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It is vital to employ efficient methods to calculate and determine the threshold of river ecological flow. These methods help to get the river ecological status control countermeasures in the plain river networks and construct a flawless long-term mechanism of ecological flow control (water level). According to the river's current environment and the actual circumstances surrounding its operation and administration, the upper, middle, and lower reaches make up the three sections of the Zong-Liutang River in the Plain of Northern Jiangsu. Furthermore, the ecological water level governing factor for each reach was analyzed and studied. The ecological water level threshold in the upper and lower reaches of the Zong-Liutang River adopted the specified values of Jiangsu Provincial Department of water resources. The threshold of the middle reach was thoroughly analyzed by using the determination method with multi-criteria, which consisted of the hydrological and hydraulic methods (including yearly minimum water level with a 90% assured rate method; wetted perimeter method; minimum monthly average water level method), aquatic living conditions method, and river landscape entertainment factor method. Taking into account the hydrological and hydrodynamic characteristics, observed hydrological data conditions of rivers, and the actual operation rules of rivers and water projects regulations in the Northern Jiangsu plain. Through comparing and contrasting actual operation and management plans, the target values of the ecological water level for the river's upper, middle, and lower reaches were 17.4 m, 8.96 m, and 7.5 m, respectively. Based on the river's ecological water level's control value, which was found through a thorough analysis, and the river's real operation and management conditions, specific measures to protect the river's ecological water level were suggested. These included developing a perfect and workable ecological flow control method, speeding up the development of an ecological water level goal assurance early warning system, and an ecological flow and inlet system.

Intra-articular delivery of disease-modifying osteoarthritis drugs (DMOADs) is likely to be most effective in early post-traumatic osteoarthritis (PTOA) when symptoms are minimal and patients are physically active. DMOAD delivery systems therefore must withstand repeated mechanical loading without affecting the drug release kinetics. Although soft materials are preferred for DMOAD delivery, mechanical loading can compromise their structural integrity and disrupt drug release. Here, we report a mechanically resilient soft hydrogel that rapidly self-heals under conditions resembling human running while maintaining sustained release of the cathepsin-K inhibitor L-006235 used as a proof-of-concept DMOAD. Notably, this hydrogel outperformed a previously reported hydrogel designed for intra-articular drug delivery, used as a control in our study, which neither recovered nor maintained drug release under mechanical loading. Upon injection into mouse knee joints, the hydrogel showed consistent release kinetics of the encapsulated agent in both treadmill-running and non-running mice. In a mouse model of aggressive PTOA exacerbated by treadmill running, L-006235 hydrogel markedly reduced cartilage degeneration. To our knowledge, this is the first hydrogel proven to withstand human running conditions and enable sustained DMOAD delivery in physically active joints, and the first study demonstrating reduced disease progression in a severe PTOA model under rigorous physical activity, highlighting the hydrogel's potential for PTOA treatment in active patients.

Human transcriptome can undergo RNA mis-splicing due to spliceopathies contributing to the increasing number of genetic diseases including muscular dystrophy (MD), Alzheimer disease (AD), Huntington disease (HD), myelodysplastic syndromes (MDS). Intron retention (IR) is a major inducer of spliceopathies where two or more introns remain in the final mature mRNA and account for many intronic expansion diseases. Potential removal of such introns for therapeutic purposes can be feasible when utilizing bioinformatics, catalytic RNAs, and nano-drug delivery systems. Overcoming delivery challenges of catalytic RNAs was discussed in this review as a future perspective highlighting the significance of utilizing synthetic biology in addition to high throughput deep sequencing and computational approaches for the treatment of mis-spliced transcripts., 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., (Copyright © 2023 Khalifah, Alghamdi and Alhasan.)

At nanoconfined interfaces, a micellar ink of lipids was programmed to transform into various secondary structures such as discs, sheets, or sheet and discs via patterning-mediated self-assembly facilitated by polymer pen lithography. Nanoconfinement with printing force, humidity, temperature, pattern size, and total printing time all governed the intramolecular assembly of lipids and determined their structural shape and size. For example, disc or sheet architectures self-organized to produce cochleates or discotic liquid crystals, respectively. In contrast, the combined structure of sheet and discs produced a novel supramolecular output referred to as "nanopalms". The mechanism of nanopalms formation and the origin of their stability were investigated and discussed. Post patterning treatment helped to transform the patterned discs into ribbons and sheets into cochleates that could facilitate the curling of ribbons along their folding direction in a programmed manner via intermolecular self-organization producing the nanopalms., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors.)

