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.

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.

Ethical principles for artificial intelligence in education.

The advancement of artificial intelligence in education (AIED) has the potential to transform the educational landscape and influence the role of all involved stakeholders. In recent years, the applications of AIED have been gradually adopted to progress our understanding of students' learning and enhance learning performance and experience. However, the adoption of AIED has led to increasing ethical risks and concerns regarding several aspects such as personal data and learner autonomy. Despite the recent announcement of guidelines for ethical and trustworthy AIED, the debate revolves around the key principles underpinning ethical AIED. This paper aims to explore whether there is a global consensus on ethical AIED by mapping and analyzing international organizations' current policies and guidelines. In this paper, we first introduce the opportunities offered by AI in education and potential ethical issues. Then, thematic analysis was conducted to conceptualize and establish a set of ethical principles by examining and synthesizing relevant ethical policies and guidelines for AIED. We discuss each principle and associated implications for relevant educational stakeholders, including students, teachers, technology developers, policymakers, and institutional decision-makers. The proposed set of ethical principles is expected to serve as a framework to inform and guide educational stakeholders in the development and deployment of ethical and trustworthy AIED as well as catalyze future development of related impact studies in the field.

Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type.

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).

Development of a new Agrobacterium-mediated transformation system based on a dual auxotrophic approach in the filamentous fungus Aspergillus oryzae.

Genetic engineering of the filamentous fungus Aspergillus oryzae still requires more suitable selection markers for fungal transformation. Our previous work has shown that Agrobacterium tumefaciens-mediated transformation (ATMT) based on the uridine/uracil auxotrophic mechanism with pyrG as the selection marker is very efficient for gene transfer in A. oryzae. In the present study, we delete the hisB gene, which is essential for histidine biosynthesis, in A. oryzae via homologous recombination and demonstrate that hisB is a reliable selection marker for genetic transformation of this fungus. Under optimal conditions, the ATMT efficiency of the histidine auxotrophic A. oryzae reached 515 transformants per 106 spores. Especially, we have succeeded in constructing a new ATMT system based on dual auxotrophic A. oryzae mutants with two different selection markers including hisB and pyrG. This dual auxotrophic ATMT system displayed a transformation efficiency of 232 transformants per 106 spores for the hisB marker and 318 transformants per 106 spores for the pyrG marker. By using these selectable markers, the co-expression of the DsRed and GFP fluorescent reporter genes was implemented in a single fungal strain. Furthermore, we could perform both the deletion and complementation of the laeA regulatory gene in the same strain of A. oryzae to examine its function. Conclusively, the ATMT system constructed in our work represents a promising genetic tool for studies on recombinant expression and gene function in the industrially important fungus A. oryzae.

Reduced extrinsic recombination process in anatase and rutile TiO2 epitaxial thin films for efficient electron transport layers.

TiO2 is the most widely used material for the electron transport layers (ETLs) because it is characterized by proper band alignment with light absorbers, adequate optical transmittance, and high electron mobility. There are two thermodynamically stable crystal phases of TiO2: anatase and rutile. However, understanding which phase is more effective as the ETL is still required. In this paper, we demonstrate the different effects of using epitaxial anatase TiO2 and epitaxial rutile TiO2 (both grown using pulsed laser deposition) as the ETL material on the electrical and optical properties. Epitaxial Nb-doped TiO2 layers were used as the common electrode material for the both epitaxial ETLs for which the crystalline structural analysis revealed high crystalline qualities and good coherency for both phases. By analyzing the recombination kinetics, the anatase phase shows a preferable performance in comparison with the rutile phase, although both epitaxial phases show remarkably reduced extrinsic recombination properties, such as trap-assisted recombination. This study demonstrates not only a better electron transporting performance of anatase phase but also reduced extrinsic recombination through epitaxy growth.

Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?

The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account.

Enhanced carrier transport over grain boundaries in lead-free CH3NH3Sn(I1-x Br x )3 (0 ≤ x ≤ 1) perovskite solar cells.

