Kaempferol promotes melanogenesis and reduces oxidative stress in PIG1 normal human skin melanocytes.

Vitiligo is an autoimmune disease characterized by depigmentation. Kaempferol is a flavonoid compound with broad anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of kaempferol on melanogenesis in PIG1 normal human skin melanocytes and its response to oxidative stress. The effect of kaempferol on melanin synthesis in PIG1 normal human skin melanocytes was explored by measuring tyrosinase activity, melanin content, mRNA and protein expression of key enzymes and expression of related pathway proteins. The effects of kaempferol pretreatment on cell viability, apoptosis, ROS level and HO-1 protein level under H2 O2 stimulation were explored. When treated with kaempferol, the tyrosinase activity and melanin content of PIG1 cells increased, the mRNA and protein expressions of TYR, TRP1, TRP2 and MITF increased, and the phosphorylation level of ERK1/2 increased. Upon the stimulation of H2 O2 , kaempferol reduced the production of ROS, decreased apoptosis and increased the protein expression of HO-1 in PIG1 cells. In addition, kaempferol inhibited oxidative stress-induced melanin reduction and promoted melanin synthesis in PIG1 cells and protected against H2 O2 -induced oxidative stress damage.

Lewis Acid-Induced Reversible Disproportionation of TEMPO Enables Aqueous Aluminum Radical Batteries.

Nitroxide radicals, such as 2,2,6,6-tetramethylpiperidyl-1-oxy (TEMPO), are typical organic electrode materials featuring high redox potentials and fast electrochemical kinetics and have been widely used as cathode materials in multivalent metal-ion batteries. However, TEMPO and its derivatives have not been used in emerging rechargeable aluminum-ion batteries (AIBs) due to the known disproportionation and possible degradation of nitroxide radicals in acidic conditions. In this study, the (electro)chemical behavior of TEMPO is examined in organic and aqueous Lewis acid electrolytes. Through in situ (electro)chemical characterizations and theoretical computation, we reveal for the first time an irreversible disproportionation of TEMPO in organic Al(OTf)3 electrolytes that can be steered to a reversible process when switching to an aqueous media. In the latter case, a fast hydrolysis and ligand exchange between [Al(OTf)3TEMPO]- anion and water enable the overall reversible electrochemical redox reaction of TEMPO. These findings lead to the first design of radical polymer aqueous AIBs that are fire-retardant and air-stable, delivering a stable voltage output of 1.25 V and a capacity of 110 mAh g-1 over 800 cycles with 0.028% loss per cycle. This work demonstrates the promise of using nonconjugated organic electroactive materials for cost-effective and safe AIBs that currently rely on conjugated organic molecules.

Postoperative intermittent pneumatic compression for preventing venous thromboembolism in Chinese lung cancer patients: a randomized clinical trial.

BACKGROUND: Postoperative lung cancer patients belong to the high-risk group for venous thromboembolism (VTE). The standardized preventive measures for perioperative VTE in lung cancer are not perfect, especially for the prevention and treatment of catheter-related thrombosis (CRT) caused by carried central venous catheters (CVCs) in lung cancer surgery. PATIENTS AND METHODS: This study included 460 patients with lung cancer undergoing video-assisted thoracic surgery (VATS) in our center from July 2020 to June 2021. Patients were randomized into two groups, and intraoperatively-placed CVCs would be carried to discharge. During hospitalization, the control group was treated with low-molecular-weight heparin (LMWH), and the experimental group with LMWH + intermittent pneumatic compression (IPC). Vascular ultrasound was performed at three time points which included before surgery, before discharge, and one month after discharge. The incidence of VTE between the two groups was studied by the Log-binomial regression model. RESULTS: CRT occurred in 71.7% of the experimental group and 79.7% of the control group. The multivariate regression showed that the risk of developing CRT in the experimental group was lower than in the control group (Adjusted RR = 0.889 [95%CI0.799-0.989], p = 0.031), with no heterogeneity in subgroups (P for Interaction > 0.05). Moreover, the fibrinogen of patients in the experimental group was lower than control group at follow-up (P = 0.019). CONCLUSION: IPC reduced the incidence of CRT during hospitalization in lung cancer patients after surgery. TRIAL REGISTRATION: No. ChiCTR2000034511.

Spiroligomer-Based Macrocycles for Atomically Precise Membranes.

