Self-assembly of peptides in living cells for disease theranostics.

The past few decades have witnessed substantial progress in biomedical materials for addressing health concerns and improving disease therapeutic and diagnostic efficacy. Conventional biomedical materials are typically created through an ex vivo approach and are usually utilized under physiological environments via transfer from preparative media. This transfer potentially gives rise to challenges for the efficient preservation of the bioactivity and implementation of theranostic goals on site. To overcome these issues, the in situ synthesis of biomedical materials on site has attracted great attention in the past few years. Peptides, which exhibit remarkable biocompability and reliable noncovalent interactions, can be tailored via tunable assembly to precisely create biomedical materials. In this review, we summarize the progress in the self-assembly of peptides in living cells for disease diagnosis and therapy. After a brief introduction to the basic design principles of peptide assembly systems in living cells, the applications of peptide assemblies for bioimaging and disease treatment are highlighted. The challenges in the field of peptide self-assembly in living cells and the prospects for novel peptide assembly systems towards next-generation biomaterials are also discussed, which will hopefully help elucidate the great potential of peptide assembly in living cells for future healthcare applications.

Facial adult female acne in China: An analysis based on artificial intelligence over one million.

BACKGROUND: To further clarify the acne profile of Chinese adult women, we included 1,156,703 adult women. An artificial intelligence algorithm was used to analyze images taken by high-resolution mobile phones to further explore acne levels in Chinese adult women. METHOD: In this study, we assessed the severity of acne by evaluating patients' selfies through a smartphone application. Furthermore, we gathered basic user information through a questionnaire, including details such as age, gender, skin sensitivity, and dietary habits. RESULTS: This study showed a gradual decrease in acne severity from the age of 25 years. A trough was reached between the ages of 40 and 44, followed by a gradual increase in acne severity. In terms of skin problems and acne severity, we have found that oily skin, hypersensitive skin, frequent makeup application and unhealthy dietary habits can affect the severity of acne. For environment and acne severity, we observed that developed city levels, cold seasons and high altitude and strong radiation affect acne severity in adult women. For the results of the AI analyses, the severity of blackheads, pores, dark circles and skin roughness were positively associated with acne severity in adult women. CONCLUSIONS: AI analysis of high-res phone images in Chinese adult women reveals acne severity trends. Severity decreases after 25, hits a low at 40-44, then gradually rises. Skin type, sensitivity, makeup, diet, urbanization, seasons, altitude, and radiation impact acne. Blackheads, pores, dark circles, and skin roughness are linked to acne severity. These findings inform personalized skincare and public health strategies for adult women.

Microfungi Associated with Peach Branch Diseases in China.

Peach (Prunus persica L.) is one of the most important and oldest stone fruits grown in China. Even though P. persica is one of the most commonly grown stone fruits in China, little is known about the biodiversity of microfungi associated with peach branch diseases. In the present study, samples were collected from a wide range of peach growing areas in China, and fungal pathogens associated with peach branch diseases were isolated. In total, 85 isolates were obtained and further classified into nine genera and 10 species. Most of the isolates belonged to Botryosphaeriaceae (46), including Botryosphaeria, Diplodia, Neofusicoccum, Phaeobotryon, and Lasiodiplodia species; Ascochyta, Didymella, and Nothophoma species representing Didymellaceae were also identified. Herein, we introduce Ascochyta prunus and Lasiodiplodia pruni as novel species. In addition, we report the first records of Nothophoma pruni, Neofusicoccum occulatum, and Phaeobotryon rhois on peach worldwide, and Didymella glomerata, Nothophoma quercina, and Phaeoacremonium scolyti are the first records from China. This research is the first comprehensive investigation to explore the microfungi associated with peach branch disease in China. Future studies are necessary to understand the pathogenicity and disease epidemiology of these identified species.

Redox-Regulated In Situ Seed-Induced Assembly of Peptides.