Robust inflammation-suppressing nanoparticles based on α 1 -acid glycoprotein (AGP)-conjugated hyaluronic acid nanoparticles (AGP-HA NPs) were designed to regulate breast cancer cells' sensitivity to chemotherapy and to suppress tumor metastasis. The successful conjugation between AGP and HA NPs was confirmed using FTIR, zeta potential, and UV-vis spectroscopy. In vitro studies on MCF-7 cells indicated the remarkable ability of AGP-HA NPs in suppressing migratory tumor ability by 79% after 24 h. Moreover, the efficacy study showed the high capability of AGP-HA NPs in modulating MDA-MB-231 cells and restoring cell sensitivity to the chemotherapeutic drug doxorubicin (DOX). Furthermore, the finding obtained by flow cytometry and confocal spectroscopy demonstrated that AGP-HA NPs enhanced DOX uptake/retention and aided it to reach cell nucleus within 4 h of incubation. Therefore, AGP-HA NPs represent a viable and effective treatment option to strengthen the anticancer effects of chemotherapeutic agents and potentially improve patients' survival rates.

Oxidative chemical etching of metal nanoparticles (NPs) to produce holey graphene (hG) suffers from the presence of aggregated NPs on the graphene surface triggering heterogeneous etching rates and thereby producing irregular sized holes. To encounter such a challenge, we investigated the use of scanning probe block co-polymer lithography (SPBCL) to fabricate precisely positioned silver nanoparticles (AgNPs) on graphene surfaces with exquisite control over the NP size to prevent their aggregation and consequently produce uniformly distributed holes after oxidative chemical etching. SPBCL experiments were carried out via printing an ink suspension consisting of poly(ethylene oxide- b -2-vinylpyridine) and silver nitrate on a graphene surface in a selected pattern under controlled environmental and instrumental parameters followed by thermal annealing in a gaseous environment to fabricate AgNPs. Scanning electron microscopy revealed the uniform size distribution of AgNPs on the graphene surface with minimal to no aggregation. Four main sizes of AgNPs were obtained (37 ± 3, 45 ± 3, 54 ± 2, and 64 ± 3 nm) via controlling the printing force, z -piezo extension, and dwell time. Energy dispersive X-ray spectroscopy analysis validated the existence of elemental Ag on the graphene surface. Subsequent chemical etching of AgNPs using nitric acid (HNO 3 ) with the aid of sonication and mechanical agitation produced holes of uniform size distribution generating hG. The obtained I D / I G ratios ≤ 0.96 measured by Raman spectroscopy were lower than those commonly reported for GO ( I D / I G > 1), indicating the removal of more defective C atoms during the etching process to produce hG while preserving the remaining C atoms in ordered or crystalline structures. Indeed, SPBCL could be utilized to fabricate uniformly distributed AgNPs of controlled sizes on graphene surfaces to ultimately produce hG of uniform hole size distribution., Competing Interests: There are no competing interests to declare., (This journal is © The Royal Society of Chemistry.)

Superparamagnetic iron oxide nanoparticles (SPIONs) have high saturation magnetization and are promising candidates for hyperthermia. They may act as magnetic heating agents when subjected to magnetic field in nano-based hyperthermia. In this work, cube-like Fe 3 O 4 nanoparticles (labelled as cubic SPIONs) with reduced graphene oxide (RGO) nanocomposites were prepared by a microwave hydrothermal method. The shape and size of magnetic nanoparticles were controlled by varying synthesis parameters, including reaction time, pressure and microwave power. This study successfully synthesized cubic SPIONs nanocomposites with an average particle size between 24-34 nm. Poly-(ethylene) glycol (PEG) was used as a coating material on SPIONs to enhance biocompatibility. The RGO sheets provided a high surface area-to-volume ratio for SPIONs to be dispersed on their surface, and hence, they prevented aggregation of the SPIONs in the nanocomposites. Magnetically induced heating studies on the optimized nanocomposite (Fe 3 O 4 /RGO/PEG) demonstrated heating capabilities for magnetic hyperthermia application with a promising specific absorption rate (SAR) value of 58.33 W/g in acidic solution. Cytotoxicity tests were also performed to ensure low nanoparticle toxicity before incorporation into the human body. The results of the standard assay for the toxicity determination of the nanocomposites revealed over 70% cell survival after 48 h, suggesting the feasibility of using the synthesized nanocomposites for magnetic hyperthermia.

