T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals.

The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and revealed that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.

Efficient Model Updating of a Prefabricated Tall Building by a DNN Method.

The significance of model updating methods is becoming increasingly evident as the demand for greater precision in numerical models rises. In recent years, with the advancement of deep learning technology, model updating methods based on various deep learning algorithms have begun to emerge. These methods tend to be complicated in terms of methodological architectures and mathematical processes. This paper introduces an innovative model updating approach using a deep learning model: the deep neural network (DNN). This approach diverges from conventional methods by streamlining the process, directly utilizing the results of modal analysis and numerical model simulations as deep learning input, bypassing any additional complex mathematical calculations. Moreover, with a minimalist neural network architecture, a model updating method has been developed that achieves both accuracy and efficiency. This distinctive application of DNN has seldom been applied previously to model updating. Furthermore, this research investigates the impact of prefabricated partition walls on the overall stiffness of buildings, a field that has received limited attention in the previous studies. The main finding was that the deep neural network method achieved a Modal Assurance Criterion (MAC) value exceeding 0.99 for model updating in the minimally disturbed 1st and 2nd order modes when compared to actual measurements. Additionally, it was discovered that prefabricated partitions exhibited a stiffness ratio of about 0.2-0.3 compared to shear walls of the same material and thickness, emphasizing their role in structural behavior.

Emergency Department-Based Human Immunodeficiency Virus Preexposure Prophylaxis Referral Program-Using Emergency Departments as a Portal for Preexposure Prophylaxis Services.

ABSTRACT: A pilot program was implemented to assess the feasibility of emergency department (ED) preexposure prophylaxis (PrEP) referral. Of 119 eligible patients approached and assessed, 39 (33%) expressed interest and were referred to peer navigators. Of these, 16 (41%) scheduled for appointments; four (10%) initiated PrEP, which demonstrated ED-based PrEP referral was feasible.

pH Dependence of Arsenic Oxidation by Rice-Husk-Derived Biochar: Roles of Redox-Active Moieties.

Biochars have demonstrated great potential for water decontamination and soil remediation; however, their redox reactivity toward trace contaminants and the corresponding redox-active moieties (RAMs, i.e., phenolic -OH, semiquinone-type persistent free radicals (PFRs), and quinoid C═O) remain poorly understood. Here we investigated the roles of the RAMs on biochar in oxidation of As(III) under varying pH and O2 conditions. The results showed that the promoted oxidation of As(III) by the RAMs is strongly pH dependent. Under acidic and neutral conditions, only the oxidation of As(III) by •OH and H2O2 produced from activation of O2 by phenolic -OH and semiquinone-type PFRs occurred. In contrast, the oxidation by semiquinone-type PFRs, quinoid C═O, and H2O2 (if O2 was introduced) appeared under alkaline conditions. This pH-dependent oxidation behavior was attributed to the varying redox activities of RAMs, as confirmed by multiple characterization and validation experiments using biochar with tuned RAMs compositions, as well as thermodynamics evaluation. Our findings provide new insights into the roles of the RAMs on biochar in the promoted oxidation of trace As(III) over a broader pH range under both anoxic and oxic conditions. This study also paves a promising way to oxidize As(III) with biochar.

Time-varying contributions of FeII and FeIII to AsV immobilization under anoxic/oxic conditions: The impacts of biochar and dissolved organic carbon.

