Construction of a Label-Detection Integrated Visual Probe to Reveal the Double-Edged Sword Principle of Ferroptosis in Liver Injury.

Ferroptosis has been confirmed as a potential mediator and an indicator of the severity of liver injury. Despite the fruitful results, there are still two deficiencies in the research on the association between ferroptosis and liver injury. First, iron ions are usually selected as the target bioanalyte, but its detection based on a fluorescent probe is interfered with by specific chemical reaction mechanisms, leading to low sensitivity and poor physiological stability. Second, more efforts were focused on the harmful effects of ferroptosis on liver injury and less involved in the therapeutic value of ferroptosis for liver injury. Hence, in this work, we proposed a new nonreactive analyte (mitochondrial viscosity) as an analysis marker, which can circumvent the challenges caused by specific reaction mechanisms of iron ions. Meanwhile, we constructed a novel label-detection integrated visual probe (VPF) to explore the feasibility of ferroptosis in the treatment of liver injury. As expected, we not only successfully traced the dynamic changes in mitochondrial viscosity but also visualized the changes in cell morphology during induced and inhibited ferroptosis. Conspicuously, this work revealed that liver injury can be alleviated by regulating ferroptosis, confirming the therapeutic value of ferroptosis in liver injury. In addition, a complex biological communication network between ferroptosis and liver injury was constructed by western blotting, providing an important theoretical mechanism for revealing their double-edged sword relationship. This study not only provides a new strategy for studying the complex relationship between ferroptosis and liver injury but also facilitates the future treatment of liver injury.

Interaction of Cyclodextrins with Amphiphilic Alternating Cooligomers Possessing the Dense Triazole Backbone.

The interaction of cyclodextrins (CDs) with structure-controlled polymers is expected to provide significant insights into macromolecular recognition. However, the interaction of CDs with structure-controlled polymers has been an underexamined issue of investigation. Herein, alternating amphiphilic cooligomers (oligoCnAH, where n denotes the carbon number of alkyl groups; n = 4, 8, and 12) were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition polymerization of heterodimers of 4-azido-5-hexynoic acid (AH) derivatives carrying N-alkylamide and t-butyl (tBu) ester side chains, followed by hydrolysis of the tBu ester, to study the interaction of CDs with oligoCnAH by 1H NMR, nuclear Overhauser effect spectroscopy, and pulse-field-gradient spin-echo NMR. These NMR studies indicated that αCD interacted with oligoC4AH, αCD and ßCD interacted with oligoC8AH, and all CDs interacted with oligoC12AH. Based on the equilibrium models proposed, the binding constants were evaluated for the binary mixtures, which showed interaction. Comparing the interactions of the CDs/oligoC12AH binary mixtures with those of the binary mixtures of CDs and alternating copolymers of sodium maleate and dodecyl vinyl ether (polyC12M), it is concluded that oligoC12AH forms less stable micelles than does polyC12M presumably because of the lower molecular weight, the hydrophilic amide groups in the side chain, and the longer interval between neighboring C12 groups in oligoC12AH.

Melatonin alleviates di-butyl phthalate (DBP)-induced ferroptosis of mouse leydig cells via inhibiting Sp2/VDAC2 signals.

As one of the endocrine-disrupting chemicals (EDCs), dibutyl phthalate (DBP) has been extensively used in industry. DBP has been shown to cause damage to Leydig cells, yet its underlying mechanism remains elusive. In this study, we show that DBP induces ferroptosis of mouse Leydig cells via upregulating the expression of Sp2, a transcription factor. Also, Sp2 is identified to promote the transcription of Vdac2 gene by binding to its promoter and subsequently involved in DBP-induced ferroptosis of Leydig cells. In addition, DBP is proved to induce ferroptosis via inducing oxidative stress, while inhibition of oxidative stress by melatonin alleviates DBP-induced ferroptosis and upregulation of Sp2 and VDAC2. Taken together, our findings demonstrate that melatonin can alleviate DBP-induced ferroptosis of mouse Leydig cells via inhibiting oxidative stress-triggered Sp2/VDAC2 signals.

Effect of Breathing Meditation Training on Nursing Work Quality, Occurrence Risk of Adverse Events, and Attention Level of Operating Room Nurses.

