Search

Abstract In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple “wisdom” by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Introduction: In the past decades, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have sparked interest in cellular therapy due to their immunomodulatory properties. Nevertheless, the fate of hUC-MSCs in the body remains poorly understood. This study aimed to investigate the biodistribution, homing and clearance of systemically administered hUC-MSCs in healthy BALB/c mice model. Methods: hUC-MSCs were labelled with GFP-Luc2 protein, followed by characterisation with flow cytometry. Upon intravenous infusion of transduced hUC-MSCs into the healthy BALB/c mice, the cells were dynamically monitored through the bioluminescent imaging (BLI) approach. Results: Transduction of hUC-MSCs with GFP-Luc2 not only preserved the characteristics of MSCs, but also allowed live monitoring of transduced cells in the mice model. Upon systemic administration, BLI showed that transduced hUC-MSCs first localised predominantly in the lungs of healthy BALB/c mice and mainly remained in the lungs for up to 3 days before eventually cleared from the body. At terminal sacrifice, plasma chemistry biomarkers remained unchanged except for C-peptide levels, which were significantly reduced in the hUC-MSCs group. Histopathological findings further revealed that hUC-MSCs infusion did not cause any adverse effects and toxicity to lung, liver and heart tissues. Conclusions: Collectively, systemically administrated hUC-MSCs was safe and demonstrated dynamic homing capacity before eventually disappearing from the body.

Abstract Objective Preterm infants are at a high risk of developing BPD. Although progression in neonatal care has improved, BPD still causes significant morbidity and mortality, which can be attributed to the limited therapeutic choices for BPD. This review discusses the potential of MSC in treating BPD as well as their hurdles and possible solutions. Data Sources The search for data was not limited to any sites but was mostly performed on all clinical trials available in ClinicalTrials.gov as well as on PubMed by applying the following keywords: lung injury, preterm, inflammation, neonatal, bronchopulmonary dysplasia and mesenchymal stem cells. Study Selections The articles chosen for this review were collectively determined to be relevant and appropriate in discussing MSC not only as a potential treatment strategy for curbing the incidence of BPD but also including insights on problems regarding MSC treatment for BPD. Results Clinical trials regarding the use of MSC for BPD had good results but also illustrated insights on problems to be addressed in the future regarding the treatment strategy. Despite that, the clinical trials had mostly favourable reviews. Conclusion With BPD existing as a constant threat and there being no permanent solutions, the idea of regenerative medicine such as MSC may prove to be a breakthrough strategy when it comes to treating BPD. The success in clinical trials led to the formulation of prospective MSC‐derived products such as PNEUMOSTEM®, and there is the possibility of a stem cell medication and permanent treatment for BPD in the near future.

Purpose: This study aimed to investigate the efficacy of human-derived umbilical cord mesenchymal stem cells (HDUMSC) and human-derived umbilical cord mesenchymal stem cells expressing erythropoietin (HDUMSC-EPO) to rescue total degenerated retina in a rat model. Methods: The study included four treatment groups, namely negative control using normal saline (HBSS) injection, positive control using sodium iodide 60 mg/kg (SI), SI treated with HDUMSC, and SI treated with HDUMSC-EPO given via subretinal and intravenous routes, to test the efficacy of retinal regeneration following SI-induced retinal degeneration. Retinal function in both phases was tested via electroretinography (ERG) and histological staining examining the outer nuclear layer (ONL). Results: There was a statistically significant result (P < 0.05) in the SI treated with HDUMSC-EPO only when comparing day 11 (mean = 23.6 μv), day 18 (mean = 25.2 μv), day 26 (mean = 26.3 μv), and day 32 (mean = 28.2 μv) to the b-wave ERG on day 4 rescue injection day (mean = 12.5 μv). The SI treated with HDUMSC-EPO showed significant improvement in b-wave ERG readings in the Sprague–Dawley (SD) rat but did not restore baseline readings prior to degeneration (day 0). Both treated groups' ONL thicknesses did not show significant changes compared to the negative control group (HBSS) following rescue therapy. Conclusion: Total retinal degeneration following intravenous SI injection was observed at 60 mg/kg. SI treated with HDUMSC and HDUMSC-EPO showed no regenerative potential compared to baseline in SI-induced total retina degeneration on ERG or histology, whereas SI treated with HDUMSC-EPO group showed a substantial increase in b-wave ERG amplitude over time.

Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1β, IL-8, and TNF-α, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log10 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log10 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the host’s versatile immune armory against viral persistence.

The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (

It is rare for young, healthy patients to have retinal venous or arterial occlusions and even rarer for both to occur in concert. Such an occurrence should prompt a rapid and extensive workup to prevent further complications. We present our patient, a 37-year-old Lebanese male, who reported a 3-day history of blurring of vision in his left eye. He had no medical or ocular history and is a nonsmoker. Examination of the left fundus revealed inferior macular edema and retinal whitening associated with tortuous retinal veins. He was diagnosed with a combined central retinal vein and cilioretinal artery occlusion. Emergency treatment was done for an acute arterial occlusion. Embolic and thrombotic causes were excluded with investigations. The only positive result was homozygosity for 677C>T mutation of the 5,10 methylenetetrahydrofolate reductase (MTHFR) enzyme gene. MTHFR enzyme breaks down homocysteine, which is atherogenic and prothrombotic. This mutation can lead to a prothrombotic state, precipitating this occurrence. In fact, the Lebanese population is known to have the highest incidence of such mutations, but there are surprisingly few reports on retinal vascular occlusions attributed to this. He was promptly treated with antiplatelet therapy, possibly preventing a full-blown central retinal vein occlusion. After 4 weeks, his vision improved to 6/6 bilaterally. Examination showed less tortuous veins, no more retinal whitening, resolution of macula edema and visual field defect. Hyperhomocysteinemia can be significant in patients without ischemic risk factors. It is vital to manage these patients promptly, preventing future sight and life-threatening events.

The dynamics of host-virus interactions, and impairment of the host’s immune surveillance by dengue virus (DENV) serotypes largely remain ambiguous. Several experimental and preclinical studies have demonstrated how the virus brings about severe disease by activating immune cells and other key elements of the inflammatory cascade. Plasmablasts are activated during primary and secondary infections, and play a determinative role in severe dengue. The cross-reactivity of DENV immune responses with other flaviviruses can have implications both for cross-protection and severity of disease. The consequences of a cross-reactivity between DENV and anti-SARS-CoV-2 responses are highly relevant in endemic areas. Here, we review the latest progress in the understanding of dengue immunopathogenesis and provide suggestions to the development of target strategies against dengue.

Summary: Neuroinflammation exacerbates the progression of SOD1-driven amyotrophic lateral sclerosis (ALS), although the underlying mechanisms remain largely unknown. Herein, we demonstrate that misfolded SOD1 (SOD1Mut)-causing ALS results in mitochondrial damage, thus triggering the release of mtDNA and an RNA:DNA hybrid into the cytosol in an mPTP-independent manner to activate IRF3- and IFNAR-dependent type I interferon (IFN-I) and interferon-stimulating genes. The neuronal hyper-IFN-I and pro-inflammatory responses triggered in ALS-SOD1Mut were sufficiently robust to cause a strong physiological outcome in vitro and in vivo. cGAS/DDX41-STING-signaling is amplified in bystander cells through inter-neuronal gap junctions. Our results highlight the importance of a common DNA-sensing pathway between SOD1 and TDP-43 in influencing the progression of ALS.

