Conjugated Polymer-Based Photo-Crosslinker for Efficient Photo-Patterning of Polymer Semiconductors.

Photo-patterning of polymer semiconductors using photo-crosslinkers has shown potential for organic circuit fabrication via solution processing techniques. However, the performance of patterning, including resolution (R), UV light exposure dose, sensitivity (S), and contrast (γ), remains unsatisfactory. In this study, a novel conjugated polymer based photo-crosslinker (PN3, Figure 1a) is reported for the first time, which entails phenyl-substituted azide groups in its side chains. Due to the potential π-π interactions between the conjugated backbone of PN3 and those of polymer semiconductors, PN3 exhibits superior miscibility with polymer semiconductors compared to the commonly used small molecule photo-crosslinker 4Bx (Figure 1a). Consequently, photo-patterning of polymer semiconductors with PN3 demonstrates improved performance with much lower UV light exposure dose, higher S and higher γ compared to 4Bx. By utilizing electron beam lithography, patterned arrays of polymer semiconductors with resolutions down to 500 nm and clearer edges are successfully fabricated using PN3. Furthermore, patterned arrays of PDPP4T, the p-type semiconductor (Figure 1b), after being doped, can function as source-drain electrodes for fabricating field-effect transistors (FETs) with comparable charge mobility and significantly lower sub-threshold swing value compared to those with gold electrodes.

Integrated bacterial transcriptome and host metabolome analysis reveals insights into "Candidatus Liberibacter asiaticus" population dynamics in the fruit pith of three citrus cultivars with different tolerance.

"Candidatus Liberibacter asiaticus" (CLas), the causal agent of citrus Huanglongbing (HLB), is able to multiply to a high abundance in citrus fruit pith. However, little is known about the biological processes and phytochemical substances that are vital for CLas colonization and growth in fruit pith. In this study, CLas-infected fruit pith of three citrus cultivars ("Shatangju" mandarin, "Guanxi" pomelo, and "Shatian" pomelo) exhibiting different tolerance to CLas were collected and used for dual RNA-Seq and untargeted metabolome analysis. Comparative transcriptome analysis found that the activation of the CLas noncyclic TCA pathway and pathogenic-related effectors could contribute to the colonization and growth of CLas in fruit pith. The pre-established Type 2 prophage in the CLas genome and the induction of its CRISPR/cas system could enhance the phage resistance of CLas and, in turn, facilitate CLas population growth in fruit pith. CLas infection caused the accumulation of amino acids that were correlated with tolerance to CLas. The accumulation of most sugars and organic acids in CLas-infected fruit pith, which could be due to the phloem blockage caused by CLas infection, was thought to be beneficial for CLas growth in localized phloem tissue. The higher levels of flavonoids and terpenoids in the fruit pith of CLas-tolerant cultivars, particularly those known for their antimicrobial properties, could hinder the growth of CLas. This study advances our understanding of CLas multiplication in fruit pith and offers novel insight into metabolites that could be responsible for tolerance to CLas or essential to CLas population growth.IMPORTANCECitrus Huanglongbing (HLB, also called citrus greening disease) is a highly destructive disease currently threatening citrus production worldwide. HLB is caused by an unculturable bacterial pathogen, "Candidatus Liberibacter asiaticus" (CLas). However, the mechanism of CLas colonization and growth in citrus hosts is poorly understood. In this study, we utilized the fruit pith tissue, which was able to maintain the CLas at a high abundance, as the materials for dual RNA-Seq and untargeted metabolome analysis, aiming to reveal the biological processes and phytochemical substances that are vital for CLas colonization and growth. We provided a genome-wide CLas transcriptome landscape in the fruit pith of three citrus cultivars with different tolerance and identified the important genes/pathways that contribute to CLas colonization and growth in the fruit pith. Metabolome profiling identified the key metabolites, which were mainly affected by CLas infection and influenced the population dynamic of CLas in fruit pith.

Nonhalogenated Solvent Processable and High-Density Photopatternable Polymer Semiconductors Enabled by Incorporating Hydroxyl Groups in the Side Chains.