Here, we report a new class of peptidomimetic macrocycles with well-defined three-dimensional structures and low conformational flexibility. They are assembled from fused-ring spiro-ladder oligomers (spiroligomers) by modular solid-phase synthesis. Two-dimensional nuclear magnetic resonance confirms their shape persistency. Triangular macrocycles of tunable sizes assemble into membranes with atomically precise pores, which exhibit size and shape-dependent molecular sieving towards a series of structurally similar compounds. The exceptional structural diversity and stability of spiroligomer-based macrocycles will be explored for more applications.

Polymer and Membrane Design for Low Temperature Catalytic Reactions.

Catalytically active asymmetric membranes have been developed with high loadings of palladium nanoparticles located solely in the membrane's ultrathin skin layer. The manufacturing of these membranes requires polymers with functional groups, which can form insoluble complexes with palladium ions. Three polymers have been synthesized for this purpose and a complexation/nonsolvent induced phase separation followed by a palladium reduction step is carried out to prepare such membranes. Parameters to optimize the skin layer thickness and porosity, the palladium loading in this layer, and the palladium nanoparticles size are determined. The catalytic activity of the membranes is verified with the reduction of a nitro-compound and with a liquid phase Suzuki-Miyaura coupling reaction. Very low reaction times are observed.

[Effects of extractionfrom raspberry on hippocampus proteomics of mice suffered from ovariectomized-induced AD].

This paper was aimed to investigate the impact of the extraction from raspberry on the Alzheimer disease model protein expression. According to weight, the ovariectomized mice were randomly divided into shame operation group, model group, estrogen positive control group(0.1 g•L⁻¹) and ethyl acetate extraction part control group(in dose of 18 g•kg⁻¹). Each mouse in positive control group was subcutaneous injected of estradiol with 0.2 mL every two days. Raspberry effective parts group were given 0.01 mL•g⁻¹ raspberry ethylacetate extracts, model group and control group were given 0.01 mL•g⁻¹ saline once a day. The drug administration lasted for 32 days. Proteins from mice's hippocampus were extracted, then Nanol-ESI liquid-mass spectrometry system was used for detection and ProteinDiscovery software was used for identification to qualitative analysis different groups of hippocampal proteins by using the software of SIEVE. The results showed that model group compared with the mice of ethyl acetate extraction part control group have 66 differentially expressed proteins including heat shock protein, microtubule protein, protein involved in energy metabolism and protein of brain protection related proteins associated with AD. Those differences protein may be the target that Raspberry prevention and treatment of AD.

Biological function and application of melanocytes induced and transformed by mouse bone marrow mesenchymal stem cells.

Background: A large number of autologous melanocytes are required for surgical treatment of depigmentation diseases such as vitiligo. The purpose of this experiment is to explore the application of melanocytes induced by mesenchymal stem cells to clinical treatment. Therefore, we have induced mouse bone marrow mesenchymal stem cells (BMMSCs) into melanocytes (miMels) in the previous experiment. This experiment continues the previous experiment to further study the biological functions of miMels and their application in tissue engineering. Methods: We examined whether miMels can produce active tyrosinase, melanin, and response to α-MSH. The ability of miMels to produce melanin to keratinocytes was tested by co-culture. By applying miMels to tissue-engineered skin, the survival and function of miMels on the surface of nude mice were verified. Results: MiMels can produce active tyrosinase and melanin, and can pass melanin to the co-cultured keratinocytes. Under the stimulation of α-MSH, the active tyrosinase and melanin content of miMels increased. We tried to apply it to the establishment of tissue-engineered skin and obtained tissue-engineered skin containing miMels. Then we tried to transplant tissue-engineered skin on the back skin of nude mice and succeeded. The transplanted miMels survived in local tissues, synthesized active tyrosinase and melanin, and expressed the marker protein of melanocytes. Conclusion: In short, miMels can be used as a cell source for tissue engineering skin. MiMels not only have a typical melanocyte morphology but also have the same biological functions as normal melanocytes. What's more important is its successful application in mouse tissue-engineered experiments.

A Necroptosis-Related Gene Signature to Predict the Prognosis of Skin Cutaneous Melanoma.