Engineering black carbon (e.g. biochar) has been widely found in natural environments due to natural processes and extensive applications in engineering systems, and could influence the geochemical processes of coexisting arsenic (AsV) and FeII, especially when they are exposed to oxic conditions. Here, we studied time-varying kinetics and efficiencies of AsV immobilization by solid-phase FeII (FeIIsolid) and FeIII (FeIIIsolid) in FeII-AsV-biochar systems under both anoxic and oxic conditions at pH 7.0, with focuses on the effects of biochar surface and biochar-derived dissolved organic carbon (DOC). Under anoxic conditions, FeII could rapidly immobilize AsV via co-adsorption onto biochar surfaces, which also serves as the dominant pathway of AsV immobilization at the initial stage of reaction (0-5 min) under oxic conditions at high biochar concentrations. Subsequently, with increasing biochar concentrations, FeIIIsolid precipitation from aqueous FeII (FeIIaq) oxidation (5-60 min) starts to play an important role in AsV immobilization but in decreased efficiencies of AsV immobilization per unit iron. In the following stage (60-300 min), FeIIsolid oxidation is suppressed and leads to AsV release into solutions at >1.0 g·L-1 biochar. The decreasing efficiency of AsV immobilization over time is attributed to the gradual release of DOC into solution from biochar particles, which significantly inhibit AsV immobilization when FeIIIsolid is generated from FeIIsolid oxidation in the vicinity of biochar surfaces. Specifically, 4.06 mg·L of biochar-derived DOC can completely inhibit the immobilization of AsV in the 100 µM FeII system under oxic conditions. The findings are crucial to comprehensively understand and predict the behavior of FeII and AsV with coexisting engineering black carbon in natural environments.

Roles of the SOM and clay minerals in alleviating the leaching of Pb, Zn, and Cd from the Pb/Zn smelter soil: Multi-surface model and DFT study.

Soil organic matter (SOM) and clay minerals are important sinks for reactive heavy metals (HMs) and exogenous hydrogen ions (H+). Therefore, HMs are likely to be released into soil porewater under acid rainfall conditions due to the competitive adsorption of H+. However, negligible Lead, Zinc, and Cadmium (<6 ‰) in the Pb/Zn smelter soil were leached, and the effects of SOM and clay minerals on HMs leaching were unclear. Herein, the H+ consumption and HMs redistribution on SOM and clay minerals were quantitated by the multi-surface model and density functional theory calculations to reveal the roles of SOM and clay minerals in alleviating HMs' leaching. Clay minerals consumed 43.2 %-52.0 % of the exogenous H+, serving as the dominant sink for the exogenous H+ due to its high content and hindering H+ competitive adsorption on SOM. Protonation of the functional groups constituted >90 % of the total H+ captured by clay minerals. Meanwhile, some H+ also competed with HMs for adsorption sites on clay minerals due to its 0.497-fold to 1.54-fold higher binding energies than HMs, resulting in the release of HMs. On the contrary, SOM served as an accommodator for taking over the released HMs from clay minerals. The HMs complexation on the low-affinity sites (R-L-) of SOM was responsible for the recapture of HMs. In Ca-enriched soil, the released HMs were also recaptured by SOM via ion exchange on the R-L-Ca+ and the high-affinity sites (R-H-Ca+) sites due to the 30.8 %-178 % higher binding energies of HMs on these sites than those of Ca. As a result, >63.4 % of the released HMs from clay minerals were transferred to the SOM. Thus, the synergy of SOM and clay minerals in alleviating the leaching of HMs in Pb/Zn smelter soils cannot be ignored in risk assessment and soil remediation.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components.

BACKGROUND: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. METHODS: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. RESULTS: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. CONCLUSIONS: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.

Recycled biochar adsorption combined with CaCl2 washing to increase rice yields and decrease Cd levels in grains and paddy soils: A field study.

Field-scale trials were conducted to remove cadmium (Cd) from paddy soil by using recycled hydroxyapatite modified biochar (HBC) plus low-level CaCl2 washing. Synergistic reduction efficiencies of total and available Cd in soil (45.6 % and 36.8 %) were achieved by the combined amendments compared with only HBC or CaCl2. The release of Cd from soil particulates was facilitated by CaCl2 washing and the increased soluble Cd in soil water (hardly removed by drainage) could be removed efficiently by recycled HBC adsorption. Significantly decreases in Cd translocation and accumulation in rice plants benefited from the decrease of Cd level and availability in soil and the increase of available silicon (Si). As a result, Cd contents in early/late rice grains decreased by ~85 % and met the Chinese national food standard. SOM, CEC, and soil nutrients after remediation were increased due to 10 %-15 % of HBC residual. Grain yields of the early and late rice increased by 34.1 % and 9.91 %, respectively. The collected HBC (>85 % of the total used HBC) was in-situ regenerated and could be used in the next field trials. The generated wastewater together with drainage from field treatment could be reused as irrigation water after the treatment with a small-scale reclamation ecosystem. The work provides a novelty remediation strategy for Cd-contaminated paddy soil. The noticeable remediation efficiency for Cd reduction in soil and grains, and improved productivity-relevant soil properties have important implications for paddy soil with poor fertility, severe desilicification, and Cd contamination in South China whereas the application of biochar or chemical washing alone did not.

