3D Amplified Single-Cell RNA and Protein Imaging Identifies Oncogenic Transcript Subtypes in B-Cell Acute Lymphoblastic Leukemia.

Simultaneous in situ detection of transcript and protein markers at the single-cell level is essential for gaining a better understanding of tumor heterogeneity and for predicting and monitoring treatment responses. However, the limited accessibility to advanced 3D imaging techniques has hindered their rapid implementation. Here, we present a 3D single-cell imaging technique, termed 3D digital rolling circle amplification (4DRCA), capable of the multiplexed and amplified simultaneous digital quantification of single-cell RNAs and proteins using standard fluorescence microscopy and off-the-shelf reagents. We generated spectrally distinguishable DNA amplicons from molecular markers through an integrative protocol combining single-cell RNA and protein assays and directly enumerated the amplicons by leveraging an open-source algorithm for 3D deconvolution with a custom-built automatic gating algorithm. With 4DRCA, we were able to simultaneously quantify surface protein markers and cytokine transcripts in T-lymphocytes. We also show that 4DRCA can distinguish BCR-ABL1 fusion transcript positive B-cell acute lymphoblastic leukemia cells with or without CD19 protein expression. The accessibility and extensibility of 4DRCA render it broadly applicable to other cell-based diagnostic workflows, enabling sensitive and accurate single-cell RNA and protein profiling.

Clinical Evaluation of Conditioned Media of Human Umbilical Cord Blood Mesenchymal Stem Cells for Improvement of Symptoms of Sensitive Skin: Prospective, Single Blinded, Split-face Study.

BACKGROUND: The exact definition of sensitive skin is not established yet. Since its high prevalence and significant influence on quality of life, it has become an important topic of research. Among various ingredients, conditioned media from umbilical cord blood-derived mesenchymal stem cells (UCB-MSC-CM) can be a promising source for the treatment of sensitive skin. OBJECTIVE: We evaluated the efficacy and safety of UCB-MSC-CM on patients with sensitive skin. METHODS: We designed a randomized, single blinded, prospective, split-face comparison study and enrolled thirty patients. All patients underwent nonablative fractional laser over the entire face before UCB-MSC-CM or normal saline was applied. Each facial area was randomly assigned to undergo treatment with either UCB-MSC-CM or normal saline. We performed three sessions at two-week intervals, and final results were assessed on six weeks after the last session. As an outcome measure, we evaluated a five-point global assessment scale, transepidermal water loss (TEWL), erythema index (EI) and Sensitive Scale-10. Twenty seven subjects were included in final analysis. RESULTS: The treated side exhibited greater improvement compared to the untreated side based on a five-point global assessment scale. TEWL, EI of the treated side were significantly lower than those of the untreated side throughout study period. Sensitive Scale-10 was significantly improved after treatment. CONCLUSION: The application of UCB-MSC-CM resulted in improved skin barrier function and reduced inflammatory responsiveness, which could provide beneficial effect on sensitive skin.

ACR Appropriateness Criteria® Radiologic Management of Mesenteric Ischemia: 2022 Update.

Mesenteric ischemia is a serious medical condition characterized by insufficient vascular supply to the small bowel. In the acute setting, endovascular interventions, including embolectomy, transcatheter thrombolysis, and angioplasty with or without stent placement, are recommended as initial therapeutic options. For nonocclusive mesenteric ischemia, transarterial infusion of vasodilators, such as papaverine or prostaglandin E1, is the recommended initial treatment. In the chronic setting, endovascular means of revascularization, including angioplasty and stent placement, are generally recommend, with surgical options, such as bypass or endarterectomy, considered alternative options. Although the diagnosis of median arcuate ligament syndrome remains controversial, diagnostic angiography can be helpful in rendering a diagnosis, with the preferred treatment option being a surgical release. Systemic anticoagulation is recommended as initial therapy for venous mesenteric ischemia with acceptable rates of recanalization. If anticoagulation fails, transcatheter thrombolytic infusion can be considered with possible adjunctive placement of a transjugular intrahepatic portosystemic shunt to augment antegrade flow. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Sessile droplet array for sensitive profiling of multiple extracellular vesicle immuno-subtypes.

