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1.
Plant Physiol ; 187(1): 409-429, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34618145

RESUMO

Phytopathogen xylanases play critical roles in pathogenesis, likely due to their ability to degrade plant structural barriers and manipulate host immunity. As an invader of plant xylem vessels, the fungus Verticillium dahliae is thought to deploy complex cell wall degrading enzymes. Comparative genomics analyses revealed that the V. dahliae genome encodes a family of six xylanases, each possessing a glycosyl hydrolase 11 domain, but the functions of these enzymes are undetermined. Characterizing gene deletion mutants revealed that only V. dahliae xylanase 4 (VdXyn4) degraded the plant cell wall and contributed to the virulence of V. dahliae. VdXyn4 displayed cytotoxic activity and induced a necrosis phenotype during the late stages of infection, leading to vein and petiole collapse that depended on the enzyme simultaneously localizing to nuclei and chloroplasts. The internalization of VdXyn4 was in conjunction with that of the plasma membrane complexLeucine-rich repeat (LRR)-receptor-like kinase suppressor of BIR1-1 (SOBIR1)/LRR-RLK BRI1-associated kinase-1 (BAK1), but we could not rule out the possibility that VdXyn4 may also act as an apoplastic effector. Immune signaling (in the SA-JA pathways) induced by VdXyn4 relative to that induced by known immunity effectors was substantially delayed. While cytotoxic activity could be partially suppressed by known effectors, they failed to impede necrosis in Nicotiana benthamiana. Thus, unlike typical effectors, cytotoxicity of VdXyn4 plays a crucial intracellular role at the late stages of V. dahliae infection and colonization, especially following pathogen entry into the xylem; this cytotoxic activity is likely conserved in the corresponding enzyme families in plant vascular pathogens.

2.
J Asian Nat Prod Res ; : 1-12, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34657526

RESUMO

A novel series of 1-substituted phenazines 4a-4l were designed and synthesized via Palladium-catalyzed reactions from 1-phenazine trifluoromethanesulfonate. These phenazines showed antichlamydial activity with IC50 values from 1 to 10 µM. Among them, compounds 4c and 4i exhibited the best antichlamydial activity with IC50 values from 2.06 to 2.74 µM without apparent cytotoxicity to host cells.

3.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3053-3060, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658189

RESUMO

Fine roots play an important role in energy flow and substance cycling in forests. How-ever, the estimates of biomass, production and turnover of fine roots remain large uncertainties, and the mechanism underlying local-scale spatial variation in fine roots is still unclear. In a temperate secondary forest in the Maoer Mountain in Northeast China, we investigated the vertical distribution of fine root biomass and necromass at the 0-100 cm profile and the dynamics, production and turnover rate of fine root in 0-20 cm soil layer. The sequential coring (including the Decision Matrix and the Maximum-Minimum formula) and the ingrowth core (3 cm diameter and 5 cm diameter) were compared in estimating production and turnover rate of fine roots. Forest stand variables that might affect fine roots were also explored. The results showed that 76.8% of fine root biomass and 62.9% of necromass concentrated in the 0-20 cm soil layer, and that both decreased exponentially with increa-sing soil depth. The seasonal variation in both fine root biomass and necromass was not significant in 0-20 cm soil layer, which might be related to the negligible snowfall in winter and the extremely high precipitation in summer. There was no significant difference in the results of the estimated fine root production between two diameter ingrowth cores. After log-transformed, fine root production and turnover rate estimated by the Decision Matrix, the Maximum-Minimum formula and ingrowth cores were significantly different among methods. With the increases of soil nutrient concentrations, fine root biomass/fine root necromass ratio significantly increased, fine root necromass significantly decreased, whereas fine root biomass, productivity, and turnover rate were not related to soil nutrient. There was a significant positive correlation between fine root production and aboveground woody biomass increment in the previous-year but not current-year.

4.
Chin Med J (Engl) ; 134(19): 2322-2332, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34629418

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD. METHODS: The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed. RESULTS: Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE. CONCLUSIONS: Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.


Assuntos
Degeneração Macular , Complexo de Endopeptidases do Proteassoma , Replicação do DNA , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Degeneração Macular/genética
5.
J Cosmet Dermatol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648670

RESUMO

BACKGROUND: Salvianolic acid B (SAB) is one of the main active ingredients of Salvia Miltiorrhiza. It has significant skin anti-aging, whitening, and sun protection properties. AIMS: The study aimed at studying the mechanism underlying the effect of salvianolic acid Bon collagen synthesis, which has good anti-aging efficacy and modulates microcirculation. METHODS: This study employed available public databases, bioinformatics methodologies, and the inverse docking approach to explore the effectiveness of SAB in the regulating collagen synthesis, and then used an human dermal fibroblast (HDF)- Human dermal microvascular endothelial cell (HDMEC) in vitro model to validate the predicted mechanism of SAB in influencing collagen synthesis. RESULTS: The results showed that NO production in SAB-treated HDMEC-conditioned medium was increased compared to that in control media, and the same tendency was also observed for growth factor production. SAB also upregulated HDMEC cellular eNOS and VEGF. When SAB-treated HDMEC conditioned medium was transferred to HDFs, the expression of collagen I, collagen III, and elastin in HDFs was upregulated and MMP-1 was downregulated. CONCLUSIONS: The results show that SAB regulates collagen through the HDMEC-HDF pathway. Furthermore, the mechanisms might be closely related to the microcirculation factors NO and VEGF.

