Anti-SARS-CoV-2 Viral Activity of Sweet Potato Trypsin Inhibitor via Downregulation of TMPRSS2 Activity and ACE2 Expression In Vitro and In Vivo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Known as COVID-19, it has affected billions of people worldwide, claiming millions of lives and posing a continuing threat to humanity. This is considered one of the most extensive pandemics ever recorded in human history, causing significant losses to both life and economies globally. However, the available evidence is currently insufficient to establish the effectiveness and safety of antiviral drugs or vaccines. The entry of the virus into host cells involves binding to angiotensin-converting enzyme 2 (ACE2), a cell surface receptor, via its spike protein. Meanwhile, transmembrane protease serine 2 (TMPRSS2), a host surface protease, cleaves and activates the virus's S protein, thus promoting viral infection. Plant protease inhibitors play a crucial role in protecting plants against insects and/or microorganisms. The major storage proteins in sweet potato roots include sweet potato trypsin inhibitor (SWTI), which accounts for approximately 60% of the total water-soluble protein and has been found to possess a variety of health-promoting properties, including antioxidant, anti-inflammatory, ACE-inhibitory, and anticancer functions. Our study found that SWTI caused a significant reduction in the expression of the ACE2 and TMPRSS2 proteins, without any adverse effects on cells. Therefore, our findings suggest that the ACE2 and TMPRSS2 axis can be targeted via SWTI to potentially inhibit SARS-CoV-2 infection.

An Emerging Era: Conformable Ultrasound Electronics.

Conformable electronics are regarded as the next generation of personal healthcare monitoring and remote diagnosis devices. In recent years, piezoelectric-based conformable ultrasound electronics (cUSE) have been intensively studied due to their unique capabilities, including nonradiative monitoring, soft tissue imaging, deep signal decoding, wireless power transfer, portability, and compatibility. This review provides a comprehensive understanding of cUSE for use in biomedical and healthcare monitoring systems and a summary of their recent advancements. Following an introduction to the fundamentals of piezoelectrics and ultrasound transducers, the critical parameters for transducer design are discussed. Next, five types of cUSE with their advantages and limitations are highlighted, and the fabrication of cUSE using advanced technologies is discussed. In addition, the working function, acoustic performance, and accomplishments in various applications are thoroughly summarized. It is noted that application considerations must be given to the tradeoffs between material selection, manufacturing processes, acoustic performance, mechanical integrity, and the entire integrated system. Finally, current challenges and directions for the development of cUSE are highlighted, and research flow is provided as the roadmap for future research. In conclusion, these advances in the fields of piezoelectric materials, ultrasound transducers, and conformable electronics spark an emerging era of biomedicine and personal healthcare.

A Conformable Ultrasound Patch for Cavitation-Enhanced Transdermal Cosmeceutical Delivery.

Increased consumer interest in healthy-looking skin demands a safe and effective method to increase transdermal absorption of innovative therapeutic cosmeceuticals. However, permeation of small-molecule drugs is limited by the innate barrier function of the stratum corneum. Here, a conformable ultrasound patch (cUSP) that enhances transdermal transport of niacinamide by inducing intermediate-frequency sonophoresis in the fluid coupling medium between the patch and the skin is reported. The cUSP consists of piezoelectric transducers embedded in a soft elastomer to create localized cavitation pockets (0.8 cm2 , 1 mm deep) over larger areas of conformal contact (20 cm2 ). Multiphysics simulation models, acoustic spectrum analysis, and high-speed videography are used to characterize transducer deflection, acoustic pressure fields, and resulting cavitation bubble dynamics in the coupling medium. The final system demonstrates a 26.2-fold enhancement in niacinamide transport in a porcine model in vitro with a 10 min ultrasound application, demonstrating the suitability of the device for short-exposure, large-area application of sonophoresis for patients and consumers suffering from skin conditions and premature skin aging.

Accurate prediction of drug-induced heterogeneous response of red cell in vivo using a gravity-driven flow cytometry based on a microfluidic chip.