BackgroundThe magnitude of protection conferred following recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.MethodsWe investigated the factors associated with anti-SARS-CoV-2 S1 IgG decay in 519 individuals who recovered from COVID-19 illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March to December 2021. Blood samples collected during regular follow-up post-infection/-vaccination were examined for anti-SARS-CoV-2 S1 IgG by a commercial automated chemiluminescent immunoassay (CLIA).ResultsAge and underlying comorbidities were the two variables that were independently associated with the development of a breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions (viz., hypertension, diabetes mellitus and cardiovascular disease) had a ~15 times and ~10 times greater odds for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the anti-SARS-CoV-2 IgG antibody levels by a coefficient of −6 units.ConclusionsOur findings advocate that the elderly with underlying comorbidities be administered with appropriate number of booster doses with AZD1222 and BBV152 against COVID-19.

Abstract Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

Radiation-induced optic neuropathy (RION) is a severely disabling complication of radiotherapy, without any known effective treatment. Three patients, one female and two males, aged 60, 34, and 45 years, respectively, developed progressive deterioration in visual acuity over 1 month, 8 years, and 2 months, starting 3, 12, and 9 years after radiotherapy for nasopharyngeal carcinoma. They received 70.15, 60.89, and 56.11 Gy over a period of 6–7 weeks, with fractionated doses of 2, 1.79, and 1.81 Gy, respectively. Ophthalmological examination revealed a relative afferent pupillary defect in the latter 2 patients, best-corrected visual acuity was 6/12 or better in all. Visual field charting showed a superior altitudinal field defect in the first two, and generalised visual loss in the third patient in the symptomatic eyes. Anticoagulation with heparin bridging and oral warfarin with an INR target of 2.0–3.0 was commenced within 2 months of symptom onset. All showed improvement in visual fields within 2 weeks, and remained stable for at least 2 years while on warfarin. Our encouraging findings will need to be confirmed in a randomised controlled clinical trial.

Ethnicity, native and/or foreign language knowledge, as well as the learned writing systems potentially influence the development of an individual's handwriting. The unique education system consisting of National schools, Chinese-medium vernacular schools, Tamil-medium vernacular schools, and Islamic religious schools in Malaysia may have established specific characteristic handwritten allographic features that deserve investigation within the intelligence context. This study was aimed to explore handwritten allographic features of handwriting samples from 120 subjects (30 writers from four different educational backgrounds mentioned above). Characteristic features which could be attributed to the study groups were statistically analyzed and identified. In this study, thirteen allographic features, including letters "A", "B", "D", "H", "p", "T", "t", "w", "X" and "x", were found to be discriminative. Such information could serve to indicate the primary education system undergone by a writer; enabling the comparison of different handwriting profiles and allowing characterization of writers to a specific group of people.

Geophysical flows impacting a flexible barrier can create complex flows and solid-fluid-structure interactions, which are challenging to quantify and characterize towards a unified description. Here, we examine the common physical laws of multiphase, multiway interactions during debris flows, debris avalanches and rock avalanches against a flexible barrier system using a coupled computational fluid dynamics and discrete element (CFD-DEM) method. This model captures essential physics observed in experiments and fields. The bi-linear, positive correlations are found between peak impact load and Fr or maximum barrier deflection, with inflection points due to the transitions from trapezoid- to triangle-shaped dead zones. Our findings quantitatively elucidate how flow materials (wet versus dry) and impact dynamics (slow versus fast) control the patterns of the identified bi-linear correlations. This work offers a physics-based reference and insights for improving widely-used impact solutions for geophysical flows against flexible barriers.

The lethal combination involving TB and HIV, known as “syndemic” diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART, eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although a significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic marker still remain a grey area of investigation. Here, we reviewed the latest research developments into IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Mesenchymal stem cells (MSC) are highly regarded as a potential treatment for retinal degenerative disorders like retinitis pigmentosa and age-related macular degeneration. However, donor cell heterogeneity and inconsistent protocols for transplantation have led to varied outcomes in clinical trials. We previously showed that genetically-modifying MSCs to express erythropoietin (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO were cultured and expanded before being intravitreally transplanted into the sodium iodate-induced model. After the procedure, electroretinography (ERG) was performed bi-weekly for 30 days. Histological analyses were performed after the ERG assessment. The retina was then harvested for RNA extraction. After mRNA-enrichment and library preparation, paired-end RNA-Seq was performed. Salmon and DESeq2 were used to process the output files. The generated dataset was then analyzed using over-representation (ORA), functional enrichment (GSEA), and pathway topology analysis tools (SPIA) to identify enrichment of key pathways in the experimental groups. The results showed that the MSCEPO-treated group had detectable ERG waves (P

