Search

Facial inference, a cornerstone of person perception, has traditionally been studied through human judgments about personality traits and abilities based on people's faces. Recent advances in artificial intelligence (AI) have introduced new dimensions to this field, employing machine learning algorithms to reveal people's character, capabilities, and social outcomes based just on their faces. This review examines recent research on human and AI-based facial inference across psychology, business, computer science, legal, and policy studies to highlight the need for scientific consensus on whether or not people's faces can reveal their inner traits, and urges researchers to address the critical concerns around epistemic validity, practical relevance, and societal welfare before recommending AI-based facial inference for consequential uses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Autophagy is known to suppress tumor initiation by removing genotoxic stresses in normal cells. Conversely, autophagy is also known to support tumor progression by alleviating metabolic stresses in neoplastic cells. Centered on this pro-tumor role of autophagy, there have been many clinical trials to treat cancers through systemic blocking of autophagy. Such systemic inhibition affects both tumor cells and non-tumor cells, and the consequence of blocked autophagy in non-tumor cells in the context of tumor microenvironment is relatively understudied. Here, we examined the effect of autophagy-deficient myeloid cells on the progression of autophagy-competent tumors. We found that blocking autophagy only in myeloid cells modulated tumor progression markedly but such effects were context dependent. In a tumor implantation model, the growth of implanted tumor cells was substantially reduced in mice with autophagy-deficient myeloid cells; T cells infiltrated deeper into the tumors and were responsible for the reduced growth of the implanted tumor cells. In an oncogene-driven tumor induction model, however, tumors grew faster and metastasized more in mice with autophagy-deficient myeloid cells. These data demonstrate that the autophagy status of myeloid cells plays a critical role in tumor progression, promoting or suppressing tumor growth depending on the context of tumor-myeloid cell interactions. This study indicates that systemic use of autophagy inhibitors in cancer therapy may have differential effects on rates of tumor progression in patients due to effects on myeloid cells and that this warrants more targeted use of selective autophagy inhibitors in a cancer therapy in a clinical setting., Competing Interests: Conflicts of Interest All authors declare no conflict of interest.

Background: Assessing and managing patient anxiety is essential to reduce postoperative complications in elderly patients. However, monitoring patient anxiety objectively is impossible. This study aimed to investigate the correlation between the level of fNIRS signals and anxiety in patients aged 65 and older undergoing artificial joint replacement surgery. Material and Methods: Sixty patients aged ≥65 years scheduled for elective total knee arthroplasty under spinal anesthesia were included. To differentiate the degree of anxiety, the patients were randomly divided into three groups, each consisting of 20 patients (group 1: administered normal saline as a placebo; groups 2 and 3: administered dexmedetomidine at a rate of 0.2 and 0.5 μg/kg/h, respectively, for 10 min). Functional near-infrared spectroscopy was measured continuously for 10 min in each session (session 1: pre-anesthetic period; session 2: immediately after the spinal anesthesia period; session 3: normal saline or dexmedetomidine receiving period) in all patients. Vital signs were measured thrice at 5-min intervals during each session. State-Trait Anxiety Inventory -S (STAI-S) and Ramsay Sedation Scale (RSS) scores were assessed at the end of each session. Results: The STAI-S score was significantly correlated with power of bandwidth ( p = 0.034). In addition, the RSS score was significantly correlated with BW 1, 2, and 3 ( p = 0.010, p < 0.001, and p = 0.003, respectively). Conclusion: The STAI-S score and BW 3 were significantly correlated, suggesting that fNIRS might help objectively and directly monitor anxiety levels., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Video head impulse tests (vHITs), assessing the vestibulo-ocular reflex (VOR), may be helpful in the differential diagnosis of acute dizziness. We aimed to investigate vHITs in patients with acute posterior circulation stroke (PCS) to examine whether these findings could exhibit significant abnormalities based on lesion locations, and to evaluate diagnostic value of vHIT in differentiating dizziness between PCS and vestibular neuritis (VN)., Methods: We prospectively recruited consecutive 80 patients with acute PCS and analyzed vHIT findings according to the presence of dorsal brainstem stroke (DBS). We also compared vHIT findings between PCS patients with dizziness and a previously studied VN group ( n  = 29). Receiver operating characteristic (ROC) analysis was performed to assess the performance of VOR gain and its asymmetry in distinguishing dizziness between PCS and VN., Results: Patients with PCS underwent vHIT within a median of 2 days from stroke onset. Mean horizontal VOR gain was 0.97, and there was no significant difference between PCS patients with DBS ( n = 15) and without ( n = 65). None exhibited pathologic overt corrective saccades. When comparing the PCS group with dizziness ( n  = 40) to the VN group ( n  = 29), patients with VN demonstrated significantly lower mean VOR gains in the ipsilesional horizontal canals (1.00 vs. 0.57, p  < 0.001). VOR gain and their asymmetry effectively differentiated dizziness in the PCS from VN groups, with an area under the ROC curve of 0.86 (95% CI 0.74-0.98) and 0.91 (95% CI 0.83-0.99, p  < 0.001), respectively., Conclusion: Significantly abnormal vHIT results were rare in patients with acute PCS, even in the presence of DBS. Moreover, vHIT effectively differentiated dizziness between PCS and VN, highlighting its potential for aiding differential diagnosis of acute dizziness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Ha, Lee, Park, Kim, Chang, Kang, Kwon, Kim, Park and Lee.)