Morphology-transformational self-assembly of peptides allows for manipulation of the performance of nanostructures and thereby advancing the development of biomaterials. Acceleration of the morphological transformation process under a biological microenvironment is important to efficiently implement the tailored functions in living systems. Herein, we report redox-regulated in situ seed-induced assembly of peptides via design of two co-assembled bola-amphiphiles serving as a redox-resistant seed and a redox-responsive assembly monomer, respectively. Both of the peptides are able to independently assemble into nanoribbons, while the seed monomer exhibits stronger assembling propensity. The redox-responsive monomer undergoes morphological transformation from well-defined nanoribbons to nanoparticles. Kinetics studies validate the role of the assembled inert monomer as the seeds in accelerating the assembly of the redox-responsive monomer. Alternative addition of oxidants and reductants into the co-assembled monomers promotes the redox-regulated assembly of the peptides facilitated by the in situ-formed seeds. The reduction-induced assembly of the peptide could also be accelerated by in situ-formed seeds in cancer cells with a high level of reductants. Our findings demonstrate that through precisely manipulating the assembling propensity of co-assembled monomers, the in situ seed-induced assembly of peptides could be achieved. Combining the rapid assembly kinetics of the seed-induced assembly with the common presence of redox agents in a biological microenvironment, this strategy potentially offers a new method for developing biomedical materials in living systems.

Artificial intelligence analysis of over a million Chinese men and women reveals level of dark circle in the facial skin aging process.

BACKGROUND: To better compare the progression of dark circles and the aging process in Chinese skin. A total of 100 589 Chinese males and 1 838 997 Chinese females aged 18 to 85, without facial skin conditions, and who had access to a smartphone with a high-resolution camera all took selfies. METHOD: Using a smartphone application with a built-in artificial intelligence algorithm, facial skin diagnostic evaluated the selfies and score the severity of the dark circles with four other facial indicators (including skin type, Pores, Acne vulgaris, and Blackheads). Basic information was collected with online questionnaire, including their age, gender, skin sensitivity, and dietary habits. RESULTS: In users between the age of 18 and 59, the prevalence of comprehensive, pigmented, and structural type of dark circles all rose with age. However, between the age of 60 and 85, the intensity of all types of dark circles diminished. Besides, vascular dark circles progressively worsen from the age of 18 to their peak at 39, and then gradually decline with age. Females typically have more pronounced black circles under their eyes than males in China. Bad eating habits, urbanization, regular cosmetics use, and sensitive skin positively correlate with severe dark circles. Vascular, comprehensive dark circles were worse in spring. Both pigmented and structural dark circles were worse in the summer. The results indicated that the intensity of dark circles was influenced by oily skin, wide pores, severe blackheads, and severe acne. CONCLUSIONS: Chinese men and women differed noticeably in the prevalence of each face aging indicator and the appearance of aging dark circles. Selfies could be automatically graded and examined by artificial intelligence, which is a quick and private method for quantifying signs of facial aging and identifying major problems for different populations. Artificial intelligence would assist in the development of individualized preventive and therapeutic interventions.

Arginine Methylation Regulates Self-Assembly of Peptides.

Bio-inspired design of peptides represents one facile strategy for development of supramolecular monomers for self-assembly into well-defined nanostructures. Inspired by methylation of arginine during post-translational modification for manipulating protein functions, herein, the controllable self-assembly of peptides via rational incorporation of methylated arginine residues into bola-amphiphilic peptides is reported. A series of bola-amphiphilic peptides are designed and synthesized either containing natural arginine or methylated arginine and investigate the influence of arginine methylation on peptide assembly. This study finds that incorporation of symmetrically di-methylated arginine into oppositely charged hexapeptide hex-SDMAE leads to distinct assembling performance compare to natural peptide hex-RE. The findings demonstrate that the methylation of rationally designed peptide sequences allows for regulation of self-assembly of peptides, thus implying the great potential of arginine methylation in establishing controllable peptide assembling systems and creating in situ formulation of biomedical materials in the future.

Direct Synthesis of Sulfonylated Spiro[indole-3,3'-pyrrolidines] by Silver-Mediated Sulfonylation of Acrylamides Coupled with Indole Dearomatization.

