Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1.

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.

Systematic establishment of the relationship between skin absorption and toxicity of furanoids via in silico, in vitro, and in vivo assessments.

Furanoids are a class of contaminants prevalent in both airborne and occupational environments, with potential health implications through inhalation, oral ingestion, and skin penetration. Given their diminutive molecular size, there is a presumption that furanoids can readily permeate the skin. To systematically explore this presumption, we investigated the skin absorption and toxicity of a series of furans (furfuryl alcohol, furfuryl acetate, furfural, methyl 2-furoate, and 5-methylfurfural) using in silico, in vitro, and in vivo models. The in vitro permeation test (IVPT) from neat and aqueous suspension (5 mM) of furans demonstrated a facile absorption through pig and nude mouse skins. The lipophilicity of furans significantly influenced skin deposition, with higher lipophilicity displaying greater deposition. However, an opposing trend emerged in the receptor compartment accumulation. In barrier-defective skin simulating atopic dermatitis (AD) and psoriasis, enhanced deposition occurred with more hydrophilic furans but not with the more lipophilic ones. In the cell-based study, furanoids induced the proliferation of keratinocytes and skin fibroblasts except for the compounds with the aldehyde group (furfural and 5-methylfurfural). Both furfuryl acetate and 5-methylfurfural activated keratinocytes via the overexpression of COX-2 and PGE2 by 1.5‒2-fold. This stimulation involved the mitogen-activated protein kinase (MAPK) signaling pathway. For the in vivo mouse skin treatment, we selected furfuryl acetate (hydrophilic) and 5-methylfurfural (lipophilic). Both furans showed different patterns of skin lesions, where repeated application of furfuryl acetate caused epidermal hyperplasia and scaling, while 5-methylfurfural predominantly evoked skin inflammation and barrier disintegration. Toxicokinetics analysis revealed a higher plasma concentration of topically applied furfuryl acetate than that of the 5-methylfurfural (5.04 versus 2.34 nmol/ml), resulting in the mild injury of furfuryl acetate-treated peripheral organs. Conversely, no notable adverse effects on organs were observed for the 5-methylfurfural. This study established the relationship between cutaneous absorption and the toxicity of furans following skin exposure.

Facile adipocyte uptake and liver/adipose tissue delivery of conjugated linoleic acid-loaded tocol nanocarriers for a synergistic anti-adipogenesis effect.

Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way.

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. MATERIALS AND METHODS: In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. RESULTS: Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. CONCLUSIONS: We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.

The anti-inflammatory activity of flavonoids and alkaloids from Sophora flavescens alleviates psoriasiform lesions: Prenylation and methoxylation beneficially enhance bioactivity and skin targeting.

The herb Sophora flavescens displays anti-inflammatory activity and can provide a source of antipsoriatic medications. We aimed to evaluate whether S. flavescens extracts and compounds can relieve psoriasiform inflammation. The ability of flavonoids (maackiain, sophoraflavanone G, leachianone A) and alkaloids (matrine, oxymatrine) isolated from S. flavescens to inhibit production of cytokine/chemokines was examined in keratinocytes and macrophages. Physicochemical properties and skin absorption were determined by in silico molecular modeling and the in vitro permeation test (IVPT) to establish the structure-permeation relationship (SPR). The ethyl acetate extract exhibited higher inhibition of interleukin (IL)-6, IL-8, and CXCL1 production in tumor necrosis factor-α-stimulated keratinocytes compared to the ethanol and water extracts. The flavonoids demonstrated higher cytokine/chemokine inhibition than alkaloids, with the prenylated flavanones (sophoraflavanone G, leachianone A) led to the highest suppression. Flavonoids exerted anti-inflammatory effects via the extracellular signal-regulated kinase, p38, activator protein-1, and nuclear factor-κB signaling pathways. In the IVPT, prenylation of the flavanone skeleton significantly promoted skin absorption from 0.01 to 0.22 nmol/mg (sophoraflavanone G vs. eriodictyol). Further methoxylation of a prenylated flavanone (leachianone A) elevated skin absorption to 2.65 nmol/mg. Topical leachianone A reduced the epidermal thickness in IMQ-treated mice by 47%, and inhibited cutaneous scaling and cytokine/chemokine overexpression at comparable levels to a commercial betamethasone product. Thus, prenylation and methoxylation of S. flavescens flavanones may enable the design of novel antipsoriatic agents.

Long stem revision versus short stem revision with plate osteosynthesis for Vancouver type B2 periprosthetic femoral fracture: a comparative study of eighty five cases.