The sensitive detection of the multiple immuno-subtypes of cancer-specific extracellular vesicles (EVs) has emerged as a promising method for multiclass cancer diagnosis; however, its limitations in sensitivity, accessibility, and multiple detection of EV subtypes have hindered its further implementation. Here, we present a platform for sensitive EV detection enabled by sessile droplet array (eSD) that exploits enhanced immuno-capture of EVs via evaporation-driven radial flows in a sessile droplet. Compared to a micro-well without internal flows, this platform demonstrates significantly enhanced EV capture and detection by detecting low levels of EVs with a detection limit of 384.7 EVs per microliter, which is undetectable in the micro-well. In addition, using a small sample consumption of ∼0.2 µL plasma per droplet, the platform detects EV immuno-subtypes against seven different antibodies in patient plasma samples of different cancer types (liver, colon, lung, breast and prostate cancers). Further, using the profiling data, the platform exhibits a sensitivity of 100% (95% confidence interval (CI): 83-100%) and a specificity of 100% (95% CI: 40-100%) for the diagnosis of cancer, and classified cancer types with an overall accuracy of 96% (95% CI: 86-100%) using a two-staged algorithm based on quadratic discriminant analysis technique for machine learning.

Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events.

PURPOSE: To assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events. MATERIALS AND METHODS: This multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS). RESULTS: TIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476-1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively. CONCLUSIONS: Although TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.

Radiofrequency Ablation of Solid Benign Thyroid Nodules.

Symptomatic solid benign thyroid nodules may present either as nonfunctioning nodules causing compressive symptoms or as hyperfunctioning nodules causing symptoms of hyperthyroidism. While surgical resection or radioiodine ablation of these nodules can be performed, percutaneous radiofrequency ablation (RFA) of benign solid thyroid nodules has been shown to be a safe and effective alternative in select patients. Preprocedural evaluation should include a history focusing on signs and symptoms of thyroid dysfunction, a physical exam, thyroid ultrasound, thyroid function tests, and discussion of key intraprocedural details with the patient such as the anesthesia plan and risks. Thyroid RFA can be safely performed as an outpatient procedure with less than 2% major and minor complication rates. This report will focus on the basic technique of performing RFA for symptomatic thyroid nodules.

ROR activation by Nobiletin enhances antitumor efficacy via suppression of IκB/NF-κB signaling in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by poor response to standard therapies and therefore unfavorable clinical outcomes. Better understanding of TNBC and new therapeutic strategies are urgently needed. ROR nuclear receptors are multifunctional transcription factors with important roles in circadian pathways and other processes including immunity and tumorigenesis. Nobiletin (NOB) is a natural compound known to display anticancer effects, and our previous studies showed that NOB activates RORs to enhance circadian rhythms and promote physiological fitness in mice. Here, we identified several TNBC cell lines being sensitive to NOB, by itself or in combination. Cell and xenograft experiments showed that NOB significantly inhibited TNBC cell proliferation and motility in vitro and in vivo. ROR loss- and gain-of-function studies showed concordant effects of the NOB-ROR axis on MDA-MB-231 cell growth. Mechanistically, we found that NOB activates ROR binding to the ROR response elements (RRE) of the IκBα promoter, and NOB strongly inhibited p65 nuclear translocation. Consistent with transcriptomic analysis indicating cancer and NF-κB signaling as major pathways altered by NOB, p65-inducible expression abolished NOB effects, illustrating a requisite role of NF-κB suppression mediating the anti-TNBC effect of NOB. Finally, in vivo mouse xenograft studies showed that NOB enhanced the antitumor efficacy in mammary fat pad implanted TNBC, as a single agent or in combination with the chemotherapy agent Docetaxel. Together, our study highlights an anti-TNBC mechanism of ROR-NOB via suppression of NF-κB signaling, suggesting novel preventive and chemotherapeutic strategies against this devastating disease.

