Explore the vast range of titles available.

A recent metaanalysis shows that 0.7% of nanoparticles are delivered to solid tumors. This low delivery efficiency has major implications in the translation of cancer nanomedicines, as most of the nanomedicines are sequestered by nontumor cells. To improve the delivery efficiency, there is a need to investigate the quantitative contribution of each organ in blocking the transport of nanoparticles to solid tumors. Here, we hypothesize that the removal of the liver macrophages, cells that have been reported to take up the largest amount of circulating nanoparticles, would lead to a significant increase in the nanoparticle delivery efficiency to solid tumors. We were surprised to discover that the maximum achievable delivery efficiency was only 2%. In our analysis, there was a clear correlation between particle design, chemical composition, macrophage depletion, tumor pathophysiology, and tumor delivery efficiency. In many cases, we observed an 18–150 times greater delivery efficiency, but we were not able to achieve a delivery efficiency higher than 2%. The results suggest the need to look deeper at other organs such as the spleen, lymph nodes, and tumor in mediating the delivery process. Systematically mapping the contribution of each organ quantitatively will allow us to pinpoint the cause of the low tumor delivery efficiency. This, in effect, enables the generation of a rational strategy to improve the delivery efficiency of nanoparticles to solid tumors either through the engineering of multifunctional nanosystems or through manipulation of biological barriers.

Anaerobic reactors are often used to control emissions and capture greenhouse gas (GHG) (biogas, a mixture of carbon dioxide and methane) from waste such as dairy manure. However, real-time monitoring of biogas production during in vitro anaerobic experiments is often challenging mainly due to the unpredictable and low levels of biogas production in a lab reactor system. The application of Internet of Things (IoT) technologies can enhance real-time monitoring of biogas production and GHG emissions from livestock waste. Integration of IoT to anaerobic reactors provides transformative solutions for low-cost monitoring. In this study, an IoT based sensor system that included a highly sensitive Renesas mass flow sensor module for biogas monitoring, Adafruit ported pressure sensor for monitoring of reactor pressure, and ultra-small DROK temperature probe for temperature monitoring was built and implemented for determining the biogas production in anaerobic reactors. Further, impacts of anaerobic process on the reduction of pathogenic organisms such as E. coli were determined using the conventional culture-based method. Results showed that the application of the IoT based system was able to monitor biogas production in real-time, and transmit the data to mobile phone using the ThingSpeak IoT platform offered by MathWorks (MATLAB) (Natick, MA, USA). The difference between the sensor’s biogas volume readings and actual observations over a 30-day time interval was 5–6% indicating the high level of accuracy and low error levels of the system. Further, results showed 1.6–4.8 log reductions of E. coli in effluent of anaerobic reactors indicating substantial impacts of the anaerobic process on pathogen indicator reduction. We anticipate that the system we used in this study has a substantial potential to enhance monitoring of anaerobic reactors and GHG emissions from livestock waste.

The EU has approved the usage of gold as a food additive (E175) and it has been applied in numerous foods for coloring and decoration purposes. Different from the general assumption that edible gold is mainly present in the form of flakes or external coating in foods, this work demonstrated that gold nanoparticles (Au NPs) can be released from gold flakes and extracted under optimized conditions. To support future risk assessment associated with the exposure of Au NPs to human health, an effective approach was established in this study for both size characterization and mass determination of Au NPs released in a commercial gold-containing liquor using Asymmetric Flow Field-flow Fractionation (AF4) hyphenated with Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Our results showed that no Au NPs were detected in the original liquor product and only after ultrasonication for several minutes did Au NPs occur in the ultrasound-treated liquor. Particularly, Au NPs released in the liquor can be well extracted after 100-fold enrichment of gold flakes and the subsequent ultrasonication for 25 min. Size characterization of Au NPs was conducted by AF4-ICP-MS under calibration with Au NP standards. The gold particle sizes detected ranged from 8.3–398.0 nm and the dominant size of the released Au NPs was around 123.7 nm in the processed liquor. The mass concentration of gold particles determined in the liquor sample with gold flakes concentrated and subsequently sonicated was 48.1 μg L−1 by pre-channel calibration and the overall detection recoveries ranged over 82–95%. For the comparison control samples without ultrasonication, there was no detection of Au NPs. The established method was demonstrated to be useful for monitoring Au NPs in liquor and is possibly applied to other similar foodstuffs.

Macrophages densely populate the arterial wall, yet their origin and homeostasis are poorly understood. Robbins and colleagues show that arterial macrophages arise from CX3CR1 + embryonic precursors and adult bone marrow–derived monocytes that colonize the tissue immediately after birth. Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1 + precursors and postnatally from bone marrow–derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche.