Motivation: Kethoxal-assisted ssDNA sequencing (KAS-seq) is rapidly gaining popularity as a robust and effective approach to study the nascent dynamics of transcriptionally engaged RNA polymerases through profiling of genome-wide single-stranded DNA (ssDNA). Its latest variant, spKAS-seq, a strand-specific version of KAS-seq, has been developed to map genome-wide R-loop structures by detecting imbalances of ssDNA on two strands. However, user-friendly, open-source computational tools tailored for KAS-seq data are still lacking., Results: Here, we introduce KAS-Analyzer, the first comprehensive computational framework aimed at streamlining and enhancing the analysis and interpretation of KAS-seq and spKAS-seq data. In addition to standard analyses, KAS-Analyzer offers many novel tools specifically designed for KAS-seq data, including, but not limited to: calculation of transcription-related metrics, identification of single-stranded transcribing (SST) enhancers, high-resolution mapping of R-loops, and differential RNA polymerase activity analysis. We provided a detailed overview of KAS-seq data and its diverse applications through the implementation of KAS-Analyzer. Using the example time-course KAS-seq datasets, we further showcase the robust capabilities of KAS-Analyzer for investigating dynamic transcriptional regulatory programs in response to UVB radiation., Availability and Implementation: KAS-Analyzer is available at https://github.com/Ruitulyu/KAS-Analyzer., Competing Interests: The University of Chicago has filed a patent application on KAS-seq. C.H. is a scientific founder and a member of the scientific advisory board of Accent Therapeutics, Inc., Inferna Green, Inc., and AccuraDX Inc. T.W. is a shareholder of AccuraDX Inc., (© The Author(s) 2023. Published by Oxford University Press.)

This study aimed to investigate the overall effects of a tailored dietary education program for older adult patients on hemodialysis (HD) based on self-efficacy theory, dietary knowledge and habits, nutritional intake, and biochemical parameters. A nonequivalent control group pre-test-post-test design was conducted for 8 weeks. The experimental and control groups received a weekly nutritional program and standard nursing care with an additional educational session, respectively. A clinical survey was conducted before and after the intervention. After the intervention, self-efficacy, dietary knowledge, and dietary habits were higher in the experimental group than in the control group. Moreover, carbohydrate, phosphorus, and sodium intake significantly decreased post-intervention in the experimental group but not in the control group. The dietary education program for older HD patients showed positive effects on boosting their self-efficacy, increasing dietary knowledge, improving dietary habits, and decreasing carbohydrate, calcium, phosphorus, and sodium intake.

