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Selective logging is one of the largest drivers of tropical forest degradation. While logged forests often retain high alpha‐diversity of tropical trees at local spatial scales, understanding how selective logging impacts tree beta‐diversity and community composition across far larger spatial scales remains a key unresolved question.We leverage large datasets of more than 155,000 adult trees over 35 cm DBH covering 3100 ha of Amazonian rainforest to inform simulations of selective logging harvests across a gradient of logging intensity (0–40 m3 ha−1). These simulations incorporate real world price data, account for all forest damage throughout the harvest process and assume preferential harvest of the most valuable stems. We use the simulations to assess how selective logging affects canopy tree beta‐diversity and composition across large spatial scales, whether nestedness or turnover of species best explains variation in communities across space, and how the spatial scale of sampling influences observed beta‐diversity effects.Selective logging had minimal impacts on beta‐diversity across the canopy tree community, but caused substantial subtractive heterogenization in community composition for larger trees, in particular very large trees over 110 cm DBH. Turnover is the dominant component of tree beta‐diversity in unlogged and logged forests. Increasing the spatial grain of sampling reduced the observed importance of logging in explaining patterns of beta‐diversity in very large tree communities.Synthesis and applications. Minimal impacts on tree beta‐diversity across large spatial scales points towards the retention of substantial conservation value in logged tropical forests. Strong subtractive heterogenization in very large trees indicates the breakdown of broad scale patterns of composition with potential negative consequences for recruitment processes, fauna reliant upon emergent trees, and other ecosystem functions and services. Avoiding large‐scale erosion of very large tree community composition in the Amazon requires stronger conservation policies, including enforced retention or maximum cutting diameters. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the potential adjunctive effect of a resorbable collagen membrane covering a xenogeneic bone replacement graft in the reconstructive surgical therapy of peri‐implantitis. Materials and Methods: Forty‐three patients (43 implants) diagnosed with peri‐implantitis associated with intra‐bony defects were treated with a surgical reconstructive approach that included a xenogeneic bone substitute material. Additionally, resorbable collagen membranes were placed over the grafting material at sites randomly allocated to the test group; conversely, no membranes were placed in the control group. Clinical outcomes, namely probing pocket depth (PPD), bleeding and suppuration on probing (BoP and SoP), marginal mucosal level (REC) and keratinized mucosa width (KMW), were recorded at baseline and 6 and 12 months after surgery. Radiographic marginal bone levels (MBLs) and patient‐reported outcomes (PROs) were assessed at baseline and 12 months. A composite outcome (success) was evaluated at 12 months, which included the absence of BoP/SoP, PPD ≤5 mm and reduction of buccal marginal mucosal level (buccal REC) of ≤1 mm. Results: At 12 months, no implants were lost and treatment success was observed at 36.8% and 45.0% of implants in the test and control groups, respectively (p =.61). Similarly, there were no significant differences between groups in terms of changes of PPD, BoP/SoP, KMW, MBL or buccal REC. Post‐surgical complications were observed in the test group only (e.g., soft tissue dehiscence, exposure of particulate bone graft and/or resorbable membrane). Longer surgical times (~10 min; p <.05) and higher levels of self‐reported pain at 2 weeks (p <.01) were observed in the test group. Conclusions: This study failed to demonstrate the presence of added clinical or radiographic benefits of the use of a resorbable membrane to cover a bone substitute material within the reconstructive surgical therapy of peri‐implantitis associated with intra‐bony defects. [ABSTRACT FROM AUTHOR]

Copyright of Rudarsko-Geolosko-Naftni Zbornik is the property of Faculty of Mining, Geology & Petroleum Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper proposes a framework for creating trained models for object detection in digital documents using convolutional neural networks (CNNs). CNNs are artificial networks that are capable of learning at different levels of abstraction and are structured to resemble neurons in the primary visual cortex of a biological brain. The X101-FPN model, which is based on pre-trained neural networks exposed within the collections offered by the Detectron 2 library, is selected for this research. The model contains a hierarchical structure of 101 CNN layers, a residual neural network, and a pyramidal network of functions. This research presents a case study for the detection of QR codes using Artificial Intelligence (AI) techniques with convolutional neural networks, based on successful case studies using different Deep Learning techniques. The pre-trained model is trained on different types of preprocessed images and with various approaches to measuring correct accuracy and performance against proposed scenarios. Finally, various tests are performed to conclude the conditions and best versions of training for QR code detection. [ABSTRACT FROM AUTHOR]

Epithelial folding depends on mechanical properties of both epithelial cells and underlying basement membrane (BM). While folding is essential for tissue morphogenesis and functions, it is difficult to recapitulate features of a growing epithelial monolayer for in vitro modeling due to lack of in vivo like BM. Herein, we report a method to overcome this difficulty by culturing on an artificial basement membrane (ABM) the primordial lung progenitors (PLPs) from human induced pluripotent stem cells (hiPSCs). The ABM was achieved by self-assembling collagen IV and laminin, the two principal natural BM proteins, in the pores of a monolayer of crosslinked gelatin nanofibers deposited on a honeycomb micro-frame. The hiPSC-PLPs were seeded on the ABM for alveolar differentiation under submerged and air-liquid interface culture conditions. As results, the forces generated by the growing epithelial monolayer led to a geometry-dependent folding. Analysis of strain distribution in a clamped membrane provided instrumental insights into some of the observed phenomena. Moreover, the forces generated by the growing epithelial layer led to a high-level expression of surfactant protein C and a high percentage of aquaporin 5 positive cells compared with the results obtained with a nanofiber-covered bulk substrate. Thus, this work demonstrated the importance of recapitulating natural BM for advanced epithelial modeling. The effort to develop in vitro epithelial models has not been entirely successful to date, due to lack of in vivo like basement membrane (BM). This lack has been overcome by using a microfabricated dense thin and pliable sheet like structure made of natural BM proteins. With such an artificial BM, alveolar epithelial deformation and folding could be studied and date could be correlated to numerical analyses of a plate theory. This method is simple and effective, enabling further developments in epithelial tissue modeling. [Display omitted] [ABSTRACT FROM AUTHOR]