The drug-induced diverse response among patients is a severe problem for improving hemorheological character. However, there is no validated method for personalized therapy to the best of our knowledge. Here, we apply a gravity-driven deformability cytometry platform (GD-DCP) to profile the drug response of the red cell deformability (RCD) at the single-cell level using pentoxifylline (PTX) as a model drug, the effect of different concentrations of PTX (0, 2, 20, 200 µg mL-1, the clinical dosage of PTX is 20 µg mL-1) on RCD in patients with cardiovascular disease was explored. Based on the GD-DCP, about 38 and 56% of the acute phase of acute myocardial infarction (AMI) patients in the acute phase and coronary heart disease (CHD) patients respond positively to PTX, respectively, indicating that PTX has a strong patient dependency on RCD. Moreover, RCD is observed to be significantly inversely correlated with the activation of membrane protein kinase C (PKC) as well as the concentration of Ca2+ (both P < 0.001). The results of animal experiments show that the protective effects of PTX on myocardial ischemia rats have substantial individual variation, too. It is noted that the effect of PTX is highly consistent between RCD in vitro and in vivo outcomes (blood viscosity, myocardial injury, and electrocardiogram (ECG)) in the same rat. All these new findings suggest that the GD-DCP is a promising method that uses deformability in vitro as one of the important criteria in personalized medicine, and our study provides unique insight into the individual-dependent mechanisms of PTX for improving RCD.

Label-free separation of mesenchymal stem cell subpopulations with distinct differentiation potencies and paracrine effects.

Mesenchymal stem cells (MSCs) have the capability to differentiate into multiple cell lineages, and produce trophic factors to facilitate tissue repair and regeneration, and disease regression. However, the heterogeneity of MSCs, whether inherent or developed during culture expansion, has a significant impact on their therapeutic efficacy. Therefore, the ability to identify and select an efficacious subpopulation of MSCs targeting specific tissue damage or disease holds great clinical significance. In this study, we separated three subpopulations from culture expanded human bone marrow derived MSCs according to cell size, using a high-throughput label-free microfluidic cell sorting technology. The size-sorted MSC subpopulations varied in tri-lineage differentiation potencies. The large MSCs showed the strongest osteogenesis, medium-size MSCs were advantageous in chondrogenesis and adipogenesis, and the small MSCs showed the weakest tri-lineage differentiation. The size-sorted MSC subpopulations also exhibited different secretome profiles. The large MSC secretome possessed highest levels of osteogenic promotor proteins and senescence-associated factors, but lower levels of osteogenic inhibitor proteins compared to the medium-size MSC secretome. The medium-size MSC secretome had high levels of chondrogenic promotor proteins, and contained lower levels of chondrogenic inhibitor proteins compared to the large MSC secretome. The secretome of size-sorted MSC subpopulations showed differences in paracrine effects. We found that the secretome of large MSCs enhanced osteogenic and adipogenic potencies during MSC culture expansion, but also induced cell senescence; and the secretome of medium-size MSCs promoted chondrogenesis. This study demonstrates size-dependent differentiation potency and secretome profile of MSC subpopulations, and provides an effective and practical technology to isolate the respective subpopulations, which may be used for more targeted tissue repair and regeneration.

Positive effects of art therapy on depression and self-esteem of older adults in nursing homes.

Depression and self-esteem affects the health and quality of life of older adults who live in nursing homes. This study tested the effectiveness of art therapy activities on reducing the depression and improving the self-esteem of elderly living in long-term care institutes. This was a quasi-experimental study. A purposive sampling strategy was used to select 55 subjects who were aged 65 and above with intact mental functions and depression tendencies and currently residing in nursing homes in Kaohsiung, Taiwan. 29 subjects who participated in a selection of 12 artistic activities were assigned to the experimental group and 26 subjects who adhered to their ordinary activities were allocated to the control group. Structured questionnaires of the artistic group were used for data collection. The art therapy programs showed promising effects in improving the depression and self-esteem of older adults living in nursing homes. Art therapy activities benefit the mental health of older adults. Incorporating artistic activities into social work care may help develop long-term care into a more diverse, unique, and innovative direction.

Neural mechanisms for integrating prior knowledge and likelihood in value-based probabilistic inference.

