Development and characterization of a bacterial enzyme cascade reaction system for efficient and stable PET degradation.

The widespread use of polyethylene terephthalate (PET) in various industries has led to a surge in microplastics (MPs) pollution, posing a significant threat to ecosystems and human health. To address this, we have developed a bacterial enzyme cascade reaction system (BECRS) that focuses on the efficient degradation of PET. This system harnesses the Escherichia coli (E. coli) surface to display CsgA protein, which forms curli fibers, along with the carbohydrate-binding module 3 (CBM3) and PETases, to enhance the adsorption and degradation of PET. The study demonstrated that the BECRS achieved a notable PET film degradation rate of 3437 ± 148 µg/(d*cm²), with a degradation efficiency of 21.40% for crystalline PET MPs, and the degradation products were all converted to TPA. The stability of the system was evidenced by retaining over 80% of its original activity after multiple uses and during one month of storage. Molecular dynamics simulations confirmed that the presence of CsgA did not interfere with the enzymatic activity of PETases. This BECRS represents a significant step forward in the biodegradation of PET, particularly microplastics, offering a practical and sustainable solution for environmental pollution control.

The Role of Aryl Hydrocarbon Receptor in the Pathogenesis and Treatment of Psoriasis.

The pathogenesis of psoriasis is complex. Aryl hydrocarbon receptor (AhR) is a transcription factor that can be bound and activated by structurally diverse ligands and plays an important role in a range of biological processes and in the pathogenesis of different diseases. Recently, the role of AhR in psoriasis has attracted attention. AhR has toxicological functions and physiological functions. The overexpression and activation of AhR induced by the environmental pollutant and exogenous AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can drive the development of psoriasis. This TCDD-mediated toxicological response disrupts the physiological functions of AhR resulting in skin barrier disorders and the release of inflammatory cytokines, 2 of the pivotal factors of psoriasis. In addition, highly upregulated kynureninase in psoriasis decreases endogenous AhR agonists, thereby weakening the physiological functions of AhR. Activating AhR physiological signalling should be useful in the treatment of psoriasis. Studies have demonstrated that physiological activation of AhR can dampen the severity of psoriasis. The oldest and effective treatment for psoriasis coal tar works by activating AhR, and both new anti-psoriasis drugs tapinarof and benvitimod are formulations of AhR agonist, supporting that activation of AhR can be used as a new strategy for the treatment of psoriasis. Preclinical and preliminary clinical studies have revealed the anti-psoriasis effects of a number of AhR agonists, providing potential candidates for the development of new drugs for the treatment of psoriasis.

Recent Advances of Lignin Functionalization for High-Performance and Advanced Functional Rubber Composites.

The biomass lignin is the only large-volume renewable feedstock that is composed of aromatics but has been largely underutilized and is sought for valorization as a value-added material. Recent research has highlighted lignin as a promising alternative to traditional petrol-based reinforcements and functional additives for rubber composites. This review summarized the recent advances in the functionalization of lignin for a variety of rubber composites, as well as the compounding techniques for effectively dispersing lignin within the rubber matrix. Significant progress has been achieved in the development of high-performance and advanced functional rubber/lignin composites through carefully designing the structure of lignin-based additives and the optimization of interfacial morphologies. This Review discussed the effect of lignin on composite properties, including mechanical reinforcement, dynamic properties, antiaging performance, and oil resistance, and also the advanced stimuli-responsive performance in detail. A critical analysis for the future development of rubber/lignin composites is presented as concluding remarks.

The possible role of Wnt/ß-catenin signalling in vitiligo treatment.

Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS). Autoimmunity leads to the loss of epidermal melanocytes and the formation of the depigmented patches of the disease. Treatment of vitiligo should control the exaggerated immune response to arrest the progress of active disease, and then promote melanocytes to repigmentation. Wnt/ß-catenin signalling pathway has been of recent interest in vitiligo. Wnt/ß-catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/ß-catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8+ T cell effector cell differentiation and enhancing Treg. Wnt/ß-catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/ß-catenin signalling can not only arrest the progress of active disease of vitiligo but also promote repigmentation. Some of the main effective therapies for vitiligo are likely to work by activating Wnt/ß-catenin signalling. Agents that can enhance the effect of Wnt/ß-catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment.