6.
Anal Chem ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643369

RESUMO

The hydroxyl radical (·OH), one of the reactive oxygen species (ROS) in biosystems, is found to be involved in many physiological and pathological processes. However, specifically detecting endogenous ·OH remains an outstanding challenge owing to the high reactivity and short lifetime of this radical. Herein, inspired by the scavenging mechanism of a neuroprotective drug edaravone toward ·OH, we developed a new ·OH-specific fluorescent probe RH-EDA. RH-EDA is a hybrid of rhodamine and edaravone and exploits a ·OH-specific 3-methyl-pyrazolone moiety to control its fluorescence behavior. RH-EDA itself is almost nonfluorescent in physiological conditions, which was attributed to the formation of a twisted intramolecular charge transfer (TICT) state upon photoexcitation and the acylation of its rhodamine nitrogen at the 3' position. However, upon a treatment with ·OH, its edaravone subunit was converted to the corresponding 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB) derivative (to afford RH-OPB), thus leading to a significant fluorescence increase (ca. 195-fold). RH-EDA shows a high sensitivity and selectivity to ·OH without interference from other ROS. RH-EDA has been utilized for imaging endogenous ·OH production in living cells and zebrafishes under different stimuli. Moreover, RH-EDA allows a high-contrast discrimination of cancer cells from normal ones by monitoring their different ·OH levels upon stimulation with ß-Lapachone (ß-Lap), an effective ROS-generating anticancer therapeutic agent. The present study provides a promising methodology for the construction of probes through a drug-guided approach.

7.
Front Immunol ; 12: 731842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630412

RESUMO

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N 6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

8.
BMC Cancer ; 21(1): 1082, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620148

RESUMO

BACKGROUND: Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention. METHODS: Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC. RESULTS: Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41-1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend. CONCLUSION: The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.

9.
Endocrinology ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618891

RESUMO

Psychosocial stress disrupts reproduction and interferes with pulsatile LH secretion. The posterodorsal medial amygdala (MePD) is an upstream modulator of the reproductive axis and stress. Corticotropin-releasing factor type-2 receptors (CRFR2) are activated in the presence of psychosocial stress together with increased expression of the CRFR2 ligand Urocortin3 (Ucn3) in the MePD of rodents. We investigate whether Ucn3 signalling in the MePD is involved in mediating the suppressive effect of psychosocial stress on LH pulsatility. Firstly, we administered Ucn3 into the MePD and monitored the effect on LH pulses in ovariectomised mice. Next, we delivered Astressin2B, a selective CRFR2 antagonist, intra-MePD in the presence of predator odor, 2,4,5-Trimethylthiazole (TMT) and examined the effect on LH pulses. Subsequently, we virally infected Ucn3-cre-tdTomato mice with inhibitory DREADDs targeting MePD Ucn3 neurons while exposing mice to TMT or restraint stress and examined the effect on LH pulsatility as well as corticosterone release. Administration of Ucn3 into the MePD dose-dependently inhibited LH pulses and administration of Astressin2B blocked the suppressive effect of TMT on LH pulsatility. Additionally, DREADDs inhibition of MePD Ucn3 neurons blocked TMT and restraint stress-induced inhibition of LH pulses and corticosterone release. These results demonstrate for the first time that Ucn3 neurons in the MePD mediate psychosocial stress-induced suppression of the GnRH pulse generator and corticosterone secretion. Ucn3 signalling in the MePD plays a role in modulating the hypothalamic-pituitary-ganadal and hypothalamic-pituitary-adrenal axes, and this brain locus may represent a nodal centre in the interaction between the reproductive and stress axes.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34622558

RESUMO

A novel copper-catalyzed carbonylative trifluoromethylation of unactivated alkenes has been developed. A broad range of ß -trifluoromethylated carboxylic acid derivatives were prepared in moderate to excellent yields from simple alkenes with excellent regioselectivity. It is noteworthy that ethylene gas, as the simplest olefin, can also be applied directly to obtain ß -trifluoromethylated amides and ester. This transformation presents the first example on carbonylative trifluoromethylation of alkenes.