Repetitive outbreaks and prolonged epidemics represent mortal threats to global health, creating chaos in our globalized world. To date, scientists have been compelled to follow FDA guidelines for conventional clinical trials, which decelerates the release of effective therapies to battle outbreaks and safeguard global health security. Developing multi-purpose platform nanotechnologies to self-target specific organs in response to the disease microenvironment could greatly help to rapidly anticipate and efficiently manage outbreaks. Nano-interventions in the form of self-targeting nanoparticles (NPs) could accelerate the clinical translation of potential drugs to fight future outbreaks via innovating their clinical trials. This review sets the foundation of the self-targeting concept to govern the in vivo fate of NPs without the need to complicate the engineering designs with targeting ligands. The proposed catalogue of accelerated nano-innovations offers self-targeting, physiological trafficking, bio-compliance, and controllable drug release in response to associated smart linkers.

Mesenchymal stem cells (MSCs) are promising candidates for the development of cell-based drug delivery systems for autoimmune inflammatory diseases, such as multiple sclerosis (MS). Here, we investigated the effect of Ro-31-8425, an ATP-competitive kinase inhibitor, on the therapeutic properties of MSCs. Upon a simple pretreatment procedure, MSCs spontaneously took up and then gradually released significant amounts of Ro-31-8425. Ro-31-8425 (free or released by MSCs) suppressed the proliferation of CD4 + T cells in vitro following polyclonal and antigen-specific stimulation. Systemic administration of Ro-31-8425-loaded MSCs ameliorated the clinical course of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, displaying a stronger suppressive effect on EAE than control MSCs or free Ro-31-8425. Ro-31-8425-MSC administration resulted in sustained levels of Ro-31-8425 in the serum of EAE mice, modulating immune cell trafficking and the autoimmune response during EAE. Collectively, these results identify MSC-based drug delivery as a potential therapeutic strategy for the treatment of autoimmune diseases. KEY MESSAGES: MSCs can spontaneously take up the ATP-competitive kinase inhibitor Ro-31-8425. Ro-31-8425-loaded MSCs gradually release Ro-31-8425 and exhibit sustained suppression of T cells. Ro-31-8425-loaded MSCs have more sustained serum levels of Ro-31-8425 than free Ro-31-8425. Ro-31-8425-loaded MSCs are more effective than MSCs and free Ro-31-8425 for EAE therapy.

Metal nanomaterials such as bismuth oxide nanoparticles (Bi 2 O 3 NPs) have been extensively used in cosmetics, dental materials, pulp capping, and biomedical imaging. There is little knowledge about the health risk of Bi 2 O 3 NPs in humans, which warrants a thorough toxicity investigation of Bi 2 O 3 NPs at the cellular level. In this experiment, we investigated the cytotoxic effect of Bi 2 O 3 NPs on human breast cancer (MCF-7) cells over 24 and 48 h. MCF-7 cells were exposed to Bi 2 O 3 NPs at varying doses (0.1, 0.5, 1.0, 5, 10, 20, 40 μg/mL) for 24 and 48 h. We assessed the toxicity of Bi 2 O 3 NPs by measuring its effect on the viability and oxidative stress biomarkers, e.g., GSH, SOD, and catalase in MCF-7 cells. The pro-apoptotic effects of Bi 2 O 3 NPs on MCF-7 cells were determined via evaluating dysfunction of mitochondrial membrane potential (MMP), caspase-3 activity, externalization of phosphatidylserine, and chromosome condensation. Furthermore, apoptotic cells were evaluated using 7-AAD fluorescence stain and Annexin V-FITC. Bi 2 O 3 NPs induced oxidative stress in MCF-7 cells in a time- and dose-dependent manner. Bi 2 O 3 NPs increased the rate of both necrotic cells and apoptotic cells. In addition, the blue fluorescence of MCF-7 cells with condensed chromatin was increased in a time- and dose-dependent manner. In conclusion, the present study highlights the potential toxic effects of Bi 2 O 3 NPs at the cellular level and suggests further investigation of Bi 2 O 3 NPs before any medical purposes.