High dose isoleucine stabilizes nuclear PTEN to suppress the proliferation of lung cancer.

PURPOSE: Cancer cells require a supply of amino acids, particularly essential amino acids such as branched-chain amino acids (BCAAs, i.e., valine, leucine, and isoleucine), to meet the increased nutrient demands of malignant tumors. The cell-autonomous and non-autonomous roles of altered BCAA supply have been implicated in cancer progression. The critical proteins involved in BCAA uptake, transport, metabolism, etc. serve as potential therapeutic biomarkers in human cancers. Here, we summarize the potential anti-tumor mechanism of BCAA by exploring the chain reaction triggered by increased BCAA supply in the tumor. METHOD: A system-wide strategy was employed to provide a generic solution to establish the links between BCAA and cancer based on comprehensive omics, molecular experimentation, and data analysis. RESULTS: BCAA over-supplementation (900 mg/kg) significantly inhibited tumor growth and reduced tumor burden, with isoleucine having the most pronounced effect. Surprisingly, isoleucine inhibited tumor growth independently of mTORC1 activation, a classical amino acid sensor. Exploratory transcriptome analysis revealed that Phosphatase and tensin homolog (PTEN) is the critical factor in the anti-tumor effect of isoleucine. By inhibiting PTEN ubiquitination, isoleucine can promote PTEN nuclear import and maintain PTEN nuclear stability. Interestingly, this process was regulated by isoleucine-tRNA ligase, cytoplasmic (IARS), a direct target of isoleucine. We demonstrated the enhanced interaction between IARS and PTEN in the presence of excess isoleucine. At the same time, IARS knockout leads to loss of isoleucine tumor suppressor ability. CONCLUSION: Overall, our results provide insights into the regulation of the IARS-PTEN anti-tumor axis by isoleucine and reveal a unique therapeutic approach based on enhancing cellular isoleucine supply.

Reduction of cadmium bioavailability in paddy soil and its accumulation in brown rice by FeCl3 washing combined with biochar: A field study.

Cadmium (Cd) removal from paddy soil to reduce Cd accumulation in brown rice is essential for agroecology, food safety, and human health. In this study, we demonstrate that ferric chloride (FeCl3) washing combined with biochar treatment efficiently remediates Cd-contaminated paddy soil in field trials. Our results showed that 30.9 % of total Cd and 41.6 % of bioavailable Cd were removed by the addition of 0.03 M FeCl3 at a liquid/soil ratio of 1.5:1. The subsequent addition of 1 % biochar further reduced bioavailable Cd by 36.5 and 41.5 %, compared with FeCl3 washing or biochar treatment alone. The principal component regression analysis showed that the Cd content in brown rice was primarily affected by the bioavailable Cd in soil. The combined remediation contributed to the decreased Cd contents in brown rice by 45.5-62.5 %, as well as a 2.7-11.8 % increase in rice yield. The Cd contents in brown rice decreased to 0.12 and 0.04 mg kg-1 in two cultivars of rice (Zhuliangyou189 and Zhuliangyou929), lower than the national food safety standard limit value of China (0.2 mg kg-1). Meanwhile, the combined remediation promoted the restoration of soil pH and organic matter as well as the improvement of available nutrients. This finding suggests that the combination of FeCl3 washing and biochar is an effective remediation strategy to minimize Cd bioavailability in paddy soil, and improves soil quality, thus contributing to food safety.

Synergistic effect of floatable hydroxyapatite-modified biochar adsorption and low-level CaCl2 leaching on Cd removal from paddy soil.

