Orally ingestible medication utilizing layered double hydroxide nanoparticles strengthened alginate and hyaluronic acid-based hydrogel bead for bowel disease management.

In the treatment of bowel diseases such as ulcerative colitis through oral administration, an effective drug delivery system targeting the colon is crucial for enhancing efficacy and minimizing side effects of therapeutic agents. This study focuses on the development of a novel nanocomposite hydrogel bead comprising a synergistic blend of biological macromolecules, namely sodium alginate (ALG) and hyaluronic acid (HA), reinforced with layered double hydroxide nanoparticles (LDHs) for the oral delivery of dual therapeutics. The synthesized hydrogel bead exhibits significantly enhanced gel strength and controllable release of methylprednisolone (MP) and curcumin (CUR), serving as an anti-inflammatory drug and a mucosal healing agent, compared to native ALG or ALG/HA hydrogel beads without LDHs. The physicochemical properties of the synthesized LDHs and hydrogel beads were characterized using various techniques, including scanning electron microscopy, zeta potential measurement, transmission electron microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. In vitro release studies of MP and CUR under simulated gastrointestinal tract (GIT) conditions demonstrate the superior controlled release property of the nanocomposite hydrogel bead, particularly in minimizing premature drug release in the upper GIT environment while sustaining release of over 82 % of drugs in the colonic environment. Thus, the modularly engineered carrier designed for oral colon targeting holds promise as a potential candidate for the treatment of ulcerative colitis.

Correction: Nguyen et al. Green Silver Nanoparticles Formed by Phyllanthus urinaria, Pouzolzia zeylanica, and Scoparia dulcis Leaf Extracts and the Antifungal Activity. Nanomaterials 2020, 10, 542.

In the original publication [...].

Triple-Hybrid BioScaffold Based on Silk Fibroin, Chitosan, and nano-Biphasic Calcium Phosphates: Preparation, Characterization of Physiochemical and Biopharmaceutical Properties.

Bioscaffolds, which promote cell regeneration and restore tissues' functions, have emerged as significant need in clinic. The hybrid of several biomaterials in a bioscaffold renders clinically advanced and relevant properties for applications yet add challenges in cost efficiency, production, and clinical investigation. This study proposes a facile and sustainable method to formulate a triple-hybrid bioscaffold based on Vietnamese cocoon origin Silk Fibroin, Chitosan, and nano-Biphasic Calcium Phosphates (nano-BCP) that can be easily molded, has high porosity (55-80%), and swelling capacity that facilitates cell proliferation and nutrient diffusion. Notably, their mechanical properties, in particular compressive strength, can easily be tuned in a range from 50 - 200 kPa by changing the amount of nano-BCP addition, which is comparable to the successful precedents for productive cell regeneration. The latter parts investigate the biopharmaceutical properties of a representative bioscaffold, including drug loading and release studies with two kinds of active compounds, salmon calcitonin and methylprednisolone. Furthermore, the bioscaffold is highly biocompatible as the results of hemocompatibility and hemostasis tests, as well as ovo chick chorioallantoic membrane investigation. The findings of the study suggest the triple-hybrid scaffold as a promising platform for multi-functional drug delivery and bone defect repair.

Nanoengineered injectable hydrogels derived from layered double hydroxides and alginate for sustained release of protein therapeutics in tissue engineering applications.