Intramuscular fatty infiltration in muscle injuries and diseases, caused by aberrant adipogenesis of fibro-adipogenic progenitors, negatively impacts function. Intramuscular delivery of wingless-type MMTV integration site family 7a (WNT7A) offers a promising strategy to stimulate muscle regeneration, but its effects on adipogenic conversion of fibro-adipogenic progenitors remain unknown. Here, we show that WNT7A decreases adipogenesis of fibro-adipogenic progenitors (FAPs) by inducing nuclear localization of Yes-associated protein (YAP) through Rho in a β-CATENIN-independent manner and by promoting nuclear retention of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in differentiating FAPs. Furthermore, intramuscular injection of WNT7A in vivo effectively suppresses fatty infiltration in mice following glycerol-induced injury. Our results collectively suggest WNT7A as a potential protein-based therapeutic for diminishing adipogenesis of FAPs and intramuscular fatty infiltration in pathological muscle injuries or diseases., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Excessive, high doses of ultraviolet B (UVB) UVB irradiation are known to cause skin cancer, aging and immunosuppression. On the contrary, moderate low doses of UVB irradiation are shown to be essential and beneficial to human health, including a tumor-suppressive effect. However, the mechanism by which low levels of UVB suppress tumorigenesis remains unclear. Here, using tumor-bearing mouse models, we show that moderate low repetitive UVB irradiation increases the percentage of activated CD4 + and CD8 + T cells, and CD103 + conventional type 1 dendritic cells (cDC1s), while it decreases the number of immunosuppressive, M2-like macrophages in the tumors. Finally, in mice, deletion of Batf3, a transcription factor critical for the development of conventional dendritic cells, including the CD103 + cDC1s, showed increased tumor growth in both sham- and UVB-irradiated mice. Our findings demonstrate that moderate low UVB irradiation inhibits M2-like tumor-associated macrophages, increases CD103 + cDC1s and promotes antitumor immunity in mice with an established tumor., (© 2022 American Society for Photobiology.)

The cortical actin cytoskeleton plays a critical role in maintaining intestinal epithelial integrity, and the loss of this architecture leads to chronic inflammation, as seen in inflammatory bowel disease (IBD). However, the exact mechanisms underlying aberrant actin remodeling in pathological states remain largely unknown. Here, we show that a subset of patients with IBD exhibits substantially higher levels of tripartite motif-containing protein 40 (TRIM40), a gene that is hardly detectable in healthy individuals. TRIM40 is an E3 ligase that directly targets Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), an essential kinase involved in promoting cell-cell junctions, markedly decreasing the phosphorylation of key signaling factors critical for cortical actin formation and stabilization. This causes failure of the epithelial barrier function, thereby promoting a long-lived inflammatory response. A mutant TRIM40 lacking the RING, B-box, or C-terminal domains has impaired ability to accelerate ROCK1 degradation-driven cortical actin disruption. Accordingly, Trim40-deficient male mice are highly resistant to dextran sulfate sodium (DSS)-induced colitis. Our findings highlight that aberrant upregulation of TRIM40, which is epigenetically silenced under healthy conditions, drives IBD by subverting cortical actin formation and exacerbating epithelial barrier dysfunction., (© 2023. The Author(s).)

