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Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs.

Obesity and type 2 diabetes are major health burdens for which no effective therapy is available today. One treatment strategy could be to balance the metabolic functions of adipose tissue by regulating gene expressions using miRNAs. Here, we have loaded two anti-adipogenic miRNAs (miR26a and miR27a) into a pegylated lipid nanoparticle (PEG-LNP) formulation by a single-step microfluidic-assisted synthesis step. For the miRNA-loaded LNPs, the following system properties were determined: particle size, zeta potential, miRNA complexation efficiency, and cytotoxicity. We have used a human preadipocyte cell line to address the transfection efficiency and biological effects of the miRNA candidates at the gene and protein level. Our findings revealed that the upregulation of miR27a in preadipocytes inhibits adipogenesis by the downregulation of PPARγ and the reduction of lipid droplet formation. In contrast, miR26a transfection in adipocytes induced white adipocyte browning detected as the upregulation of uncoupling protein 1 (UCP1) as a marker of non-shivering thermogenesis. We conclude that the selective delivery of miRNAs by PEG-LNPs to adipocytes could offer new perspectives for the treatment of obesity and related metabolic diseases.

This study aimed to design a hybrid oral liposomal delivery system for selenium nanoparticles (Lip-SeNPs) to improve the bioavailability of selenium. Thiolated chitosan, a multifunctional polymer with mucoadhesive properties, was used for surface functionalization of Lip-SeNPs. Selenium nanoparticle (SeNP)-loaded liposomes were manufactured by a single step microfluidics-assisted chemical reduction and assembling process. Subsequently, chitosan-N-acetylcysteine was covalently conjugated to the preformed Lip-SeNPs. The Lip-SeNPs were characterized in terms of composition, morphology, size, zeta potential, lipid organization, loading efficiency and radical scavenging activity. A co-culture system (Caco-2:HT29-MTX) that integrates mucus secreting and enterocyte-like cell types was used as a model of the human intestinal epithelium to determine adsorption, mucus penetration, release and transport properties of Lip-SeNPs in vitro. Thiolated Lip-SeNPs were positively charged with an average size of about 250 nm. Thiolated Lip-SeNPs tightly adhered to the mucus layer without penetrating the enterocytes. This finding was consistent with ex vivo adsorption studies using freshly excised porcine small intestinal tissues. Due to the improved mucoadhesion and retention in a simulated microenvironment of the small intestine, thiolated Lip-SeNPs might be a promising tool for oral selenium delivery.

In burn injuries, risk factors and limitations to treatment success are difficult to assess clinically. However, local cellular responses are characterized by specific gene-expression patterns. MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a posttranscriptional level. Secreted through exosome-like vesicles (ELV), miRNAs are intracellular signalers and epigenetic regulators. To date, their role in the regulation of the early burn response remains unclear. Here, we identified 43 miRNAs as potential regulators of the early burn response through the bioinformatics analysis of an existing dataset. We used an established human ex vivo skin model of a deep partial-thickness burn to characterize ELVs and miRNAs in dermal interstitial fluid (dISF). Moreover, we identified miR-497-5p as stably downregulated in tissue and dISF in the early phase after a burn injury. MiR-218-5p and miR-212-3p were downregulated in dISF, but not in tissue. Target genes of the miRNAs were mainly upregulated in tissue post-burn. The altered levels of miRNAs in dISF of thermally injured skin mark them as new biomarker candidates for burn injuries. To our knowledge, this is the first study to report miRNAs altered in the dISF in the early phase of deep partial-thickness burns.