Polymer semiconductors hold tremendous potential for applications in flexible devices, which is however hindered by the fact that they are usually processed by halogenated solvents rather than environmentally more friendly solvents. An effective strategy to boost the solubility of high-performance polymer semiconductors in nonhalogenated solvents such as tetrahydrofuran (THF) by appending hydroxyl groups in the side chains is herein presented. The results show that hydroxyl groups, which can be easily incorporated into the side chains, can significantly improve the solubility of typical p- and n-types as well as ambipolar polymer semiconductors in THF. Meanwhile, the thin films of these polymer semiconductors from the respective THF solutions show high charge mobilities. With THF as the processing and developing solvents these polymer semiconductors with hydroxyl groups in the side chains can be well photopatterned in the presence of the photo-crosslinker, and the charge mobilities of the patterned thin films are mostly maintained by comparing with those of the respective pristine thin films. Notably, THF is successfully utilized as the processing and developing solvent to achieve high-density photopatterning with ≈82 000 device arrays cm-2 for polymer semiconductors in which hydroxyl groups are appended in the side chains.

Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice.

The clinic application of doxorubicin (DOX) is severely limited by its severe cardiotoxicity. Tripartite motif-containing protein 16 (TRIM16) has E3 ubiquitin ligase activity and is upregulated in cardiomyocytes under pathological stress, yet its role in DOX-induced cardiotoxicity remains elusive. This study aims to investigate the role and mechanism of TRIM16 in DOX cardiotoxicity. Following TRIM16 overexpression in hearts with AAV9-TRIM16, mice were intravenously administered DOX at a dose of 4 mg/kg/week for 4 weeks to assess the impact of TRIM16 on doxorubicin-induced cardiotoxicity. Transfection of OE-TRIM16 plasmids and siRNA-TRIM16 was performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that DOX challenge elicited a significant upregulation of TRIM16 proteins in cardiomyocytes. TRIM16 overexpression efficiently ameliorated cardiac function while suppressing inflammation, ROS generation, apoptosis and fibrosis provoked by DOX in the myocardium. TRIM16 knockdown exacerbated these alterations caused by DOX in NRCMs. Mechanistically, OE-TRIM16 augmented the ubiquitination and degradation of p-TAK1, thereby arresting JNK and p38MAPK activation evoked by DOX in cardiomyocytes. Furthermore, DOX enhanced the interaction between p-TAK1 and YAP1 proteins, resulting in a reduction in YAP and Nrf2 proteins in cardiomyocytes. OE-TRIM16 elevated YAP levels and facilitated its nuclear translocation, thereby promoting Nrf2 expression and mitigating oxidative stress and inflammation. This effect was nullified by siTRIM16 or TAK1 inhibitor Takinib. Collectively, the current study elaborates that upregulating TRIM16 mitigates DOX-induced cardiotoxicity through anti-inflammation and anti-oxidative stress by modulating TAK1-mediated p38 and JNK as well as YAP/Nrf2 pathways, and targeting TRIM16 may provide a novel strategy to treat DOX-induced cardiotoxicity.

Intrinsically Stretchable and Healable Polymer Semiconductors.

In recent decades, polymer semiconductors, extensively employed as charge transport layers in devices like organic field-effect transistors (OFETs), have undergone thorough investigation due to their capacity for large-area solution processing, making them promising for mass production. Research efforts have been twofold: enhancing the charge mobilities of polymer semiconductors and augmenting their mechanical properties to meet the demands of flexible devices. Significant progress has been made in both realms, propelling the practical application of polymer semiconductors in flexible electronics. However, integrating excellent semiconducting and mechanical properties into a single polymer still remains a significant challenge. This review intends to introduce the design strategies and discuss the properties of high-charge mobility stretchable conjugated polymers. In addition, another key challenge faced in this cutting-edge field is maintaining stable semiconducting performance during long-term mechanical deformations. Therefore, this review also discusses the development of healable polymer semiconductors as a promising avenue to improve the lifetime of stretchable device. In conclusion, challenges and outline future research perspectives in this interdisciplinary field are highlighted.

Comparative transcriptome profiling of susceptible and tolerant citrus species at early and late stage of infection by "Candidatus Liberibacter asiaticus".