Chronic Kidney Disease (CKD) which involves gradual loss of kidney function is characterized by low levels of a glycoprotein called Erythropoietin (EPO) that leads to red blood cell  deficiency and anemia. Recombinant human EPO (rhEPO) injections that are administered intravenously or subcutaneously is the current gold standard for treating CKD. The rhEPO injections have very short half-lives and thus demands frequent administration with a risk of high endogenous EPO levels leading to severe side effects that could prove fatal. To this effect, this work provides a novel approach of using lamellar inorganic solids with a brucite-like structure for controlling the release of protein therapeutics such as rhEPO in injectable hydrogels. The nanoengineered injectable system was formulated by incorporating two-dimensional layered double hydroxide (LDH) clay materials with a high surface area into alginate hydrogels for sustained delivery. The inclusion of LDH in the hydrogel network not only improved the mechanical properties of the hydrogels (5-30 times that of alginate hydrogel) but also exhibited a high binding affinity to proteins without altering their bioactivity and conformation. Furthermore, the nanoengineered injectable hydrogels (INHs) demonstrated quick gelation, injectability, and excellent adhesion properties on human skin. The in vitro release test of EPO from conventional alginate hydrogels (Alg-Gel) showed 86% EPO release within 108 h while INHs showed greater control over the initial burst and released only 24% of EPO in the same incubation time. INH-based ink was successfully used for 3D printing, resulting in scaffolds with good shape fidelity and stability in cell culture media. Controlled release of EPO from INHs facilitated superior angiogenic potential in ovo (chick chorioallantoic membrane) compared to Alg-Gel. When subcutaneously implanted in albino mice, the INHs formed a stable gel in vivo without inducing any adverse effects. The results suggest that the proposed INHs in this study can be utilized as a minimally invasive injectable platform or as 3D printed patches for the delivery of protein therapeutics to facilitate tissue regeneration.

Farm level bio-economic modelling of aquatic animal disease and health interventions.

A farm level bio-economic model, for aquatic animal production, of the relationships between inputs (e.g. purchased animals), outputs (e.g. harvested animals) and gross margin (GM) was developed to assess ex-ante the economics of disease and animal health interventions. Feed costs were calculated from estimates of food conversion ratio (FCR), animals harvested and mortality. The model was applied to a typical grow-out rainbow trout (Oncorhynchus mykiss) farm on Lake Titicaca, Peru and a typical shrimp (Paenus vannamei) farm in the Mekong Delta, Vietnam. The model was used in two analyses. Firstly, an approach to assess the burden of disease developed by the Global Burden of Animal Diseases (GBADs) project was adopted. Output under conditions of 'ideal health' was estimated by reducing mortality to zero and removing health costs. GM in both systems increased by approximately 25% when production was kept constant (and stocking rates reduced) and more than doubled if production was allowed to rise (and initial stocking increased). The increase in GM under conditions of ideal compared with current production provided an estimate of the maximum possible benefit from improved health management. Secondly, break-even analysis was used to assess the economics of vaccination against infectious pancreatic necrosis (IPN) vaccine (rainbow trout - RBT) and probiotics (shrimp). If initial stocking was kept constant, and production allowed to rise, break-even points for the intervention (when GM was the same with and without the intervention) were achieved when mortality was reduced by 16% in RBT fry and juvenile and 28% in shrimp. If production was kept constant and benefit realised by reduced initial stocking, the break-even point was achieved for i) vaccination of RBT when mortality in fry and juveniles was reduced by 39%, and ii) probiotics in shrimp production when there was a 15% reduction in mortality (nursery and grow-out), 10% increase in shrimp weight at harvest and 10% improvement in FCR. The results demonstrate how relatively simple models, parameterised with basic farm production data, can assess the burden of disease and quantify ex-ante the potential benefit of interventions. In the absence of trial data, these analyses support decision-making by farmers. The models can be adapted for many aquaculture systems. Farm level results can be extrapolated to estimate disease burden, and benefits of interventions, at regional or national level and thus support informed decision-making and allocation of resources to health management.

Antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells for synergistic chemo-photothermal therapy of drug-resistant bacterial infection.