Intrasynovial flexor tendon lacerations of the hand are clinically problematic, typically requiring operative repair and extensive rehabilitation. The small-molecule connective tissue growth factor (CTGF) mimics, oxotremorine M (Oxo-M) and 4-PPBP maleate (4-PPBP), have been shown to improve tendon healing in small animal models by stimulating the expansion and differentiation of perivascular CD146+ cells. To enhance intrasynovial flexor tendon healing, small-molecule CTGF mimics were delivered to repaired canine flexor tendons via porous sutures. In vitro studies demonstrated that Oxo-M and 4-PPBP retained their bioactivity and could be released from porous sutures in a sustained manner. However, in vivo delivery of the CTGF mimics did not improve intrasynovial tendon healing. Histologic analyses and expression of tenogenic, extracellular matrix, inflammation, and remodeling genes showed similar outcomes in treated and untreated repairs across two time points. Although in vitro experiments revealed that CTGF mimics stimulated robust responses in extrasynovial tendon cells, there was no response in intrasynovial tendon cells, explaining the lack of in vivo effects. The results of the current study indicate that therapeutic strategies for tendon repair must carefully consider the environment and cellular makeup of the particular tendon for improving the healing response., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Global genome repair (GGR), a subpathway of nucleotide excision repair, corrects bulky helix-distorting DNA lesions across the whole genome and is essential for preventing mutagenesis and skin cancer. Here, we show that METTL14 (methyltransferase-like 14), a critical component of the N 6 -methyladenosine (m 6 A) RNA methyltransferase complex, promotes GGR through regulating m 6 A mRNA methylation-mediated DDB2 translation and suppresses ultraviolet B (UVB) radiation-induced skin tumorigenesis. UVB irradiation down-regulates METTL14 protein through NBR1-dependent selective autophagy. METTL14 knockdown decreases GGR and DDB2 abundance. Conversely, overexpression of wild-type METTL14 but not its enzymatically inactive mutant increases GGR and DDB2 abundance. METTL14 knockdown decreases m 6 A methylation and translation of the DDB2 transcripts. Adding DDB2 reverses the GGR repair defect in METTL14 knockdown cells, indicating that METTL14 facilitates GGR through regulating DDB2 m 6 A methylation and translation. Similarly, knockdown of YTHDF1, an m 6 A reader promoting translation of m 6 A-modified transcripts, decreases DDB2 protein levels. Both METTL14 and YTHDF1 bind to the DDB2 transcript. In mice, skin-specific heterozygous METTL14 deletion increases UVB-induced skin tumorigenesis. Furthermore, METTL14 as well as DDB2 is down-regulated in human and mouse skin tumors and by chronic UVB irradiation in mouse skin, and METTL14 level is associated with the DDB2 level, suggesting a tumor-suppressive role of METTL14 in UVB-associated skin tumorigenesis in association with DDB2 regulation. Taken together, these findings demonstrate that METTL14 is a target for selective autophagy and acts as a critical epitranscriptomic mechanism to regulate GGR and suppress UVB-induced skin tumorigenesis., Competing Interests: Competing interest statement: C.H. is a scientific founder and a member of the scientific advisory board of Accent Therapeutics, Inc.

The development of a vaccine to prevent Zika virus (ZIKV) infection has been one of the priorities in infectious disease research in recent years. There have been numerous attempts to develop an effective vaccine against ZIKV. It is imperative to choose the safest and the most effective ZIKV vaccine from all candidate vaccines to control this infection globally. We have employed a dual serotype of prime-boost recombinant vesicular stomatitis virus (VSV) vaccine strategy, to develop a ZIKV vaccine candidate, using a type 1 IFN-receptor knock-out ( Ifnar -/- ) mouse model for challenge studies. Prime vaccination with an attenuated recombinant VSV Indiana serotype (rVSV Ind ) carrying a genetically modified ZIKV envelope (E) protein gene followed by boost vaccination with attenuated recombinant VSV New Jersey serotype (rVSV NJ ) carrying the same E gene induced robust adaptive immune responses. In particular, rVSV carrying the ZIKV E gene with the honeybee melittin signal peptide (msp) at the N terminus and VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the C terminus of the E gene induced strong protective immune responses. This vaccine regimen induced highly potent neutralizing antibodies and T cell responses in the absence of an adjuvant and protected Ifnar -/- mice from a lethal dose of the ZIKV challenge.

