Strong effect-correlated electrochemical CO2 reduction.

Electrochemical CO2 reduction (ECR) holds great potential to alleviate the greenhouse effect and our dependence on fossil fuels by integrating renewable energy for the electrosynthesis of high-value fuels from CO2. However, the high thermodynamic energy barrier, sluggish reaction kinetics, inadequate CO2 conversion rate, poor selectivity for the target product, and rapid electrocatalyst degradation severely limit its further industrial-scale application. Although numerous strategies have been proposed to enhance ECR performances from various perspectives, scattered studies fail to comprehensively elucidate the underlying effect-performance relationships toward ECR. Thus, this review presents a comparative summary and a deep discussion with respect to the effects strongly-correlated with ECR, including intrinsic effects of materials caused by various sizes, shapes, compositions, defects, interfaces, and ligands; structure-induced effects derived from diverse confinements, strains, and fields; electrolyte effects introduced by different solutes, solvents, cations, and anions; and environment effects induced by distinct ionomers, pressures, temperatures, gas impurities, and flow rates, with an emphasis on elaborating how these effects shape ECR electrocatalytic activities and selectivity and the underlying mechanisms. In addition, the challenges and prospects behind different effects resulting from various factors are suggested to inspire more attention towards high-throughput theoretical calculations and in situ/operando techniques to unlock the essence of enhanced ECR performance and realize its ultimate application.

Physiological and transcriptomic analyses provide insight into thermotolerance in desert plant Zygophyllum xanthoxylum.

BACKGROUND: Heat stress has adverse effects on the growth and reproduction of plants. Zygophyllum xanthoxylum, a typical xerophyte, is a dominant species in the desert where summer temperatures are around 40 °C. However, the mechanism underlying the thermotolerance of Z. xanthoxylum remained unclear. RESULTS: Here, we characterized the acclimation of Z. xanthoxylum to heat using a combination of physiological measurements and transcriptional profiles under treatments at 40 °C and 45 °C, respectively. Strikingly, moderate high temperature (40 °C) led to an increase in photosynthetic capacity and superior plant performance, whereas severe high temperature (45 °C) was accompanied by reduced photosynthetic capacity and inhibited growth. Transcriptome profiling indicated that the differentially expressed genes (DEGs) were related to transcription factor activity, protein folding and photosynthesis under heat conditions. Furthermore, numerous genes encoding heat transcription shock factors (HSFs) and heat shock proteins (HSPs) were significantly up-regulated under heat treatments, which were correlated with thermotolerance of Z. xanthoxylum. Interestingly, the up-regulation of PSI and PSII genes and the down-regulation of chlorophyll catabolism genes likely contribute to improving plant performance of Z. xanthoxylum under moderate high temperature. CONCLUSIONS: We identified key genes associated with of thermotolerance and growth in Z. xanthoxylum, which provide significant insights into the regulatory mechanisms of thermotolerance and growth regulation in Z. xanthoxylum under high temperature conditions.

Massive increases in C31 alkane on Zygophyllum xanthoxylum leaves contribute to its excellent abiotic stress tolerance.

BACKGROUND AND AIMS: Desert plants possess excellent water-conservation capacities to survive in extreme environments. Cuticular wax plays a pivotal role in reducing water loss through plant aerial surfaces. However, the role of cuticular wax in water retention by desert plants is poorly understood. METHODS: We investigated leaf epidermal morphology and wax composition of five desert shrubs from north-west China and characterized the wax morphology and composition for the typical xerophyte Zygophyllum xanthoxylum under salt, drought and heat treatments. Moreover, we examined leaf water loss and chlorophyll leaching of Z. xanthoxylum and analysed their relationships with wax composition under the above treatments. KEY RESULTS: The leaf epidermis of Z. xanthoxylum was densely covered by cuticular wax, whereas the other four desert shrubs had trichomes or cuticular folds in addition to cuticular wax. The total amount of cuticular wax on leaves of Z. xanthoxylum and Ammopiptanthus mongolicus was significantly higher than that of the other three shrubs. Strikingly, C31 alkane, the most abundant component, composed >71 % of total alkanes in Z. xanthoxylum, which was higher than for the other four shrubs studied here. Salt, drought and heat treatments resulted in significant increases in the amount of cuticular wax. Of these treatments, the combined drought plus 45 °C treatment led to the largest increase (107 %) in the total amount of cuticular wax, attributable primarily to an increase of 122 % in C31 alkane. Moreover, the proportion of C31 alkane within total alkanes remained >75 % in all the above treatments. Notably, the water loss and chlorophyll leaching were reduced, which was negatively correlated with C31 alkane content. CONCLUSION: Zygophyllum xanthoxylum could serve as a model desert plant for study of the function of cuticular wax in water retention because of its relatively uncomplicated leaf surface and because it accumulates C31 alkane massively to reduce cuticular permeability and resist abiotic stressors.