Objective: To explore the effect of breathing meditation training on nursing work quality, occurrence risk of adverse events, and attention level of operating room nurses. Methods: Taking the starting time of breathing meditation training of operating room nurses in our hospital in July 2020 as the dividing line, operating room nurses who implemented routine management from April 2020 to June 2020 were selected as the control group (n=30), and operating room nurses who carried out breathing meditation training from July 2020 to September 2020 were included in the intervention group (n=30). The emotional state [Hamilton Anxiety Scale (HAMA) score, Hamilton Depression Scale (HAMD) score], Mindfulness Attention Awareness Scale (MAAS) score, electrocardiogram indicators (blood pressure, pulse, and respiration), electroencephalogram indicators (SMR wave, ß wave, and θ wave EEG frequency), attention level (attention quotient, visual attention, and auditory attention), nursing work quality (health education, theoretical knowledge, nursing operation, and operating room management) and the number of reported adverse events were compared between the two groups before and after training. Results: After breathing meditation training, the intervention group's Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) scores were significantly reduced (P < .05), while the Mindfulness Attention Awareness Scale (MAAS) score was significantly increased (P < .05). ). In addition, blood pressure and respiratory rate were reduced in the intervention group (P < .05), with significant differences compared with the control group (P < .05). The SMR waves and beta waves in the intervention group increased (P < .05), while theta waves decreased (P < .05). Attention quotient, visual attention and auditory attention scores were improved in the intervention group compared with the control group (P < .05). The scores of health education, theoretical knowledge, nursing operations and operating room management of the intervention group after training were higher than those of the control group (P < .05). The intervention group reported a lower number of adverse events than the control group (74.42% vs. 25.58%). The application of breathing meditation training in special training for operating room nurses can effectively relieve negative emotions, enhance mindfulness scores, reduce blood pressure and respiratory rate, regulate brain wave frequency, improve attention status and quality of nursing work, and reduce the risk of adverse events. These outcomes may have a positive impact on improving the quality of nursing practice and patient care in the operating room. For operating room nurses, the negative emotional stress caused by sustained high levels of mental concentration may affect work efficiency and the entire surgical process. Breathing meditation training can enhance nurses' emotional resilience, thereby improving the efficiency and safety of operating room care. Conclusion: The application of breathing meditation training in the special training of operating room nurses can effectively alleviate negative emotions, enhance the mindfulness score, reduce blood pressure and respiratory rate, regulate brain wave frequency, improve the attention state and nursing work quality, and reduce the occurrence risk of adverse events. Future research should conduct longitudinal studies to evaluate the long-term effects of breathing meditation training on the quality of nursing work and the prevention of adverse events. Additionally, research could explore advanced neuroimaging techniques to gain structural insights, integrate meditation into existing training programs, tailor interventions for different healthcare settings, assess patient outcomes, explore technology-assisted meditation, and investigate interprofessional collaboration. Through these pathways, a more complete understanding of the impact and best integration of breath meditation in healthcare settings can be achieved, providing valuable insights into improving the well-being of healthcare professionals and potentially overall patient care and satisfaction.

ARTS is essential for di-2-ethylhexyl phthalate (DEHP)-induced apoptosis of mouse Leydig cells.

As an extensively employed plasticizer in industrial applications, di-2-ethylhexyl phthalate (DEHP) can induce apoptosis of mouse Leydig cells, yet the precise mechanism remains elusive. In the current study, we identified that DEHP could specially induced apoptosis in the Leydig cells of the testis tissue, accompanied with the upregulation of apoptosis-related protein in the TGF-ß signaling pathway (ARTS) in the cells. Overexpression of ARTS significantly induced apoptosis of TM3 cells, while knockdown of ARTS inhibited apoptosis. Furthermore, DEHP-induced apoptosis of TM3 cells could be alleviated by knockdown of ARTS, which indicated that ARTS was involved in DEHP-induced apoptosis of mouse Leydig cells. Bioinformation assay predicts that there are four potential p53-responsive elements (p53-REs) located at - 6060, - 5726, - 5631 and - 5554 before the transcription start site of ARTS gene, implying that gene transcription of ARTS could be regulated by p53. Interestingly, DEHP was shown to specifically upregulate the expression of p53 in the Leydig cells of the testis tissue and TM3 cells. Consistently, p53 was proved to bind to the RE4 site of the ARTS gene promoter and transcriptionally activated the promoter-driven expression of the luciferase reporter gene. Overexpression of p53 could induce apoptosis of TM3 cells; while knockdown of p53 could not only rescue DEHP-induced apoptosis of the cells, but also inhibit DEHP-caused upregulation of ARTS. Meanwhile, we showed that oxidative stress could induce apoptosis of TM3 cells, accompanied with the increased protein levels of p53 and ARTS; while inhibition of oxidative stress dramatically alleviated DEHP-induced apoptosis and the up-regulation of p53 and ARTS. Taken together, these results indicated that DEHP-induced oxidative stress activates the p53-ARTS cascade to promote apoptosis of mouse Leydig cells.