The prognosis of skin cutaneous melanoma (SKCM) remains poor, and patients with SKCM show a poor response to immunotherapy. Thus, we aimed to identify necroptosis-related biomarkers, which can help predict the prognosis of SKCM and improve the effectiveness of precision medicine. Data of SKCM were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. TCGA samples were classified into two clusters by consensus clustering of necroptosis-related genes. Univariate Cox and least absolute shrinkage and selection operator regression analyses led to the identification of 11 genes, which were used to construct a prognostic model. GSE65904 was used as the test set. Principal component, t-distributed stochastic neighbor embedding, and Kaplan-Meier survival analyses indicated that samples in the train and test sets could be divided into two groups, with the high-risk group showing a worse prognosis. Univariate and multivariate Cox regression analyses were performed, and a nomogram, calibration curve, and time-dependent receiver operating characteristic curve were constructed to verify the efficacy of our model. The 1-, 3-, and 5-year areas under the receiver operating characteristic curves for the train set were 0.702, 0.663, and 0.701 and for the test set were 0.613, 0.627, and 0.637, respectively. Moreover, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses between the high- and low-risk groups. Single sample gene set enrichment analysis, immune cell infiltration analysis, tumor microenvironment scores, immune checkpoint analysis, and half-maximal inhibitory concentration prediction indicated that the high-risk group showed weaker antitumor immunity; further, the response to immune checkpoint inhibitors was worse, and the high-risk group was sensitive to fewer antitumor drugs. Tumor mutational burden analysis, Kaplan-Meier survival analysis, and correlation analysis between risk score and RNA stemness score revealed that the high-risk group with low tumor mutational burden and high RNA stemness score was potentially associated with poor prognosis. To conclude, our model, which was based on 11 necroptosis-related genes, could predict the prognosis of SKCM; in addition, it has guiding significance for the selection of clinical treatment and provides new research directions to enhance necroptosis against SKCM.

Mechanism of Action of a Chinese Herbal Compound Containing Quercetin, Luteolin, and Kaempferol in the Treatment of Vitiligo Based on Network Pharmacology and Experimental Verification.

Objective: This study aimed to explore the mechanisms of Baishi tablets (BSTs) in the treatment of vitiligo through network pharmacology-based identification and experimental validation. Methods: In brief, the compounds and related targets of BST were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to visualize the common targets of BST and vitiligo. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using STRING and Cytoscape software. In addition, the measurement of apoptosis in PIG1 cells and intracellular reactive oxygen species were measured using quercetin (QU), luteolin (LU), and kaempferol (KA) to protect melanocytes from oxidative stress. Results: A total of 55 compounds with 236 targets and 1205 vitiligo-related genes were obtained from the TCMSP database. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways, revealing that BST may cure vitiligo by influencing the biological processes of cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained with 13 core genes by analyzing the PPI network, which includes HMOX1, CXCL8, CCL2, IL6, MAPK8, CASP3, PTGS2, AKT1, IL1B, MYC, TP53, IFNG, and IL2. Furthermore, a molecular docking analysis was conducted to simulate the combination of compounds and gene proteins, reflecting that QU, LU, and KA can strongly bind the core genes. Through a series of experimental validations, we found that QU, LU, and KA could attenuate H2O2-induced apoptosis in melanocytes. Further evidence revealed that QU, LU, and KA could enhance the scavenging of intracellular reactive oxygen species (ROS). Conclusion: Based on the results of network pharmacology analysis and experimental verification, QA, LU, and KA can be utilized to protect PIG1 cells by inhibiting oxidative stress and reducing the intracellular level of ROS. This may explain the underlying mechanism of BST therapy and provide a novel strategy for the treatment of vitiligo.

Development of Fmoc-Protected Bis-Amino Acids toward Automated Synthesis of Highly Functionalized Spiroligomers.

We report the fluorenylmethoxycarbonyl (Fmoc) protection of functionalized bis-amino acid building blocks using a temporary Cu2+ complexation strategy, together with an efficient multikilogram-scale synthesis of bis-amino acid precursors. This allows the synthesis of stereochemically and functionally diverse spiroligomers utilizing solid-phase Fmoc/tBu chemistry to facilitate the development of applications. Four tetramers were assembled on a semiautomated microwave peptide synthesizer. We determined their secondary structures with two-dimensional nuclear magnetic resonance spectroscopy.

Efficacy of a mixed preparation containing piperine, capsaicin and curcumin in the treatment of alopecia areata.

BACKGROUND: Alopecia areata is a common non-scarring alopecia, mainly manifested as sudden localized patchy alopecia. It is currently believed to be related to autoimmune, genetic, emotional stress, and endocrine factors. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the mixed preparation of piperine, capsaicin, and curcumin on alopecia areata treatment. METHODS: Sixty patients were enrolled in this study and divided into 2 groups randomly: topical treated with the mixed preparation (case) twice daily and 5%minoxidil (control) once daily for 3 months. The degree of hair loss was assessed by SALT and dermoscopy. RESULTS: On the completion of the study, compared with baseline, statistically significant regrowth occurred in both groups (p < 0.05). The mean SALT scores and hair follicle status under trichoscopy at baseline and at the end of 12 weeks in the mixed preparation group and in the minoxidil group were comparable, respectively. The effective rate of mixed preparation group was 63.33% and minoxidil group was 70%. Adverse symptoms were temporary and no serious adverse event occurred. CONCLUSION: Based on our findings, the mixed preparation of piperine, capsaicin, and curcumin is effective in treating alopecia areata, but it has not been shown to be superior to minoxidil in short-term therapy.