The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding.

Autophagy dysregulation is implicated in metabolic diseases, including type 2 diabetes. However, the mechanism by which the autophagy machinery regulates metabolism is largely unknown. Autophagy is generally considered a degradation process via lysosomes. Here, we unveil a metabolically important non-cell-autonomous, non-degradative mechanism regulated by the essential autophagy protein Becn1 in adipose tissue. Upon high-fat diet challenge, autophagy-hyperactive Becn1F121A mice show systemically improved insulin sensitivity and enhanced activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis, via a non-cell-autonomous mechanism mediated by adiponectin, an adipose-derived metabolic hormone. Adipose-specific Becn1F121A expression is sufficient to activate AMPK in non-adipose tissues and improve systemic insulin sensitivity by increasing adiponectin secretion. Further, Becn1 enhances adiponectin secretion by interacting with components of the exocyst complex via the coiled-coil domain. Together, our study demonstrates that Becn1 improves insulin sensitivity by facilitating adiponectin secretion through binding the exocyst in adipose tissue.

Percutaneous approach options for embolization of endoleak after iliac artery aneurysm repair: stick the sac or stick the gluteal artery.

Internal iliac artery aneurysms (IIAAs), isolated or associated with abdominal aortic aneurysms, are at rupture risk with growth. Treatment is recommended when symptomatic or greater than 3 cm. Surgical or endovascular therapy should exclude the arterial origin and outflow branches. If all outflow branches are not completely embolized, an endoleak can develop, pressurizing the sac leading to growth and rupture. Accessing the arteries involved can be technically challenging and understanding potential targets is critical. We describe two percutaneous approaches for treatment: percutaneously accessing the sac from an anterior trans-iliopsoas approach and percutaneously accessing the gluteal artery from a posterior approach.

An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system.

Drug abuse is a foremost public health problem. Cocaine is a widely abused drug worldwide that produces various reward-related behaviors. The mechanisms that underlie cocaine-induced disorders are unresolved, and effective treatments are lacking. Here, we found that an autophagy-related protein Becn2 is a previously unidentified regulator of cocaine reward behaviors. Becn2 deletion protects mice from cocaine-stimulated locomotion and reward behaviors, as well as cocaine-induced dopamine accumulation and signaling, by increasing presynaptic dopamine receptor 2 (D2R) autoreceptors in dopamine neurons. Becn2 regulates D2R endolysosomal trafficking, degradation, and cocaine-induced behaviors via interacting with a D2R-bound adaptor GASP1. Inactivating Becn2 by upstream autophagy inhibitors stabilizes striatal presynaptic D2R, reduces dopamine release and signaling, and prevents cocaine reward in normal mice. Thus, the autophagy protein Becn2 is essential for cocaine psychomotor stimulation and reward through regulating dopamine neurotransmission, and targeting Becn2 by autophagy inhibitors is a potential strategy to prevent cocaine-induced behaviors.

Adsorptive removal and recovery of organic pollutants from wastewater using waste paper-derived carbon-based aerogel.

In this study, carbon-based aerogels derived from waste paper (CWP) were explored as an efficent adsorbent to remove organic pollutants including phenol (Ph) and 2-chlorophenol (2CP) from wastewater. CWP exhibited a highly porous structure and large specific surface area of 892 m2 g-1, which facilitated the adsorption of Ph and 2CP in wastewater. The adsorption behavior of Ph and 2CP on CWP could be well described by the pseudo-second-order kinetics and Langmuir isotherm models. Based on the Langmuir isotherm, the maximum adsorption capacities of CWP for Ph and 2CP were 238 and 278 mg g-1, respectively, and these values were much higher than those of other adsorbents. The removal of the organic pollutants mainly occurred through electrostatic attraction, pore-filling, hydrogen bonding, and π-π interactions. The CWP can be directly applied for the removal of Ph and 2CP at low concentration (<200 mg L-1) in the wastewater, while they can be used with additional pre-treatment for wastewater containing high concentration of organic pollutants. The adsorptive recovery of organic compounds and potential reuse of treated wastewater were also discussed. This work provides an efficient approach to produce effective adsorbent for the removal and recovery of chemicals from wastewater.

