought to be an essential process in the pathogenesis of CRSwNP. However, the mechanisms of epithelial and fibroblastic changes at the single-cell level are unclear. In this study, we investigated the epithelial cell, fibroblast, and key gene alterations in the development of CRSwNP. We revealed major cell types involved in CRSwNP and nasal mucosal inflammation formation, then mapped epithelial and fibroblast subpopulations. We showed that the apical and glandular epithelial cells and the ADGRB3+ and POSTN+ fibroblasts were the key cell subtypes in the progression of CRSwNP. Pseudotime and cell cycle analysis identified dynamic changes between epithelial cells and fibroblasts during its development. WFDC2 and CCL26 were identified as the key marker genes involved in the development of CRSwNP and were validated by IHC staining, which may provide a potential novel target for future CRSwNP therapy. ScRNA-seq data provided insights into the cellular landscape and the relationship between epithelial cells and fibroblasts in the progression of CRSwNP. WFDC2 and CCL26 were identified as the key genes involved in the development of CRSwNP and may be the potential markers for gene therapy.


Asunto(s)
Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Rinitis/complicaciones , Rinitis/genética , Rinitis/metabolismo , Pólipos Nasales/complicaciones , Pólipos Nasales/genética , Pólipos Nasales/metabolismo , Sinusitis/complicaciones , Sinusitis/genética , Sinusitis/metabolismo , Mucosa Nasal/metabolismo , Enfermedad Crónica , Células Epiteliales/metabolismo , Fibroblastos/metabolismo , Análisis de Secuencia de ARN
20.
Anal Methods ; 16(4): 583-588, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38189485

RESUMEN

Exciting an object with a laser-focus array and randomly interleaving its scattering projection has been proved to be an effective strategy for speeding up Raman imaging. The so-called scattering interleaved Raman imaging (SIRI) method allows Raman hyperspectral imaging with a single snapshot and exhibits excellent reconstruction fidelity and signal-to-noise ratios (SNRs). Here, we show that the performance of SIRI is significantly improved when combined with context-aware excitation. The experiments on micro-plastics demonstrate that the restriction of Raman excitation within a smaller region of interest as guided by bright-field microscopy improves the signal intensity and the SNR, and it is surprising that the spectral resolution is also significantly improved. The context-aware SIRI method is successfully used for imaging of lipid-producing yeast cells, suggesting that it is a promising analytical tool for studying live cells or tissues.

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