Cat manure (CM) possesses high level of nutrients for growing food crop. However, animal manure may contain toxic elements that may contaminate food crop. Spent coffee ground (SCG) may be used to reduce mobility of heavy metals and reduce crop uptake. In this study, SCG was composted with CM for 31 days to produce a co-compost (SCG-CM) for growing spinach (Spinacia oleracea). The growth rate of spinach was assessed until its maturity, and the metal uptake of spinach shoot was determined thereafter using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The effect of soil treatment with SCG-CM on the height and elemental composition of spinach were compared with that of chicken manure compost (CMC). The prepared composts were primarily organic matter (72.9–81.4 % w/w) with the rest are ash (13.3–23.4 % w/w) and moisture (1.2–2.6 % w/w). Zinc content in SCG-CM (1261 ± 0.1 mg/kg) is significantly higher than that of soil and CMC (p < 0.05) and has exceeded the maximum permissible limit set by European Union Standard (2002) and the Malaysian Compost Quality Standard and Guidelines (2000). Matured spinach reached maximum plant height after 33 days. The amendment of SCG-CM significantly increased the height of spinach (32 ± 6 cm) compared to that of CMC (13 ± 1 cm) (p < 0.05). However, contents of Zn, Cu, Pb and Cd were not increased for spinach grown in the SCG-CM-amended soil, and the level of those elements are below permissible limit set by the Malaysian Food Act 1983 and Food Regulations 1985. This study shows that SCG-CM is effective in improving yield without causing accumulation of toxic trace elements in spinach.

Background. Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Results. 11 healthy subjects (LD, n=5; HD, n=6; mean age of 55±13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA (705±160 vs. 306±36 pg/mL; p=0.02) and IL-10 (321±27 vs. 251±28 pg/mL; p=0.02); and lower levels of proinflammatory marker TNF-α (74±23 vs. 115±15 pg/mL; p=0.04) compared to LD group. Conclusion. Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.

Background: Currently, drug-eluting balloon (DEB) appears to be an attractive alternative option for the treatment of in-stent restenosis (ISR). Nevertheless, the clinical outcomes of DEB have seldom been compared to those of new-generation drug-eluting stent (DES). Thus, this meta-analysis aimed to evaluate the safety and efficacy of DEB compared to those of new-generation DES in the treatment of ISR. Methods: A comprehensive search of electronic databases including PubMed, EMBASE, and Cochrane Library up to November 2, 2017 was performed to identify pertinent articles comparing DEB to new-generation DES for the treatment of ISR. In addition, conference proceedings for the scientific sessions of the American College of Cardiology, American Heart Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, and EuroPCR were also searched. The primary endpoint was target lesion revascularization (TLR) at the longest follow-up. Dichotomous variables were presented as risk ratios (RR s) with 95% confidence intervals (CI s), while the overall RR s were estimated using the Mantel-Haenszel random-effects model. Results: Five randomized controlled trials (RCTs) and eight observational studies involving 2743 patients were included in the present meta-analysis. Overall, DEB was comparable to new-generation DES in terms of TLR (RR = 1.24, 95% CI: 0.89–1.72, P = 0.21), cardiac death (RR = 1.55, 95% CI: 0.89–2.71, P = 0.12), major adverse cardiovascular event (RR = 1.21, 95% CI: 0.98–1.48, P = 0.07), myocardial infarction (RR = 1.12, 95% CI: 0.72–1.76, P = 0.62), and stent thrombosis (RR = 0.95, 95% CI: 0.38–2.42, P = 0.92). However, DEB was associated with higher risk of all-cause mortality than new-generation DES (RR = 1.65, 95% CI: 1.09–2.50, P = 0.02). This was especially true in the real-world observational studies (RR = 1.79, 95% CI: 1.12–2.88, P = 0.02). In RCTs, however, no significant difference was found between the two treatment strategies in the risk of all-cause mortality. Conclusions: The current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies.