Thymosin beta-4 (Tβ4) is an actin-sequestering peptide that plays important roles in regeneration and remodeling of injured tissues. However, its function in a naturally occurring pathogenic bacterial infection model has remained elusive. We adopted Tβ4-overexpressing transgenic (Tg) mice to investigate the role of Tβ4 in acute pulmonary infection and systemic sepsis caused by Legionella pneumophila Upon infection, Tβ4-Tg mice demonstrated significantly lower bacterial loads in the lung, less hyaline membranes and necrotic abscess, with lower interstitial infiltration of neutrophils, CD4 + , and CD8 + T cells. Bronchoalveolar lavage fluid of Tβ4-Tg mice possessed higher bactericidal activity against exogenously added L. pneumophila , suggesting that constitutive expression of Tβ4 could efficiently control L. pneumophila Furthermore, qPCR analysis of lung homogenates demonstrated significant reduction of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), which primarily originate from lung macrophages, in Tβ4-Tg mice after pulmonary infection. Upon L. pneumophila challenge of bone marrow-derived macrophages (BMDM) in vitro , secretion of IL-1β and TNF-α proteins was also reduced in Tβ4-Tg macrophages, without affecting their survival. The anti-inflammatory effects of BMDM in Tβ4-Tg mice on each cytokine were affected when triggering with tlr2, tlr4, tlr5, or tlr9 ligands, suggesting that anti-inflammatory effects of Tβ4 are likely mediated by the reduced activation of Toll-like receptors (TLR). Finally, Tβ4-Tg mice in a systemic sepsis model were protected from L. pneumophila -induced lethality compared to wild-type controls. Therefore, Tβ4 confers effective resistance against L. pneumophila via two pathways, a bactericidal and an anti-inflammatory pathway, which can be harnessed to treat acute pneumonia and septic conditions caused by L. pneumophila in humans., (Copyright © 2021 American Society for Microbiology.)

Purpose/Aim: Knee meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Injuries to the meniscus, particularly with the avascular inner third zone, hardly heal and frequently progress into structural breakdown, followed by the initiation of osteoarthritis. As the importance of meniscus in joint function and diseases is being recognized, the field of meniscus research is growing. Not only development, biology, and metabolism but also injury, repair, and healing of meniscus are being actively investigated. As meniscus functions as an integrated unit of a knee joint, in vivo models with various species have been the predominant method for studying meniscus pathophysiology and for testing healing/regeneration strategies. However, in vivo models for meniscus studies suffer from low reproducibility and high cost. To complement the limitations of in vivo animal models, several types of meniscus explants have been applied as highly controlled, standardized in vitro models to investigate meniscus metabolism, pathophysiology, and repair or regeneration process. This review summarizes and compares the existing meniscus explant models. We also discuss the advantages and disadvantages of each explant model. Conclusion: Despite few outstanding challenges, meniscus explant models have potential to serve as an effective tool for investigations of meniscus metabolism, injury, repair and healing.

CD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160 -/- mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160 -/- mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160 -/- mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160 -/- mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activation.

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N 6 -methyladenosine (m 6 A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m 6 A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m 6 A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m 6 A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma.

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans worldwide. Although hepatitis E is self-limiting without chronic infection development, HEV infection often leads to severe liver diseases causing high mortality in pregnant women in addition to chronic hepatitis and cirrhosis in immunosuppressed patients. In this study, we investigated the effect of a Liriope platyphylla ethanol extract (LPE) on HEV replication. Interestingly, LPE suppressed replication of the genotype 3 HEV replicon. Sequential solvent fractionation revealed that the ethyl acetate (EA) fraction of LPE exerts the most potent inhibitory effects. With the aid of activity-guided fractionation and multi-step column chromatography, spicatoside A was subsequently isolated in the EA fraction of LPE and specifically shown to exert inhibitory effects on replication of the genotype 3 HEV replicon. In addition, spicatoside A interfered with replication of the HEV genotype 3 strain 47832c and expression of HEV ORF2 capsid proteins. Our findings clearly support the potential utility of spicatoside A as an effective anti-HEV agent.