Water pollution caused by oil spills at sea and industrial and daily wastewater discharges are causing serious damage to the ecological environment, not only in terms of economic losses but also in terms of human health and survival, a problem that needs to be addressed urgently. Oil/water separation is a global challenge, and while these problems are frequent, various oil/water separation strategies have been extensively investigated in recent years. The efficiency of the materials prepared is a key factor, as are the environmental friendliness and low cost of the methods and raw materials used in the experiments. This work reviews methods and materials applied in oil/water separation in recent years, including natural textile materials, metal meshes, synthetic membranes, particulate adsorbent materials, foams, sponges, aerogels, smart controllable special wettable separation materials. [ABSTRACT FROM AUTHOR]

Non-aqueous organic redox flow batteries (NAORFBs) suffer from rapid capacity fading mainly due to the crossover of redox-active species across the membrane. Minimizing the crossover of redox-active species through ion exchange membranes remains a complex challenge in NAORFBs. To address the crossover issue, we approached the problem through a molecular size exclusion principle designing a dimer of viologen derivative as an anode material. Coupled with N-hexyl phenothiazine as a catholyte, a static cell was demonstrated, which exhibits an excellent cycling stability (100 cycles) with an average Coulombic efficiency of 90% at 10 mA cm−2 current density. [ABSTRACT FROM AUTHOR]

Objective: To construct a hollow copper sulfide nano-enzyme lipid composite nanocarrier CuS@LIP, and to further investigate the effect and mechanism of CuS@LIP combined laser irradiation on killing melanoma B6-F10 cells. Methods: (2, 3-dioleoyloxy-propyl) -3-trimethylammonium-propane (chloride salt) (DOTAP) cationic liposomes (LIPs) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome-coated copper sulfide nanocarriers (CuS@LIP). The photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1 064 nm laser irradiation. The peroxidase-like activity of CuS@LIP was verified by a catalytic activity detecting system of hydrogen peroxide (H2O2) and 3, 3', 5, 5' -tetramethylbenzidine (TMB). B16-F10 cells were treated respectively with a series of mass concentration gradients of CuS or CuS@LIP with or without laser. The cell viability of B16-F10 cells was determined via CCK-8 assay. Calcein-AM/PI staining and Annexin V-FITC/PI staining combined with flow cytometry detected the effects of 20 μg/mL CuS or CuS@LIP on the cell viability and apoptosis of B16-F10 cells under laser or non-laser irradiation, respectively. Results: The average particle size of successfully prepared CuS@LIP was (178.23±6.46) nm and the average Zeta potential was (20.47±0.93) mV. The highest temperature of 80 μg/mL CuS@LIP under laser irradiation was 65.4 °C, which was higher than that of CuS at 63.4 °C. The endpoint temperature of CuS@LIP was basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP had the same peroxidase-like catalytic activity as CuS. CuS@LIP had no significant effect on the proliferation activity of B16-F10 cells in vitro when it was less than 20 μg/mL (P>0.05), but the survival rate was significantly reduced by 58.18% after laser irradiation ([29.76±3.60]% vs [87.95±8.18]%, P<0.000 1). The apoptosis rate was significantly increased ([19.34±4.41]% vs [13.36±0.86]%, P<0.01). Conclusion: The prepared CuS@LIP has physical and chemical properties, good photothermal properties and excellent peroxidase-like catalytic activity that meet the design requirements, and it shows a better effect of killing B16-F10 cells when combined with laser irradiation. [ABSTRACT FROM AUTHOR]

The X oilfield is the first sandstone reservoir under the influence of igneous rock, which is discovered and put into development in Bohai Sea. Compared with the conventional sandstone reservoir, the oilfield is affected by magmatic activity, the reservoir heterogeneity is serious and the micro pore structure is complex, which results in the poor correlation between mobility calculated by traditional methods and specific oil production index. In order to predict oil well productivity and guide oilfield well location deployment, the quantitative transformation of sandstone reservoir affected by igneous rock is studied in this paper. According to the distribution mode of igneous rock in the reservoir, a permeability model of quantitative characterization for sandstone reservoir permeability is established, in which the influences of heat conduction, reservoir skeleton deformation and stress sensitivity are considered, and then the igneous rock influence on the ground temperature field of surrounding rock is simulated by ANSYS software. According to the relationship between porosity and permeability, the quantitative transformation effect of igneous rock thermal effect on sandstone reservoir is quantitatively characterized. The reservoir temperature field variation law, different baking types and igneous rock thickness influence on the transformation degree of sandstone reservoir are analyzed. Finally, the X oilfield is taken as an example to verify the research method, and the second batch of wells location deployment is successfully guided. The results show that the thermal effect of igneous rock reduces the permeability of reservoir, and the temperature of reservoir increases first and then decreases with time, the rising speed is faster than the falling speed, with the increase in distance from igneous rock, the maximum temperature of reservoir shows a downward trend, in the case of baking on both sides, the heat of igneous rock is greater, which makes the temperature of surrounding reservoir rise more, and the transformation effect on reservoir is more obvious. The influence range of igneous rock thickness on permeability is basically the same, but with the increase in thickness, igneous rock has a greater influence on surrounding rock. The research example of the X oilfield shows that the existence of igneous rock reduces the reservoir physical properties of development wells by 1.2–5.9 times. The correlation between igneous rock physical properties and specific oil production index corrected by this method can reach 0.9478. By avoiding igneous rock, the comparative production of the second batch of development wells is 1.5 times that of the first batch of development wells. [ABSTRACT FROM AUTHOR]