Despite the many advanced strategies that are available, rapid gene mutation in multidrug-resistant bacterial infections remains a major challenge. Combining new therapeutic strategies such as chemo-photothermal therapy (PTT) with high antibacterial efficiency against drug-resistant Listeria monocytogenes (LM) is urgently needed. Here, we report synergistic chemo-PTT against drug-resistant LM based on antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells (anti-STR-CO-GNSs) as all-in-one nanotheranostic agents for the first time, which was used for accurate antibacterial applications. The anti-STR-CO-GNSs showed excellent photothermal conversion efficiency (31.97 %) and were responsive to near-infrared (NIR) and pH dual stimuli-triggered antibiotic release, resulting in outstanding chemo-photothermal effects against LM. In vitro chemo-photothermal effect of anti-STR-CO-GNSs with laser irradiation caused a greater antibacterial effect (1.37 %), resulting in more rapid killing of LM and prevention of LM regrowth. Most importantly, the mice receiving the anti-STR-CO-GNSs with laser irradiation specifically at the sites of LM infections healed almost completely, leaving only scars on the surface of the skin and resulting in superior inhibitory effects from combined chemo-PTT. Overall, our findings suggest that chemo-PTT using smart biocompatible anti-STR-CO-GNSs is a favorable potential alternative to combat the increasing threat of drug-resistant LM, which opens a new door for clinical anti-infection therapy in the future.

Cellulose Nanocrystals-Incorporated Thermosensitive Hydrogel for Controlled Release, 3D Printing, and Breast Cancer Treatment Applications.

In situ-gel-forming thermoresponsive copolymers have been widely exploited in controlled delivery applications because their critical gel temperature is similar to human body temperature. However, there are limitations to controlling the delivery of biologics from a hydrogel network because of the poor networking and reinforcement between the copolymer networks. This study developed an in situ-forming robust injectable and 3D printable hydrogel network based on cellulose nanocrystals (CNCs) incorporated amphiphilic copolymers, poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA). In addition, the physicochemical and mechanical properties of injectable hydrogels were controlled by physically incorporating CNCs with amphiphilic PCLA copolymers. CNCs played an unprecedented role in physically reinforcing the PCLA copolymers' micelle network via intermicellar bridges. Apart from that, the free-flowing closely packed rod-like CNCs incorporated PCLA micelle networks at low temperature transformed to a stable viscoelastic hydrogel network at physiological temperature. CNC incorporated PCLA copolymer sols effectively coordinated with hydrophobic doxorubicin and water-soluble lysozyme by a combination of hydrophobic and hydrogen bonding interaction and controlled the release of biologics. As shown by the 3D printing results, the biocompatible PCLA hydrogels continuously extruded during printing had good injectability and maintained high shape fidelity after printing without any secondary cross-linking steps. The interlayer bonding between the printed layers was high and formed stable 3D structures up to 10 layers. Subcutaneous injection of free-flowing CNC incorporated PCLA copolymer sols to BALB/c mice formed a hydrogel instantly and showed controlled biodegradation of the hydrogel depot without induction of toxicity at the implantation sites or surrounding tissues. At the same time, the in vivo antitumor effect on the MDA-MB-231 tumor xenograft model demonstrated that DOX-loaded hydrogel formulation significantly inhibited the tumor growth. In summary, the CNC incorporated biodegradable hydrogels developed in this study exhibit a prolonged release with special release kinetics for hydrophobic and hydrophilic biologics.

Biomimetic injectable hydrogel based on silk fibroin/hyaluronic acid embedded with methylprednisolone for cartilage regeneration.

Articular cartilage injury is characterized by limited self-repair capacity due to the shortage of blood vessels, lymphatics, and nerves. Hence, this study aims to exploit a classic injectable hydrogel platform that can restore the cartilage defects with minimally invasive surgery, which is similar to the natural extracellular microenvironment, and highly porous network for cell adhesion and proliferation. In this study, an injectable scaffold system comprised of silk fibroin (SF) and hyaluronic acid (HA) was developed to adapt the above requirements. Besides, methylprednisolone (MP) was encapsulated by SF/HA scaffold for alleviating inflammation. The SF/HA hydrogel scaffold was prepared by chemical cross-linking between the lysine residues of SF via Schiff base formation, and pore diameter of the obtained hydrogels was 100.47 ± 32.09 µm. The highly porous nature of hydrogel could further benefit the soft tissue regeneration. Compared with HA-free hydrogels, SF/HA hydrogel showed more controlled release on MP. In ovo experiment of chick embryo chorioallantoic membrane (CAM) demonstrated that SF/HA hydrogels not altered the angiogenesis and formation of blood vessels, thus making it suitable for cartilage regeneration. Furthermore, in vivo gel formation was validated in mice model, suggesting in situ gel formation of SF/HA hydrogels. More importantly, SF/HA hydrogels exhibited the controlled biodegradation. Overall, SF/HA hydrogels provide further insights to the preparation of effective scaffold for tissue regeneration and pave the way to improve the articular cartilage injury treatment.