Structure-activity study of fluorine or chlorine-substituted cinnamic acid derivatives with tertiary amine side chain in acetylcholinesterase and butyrylcholinesterase inhibition.

In this study, a series of new fluorine or chlorine-substituted cinnamic acid derivatives that contain tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results show that almost all the derivatives containing tertiary amine side chain (compounds 4a-9d) exhibit moderate or potent activity in AChE inhibition. By contrast, their parent compounds (compounds 3a-3f) in the absence of tertiary amine moitery exhibit poor inhibitory activity against AChE. For the compounds containing pyrroline or piperidine side chain, the bioactivity in AChE inhibition is much intense than those containing N,N-diethylamino side chain. The chlorine or fluorine substituted position produces a significant effect on the bioactivity and selectivity in AChE inhibition. Most of the compounds that contain para-substituted fluorine or chlorine exhibit potent activity against AChE and poor activity against BChE, while ortho-substituted analogs show the opposite effect. It is worth noticing that the compounds containing N,N-diethylamino side chain are exceptions to this pattern. Among the newly synthesized compounds, compounds 6d are the most potent in AChE inhibition (IC50 = 1.11 ± 0.08 µmol/L) with high selectivity for AChE over BChE (selectivity ratio: 46.58). An enzyme kinetic study of compounds 6d suggests it produces a mixed-type inhibitory effect in AChE.

Structure-activity relationship investigation of benzamide and picolinamide derivatives containing dimethylamine side chain as acetylcholinesterase inhibitors.

A series of benzamide and picolinamide derivatives containing dimethylamine side chain (4a-4c and 7a-7i) were synthesised and evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity in vitro. Structure-activity relationship investigation revealed that the substituted position of dimethylamine side chain markedly influenced the inhibitory activity and selectivity against AChE and BChE. In addition, it seemed that the bioactivity of picolinamide amide derivatives was stronger than that of benzamide derivatives. Among them, compound 7a revealed the most potent AChE inhibitory activity (IC50: 2.49 ± 0.19 µM) and the highest selectivity against AChE over BChE (Ratio: 99.40). Enzyme kinetic study indicated that compound 7a show a mixed-type inhibition against AChE. The molecular docking study revealed that this compound can bind with both the catalytic site and the peripheral site of AChE.

Tertiary amine derivatives of chlorochalcone as acetylcholinesterase (AChE) and buthylcholinesterase (BuChE) inhibitors: the influence of chlorine, alkyl amine side chain and α,ß-unsaturated ketone group.

A new series of tertiary amine derivatives of chlorochalcone (4a∼4l) were designed, synthesized and evaluated for the effect on acetylcholinesterase (AChE) and buthylcholinesterase (BuChE). The results indicated that all compounds revealed moderate or potent inhibitory activity against AChE, and some possessed high selectivity for AChE over BuChE. The structure-activity investigation showed that the substituted position of chlorine significantly influenced the activity and selectivity. The alteration of tertiary amine group also leads to obvious change in bioactivity. Among them, IC50 of compound 4l against AChE was 0.17 ± 0.06 µmol/L, and the selectivity was 667.2 fold for AChE over BuChE. Molecular docking and enzyme kinetic study on compound 4l suggested that it simultaneously binds to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Further study showed that the pyrazoline derivatives synthesized from chlorochalcones had weaker activity and lower selectivity in inhibiting AChE compared to that of chlorochalcone derivatives.

Snapshot depth sensitive Raman spectroscopy in layered tissues.