Copyright of Iraqi Journal of Chemical & Petroleum Engineering is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A one‐selector one resistor (1S1R) array formed of a selector and resistive random access memory (RRAM) is an important way to achieve high‐density storage and neuromorphic computing. However, the low durability and poor consistency of the selector limit its practical application. The fabrication of a selector based on egg albumen (EA) is reported in this paper. The device exhibits excellent bidirectional threshold switching characteristics, including a low leakage current (10−7 A), a high ON/OFF current ratio (106), and good endurance (>700 days). It is used as a selector to form a 1S1R unit in combination with an EA‐based RRAM to effectively solve the leakage current in a crossbar array. A feasible solution is provided for the realization of a protein‐based 1S1R array to achieve high‐density storage. The 1S1R unit shows characteristics similar to those of synapses in the human brain under impulse excitation and has great potential in simulating the human brain for neuromorphic calculations.) [ABSTRACT FROM AUTHOR]

With the rapid development of artificial intelligence (AI), there is an urgent need for developing a biological sensory perception system that can simulate the human brain for information processing. Inspired by the biological vision system, photo‐responsive photonic synapses are ideal devices for constructing photosensitive artificial neural networks for neuromorphic computing tasks. This paper reports a stable photonic synaptic device in an array layout with adjustable synaptic plasticity under ultraviolet light pulses. Since the heterojunction has a photoconductivity effect and the trap layer provides superior charge carrier trapping capability, optical sensing, memory, and neuromorphic computing are integrated into a single device. Meanwhile, supervised learning of handwritten digitals is achieved by exploiting the multistate conductance by photoelectric co‐modulation and the specific decay law. The recognition rate reaches 90.6% and hardly changes with time. Additionally, the device can simplify the artificial neural network (ANN) and reduce its size to 3.78% of the original network while retaining strong fault tolerance and learning ability. The photonic artificial synapses based on ultraviolet light modulation provide a novel and effective approach for photosensory ANNs to perform in situ computation. [ABSTRACT FROM AUTHOR]

Organic phototransistors can enable many important applications such as nonvolatile memory, artificial synapses, and photodetectors in next‐generation optical communication and wearable electronics. However, it is still a challenge to achieve a big memory window (threshold voltage response ∆Vth) for phototransistors. Here, a nanographene‐based heterojunction phototransistor memory with large ∆Vth responses is reported. Exposure to low intensity light (25.7 µW cm−2) for 1 s yields a memory window of 35 V, and the threshold voltage shift is found to be larger than 140 V under continuous light illumination. The device exhibits both good photosensitivity (3.6 × 105) and memory properties including long retention time (>1.5 × 105 s), large hysteresis (45.35 V), and high endurance for voltage‐erasing and light‐programming. These findings demonstrate the high application potential of nanographenes in the field of optoelectronics. In addition, the working principle of these hybrid nanographene‐organic structured heterojunction phototransistor memory devices is described which provides new insight into the design of high‐performance organic phototransistor devices. [ABSTRACT FROM AUTHOR]

Software-based mold flow analysis is often performed to confirm optimized resin pipe arrangements. In this study, the GeoDict software and reverse scanning were employed to develop a method for performing rapid porosity and permeability estimation. A comparison of the results from one-dimensional resin flow and Easyperm tests revealed a 10% variation in the porosity and permeability parameters obtained through the proposed rapid estimation method. In addition, the obtained parameters were substituted into a Moldex3D model to simulate the resin flow on the personal watercraft hull during vacuum-assisted resin transfer molding (VARTM). A comparison of simulation results and hull infusion results revealed that the integration of the proposed rapid estimation method with Moldex3D allowed for the accurate simulation of the resin flow in large fiber-reinforced-plastic (FRP) products (variation <8%). The proposed method can be applied to large wind turbine FRP parts and large FRP yacht components to increase process planning efficiency and product stability. [ABSTRACT FROM AUTHOR]

The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections. [ABSTRACT FROM AUTHOR]

Simple Summary: The research paper reported on a newly developed screening technique called Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA) used for determining the most effective medication for breast cancer patients. The study found that the MTAM-HFA approach had a high level of accuracy in predicting the patient's response to the medication therapy, and there was a significant correlation between the screening outcome and the clinical outcome. The findings suggest that the MTAM-HFA technique has great potential for developing customized therapy for cancer care. With its ability to identify precise therapies for breast cancer patients, the MTAM-HFA screening method could transform cancer therapy, resulting in better outcomes for patients. The study provides valuable information for healthcare professionals and researchers working on breast cancer therapy research. Breast cancer is a severe public health problem, and early treatment with powerful anticancer drugs is critical for success. The researchers investigated the clinical results of a novel screening tool termed Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA) in breast cancer patients in this clinical investigation. In all trial participants, the MTAM-HFA was utilized to identify active medicines for the treatment of breast cancer. The MTAM-HFA was shown to be extremely useful in predicting patient response to anticancer medication therapy in this study. Furthermore, the substantial association between the MTAM-HFA screening outcome and the clinical outcome of the respective patients emphasizes the promise of this unique screening technology in discovering effective anticancer medication combinations for the treatment of breast cancer. These findings indicate that the MTAM-HFA has clinical significance and might be a valuable tool in the development of tailored therapy for cancer care. This study provides helpful information for physicians and scientists working on breast cancer therapy research. The potential benefits of employing MTAM-HFA to find accurate therapies for breast cancer patients might lead to enhanced personalized medicine approaches to cancer care, resulting in better patient outcomes. Overall, the MTAM-HFA screening approach has the potential to revolutionize customized cancer therapy, providing hope to both patients and physicians. [ABSTRACT FROM AUTHOR]