Aneuploidy accounts for many pregnancy failures and congenital anomalies. Preimplantation genetic testing for aneuploidy (PGT-A) is a screening test applied to embryos created from in vitro fertilization to diminish the chance of an aneuploid conception. The rate of misdiagnosis for both false aneuploidy (false positive) and false euploidy (false negative) test results is unknown. The objective of this study was to determine the rate of misclassification of both aneuploidy and euploidy after PGT-A. We conducted a systematic review and meta-analysis. We searched Medline, Embase, Cochrane Central, CINAHL and WHO Clinical Trials Registry from inception until April 10, 2024. The protocol was registered in International Prospective Register of Systematic Reviews (PROSPERO CRD 42020219074). We included studies that conducted either a pre-clinical validation of the genetic platform for PGT-A using a cell line, studies that compared the embryo biopsy results to those from the whole dissected embryo or its inner cell mass (WE/ICM), and studies that compared the biopsy results to prenatal or postnatal genetic testing. Two independent reviewers extracted true and false positives and negatives comparing biopsy results to the reference standard (known karyotype, WE/ICM, pregnancy outcome). For preclinical studies, the main outcome was the positive and negative predictive values. Misdiagnosis rate was the outcome for pregnancy outcome studies. The electronic search yielded 6674 citations, of which 109 were included. For WE/ICM studies (n=40), PPV was 89.2% (95% CI 83.1-94.0) and NPV was 94.2% (95% CI 91.1-96.7, I2=42%) for aneuploid and euploid embryos, respectively. The PPV for mosaic embryos of either a confirmatory mosaic or aneuploid result was 52.8% (95% CI 37.9-67.5). For pregnancy outcome studies (n=43), the misdiagnosis rate after euploid embryo transfer was 0.2% (95% CI 0.0-0.7%, I2=65%). However, the rate for mosaic transfer, with a confirmatory euploid pregnancy outcome, was 21.7% (95% CI: 9.6-36.9, I2=95%). The accuracy of an aneuploid result from PGT-A is excellent and can be relied upon as a screening tool for embryos to avoid aneuploid pregnancies. Similarly, the misdiagnosis rate after euploid embryo transfer is less than 1%. However, there is a significant limitation in the accuracy of mosaic embryos.

The engineered silver nanoparticles (AgNPs) have been widely used in various food contact materials (FCMs) based on their antibacterial properties. This widespread use of nanosilver has, however, increased the risk of exposure of AgNPs to human due to their migration from FCMs causing a potential hazard present in foods. Therefore, it is important to establish a reliable and practical method for the detection of AgNPs in food matrices to support risk assessment on AgNPs exposure. Taking the examples of milk and AgNPs-containing breast milk storage bags, this study established an approach for size characterization and quantification of AgNPs in milk and evaluated the relevant silver migration, based on enzymatic digestion and the analysis by asymmetric flow field–flow fractionation (AF4) hyphenated with inductively coupled plasma mass spectrometry (ICP-MS) and single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). No migration of AgNPs was found from breast milk storage bags under various simulated storage conditions as well as extreme scenarios. The suitability and reliability of this method were also validated by the determination of multiple parameters, including accuracy, repeatability, limit of detection (LOD), limit of quantification (LOQ), and recovery, for AF4-ICP-MS and SP-ICP-MS, respectively, with good and overall acceptable evaluation results obtained for all. The established and validated approach was demonstrated to be suitable for the characterization and quantitation of AgNPs in milk as well as the analysis of their migration from breast milk storage bags.

The tyrosine kinase c-Met promotes the formation and malignant progression of multiple cancers. It is well known that c-Met hyperactivation increases tumorigenicity and tumor cell resistance to DNA damaging agents, properties associated with tumor-initiating stem cells. However, a link between c-Met signaling and the formation and/or maintenance of neoplastic stem cells has not been previously identified. Here, we show that c-Met is activated and functional in glioblastoma (GBM) neurospheres enriched for glioblastoma tumor-initiating stem cells and that c-Met expression/function correlates with stem cell marker expression and the neoplastic stem cell phenotype in glioblastoma neurospheres and clinical glioblastoma specimens. c-Met activation was found to induce the expression of reprogramming transcription factors (RFs) known to support embryonic stem cells and induce differentiated cells to form pluripotent stem (iPS) cells, and c-Met activation counteracted the effects of forced differentiation in glioblastoma neurospheres. Expression of the reprogramming transcription factor Nanog by glioblastoma cells is shown to mediate the ability of c-Met to induce the stem cell characteristics of neurosphere formation and neurosphere cell self-renewal. These findings show that c-Met enhances the population of glioblastoma stem cells (GBM SCs) via a mechanism requiring Nanog and potentially other c-Met-responsive reprogramming transcription factors.