Depth sensitive Raman spectroscopy has been shown effective in the detection of depth dependent Raman spectra in layered tissues. However, the current techniques for depth sensitive Raman measurements based on fiber-optic probes suffer from poor depth resolution and significant variation in probe-sample contact. In contrast, those lens based techniques either require the change in objective-sample distance or suffer from slow spectral acquisition. We report a snapshot depth-sensitive Raman technique based on an axicon lens and a ring-to-line fiber assembly to simultaneously acquire Raman signals emitted from five different depths in the non-contact manner without moving any component. A numerical tool was developed to simulate ray tracing and optimize the snapshot depth sensitive setup to achieve the tradeoff between signal collection efficiency and depth resolution for Raman measurements in the skin. Moreover, the snapshot system was demonstrated to be able to acquire depth sensitive Raman spectra from not only transparent and turbid skin phantoms but also from ex vivo pork tissues and in vivo human thumbnails when the excitation laser power was limited to the maximum permissible exposure for human skin. The results suggest the great potential of snapshot depth sensitive Raman spectroscopy in the characterization of the skin and other layered tissues in the clinical setting or other similar applications such as quality monitoring of tablets and capsules in pharmaceutical industry requiring the rapid measurement of depth dependent Raman spectra.

Internal Mammary Artery Perforator-Supercharged Prefabricated Cervicothoracic Flap for Face and Neck Reconstruction.

BACKGROUND: Prefabricated flap is an important technique to reconstruct massive face and neck skin defects. But its vascularization remains unpredictable and often leads to abnormal blood supply of the harvested flap, even necrosis. Flap supercharging and turbo supercharging techniques are effectively used to improve flap blood supply. However, few studies have been reported on the application of these techniques in prefabricated induced expanded flaps. METHODS: From March 2008 to September 2012, 13 patients who have face and neck soft tissue defects were treated with prefabricated cervicothoracic flap. To overcome insufficient blood supply, 5 of them received additional microvascular augmentation in which the second or third perforator of the internal mammary artery (IMAP) and its venae comitantes were anastomosed to facial or superficial temporal vessels, contrary to the remaining 8 patients. The following results were compared: flap viability, hospital stay, complications, frequency of dressing change, reoperation rate, and remaining scars. RESULTS: No flap necrosis was observed in patients who received the supercharging procedure. By contrast, of the 8 patients who were not treated with supercharging technique, various degrees of flap necrosis occurred in 3 patients, 2 of whom received secondary operations. The frequency of dressing changes, the hospital stay, and hospital cost were reduced. Postoperative view showed better aesthetic restoration. CONCLUSIONS: The IMAP-supercharged cervicothoracic flap technique offers a reliable method for massive face and neck reconstruction. We recommended that the IMAP should always be preserved in the flap as a saving option for potential flap congestion or arterial insufficiency.

Meta-analysis of the safety and factors contributing to complications of MS-TRAM, DIEP, and SIEA flaps for breast reconstruction.

BACKGROUND: Muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM), deep inferior epigastric perforator (DIEP), and superficial inferior epigastric artery (SIEA) flaps have been increasingly adopted for breast reconstruction. However, their safety, patient satisfaction with them, and factors contributing to complications are not well understood. METHODS: PubMed, MEDLINE, EMBASE, and The Cochrane Library were searched to identify eligible studies for inclusion in our analysis. The complication rates of and patient satisfaction rates with the flaps were measured as the outcome, and factors contributing to complications and patient satisfaction were also studied. The data were extracted, and pooled relative risks (RRs) and 95 % confidence intervals (CIs) were calculated. RESULTS: Thirteen studies involving 1,843 patients met the inclusion criteria. The results of the meta-analysis showed that patients with MS-TRAM had a higher rate of abdominal hernias (RR 2.354, 95 % CI 1.154-4.802, P = 0.019) and a lower rate of fat necrosis (RR 0.502, 95 % CI 0.347-0.727, P = 0.000) than patients with DIEP. In addition, there was no significant difference between MS-TRAM and DIEP with respect to other complications (P > 0.05), between MS-TRAM and DIEP with respect to patient satisfaction (P = 0.923), and between DIEP and SIEA with respect to complication rates (P = 0.377). The complication rates of MS-TRAM, DIEP, and SIEA were 25.6, 27.9, and 26.7 %, respectively. Diabetes mellitus (P = 0.078) influenced the complication rate of MS-TRAM, and obesity (P = 0.086) and diabetes mellitus (P = 0.110) were the potential factors correlated with complications with DIEP flaps. CONCLUSION: There were no obvious differences in the overall incidence of complications between MS-TRAM and DIEP and between DIEP and SIEA. In addition, the patient satisfaction rates of MS-TRAM and DIEP were similar. However, MS-TRAM showed a higher rate of abdominal hernias and a lower rate of fat necrosis than DIEP. Obesity and diabetes mellitus were potential factors associated with the incidence of complications. Additional multicenter, large-sample-size, randomized controlled trials with long-term follow-up visits are necessary. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ethical issues in Chinese aesthetic surgery.