Transient electronics represents an emerging technology whose defining feature is an ability to dissolve, disintegrate or otherwise physically disappear in a controlled manner. Envisioned applications include resorbable/degradable biomedical implants, hardware-secure memory devices, and zero-impact environmental sensors. 2D materials may have essential roles in these systems due to their unique mechanical, thermal, electrical, and optical properties. Here, we study the bioabsorption of CVD-grown monolayer MoS 2 , including long-term cytotoxicity and immunological biocompatibility evaluations in biofluids and tissues of live animal models. The results show that MoS 2 undergoes hydrolysis slowly in aqueous solutions without adverse biological effects. We also present a class of MoS 2 -based bioabsorbable and multi-functional sensor for intracranial monitoring of pressure, temperature, strain, and motion in animal models. Such technology offers specific, clinically relevant roles in diagnostic/therapeutic functions during recovery from traumatic brain injury. Our findings support the broader use of 2D materials in transient electronics and qualitatively expand the design options in other areas.

Dysregulated activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by self-DNA contributes to interferonopathy and promotes autoimmune diseases. To identify potential suppressors of STING-induced type I interferon (IFN) induction, ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-ß promoter activation. Notably, 70% ethanol extract of Cephalotaxus koreana specifically down-regulated STING-induced, but not TBK1- or IRF3-induced, IFN-ß promoter activity. The compounds exerting inhibitory activity specifically against STING-mediated IFN-ß promoter activation were identified as ester alkaloids isolated from the genus, Cephalotaxus, homoharringtonine and harringtonine. Furthermore, these two compounds inhibited 2'3'-cGAMP-induced IFN-stimulated gene expression and interaction between STING and TBK1. These suppressive effects were not observed with cephalotaxine devoid of the ester side-chain. Our data support the potential utility of homoharringtonine and harringtonine to treat STING-associated interferonopathy and autoimmune diseases.

The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia's megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans.

Development of CNT-based CD4 + T cell imunosensors remains in its infancy due to the poor immobilization efficiency, lack of reproducibility, and difficulty in providing linear quantification. Here, we developed a fully-integrated single wall carbon nanotube (SWCNT)-based immunosensor capable of selective capture and linear quantification of CD4 + T cells with greater dynamic range. By employing repeated two-step oxygen (O 2 ) plasma treatment processes with 35 days of recovery periods, we achieved the enhanced functionalization of the CNT surface and the removal of the byproduct of spray-coated SWCNTs that hinders charge transfer and stable CD4 + T cell sensing. As a result, a linear electrochemical signal was generated in direct proportion to the bound cells. The slope of a SWCNT electrode in a target concentration range (10 2 ~10 6 cells/mL) was 4.55×10 -2 μA per concentration decade, with the lowest detection limit of 1×10 2 cells/mL. Since the reduced number of CD4 + T cell counts in patients' peripheral blood corresponds to the progression of HIV disease, our CD4 + T cell-immunosensor provides a simple and low-cost platform which can fulfill the requirement for the development of point-of-care (POC) diagnostic technologies for human immunodeficiency virus (HIV) patients in resource-limited countries., (Copyright © 2016. Published by Elsevier B.V.)