In Bayesian decision theory, knowledge about the probabilities of possible outcomes is captured by a prior distribution and a likelihood function. The prior reflects past knowledge and the likelihood summarizes current sensory information. The two combined (integrated) form a posterior distribution that allows estimation of the probability of different possible outcomes. In this study, we investigated the neural mechanisms underlying Bayesian integration using a novel lottery decision task in which both prior knowledge and likelihood information about reward probability were systematically manipulated on a trial-by-trial basis. Consistent with Bayesian integration, as sample size increased, subjects tended to weigh likelihood information more compared with prior information. Using fMRI in humans, we found that the medial prefrontal cortex (mPFC) correlated with the mean of the posterior distribution, a statistic that reflects the integration of prior knowledge and likelihood of reward probability. Subsequent analysis revealed that both prior and likelihood information were represented in mPFC and that the neural representations of prior and likelihood in mPFC reflected changes in the behaviorally estimated weights assigned to these different sources of information in response to changes in the environment. Together, these results establish the role of mPFC in prior-likelihood integration and highlight its involvement in representing and integrating these distinct sources of information.

Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.

BACKGROUND: Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). METHODS: A case-control study was conducted on 305 young ischemic stroke subjects aged

Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan.

BACKGROUND: The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample. METHODS: We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke. RESULTS: There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively. CONCLUSIONS: This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.

High performance 3-coil wireless power transfer system for the 512-electrode epiretinal prosthesis.

The next-generation retinal prostheses feature high image resolution and chronic implantation. These features demand the delivery of power as high as 100 mW to be wireless and efficient. A common solution is the 2-coil inductive power link, used by current retinal prostheses. This power link tends to include a larger-size extraocular receiver coil coupled to the external transmitter coil, and the receiver coil is connected to the intraocular electrodes through a trans-sclera trans-choroid cable. In the long-term implantation of the device, the cable may cause hypotony (low intraocular pressure) and infection. However, when a 2-coil system is constructed from a small-size intraocular receiver coil, the efficiency drops drastically which may induce over heat dissipation and electromagnetic field exposure. Our previous 2-coil system achieved only 7% power transfer. This paper presents a fully intraocular and highly efficient wireless power transfer system, by introducing another inductive coupling link to bypass the trans-sclera trans-choroid cable. With the specific equivalent load of our customized 512-electrode stimulator, the current 3-coil inductive link was measured to have the overall power transfer efficiency around 36%, with 1-inch separation in saline. The high efficiency will favorably reduce the heat dissipation and electromagnetic field exposure to surrounding human tissues. The effect of the eyeball rotation on the power transfer efficiency was investigated as well. The efficiency can still maintain 14.7% with left and right deflection of 30 degree during normal use. The surgical procedure for the coils' implantation into the porcine eye was also demonstrated.

Prospective randomized trial comparing shock wave lithotripsy and ureteroscopic lithotripsy for management of large upper third ureteral stones.

OBJECTIVES: To conduct a prospective and randomized trial to compare the efficiency quotient and cost-effectiveness index of shock wave lithotripsy (SWL) and ureteroscopic lithotripsy (URSL) for the treatment of large upper third ureteral stones. METHODS: A total of 35 male patients and 7 female patients with a solitary, radiopaque upper ureteral stone, 15 mm or more in diameter, who underwent SWL or URSL were enrolled in this study. The mean patient age was 53.1 +/- 14.5 years. The endpoint of the study was for the patient to be stone free or to have insignificant residual stone (3 mm or less) within the kidney. RESULTS: The mean stone length +/- SD was 17.9 +/- 3.9 cm in the SWL group and 18.5 +/- 2.9 cm in the URSL group (P > 0.05). The efficiency quotient for SWL and URSL was 0.61 and 0.63, respectively. The cost-effectiveness index, treatment time, pain score, and hospital stay were greater in the URSL group. However, the degree of hydronephrosis significantly influenced the success rate of SWL. All patients with severe hydronephrosis in the SWL group needed auxiliary surgical procedures to become stone free. CONCLUSIONS: The efficiency quotients of SWL and URSL were comparable in the treatment of large upper third ureteral stones. However, SWL should not be recommended as the first-line treatment option for the management of upper third ureteral stones larger than 1.5 cm with severe hydronephrosis. Understanding the cost-effectiveness, success rate, pain score, and patient satisfaction score for the two different approaches constitutes the indispensable requisites for choosing the optimal first-line therapeutic strategy.