Guided by the medical ethics principles of "four principles plus scope," Chinese aesthetic medical practitioners have proposed some extremely valuable ethical principles combined with the construction of aesthetic medicine and the requirements of clinical practice such as the principle of general nonmaleficence, the principle of local minimal invasiveness, the principle of informed consent, and the principle of respect and confidentiality. Chinese aesthetic surgical ethics provide valuable guidance for the practice of aesthetic medicine. Adherence to the ethics of Chinese aesthetic surgery provides an essential guide for the practice of aesthetic medicine in China. These principles protect both the medical practitioner and the patient, helping them to avoid unnecessary risks and disputes and ultimately promoting the sustainable development of aesthetic medicine.

Local hydroxide ion enrichment at the inner surface of lacunaris perovskite nanotubes facilitates the oxygen evolution reaction.

Numerous strategies have been devised to optimize the intrinsic activity of perovskite oxides for the oxygen evolution reaction (OER). However, conventional synthetic routes typically yield limited numbers of active sites and low mass activities. More critically, the sluggish mass transfer poses a huge challenge, particularly under high polarization conditions, which impedes the overall reaction kinetics. Herein, lacunaris La0.5Pr0.25Ba0.25Co0.8Ni0.2O3-δ nanotubes (LPBCN-NTs) were prepared via electrospinning and post-annealing, which exhibited a small overpotential of 358.8 mV at 10 mA cm-2 and a lower Tafel slope of 71.46 mV dec-1, superior to the values for the same stoichiometric LPBCN nanoparticles and solid nanofibers, state-of-the-art counterparts and commercial IrO2. Density functional theory calculations revealed that the surface oxygen vacancies in LPBCN-NTs significantly lowered the OH- adsorption energy, while finite element analysis indicated that the precisely constructed lacunaris NT structure enriched the OH- concentration at its inner surface by an order of magnitude, both of which collectively resulted in accelerated OER kinetics. This study clarifies the underlying mechanism of how the lacunaris nanotubular architecture and the surface oxygen vacancies of perovskite oxides affect heterocatalysis, which undoubtedly paves the way to handling the long-standing issues of sluggish mass transfer rates and poor intrinsic catalytic activity.

Perovskite Oxides Toward Oxygen Evolution Reaction: Intellectual Design Strategies, Properties and Perspectives.

Developing electrochemical energy storage and conversion devices (e.g., water splitting, regenerative fuel cells and rechargeable metal-air batteries) driven by intermittent renewable energy sources holds a great potential to facilitate global energy transition and alleviate the associated environmental issues. However, the involved kinetically sluggish oxygen evolution reaction (OER) severely limits the entire reaction efficiency, thus designing high-performance materials toward efficient OER is of prime significance to remove this obstacle. Among various materials, cost-effective perovskite oxides have drawn particular attention due to their desirable catalytic activity, excellent stability and large reserves. To date, substantial efforts have been dedicated with varying degrees of success to promoting OER on perovskite oxides, which have generated multiple reviews from various perspectives, e.g., electronic structure modulation and heteroatom doping and various applications. Nonetheless, the reviews that comprehensively and systematically focus on the latest intellectual design strategies of perovskite oxides toward efficient OER are quite limited. To bridge the gap, this review thus emphatically concentrates on this very topic with broader coverages, more comparative discussions and deeper insights into the synthetic modulation, doping, surface engineering, structure mutation and hybrids. More specifically, this review elucidates, in details, the underlying causality between the being-tuned physiochemical properties [e.g., electronic structure, metal-oxygen (M-O) bonding configuration, adsorption capacity of oxygenated species and electrical conductivity] of the intellectually designed perovskite oxides and the resulting OER performances, coupled with perspectives and potential challenges on future research. It is our sincere hope for this review to provide the scientific community with more insights for developing advanced perovskite oxides with high OER catalytic efficiency and further stimulate more exciting applications.

Reconstruction of singular eyelid defects in aging individuals based on facial aesthetic subunits.