The utilization of recycled biochar combined with chemical leaching is an appropriate method to remove cadmium (Cd) from paddy soil. Some Cd-rich soil clay particulates (particulate Cd) are reported to be removed via biochar adsorption and the potential impact of biochar on soil properties need further study. The removal efficiencies and mechanisms of Cd from soil by using floatable hydroxyapatite modified biochar (HBC) combined with CaCl2 were studied. Synergetic removal efficiencies of total Cd (46.5%) and bioavailable Cd (37.9%) from the paddy soil were achieved with 2% HBC and 1 mM CaCl2. The increased soluble Cd in soil pore water by CaCl2 leaching could be efficiently adsorbed on HBC, and removed by HBC collection, reducing the risk of the residual soluble Cd in soil pore water to rice plants caused by the inefficient drainage in the field. The suspendability of clay particulates in overlying water was little affected by the low-level CaCl2 based on Derjaguin-Landau-Verwey-Overbeek (DLVO) calculation. Moreover, low-level CaCl2 facilitated the accumulation of particulate Cd on the floating HBC via decreasing the interaction energy (by 25%) between clay particulates and HBC. HBC-mediated Cd migration contributed ~70% of total Cd removal, while soluble and particulate Cd removed through the drainage accounted for ~30%. Soil clay proportion maintained at 25.3% due to the replenishment of HBC residues. In addition, soil nutrient and physicochemical conditions were improved with HBC residues. This work provides a novel soil remediation method by using floatable biochar combined with low-level CaCl2 for Cd-contaminated paddy soil remediation.

Feeding intolerance in critically ill patients with COVID-19.

BACKGROUND & AIMS: Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19. METHODS: We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11 and June 28, 2020 who received enteral nutrition. Systematic chart review determined prevalence, clinical characteristics, and hospital outcomes (ICU complications, length of stay, and mortality) of feeding intolerance. RESULTS: Feeding intolerance developed in 56% of the patients and most commonly manifested as large gastric residual volumes (83.9%), abdominal distension (67.2%), and vomiting (63.9%). Length of intubation (OR 1.05, 95% CI 1.03-1.08), ≥1 GI symptom on presentation (OR 0.76, 95% CI 0.59-0.97), and severe obesity (OR 0.29, 95% CI 0.13-0.66) were independently associated with development of feeding intolerance. Compared to feed-tolerant patients, patients with incident feeding intolerance were significantly more likely to suffer cardiac, renal, hepatic, and hematologic complications during their hospitalization. Feeding intolerance was similarly associated with poor outcomes including longer ICU stay (median [IQR] 21.5 [14-30] vs. 15 [9-22] days, P < 0.001), overall hospitalization time (median [IQR] 30.5 [19-42] vs. 24 [15-35], P < 0.001) and in-hospital mortality (33.9% vs. 16.1%, P < 0.001). Feeding intolerance was independently associated with an increased risk of death (HR 3.32; 95% CI 1.97-5.6). CONCLUSIONS: Feeding intolerance is a frequently encountered complication in critically ill COVID-19 patients in a large tertiary care experience and is associated with poor outcomes.

Rice husk-derived biochar can aggravate arsenic mobility in ferrous-rich groundwater during oxygenation.

Elevated As(III) and Fe(II) in shallow reducing groundwater can be frequently re-oxidized by introducing O2 due to natural/anthropogenic processes, thus leading to oxidative precipitation of As as well as Fe. Nevertheless, the geochemical process may be impacted by co-existing engineered black carbon due to its considerable applications, which remains poorly understood. Taking rice husk-derived biochar prepared at 500 °C as an example, we explored its impact on the process particularly for the As(III) oxidation and (im)mobilization during the oxygenation. The presence of the biochar had a negligible effect on the As(III) oxidation and immobilization extents within 1 d, while accelerating their rates. However, the immobilized As(III) was significantly liberated from the formed Fe(III) minerals afterward within 21 d, which was 2.2-fold higher than that in the absence of the biochar. The enhanced As(III) liberation was attributed to the presence of the surface silicon-carbon structure, consisting of the outer silicon and inner carbon layers, of the rice husk-derived biochar. The outer silicon components, particularly for the dissolved silicate primarily promoted the As(III) release via ligand exchange, while significantly impeding the transformation of ferrihydrite to lepidocrocite and goethite still resulted secondarily in the As(III) release. Our findings reveal the possible impact of biochar on the environmental behavior and fate of As(III) in the Fe(II)-rich groundwater during the oxygenation. This work highlights that biochar, particularly for its structural features should be a concern in re-mobilizing As in such scenarios when the oxygenation time reaches several days or weeks.