From Biomimicking to Bioinspired Design of Electrocatalysts for CO2 Reduction to C1 Products.

The electrochemical reduction of CO2 (CO2 RR) is a promising approach to maintain a carbon cycle balance and produce value-added chemicals. However, CO2 RR technology is far from mature, since the conventional CO2 RR electrocatalysts suffer from low activity (leading to currents <10 mA cm-2 in an H-cell), stability (<120 h), and selectivity. Hence, they cannot meet the requirements for commercial applications (>200 mA cm-2 , >8000 h, >90 % selectivity). Significant improvements are possible by taking inspiration from nature, considering biological organisms that efficiently catalyze the CO2 to various products. In this minireview, we present recent examples of enzyme-inspired and enzyme-mimicking CO2 RR electrocatalysts enabling the production of C1 products with high faradaic efficiency (FE). At present, these designs do not typically follow a methodical approach, but rather focus on isolated features of biological systems. To achieve disruptive change, we advocate a systematic design methodology that leverages fundamental mechanisms associated with desired properties in nature and adapts them to the context of engineering applications.

Electrochemical Ni-Catalyzed Decarboxylative C(sp3 )-N Cross-Electrophile Coupling.

A new electrochemical transformation is presented that enables chemists to couple simple alkyl carboxylic acid derivatives with an electrophilic amine reagent to construct C(sp3 )-N bond. The success of this reaction hinges on the merging of cooperative electrochemical reduction with nickel catalysis. The chemistry exhibits a high degree of practicality, showcasing its wide applicability with 1°, 2°, 3° carboxylic acids and remarkable compatibility with diverse functional groups, even in the realm of late-stage functionalization. Furthermore, extensive mechanistic studies have unveiled the engagement of alkyl radicals and iminyl radicals; and elucidated the multifaceted roles played by i Pr2 O, Ni catalyst, and electricity.

MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy.

Multiple genome-wide association studies (GWASs) have reproducibly identified the MTMR3/HORMAD2/LIF/OSM locus to be associated with IgA nephropathy (IgAN). However, the causal variant(s), implicated gene(s), and altered mechanisms remain poorly understood. Here, we performed fine-mapping analyses based on GWAS datasets encompassing 2762 IgAN cases and 5803 control individuals, and identified rs4823074 as the candidate causal variant that intersects the MTMR3 promoter in B-lymphoblastoid cells. Mendelian randomization studies suggested the risk allele may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, elevated MTMR3 expression in peripheral blood mononuclear cells was observed in patients with IgAN. Further mechanistic studies in vitro demonstrated that MTMR3 increased IgA production dependent upon its phosphatidylinositol 3-phosphate binding domain. Moreover, our study provided the in vivo functional evidence that Mtmr3-/- mice exhibited defective Toll Like Receptor 9-induced IgA production, glomerular IgA deposition, as well as mesangial cell proliferation. RNA-seq and pathway analyses showed that MTMR3 deficiency resulted in an impaired intestinal immune network for IgA production. Thus, our results support the role of MTMR3 in IgAN pathogenesis by enhancing Toll Like Receptor 9-induced IgA immunity.

Investigation of the mechanism of copy number variations involving the α-globin gene cluster on chromosome 16: two case reports and literature review.

Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs. In this study, two novel CNVs, a tandem duplication (αααα159) and deletion (--259), were identified in two Chinese families with thalassemia patients, according to the results of hematologic analysis, routine genetic testing for thalassemia, multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and other molecular methods. Co-inherited with ßCD41-42 mutation and --SEA deletion separately, αααα159 and --259 resulted in a patient with ß-thalassemia intermedia and a lethal fetus with Hb Bart's hydrops fetalis syndrome, respectively. Next, a literature review was performed to summarize all known CNVs involving the α-globin gene cluster. The molecular structure characteristics of these CNVs were analyzed and the possible mechanism was explored. It is the first time to analyze the generation mechanism of genome arrangements in the α-globin gene cluster systematically.

Combinatorial optimization and spatial remodeling of CYPs to control product profile.