Effects of conditioned media from human umbilical cord blood-derived mesenchymal stem cells in the skin immune response.

Atopic dermatitis (AD) is an inflammatory skin disease in which type 2 allergic inflammation plays a critical role. In this study, the anti-inflammatory effect of conditioned media from human umbilical cord blood-derived mesenchymal stem cells (USC-CM) was investigated in order to apply it as an effective treatment with a low risk of side effects that can overcome the limitations of AD treatment which is currently in use. We found that USC-CM has various growth factors and cytokines associated with anti-inflammatory effect. RT-PCR and ELISA analysis showed that USC-CM inhibited the levels of type 2 cytokine and chemokine Thymus and activation-regulated chemokine (TARC), TNF-α and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells. In addition, USC-CM inhibited IL-4 and IL-13 levels in Th2 cells. Therefore, the results of our study demonstrated that USC-CM has anti-inflammatory effect in TNF-α/IFN-γ-stimulated HaCaT cells which associated with the inhibition of the immunoglobulin (IgE) secretion by activating B cell line. Our In vivo results showed that when the USC-CM was applied to lesions of patients with the mild AD for 4 weeks, the skin barrier was strengthened by increasing the level of Corneometer and decreasing the value of transepidermal water loss (TEWL). In conclusion, the results suggest that USC-CM may have therapeutic effect for AD as cosmetics and drug materials.

Differences in negative predictive value of prostate MRI based in men with suspected or known cancer.

OBJECTIVE: To compare the negative predictive value (NPV) of multiparametric MRI for Gleason score (GS) ≥ 3+4 cancer and evaluate predictors of these tumors in men with suspected disease and under active surveillance (AS). MATERIALS AND METHODS: This retrospective study included 38 men with suspected prostate cancer and 38 under AS with scans assigned PI-RADS v2 scores 1 or 2 between May 2016 and September 2017. Biopsy results were no cancer, GS = 3+3, or GS ≥ 3+4. Pre-MRI PSA, gland volume, and PSA density were recorded. Chi-square, equality of proportions, and logistic regressions were used to analyze the data. RESULTS: Intermediate to high-grade cancer was found in 12.8% (95% CI = 2.3-23.3) and 35.9% (95% CI = 20.8-50.9) of men with suspected cancer, and under AS (p = 0.02), respectively. The NPV for GS ≥ 3+4 were 87.2% (suspected cancer; 76.7-97.7) and 64.1% (AS; 49.0-79.2). In neither group PSA significantly predicted cancer grade (p = 0.75 and 0.63). Although it did not reach conventional statistical significance, PSA density was a good predictor of cancer grade in men with suspected disease (p = 0.06), but not under AS (p = 0.62). CONCLUSION: The NPV of multiparametric MRI for GS ≥ 3+4 is higher in men with suspected prostate cancer than in men under AS. PSA density ≤ 0.15 improved the prediction of intermediate to high-grade disease in patients without known cancer.