T-cell exhaustion is a phenomenon of dysfunction or physical elimination of antigen-specific T cells reported in human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections as well as cancer. Exhaustion appears to be often restricted to CD8+ T cells responses in the literature, although CD4+ T cells have also been reported to be functionally exhausted in certain chronic infections. Although our understanding of the molecular mechanisms associated with the transcriptional regulation of T-cell exhaustion is advancing, it is imperative to also explore the central mechanisms that control the altered expression patterns. Targeting metabolic dysfunctions with mitochondrion-targeted antioxidants are also expected to improve the antiviral functions of exhausted virus-specific CD8+ T cells. In addition, it is crucial to consider the contributions of mitochondrial biogenesis on T-cell exhaustion and how mitochondrial metabolism of T cells could be targeted whilst treating chronic viral infections. Here, we review the current understanding of cardinal features of T-cell exhaustion in chronic infections, and have attempted to focus on recent discoveries, potential strategies to reverse exhaustion and reinvigorate optimal protective immune responses in the host.

With the development of new generation Internet technology, Digital Object Architecture (DOA)/Handle system plays an important role in industrial system. The development and technical characteristics of DOA/Handle technology is studied in this paper. Then function architecture of distributed data acquisition system based on DOA/Handle technology is proposed. Through the detailed design of the functions and characteristics of the architecture, the core functions such as distributed data acquisition, distributed data management, data security sharing, and data security governance are realized in the industrial Internet environment. At the end of the paper, the typical scenarios of this architecture are summarized, and a prospect of the application prospect of DOA/Handle technology is introduced.

This case report aims to share the successful management of Epithelial Downgrowth (ED) which occurred following persistent wound leak, after Removal of Silicone Oil (ROSO) via the anterior chamber. A teenage male with history of high myopia underwent bilateral phacoemulsification and implantation of Multifocal Intraocular Lens (MFIOLs). Four months later, he complained of left eye floaters and blurring of vision. Fundus showed left vitreous haemorrhage with lens subluxation. Left 23 gauge pars plana vitrectomy revealed multiple retinal tears. Endolaser and gas injection with MFIOL repositioning was done. Retinal redetachment and MFIOL subluxation occurred six weeks postoperatively. Revision vitrectomy with silicone oil and explantation of MFIOL was performed rendering left eye aphakic. Four months later, he underwent ROSO via a superior corneal incision. Positive Seidels was seen two weeks post-ROSO and resuturing was performed. Unfortunately, advancing ED was noted at the superior cornea. One month after ROSO, scleral fixated IOL implantation with manual removal of ED and intracameral injection of 5-fluorouracil (5-FU) were performed. Twelve months postoperatively, cornea remained clear with a pinhole vision of 6/7.5 and retina was flat. In conclusion, wound leak after ROSO via the anterior chamber in aphakic individuals may predispose to ED. Key to treatment of this sight threatening condition is thoughtful anterior segment examination. Manual removal of the membrane combined with 5-FU injection during secondary lens implantation surgery is an effective treatment.