Ferroptosis-Related Gene Signature Predicts the Prognosis of Skin Cutaneous Melanoma and Response to Immunotherapy.

Ferroptosis is a non-apoptotic regulated cell death process, and much research has indicated that ferroptosis can induce the non-apoptotic death of tumor cells. Ferroptosis-related genes are expected to become a biological target for cancer treatment. However, the regulation of ferroptosis-related genes in skin cutaneous melanoma (SKCM) has not been well studied. In the present study, we conducted a systematic analysis of SKCM based on RNA sequencing data and clinical data obtained from The Cancer Genome Atlas (TCGA) database and the FerrD database. SKCM patients from the GSE78220 and MSKCC cohorts were used for external validation. Applying consensus clustering on RNA sequencing data from TCGA the generated ferroptosis subclasses of SKCM, which were analyzed based on the set of differentially expressed ferroptosis-related genes. Then, a least absolute shrinkage and selection operator (LASSO)-Cox regression was used to construct an eight gene survival-related linear signature. The median cut-off risk score was used to divide patients into high- and low-risk groups. The time-dependent receiver operating characteristic curve was used to examine the predictive power of the model. The areas under the curve of the signature at 1, 3, and 5 years were 0.673, 0.716, and 0.746, respectively. Kaplan-Meier survival analysis showed that the prognosis of high-risk patients was worse than that of low-risk patients. Univariate and multivariate Cox regression analyses showed that the risk signature was a robust independent prognostic indicator. By incorporating risk scores with tumor staging, a nomogram was constructed to predict prognostic outcomes for SKCM patients. In addition, the immunological analysis showed different immune cell infiltration patterns. Programmed-death-1 (PD-1) immunotherapy showed more significant benefits in the low-risk group than in the high-risk group. In summary, a model based on ferroptosis-related genes can predict the prognosis of SKCM and could have a potential role in guiding targeted therapy of SKCM.

The cytoplasmic loops of AgrC contribute to the quorum-sensing activity of Staphylococcus aureus.

In Staphylococcus aureus, the accessory gene regulator (agr) quorum-sensing system is thought to play an important role in biofilm formation. The histidine kinase AgrC is one of the agr system components and activated by the self-generated auto-inducing peptide (AIP), which is released continuously into the extracellular environment during bacterial growth. The extracellular loops (Extra-loops) of AgrC are crucial for AIP binding. Here, we reported that the cytoplasmic loops (Cyto-loops) of AgrC are also involved in Agr activity. We identified S. aureus ST398 clinical isolates containing a naturally occurring single amino acid substitution (lysine to isoleucine) at position 73 of an AgrC Cyto-loop that exhibited significantly stronger biofilm formation and decreased Agr activity compared to the wild-type strain. A constructed strain containing the K73I point mutation in AgrC Cyto-loop continued to show a growth dependent induction of the agr system, although the growth dependent induction was delayed by about 6 h compared to the wild-type. In addition, a series of strains containing deletion mutants of the AgrC Cyto- and Extra-loops were constructed and revealed that the removal of the two Cyto-loops and Extra-loops 2 and 3 totally abolished the Agr activity and the growth-dependence on the agr system induction. Remarkably, the Extra-loop 1 deletion did not affect the Agr activity. In conclusion, the AgrC Cyto-loops play a crucial role in the S. aureus quorum-sensing activity.

Nanostructured Polymer Monoliths for Biomedical Delivery Applications.

Drug delivery systems are designed to control the release rate and location of therapeutic agents in the body to achieve enhanced drug efficacy and to mitigate adverse side effects. In particular, drug-releasing implants provide sustained and localized release. We report nanostructured polymer monoliths synthesized by polymerization-induced microphase separation (PIMS) as potential implantable delivery devices. As a model system, free poly(ethylene oxide) homopolymers were incorporated into the nanoscopic poly(ethylene oxide) domains contained within a cross-linked polystyrene matrix. The in vitro release of these poly(ethylene oxide) molecules from monoliths was investigated as a function of poly(ethylene oxide) loading and molar mass as well as the molar mass and weight fraction of poly(ethylene oxide) macro-chain transfer agent used in the PIMS process for forming the monoliths. We also developed nanostructured microneedles targeting efficient and long-term transdermal drug delivery by combining PIMS and microfabrication techniques. Finally, given the prominence of poly(lactide) in drug delivery devices, the degradation rate of microphase-separated poly(lactide) in PIMS monoliths was evaluated and compared with bulk poly(lactide).