Citrus Huanglongbing (HLB), caused by "Candidatus Liberibacter asiaticus" (CLas), is the most destructive disease threatening global citrus industry. Most commercial cultivars were susceptible to HLB, although some showed tolerant to HLB phenotypically. Identifying tolerant citrus genotypes and understanding the mechanism correlated with tolerance to HLB is essential for breeding citrus variety tolerance/resistance to HLB. In this study, the graft assay with CLas-infected bud were performed in four citrus genotypes, including Citrus reticulata Blanco, C. sinensis, C. limon, and C. maxima. HLB tolerance was observed in C. limon and C. maxima, while C. Blanco and C. sinensis were susceptible to HLB. The time-course transcriptomic analysis revealed a significant variation in differentially expressed genes (DEGs) related to HLB between susceptible and tolerant cultivar group at early and late infection stage. Functional analysis of DEGs indicated that the activation of genes involved in SA-mediated defense response, PTI, cell wall associated immunity, endochitinase, phenylpropanoid and alpha-linolenic/linoleic lipid metabolism played an important in the tolerance of C. limon and C. maxima to HLB at early infection stage. In addition, the overactive plant defense combined with the stronger antibacterial activity (antibacterial secondary and lipid metabolism) and the suppression of pectinesterase were contributed to the long-term tolerance to HLB in C. limon and C. maxima at late infection stage. Particularly, the activation of ROS scavenging genes (catalases and ascorbate peroxidases) could help to reduce HLB symptoms in tolerant cultivars. In contrast, the overexpression of genes involved in oxidative burst and ethylene metabolism, as well as the late inducing of defense related genes could lead to the early HLB symptom development in susceptible cultivars at early infection stage. The weak defense response and antibacterial secondary metabolism, and the induce of pectinesterase were responsible for sensitivity to HLB in C. reticulata Blanco and C. sinensis at late infection stage. This study provided new insights into the tolerance/sensitivity mechanism against HLB and valuable guidance for breeding of HLB-tolerant/resistant cultivars.

Intrinsically Stretchable Polymer Semiconductors with Good Ductility and High Charge Mobility through Reducing the Central Symmetry of the Conjugated Backbone Units.

Intrinsically stretchable polymer semiconductors are highly demanding for flexible electronics. However, it still remains challenging to achieve synergy between intrinsic stretchability and charge transport property properly for polymer semiconductors. In this paper, terpolymers are reported as intrinsically stretchable polymeric semiconductors with good ductility and high charge mobility simultaneously by incorporation of non-centrosymmetric spiro[cycloalkane-1,9'-fluorene] (spiro-fluorene) units into the backbone of diketopyrrolopyrrole (DPP) based conjugated polymers. The results reveal that these terpolymers show obviously high crack onset strains and their tensile moduli are remarkably reduced, by comparing with the parent DPP-based conjugated polymer without spiro-fluorene units. They exhibit simultaneously high charge mobilities (>1.0 cm2 V-1 s-1 ) at 100% strain and even after repeated stretching and releasing cycles for 500 times under 50% strain. The terpolymer P2, in which cyclopropane is linked to the spiro-fluorene unit, is among the best reported intrinsically stretchable polymer semiconductors with record mobility up to 3.1 cm2 V-1 s-1 at even 150% strain and 1.4 cm2 V-1 s-1 after repeated stretching and releasing cycles for 1000 times.

Activation of FMS-like tyrosine kinase 3 protects against isoprenaline-induced cardiac hypertrophy by improving autophagy and mitochondrial dynamics.

FMS-like receptor tyrosine kinase 3 (Flt3) expression was reported to increase in the heart in response to pathological stress, but the role of Flt3 activation and its underlying mechanisms remain poorly elucidated. This study was designed to investigate the role of Flt3 activation in sympathetic hyperactivity-induced cardiac hypertrophy and its mechanisms through autophagy and mitochondrial dynamics. In vivo, cardiac hypertrophy was established by subcutaneous injection of isoprenaline (6 mg/kg·day) in C57BL/6 mice for 7 consecutive days. The Flt3-ligand intervention was launched 2 h prior to isoprenaline each day. In vitro, experiments of cardiomyocyte hypertrophy, autophagy, and mitochondrial dynamics were performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that the expression level of Flt3 protein was significantly increased in the hypertrophic myocardium provoked by isoprenaline administration. Flt3-ligand intervention alleviated isoprenaline-induced cardiac oxidative stress, hypertrophy, fibrosis, and contractile dysfunction. Isoprenaline stimulation impaired autophagic flux in hypertrophic mouse hearts, supported by the accumulation of LC3II and P62 proteins, while Flt3-ligand restored the impairment of autophagic flux. Flt3 activation normalized the imbalance of mitochondrial fission and fusion in the hearts of mice evoked by isoprenaline as evidenced by the neutralization of elevated mitochondrial fission markers and reduced mitochondrial fusion markers. In NRCMs, Flt3-ligand treatment attenuated isoprenaline-stimulated hypertrophy, which was abolished by a Flt3-specific blocker AC220. Activating Flt3 reversed isoprenaline-induced autophagosome accumulation and impairment of autophagic flux probably by enhancing SIRT1 expression and consequently TFEB nuclear translocation. Flt3 activation improved the imbalance of mitochondrial dynamics induced by isoprenaline in NRCMs through the SIRT1/P53 pathway. Activation of Flt3 mitigated ISO-stimulated hypertrophy probably involves the restoration of autophagic flux and balance of mitochondrial dynamics. Therefore, activation of Flt3 attenuates isoprenaline-induced cardiac hypertrophy in vivo and in vitro, the potential mechanism probably attributes to SIRT1/TFEB-mediated autophagy promotion and SIRT1/P53-mediated mitochondrial dynamics balance. These findings suggest that activation of Flt3 may be a novel target for protection against cardiac remodeling and heart failure during sympathetic hyperactivity.