11.
Phys Chem Chem Phys ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623359

RESUMO

Si/Ge superlattices (SLs) are good candidates for thermoelectric materials because of their remarkable thermal insulating performance compared with their bulk counterparts. In this paper, the non-equilibrium molecular dynamics (NEMD) simulation method was applied to investigate the thermal conductivity of Si/Ge SLs containing tilted interfaces. It was found that the thermal conductivity will be 4-5 times higher than that of other angles when the period length is 4-8 atomic layers and the interface angle is 45°. This phenomenon can be attributed to the smooth arrangement of the 45° interface which induces phonon coherent transport. Meanwhile, the thermal conductivity has not been improved due to the phonon localization although the phonons satisfy the coherent transport when the interface angle is 90°. Interestingly, the thermal conductivity is almost unchanged with the increasing interface angle when the period length is large enough which exceeds 20 atomic layers. The main reason for the unchanged thermal conductivity is due to the period length which is greater than the phonon coherence length inducing the phonon incoherent transport.

12.
Org Lett ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609152

RESUMO

A copper-catalyzed alkoxycarbonylation transformation of unactivated alkyl iodides has been developed. Various alkyl iodides can be converted into the corresponding tert-butyl esters in good yields. NaOtBu acts as both a nucleophile and a base. Moreover, other types of aliphatic esters can also be obtained in moderated yields if extra alcohols are added. Both primary and secondary alkyl alcohols can react successfully.

13.
Chemistry ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617652

RESUMO

Transition-metal-catalyzed multicomponent carbonylation is one of the most efficient strategies to construct carbonyl-containing compounds. Herein, we developed a palladium-catalyzed four-component per fluoroalkylation/aminocarbonylation of unactivated alkenes with perfluoroalkyl halides , and amines. A wide range of substrates, including anilines, alkylamines, sulfonamides, and hydrazines are all suitable reaction partners for this catalyst system, which resulting various ß -perfluoroalkyl amides with good functional-group tolerance and excellent chemoselectivity. Furthermore, not only alkyl olefins, but also aliphatic alkynes, and even alkyl allenes can all be employed. Notably, several medical and bio-active related molecules are compatible here as well.

14.
Mol Neurobiol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618330

RESUMO

We recently reported that intraperitoneal injection of 7,8-dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor-mimicking small compound, could attenuate alcohol-related behaviors in a two-bottle choice ethanol consumption procedure (IA2BC) in rats via tropomyosin receptor kinase B in the ventral tegmental area (VTA), which is closely related to alcohol use disorder. However, the detailed mechanisms underlying the regulation of 7,8-DHF on alcohol drinking behavior remain elusive. In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72 h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibited alcohol intake, whereas application of S-Nitroso-N-acetyl-DL-penicillamine (SNAP, the NO donor) in the VTA further enhanced alcohol consumption in IA2BC rats. Interestingly, either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (a sGC inhibitor) or KT5823 [a selective protein kinase G (PKG) inhibitor] blocked NO's enhancing effect on ethanol intake. Intraperitoneal injection of 7,8-DHF reduced the overexpression of NO; SNAP microinjected into the VTA reversed the inhibitory effects of 7,8-DHF on alcohol consumption. Our findings suggest that NO-cGMP-PKG might be involved in regulation of 7,8-DHF on alcohol consumption in IA2BC rats.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34609929

RESUMO

Background: Genome-wide association studies (GWASs) have identified many genetic variants that are risk factors for numerous immune-mediated diseases. In particular, different immune-mediated diseases have been found to share the same susceptibility loci. Therefore, exploring the overlap between atopic dermatitis (AD) and other immune-mediated diseases in more detail may help identify additional common susceptibility loci shared by the common immune-mediated diseases. The latest evidence suggests that the 11q23.3 locus is a susceptibility locus shared between multiple immune-mediated diseases. Objective: This study investigated whether 11q23.3 locus single nucleotide polymorphisms (SNPs) are also associated with AD in the Han Chinese population. Methods: In total, 16 SNPs at 11q23.3 were genotyped using TaqMan genotyping assays in 1012 AD cases and 1362 controls. Among these SNPs, we selected rs638893 with association values of p < 5 × 10-2 for AD for further replication in the independent replication samples (1288 cases and 1380 controls) using the Sequenom MassARRAY system. The combined analyses were performed in two stages using a meta-analytical method. Results: We identified that a common variant at 11q23.3 (rs638893, p = 1.58 × 10-3, OR = 1.22) was significantly associated with AD. The genotype-based association analysis revealed that the recessive model provided the best fit for rs638893. Conclusion: Our study identified a novel variant on chromosome 11q23.3 that confers susceptibility to AD, thereby advancing our understanding of the genetic basis of AD.