This paper reports on grain boundary (GB) roles in lead-free tin halide perovskite thin films. Nano scale spatial mapping of charge separation efficiency in methylammonium tin halide (MASn(I1-x Br x )3, MA = CH3NH3) thin films were constructed by Kelvin probe force microscopy and conductive atomic force microscopy (C-AFM). We observed downward band bending at GBs under dark conditions and higher surface photovoltage along the GBs, confirmed by C-AFM which showed high local current flows along the GBs. The band bending degree and local current intensity were affected by the Br/I ratio. Photo-generated carriers were more effectively separated and collected at GBs with increased Br content, and hysteresis was observed in Br-rich Sn-halide perovskite.

Trapping charges at grain boundaries and degradation of CH3NH3Pb(I1-x Br x )3 perovskite solar cells.

The electrical properties of CH3NH3Pb(I1-x Br x )3 (x = 0.13) perovskite materials were investigated under ambient conditions. The local work function and the local current were measured using Kelvin probe force microscopy and conductive atomic force microscopy, respectively. The degradation of the perovskite layers depends on their grain size. As the material degrades, an additional peak in the surface potential appears simultaneously with a sudden increase and subsequent relaxation of the local current. The potential bending at the grain boundaries and the intragrains is the most likely reason for the change of the local current surface of the perovskite layers. The improved understanding of the degradation mechanism garnered from this study helps pave the way toward an improved photo-conversion efficiency in perovskite solar cells.

Efficient Carrier Separation and Intriguing Switching of Bound Charges in Inorganic-Organic Lead Halide Solar Cells.

We fabricated a mesoporous perovskite solar cell with a ∼14% conversion efficiency, and we investigated its beneficial grain boundary properties of the perovskite solar cells through the use of scanning probe microscopy. The CH3NH3Pb(I0.88,Br0.12)3 showed a significant potential barrier bending at the grain boundary and induced passivation. The potential difference value in the x = 0.00 sample is ∼50 mV, and the distribution of the positive potential is lower than that of the x = 0.12 sample. We also investigated the polarization and hysteretic properties of the perovskite thin films by measuring the local piezoresponse. Specifically, the charged grain boundaries play a beneficial role in electron-hole depairing and in suppressing recombination in order to realize high-efficiency perovskite solar cells.

Cortical and trabecular load sharing in the human femoral neck.

The relative role of the cortical vs trabecular bone in the load-carrying capacity of the proximal femur-a fundamental issue in both basic-science and clinical biomechanics-remains unclear. To gain insight into this issue, we performed micro-CT-based, linear elastic finite element analysis (61.5-micron-sized elements; ~280 million elements per model) on 18 proximal femurs (5M, 13F, ages 61-93 years) to quantify the fraction of frontal-plane bending moment shared by the cortical vs trabecular bone in the femoral neck, as well as the associated spatial distributions of stress. Analyses were performed separately for a sideways fall and stance loading. For both loading modes and across all 18 bones, we found consistent patterns of load-sharing in the neck: most proximally, the trabecular bone took most of the load; moving distally, the cortical bone took increasingly more of the load; and more distally, there was a region of uniform load-sharing, the cortical bone taking the majority of the load. This distal region of uniform load-sharing extended more for fall than stance loading (77 ± 8% vs 51 ± 6% of the neck length for fall vs. stance; mean ± SD) but the fraction of total load taken by the cortical bone in that region was greater for stance loading (88 ± 5% vs. 64 ± 9% for stance vs. fall). Locally, maximum stress levels occurred in the cortical bone distally, but in the trabecular bone proximally. Although the distal cortex showed qualitative stress distributions consistent with the behavior of an Euler-type beam, quantitatively beam theory did not apply. We conclude that consistent and well-delineated regions of uniform load-sharing and load-transfer between the cortical and trabecular bone exist within the femoral neck, the details of which depend on the external loading conditions.