Characterization of extracellular vesicles and synthetic nanoparticles with four orthogonal single-particle analysis platforms.

We compared four orthogonal technologies for sizing, counting, and phenotyping of extracellular vesicles (EVs) and synthetic particles. The platforms were: single-particle interferometric reflectance imaging sensing (SP-IRIS) with fluorescence, nanoparticle tracking analysis (NTA) with fluorescence, microfluidic resistive pulse sensing (MRPS), and nanoflow cytometry measurement (NFCM). EVs from the human T lymphocyte line H9 (high CD81, low CD63) and the promonocytic line U937 (low CD81, high CD63) were separated from culture conditioned medium (CCM) by differential ultracentrifugation (dUC) or a combination of ultrafiltration (UF) and size exclusion chromatography (SEC) and characterized by transmission electron microscopy (TEM) and Western blot (WB). Mixtures of synthetic particles (silica and polystyrene spheres) with known sizes and/or concentrations were also tested. MRPS and NFCM returned similar particle counts, while NTA detected counts approximately one order of magnitude lower for EVs, but not for synthetic particles. SP-IRIS events could not be used to estimate particle concentrations. For sizing, SP-IRIS, MRPS, and NFCM returned similar size profiles, with smaller sizes predominating (per power law distribution), but with sensitivity typically dropping off below diameters of 60 nm. NTA detected a population of particles with a mode diameter greater than 100 nm. Additionally, SP-IRIS, MRPS, and NFCM were able to identify at least three of four distinct size populations in a mixture of silica or polystyrene nanoparticles. Finally, for tetraspanin phenotyping, the SP-IRIS platform in fluorescence mode was able to detect at least two markers on the same particle, while NFCM detected either CD81 or CD63. Based on the results of this study, we can draw conclusions about existing single-particle analysis capabilities that may be useful for EV biomarker development and mechanistic studies.

Contrasting abiotic As(III) immobilization by undissolved and dissolved fractions of biochar in Ca2+-rich groundwater under anoxic conditions.

Engineered black carbon (biochar) can be introduced into groundwater through its extensive engineered applications (e.g., in-situ remediation of groundwater/soils), which can participate in geochemical processes that may alter the fate of trace contaminants such as arsenic (As(III)). Here we examined the impacts of the undissolved and dissolved fractions of reduced biochar (hereafter denoted as rUBC and rDBC, respectively) on the As(III) immobilization in the absence/presence of Ca2+ (50 mM) at pH 11.5 under anoxic conditions. While neither rUBC nor rDBC alone was capable of immobilizing As(III), the apparent As(III) immobilization by rUBC and rDBC synergistically occurred in the presence of Ca2+, with an efficiency of 73.1% and 89.6% within 24 h, respectively. In the rUBC/Ca2+/As(III) system, rUBC enabled full oxidation of As(III) to As(V) by its residual redox-active moieties such as quinoid CO and persistent free radicals, thereby facilitating precipitation of the newly generated As(V) with Ca2+ adsorbed onto the rUBC's surface. In contrast, rDBC induced in-situ local enrichment of Ca2+ in the nascent rDBC-derived flocs with predominant non-oxidative and slight oxidative precipitation of As(III) via ternary rDBC-Ca-As complexation. This ternary complex was created by Ca2+-bridging interactions between As species and oxygen-containing functional groups of rDBC, as evidenced by the FTIR results and the Ca2+-impeded As(III) oxidation. The generation of the flocs physically trapped a small amount of As species particularly As(III). Both the increases in Ca2+ concentration (0-100 mM) and solution pH (10.0-12.5) enhanced the apparent As(III) immobilization. This study provides new insights into the environmental impacts of two reduced biochar fractions released into typical Ca2+-rich aquifers on the fate and transport of As species.

miRNA profiling of primate cervicovaginal lavage and extracellular vesicles reveals miR-186-5p as a potential antiretroviral factor in macrophages.