: Background: Annually, approximately 10 million pilgrims travel to the Kingdom of Saudi Arabia (KSA) for Umrah from more than 180 countries. This event presents major challenges for the Kingdom's public health sector, which strives to decrease the burden of infectious diseases and to adequately control their spread both in KSA and pilgrims home nations. The aims of the study were to assess preventative measures practice, including vaccination history and health education, among Umrah pilgrims in Saudi Arabia. Methods: A cross sectional survey was administered to pilgrims from February to April 2019 at the departure lounge at King Abdul Aziz International airport, Jeddah city. The questionnaire comprised questions on sociodemographic information (age, gender, marital status, level of education, history of vaccinations and chronic illnesses), whether the pilgrim had received any health education and orientation prior to coming to Saudi Arabia or on their arrival, and their experiences with preventative practices. Results: Pilgrims ( n = 1012) of 41 nationalities completed the survey. Chronic diseases were reported among pilgrims ( n = 387, 38.2%) with cardiovascular diseases being the most reported morbidity ( n = 164, 42.3%). The majority of pilgrims had been immunized prior to travel to Saudi Arabia ( n = 770, 76%). The most commonly reported immunizations were influenza ( n = 514, 51%), meningitis ( n = 418, 41%), and Hepatitis B virus vaccinations ( n = 310, 31%). However, 242 (24%) had not received any vaccinations prior to travel, including meningitis vaccine and poliomyelitis vaccine, which are mandatory by Saudi Arabian health authorities for pilgrims coming from polio active countries. Nearly a third of pilgrims ( n = 305; 30.1%) never wore a face mask in crowded areas during Umrah in 2019. In contrast, similar numbers said they always wore a face mask ( n = 351, 34.6%) in crowded areas, while 63.2% reported lack of availability of face masks during Umrah. The majority of participants had received some form of health education on preventative measures, including hygiene aspects ( n = 799, 78.9%), mostly in their home countries ( n = 450, 44.4%). A positive association was found between receiving health education and practicing of preventative measures, such as wearing face masks in crowded areas (p = 0.04), and other health practice scores (p = 0.02). Conclusion: Although the experiences of the preventative measures among pilgrims in terms of health education, vaccinations, and hygienic practices were at times positive, this study identified several issues. These included the following preventative measures: immunizations, particularly meningitis and poliomyelitis vaccine, and using face masks in crowded areas. The recent COVID-19 pandemic highlights the need for further studies that focus on development of accessible health education in a form that engages pilgrims to promote comprehensive preventative measures during Umrah and Hajj and other religious pilgrimages., Competing Interests: The authors declare no conflict of interest.

Background: Antipyretics and analgesics, including non-steroidal anti-inflammatory drugs, are medications commonly used in the Kingdom of Saudi Arabia (KSA) and elsewhere to manage fever and pain in the paediatric age group.Research work investigating misuse of these medications in paediatric populations and pertinent healthcare professionals' (HCPs) perceptions as a major determinant of the severity of these errors is scarce., Objectives: The aim of this study was to explore the perceptions of HCPs about analgesic and antipyretic use in paediatric patients at four major hospitals in Jeddah, KSA. The study also sought to explore factors believed by HCPs to be associated with occurrence of medication errors and adverse drug reactions (ADRs) due to analgesic and antipyretic use., Methods: A cross-sectional survey employing a pre-piloted online questionnaire with an information sheet was delivered to HCPs in four hospitals in the western region of KSA. The questionnaire comprised a mix of a tick list and open and closed questions with Likert scales for attitudinal statements, and it also comprised items including demographics, healthcare professions and the respondents' work experience, HCPs' views and perceptions relating to occurrence of ADRs and medication errors in children who attended the hospital in the preceding three months and the severity and outcomes of the ADRs., Results: Two-hundred seventy-four HCPs were approached, and 200 agreed to participate, yielding a response rate of 73%, including physicians (50%), nurses (24.5%), and pharmacists (16.5%).The majority of HCPs reported that ADRs could be minimized with appropriate actions. They believed that their lack of experience may have contributed to ADRs. Most HCPs (81%) reported that parental knowledge was a key factor contributing to the decreased occurrence of ADRs in children. They also believed that other factors contributed to the occurrence of ADRs, such as lack of reconciliation (65%), parents' anxiety leading to overmedication (69%) and the easy availability of these medications at home (77%).Twenty-nine respondents (n = 29, 14.5%) reported medication errors related to the use of analgesics or antipyretics. Specifically, they reported that possible contributing factors included poor communication of information (69.5%); interruptions (67.5%) and work pressure (66.0%)., Conclusion: HCPs reported that ADRs and medication errors related to using analgesics and antipyretics in paediatric patients are not uncommon. In their opinion, several factors were associated with occurrence of these events, including parental knowledge about medications and insufficient training of HCPs., (© 2020 The Author(s).)