17.
J Org Chem ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542996

RESUMO

A palladium-catalyzed straightforward procedure for the synthesis of 3-arylquinolin-2(1H)-ones has been developed. The synthesis proceeds through a palladium-catalyzed reductive aminocarbonylation reaction of benzylic ammonium triflates with o-nitrobenzaldehydes, and a wide range of 3-arylquinolin-2(1H)-ones was obtained in moderate to good yields with very good functional group compatibility.

18.
Orthop Surg ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523793

RESUMO

OBJECTIVE: To analyze correlations between the selection of microtitanium plates with different specifications for use in a cervical vertebral dome expansion laminoplasty. METHODS: Sixteen patients that underwent the cervical vertebral dome expansion laminoplasty with a cervical spinal stenosis angioplasty procedure for treatment of their cervical spinal cords were recruited at our hospital. From February 2017 to September 2018, medical records confirmed that all patients underwent cervical CT and MRI tests pre- and postsurgery. The anteroposterior diameter of the spinal canal, changes in the cross-sectional area of the spinal canal, and the pre- and postsurgery distance of the cervical spinal cord after applying microtitanium plates with different lengths were measured by Mimics version 17.0 software (Materialise NV, Leuven, Belgium). A statistical regression and correlation analysis of relevant specification parameters of the microtitanium plate was then studied. RESULTS: As the size of the microtitanium plate increased, we found that the cross-sectional area of cervical spinal canal and distance between the descendants of the lamina and the distance of cervical spinal cord concordantly increased, and these data changes linearly. The regression equation associated with sagittal diameter, cross-sectional area, and posterior movement distance of the cervical spinal cord was obtained. CONCLUSION: According to the correlation analysis of imaging data changes, the regression equation was obtained to guide the selection of microtitanium plates with appropriate specifications in a cervical vertebral dome expansion laminoplasty.

19.
Orthop Surg ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523808

RESUMO

OBJECTIVE: To evaluate the safety and stability of 3D-printed interbody fusion cages (3D-printed cages) in anterior cervical discectomy and fusion (ACDF) by investigating the mid- and long-term follow-up outcomes. METHODS: In this prospective study, the clinical data of 30 patients with CSM admitted to the Second Hospital of Shanxi Medical University from May 2012 to May 2014 were analyzed. The cohort comprised 18 males and 12 females with an average age of 60.22 ± 3.2 years. All patients were examined by X-ray, CT and MRI before the operation. A total of 30 cases of CSM were treated by ACDF with 3D printed cage implantation. Mid- and long-term follow-ups were performed after the surgery. Clinical efficacy was evaluated by comparing the JOA score, SF-36 score, change in neurological function, cervical curvature index (CCI), vertebral intervertebral height (VIH) and fusion rate before the operation, 6 months after the operation, and at the last follow-up. RESULTS: Two of the 30 patients were lost to follow-up. The remaining patients were followed up for 48-76 (65.23 ± 3.54) months. The patients recovered satisfactorily with a significant clinical effect. The JOA score increased meanfully and the improvement rate was 89.4% at the final follow-up. The SF-36 score increased significantly from pre- to postoperatively. The height of the intervertebral space at the last follow-up was not statistically significantly different from that at 6 months after surgery (P > 0.05), showing that the height of the intervertebral space did not change much and the severity of cage subsidence (CS) decreased. The CCI improved from pre- to postoperatively. The CCI did not change much from the 6-month follow-up to the last follow-up. and the cage rate (CR) was 100% at the 6-month and last follow-ups. No severe complications, such as spinal cord injury, esophageal fistula, cerebrospinal fluid leakage, cervical hematoma or wound infection, occurred in any of the patients. CONCLUSION: The clinical and radiological results show that the application of 3D-printed cages in ACDF can significantly relieve symptoms. Moreover, 3D-printed cages can restore the curvature of the cervical spine, effectively maintain the intervertebral height for a long time, and prevent complications related to postoperative subsidence.

20.
J Am Chem Soc ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467760

RESUMO

The photovoltaic performance of Cs2AgBiBr6 perovskite is limited by its light-harvesting ability owing to its broad bandgap. Here, we introduced three indoline dyes, D102, D131, and D149, to sensitize the TiO2 electron transport layer that was employed in the Cs2AgBiBr6 perovskite solar cells (PSCs). The perovskite-indoline dye hybrid cells worked with higher power conversion efficiencies (PCEs) than the corresponding dye-sensitized solar cells and the PSC. Extended absorption resulted in a higher short-circuit current density, up to 8.24 mA cm-2, and a maximum PCE of 4.23% in the case of D149, for instance. The double perovskite worked as a p-type interlayer between the dyes and spiro-OMeTAD to convey the holes from the former to the latter, resulting in enhancement in the overall performance.

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