Cervicovaginal secretions, or their components collected, are referred to as cervicovaginal lavage (CVL). CVL constituents have utility as biomarkers and play protective roles in wound healing and against HIV-1 infection. However, several components of cervicovaginal fluids are less well understood, such as extracellular RNAs and their carriers, for example, extracellular vesicles (EVs). EVs comprise a wide array of double-leaflet membrane extracellular particles and range in diameter from 30 nm to over one micron. The aim of this study was to determine whether differentially regulated CVL microRNAs (miRNAs) might influence retrovirus replication. To this end, we characterized EVs and miRNAs of primate CVL during the menstrual cycle and simian immunodeficiency virus (SIV) infection of macaques. EVs were enriched by stepped ultracentrifugation, and miRNA profiles were assessed with a medium-throughput stem-loop/hydrolysis probe qPCR platform. Whereas hormone cycling was abnormal in infected subjects, EV concentration correlated with progesterone concentration in uninfected subjects. miRNAs were present predominantly in the EV-depleted CVL supernatant. Only a small number of CVL miRNAs changed during the menstrual cycle or SIV infection, for example, miR-186-5p, which was depleted in retroviral infection. This miRNA inhibited HIV replication in infected macrophages in vitro. In silico target prediction and pathway enrichment analyses shed light on the probable functions of miR-186-5p in hindering HIV infections via immunoregulation, T-cell regulation, disruption of viral pathways, etc. These results provide further evidence for the potential of EVs and small RNAs as biomarkers or effectors of disease processes in the reproductive tract.

The future of Extracellular Vesicles as Theranostics - an ISEV meeting report.

The utilization of extracellular vesicles (EVs) in clinical theranostics has rapidly advanced in the past decade. In November 2018, the International Society for Extracellular Vesicles (ISEV) held a workshop on "EVs in Clinical Theranostic". Here, we report the conclusions of roundtable discussions on the current advancement in the analysis technologies and we provide some guidelines to researchers in the field to consider the use of EVs in clinical application. The main challenges and the requirements for EV separation and characterization strategies, quality control and clinical investigation were discussed to promote the application of EVs in future clinical studies.

Extracellular vesicles and chronic inflammation during HIV infection.

Inflammation is a hallmark of HIV infection. Among the multiple stimuli that can induce inflammation in untreated infection, ongoing viral replication is a primary driver. After initiation of effective combined antiretroviral therapy (cART), HIV replication is drastically reduced or halted. However, even virologically controlled patients may continue to have abnormal levels of inflammation. A number of factors have been proposed to cause inflammation in HIV infection: among others, residual (low-level) HIV replication, production of HIV protein or RNA in the absence of replication, microbial translocation from the gut to the circulation, co-infections, and loss of immunoregulatory responses. Importantly, chronic inflammation in HIV-infected individuals increases the risk for a number of non-infectious co-morbidities, including cancer and cardiovascular disease. Thus, achieving a better understanding of the underlying mechanisms of HIV-associated inflammation in the presence of cART is of utmost importance. Extracellular vesicles have emerged as novel actors in intercellular communication, involved in a myriad of physiological and pathological processes, including inflammation. In this review, we will discuss the role of extracellular vesicles in the pathogenesis of HIV infection, with particular emphasis on their role as inducers of chronic inflammation.

miRNAs in platelet-poor blood plasma and purified RNA are highly stable: a confirmatory study.

OBJECTIVE: We wished to re-assess the relative stability of microRNAs (miRNAs) as compared with other RNA molecules, which has been confirmed in many contexts. When bound to Argonaute proteins, miRNAs are protected from degradation, even when released into the extracellular space in ribonucleoprotein complexes, and with or without the protection of membranes in extracellular vesicles. Purified miRNAs also appear to present less of a target for degradation than other RNAs. Although miRNAs are by no means immune to degradation, biological samples subjected to prolonged incubation at room temperature, multiple freeze/thaws, or collection in the presence of inhibitors like heparin, can typically be remediated or used directly for miRNA measurements. RESULTS: Here, we provide additional confirmation of early, well validated findings on miRNA stability and detectability. Our data also suggest that inadequate depletion of platelets from plasma may explain the occasional report that freeze-thaw cycles can adversely affect plasma miRNA levels. Overall, the repeated observation of miRNA stability is again confirmed.