A Dual Functional Diketopyrrolopyrrole-Based Conjugated Polymer as Single Component Semiconducting Photoresist by Appending Azide Groups in the Side Chains.

Molecular systems that can function as photoresists are essential for the fabrication of flexible electronics through all-photolithographic processes. Most of the reported molecular systems for photo-patterning of polymeric semiconductors contain binary or multi-components. In comparison, single component semiconducting photoresist is advantageous since it will circumvent the optimization of phase separation and ensure the patterned semiconducting thin films to be more uniform. In this paper, a single component semiconducting photoresist (PDPP4T-N3 ) by incorporating azide groups into the branching alkyl chains of a diketopyrrolopyrrole-based conjugated polymer is reported. The results reveal that i) the azide groups make the side chains to be photo-cross-linkable; ii) uniform patterns with size as small as 5 µm form under mild UV irradiation (365 nm, 85 mW cm-2 ) at ambient conditions; iii) such photo-induced cross-linking does not affect the inter-chain packing; iv) benefiting from the single component feature, field-effect transistors (FETs) with the individual patterned thin films display satisfactorily uniform performances with average charge mobility of 0.61 ± 0.10 cm2  V-1  s-1 and threshold voltage of 3.49 ± 1.43 V. These results offer a simple yet effective design strategy for high-performance single component semiconducting photoresists, which hold great potentials for flexible electronics processed by all-photolithography.

miR-378a regulates keratinocyte responsiveness to interleukin-17A in psoriasis.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease, in which an interplay between infiltrating immune cells and keratinocytes sustains chronic skin inflammation. Interleukin (IL)-17A is a key inflammatory cytokine in psoriasis and its main cellular targets are keratinocytes. OBJECTIVES: To explore the role of miR-378a in psoriasis. METHODS: Keratinocytes obtained from psoriatic skin and healthy epidermis were separated by magnetic sorting, and the expression of miR-378a was analysed by quantitative polymerase chain reaction. The regulation and function of miR-378a was studied using primary human keratinocytes. The expression of miR-378a was modulated by synthetic mimics, and nuclear factor kappa B (NF-κB) activity and transcriptomic changes were studied. Synthetic miR-378a was delivered to mouse skin in conjunction with induction of psoriasiform skin inflammation by imiquimod. RESULTS: We show that miR-378a is induced by IL-17A in keratinocytes through NF-κB, C/EBP-ß and IκBζ and that it is overexpressed in psoriatic epidermis. In cultured keratinocytes, ectopic expression of miR-378a resulted in the nuclear translocation of p65 and enhanced NF-κB-driven promoter activity even in the absence of inflammatory stimuli. Moreover, miR-378a potentiated the effect of IL-17A on NF-κB nuclear translocation and downstream activation of the NF-κB pathway. Finally, injection of miR-378a into mouse skin augmented psoriasis-like skin inflammation with increased epidermal proliferation and induction of inflammatory mediators. Mechanistically, miR-378a acts as a suppressor of NFKBIA/IκBζ, an important negative regulator of the NF-κB pathway in keratinocytes. CONCLUSIONS: Collectively, our findings identify miR-378a as an amplifier of IL-17A-induced NF-κB signalling in keratinocytes and suggest that increased miR-378a levels contribute to the amplification of IL-17A-driven skin inflammation in psoriasis.