PURPOSE: Periprosthetic femoral fractures (PPFs) around the hip are challenging complications in orthopaedic surgery, particularly Vancouver type B2 (VTB2) fractures. The surgical management of these fractures is crucial and depends on various factors. Cementless short taper stem with plate osteosynthesis is an alternative surgical technique. This study aims to compare the outcomes of this surgical technique with revision arthroplasty (RA) with long stem in the treatment of VTB2 PPFs. METHODS: This retrospective study was conducted in a single medical institute from February 2010 to May 2019. Patients who had received either total hip arthroplasty or bipolar hemiarthroplasty and subsequently developed a VTB2 PPF were included; patients who sustained intra-operative fractures or received a cemented stem previously were excluded from the analysis. The patients were divided into two groups: group I received RA with cementless long stem, while group II underwent RA with cementless short taper stem with plate osteosynthesis. Demographic data, radiographic and functional outcomes, and complications were analyzed between the two groups. RESULTS: A total of 85 patients diagnosed with VTB2 PPFs were included in the study. There were no significant differences between the two groups in terms of demographic data, including age, gender, mean follow-up times, estimated blood loss, and operative times. The radiographic results showed that there was no significant difference in the incidence of subsidence and implant stability between the two groups. However, group II tended to have less subsidence and periprosthetic osteolysis. Patients in group II had significantly better functional scores (mean Harris hip score: post-operative: 60.2 in group I and 66.7 in group ii; last follow-up: 77.4 in group 1 and 83.2 in group II (both p < 0.05)). There were no significant differences in the overall complication rate, including infection, dislocation, re-fracture, and revision surgery, between the two groups. CONCLUSIONS: Both surgical techniques, cementless long stem and cementless short taper stem with plate osteosynthesis, are effective in the treatment of Vancouver B2 PPFs, with no significant differences in outcomes or complications. However, patients in cementless short taper stem with plate osteosynthesis had better functional scores at both post-operative and the last follow-up.

Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

[Impacts of testis aging on overall health: Advances in studies].

The testis, as one of the important reproductive organs in men, has two major functions of secreting androgens and producing sperm. Androgen and spermatogenesis are the key factors for the evaluation of the testicular function. The lack of androgen or the decline of spermatogenic function is both a symbolic manifestation and a "product" of testis aging. In order to gain a deeper insight into the relationship between testis aging and overall health, this article reviews the relevant literature based on the correlation of androgen deficiency with various systemic diseases and the belief in the impacts of testis aging on the health of the cardiovascular and nervous systems through different channels, the development and progression of metabolic diseases, orthopedic diseases, PCa, kidney disease, peptic ulcer and other diseases. All these suggest that adequate attention should be paid to the studies of male reproductive health and its impact on overall health, so as to provide some new ideas and evidence for clinical diagnosis and treatment of relevant conditions.

Association between metal exposure from e-cigarette components and toxicity endpoints: A literature review.

Electronic cigarette is often promoted and perceived as an 'healthy' alternative compared to conventional cigarettes. However, growing body of evidence indicate the possible adverse health effect associated with e-cigarette. Here we reviewed the literature with a focus on metal exposure in relation to e-cigarette use and related toxicity endpoints. Twenty-nine studies were identified for full text screening after applying the screening criteria of which 5 in vitro studies and 11 epidemiological studies were included for data extraction. Cr, Cu, Ni, Sn are the most found metal in all studies. In vitro, metal from e-cigarette (liquid or aerosols) induced cytotoxicity, oxidative stress, genotoxicity and pro-inflammatory responses. It was observed that the presence of nicotine can influence metal-induced in vitro toxicity. Based on epidemiological studies, the metal burden in e-cigarette users showed to be elevated in different populations (including e.g. NHANES). However, most often such studies were limited by the missing user characteristics, and information of other potential sources of metal exposure. In general, metals from e-cigarette use can be associated with toxicity endpoints but to uncover the metal related hazard of e-cigarette in users, more detailed data on metals in vapors and e-liquids; user habits and user demographics are needed.

Dynamic Resource Allocation for Network Slicing with Multi-Tenants in 5G Two-Tier Networks.