Peroxisome proliferator-activator receptor γ and psoriasis, molecular and cellular biochemistry.

The pathophysiology of psoriasis is complex and has not been completely elucidated. Better understanding of the pathogenesis may contribute to further improvement of our therapeutic strategies controlling psoriasis. Emerging evidence points to a causative relationship between altered activity of peroxisome proliferator-activated receptor γ (PPARγ) and psoriasis. The present review focuses on deeper understanding of the possible role of PPARγ in the pathogenesis of psoriasis and the potential of PPARγ agonist to improve the treatment of psoriasis. PPARγ is decreased in psoriasis. PPARγ possibly has effects on the multiple aspects of the pathogenesis of psoriasis, including abnormal lipid metabolism, insulin resistance, immune cells, pro-inflammatory cytokines, keratinocytes, angiogenesis, oxidative stress, microRNAs and nuclear factor kappa B. As defective activation of PPARγ is involved in psoriasis development, PPARγ agonists may be promising agents for treatment of psoriasis. Pioglitazone appears an effective and safe option in the treatment of patients with psoriasis, but there are still concerns about its potential side effects. Research effort has recently been undertaken to explore the PPARγ-activating potential of natural products. Among them some have been studied clinically or preclinically for treatment of psoriasis with promising results.

Enhanced Mechanical Properties of Polyvinyl Chloride-Based Wood-Plastic Composites With Pretreated Corn Stalk.

Wood-plastic composites (WPCs) are a type of environmentally friendly materials widely used in daily life. This paper selected low-value biomass, corn stalk (CS), as the lignocellulosic resource for polyvinyl chloride (PVC)-based WPCs. To depict the relationship between lignocellulosic composition (cellulose, hemicellulose, and lignin) and mechanical performance of WPCs, pretreatments have been optimized to selective removal of lignin using an alkaline-EtOH stewing process and selective removal of hemicellulose using an acid stewing process. The αC sample, in which both lignin and hemicellulose were removed, shows the highest degree of crystallinity (72.60%) as estimated from X-ray diffraction analysis results and fibrous morphology with the highest aspect ratio as seen in scanning electron microscopy images. Compared with PVC/CS, PVC/αC gives a substantial increase in tensile strength and modulus by 37.21 and 21.66% and flexural strength and modulus by 29.98 and 34.88%, respectively. These improvements lie in the reinforcing effect of a fibrous structure and the improved interfacial compatibility as proven by scanning electron microscopy and dynamic mechanical analyzer results. Considering the extracted lignin and hemicellulose can be further developed to valuable biochemicals, the pretreatment to CS adds value to both WPC materials and biorefinery products.

Nuclear factor erythroid 2-related factor 2 (Nrf2) as a potential therapeutic target for vitiligo.

Vitiligo is an autoimmune disease of the skin which causes loss of melanocytes from the epidermis. Recently, it is demonstrated that oxidative stress (OS) plays a significant role in the immuno-pathogenesis of vitiligo. A major mechanism in the cellular defense against OS is activation of the nuclear factor erythroid2-related factor (Nrf2)-Kelch-like ECH-associated protein 1(Keap1)-antioxidant responsive element (ARE) signaling pathway. Recently it has been shown that vitiligo melanocytes have impaired Nrf2-ARE signaling. A number of drugs including those known as Nrf2 activators and those known to possess effects to activate Nrf2, have been used in treating vitiligo with certain therapeutic effects. Also, studies have shown that a number of compounds can protect melanocytes against OS via activating Nrf2. These compounds may be considered as candidates for developing new drugs for vitiligo in the future. Nrf2 can be considered as a potential therapeutic target for vitiligo.

Homocysteine and psoriasis.

Psoriasis is caused by a complex interplay among the immune system, genetic background, autoantigens, and environmental factors. Recent studies have demonstrated that patients with psoriasis have a significantly higher serum homocysteine (Hcy) level and a higher prevalence of hyperhomocysteinaemia (HHcy). Insufficiency of folic acid and vitamin B12 can be a cause of HHcy in psoriasis. Hcy may promote the immuno-inflammatory process in the pathogenesis of psoriasis by activating Th1 and Th17 cells and neutrophils, while suppressing regulatory T cells. Moreover, Hcy can drive the immuno-inflammatory process by enhancing the production of the pro-inflammatory cytokines in related to psoriasis. Hcy can induce nuclear factor kappa B activation, which is critical in the immunopathogenesis of psoriasis. There may be a link between the oxidative stress state in psoriasis and the effect of HHcy. Hydrogen sulfide (H2S) may play a protective role in the pathogenesis of psoriasis and the deficiency of H2S in psoriasis may be caused by HHcy. As the role of Hcy in the pathogenesis of psoriasis is most likely established, Hcy can be a potential therapeutic target for the treatment of psoriasis. Systemic folinate calcium, a folic acid derivative, and topical vitamin B12 have found to be effective in treating psoriasis.