Hyaline cartilage has very limited repair capability and cannot be rebuilt predictably using conventional treatments. This study presents Autologous Chondrocyte Implantation (ACI) on two different scaffolds for the treatment of lesions in hyaline cartilage in rabbits. The first one is a commercially available scaffold (Chondro–Gide) made of collagen type I/III and the second one is a polyethersulfone (PES) synthetic membrane, manufactured by phase inversion. The revolutionary idea in the present study is the fact that we used PES membranes, which have unique features and benefits that are desirable for the 3D cultivation of chondrocytes. Sixty-four White New Zealand rabbits were used in this research. Defects penetrating into the subchondral bone were filled with or without the placement of chondrocytes on collagen or PES membranes after two weeks of culture. The expression of the gene encoding type II procollagen, a molecular marker of chondrocytes, was evaluated. Elemental analysis was performed to estimate the weight of tissue grown on the PES membrane. The reparative tissue was analyzed macroscopically and histologically after surgery at 12, 25, and 52 weeks. RT-PCR analysis of the mRNA isolated from cells detached from the polysulphonic membrane revealed the expression of type II procollagen. The elementary analysis of polysulphonic membrane slices after 2 weeks of culture with chondrocytes revealed a concentration of 0.23 mg of tissue on one part of the membrane. Macroscopic and microscopic evaluation indicated that the quality of regenerated tissue was similar after the transplantation of cells placed on polysulphonic or collagen membranes. The established method for the culture and transplantation of chondrocytes placed on polysulphonic membranes resulted in the growth of the regenerated tissue, revealing the morphology of hyaline-like cartilage to be of similar quality to collagen membranes. [ABSTRACT FROM AUTHOR]

Anthracyclines have contributed significantly to remarkable improvements in overall survival and are regarded as the most effective cytostatic drug for cancer treatment in various malignancies. However, anthracyclines are a significant cause of acute and chronic cardiotoxicity in cancer patients, and long-term cardiotoxicity can lead to death in about one-third of patients. Several molecular pathways have been implicated in the development of anthracycline-induced cardiotoxicity, although the underlying mechanisms of some molecular pathways are not fully elucidated. It is now generally believed that anthracycline-induced reactive oxygen species (resulting from intracellular metabolism of anthracyclines) and drug-induced inhibition of topoisomerase II beta are the key mechanisms responsible for the cardiotoxicity. To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L -Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia. • Novel anthracycline derivatives. • Less or no cardiotoxicity. • Early clinical trials in different indications. [ABSTRACT FROM AUTHOR]

Kidney renal clear cell carcinoma (KIRC) accounts for approximately 75% of all renal cancers. The prognosis for patients with metastatic KIRC is poor, with less than 10% surviving five years after diagnosis. Inner membrane mitochondrial protein (IMMT) plays a crucial role in shaping the inner mitochondrial membrane (IMM), regulation of metabolism and innate immunity. However, the clinical relevance of IMMT in KIRC is not yet fully understood, and its role in shaping the tumor immune microenvironment (TIME) remains unclear. This study aimed to investigate the clinical significance of IMMT in KIRC using a combination of supervised learning and multi-omics integration. The supervised learning principle was applied to analyze a TCGA dataset, which was downloaded and split into training and test datasets. The training dataset was used to train the prediction model, while the test and the entire TCGA dataset were used to evaluate its performance. Based on the risk score, the cutoff between the low and high IMMT group was set at median value. A Kaplan-Meier curve, receiver operating characteristic (ROC) curve, principal component analysis (PCA) and Spearman's correlation were conducted to evaluate the prediction ability of the model. Gene Set Enrichment Analysis (GSEA) was used to investigate the critical biological pathways. Immunogenicity, immunological landscape and single-cell analysis were performed to examine the TIME. Databases including Gene Expression Omnibus (GEO), Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were employed for inter-database verification. Pharmacogenetic prediction was analyzed via single-guide RNA (sgRNA)-based drug sensitivity screening using Q-omics v.1.30. Low expressions of IMMT in tumor predicted dismal prognosis in KIRC patients and correlated with KIRC progression. GSEA revealed that low expressions of IMMT were implicated in mitochondrial inhibition and angiogenetic activation. In addition, low IMMT expressions had associations with reduced immunogenicity and an immunosuppressive TIME. Inter-database verification corroborated the correlation between low IMMT expressions, KIRC tumors and the immunosuppressive TIME. Pharmacogenetic prediction identified lestaurtinib as a potent drug for KIRC in the context of low IMMT expressions. This study highlights the potential of IMMT as a novel biomarker, prognostic predictor and pharmacogenetic predictor to inform the development of more personalized and effective cancer treatments. Additionally, it provides important insights into the role of IMMT in the mechanism underlying mitochondrial activity and angiogenesis development in KIRC, which suggests IMMT as a promising target for the development of new therapies. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr. Techniques such as thermal analysis, electron microscopy, spectroscopy and in vitro assays were used to characterize RocBr. A topical oil/water emulsion lotion formulation of RocBr was successfully developed and evaluated. The in vitro permeation behavior of RocBr from its lotion formulation was quantified with Strat-M® synthetic biomimetic membrane and EpiDerm™ 3D human skin tissue. Significant membrane retention of RocBr drug was evident and more retention was obtained with the lotion formulation compared with the solution. This is the first systematic and comprehensive study to report these findings. [ABSTRACT FROM AUTHOR]