Virtualization is a core 5G network technology which helps telecom companies significantly reduce capital expenditure and operating expenses by deploying multiple services on the same hardware infrastructure. However, providing QoS-guaranteed services for multi-tenants poses a significant challenge due to multi-tenant service diversity. Network slicing has been proposed as a means of addressing this problem by isolating computing and communication resources for the different tenants of different services. However, optimizing the allocation of the network and computation resources across multiple network slices is a critical but extremely difficult problem. Accordingly, this study proposes two heuristic algorithms, namely Minimum Cost Resource Allocation (MCRA) and Fast Latency Decrease Resource Allocation (FLDRA), to perform dynamic path routing and resource allocation for multi-tenant network slices in a two-tier architecture. The simulation results show that both algorithms significantly outperform the Upper-tier First with Latency-bounded Overprovisioning Prevention (UFLOP) algorithm proposed in previous work. Furthermore, the MCRA algorithm achieves a higher resource utilization than the FLDRA algorithm.

Adversarial Patch Attacks on Deep-Learning-Based Face Recognition Systems Using Generative Adversarial Networks.

Deep learning technology has developed rapidly in recent years and has been successfully applied in many fields, including face recognition. Face recognition is used in many scenarios nowadays, including security control systems, access control management, health and safety management, employee attendance monitoring, automatic border control, and face scan payment. However, deep learning models are vulnerable to adversarial attacks conducted by perturbing probe images to generate adversarial examples, or using adversarial patches to generate well-designed perturbations in specific regions of the image. Most previous studies on adversarial attacks assume that the attacker hacks into the system and knows the architecture and parameters behind the deep learning model. In other words, the attacked model is a white box. However, this scenario is unrepresentative of most real-world adversarial attacks. Consequently, the present study assumes the face recognition system to be a black box, over which the attacker has no control. A Generative Adversarial Network method is proposed for generating adversarial patches to carry out dodging and impersonation attacks on the targeted face recognition system. The experimental results show that the proposed method yields a higher attack success rate than previous works.

[Craving in Substance Addiction: A Concept Analysis].

Craving in the context of substance addiction is considered an important predictor of substance addictive disorders and relapse risk. Behavior therapy, mindfulness, and exercise may be employed clinically to alleviate cravings. However, many scholars have offered various interpretations of craving in substance addiction. Despite these definitions sharing some overlapping elements, a consensus has yet to be reached. Although many studies have presented the effects of and interventions for craving to alleviate substance addiction, this issue has rarely been explored in the clinical nursing context, resulting in a lack of understanding of the concept of craving in substance addiction among nursing professionals. Therefore, based on the conceptual analysis approach proposed by Walker and Avant (2019), a conceptual analysis of craving in substance addiction was conducted in this study by interpreting and defining the characteristics, pre-factors, consequences, and effects of craving in substance addiction using examples of typical, borderline, related, and contrary cases. The findings are intended to help nurses gain a more comprehensive understanding of craving in substance addiction and become more familiar with cases requiring clinical care.

[A cross-sectional study on the prevalence rate and influencing factors of non-alcoholic fatty liver disease in overweight/obese children]. / è¶ é‡/è‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªè‚ç— æ‚£ç— çŽ‡åŠå ¶å½±å“å› ç´ çš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS: The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.

Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats.

BACKGROUND: The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown. METHODS: Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior. RESULTS: The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats. CONCLUSIONS: These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.

Optimizing the Rydberg EIT spectrum in a thermal vapor.

We present Rydberg-state electromagnetically-induced-transparency (EIT) measurements examining the effects of laser polarization, magnetic fields, laser intensities, and the optical density of the thermal 87Rb medium. Two counter-propagating laser beams with wavelengths of 480 nm and 780 nm were employed to sweep the spectrum across the Rydberg states |33D3/2〉 and |33D5/2〉. An analytic transmission expression well fits the Rydberg-EIT spectra with multiple transitions under different magnetic fields and laser polarization after accounting for the relevant Clebsch-Gordan coefficients, Zeeman splittings, and Doppler shifts. In addition, the high-contrast Rydberg EIT can be optimized with the probe laser intensity and optical density. Rydberg EIT peak height was achieved at 13%, which is more than twice as high as the maximum peak height at room temperature. A quantitative theoretical model is employed to represent the spectra properties and to predict well the optimization conditions. A Rydberg EIT spectrum with high contrast in real time can be served as a quantum sensor to detect the electromagnetic field within an environment.

The post-translational modification of Fascin: impact on cell biology and its associations with inhibiting tumor metastasis.