Legionella pneumophila is an etiological agent of the severe pneumonia known as Legionnaires' disease (LD). This gram-negative bacterium is thought to replicate naturally in various freshwater amoebae, but also replicates in human alveolar macrophages. Inside host cells, legionella induce the production of non-endosomal replicative phagosomes by injecting effector proteins into the cytosol. Innate immune responses are first line defenses against legionella during early phases of infection, and distinguish between legionella and host cells using germline-encoded pattern recognition receptors such as Toll-like receptors , NOD-like receptors, and RIG-I-like receptors, which sense pathogen-associated molecular patterns that are absent in host cells. During pulmonary legionella infections, various inflammatory cells such as macrophages, neutrophils, natural killer (NK) cells, large mononuclear cells, B cells, and CD4+ and CD8+ T cells are recruited into infected lungs, and predominantly occupy interstitial areas to control legionella. During pulmonary legionella infections, the interplay between distinct cytokines and chemokines also modulates innate host responses to clear legionella from the lungs. Recognition by NK cell receptors triggers effector functions including secretion of cytokines and chemokines, and leads to lysis of target cells. Crosstalk between NK cells and dendritic cells, monocytes, and macrophages provides a major first-line defense against legionella infection, whereas activation of T and B cells resolves the infection and mounts legionella-specific memory in the host.

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

On-demand, localized release of drugs in precisely controlled, patient-specific time sequences represents an ideal scenario for pharmacological treatment of various forms of hormone imbalances, malignant cancers, osteoporosis, diabetic conditions and others. We present a wirelessly operated, implantable drug delivery system that offers such capabilities in a form that undergoes complete bioresorption after an engineered functional period, thereby obviating the need for surgical extraction. The device architecture combines thermally actuated lipid membranes embedded with multiple types of drugs, configured in spatial arrays and co-located with individually addressable, wireless elements for Joule heating. The result provides the ability for externally triggered, precision dosage of drugs with high levels of control and negligible unwanted leakage, all without the need for surgical removal. In vitro and in vivo investigations reveal all of the underlying operational and materials aspects, as well as the basic efficacy and biocompatibility of these systems.

Semiconducting materials are central to the development of high-performance electronics that are capable of dissolving completely when immersed in aqueous solutions, groundwater, or biofluids, for applications in temporary biomedical implants, environmentally degradable sensors, and other systems. The results reported here include comprehensive studies of the dissolution by hydrolysis of polycrystalline silicon, amorphous silicon, silicon-germanium, and germanium in aqueous solutions of various pH values and temperatures. In vitro cellular toxicity evaluations demonstrate the biocompatibility of the materials and end products of dissolution, thereby supporting their potential for use in biodegradable electronics. A fully dissolvable thin-film solar cell illustrates the ability to integrate these semiconductors into functional systems.

Single-crystalline silicon nanomembranes (Si NMs) represent a critically important class of material for high-performance forms of electronics that are capable of complete, controlled dissolution when immersed in water and/or biofluids, sometimes referred to as a type of "transient" electronics. The results reported here include the kinetics of hydrolysis of Si NMs in biofluids and various aqueous solutions through a range of relevant pH values, ionic concentrations and temperatures, and dependence on dopant types and concentrations. In vitro and in vivo investigations of Si NMs and other transient electronic materials demonstrate biocompatibility and bioresorption, thereby suggesting potential for envisioned applications in active, biodegradable electronic implants.