A dearomative tandem spiro-cyclization reaction of N-[(1H-indol-3-yl)methyl]methacrylamide derivatives with sulfinate sodium in the presence of AgNO3 and K2CO3 is reported, which produced sulfonylated spiro[indole-3,3'-pyrrolidines] in medium to excellent yields. The characteristics of this transformation contain good functional group tolerance and ease of operation.

[Effect of human monocytes on coal tar pitch extract-induced TRAF2 mRNA expression in human bronchial epithelial cells].

OBJECTIVE: To explore the regulation mechanism of coal tar pitch smoke extracts( CTPE) on tumor necrosis factor receptor-associated factor 2( TRAF2) mRNA expression in co-cultured model of human monocytes( THP-1) and BEAS-2B cells. METHODS: The co-cultured THP-1 and BEAS-2B cells were simulated by 3 µg/m L CTPE. The cells at passage 9 were treated with tumor necrosis factor-α( TNF-α) neutralization antibody and c-Jun N-terminal kinase( JNK) inhibitors SP600125, and continued toculture at passage 15( neutralizing antibody group) and established the BEAS-2B cells of same generation as control group. The expression of TRAF2 mRNA was detected by realtime fluorescent quantitative polymerase chain reaction. RESULTS: The expression of TRAF2 mRNA and c-Jun mRNA in different groups of TNF-α neutralization antibody and JNK kinase inhibitors SP600125 groups were decreased compared with CC10, respectively the groups of 48h( 0. 19 ± 0. 02) and 36h( 0. 03 ± 0. 02) were lowest. The expression of TRAF2 mRNA in groups of TNF-α neutralization antibody and JNK kinase inhibitors SP600125 groups( respectively 1. 73 ± 0. 04 and 1. 88 ± 0. 05) were both significantly increased compared with control group( 1. 07 ± 0. 06), and lower than CC15( 2. 23 ±0. 09). CONCLUSION: THP-1 could up-regulate the expression of TRAF2 mRNA through TNF-α in the BEAS-2B cells stimulated by CTPE, and there maybe negative feedback effect between TRAF2 and AP-1.

[Pyroptosis induced by zinc oxide nanoparticles in A549 cells].

OBJECTIVE: To explore whether exposure to zinc oxide nanoparticles (ZnO-NPs) induced pyroptosis in human alveolar type II epithelial cells (A549). METHODS: A549 cells were stimulated with different concentrations of ZnO-NPs (10 and 20 microg/ml) for 8 and 24h, respectively. The activity of lactic dehydrogenase (LDH) and the levels of interleukin-1beta (IL-1beta) in cell culture media were respectively measured by LDH activity kit and human IL-1beta ELISA kit. The activity of caspase-1 in A549 cells was detected by caspase-1 colorimetric assay kit. RESULTS: At 8h exposure to ZnO-NPs, there was no significant difference in the activity of LDH in the cell culture media among the ZnO-NPs-treated and control groups, but the activity of caspase-1 and the levels of IL-1beta in A549 cells were significantly increased in 20 microg/ml ZnO-NPs group compared to that in the control group (P < 0.05). Levels of IL-1beta and activity of LDH in the groups treated with ZnO-NPs (10 or 20 microg/ml) were significantly higher than that in the control group after 24 h exposure to ZnO-NPs, but there was no significant difference in the activity of caspase-1 among ZnO-NPs and control group. CONCLUSION: ZnO-NPs (20 microg/ml) treatment induces early increase in caspase-1 activity followed by the increase in LDH activity and IL-1 levels, indicative of pyroptosis in A549 cells.

[Coal tar pitch smoke extract-induced pyroptosis in human bronchial epithelial cells].