The use of biomaterials and bioactive agents has shown promise in bone defect repair, leading to the development of strategies for bone regeneration. Various artificial membranes, especially collagen membranes (CMs) that are widely used for periodontal therapy and provide an extracellular matrix-simulating environment, play a significant role in promoting bone regeneration. In addition, numerous growth factors (GFs) have been used as clinical applications in regenerative therapy. However, it has been established that the unregulated administration of these factors may not work to their full regenerative potential and could also trigger unfavorable side effects. The utilization of these factors in clinical settings is still restricted due to the lack of effective delivery systems and biomaterial carriers. Hence, considering the efficiency of bone regeneration, both spaces maintained using CMs and GFs can synergistically create successful outcomes in bone tissue engineering. Therefore, recent studies have demonstrated a significant interest in the potential of combining CMs and GFs to effectively promote bone repair. This approach holds great promise and has become a focal point in our research. The purpose of this review is to highlight the role of CMs containing GFs in the regeneration of bone tissue, and to discuss their use in preclinical animal models of regeneration. Additionally, the review addresses potential concerns and suggests future research directions for growth factor therapy in the field of regenerative science. [ABSTRACT FROM AUTHOR]

Background: Quercetin is a flavonoid having anti-cancer properties; however, it has low stability, insufficient bioavailability, and poor solubility. This study aimed to load quercetin on nanoliposomes to enhance its efficiency against SW48 colorectal cancer cells. The cytotoxicity of free-quercetin and quercetin-loaded nanoliposomes on the expression of the epidermal growth factor receptor (EGER) gene was investigated. Methods: This present in vitro study was conducted at Yasuj University of Medical Sciences (Yasuj, Iran) in 2021. In this in vitro study, the lipid thin-film hydration method was used to synthesize quercetin-loaded liposomes. Additionally, high-performance liquid chromatography (HPLC) analyses, dynamic light scattering (DLS), and transmission electron microscopy (TEM) investigations were used to characterize nanomaterials. Following that, MTT, flow cytometry, and real-time PCR were used to investigate the cytotoxicity of quercetin-loaded liposomes on the colorectal cancer cells SW48 cell line, the incidence of apoptosis, and the expression of the EGFR gene in these cells. Statistical analysis was performed using the SPSS (version 26.0), and the graphs were created with the GraphPad Prism version 8.4.3. P<0.05 was considered statistically significant. Results: The nanoparticles were spherical, homogenous, and 150±10 nm in size. According to HPLC, Quercetin had a 98% loading capacity. Although both free quercetin and quercetin-loaded liposomes indicated significant cytotoxicity against cancer cells (P<0.001), the combined form was significantly more active (P=0.008). 50 µg/mL of this compound reduced the viability of SW48 cells by more than 80% (IC50: 10.65 µg/mL), while the viability of cells treated with free quercetin was only 66% (IC50: 18.74 µg/mL). The apoptosis was nearly doubled in the cells treated with quercetin-loaded nanoliposomes compared to free quercetin (54.8% versus 27.6%). EGFR gene expression, on the other hand, was significantly lower in cells treated with quercetin-loaded liposomes than the quercetin alone (P=0.006). Conclusion: When combined with nanoliposomes, quercetin had greater anti-proliferative, apoptotic, and anti-EGFR expression than free quercetin. [ABSTRACT FROM AUTHOR]

Membrane permeability of copper complexes with potential anti-inflammatory activity were measured using an artificial membrane in a modified Franz cell. Using CuCl2 as the control, all the ligands tested enhanced the diffusion of copper, with enhancement factors ranging from 2 to 7. Octanol/water partition coefficients (log Ko/w) were measured and correlated with the permeability coefficients (Kp). In addition, chemical speciation was used to determine the predominant complex in solution at physiological pH. No correlation was found between the measured permeability coefficients and either molecular weight (MW) or log Ko/w. [ABSTRACT FROM AUTHOR]

Active inference is a probabilistic framework for modeling the behavior of biological and artificial agents, which derives from the principle of minimizing free energy. In recent years, this framework has been applied successfully to a variety of situations where the goal was to maximize reward, often offering comparable and sometimes superior performance to alternative approaches. In this article, we clarify the connection between reward maximization and active inference by demonstrating how and when active inference agents execute actions that are optimal for maximizing reward. Precisely, we show the conditions under which active inference produces the optimal solution to the Bellman equation, a formulation that underlies several approaches to model-based reinforcement learning and control. On partially observed Markov decision processes, the standard active inference scheme can produce Bellman optimal actions for planning horizons of 1 but not beyond. In contrast, a recently developed recursive active inference scheme (sophisticated inference) can produce Bellman optimal actions on any finite temporal horizon. We append the analysis with a discussion of the broader relationship between active inference and reinforcement learning. [ABSTRACT FROM AUTHOR]

