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Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth. Our present study found that dual-frequency US-mediated microbubble (MB) cavitation significantly enhanced minoxidil (Mx) delivery in both in vitro and in vivo models, while increasing the hair growth efficacy compared to single-frequency US sonication. The in vitro experiments showed that cavitation activity was enhanced more significantly during dual-frequency sonication than single-frequency sonication in higher concentration of MBs. The pigskin penetration depth in the group in which dual-frequency US was combined with MBs was 1.54 and 2.86 times greater than for single-frequency US combined with MBs and in the control group, respectively; the corresponding increases in the release rate of Mx at 18 hours in in vitro Franz-diffusion-cell experiments were 24.9% and 43.7%. During 21 days of treatment in C57BL/6J mice experiments, the growth rate at day 11 in the group in which dual-frequency US was combined with MBs increased by 2.07 times compared to single-frequency US combined with MBs. These results indicate that dual-frequency US-mediated MB cavitation can significantly increase both skin permeability and transdermal drug delivery. At the same US power density, hair growth was greater in the group with dual-frequency US plus MBs than in the group with single-frequency US plus MBs, without damaging the skin in mice.

Blood stream infection is one of the major public health issues characterized with high cost and high mortality. Timely effective antibiotics usage to control infection is crucial for patients’ survival. The standard microbiological diagnosis of infection however can last days. The delay in accurate antibiotic therapy would lead to not only poor clinical outcomes, but also to a rise in antibiotic resistance due to widespread use of empirical broad-spectrum antibiotics. An important measure to tackle this problem is fast determination of bacterial antibiotic susceptibility to optimize antibiotic treatment. We show that a protocol based on surface-enhanced Raman spectroscopy can obtain consistent antibiotic susceptibility test results from clinical blood-culture samples within four hours. The characteristic spectral signatures of the obtained spectra of Staphylococcus aureus and Escherichia coli—prototypic Gram-positive and Gram-negative bacteria—became prominent after an effective pretreatment procedure removed strong interferences from blood constituents. Using them as the biomarkers of bacterial metabolic responses to antibiotics, the protocol reported the susceptibility profiles of tested drugs against these two bacteria acquired from patients’ blood with high specificity, sensitivity and speed.

Cholesteatoma has attracted many studies seeking to uncover its nature and the pathogenesis of related diseases. However, no researchers have explored the mitochondrial bioenergetics of cholesteatoma. The aim of this study was to investigate the energy demand and differential mitochondrial respiration profiles between keratinocytes in external auditory canal (EAC) skin and cholesteatoma samples cultured in normoxic (20% O2) and hypoxic (5% O2) conditions. Enhanced cellular proliferation of both types of keratinocytes was found in hypoxia compared to normoxia. In 20% O2 conditions, cholesteatoma keratinocytes exhibited less mitochondrial mass, lower ATP levels, and significantly lower basal oxygen consumption rate (OCR) and reserve capacity compared to normal skin keratinocytes. In contrast, in hypoxic conditions, cholesteatoma keratinocytes showed markedly higher levels in maximal OCR and reserve capacity, as well as lower proton leak OCRs, compared to normal skin keratinocytes. Hypoxia induced the reverse mitochondrial bioenergy profile from that in normoxia between these two types of keratinocytes, implying that an adaptive change of mitochondrial respiration to oxygen fluctuations may develop in cases of cholesteatoma. Such adaptation in response to hypoxic conditions may play a role in explaining the pathogenesis of acquired cholesteatoma.

Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) correlate with morbidity and mortality in dialysis patients. However, the comparative roles of each CKD-MBD biomarker remained undetermined on long-term peritoneal dialysis (PD) patients. This retrospective study, employing a population-based database, aimed to evaluate the performance and provide the best evidence of each biomarker of CKD-MBD as predictor of all-cause mortality. Throughout the 8-year study period, total 12,116 PD patients were included in this study. Cox proportional regression and Kaplan-Meier method were used for survival analysis. For Cox regression model, baseline measurements and time-varying covariates were used for analysis. In Cox regression model using time-dependent covariates, serum calcium level of ≧9.5 mg/dL was associated with increased mortality. For phosphorus, serum levels of either ≧6.5 mg/dL or

Acne vulgaris is the most common skin disorder, and is caused by Propionibacterium acnes (P. acnes) and can induce inflammation. Antibiotic therapy often needs to be administered for long durations in acne therapy, which results in extensive antibiotic exposure. The present study investigated a new treatment model for evaluating the antibacterial effects of lysozyme (LY)-shelled microbubbles (MBs) and ultrasound (US)-mediated LY-shelled MBs cavitation against P. acnes both in vitro and in vivo, with the aims of reducing the dose and treatment duration and improving the prognosis of acne vulgaris. In terms of the in vitro treatment efficacy, the growth of P. acnes was inhibited by 86.08 ± 2.99% in the LY-shelled MBs group and by 57.74 ± 3.09% in the LY solution group. For US power densities of 1, 2, and 3 W/cm2 in the LY-shelled MBs group, the growth of P. acnes was inhibited by 95.79 ± 3.30%, 97.99 ± 1.16%, and 98.69 ± 1.13%, respectively. The in vivo results showed that the recovery rate on day 13 was higher in the US group with LY-shelled MBs (97.8 ± 19.8%) than in the LY-shelled MBs group (90.3 ± 23.3%). Our results show that combined treatments of US and LY-shelled MBs can significantly reduce the treatment duration and inhibit P.-acnes-induced inflammatory skin diseases.

Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm−1) and lipid (~2845 cm−1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.