OBJETIVO: Comparar o valor preditivo negativo (VPN) da RM multiparamétrica da próstata para o diagnóstico de tumores escore de Gleason (EG) ≥ 3+4 e avaliar os preditores desses tumores em homens com suspeita de doença e nos sob vigilância ativa (VA). MATERIAIS E MÉTODOS: Este estudo retrospectivo incluiu 38 homens com suspeita de câncer de próstata e 38 em VA com RM, aos quais foram atribuídos escores PI-RADS v2 1 ou 2 entre maio de 2016 e setembro de 2017. Os resultados da biópsia foram ausência de câncer, câncer EG = 3+3 ou câncer EG ≥ 3+4. PSA pré-RM, volume da glândula e densidade de PSA foram anotados. Qui-quadrado, igualdade de proporções e regressões logísticas foram utilizados para analisar os dados. RESULTADOS: Câncer de grau intermediário a alto grau foi encontrado em 12,8% (IC 95% = 2,3­23,3) e 35,9% (IC 95% = 20,8­50,9) dos homens com suspeita de câncer e nos sob VA (p = 0,02), respectivamente. O VPN para GS ≥ 3+4 foi 87,2% (suspeita de câncer; IC 95% = 76,7­97,7) e 64,1% (VA; IC 95% = 49,0­79,2). Em nenhum dos grupos o PSA previu significativamente o grau de câncer (p = 0,75 e 0,63. Embora não tenha alcançado o limiar de significância estatística usual, a densidade de PSA foi um bom preditor de grau de câncer em homens com suspeita de doença (p = 0,06), mas não sob VA (p = 0,62). CONCLUSÃO: O VPN da RM multiparamétrica para GS ≥ 3+4 é maior em homens com suspeita de câncer de próstata do que em homens sob VA. Uma densidade de PSA ≤ 0,15 melhorou a previsão de doença de grau intermediário a alto grau em pacientes sem diagnóstico prévio de câncer.

Differences in negative predictive value of prostate MRI based in men with suspected or known cancer / Diferenças no valor preditivo negativo da ressonância magnética da próstata baseada em homens com câncer suspeito ou conhecido

Abstract Objective: To compare the negative predictive value (NPV) of multiparametric MRI for Gleason score (GS) ≥ 3+4 cancer and evaluate predictors of these tumors in men with suspected disease and under active surveillance (AS). Materials and Methods: This retrospective study included 38 men with suspected prostate cancer and 38 under AS with scans assigned PI-RADS v2 scores 1 or 2 between May 2016 and September 2017. Biopsy results were no cancer, GS = 3+3, or GS ≥ 3+4. Pre-MRI PSA, gland volume, and PSA density were recorded. Chi-square, equality of proportions, and logistic regressions were used to analyze the data. Results: Intermediate to high-grade cancer was found in 12.8% (95% CI = 2.3-23.3) and 35.9% (95% CI = 20.8-50.9) of men with suspected cancer, and under AS (p = 0.02), respectively. The NPV for GS ≥ 3+4 were 87.2% (suspected cancer; 76.7-97.7) and 64.1% (AS; 49.0-79.2). In neither group PSA significantly predicted cancer grade (p = 0.75 and 0.63). Although it did not reach conventional statistical significance, PSA density was a good predictor of cancer grade in men with suspected disease (p = 0.06), but not under AS (p = 0.62). Conclusion: The NPV of multiparametric MRI for GS ≥ 3+4 is higher in men with suspected prostate cancer than in men under AS. PSA density ≤ 0.15 improved the prediction of intermediate to high-grade disease in patients without known cancer.