Lipoproteins are endogenous nanoparticles which are the major transporter of fats and cholesterol in the human body. They play a key role in the regulatory mechanisms of cardiovascular events. Lipoproteins can be modified and manipulated to act as drug delivery systems or nanocarriers for contrast agents. In particular, high density lipoproteins (HDL), which are the smallest class of lipoproteins, can be synthetically engineered either as nascent HDL nanodiscs or spherical HDL nanoparticles. Reconstituted HDL (rHDL) particles are formed by self-assembly of various lipids and apolipoprotein AI (apo-AI). A variety of substances including drugs, nucleic acids, signal emitting molecules, or dyes can be loaded, making them efficient nanocarriers for therapeutic applications or medical diagnostics. This review provides an overview about synthesis techniques, physicochemical properties of rHDL nanoparticles, and structural determinants for rHDL function. We discuss recent developments utilizing either apo-AI or apo-AI mimetic peptides for the design of pharmaceutical rHDL formulations. Advantages, limitations, challenges, and prospects for clinical translation are evaluated with a special focus on promising strategies for the treatment and diagnosis of atherosclerosis and cardiovascular diseases.

Background: In this retrospective study, we examine the impact that employing a permanent derotation screw (DRS) has on the rate of revision for 2-hole dynamic hip screws (DHS, a.k.a. sliding hip screws), used for internal fixation of intracapsular neck of femur (NOF) fractures. To the best of our knowledge, we are the first to examine the impact of using a derotation screw on DHS revision rate. Methods: We obtained a list of 64 patients suffering intracapsular NOF fracture treated with 2-hole DHS over a 5-year period, 28 of these were also treated with a DRS, forming our DRS group, 36 were not (non-DRS group). Fracture severity and patient demographics between the groups were compared to ensure homogeneity. The rate of revision to arthroplasty (total or hemi) of the two groups were compared. Results: The mean age in the DRS group was 70.79 years, 1.77 years lower than the non-DRS group (p=0.570). The DRS group had a rate of revision of 14%, in comparison with 39% in the non-DRS group (p=0.0299), corresponding with a number needed to treat of 4.06 derotation screws to prevent a single failure. Conclusions: In this study, employing a permanent derotation screw alongside a 2-hole DHS was associated with a significantly lower rate of revision to arthroplasty than using a 2-hole DHS alone. We would recommend this be further investigated with prospective randomized trials, to provide robust evidence and make clinical recommendations.

Ova knjiga, rezultat istraživačkog projekta "Človekove pravice in regulacija umetne inteligence vredne zastupanja," predstavlja sveobuhvatan pristup pitanjima koja proizlaze iz sveprisutne implementacije umjetne inteligencije (UI) u životnu svakodnevicu. Autori su se bavili kompleksnim i mnogobrojnim aspektima utjecaja UI na pravo, demokraciju, kazneno pravo te pitanja etičkog razvoja i uporabe UI. Knjiga, objavljena 2023. od strane izdavača "Dobra knjiga" iz Sarajeva, ima dodanu vrijednost u obliku predgovora profesorice emerite dr. Hajrije Sijerčić-Čolić. Njezin predgovor naglašava važnost sustavnog i višedimenzionalnog pristupa temi, koji prelazi granice klasične pravne analize i uključuje sociološko-psihološki i filozofsko-historijski kontekst. Jedan od ključnih doprinosa knjige je jezična prilagodba kompleksnih i internacionaliziranih termina specifičnih za UI područje. Autori su prepoznali izazove jezične prilagodbe u hrvatskoj akademskoj zajednici te istaknuli važnost stvaranja novih termina koji odgovaraju specifičnim jezičnim izričajima i pravilima prostora na kojem se knjiga obrađuje. Kroz svih pet poglavlja knjige i radove 16 autora naglašava se važnost ozbiljnog pristupa razvoju i primjeni UI, ističući neograničeni potencijal, ali i opasne rizike koje ne smijemo zanemariti. S obzirom na brz razvoj UI i mogućnost zaostajanja pravne regulacije, postavljaju se otvorena pitanja koja predstavljaju izvrsnu polaznu točku za razmatranje odgovornih i etičkih pristupa. Kroz holistički pristup, knjiga analizira opća pitanja regulacije, utjecaja UI na pravo i društvene procese, te etičkih implikacija. Pored teorijskih rasprava, autori se oslanjaju na analizu konkretnih sustava UI, istraživanja, regulacija, sudskih presuda i primjera, čineći knjigu prikladnom ne samo za akademsku zajednicu, već i za pravne praktičare, savjetodavna tijela, zakonodavna tijela, nevladine organizacije te zainteresiranu javnost. Ova knjiga će služiti kao vodič kroz kompleksne koncepte, regulacije i istraživanja na raskrižju prava i UI, pružajući čitateljima smjernice za suočavanje s izazovima i pridonošenje rješenjima.