Several challenges, including rapid drug release from the carrier, repeated drug administration, fluctuations in plasma drug concentration, and reduced patient compliance have been reported for conventional drug delivery systems. Liposomes were first developed by a scientist, A.D. Bangham, in 1961. The word liposome is a combination of the two Greek words "lipos" meaning fat and "soma" meaning body. A liposome is a system, which its membrane is made up of fatty compounds such as lipids. The lipid membrane and its entrapped space are suitable for the loading of lipophilic and hydrophilic drug molecules, respectively. Liposomes, as optimal drug delivery systems, could be an appropriate solution to many of the challenges of conventional drug delivery systems. Liposomes, which are made from phospholipid and cholesterol, have many benefits as optimal drug delivery systems. A wide range of therapeutics could be incorporated within liposomal carriers. They are biodegradable and biocompatible. They do not stimulate the immune system and are used as a synthetic membrane model. These systems increase the stability of drugs in the body by protecting the drug compounds within them and also reduce the toxic effects of drugs by minimizing drug exposure to sensitive tissues. Liposomes can also control drug release. The particle size of liposomes varies from nanometers to micrometers depending on the preparation method. Liposomes can be classified on the basis of their size and bilayers number, into: giant unilamellar vesicles (GUVs) 0.5 - 10 µm; multilamellar vesicles (MLV) 1 - 5 µm; large unilamellar vesicles (LUV) around 100 - 500 nm; small unilamellar vesicles (SUV) 20 - 100 nm; and multivesicular liposomes (MVL). MVL are characterized by their structure of multiple non-concentric aqueous chambers surrounded by a network of lipoidal membranes. The particle size of monolayer and multilayer liposomes is about a few hundred nanometers, while the average particle size of MVLs is 1 to 100 µm. Methods of liposomes preparation include thin layer hydration, reverse phase evaporation, solvent injection, dehydration-rehydration, and ultrasonic. The MVL system is a water in oil in water emulsion (W / O / W) that organic phase contains hydrophobic material and liquid phase contains hydrophilic material. The double emulsification method is the most common method of MVL preparation. Small drugs as well as large molecules such as peptides and proteins can be loaded in the unique structure of MVL. So far, several peptides or protein compounds have been successfully loaded in MVL and their therapeutic effects investigated in various diseases. In vitro and in vivo studies show that MVLs well control the drug release rate. There are some examples for MVL applications regarding these compounds.; MVL containing insulin or liraglutide in diabetes mellitus treatment, bevacizumab in laser-induced choroidal neovascularization, thymopentin in immune disorders, LXT-101 in the treatment of prostate cancer, angiotensin I converting enzyme (ACE) inhibitory peptide in the treatment of hypertension, alfa interferon in hepatitis C, and leridistim in chemotherapy-induced bone marrow suppression are some of the studies in this field. MVL consists of four compounds: phospholipids, cholesterol, neutral triglycerides, and negatively charged lipids. Phospholipid chains form the bilayer membrane of the liposome, and the cholesterol in the system is located between these chains. The cholesterol to phospholipids ratio, lipid to drug ratio, and lipidic composition affect the stability of the system and the rate of drug release. Neutral triglycerides such as triolein, tricaprylene, trilaureine and tributyrine allow the formation of this unique multivesicular structure, stabilize the membranes of internal vesicles at the point of contact with each other, preventing them from merging and controlling the drug release rate. Negatively charged lipids such as dicetyl phosphate (DCP) also control particle accumulation by inducing a negative charge on the surface of liposomes. Observation and determination of MVL structure are usually performed by optical and electron microscopes. The sysyems should also be characterized regarding drug encapsulation, drug release profile and kinetics, storage stability, and drug-vesicle interaction. Most studies on the MVL drug delivery system have been performed on drug-loaded MVLs. To date, application of MVLs containing tramadol in pain management, various compounds (include rose bengal, oxaliplatin, oleanolic acid, and cytarabine) in cancer, dexamethasone sodium phosphate in hearing impairment, acyclovir sodium in infectious diseases of herpes simplex virus (HSV), desferrioxamine mesylate in iron toxicity, celecoxib as an anti-inflammatory and analgesic agent, breviscapine in cardiovascular disease and cerebrovascular ischemia, flucinolone acetonide in ocular inflammatory diseases, naltrexone hydrochloride in opioid abuse and alcohol dependence and ropivacaine hydrochloride in local anesthesia has been investigated. In some treatment protocols, the simultaneous administration of two-drug combinations is required to achieve the desired result. The large aqueous space in the MVL and the division of this space into intravesicular and extra-vesicular parts, allows multiple drug combinations to be loaded in it and enter the body during an administration. The efficacy of co-delivery of mitoxantrone hydrochloride with horseradish peroxidase and insulin with metformin in a system was investigated in the treatment of cancer and diabetes mellitus, respectively, and showed satisfactory effects. Another class of drugs that have been successfully loaded in MVL is antibiotics. Antibiotics should have the least fluctuations in plasma concentrations in order to be more effective on microorganisms, so they should be prescribed according to a regular schedule. In MVL studies, researchers found satisfactory results from the study of the two antibiotics vancomycin and gentamicin. Many liposomal systems are used clinically to control drug release. These systems include daunorubicin, desferrioxamine mesylate, insulin-like growth factor 1 (IGF-1), doxorubicin, vincristine sulfate, and irinotecan respectively under the brand names DaunoXome®, DepoDFO®, DepoIGF-I®, Doxil®, Marqibo®, and Onivyde®. Depofoam is a type of MVL system with a particle size of 10 to 20 µm that could be a good depot in the body and releases the drug in a controlled manner. Depofoams are good choices for drug delivery to tumor areas and sensitive areas of the body such as the eyes, spinal cord, and epidural, and can reduce drug toxicity and side effects by minimizing drug exposure to healthy parts of the body. There are several Depofoam systems which three of these systems have been approved by the US Food and Drug Administration (FDA). DepoCyt® is a Depofoam system of the anticancer drug cytarabine by intrathecal injection. This system releases the drug in the body for two weeks and makes an optimum concentration of it in the cerebrospinal fluid (CSF). DepoDur® is the second product, which contains morphine. It relieves post-surgery pain after epidural administration and reduces the use of other injectable analgesics. Exparel® is a new formulation of bupivacaine with an analgesic effect that is injected near the surgical site. Numerous animal and human studies showed that after intrathecal, epidural, intraocular, intramuscular, intravenous, intra-arterial, and subcutaneous administration of Depofoam. This review article provides an overview of recent studies on the MVL system and its effect on optimizing rate of drug release. Successful loading of large molecules such as proteins and the possibility of loading multiple drug combinations into one system shows a hopeful view for the future of MVL in the pharmaceutical industry. It seems that this new technology, by overcoming the problems caused by frequent drug administration, has created an additional incentive for researchers to advance in this field. However, problems such as the high cost of these liposomes are some of the challenges that they face. [ABSTRACT FROM AUTHOR]