Resumo Objetivo: Comparar o valor preditivo negativo (VPN) da RM multiparamétrica da próstata para o diagnóstico de tumores escore de Gleason (EG) ≥ 3+4 e avaliar os preditores desses tumores em homens com suspeita de doença e nos sob vigilância ativa (VA). Materiais e Métodos: Este estudo retrospectivo incluiu 38 homens com suspeita de câncer de próstata e 38 em VA com RM, aos quais foram atribuídos escores PI-RADS v2 1 ou 2 entre maio de 2016 e setembro de 2017. Os resultados da biópsia foram ausência de câncer, câncer EG = 3+3 ou câncer EG ≥ 3+4. PSA pré-RM, volume da glândula e densidade de PSA foram anotados. Qui-quadrado, igualdade de proporções e regressões logísticas foram utilizados para analisar os dados. Resultados: Câncer de grau intermediário a alto grau foi encontrado em 12,8% (IC 95% = 2,3-23,3) e 35,9% (IC 95% = 20,8-50,9) dos homens com suspeita de câncer e nos sob VA (p = 0,02), respectivamente. O VPN para GS ≥ 3+4 foi 87,2% (suspeita de câncer; IC 95% = 76,7-97,7) e 64,1% (VA; IC 95% = 49,0-79,2). Em nenhum dos grupos o PSA previu significativamente o grau de câncer (p = 0,75 e 0,63. Embora não tenha alcançado o limiar de significância estatística usual, a densidade de PSA foi um bom preditor de grau de câncer em homens com suspeita de doença (p = 0,06), mas não sob VA (p = 0,62). Conclusão: O VPN da RM multiparamétrica para GS ≥ 3+4 é maior em homens com suspeita de câncer de próstata do que em homens sob VA. Uma densidade de PSA ≤ 0,15 melhorou a previsão de doença de grau intermediário a alto grau em pacientes sem diagnóstico prévio de câncer.

Preconditioning with interleukin-1 beta and interferon-gamma enhances the efficacy of human umbilical cord blood-derived mesenchymal stem cells-based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3-dioxygenase activity in dextran sulfate sodium-induced colitis.

Preconditioning with inflammatory cytokines has improved mesenchymal stem cells characteristics, including differentiation and immunomodulating functions. In this study, we developed a preconditioning combination strategy using interleukin-1beta (IL-1ß) and interferon-gamma (IFN-γ) to enhance the immuneregulatory ability of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Our results showed that hUCB-MSCs preconditioned with IL-1ß and IFN-γ (primed hUCB-MSCs) created a statistically significant decrease in peripheral blood mononuclear cell proliferation, indicating that their immunosuppressive ability was increased. The secretion of PGE2, cyclooxygenase 2 mRNA expression, and indoleamine 2,3-dioxygenase (IDO) mRNA expression in primed hUCB-MSCs was significantly higher than those in the untreated hUCB-MSCs or the IL-1ß or IFN-γ only treated hUCB-MSCs. When inhibitors of IDO and PGE2 were treated, peripheral blood mononuclear cell proliferation, which is inhibited by primed hUCB-MSCs, was recovered. We found that Th1 T cell differentiation was also inhibited by PGE2 and IDO in the primed hUCB-MSCs, and Tregs differentiation was increased by PGE2 and IDO in the primed hUCB-MSCs. Furthermore, the primed hUCB-MSCs as well as supernatants increase CD4+ T cells migration. We demonstrated the therapeutic effects of primed hUCB-MSCs in dextran sulfate sodium-induced colitis model. In conclusion, we have demonstrated that primed hUCB-MSCs simultaneously enhance PGE2 and IDO and greatly improve the immunoregulatory capacity of MSCs, and we have developed an optimal condition for pretreatment of MSCs for the treatment of immune diseases. Our results raise the possibility that the combination of PGE2 and IDO could be therapeutic mediators for controlling immunosuppression of MSCs.

Integrated microfluidic pneumatic circuit for point-of-care molecular diagnostics.

Developing simple, portable, rapid, and easy-to-use diagnostic technologies is essential for point-of-care (POC) blood molecular testing. Integrated microfluidic devices that include the functionalities of blood separation, microfluidic pumping, and molecular detection are desirable for POC testing; however, current technologies still rely on off-chip sample processing or require bulky equipment. We report a fully-integrated microfluidic diagnostic device, i.e., an integrated pneumatic microfluidic circuit (iPC), that can autonomously pump whole blood, continuously sort blood plasma, and readily enable blood plasma proteomic analysis. The iPC contains vacuum pillars as a vacuum source and waste reservoir, as well as microchannels connecting the pillars as a plasma separator or a flow stabilizer. We combined the iPC and a miniaturized fluorescence microscope to create a portable diagnostic platform that enables fluorescence-based biomarker detection. First, we performed systematic parametric studies to establish design rules for determining the transport and distribution of fluid streams in the iPC. We then demonstrated the capability of the iPC-based diagnostic platform by successfully separating blood plasma from microliter quantities of whole blood while simultaneously quantifying thrombin in blood samples using an aptamer beacon within 5 min of sample injection. Our platform holds potential as a rapid, field-deployable, essentially universal diagnostic tool in POC settings.