More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Oral antipyretic analgesic medicines are commonly used in children and have the potential for adverse drug reactions (ADRs)., Objective: The aim of this study was to explore parental experiences of potential ADRs related to their oral administration of antipyretic analgesics in children in the Kingdom of Saudi Arabia., Methods: For this cross-sectional survey, a paper-based questionnaire, consent form and information sheet were handed out to 1000 parents who had administered an oral antipyretic analgesic medicine to their children during the previous 3 months. Data were entered and analyzed using SPSS version 21.0 (IBM-SPSS Inc, Armonk, NY). Simple descriptive and inferential statistics were used. Management and ethical approvals were attained., Results: During March to April 2017, 661 parents agreed to participate, giving a response rate of 66.1%. Of the surveyed sample, 208 parents had observed 1 or more potential ADRs (31.5%, n = 208 out of 661). Parents' (n = 208) most commonly reported potential ADRs (n = 523) were loss of appetite (23%, n = 120 out of 523), stomachache (20.3%, n = 106 out of 523), abdominal colic (13%, n = 68 out of 523), and diarrhea (10.3%, n = 54 out of 523). Parents described severity of the ADRs as slight (71.8%, n = 342 out of 476), annoying to the child (7.9%, n = 85 to of 476), significant and affecting daily tasks (3.6%, n = 17 out of 476) and significant and led to the hospital (6.7%, n = 32 out of 476). Fever was the top-ranked reason for using antipyretic analgesic medicines (41.0%, n = 271 out of 661), followed by toothache (25.0%, n = 165 out of 661) and tonsillitis/laryngitis (24.7%, n = 163 out of 661). Among parents, 34.7% (n = 165 out of 476) did not seek medical attention when a potential ADR occurred, whereas 26.3% (n = 125 out of 476) of parents took their children to hospital clinics., Conclusions: Although the majority of parentally reported (but not proven) ADRs were mild, a number of significant ADRs were reported. Future research should consider whether there is a role for physicians and pharmacists in educating parents in Saudi Arabia, and perhaps more widely, about the optimal use of oral antipyretic and analgesic medicines in children. ( Curr Ther Res Clin Exp . 2020; 81:XXX-XXX)© 2020 Elsevier HS Journals, Inc., Competing Interests: The authors have indicated that they have no conflicts of interest regarding the content of this article., (© 2020 The Author(s).)

Objective: To examine the association of sociodemographic variables with the odds of being obese among adults in Saudi Arabia, and to examine whether or not the association between the educational level and the odds of being obese among adults in Saudi Arabia is modified by the income level., Methods: A total of 3,925 participants were recruited for this cross--sectional study. Sociodemographic and anthropometric data were collected using standardized procedures. Unadjusted and adjusted logistic regression models were examined, with a dichotomous obesity status variable as the outcome. Furthermore, an interaction term for income level with educational level was tested and appeared significant. Thus, additional regression models were run in order to examine the association between educational level and obesity status separately among the low- and higher-income groups., Results: Compared to participants with a college degree or higher, illiterate participants and those with an elementary education had higher odds of obesity (OR: 2.76, 95% CI: 1.81-4.22, and OR: 2.68, 95% CI: 1.89-3.82, respectively). However, participants with a low income had lower odds than participants who had a higher income (OR: 0.84, 95% CI: 0.70-0.99). Examining the association between educational level and obesity while stratifying by income revealed that a negative association between education and obesity exists among both income groups. However, the magnitude of the ORs was higher among participants with higher income, suggesting a stronger association between education and obesity among wealthier individuals., Conclusion: Individuals in the highest income bracket with lower levels of education may have greater odds of obesity. Targeting them in intervention programs is warranted., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background Misuse of prescription medicines is a global issue potentially resulting in severe consequences including adverse drug reactions, dependence, tolerance, increased healthcare utility and mortality. Objective To assess the public's perspectives of issues relating to medicines misuse. Method A survey of members of the public ( ≥ 18 years) attending medication safety awareness campaigns in Jeddah, Saudi Arabia. The questionnaire comprised: issues relating to misuse of prescription medicines; medicines used without being prescribed by a physician; and suggestions to reduce misuse. Potential participants were approached opportunistically during the campaigns, with those agreeing to participate administered the questionnaire and responses recorded electronically. Results Of the 511 respondents, 59 (11.5%) did not always have their prescription medicines prescribed by a physician, and 196 (38.4%) were uncertain. Commonly cited medicines obtained from sources other than a physician were analgesics (n = 375, 73.2%), antibiotics (n = 57, 11.2%), antipyretics (n = 33, 6.5%) and narcotics (n = 4, 0.8%). More than half (n = 282, 55.2%) claimed to know someone who had misused medicines, some with serious consequences including hospitalization (n = 96, 34.0%) and death (n = 14, 5.0%). Conclusion This general public survey has identified that issues of misuses of medicines in Jeddah, Saudi Arabia persist and may compromise safety and effectiveness of care.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) have been studied extensively for their localized homogeneous heat generation in breast cancer therapy. However, challenges such as aggregation and inability to produce sub-10 nm SPIONs limit their potential in magnetothermal ablation. We report a facile, efficient, and robust in situ method for the synthesis of SPIONs within a poly(ethylene glycol) (PEG) reactor adsorbed onto reduced graphene oxide nanosheets (rGO) via the microwave hydrothermal route. This promising modality yields crystalline, stable, biocompatible, and superparamagnetic PEGylated SPION-rGO nanocomposites (NCs) with uniform dispersibility. Our findings show that rGO acts as a breeding ground for the spatially distributed nanosites around which the ferrihydrite seeds accumulate to ultimately transform into immobilized SPIONs. PEG, in parallel, acts as a critical confining agent physically trapping the accumulated seeds to prevent their aggregation and create multiple domains on rGO for the synthesis of quantum-sized SPIONs (9 ± 1 nm in diameter). This dual functionality (rGO and PEG) exhibits a pronounced effect on reducing both the aggregation and the sizes of fabricated SPIONs as confirmed by the scanning transmission electron microscopy images, dynamic light scattering analyses, and the specific absorption rates (SARs). Reduced aggregation lowered the toxicity of NCs, where PEGylated SPION-rGO NCs are more biocompatible than PEGylated SPIONs, showing no significant induction of cell apoptosis, mitochondrial membrane injury, or oxidative stress. Significantly less lactate dehydrogenase release and hence less necrosis are observed after 48 h exposure to high doses of PEGylated SPION-rGO NCs compared with PEGylated SPIONs. NCs induce local heat generation with a SAR value of 1760 ± 97 W/g, reaching up to 43 ± 0.3 °C and causing significant MCF-7 breast tumor cell ablation of about 78 ± 10% upon applying an external magnetic field. Collectively, rGO and PEG functionalities have a synergistic effect on improving the synthesis, stability, biocompatibility, and magnetothermal properties of SPIONs.