We review recent progress in a class of silicon-based electronics that is capable of complete, controlled dissolution when immersed in water or bio-fluids. This type of technology, referred to in a broader sense as transient electronics, has potential applications in resorbable biomedical devices, eco-friendly electronics, environmental sensors, secure hardware systems and others. New results reported here include studies of the kinetics of hydrolysis of nanomembranes of single crystalline silicon in bio-fluids and aqueous solutions at various pH levels and temperatures. Evaluations of toxicity using live animal models and test coupons of transient electronic materials provide some evidence of their biocompatibility, thereby suggesting potential for use in bioresorbable electronic implants., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recent development of flexible/stretchable integrated electronic sensors and stimulation systems has the potential to establish an important paradigm for implantable electronic devices, where shapes and mechanical properties are matched to those of biological tissues and organs. Demonstrations of tissue and immune biocompatibility are fundamental requirements for application of such kinds of electronics for long-term use in the body. Here, a comprehensive set of experiments studies biocompatibility on four representative flexible/stretchable device platforms, selected on the basis of their versatility and relevance in clinical usage. The devices include flexible silicon field effect transistors (FETs) on polyimide and stretchable silicon FETs, InGaN light-emitting diodes (LEDs), and AlInGaPAs LEDs, each on low modulus silicone substrates. Direct cytotoxicity measured by exposure of a surrogate fibroblast line and leachable toxicity by minimum essential medium extraction testing reveal that all of these devices are non-cytotoxic. In vivo immunologic and tissue biocompatibility testing in mice indicate no local inflammation or systemic immunologic responses after four weeks of subcutaneous implantation. The results show that these new classes of flexible implantable devices are suitable for introduction into clinical studies as long-term implantable electronics., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Electrospun polymer nanofibers with entrapped magnetic nanoparticles (magnetic NP-NF) represent a novel scaffold substrate that can be functionalized for single-step isolation and activation of specific lymphocyte subsets. Using a surface-embedded T cell receptor ligand/trigger (anti-CD3 monoclonal antibody), we demonstrate, as proof of principle, the use of magnetic NP-NF to specifically isolate, enrich, and activate CD3(+) T cells from a heterogeneous cell mixture, leading to preferential expansion of CD8(+)CD3(+) T cells. The large surface area, adjustable antibody density, and embedded paramagnetic properties of the NP-NF permitted enhanced activation and expansion; its use represents a strategy that is amenable to an efficient selection process for adoptive cellular therapy as well as for the isolation of other cellular subsets for downstream translational applications.

Objective: Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease ovarian function by causing apoptosis in the ovary, but the mechanism is not fully understood. Therefore, we examined whether TBT increases the expression of adipogenesis-related genes in the ovary and the increased expression of these genes is associated with apoptosis induction., Methods: Three-week-old Sprague-Dawley rats were orally administered TBT (1 or 10 mg/kg body weight) or sesame oil as a control for 7 days. The ovaries were obtained and weighed on day 8, and then they were fixed for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or frozen for RNA extraction. Using the total RNA of the ovaries, adipogenesis- and apoptosis-related genes were analyzed by real-time polymerase chain reaction (PCR)., Results: The ovarian weight was significantly decreased in rats administered 10 mg/kg TBT compared to that in control rats. As determined by the TUNEL assay, the number of apoptotic follicles in ovary was significantly increased in rats administered 10 mg/kg TBT. The real-time PCR results showed that the expression of adipogenesis-related genes such as PPARγ, aP2, CD36, and PEPCK was increased after TBT administration. In addition, apoptosis-related genes such as TNFα and TNFR1 were expressed more in the TBT-administered rats compared with the control rats., Conclusion: The present study demonstrates that TBT induces the expression of adipogenesis- and apoptosis-related genes in the ovary leading to apoptosis in the ovarian follicles. These results suggest that the increased expression of adipogenesis-related genes in the ovary by TBT exposure might induce apoptosis resulting in a loss of ovarian function.

Morphology and vulcanizate properties of EPDM/SBR blends were investigated. AAHR (a mixture of aliphatic and aromatic hydrocarbon resins) was used as a compatibilizer and bis(3-triethoxysilylpropyl)tetrasulfide (TESPT) was used as a coupling agent. The vulcanizate properties and the morphological studies revealed that EPDM and SBR were incompatible, and the addition of AAHR was very effective to enhance the compatibility between EPDM and SBR. The weight percent of bound rubbers was increased with increasing SBR contents. The addition of an AAHR increased the amounts of bound rubbers, and hence the vulcanizate properties such as tear strength and fatigue resistance of the EPDM/SBR blends were improved. The dynamic mechanical analysis and the morphological studies revealed that the addition of TESPT increased the weight of bound rubbers and provided better dispersion of carbon black, resulting in good mechanical properties such as tear strength and fatigue resistance of the vulcanized EPDM/SBR blends. The smaller particle of zinc oxide (i.e., 50 nm > 100 nm > 1000 nm) yielded to the better blending properties of the polymer blend.