BACKGROUND: In consideration of the distinctive structural characteristics of the eyelid, the optimally matching donor site to the original recipient site skin should be selected when a full-thickness skin graft is anticipated in a small-sized or medium-sized eyelid defect in middle-aged or elderly patients. METHODS: Eight patients ranging in age from 47 to 71 years suffered singular eyelid defects of different causes. Based on the location, shape, and degree of the defects, we removed the redundant skin as a skin graft from the same side in the contralateral eyelid in a routine blepharoplasty procedure and transferred the graft to repair the defect. RESULTS: The skin grafts survived in all cases, and the incisions healed primarily. The eyelid laxity improved, and no complications occurred. All cases were followed up for 3 months to 2 years, the quality of skin grafts was similar to that of the surrounding skin, and the activity was ideal. CONCLUSIONS: When an eyelid defect is not amenable to direct closure and skin grafting is selected, the proper donor site is vital to the final outcome. The same facial aesthetic subunits, such as sufficient laxity in the contralateral eyelid skin in middle-aged and elderly patients, can provide the best match with the recipient skin and represent the best donor site for defect reconstruction.

Harnessing interventions during the immediate perioperative period to improve the long-term survival of patients following radical gastrectomy.

Although the incidence and mortality of gastric cancer (GC) have been decreasing steadily worldwide, especially in East Asia, the disease burden of this malignancy is still very heavy. Except for tremendous progress in the management of GC by multidisciplinary treatment, surgical excision of the primary tumor is still the cornerstone intervention in the curative-intent treatment of GC. During the relatively short perioperative period, patients undergoing radical gastrectomy will suffer from at least part of the following perioperative events: Surgery, anesthesia, pain, intraoperative blood loss, allogeneic blood transfusion, postoperative complications, and their related anxiety, depression and stress response, which have been shown to affect long-term outcomes. Therefore, in recent years, studies have been carried out to find and test interventions during the perioperative period to improve the long-term survival of patients following radical gastrectomy, which will be the aim of this review.

A Retrospective Study of Anlotinib Combined with Anti-PD-1 Inhibitors in the 2nd or Later-Line Treatment of Advanced Solid Tumors.

Objective: To investigate the clinical efficacy and safety of anlotinib combined with anti-PD-1 inhibitors in the 2nd or later-line treatment of advanced solid tumors. Patients and Methods: A total of 63 patients with advanced solid tumors who had failed or could not endure the adverse reactions after receiving first-line or more systematic treatment in the Second Affiliated Hospital of Harbin Medical University from March 2019 to April 2023 were treated with anlotinib Hydrochloride capsule combined with anti-PD-1 inhibitors. The efficacy and adverse reactions were evaluated according to RECIST1.1 and NCICTC4.0 standards. Results: The percentage of overall response rate of 63 patients during the combination administration indicated that complete response was 1.6% (n=1), partial response was 23.8% (n=15), stable disease was 39.7% (n=25) and progressive disease was 34.9% (n=22), yielding objective response rate (ORR) of 25.4% and disease control rate (DCR) of 65.1%. Furthermore, the median PFS of 63 patients with advanced solid tumors was 7 months and the median OS was not reached, and the median follow-up time is 4.5 months. In subgroup analysis, there was no significant difference in PFS between first-line, second-line, third-line and above (p=0.631); there was no significant difference in PFS between PD-1 positive patients and PD-1 negative patients (p=0.094); there was no significant difference in PFS between patients who had previously used anti-PD-1 inhibitors and patients who had not used before (p=0.204). The most common adverse reactions were hypertension, hand-foot syndrome, and fatigue, with an incidence of 28.4% (18/63), 25.6% (14/63), and 25.6% (14/63), respectively. Most of the adverse reactions were grade 1-2, and there were no grade 4 adverse reactions. Conclusion: Anlotinib combined with anti-PD-1 inhibitors demonstrated promising efficacy and tolerable safety for patients with advanced solid tumors in the 2nd or later-line treatment.

[Application of an arc-shaped transperineal incision in front of the apex of coccyx during the resection of pelvic retroperitoneal tumors].