Background: Liposuction is one of the most performed cosmetic surgery procedures. In a previously reported study, gold-nanoparticle (GNP) laser-assisted liposuction (NanoLipo) was shown to improve procedure parameters and outcomes in a porcine model., Objectives: An ex vivo human liposuction model was developed to assess the ease, efficacy, and outcomes of NanoLipo, and to further explore its mechanism of action in facilitating liposuction., Methods: NanoLipo was compared to a control without GNPs in sets of fresh, nonperfused, anatomically symmetric, matched tissue specimens from 12 patients. A subset of three experiments was performed under single-blinded conditions. Intraoperative assessments included lipoaspirate volume, percentage of free oil, ease of removal, and temperature rise. Specimens were palpated, visualized for evenness, and graded with and without skin. Postoperative assessment included viability staining of the lipoaspirate and remaining tissues. Microcomputed tomography was used to assess the distribution of infused GNPs within the tissues., Results: NanoLipo consistently removed more adipose tissue with more liberated triglycerides compared to control. NanoLipo specimens were smoother, thinner, and had fewer and smaller irregularities. Infused solutions preferentially distributed between fibrous membranes and fat pearls. After NanoLipo, selective structural-tissue disruptions, indicated by loss of metabolic activity, were observed. Thus, NanoLipo likely creates a bimodal mechanism of action whereby fat lobules are dislodged from surrounding fibro-connective tissue, while lipolysis is simultaneously induced., Conclusions: NanoLipo showed many advantages compared to control under blinded and nonblinded conditions. This technology may be promising in facilitating fat removal.

Objective: To examine the association of weight status with level of diabetes knowledge (symptoms and complications) among residents of Jeddah City, Saudi Arabia., Methods: In a cross-sectional study, a questionnaire assessing sociodemographic and health characteristics and knowledge about diabetes and its symptoms and complications was utilized. Data of 3978 adults, 18 years of age or older, were collected from public mall sites in Jeddah city and surrounding areas. Participants were divided into three tertiles based on their knowledge scores. Weight and height were measured following standardized procedures, and body weight categories were defined based on body mass index (BMI). The association between weight status and tertiles of diabetes knowledge was examined using multinomial logistic regression analysis., Results: Compared to normal-weight participants, participants who were underweight, overweight, or obese, did not differ with regards to knowledge about diabetes symptoms. Adjusted models showed that overweight and obese participants had lower odds of being in the lowest tertile of knowledge about diabetes complications compared to normal-weight participants (OR: 0.71, 95% CI: 0.58-0.86 and OR: 0.64, 95% CI: 0.51-0.79, respectively). With regards to general knowledge about diabetes, the knowledge of participants who were underweight did not differ when compared to normal-weight participants. Overweight and obese participants had lower odds of being in the lowest tertile of general knowledge about diabetes compared to normal-weight participants (OR: 0.78, 95% CI: 0.62-0.97 and OR: 0.60, 95% CI: 0.47-0.76, respectively)., Conclusions: Overweight and obese individuals have better knowledge about diabetes compared to normal-weight individuals. Public health programs need to take into account the level of diabetes knowledge and tailor interventions to aid behavior and lifestyle change.