Activating inert substrates is a challenge in nature and synthetic chemistry, but essential for creating functionally active molecules. In this work, we used a combinatorial optimization approach to assemble cytochrome P450 monooxygenases (CYPs) and reductases (CPRs) to achieve a target product profile. By creating 110 CYP-CPR pairs and iteratively screening different pairing libraries, we demonstrated a framework for establishing a CYP network that catalyzes six oxidation reactions at three different positions of a chemical scaffold. Target product titer was improved by remodeling endoplasmic reticulum (ER) size and spatially controlling the CYPs' configuration on the ER. Out of 47 potential products that could be synthesized, 86% of the products synthesized by the optimized network was our target compound quillaic acid (QA), the aglycone backbone of many pharmaceutically important saponins, and fermentation achieved QA titer 2.23 g/L.

Ultra-clean ternary Au/Ag/AgCl nanoclusters favoring cryogenic temperature-boosted broadband SERS ultrasensitive detection.

Exploring multifunctional surface-enhanced Raman scattering (SERS) substrates with high sensitivity, broadband response property and reliable practicability should be required for ultrasensitive molecular detection in complex environments, which is heavily dependent on the photo-induced charge transfer (PICT) efficiency realized on the desirable nano-architectures. Herein, we introduce ultra-clean ternary Au/Ag/AgCl nanoclusters (NCs) with broadband resonance crossing the visible light to near-infrared region created by one step laser irradiation of mixed metal ion solution. Interestingly, the surface defects and interaction among these unique cluster-like ternary nanostructures would be further enhanced by thermal annealing treatment at 300°C, providing higher broadband SERS activities than the reference ternary nanoparticles under 457, 532, 633, 785, and 1064 nm wavelengths excitation. More importantly, the further promoted SERS activities of the resultant Au/Ag/AgCl NCs with achievable ∼5-fold enhancement than the initial one can be conventionally realized by simplistically declining the temperature from normal 20°C to cryogenic condition at about -196°C, due to the lower temperature-suppressed non-radiative recombination of lattice thermal phonons and photogenerated electrons. The cryogenic temperature-boosted SERS of the resultant Au/Ag/AgCl NCs enables the limit of detection (LOD) of folic acid (FA) biomolecules to be achieved as low as 10-12 M, which is obviously better than that of 10-9 M at room temperature condition. Overall, the smart Au/Ag/AgCl NCs-based broadband SERS sensor provides a new avenue for ultrasensitive biomolecular monitoring at cryogenic condition.

Construction of Spiro[benzo[a]acridine-12,4'-imidazolidine]-2',5'-dione Derivatives via Ring-Opening and Recyclization of Isatins and C-OH Cleavage of 2-Naphthol.

An efficient three-component reaction to access spiro[benzo[a]acridine-12,4'-imidazolidine]-2',5'-dione derivatives has been developed through the ring-opening and recyclization process of isatins and dehydroxylation of 2-naphthol, which is different from their conventional reaction modes. Experimental observations suggest that p-toluenesulfonic acid is the key factor that promotes the success of this synthetic strategy. The research provided a novel approach for the construction of spiro compounds from isatins and 2-naphthol in organic synthesis.

ATF1 promotes the malignancy of lung adenocarcinoma cells by transcriptionally regulating ZNF143 expression.

The clinical oncogenic functions and mechanisms of activating transcription factor 1 (ATF1) in the progression of lung adenocarcinoma have not been completely elucidated. In this study, by employing human lung adenocarcinoma tissues and cells, we detect the correlation of ATF1 expression with the clinicopathological features and prognosis of patients with lung adenocarcinoma and find that ATF1 promotes lung adenocarcinoma cell proliferation and migration by transcriptionally enhancing zinc finger protein 143 (ZNF143) expression. ATF1 and ZNF143 are strongly expressed in lung adenocarcinoma tissues compared with those in the adjacent normal tissues, and high ATF1 and ZNF143 expressions are related to poor disease-free survival of lung adenocarcinoma patients. ATF1 overexpression results in increased proliferation and migration of lung adenocarcinoma cells, whereas knockdown of ATF1 inhibits cell proliferation and migration. Furthermore, ATF1 transcriptionally regulates the expression of ZNF143, and ATF1 and ZNF143 expressions are positively correlated in lung adenocarcinoma tissues. ZNF143 knockdown blocks lung adenocarcinoma cell migration, which is mediated by ATF1 upregulation. Hence, this study provides a potential therapeutic candidate for the treatment of lung adenocarcinoma.

DDIT4 is essential for DINP-induced autophagy of ovarian granulosa cells.