The paper presents the results of comparative wearing of cultivator hoes protected with two different materials with regard to the lifespan of the blades. During the operation of the hoes outside the track of the tractor wheels with protected blades of materials M1 and M2, equal wear of mass and surface was recorded. The hoes lost an average of 0,563 g/ha cultivated area or an average of 119,46 g with a standard deviation of 2,876 when working with both blades in compacted soil (in the tracks of tractor wheels) protected by M1 material. For hoes protected by M2 material, the average loss was 0,566 g/ha of cultivated area or an average of 120,10 g for the research period with a standard deviation of 4,609. Both materials in the most difficult working conditions showed equal resistance to wear and retention of the initial shape of the hoe.

The research results of the spraying technical factors' impact on ground and air drift, and the deposit on the treetop in cherry orchards, are presented in the paper. Two different spraying systems (classical and sensory system) are investigated, Agromehanika AGP 200 ENU sprayer being used. The research is conducted according to ISO standard 22866 (Plant Protection Equipment - Drift Measurement Methods in Field Conditions). The impact of spraying norm as factor A (A1 – 250 l/ha; A2 – 200 l/ha); the nozzle type as factor B (B1 – Lechler TR 8002 C; B2 – Lechler ITR 8002 C) and the fan air velocity as factor C (C1 – 18 m/s; C2 – 12 m/s) are examined by the variance analysis. To spray and evaluate the drift, Tartazine organic dye solution with 4% concentration is used. The filter papers, used as collectors, according to the specified ISO standard, are placed directly in the spraying zone. The sampled filter papers are washed out with 10 ml of deionised water under laboratory conditions. After washing, the colour intensity, i.e., the solution wave-length, is read by a spectrophotometer (Varian Cary 50 UV-Visible). Different drift intensity (ground and air drift) and treetop deposits are realized by the usage of various treatments of technical spraying factors and various spraying systems. Unlike the ground and air drifts, the deposit within the treetop does not show statistically significant change by using a sensory spraying system, i.e. by using a selective application.

The paper presents the recorded vibrations that affect the operator’s body when an agricultural tractor moves along three types of agrotechnical surfaces, i.e. asphalt, an alfalfa field, and a field path, and when seven different tractor seat upholsteries are used. The research was performed in accordance with the HRN ISO 2631-1 and HRN ISO 2631-4 standards. The tractor used in the research was an IMT 560 and the duration of the measurement was 30 minutes, which was repeated three times for every tractor seat upholstery type. The research was exploitative. The measurements were performed using an MMF VM30 meter. The paper reveals a different level of vibrations in dependence with different surfaces and seat upholsteries. The fewest vibrations were produced by asphalt, and the best upholsteries are memory foam and sponge.

The wear of induction cladded coating during motion was investigated through the abrasive mass at a speed of 1.0 to 3.0 m/s and the impact angle of abrasive particles with a worn surface of 0° to 90°. Cladding was performed by using Ni-Cr-Si-B-Fe flame spraying powder. Experimental research was carried out by using the Response Surface Method (RSM) and Central Composite Design (CCD). Analysis of variance proved that both motion speed and impact angle had significant impact on the wear of coating, both individually and interactively. Motion speed had the greatest influence, and the interaction of speed and angle had the least influence. The wear rate increased along with the motion speed increase, and the influence of the impact angle depends on the wear speed. At a speed of 1 m/s, the wear increases along with the increase of angle from 0° to 45° and then continues to decrease up to the angle of 90°. At a speed of 2 m/s, the wear increases along with the angle increase from 0° to 30° and then continues to decrease up to the angle of 90°. At a speed of 3 m/s, the wear increases along with the angle increase from 0° to 20° and then decreases as the angle increases up to 90°. Based on the statistical data processing, this research developed the mathematical model of wear in the form of quadratic polynomial that describes the influences of input variables in individual and interactive form.