In recent years, nanotechnology has been proven to offer promising biomedical applications for in vivo diagnostics and drug delivery, stressing the importance of thoroughly investigating the biocompatibility of potentially translatable nanoparticles (NPs). Herein, we report the cellular responses of uncoated chitosan NPs (CS NPs) and hyaluronic acid-coated chitosan NPs (HA-CS NPs) when introduced into Chinese hamster ovary cells (CHO-K1) in a dose-dependent manner (2.5, 0.25, 0.025, 0.0025, and 0.00025 mg mL -1 ) at two time points (24 and 48 h). MTS assay, cell proliferation, showed a decrease in the viability of cells when treated with 0.25 and 2.5 mg mL -1 CS NPs. When exposed to high doses of CS NPs, the lactate dehydrogenase (LDH) enzyme started to leak out of the cells and the cellular levels of mitochondrial potentials were significantly reduced accompanied by a high production of intracellular reactive oxygen species (ROS). Our study provides molecular evidence of the biocompatibility offered by HA-CS NPs, through ROS scavenging capabilities rescuing cells from the oxidative stress, showing no observed cellular stress and thereby revealing the promising effect of anionic hyaluronic acid to significantly reduce the cytotoxicity of CS NPs. Our findings are important to accelerate the translation and utilization of HA-CS NPs in drug delivery, demonstrating the pronounced effect of surface modifications on modulating the biological responses.

Studying the interactions of nanoparticles (NPs) with serum proteins is necessary for the rational development of nanocarriers. Optimum surface chemistry is a key consideration to modulate the formation of the serum protein corona (PC) and the resultant immune response. We investigated the constituent of the PC formed by hyaluronic acid-coated chitosan NPs (HA-CS NPs). Non-decorated chitosan NPs (CS NPs) and alginate-coated chitosan NPs (Alg-CS NPs) were utilized as controls. Results show that HA surface modifications significantly reduced protein adsorption relative to controls. Gene Ontology analysis demonstrates that HA-CS NPs were the least immunogenic nanocarriers. Indeed, less inflammatory proteins were adsorbed onto HA-CS NPs as opposed to CS and Alg-CS NPs. Interestingly, HA-CS NPs differentially adsorbed two unique anti-inflammatory proteins (ITIH4 and AGP), which were absent from the PC of both controls. On the other hand, CS and Alg-CS NPs selectively adsorbed a proinflammatory protein (Clusterin) that was not found on the surfaces of HA-CS NPs. While further studies are needed to investigate abilities of the PCs of only ITIH4 and AGP to modulate the interaction of NPs with the host immune system, our results suggest that this proof-of-concept could potentially be utilized to reduce the immunogenicity of a wide range of nanomaterials.

We report the identification of a molecular signature using the Scano-miR profiling platform based on the differential expression of circulating microRNAs (miRNA, miR) in serum samples specific to patients with very high-risk (VHR) prostate cancer (PCa). Five miRNA PCa biomarkers (miR-200c, miR-605, miR-135a*, miR-433, and miR-106a) were identified as useful for differentiating indolent and aggressive forms of PCa. All patients with VHR PCa in the study had elevated serum levels of miR-200c. Circulating miR-433, which was differentially expressed in patients with VHR versus low-risk (LR) forms of PCa, was not detectable by quantitative real-time PCR in samples from healthy volunteers. In blind studies, the five miRNA PCa biomarkers were able to differentiate patients with VHR PCas from those with LR forms as well as healthy individuals with at least 89% accuracy. Biological pathway analysis showed the predictive capability of these miRNA biomarkers for the diagnosis and prognosis of VHR aggressive PCa., Competing Interests: The authors declare no conflict of interest.