Vitamin D and alopecia areata: possible roles in pathogenesis and potential implications for therapy.

Alopecia areata is characterized by the loss of hair on the scalp and elsewhere on the body. It affects approximately 2% of the general population. It is believed to be an autoimmune disease. However, its pathogenesis remains incompletely understood. Recent studies have revealed a substantial link between vitamin D and alopecia areata. But the underlying mechanism still yet to be deciphered. This article reviews the current literature and discusses the possible roles of vitamin D in the pathogenesis of alopecia areata in the context of (1) loss of immune privilege in hair follicle, (2) autoreactive effector T cells and mast cells, (3) nature killer group 2 member d-positive cytotoxic T cells, (4) Janus kinase/signal transducers and activators of transcriptional signaling pathway, (5) regulatory T cells, (6) immune checkpoints, and (7) oxidative stress, which are believed to play important roles in autoimmunity in AA. This paper provides new insights into research directions to elucidate the exact mechanisms of vitamin D in the pathogenesis. Calcipotriol, a vitamin D analog, has been reported to be topically used in treating alopecia areata with promising results. Combination therapy of vitamin D analogs with corticosteroids might also be used in treating alopecia areata.

Imputation from SNP chip to sequence: a case study in a Chinese indigenous chicken population.

BACKGROUND: Genome-wide association studies and genomic predictions are thought to be optimized by using whole-genome sequence (WGS) data. However, sequencing thousands of individuals of interest is expensive. Imputation from SNP panels to WGS data is an attractive and less expensive approach to obtain WGS data. The aims of this study were to investigate the accuracy of imputation and to provide insight into the design and execution of genotype imputation. RESULTS: We genotyped 450 chickens with a 600 K SNP array, and sequenced 24 key individuals by whole genome re-sequencing. Accuracy of imputation from putative 60 K and 600 K array data to WGS data was 0.620 and 0.812 for Beagle, and 0.810 and 0.914 for FImpute, respectively. By increasing the sequencing cost from 24X to 144X, the imputation accuracy increased from 0.525 to 0.698 for Beagle and from 0.654 to 0.823 for FImpute. With fixed sequence depth (12X), increasing the number of sequenced animals from 1 to 24, improved accuracy from 0.421 to 0.897 for FImpute and from 0.396 to 0.777 for Beagle. Using optimally selected key individuals resulted in a higher imputation accuracy compared with using randomly selected individuals as a reference population for re-sequencing. With fixed reference population size (24), imputation accuracy increased from 0.654 to 0.875 for FImpute and from 0.512 to 0.762 for Beagle as the sequencing depth increased from 1X to 12X. With a given total cost of genotyping, accuracy increased with the size of the reference population for FImpute, but the pattern was not valid for Beagle, which showed the highest accuracy at six fold coverage for the scenarios used in this study. CONCLUSIONS: In conclusion, we comprehensively investigated the impacts of several key factors on genotype imputation. Generally, increasing sequencing cost gave a higher imputation accuracy. But with a fixed sequencing cost, the optimal imputation enhance the performance of WGP and GWAS. An optimal imputation strategy should take size of reference population, imputation algorithms, marker density, and population structure of the target population and methods to select key individuals into consideration comprehensively. This work sheds additional light on how to design and execute genotype imputation for livestock populations.

Copy Number Variation in SOX6 Contributes to Chicken Muscle Development.