As one of the most important phthalates, di-isononyl phthalate (DINP) has been widely used as a common plasticizer in the food and personal care products sectors. In our previous study, we found that DINP can induce autophagy of ovarian granulosa cells; while the underlying mechanism is unclear. In the study, we showed that DINP exposure could induce autophagy of ovarian granulosa cells and KGN cells, accompanied with the increase in the mRNA and protein level of DDIT4. Furthermore, overexpression of DDIT4 were shown to induce autophagy of KGN cells; while knockdown of DDIT4 inhibited DINP-induced autophagy, implying that DDIT4 played an important role in DINP-induced autophagy of ovarian granulosa cells. There were three putative binding sites of transcription factor ATF4 in the promoter region of DDIT4 gene, suggesting that DDIT4 might be regulated by ATF4. Herein, we found that overexpression of ATF4 could upregulate the expression of DDIT4 in KGN cells, while knockdown of ATF4 inhibited its expression. Subsequently, ATF4 was identified to bind to the promoter region of DDIT4 gene and promote its transcription. The expression of ATF4 was also increased in the DINP-exposed granulosa cells, and ATF4 overexpression promoted autophagy of KGN cells; whereas knockdown of ATF4 alleviated DINP-induced upregulation of DDIT4 and autophagy of the cells. Taken together, DINP triggered autophagy of ovarian granulosa cells through activating ATF4/DDIT4 signals.

Application of a time-delay SIR model with vaccination in COVID-19 prediction and its optimal control strategy.

In the classical infectious disease compartment model, the parameters are fixed. In reality, the probability of virus transmission in the process of disease transmission depends on the concentration of virus in the environment, and the concentration depends on the proportion of patients in the environment. Therefore, the probability of virus transmission changes with time. Then how to fit the parameters and get the trend of the parameters changing with time is the key to predict the disease course with the model. In this paper, based on the US COVID-19 epidemic statistics during calibration period, the parameters such as infection rate and recovery rate are fitted by using the linear regression algorithm of machine science, and the laws of these parameters changing with time are obtained. Then a SIR model with time delay and vaccination is proposed, and the optimal control strategy of epidemic situation is analyzed by using the optimal control theory and Pontryagin maximum principle, which proves the effectiveness of the control strategy in restraining the transmission of COVID-19. The numerical simulation results show that the time-varying law of the number of active cases obtained by our model basically conforms to the real changing law of the US COVID-19 epidemic statistics during calibration period. In addition, we have predicted the changes in the number of active cases in the COVID-19 epidemic in the USA over time in the future beyond the calibration cycle, and the predicted results are more in line with the actual epidemic data.

Synergistic relationship or not? Understanding the resilience and efficiency of the tourism economy: evidence from Hainan Province, China.

The COVID-19 pandemic has dealt a serious blow to the global tourism industry, causing a fracturing of and decline in tourism development efficiency and even a stagnation of tourism development in some regions. To solve the contradiction between efficiency and quality, it is necessary to ensure the endogenous power of tourism resilience while pursuing the efficiency of tourism development. This study assumes that Hainan Province follows a tourism development path led by resilience. The improved weighting method, EBM model and Haken model are used to evaluate the level of resilience, the level of efficiency and their co-evolution. The findings indicate that the core tourism cities represented by Sanya and Haikou have a high level in the individual fields of tourism development efficiency and tourism economic resilience but have limited performance in the synergistic relationship between tourism development efficiency and tourism economic resilience. In contrast, the marginal tourism cities represented by Tunchang County and Ledong County have low tourism development efficiency and resilience, but their synergistic development level is high. This result proves that co-evolution plays a dual forward and reverse driving role. Based on the identification of the order parameters, it is concluded that Hainan Province is characterized by a synergistic evolutionary synergy dominated by resilience, which is in line with the trend of social development and the sustainable development of tourism. While reasonably pursuing the tourism economy and development efficiency, we should pay attention to strengthening resilience construction based on multiple aspects, such as tourists, enterprises, organizations, governments and destinations.

Biomimic Heterostructured Graphene Oxide Membranes via Supramolecular-Mediated Intercalation Assembly for Efficient Water Transport.