The majority of broadly neutralizing antibodies to hepatitis C virus (HCV) are against conformational epitopes on the E2 glycoprotein. Many of them recognize overlapping epitopes in a cluster, designated as antigenic domain B, that contains residues G530 and D535. To gain information on other regions that will be relevant for vaccine design, we employed yeast surface display of antibodies that bound to genotype 1a H77C E2 mutant proteins containing a substitution either at Y632A (to avoid selecting non-neutralizing antibodies) or D535A. A panel of nine human monoclonal antibodies (HMAbs) was isolated and designated as HC-84-related antibodies. Each HMAb neutralized cell culture infectious HCV (HCVcc) with genotypes 1-6 envelope proteins with varying profiles, and each inhibited E2 binding to the viral receptor CD81. Five of these antibodies neutralized representative genotypes 1-6 HCVcc. Epitope mapping identified a cluster of overlapping epitopes that included nine contact residues in two E2 regions encompassing aa418-446 and aa611-616. Effect on virus entry was measured using H77C HCV retroviral pseudoparticles, HCVpp, bearing an alanine substitution at each of the contact residues. Seven of ten mutant HCVpp showed over 90% reduction compared to wild-type HCVpp and two others showed approximately 80% reduction. Interestingly, four of these antibodies bound to a linear E2 synthetic peptide encompassing aa434-446. This region on E2 has been proposed to elicit non-neutralizing antibodies in humans that interfere with neutralizing antibodies directed at an adjacent E2 region from aa410-425. The isolation of four HC-84 HMAbs binding to the peptide, aa434-446, proves that some antibodies to this region are to highly conserved epitopes mediating broad virus neutralization. Indeed, when HCVcc were passaged in the presence of each of these antibodies, virus escape was not observed. Thus, the cluster of HC-84 epitopes, designated as antigenic domain D, is relevant for vaccine design for this highly diverse virus.

Young people use social media to communicate about self-harm and suicide and this is associated with both potential risks and protective effects. The #chatsafe guidelines were originally developed in 2018 to equip young people to communicate safely online about suicide. They were shown to be safe, acceptable, and beneficial; however, they do not provide guidance on self-harm, and social media is constantly evolving. This study aimed to update the #chatsafe guidelines to reflect new evidence and current social media affordances, and to include guidance on self-harm. A Delphi expert consensus study was conducted, comprising six stages: 1) A systematic search of peer-reviewed and grey literature; 2) A series of roundtables with key stakeholders including social media companies, policymakers, and young people; 3) Questionnaire development; 4) Expert panel formation; 5) Data collection and analysis; and 6) Guideline development. A total of 191 items were included in the new #chatsafe guidelines. These were organised into eight themes, which became the overarching sections of the guidelines: 1) General tips; 2) Creating self-harm and suicide content; 3) Consuming self-harm and suicide content; 4) Livestreams of self-harm and suicide acts; 4) Self-harm and suicide games, pacts, and hoaxes; 6) Self-harm and suicide communities; 7) Bereavement and communicating about someone who has died by suicide; and 8) Guidance for influencers. The new guidelines include updated and new information on online communication about self-harm, livestreams, games, pacts, and hoaxes, as well as guidance for influencers. They will be disseminated via a national social media campaign and supported by a series of adult-facing resources. Given the acceptability of the original guidelines and the ubiquitous use of social media by young people, it is hoped that the new guidelines will be a useful resource for young people and adults alike, both in Australia and worldwide.

Background Approximately 13% of women in the United States of reproductive age seek infertility services. Assisted reproductive technology (ART), including in vitro fertilization, is used to help patients achieve pregnancy. Many people are not familiar with these treatments prior to becoming patients and possess knowledge gaps about care. Methods This study employed qualitative methods to investigate how patients interact with information sources during care. Patients who underwent ART including embryo transfer between January 2017 and April 2022 at a large urban healthcare center were eligible. Semi-structured, in-depth interviews were conducted between August and October 2022. Fifteen females with an average age of 39 years participated. Reflexive thematic analysis was performed. Results Two main themes emerged. Participants (1) utilized clinic-provided information and then turned to outside sources to fill knowledge gaps; (2) struggled to learn about costs, insurance, and mental health resources to support care. Participants preferred clinic-provided resources and then utilized academic sources, the internet, and social media when they had unfulfilled information needs. Knowledge gaps related to cost, insurance, and mental health support were reported. Conclusion ART clinics can consider providing more information about cost, insurance, and mental health support to patients. Trial registration The Massachusetts General Hospital Institutional Review Board approved this study (#2022P000474) and informed consent was obtained from each participant.