OBJECTIVE: To explore a better operative approach to resect complicated pelvic retroperitoneal tumors. METHODS: A total of 28 patients with complicated pelvic retroperitoneal tumors who received surgical resection in our hospital from 2006 to 2010 were included in this study. The surgical operation was assisted with an arc-shaped transperineal incision in front of the apex of coccyx. The operation time, intraoperative blood loss, death toll and length of hospital stay of the patients were retrospectively analyzed. RESULTS: The median operation time was 122.5 minutes. The median blood loss was 420 ml, and the median length of hospital stay of the patients was 17.5 days. There was no postoperative death in this group of patients. CONCLUSION: With the assistance of this arc-shaped transperineal incision in front of the apex of coccyx, the resection of pelvic retroperitoneal tumors can be effectively improved and the surgery risk is reduced.

Cloning and functional characterization of epidermis-specific promoter MtML1 from Medicago truncatula.

Epidermis-specific promoters are necessary for ectopic expression of specific functional genes such as the cuticle-related genes. Previous studies indicated that both ECERIFERUM 6 (AtCER6) and MERISTEM L1 LAYER (ATML1) promoters from Arabidopsis thaliana can drive gene expression specifically in the epidermis of shoot apical meristems (SAMs) and leaves. However, the epidermis-specific promoters from legume plants have not been reported. Here, we cloned a 5' flanking sequence from the upstream -2150 bp to the translational start ATG codon of MtML1 gene of legume model plant Medicago truncatula. PlantCARE analysis indicated that this sequence matches the characteristics of a promoter, having TATA box and CAAT box, as well as contains some conserved elements of epidermis-specific promoters like AtCER6 and ATML1 promoters. The ß-glucuronidase (GUS) histochemical analysis showed that MtML1 promoter can drive GUS gene expression in transiently transformed Nicotiana tabacum leaves under non-inducing condition. Furthermore, it can also control GUS expression in leaves and siliques rather than roots of the stably transformed Arabidopsis. More importantly, the leaf cross-section observations indicated that MtML1 exclusively expressed in the epidermis of leaves. These results suggested that MtML1 promoter performed the epidermis-specific in plant shoot. Our study establishes the foundation for driving the cuticle-related gene to express in epidermis, which may be very useful in genetic engineering of legume plants.

Overexpression of microRNA-612 Restrains the Growth, Invasion, and Tumorigenesis of Melanoma Cells by Targeting Espin.

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

Recombinant adenovirus expressing a dendritic cell-targeted melanoma surface antigen for tumor-specific immunotherapy in melanoma mice model.

Viral vectors represent a potential strategy for the treatment of human malignant tumors. Currently, recombinant adenovirus vectors are commonly used as gene therapy vehicles, as it possesses a proven safety profile in normal human cells. The recombinant adenovirus system has an ability to highly express exogenous genes and increase the stability of the carrier, which is only transiently expressed in the host cell genome, without integrating. Malignant melanoma cells are produced by the skin, and melanocyte tumors that exhibit higher malignant degrees lead to earlier transfer and higher mortality. In the present study, a recombinant adenovirus (rAd) was generated to express Anti-programmed death-1 (rAd-Anti-PD-1) and used to investigate the efficacy in melanoma cells and tumors. The results demonstrated that B16-F10 cell growth was significantly inhibited and the apoptosis incidence rate was markedly promoted following rAd-PD-1 treatment. The present study demonstrated that the production of α and ß interferon was increased, which led to the induction of dendritic cell (DCs) maturation in rAd-anti-PD-1-treated mice. The present study indicated that rAd-anti-PD-1 exhibited the ability to generate more cluster of differentiation (CD)4+CD8+ T cells and induce a PD-1-specific cytotoxic T lymphocyte through DC-targeted surface antigens in mice. This resulted in a further enhanced recognition of melanoma cells due to DCs being targeted by the rAd-anti-PD-1-encoded PD-1. Notably, mice treated with the rAd-anti-PD-1-targeted PD-1 demonstrated an improved protection compared with tumor-bearing mice from the challenge group treated with a recombinant gutless adenovirus and Anti-PD-1. In conclusion, the present study demonstrated that targeting the melanoma surface antigens via the rAd-anti-PD-1-infected tumor cells enhanced the ability of recombinant adenovirus to induce a potent tumor-inhibitory effect and antigen-specific immune response.

Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC50 for AChE = 0.82 ± 0.08 µmol•L-1, IC50 for BuChE = 46.30 ± 3.26 µmol•L-1) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC50 for AChE = 10.54 ± 0.86 µmol•L-1, IC50 for BuChE = 0.26 ± 0.08 µmol•L-1). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.