Ionically cross-linked alginate-chitosan core-shell hydrogel beads for oral delivery of insulin.

Here, core-shell hydrogel beads for oral insulin delivery at intestine was reported, which was a target site for insulin absorption. The core-shell hydrogel beads were prepared using naturally derived alginate and chitosan polysaccharides by simple dropping technique. In order to effectively control leakage of insulin from core-shell hydrogel beads, insulin was embedded into the layered double hydroxides (LDHs). LDH/insulin-loaded complexes were firstly coated with chitosan, and then coated with alginate to generate core-shell hydrogel beads. The biocompatibility and angiogenic response of core-shell hydrogel beads were evaluated by direct contact of the beads with chick embryo chorioallantoic membrane, which indicates safety of the core-shell beads. The beads successfully retained the insulin within the core-shell structure at pH 1.2, indicating that insulin had a good protective effect in harsh acidic environments. Interestingly, insulin release starts at the simulated intestinal fluid (pH 6.8) and continue to release for 24 h in a sustained manner.

Intention to Quit and Predictive Factors Among Current Smokers in Vietnam: Findings From Adult Tobacco Survey 2020.

BACKGROUND: Smoking leads to many smoking-attributable diseases. The promotion of quitting tobacco smoking is urgent as it has significant and immediate health benefits and improves the impacts of other tobacco control strategies. Intention to quit smoking is considered the first step before quitting smoking. METHODOLOGY: This paper used data from Vietnam provincial GATS 2020 on 80,166 participants who were 15-year-old or older. Data were collected from 34 provinces and cities throughout Vietnam and managed using REDCap. RESULTS: Among those who were current smokers, 50.3% (95% CI: 49.1%-51.4%) had the intention to quit smoking. Some predictive factors found to be positively associated with the intention to quit smoking were age (from 45-64), education level, received information about harmful effects or encouragement to quit smoking from media channels (from 6 channels), hearing about the Tobacco Control Law and noticing health warnings on the cigarette package. There was no significant difference in intention to quit smoking between current smokers from urban and rural areas or among different age groups to start smoking. CONCLUSIONS: Interventions or health promotion programs on smoking cessation should be focused on current smokers who have low education levels as they have a higher smoking rate and are less motivated to stop smoking. Received information about harmful effects or encouragement to quit smoking from media channels is also associated with stopping smoking in the future. The importance of health warning pictures on tobacco packages should be maintained and promoted as it has a specific effect on one's intention to stop smoking.

Graphene Oxide-Reinforced Alginate Hydrogel for Controlled Release of Local Anesthetics: Synthesis, Characterization, and Release Studies.

In pain relief, lidocaine has gained more attention as a local anesthetic. However, there are several side effects that limit the use of local anesthetics. Therefore, it is hypothesized that a hydrogel system with facile design can be used for prolonged release of lidocaine. In this study, we developed a formulation comprises of sodium alginate (SA) and graphene oxide (GO) to prolong the release of lidocaine. The gelation was induced by physically crosslinking the alginate with Ca2+ ions. The formation of blank SA and GO-reinforced SA hydrogels was investigated with different concentration of Ca2+ ions. The controlled release of lidocaine hydrochloride (LH) on both hydrogel systems was studied in PBS solution. The GO-reinforced SA hydrogels exhibited more sustained release than SA hydrogels without GO. In vitro biocompatibility test in L929 fibroblast cells confirmed the non-toxic property of hydrogels. Furthermore, to prove the in-situ gelation and biodegradability of hydrogels the hydrogels were injected on mice model and confirmed the stable gel formation. The hydrogels implanted onto the subcutaneous tissue of hydrogels retained over one week. These results indicate that LH-loaded GO-reinforced SA hydrogel can be a potential biomaterial for controlled release of local anesthetics.

Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitment.

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs). The Lys-PCLA bioconjugates are prepared using thiol-ene reaction between thiolated lysozyme (Lys-SH) and acrylated PCLA (PCLA-Ac). The free-flowing Lys-PCLA bioconjugate sols at low temperature transformed to immovable gel at the physiological condition and exhibited stability upon dilution with buffers. According to the in vitro toxicity test, the Lys-PCLA bioconjugate and PCLA copolymer were non-toxic to RAW 263.7 cells at higher concentrations (1000 µg/mL). In addition, subcutaneous administration of Lys-PCLA bioconjugate sols formed stable hydrogel depot instantly, which suggested the in situ gel forming ability of the bioconjugate. Moreover, the Lys-PCLA bioconjugate hydrogel depot formed at the interface between subcutaneous tissue and dermis layers allowed the active migration and recruitment of DCs. As suggested by these results, the in-situ forming injectable Lys-PCLA bioconjugate hydrogel depot may serve as an implantable immune niche for the recruitment and modification of DCs.

Diagnostic value of cerebral vasospasm by transcranial doppler ultrasound in Vietnamese patients with subarachnoid hemorrhage.

OBJECTIVE: Although the application of transcranial Doppler (TCD) ultrasonography in clinical diagnosis of cerebral vasospasm is popular in clinical practice in Vietnam, available evidence of the predictive value of vasospasm on TCD in the literature was mostly reported from large institutions in developed countries. Hence, this study was conducted to evaluate the value of TCD ultrasonography in the diagnosis of vasospasm in patients with subarachnoid hemorrhage (SAH) in Vietnam. PATIENTS AND METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between 2008 and December 2011. TCD and 64-slice computed tomographic angiography (CTA) were used to cerebral vasospasm in SAH patients. RESULTS: 316 patients were analyzed (mean age = 52.97±12.27 years, 52.2% males). There were statistically significant difference rates of the cerebral vasospasm by Hunt and Hess Classification and Fisher classification (p <0.01). The proportion of the patients with cerebral vasospasm who were diagnosed exactly by TCD was 95.2%, while the proportion of the patients without cerebral vasospasm diagnosed exactly was 91.5%. TCD predictive diagnostic value was the highest, with the sensitivity of 0.95 (95% CI: 0.91-0.98), specificity of 0.91 (95% CI: 0.85-0.96), positive predictive value of 0.94 (5% CI: 0.90-0.97) and negative predictive value of 0.93 (95 CI: 0.87-0.97). Hemiplegia was the clinical symptom with the highest diagnostic value with the sensitivity of 0.34 (95% CI: 0.27-0.41), specificity of 0.92 (95% CI: 0.86-0.96), positive predictive value of 0.86 (95% CI: 0.76-0.93) and negative predictive value of 0.49 (95% CI: 0.41-0.54). CONCLUSIONS: Evidence of vasospasm diagnosis on TCD ultrasonography was found with high accuracy. Current study enables to suggest the wide application of TCD in Vietnam health facilities from central to grassroots levels instead of the CTA use.

REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.