Human immunodeficiency virus type 1 (HIV-1) subtypes have been shown to differ in the rate of clinical progression. We studied the association between HIV-1 subtypes and the rate of CD4+ T-cell recovery in a longitudinal cohort of patients on combination antiretroviral therapy (cART). We studied 103 patients infected with CRF01_AE (69%) and subtype B (31%) who initiated cART between 2006 and 2013. Demographic data, CD4+ T-cell counts and HIV-1 viral load were abstracted from patient medical charts. Kaplan-Meier was used to estimate the time to CD4+ T-cell count increase to ≥350 between subtypes and effects of covariates were analysed using Cox proportional hazards. An 87% of the study population were male adults (mean age of 38.7 years old). Baseline CD4+ T-cell counts and viral loads, age at cART initiation, sex, ethnicity and co-infection did not differ significantly between subtypes. A shorter median time for CD4+ T-cell count increase to ≥350 cells/μL was observed for CRF01_AE (546 days; 95% confidence interval [CI], 186-906 days; P = .502) compared to subtype B (987 days; 95% CI, 894-1079 days). In multivariate analysis, female sex was significantly associated with a 2.7 times higher chance of achieving CD4+ T-cell recovery (adjusted hazard ratio [HR], 2.75; 95% CI, 1.21-6.22; P = .025) and both baseline CD4+ T-cell count (P = .001) and viral load (P = .001) were important predictors for CD4+ T-cell recovery. Immunological recovery correlated significantly with female sex, baseline CD4+ T-cell counts and viral load but not subtype.

Mesenchymal stem cells are widely used in many pre-clinical and clinical settings. Despite advances in molecular technology; the migration and homing activities of these cells in in vivo systems are not well understood. Labelling mesenchymal stem cells with gold nanoparticles has no cytotoxic effect and may offer suitable indications for stem cell tracking. Here, we report a simple protocol to label mesenchymal stem cells using 80 nm gold nanoparticles. Once the cells and particles were incubated together for 24 h, the labelled products were injected into the rat subretinal layer. Micro-computed tomography was then conducted on the 15th and 30th day post-injection to track the movement of these cells, as visualized by an area of hyperdensity from the coronal section images of the rat head. In addition, we confirmed the cellular uptake of the gold nanoparticles by the mesenchymal stem cells using transmission electron microscopy. As opposed to other methods, the current protocol provides a simple, less labour-intensive and more efficient labelling mechanism for real-time cell tracking. Finally, we discuss the potential manipulations of gold nanoparticles in stem cells for cell replacement and cancer therapy in ocular disorders or diseases.

Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

A 26-year-old woman with a recent flare-up of systemic lupus erythematosus presented with peripheral retinal hemorrhages at a routine check-up. She is on a tapering dose of immunosuppressive agents. Her visual acuity was good. Fluorescein angiogram revealed vasculitic changes with capillary non-perfusion areas. A few weeks later, she developed cerebral lupus with advanced lupus nephritis. Immunosuppressive therapy was restarted and panretinal photocoagulation was delivered. Her visual acuity remained stable, despite development of a cataract from prednisolone therapy.

The clinical features, autofluorescence, Bscan ultrasonography, optical coherence tomography and fluorescein angiography of the lesion were described. Multiple investigation modalities are needed to confirm the benign nature of the lesion. Careful evaluation and follow-up is crucial to avoid misdiagnosis and erroneous management.

Abstract Background Exome sequencing has transformed human genetic analysis and may do the same for other vertebrate model systems. However, a major challenge is sifting through the large number of sequence variants to identify the causative mutation for a given phenotype. In models like Xenopus tropicalis, an incomplete and occasionally incorrect genome assembly compounds this problem. To facilitate cloning of X. tropicalis mutants identified in forward genetic screens, we sought to combine bulk segregant analysis and exome sequencing into a single step. Results Here we report the first use of exon capture sequencing to identify mutations in a non-mammalian, vertebrate model. We demonstrate that bulk segregant analysis coupled with exon capture sequencing is not only able to identify causative mutations but can also generate linkage information, facilitate the assembly of scaffolds, identify misassembles, and discover thousands of SNPs for fine mapping. Conclusion Exon capture sequencing and bulk segregant analysis is a rapid, inexpensive method to clone mutants identified in forward genetic screens. With sufficient meioses, this method can be generalized to any model system with a genome assembly, polished or unpolished, and in the latter case, it also provides many critical genomic resources.