The post-translational modifications (PTMs), which are crucial in the regulation of protein functions, have great potential as biomarkers of cancer status. Fascin (Fascin actin-bundling protein 1, FSCN1), a key protein in the formation of filopodia that is structurally based on actin filaments (F-actin), is significantly associated with tumor invasion and metastasis. Studies have revealed various regulatory mechanisms of human Fascin, including PTMs. Although a number of Fascin PTM sites have been identified, their exact functions and clinical significance are much less explored. This review explores studies on the functions of Fascin and briefly discusses the regulatory mechanisms of Fascin. Next, to review the role of Fascin PTMs in cell biology and their associations with metastatic disease, we discuss the advances in the characterization of Fascin PTMs, including phosphorylation, ubiquitination, sumoylation, and acetylation, and the main regulatory mechanisms are discussed. Fascin PTMs may be potential targets for therapy for metastatic disease.

Neurotoxicity of four frequently used nanoparticles: a systematic review to reveal the missing data.

Systemic exposure to nanoparticles (NPs) adversely affects different organs, including the nervous system. We systematically extracted data from publication on PubMed and Embase database up to the year 2020, and analyzed in vitro and in vivo neurotoxicity of 4 of the most well studied NPs (silver NPs, carbon-based NPs, iron NPs and silica NPs). A relatively good correlation was observed between in vitro and in vivo effects, including genotoxicity, oxidative stress, apoptosis and pro-inflammatory effects. However, crucial knowledge gap exists in current understanding of the underlying mechanisms. Some of the critical knowledge gaps and research needs identified in relation to neurotoxicity of nanoparticles include (1) lack of physio-chemical characteristics of NPs used, (2) cellular/tissue uptake of NP, (3) NP translocation across the blood-brain barrier (BBB), (4) Effect of exposure routes.

Small spherical foreign bodies in the genitourinary tract and their management.

BACKGROUND: Urogenital small foreign bodies (FBs) have rarely been reported in children, and their management is still challenging. This study aimed to describe the characteristics and treatment of spherical FBs no larger than 0.6 cm in the children's genitourinary tracts.  METHODS : The clinical data of spherical FBs removed in our hospital from June 2013 to June 2020 were recorded and retrospectively analyzed, including demographics, location, symptoms, imaging examinations and treatment methods. RESULTS: A total of 10 patients were enrolled: 6 girls and 4 boys. Their ages ranged from 5.1 to 16.8 years old, with a mean age of 9.2 years. The course of the disease ranged from 3 h to 1 year, and symptoms recurred in some cases. Their imaging characteristics were reviewed and analyzed, 6 patients underwent color Doppler ultrasonography, 1 patient was suspected to have an FB in the vagina, 7 patients underwent an X-ray examination, and FBs were revealed in 6 patients. All FBs were removed under endoscopic minimally invasive surgery. Six vaginal FBs were successfully retrieved via vaginoscopy, and in the other four cases, removal by transurethral cystoscopy failed because of mutual attraction, which was eliminated by laparoscopy under pneumovesicum. Postoperative recovery was uneventful; in a follow-up of 3 months to 2 years, there was no perforation or fistula formation, and there were no urethral strictures in boys. CONCLUSION: Small spherical FBs are clinically rare; they are sometimes difficult to detect by imaging examinations and can be easily overlooked. Minimally invasive endoscopy remains the first-line approach for the diagnosis and removal of genitourinary spherical FBs.

Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy.

Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.

Putative markers for the detection of early-stage bladder cancer selected by urine metabolomics.

BACKGROUND: Early detection of bladder cancer remains challenging because patients with early-stage bladder cancer usually have no incentive to take cytology or cystoscopy tests if they are asymptomatic. Our goal is to find non-invasive marker candidates that may help us gain insight into the metabolism of early-stage bladder cancer and be examined in routine health checks. RESULTS: We acquired urine samples from 124 patients diagnosed with early-stage bladder cancer or hernia (63 cancer patients and 61 controls). In which 100 samples were included in our marker discovery cohort, and the remaining 24 samples were included in our independent test cohort. We obtained metabolic profiles of 922 compounds of the samples by gas chromatography-mass spectrometry. Based on the metabolic profiles of the marker discovery cohort, we selected marker candidates using Wilcoxon rank-sum test with Bonferroni correction and leave-one-out cross-validation; we further excluded compounds detected in less than 60% of the bladder cancer samples. We finally selected eight putative markers. The abundance of all the eight markers in bladder cancer samples was high but extremely low in hernia samples. Moreover, the up-regulation of these markers might be in association with sugars and polyols metabolism. CONCLUSIONS: In the present study, comparative urine metabolomics selected putative metabolite markers for the detection of early-stage bladder cancer. The suggested relations between early-stage bladder cancer and sugars and polyols metabolism may create opportunities for improving the detection of bladder cancer.