The major human genes regulating Mycobacterium tuberculosis-induced immune responses and tuberculosis (TB) susceptibility are poorly understood. Although IL-12 and IL-10 are critical for TB pathogenesis, the genetic factors that regulate their expression in humans are unknown. CNBP, REL, and BHLHE40 are master regulators of IL-12 and IL-10 signaling. We hypothesized that common variants in CNBP, REL, and BHLHE40 were associated with IL-12 and IL-10 production from dendritic cells, and that these variants also influence adaptive immune responses to bacillus Calmette-Guérin (BCG) vaccination and TB susceptibility. We characterized the association between common variants in CNBP, REL, and BHLHE40, innate immune responses in dendritic cells and monocyte-derived macrophages, BCG-specific T cell responses, and susceptibility to pediatric and adult TB in human populations. BHLHE40 single-nucleotide polymorphism (SNP) rs4496464 was associated with increased BHLHE40 expression in monocyte-derived macrophages and increased IL-10 from peripheral blood dendritic cells and monocyte-derived macrophages after LPS and TB whole-cell lysate stimulation. SNP BHLHE40 rs11130215, in linkage disequilibrium with rs4496464, was associated with increased BCG-specific IL-2+CD4+ T cell responses and decreased risk for pediatric TB in South Africa. SNPs REL rs842634 and rs842618 were associated with increased IL-12 production from dendritic cells, and SNP REL rs842618 was associated with increased risk for TB meningitis. In summary, we found that genetic variations in REL and BHLHE40 are associated with IL-12 and IL-10 cytokine responses and TB clinical outcomes. Common human genetic regulation of well-defined intermediate cellular traits provides insights into mechanisms of TB pathogenesis.

Therapeutic effects of boronate ester cross-linked injectable hydrogels for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is the most common malignancy with a high incidence rate and is the leading cause of cancer-related deaths. Herein, we developed a thermo-responsive hydrogel comprising poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) that exhibits acidity-accelerated delivery of the tumor-targeting glucuronic acid-bearing doxorubicin (DOX-pH-GA) conjugate into tumor tissues. The PCLA copolymer was post-modified with boronic acid (BA-PCLA) to covalently cross-link with the pH-responsive DOX-pH-GA conjugate. The BA-PCLA copolymer effectively coordinated with the DOX-pH-GA conjugate through the boronate ester formation and showed a lower critical gelation temperature. The DOX conjugated via boronate ester exhibited a sustained release in vitro. Subcutaneous administration of PCLA copolymers formed in situ gels in the subcutaneous layers of Sprague-Dawley rats and degraded after 6 weeks. Similarly, BA-PCLA copolymers coordinated with DOX-pH-GA formed a stable in situ gel in vivo. In vivo imaging studies demonstrated that DOX-pH-GA was released in a sustained manner. The anti-tumor activity of the DOX releasing injectable hydrogel was examined using a HepG2 liver cancer xenograft model. The in vivo antitumor effect demonstrated that the DOX releasing hydrogel depot remarkably suppresses the tumor growth. These results demonstrate that the pH-responsive DOX releasing thermo-responsive hydrogel depot has great potential for application in localized anticancer therapy.

Effects of dual-tasking on time-to-boundary during stance in people with PD: A preliminary study.

BACKGROUND: Quiet stance is impacted by Parkinson's disease and dual-tasking. Recently developed outcomes such as the time-to-boundary provide unique insight into balance by integrating center of pressure position with base of support. However, little is known about the effects of Parkinson's disease on time-to-boundary. In particular, the effects of distracting cognitive tasks, and how people with Parkinson's disease prioritize balance and cognitive tasks are poorly understood. METHODS: 14 people with Parkinson's disease and 13 controls completed quiet standing and cognitive Stroop tasks separately (single-task) and together (dual-task). 2-dimentional, medio-lateral, and anterior-posterior time-to-boundary were calculated via force-plate data. Traditional sway outcomes, including sway area and path length, were also calculated. Cognitive performance was measured as the verbal reaction time after auditory stimulus delivery. Prioritization was assessed by taking the difference between cognitive and postural dual-task interference. FINDINGS: Time-to-boundary was worse in Parkinson's disease compared to controls (2-dimentional: p = .019; anterior-posterior: p = .062; medio-lateral: p = .012). Medio-lateral time-to-boundary, but not anterior-posterior, was significantly worse during dual-tasking than single-tasking (p = .024). Neurotypical adults tended to prioritize cognition over medio-lateral postural outcomes. INTERPRETATION: People with Parkinson's disease exhibit worse time-to-boundary than their neurotypical peers, and medio-lateral outcomes were sensitive to single to dual-task performance changes. Further, participants generally showed cognitive prioritization, such that cognitive performance was less impacted than medio-lateral postural outcomes by dual-tasking.