The majority of anticancer agents currently used derive from natural sources: plants, frequently the ones employed in traditional medicines, are an abundant source of mono- and diterpenes, polyphenols, and alkaloids that exert antitumor activity through diverse mechanisms. Unfortunately, many of these molecules are affected by poor pharmacokinetics and limited specificity, shortcomings that may be overcome by incorporating them into nanovehicles. Cell-derived nanovesicles have recently risen to prominence, due to their biocompatibility, low immunogenicity and, above all, targeting properties. However, due to difficult scalability, the industrial production of biologically-derived vesicles and consequent application in clinics is difficult. As an efficient alternative, bioinspired vesicles deriving from the hybridization of cell-derived and artificial membranes have been conceived, revealing high flexibility and appropriate drug delivery ability. In this review, the most recent advances in the application of these vesicles to the targeted delivery of anticancer actives obtained from plants are presented, with specific focus on vehicle manufacture and characterization, and effectiveness evaluation performed through in vitro and in vivo assays. The emerging overall outlook appears promising in terms of efficient drug loading and selective targeting of tumor cells, suggesting further engrossing developments in the future. [ABSTRACT FROM AUTHOR]

Ethical restrictions as well as practical or economic issues related to use of animal and human skin has been the main reason the growth in the number of investigations with alternative models. Reconstructed skin models, for example, have been useful to evaluate the invitro toxicity of compounds; however, these models usually overestimate the amount of drug permeated due to impaired barrier properties. In this review, the performance of synthetic and biological skin models in transport studies was compared by considering two compounds with different physicochemical properties. The advantages and limitations of each skin model are discussed in detail. Although synthetic and reconstructed skin models have shown to be useful in the formulation optimization step, they present many limitations: (1) impaired barrier properties; (2) lack of follicular transport; (3) no metabolism in synthetic membranes; (4) differences in terms of lipid organization; (5) more affected by formulation constituents. Therefore, animal and human tissues should still be prioritized in drug transport studies until new advances in alternative models are achieved. Investigations of the impact of cell-culture conditions on skin formation, in turn, bring perspectives related to the development of unhealthy/injured skin models (an aspect that still deserves attention). [ABSTRACT FROM AUTHOR]

AI against Tumors A study [[53]] from the Medizinische Universität Wien (Medical University of Vienna) successfully tested the use of artificial intelligence in the fight against a tumor. 34635570 54 Philippidis A. AI-Driven Pharma Tech Firm Expands Its Discovery Platform into Biologics: Exscientia intends to double the addressable target universe of its platform by combining generative AI design and virtual screening. Machine learning (ML) [[1], [3], [5], [7], [9], [11], [13], [15]], artificial intelligence (AI) [[16], [18], [20], [22], [24], [26], [28]] and Big Data [[30], [32], [34]] can provide robust and innovative answers to long-standing problems. Although the technology under consideration is in the early stages, the provision of quick and careful artificial-intelligence-guided data might be very useful in estimating the responsiveness and need for discharging patients "at scale" for future global (and personal, individual patient-level) health emergencies. [Extracted from the article]

Bromazolam is a designer benzodiazepine that was first detected in British Columbia in January 2021. Postmortem cases were analyzed using a comprehensive blood drug screening procedure by liquid chromatography–high-resolution mass spectrometry before being retrospectively analyzed using an in-house novel psychoactive substances data processing method. Bromazolam was detected in 41 postmortem cases in 2021 and quantitatively confirmed by standard addition, using liquid chromatography–tandem mass spectrometry. The mean bromazolam concentration observed was 11.4 ± 53.7 ng/mL (median concentration: 1.6 ng/mL), with a range from 0.5 to 319.3 ng/mL and the majority of cases co-occurring with fentanyl. These low concentrations may be indicative of a presumed enhancement of opioid effects, rather than being used as a stand-alone drug. Bromazolam was always detected with opioids (fentanyl and carfentanil), stimulants (methamphetamine) and/or other benzodiazepines (etizolam and flualprazolam). To our knowledge, this is the first report to provide concentrations of bromazolam in postmortem blood samples in Canada. [ABSTRACT FROM AUTHOR]

Simple Summary: An extra-low, DC (direct current) voltage field applied to a textile was used to prevent mosquito blood feeding. A novel 3-D textile was developed based on the mosquito head structure that when charged with 15 volts was 100% effective in preventing mosquito blood feeding across an artificial membrane. Mosquito vector-borne diseases such as malaria and dengue pose a major threat to human health. Personal protection from mosquito blood feeding is mostly by treating clothing with insecticides and the use of repellents on clothing and skin. Here, we developed a low-voltage, mosquito-resistant cloth (MRC) that blocked all blood feeding across the textile and was flexible and breathable. The design was based on mosquito head and proboscis morphometrics, the development of a novel 3-D textile with the outer conductive layers insulated from each other with an inner, non-conductive woven mesh, and the use of a DC (direct current; extra-low-voltage) resistor-capacitor. Blockage of blood feeding was measured using host-seeking Aedes aegypti adult female mosquitoes and whether they could blood feed across the MRC and an artificial membrane. Mosquito blood feeding decreased as voltage increased from 0 to 15 volts. Blood feeding inhibition was 97.8% at 10 volts and 100% inhibition at 15 volts, demonstrating proof of concept. Current flow is minimal since conductance only occurs when the mosquito proboscis simultaneously touches the outside layers of the MRC and is then quickly repelled. Our results demonstrated for the first time the use of a biomimetic, mosquito-repelling technology to prevent blood feeding using extra-low energy consumption. [ABSTRACT FROM AUTHOR]

Targeted drug delivery using micro-nano robots (MNRs) is a rapidly advancing and promising field in biomedical research. MNRs enable precise delivery of drugs, addressing a wide range of healthcare needs. However, the application of MNRs in vivo is limited by power issues and specificity in different scenarios. Additionally, the controllability and biological safety of MNRs must be considered. To overcome these challenges, researchers have developed bio-hybrid micro-nano motors that offer improved accuracy, effectiveness, and safety for targeted therapies. These bio-hybrid micro-nano motors/robots (BMNRs) use a variety of biological carriers, blending the benefits of artificial materials with the unique features of different biological carriers to create tailored functions for specific needs. This review aims to give an overview of the current progress and application of MNRs with various biocarriers, while exploring the characteristics, advantages, and potential hurdles for future development of these bio-carrier MNRs. [ABSTRACT FROM AUTHOR]