Copy number variations (CNVs), which cover many functional genes, are associated with complex diseases, phenotypic diversity and traits that are economically important to raising chickens. The sex-determining region Y-box 6 (Sox6) plays a key role in fast-twitch muscle fiber differentiation of zebrafish and mice, but it is still unknown whether SOX6 plays a role in chicken skeletal muscle development. We identified two copy number polymorphisms (CNPs) which were significantly related to different traits on the genome level in chickens by AccuCopy® and CNVplex® analyses. Notably, five white recessive rock (CN = 1, CN = 3) variant individuals and two Xinghua (CN = 3) variant individuals contain a CNP13 (chromosome5: 10,500,294-10,675,531) which overlaps with SOX6. There is a disordered region in SOX6 proteins 265-579 aa coded by a partial CNV overlapping region. A quantitative real-time polymerase chain reaction showed that the expression level of SOX6 mRNA was positively associated with CNV and highly expressed during the skeletal muscle cell differentiation in chickens. After the knockdown of the SOX6, the expression levels of IGFIR1, MYF6, SOX9, SHOX and CCND1 were significantly down-regulated. All of them directly linked to muscle development. These results suggest that the number of CNVs in the CNP13 is positively associated with the expression level of SOX6, which promotes the proliferation and differentiation of skeletal muscle cells by up-regulating the expression levels of the muscle-growth-related genes in chickens as in other animal species.

Negative Glucocorticoid Response-Like Element from the First Intron of the Chicken Growth Hormone Gene Represses Gene Expression in the Rat Pituitary Tumor Cell Line.

The effects of introns, especially the first intron, on the regulation of gene expression remains unclear. Therefore, the objective of the present study was to investigate the transcriptional regulatory function of intron 1 on the chicken growth hormone (cGH) gene in the rat pituitary tumor cell line (GH4-C1). Transient transfection using first-intron-inserted cGH complete coding sequences (CDSs) and non-intron-inserted cGH CDS plasmids, quantitative RT-PCR (qRT-PCR) and western blot assays were used to detect the expression of cGH. The reporter gene assay was also used to investigate the effect of a series of fragments in the first intron of cGH on gene expression in GH4-C1. All of the results revealed that a 200-bp fragment located in the +485/+684 region of intron 1 was essential for repressing the expression of cGH. Further informatics analysis showed that there was a cluster of 13 transcriptional factor binding sites (TFBSs) in the +485/+684 region of the cGH intron 1. Disruption of a glucocorticoid response-like element (the 19-nucleotide sequence 5'-AGGCTTGACAGTGACCTCC-3') containing a T-box motif (TGACCT) located within this DNA fragment increased the expression of the reporter gene in GH4-C1. In addition, an electrophoretic mobility shift assay (EMSA) revealed a glucocorticoid receptor (GR) protein of rat binding to the glucocorticoid response-like element. Together, these results indicate that there is a negative glucocorticoid response-like element (nGRE) located in the +591/+609 region within the first intron of cGH, which is essential for the down-regulation of cGH expression.

The Long Intron 1 of Growth Hormone Gene from Reeves' Turtle (Chinemys reevesii) Correlates with Negatively Regulated GH Expression in Four Cell Lines.

Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves' turtle (Chinemys reevesii) have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH) cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp), comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS) of the turtle's GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO) cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH) gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves' turtle might correlate with downregulated gene expression.

Oxidative stress in psoriasis and potential therapeutic use of antioxidants.

The pathophysiology of psoriasis is complex and dynamic. Recently, the involvement of oxidative stress in the pathogenesis of psoriasis has been proposed. Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage. In this article, the published studies on the role of oxidative stress in psoriasis pathogenesis are reviewed, focusing on the impacts of oxidative stress on dendritic cells, T lymphocytes, and keratinocytes, on angiogenesis and on inflammatory signaling (mitogen-activated protein kinase, nuclear factor-κB, and Janus kinase/signal transducer and activator of transcription). As there is compelling evidence that oxidative stress is involved in the pathogenesis of psoriasis, the possibility of using this information to develop novel strategies for treatment of patients with psoriasis is of considerable interest. In this article, we also review the published studies on treating psoriasis with antioxidants and drugs with antioxidant activity.

Co-signaling molecules in psoriasis pathogenesis: implications for targeted therapy.

Psoriasis is a T cell-dependent immune-mediated disease of the skin and joints. It is clear that co-stimulatory and co-inhibitory molecules (currently named co-signaling molecules collectively) synergize with TCR signaling to promote or inhibit T cell activation and function. In recent years, enthusiasm in the field of co-signaling research has been fueled by the success of co-stimulatory and co-inhibitory immunotherapy for the treatment of human diseases. This review outlines the involvement of several sets of co-signaling molecules in the immunopathogenesis of psoriasis. We then describe the relevant preclinical studies and summarize recent clinical findings on targeting these molecules for the treatment of psoriasis.

Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target?

Psoriasis is a common chronic inflammatory disease of the skin. Its pathogenesis has not been completely elucidated. Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway has been identified as a key signaling pathway for important cellular functions. The data collected in this review suggest that overexpression of the PI3K/Akt/mTOR pathway may play an important role in the pathogenesis of psoriasis by mediating the immune-pathogenesis, the epidermal hyperplasia or/and the angiogenesis in the disease. Advances in understanding the pathogenesis of psoriasis has provided new insight into potential therapeutic targets, including the development of biological therapies, resulting in remarkable clinical responses in patients with severe psoriasis. More recently, small molecule oral preparations targeting intracellular signaling that may prove effective have been developed. Data suggest that PI3K/Akt/mTOR pathway may be a potential target for treatment of psoriasis.

Possible roles of B lymphocyte activating factor of the tumour necrosis factor family in vitiligo autoimmunity.

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of epidermal melanocytes. Strong evidence supports the theory that autoimmune mechanisms, namely B cell auto-antibody production and auto-reactive T cell cytotoxicity, are involved in this affliction. It is well known that autoimmunity results from a breakdown of self-tolerance. However, the mechanism which leads to the break-down of self-tolerance and subsequently causes the development of autoimmunity in vitiligo remains obscure. B lymphocyte activating factor of the tumour necrosis factor family is a recently identified ligand that is required for peripheral B-cell survival and homeostasis, the excessive production of which may lead to autoimmunity. Based on a collection of indirect evidences, we postulate that in individuals predisposed through inheritance, over-expression of the B lymphocyte activating factor may cause a breakdown of self-tolerance and subsequently cause autoimmune vitiligo via several possible mechanisms: B lymphocyte activating factor activates self-reactive B cells to produce auto-antibodies against melanocytes; these B cells may function as cellular adjuvants for the activation of the CD4+ T cells, enhancing their helper effect on the activation of the CD8+ T cells; CD4+ T cells assist CD8+ T cells to respond to melanocytes antigen, leading to the autoreactive reaction; B lymphocyte activating factor activated B cells capture antigen and present it directly to the CD8+ T cells; and, B lymphocyte activating factor delivers a complete costimulation signal to the T cells (both CD4+ and CD8+ subset), playing an additional role in the autoimmune response in vitiligo. Future challenges remain to test these propositions. Advancement in the treatment of vitiligo is still unsatisfactory, and thus novel modalities of therapy need to be developed. Recently, B lymphocyte activating factor has been evaluated as an attractive target for immune therapy. Once the hypothesis of B lymphocyte activating factor mediating the breakdown of self-tolerance in vitiligo is corroborated, it can become a novel target for treatment of vitiligo.

Effects of isocamptothecin, a novel camptothecin analogue, on proliferation, apoptosis and telomerase activity in HaCaT cells.

Camptothecin is a topoisomerase I inhibitor with definite anti-psoriatic effect. As it is limited in clinical application because of serious side effects and toxicity, many researchers are striving hard to develop derivatives or analogues of camptothecin with higher effects and less toxicity. To explore the anti-psoriatic potential of isocamptothecin, a novel camptothecin analogue, its effects on proliferation, apoptosis and telomerase activity were investigated in the human keratinocyte cell line HaCaT. Incubation with isocamptothecin resulted in a time- and concentration-dependent inhibition of HaCaT cell proliferation. However, isocamptothecin showed larger inhibitory concentration at 50% than camptothecin, suggesting far less cytotoxicity. In addition, isocamptothecin induced apoptosis in a concentration-dependent manner and induced typical morphologic features of apoptosis in HaCaT cells. Moreover, isocamptothecin downregulated the telomerase activity of HaCaT cells not only at concentrations of apoptosis induction but also at concentration insufficient to induce apoptosis, providing additional mechanisms that further account for its ability to inhibit keratinocytes proliferation and induce apoptosis. These results indicate that isocamptothecin possesses similar effects on keratinocytes with camptothecin, but shows far less cytotoxicity, it may probably become a promising agent for psoriasis therapy.