Self-Assembled Amphiphilic Starch Based Drug Delivery Platform: Synthesis, Preparation, and Interactions with Biological Barriers.

Core-shell structured nanoparticles (NPs) render the simultaneous coloading capacity of both hydrophobic and hydrophilic drugs and may eventually enhance therapeutic efficacy. In this study, we employed a facile squalenoylation technology to synthesize a new amphiphilic starch derivative from partially oxidized starch, which self-assembled into core-shell starch NPs (StNPs) only at a squalenyl degree of substitution (DoS) of ∼1%. The StNPs characteristics could be tuned as the functions of the polymer molecular weight, DoS, and NPs concentration. The biopharmaceutical features of the StNPs, including colloidal stability, carrier properties, and biocompatibility, were carefully investigated. The interaction study between StNPs and mucin glycoproteins, the main organic component of mucus, revealed a moderate mucin interacting profile. Furthermore, the StNPs also showed good penetration through Pseudomonas aeruginosa biofilms. These results nominate StNPs as a versatile drug delivery platform with potential applications for mucosal drug delivery and the treatment of persistent infections.

On the in-plane electronic thermal conductivity of biased nanosheet ß12-borophene.

The unique physical and chemical properties of ß12-borophene stem from the coexistence of the Dirac and triplet fermions. The metallic phase of ß12-borophene transitions to the semiconducting one when it is subjected to a perpendicular electric field or bias voltage. In this work, with the aid of a five-band tight-binding Hamiltonian, the Green's function approach and the Kubo-Greenwood formalism, the electronic thermal conductivity (ETC) of the semiconducting phase of ß12-borophene is studied. Two homogeneous (H) and inversion symmetric (IS) models are considered depending on the interaction of the substrate and boron atoms. In addition, due to the anisotropic structure of ß12-borophene, the swapping effect of bias poles is addressed. First of all, we find the pristine ETCIS < ETCH independent of the temperature. Furthermore, a decrease of 74.45% (80.62%) is observed for ETCH (ETCIS) when strong positive bias voltages are applied, while this is 25.2% (47.48%) when applying strong negative bias voltages. Moreover, the shoulder temperature of both models increases (fluctuates) with the positive (negative) bias voltage. Our numerical results pave the way for setting up future experimental thermoelectric devices in order to achieve the highest performance.

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study.

BACKGROUND: Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. METHODS: Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. RESULTS: Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate. CONCLUSIONS: In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment.

Green Silver Nanoparticles Formed by Phyllanthus urinaria, Pouzolzia zeylanica, and Scoparia dulcis Leaf Extracts and the Antifungal Activity.

Phytoconstituents presenting in herbal plant broths are the biocompatible, regenerative, and cost-effective sources that can be utilized for green synthesis of silver nanoparticles. Different plant extracts can form nanoparticles with specific sizes, shapes, and properties. In the study, we prepared silver nanoparticles (P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs) based on three kinds of leaf extracts (Phyllanthus urinaria, Pouzolzia zeylanica, and Scoparia dulcis, respectively) and demonstrated the antifungal capacity. The silver nanoparticles were simply formed by adding silver nitrate to leaf extracts without using any reducing agents or stabilizers. Formation and physicochemical properties of these silver nanoparticles were characterized by UV-vis, Fourier transforms infrared spectroscopy, scanning electron microscope, transmission electron microscope, and energy dispersive X-ray spectroscopy. P.uri.AgNPs were 28.3 nm and spherical. P.zey.AgNPs were 26.7 nm with hexagon or triangle morphologies. Spherical S.dul.AgNPs were formed and they were relatively smaller than others. P.uri.AgNPs, P.zey.AgNPs and S.dul.AgNPs exhibited the antifungal ability effective against Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum, demonstrating their potentials as fungicides in the biomedical and agricultural applications.