Primate-specific miR-944 activates p53-dependent tumor suppression in human colorectal cancers.

As cancers with a high incidence rate, colorectal cancers are a main cause of cancer-related death. MicroRNAs are often deregulated in cancers. The primate-specific miR-944, located in a p63 intron, is known to be highly expressed in patients exhibiting low colorectal cancer recurrence rates. However, the biological functions of miR-944 in colorectal cancers remain unclear. In this study, we found that miR-944 was downregulated in colorectal cancer tissues, and inhibited cancer cell growth in a xenograft mouse model. The overexpression of miR-944 caused G1 phase arrest and increased p53 expression in cancer cells. p53 stability was enhanced by miR-944s targeting E3 ligases COP1 and MDM2. Overexpression of COP1 and MDM2 restored cell growth inhibition caused by miR-944. Taken together, our results suggest that miR-944 acts as a potential tumor suppressor in colorectal cancers through the ubiquitin-proteasome system.

Conditioned media from human umbilical cord blood-derived mesenchymal stem cells stimulate rejuvenation function in human skin.

Developing treatments that inhibit skin aging is an important research project. Rejuvenation, which focuses on prevention of skin aging, is one of the major issues. Recent studies suggested that mesenchymal stem cells (MSCs) secrete many cytokines, which are important in wound healing. In this study, we investigated the effect of human umbilical cord blood-derived mesenchymal stem cells conditioned media (USC-CM) in cutaneous wound healing and collagen synthesis. We found that USC-CM has many useful growth factors associated with skin rejuvenation, such as Epithelial Growth Factor (EGF), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), Hepatocyte Growth Factor (HGF), Collagen type 1, and especially, one of the rejuvenation factors, the growth differentiation factor-11 (GDF-11). Our in vitro results showed that USC-CM stimulate growth and extracellular matrix (ECM) production of Human Dermal Fibroblasts (HDFs) compared to those of other MSCs conditioned media (CM) from different origins. Moreover, we evaluated the roles of GDF-11. The results showed that GDF-11 accelerates growth, migration and ECM production of HDFs. Our In vivo results showed that topical treatment of USC-CM showed anti-wrinkle effect and significantly increased dermal density in women. In conclusion, USC-CM has various useful growth factors including GDF-11 that can stimulate skin rejuvenation by increasing growth and ECM production of HDFs.

Flexible transparent conducting films with embedded silver networks composed of bimodal-sized nanoparticles for heater application.

A facile one-pot synthetic method for preparing the Ag nanoparticle inks with a bimodal size distribution was newly devised and they were successfully employed as a conducting filler to form the metal-mesh type transparent conducting electrodes on the flexible substrate. Bimodal-sized Ag nanoparticles were synthesized through the polyol process, and their size variation was occurred via finely tuned composition ratio between Ag+ ions and polymeric capping agents. The prepared bimodal-sized Ag nanoparticles exhibited the form of well-dispersed Ag nanoparticle inks without adding any dispersants and dispersion process. By filling the patterned micro-channels engraved on the flexible polymer substrate using a bimodal-sized Ag nanoparticle ink, a metal-mesh type transparent electrode (transmittance: 90% at 550 nm, haze: 1.5, area: 8 × 8 cm2) was fabricated. By applying DC voltage to the mesh type electrode, a flexible transparent joule heater was successfully achieved with a performance of 4.5 °C s-1 heat-up rate at a low input power density.