Two-dimensional (2D) lamellar membranes have attracted increasing attention for efficient water purification. However, the low water-permeability, structural failure in aqua and high production cost have significantly restricted their practical large-scale applications. Inspired by the structures of glomerular filtration barrier (GFB) and nacre, a high-performance biomimic membrane via supramolecular-mediated intercalation assembly is reported, where rod-shaped cyclodextrin (CD) functionalized attapulgite (ATP-CD) is intercalated into CD-modified graphene oxide (GO-CD) lamellar channels, followed by locking adjacent ATP-CD and GO-CD through tannic acid (TA) and CD supramolecular networks. The formed GFB-like heterostructure endows the membrane with excellent water transport capability and the bionic "brick and mortar" nacre configuration boosts its anti-swelling stability simultaneously. The heterostructured GO membranes (≈100 nm) fabricated in this way exhibit a good water permeability of 55.6 L m-2  h-1  bar-1 (≈20-fold higher than GO membrane) maintaining excellent dye rejection of >99% during 480 h immersion. Given the low-cost materials (ATP, CD, and TA) and the modification generality, this economic strategy can hopefully achieve large-scale membrane fabrication and afford high applicability, which promotes the practical engineering applications of such 2D material membranes.

An insight into the interaction between Indisulam and human serum albumin: Spectroscopic method, computer simulation and in vitro cytotoxicity assay.

Indisulam (IDM) is a sulfanilamide anticancer agent and has been identified as a molecular glue recently. It shows potential for novel therapies development and brings more hope for curing human diseases. The affinity between molecular glues and plasma protein makes it significant to understand the characteristics of such substances. Therefore, the interaction between IDM and human serum albumin (HSA) was explored through solvent experiments, computer simulation experiments, enzyme kinetics experiments, and cell viability assay. The results revealed that IDM and HSA spontaneously formed stable binary complex with the binding constant of the order 105 M-1. IDM inserted in the site I of HSA, resulting the change in HSA secondary structure. And π electrons in IDM's benzene rings, as well as van der Waals forces and the H-bond, all helped to stabilize the HSA-IDM complex. The results of molecular dynamic simulation (MD) corresponded with the results from solvent experiment well. For instance, there were approximately 1-5 H-bonds between IDM and HSA. Lys199 and Arg218 were crucial energy contributors in the binding process. The esterase-like activity experiment confirmed that IDM inhibited the catalytic activity of HSA. In addition, cell experiment revealed that serum albumin can significantly reduce the cytotoxicity of IDM towards human embryonic kidney 293T (HEK293T) cells.

Aberrant expression of the extracellular matrix component Biglycan regulated by Hedgehog signalling promotes colorectal cancer cell proliferation.

Hedgehog (Hh) signalling plays essential roles in regulating embryonic development and contributes to tumour initiation, growth and progression in multiple cancers. The detailed mechanism by which Hh signalling participates in tumour growth warrants thorough study, although several downstream target genes have been identified. Herein, a set of novel targets of Hh signalling was identified in multiple types of tumour cells via RNA-Seq analysis. Among these targets, the expression regulation and oncogenic function of the extracellular matrix component biglycan (BGN) were investigated. Further investigation verified that Hh signalling activates the expression of BGN via the transcription factor Gli2, which directly binds to the promoter region of BGN. Functional assays revealed that BGN facilitates tumour cell growth and proliferation in colorectal cancer (CRC) cells, and xenograft assays confirmed that BGN also promotes tumour growth . Moreover, analysis of clinical CRC samples showed that both the protein and mRNA levels of BGN are increased in CRC tissues compared to those in adjacent tissues, and higher expression of BGN is correlated with poorer prognosis of CRC patients, further confirming the function of BGN in CRC. Taken together, aberrantly activated Hh signalling increases the expression of BGN, possibly regulates the extracellular matrix, and thereby promotes tumour growth in CRC.

Tailoring a Nanochaperone to Regulate α-Synuclein Assembly.

Protein misassembly leads to the formation of dysfunctional and toxic molecular species relating to neurodegeneration in Parkinson's disease and Alzheimer's disease. Here, we tailored a nanochaperone (αS-nChap) for α-synuclein to regulate its assembly. The αS-nChap is capable of i) specifically recognizing α-synuclein; ii) dynamically capturing and stabilizing monomeric α-synuclein and retarding oligomerization; iii) tightly capturing oligomeric α-synuclein to prevent fibrillization; and iv) transporting α-synuclein oligomers to the lysosomal degradation system. The regulation of α-synuclein assembly by αS-nChap was studied in vitro. Moreover, the role of αS-nChap preventing α-synuclein pathology in cells and protecting neurons from apoptosis was investigated. The strategy of tailoring a nanochaperone to regulate aberrant assembly of pathogenic proteins provides important insights into protein misfolding diseases. We foresee that αS-nChap has therapeutic value for Parkinson's disease.