[Studies on the chemical constituents from Cissus assamica].

OBJECTIVE: To study the chemical constituents from Cissus assamica and obtain a more comprehensive understanding of its effective components. METHODS: Compounds were isolated by various column chromatographies with silica gel. Their structures were elucidated by spectral analysis (IR, MS, 1H-NMR, 13C-NMR) and chemical evidence. RESULTS: Eight compounds were isolated and elucidated as ursolic acid (I), lupeol (II), n-hexacosinc acid (III), isolariciresinol-9-O-beta-D-glucopyranoside (IV), dauco sterin (V), 3,3'-dimethyl ellagic acid (VI), beta-Sitosterol (VII), bergenin (VIII). CONCLUSION: Among these compounds, I-V are isolated from this plant for the first time.

Phylogenetic analysis and virulence determinant of the host-adapted Staphylococcus aureus lineage ST188 in China.

Staphylococcus aureus (S. aureus) is an important pathogen of humans and livestock species, but an understanding of the clonal distribution of S. aureus causing different host-species infections in the same geographical environment and within the same period is lacking. By characterizing infections caused by S. aureus in bovine, pediatric, and adult patients in Shanghai, China, between 2012 and 2014, we identified methicillin-sensitive S. aureus (MSSA) ST188 as the major lineage causing infections in multiple host species. Whole-genome sequencing and phenotypic analyses demonstrated that ST188 might evolve from livestock, and there was no significant genomic or virulence difference between ST188 isolated from livestock and humans. The virulence of ST188 is related to its adhesion and nasal colonization ability. This result is in accord with the strong epithelial cell adhesion and biofilm formation properties of ST188. Furthermore, the adhesion- and biofilm-formation-related genes are present in multiple copies and exhibit significantly increased expression in ST188. In conclusion, S. aureus ST188 is the major lineage causing human and livestock infections in Shanghai, China. Due to its high expression of the factors associated with bacterial adhesion and biofilm formation, ST188 has the ability to colonize and infect different host species.

Membranes prepared by self-assembly and chelation assisted phase inversion.

We combine self-assembly in solution, complexation with metallic salts and phase separation induced by solvent-non-solvent exchange to prepare nanostructured membranes for separation in the nanofiltration range. This method was applied to prepare membranes from newly synthesized poly(acrylic acid)-b-polysulfone-b-poly(acrylic acid) copolymers dissolved in a selective solvent mixture and immersed in aqueous Cu2+ or Ag+ solutions.

Antibiofilm effect enhanced by modification of 1,2,3-triazole and palladium nanoparticles on polysulfone membranes.

Biofouling impedes the performance of membrane bioreactors. In this study, we investigated the antifouling effects of polysulfone membranes that were modified by 1,2,3-triazole and palladium (Pd) nanoparticles. The modified membranes were evaluated for antibacterial and antifouling efficacy in a monoculture species biofilm (i.e., drip flow biofilm reactor, DFR) and mixed species biofilm experiment (i.e., aerobic membrane reactor, AeMBR). 1,2,3-triazole and Pd nanoparticles inhibited growth of Pseudomonas aeruginosa in both aerobic and anaerobic conditions. The decrease in bacterial growth was observed along with a decrease in the amount of total polysaccharide within the monoculture species biofilm matrix. When the modified membranes were connected to AeMBR, the increase in transmembrane pressure was lower than that of the non-modified membranes. This was accompanied by a decrease in protein and polysaccharide concentrations within the mixed species biofilm matrix. Biomass amount in the biofilm layer was also lower in the presence of modified membranes, and there was no detrimental effect on the performance of the reactor as evaluated from the nutrient removal rates. 16S rRNA analysis further attributed the delay in membrane fouling to the decrease in relative abundance of selected bacterial groups. These observations collectively point to a lower fouling occurrence achieved by the modified membranes.

[Studies on the chemical constituents from Fructus Rubi].

Five compounds have been isolated from Fructus Rubi. On the basis of spectral analysis and physicochemical properties, their structures were establised as 4-hydroxy-3-methoxybenzoic acid (I), p-hydroxybenzoic acid (II), gallic acid (III), tiliroside (IV) and ellagic acid (V). I, II and III were found from the plant for the first time.