Background: Conventional suction-assisted lipectomy (SAL) often results in contour irregularity. Selective photothermal heating of adipose tissue by polymer-coated gold nanorods energized by an external near-infrared exposure at 800 nm is introduced in this work to facilitate fat removal., Methods: The effects of NanoLipo were examined in food-grade porcine abdominal tissue (skin, fat, and fascia) by histology. The efficacy of NanoLipo was compared with that of conventional SAL in vivo in Yucatan mini pigs by quantification of removed subcutaneous tissue and fatty acids and ultrasound measurement of adipose layer thickness., Results: NanoLipo led to the appearance of disruptions in adipose tissue that were not apparent in control groups in ex vivo samples. NanoLipo allowed removal of more subcutaneous tissue (~33% vs ~25% of removed material, P < 0.05) and approximately twice as much free fatty acids (~60% vs ~30% of removed tissue, P < 0.05) in comparison with conventional SAL. Most importantly, NanoLipo led to a greater decrease in adipose layer thickness at 1 month post surgery (P < 0.001)., Conclusions: NanoLipo facilitates removal of a greater quantity of fat and requires less suction time (4 vs 10 minutes) than conventional SAL. As the safety of poly(ethylene-glycol)-coated gold nanorods is well-established, a clinical trial is currently being organized.

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

Exosomes are a class of naturally occurring nanomaterials that play crucial roles in the protection and transport of endogenous macromolecules, such as microRNA and mRNA, over long distances. Intense effort is underway to exploit the use of exosomes to deliver synthetic therapeutics. Herein, transmission electron microscopy is used to show that when spherical nucleic acid (SNA) constructs are endocytosed into PC-3 prostate cancer cells, a small fraction of them (<1%) can be naturally sorted into exosomes. The exosome-encased SNAs are secreted into the extracellular environment from which they can be isolated and selectively re-introduced into the cell type from which they were derived. In the context of anti-miR21 experiments, the exosome-encased SNAs knockdown miR-21 target by approximately 50%. Similar knockdown of miR-21 by free SNAs requires a ≈3000-fold higher concentration., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the development of a novel Scanometric MicroRNA (Scano-miR) platform for the detection of relatively low abundance miRNAs with high specificity and reproducibility. The Scano-miR system was able to detect 1 fM concentrations of miRNA in serum with single nucleotide mismatch specificity. Indeed, it provides increased sensitivity for miRNA targets compared to molecular fluorophore-based detection systems, where 88% of the low abundance miRNA targets could not be detected under identical conditions. The application of the Scano-miR platform to high density array formats demonstrates its utility for high throughput and multiplexed miRNA profiling from various biological samples. To assess the accuracy of the Scano-miR system, we analyzed the miRNA profiles of samples from men with prostate cancer (CaP), the most common noncutaneous malignancy and the second leading cause of cancer death among American men. The platform exhibits 98.8% accuracy when detecting deregulated miRNAs involved in CaP, which demonstrates its potential utility in profiling and identifying clinical and research biomarkers.

We demonstrate that polyvalent DNA-functionalized gold nanoparticles (DNA-Au NPs) selectively enhance ribonuclease H (RNase H) activity while inhibiting most biologically relevant nucleases. This combination of properties is particularly interesting in the context of gene regulation, since high RNase H activity results in rapid mRNA degradation and general nuclease inhibition results in high biological stability. We have investigated the mechanism of selective RNase H activation and found that the high DNA density of DNA-Au NPs is responsible for this unusual behavior. This work adds to our understanding of polyvalent DNA-Au NPs as gene regulation agents and suggests a new model for selectively controlling protein-nanoparticle interactions.

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western population. Although genetic factors are considered to contribute to CLL etiology, at present genomic aberrations identified in CLL are limited compared with those identified in other types of leukemia, which raises the question of the degree of genetic influence on CLL. We performed a high-resolution genome scanning study to address this issue., Findings: Using the restriction paired-end-based Ditag Genome Scanning technique, we analyzed three primary CLL samples at a kilobase resolution, and further validated the results in eight primary CLL samples including the two used for ditag collection. From 51,632 paired-end tags commonly detected in the three CLL samples representing 5% of the HindIII restriction fragments in the genomes, we identified 230 paired-end tags that were present in all three CLL genomes but not in multiple normal human genome reference sequences. Mapping the full-length sequences of the fragments detected by these unmapped tags in seven additional CLL samples confirmed that these are the genomic aberrations caused by small insertions and deletions, and base changes spreading across coding and non-coding regions., Conclusions: Our study identified hundreds of loci with insertion, deletion, base change, and restriction site polymorphism present in both coding and non-coding regions in CLL genomes, indicating the wide presence of small genomic aberrations in chronic lymphocytic leukemia. Our study supports the use of a whole genome sequencing approach for comprehensively decoding the CLL genome for better understanding of the genetic defects in CLL.