OBJECTIVE: To explore whether coal tar pitch smoke extract (CTP) induced pyroptosis in human bronchial epithelial cells (BEAS-2B). METHODS: BEAS-2B cells were treated with different concentrations of CTP (1, 3 µg/ml) for 8h and 24 h, respectively. Lactic dehydrogenase (LDH) activity and interleukin-1 beta (IL-1ß) levels in the supernatants of cell culture media were measured with LDH activity or human IL-1ß ELISA kit, respectively. The activity of Caspase-1 was measured with Caspase-1 colorimetric assay kit. RESULTS: The activity of caspase-1 in 1 and 3 µg/ml CTP groups were (9.29 ± 0.30) and (8.67 ± 0.59) µmol/ml respectively which were both significantly increased compared to that (7.42 ± 0.59) µmol/ml in the control group (P < 0.05) after 8 h exposure, but there was no significant difference in the activity of LDH and levels of IL-1ß in the cell culture media among the CTP and control groups. 24 h after exposure, the activity of LDH in the CTP (1, 3 µg/ml) groups were (1323.03 ± 28.53) and (1148.45 ± 16.42) U/dl respectively which were significantly higher than that (1091.93 ± 26.64) U/dl in the control group (P < 0.05), and the levels of IL-1ß in the CTP (1 and 3 µg/ml) groups were (125.37 ± 25.00) pg/ml and (92.04 ± 19.09) pg/ml respectively which were significantly higher than that (46.20 ± 14.43) pg/ml in the control group (P < 0.05), but there was no significant difference in the activity of Caspase-1 among CTP and control groups (P < 0.05). CONCLUSION: CTP treatment induced early increase in caspase-1 activity followed by the increase in LDH activity and IL-1 levels, indicative of pyroptosis in human bronchial epithelial cells.

Nicotine induces the expression of C-reactive protein via MAPK-dependent signal pathway in U937 macrophages.

Atherosclerosis is an inflammatory disease in the vessel wall. Nicotine, a major component of cigarette smoke, is an independent risk factor for cardiovascular diseases including atherosclerosis. As an inflammatory molecule, C- reactive protein (CRP) participates in atherogenesis. Although it has been confirmed that CRP level in smoking patient is significantly higher than non-smokers and cigarette withdrawal, it is unknown whether nicotine induces CRP expression in macrophages. The present study was to observe effect of nicotine on CRP production and the related signal pathway in U937 macrophages. The results showed that nicotine significantly increased mRNA and protein expression of CRP in U937 macrophages in time- and concentration-dependent ways. Nicotinic acetylcholine receptor (nAChR) blocker hexamethonium, MEK1/2 inhibitor PD98059, p38 MAPK inhibitor SB203580 and NF-κB inhibitor PDTC almost completely abolished nicotineinduced CRP expression in mRNA and protein levels in U937 macrophages. The further study indicated that hexamethonium, PD98059, and SB203580 significantly inhibited ERK1/2 and p38 MAPK phosphorylation. These demonstrate that nicotine has ability to induce CRP expression in macrophages through nAChR-ERK1/2/p38 MAPK-NF-κB signal pathway, which contributes to better understanding of the pro-inflammatory and pro-atherosclerotic effects of nicotine in cigarette smokers.

Subpicosecond pulse generation from a 1.56 µm mode-locked VECSEL.

Near-transform-limited subpicosecond pulses at 1.56 µm were generated from an optically pumped InP-based vertical-external-cavity surface-emitting laser (VECSEL) passively mode-locked at 2 GHz repetition rate with a fast InGaAsNSb/GaAs semiconductor saturable absorber mirror (SESAM). The SESAM microcavity resonance was adjusted via a selective etching of phase layers specifically designed to control the magnitude of both the modulation depth and the intracavity group delay dispersion of the SESAM. Using the same VECSEL chip, we observed that the mode-locked pulse duration could be reduced from several picoseconds to less than 1 ps with a detuned resonant SESAM.

[Study on in vitro release and transdermal behaviors of mumps cataplasm of complex prescription].

OBJECTIVE: To investigate the in vitro release and transdermal behaviors of mumps cataplasm of complex prescription. METHODS: The improved Franz difficusion was used and the concentration of drugs was detected. DCS was determined by HPLC and flavanoid contents were determined by UV. RESULTS: The accumulation skin permeation percentage of DCS and flavanoid was 32% and 21%, respectively, the in vitro release percentage of DCS and flavanoid was 47% and 42%, respectively. CONCLUSION: The transdermal behavior of mumps cataplasm of complex prescription is an zero-order kinetics progress. The in vitro release behavior is in accordance with the Higuchi equation.