The goal of this study is to use the deep artificial neural network (DLNN) and support vector machines (SVM) methods to predict the biochar, bio-oil, and synthesis gas yields of the Atriplex nitens S. plant. Furthermore, the study's sensitivity analysis predicted the importance levels of factors influencing carbonization yields. Three different carbonization temperatures (400 °C, 500 °C, and 600 °C), two different holding times (30 and 60 min), and two different gas flow rate rates (0.2 and 0.5 L min−1) were used as input parameters in the DLNN and SVM models for this purpose. The DLNN method employed two hidden layers. The learning function was Levenberg–Marquardt. As activation functions, the hyperbolic tangent sigmoid transfer function and the linear transfer function were used. The network was tested with various numbers of neurons, and 21 different architectures were created using the number of neurons that produced the lowest MAE value. In the SVM model, the L1QB solver was used. According to the study's findings, the DLNN method made more accurate predictions than the SVM. The DLNN11 (R2 = 0.987), DLNN19 (R2 = 0.983), and DLNN7 (R2 = 0.960) network architectures produced the best results in this method for biochar, bio-oil, and synthesis gas yield, respectively. As a result of sensitivity analysis, the effect of holding time on biochar and bio-oil yields was found to be greater than other parameters. The synthesis gas yield was most affected by the carbonization temperature. [ABSTRACT FROM AUTHOR]

Viral seasonality in the aquaculture industry is an important scientific issue for decades. While the molecular mechanisms underpinning the temperature-dependent pathogenesis of aquatic viral diseases remain largely unknown. Here we report that temperature-dependent activation of IL6-STAT3 signaling was exploited by grass carp reovirus (GCRV) to promote viral entry via increasing the expression of heat shock protein 90 (HSP90). Deploying GCRV infection as a model system, we discovered that GCRV induces the IL6-STAT3-HSP90 signaling activation to achieve temperature-dependent viral entry. Further biochemical and microscopic analyses revealed that the major capsid protein VP7 of GCRV interacted with HSP90 and relevant membrane-associated proteins to boost viral entry. Accordingly, exogenous expression of either IL6, HSP90, or VP7 in cells increased GCRV entry in a dose-dependent manner. Interestingly, other viruses (e.g., koi herpesvirus, Rhabdovirus carpio, Chinese giant salamander iridovirus) infecting ectothermic vertebrates have evolved a similar mechanism to promote their infection. This work delineates a molecular mechanism by which an aquatic viral pathogen exploits the host temperature-related immune response to promote its entry and replication, instructing us on new ways to develop targeted preventives and therapeutics for aquaculture viral diseases. Author summary: Viral seasonality in the aquaculture industry has been an important scientific issue for decades, which is causing billions of economic losses every year worldwide. However, there is a lack of understanding of how temperature influences the pathogenesis of aquatic viruses infecting fish, shellfish, and other ectotherms. Here, deploying aquatic grass carp reovirus (GCRV) as a model system, we demonstrate for the first time that the temperature-dependent IL6-STAT3-HSP90 signaling axis is exploited by GCRV to promote viral entry. We found that HSP90 interacted with viral structural proteins and membrane-associated proteins to enable viral entry. Furthermore, our study indicates other aquatic viruses might evolve a similar mechanism to promote their infection. By elucidating the molecular mechanism of temperature-dependent aquatic viral pathogenesis, our work may help to develop targeted prevention and control strategies against aquatic viral diseases. [ABSTRACT FROM AUTHOR]

Aromatic amines (AA) are carcinogenic compounds that can enter the human body through many sources, one of the most important being tobacco smoke. They are excreted with the urine, from which they can be extracted and measured. To that end, hollow fiber-liquid-phase microextraction (HF-LPME) and parallel artificial liquid membrane extraction (PALME) were optimized for the analysis of representative aromatic amines, as alternatives to liquid–liquid extraction (LLE). Relevant extraction parameters, namely organic solvent, extraction time, agitation speed, and acceptor solution pH, were studied, and the two optimized techniques—HF-LPME: dihexyl ether, 45 min, 250 rpm, and pH 1; PALME: undecane, 20 min, 250 rpm and pH 1—were compared. Comparison of the optimized methods showed that significantly higher recoveries could be obtained with PALME than with HF-LPME. Therefore, PALME was further validated. The results were successful for nine different AA, with regression coefficients (R2) of at least 0.991, limits of detection (LOD) of 45–75 ng/L, and repeatability and peak area relative standard deviations (RSD) below 20%. Furthermore, two urine samples from smokers were measured as proof of concept, and 2-methylaniline was successfully quantified in one of them. These results show that PALME is a great green alternative to LLE. Not only does it use much smaller volumes of toxic organic solvents, and sample—enabling the study of samples with limited available volumes—but it is also less time consuming and labor intensive, and it can be automated. [ABSTRACT FROM AUTHOR]

Unsymmetrical dimethylhydrazine (UDMH) is a widely used rocket propellant. Entering the environment or being stored in uncontrolled conditions, UDMH easily forms an enormous variety (at least many dozens) of transformation products. Environmental pollution by UDMH and its transformation products is a major problem in many countries and across the Arctic region. Unfortunately, previous works often use only electron ionization mass spectrometry with a library search, or they consider only the molecular formula to propose the structures of new products. This is quite an unreliable approach. It was demonstrated that a newly proposed artificial intelligence-based workflow allows for the proposal of structures of UDMH transformation products with a greater degree of certainty. The presented free and open-source software with a convenient graphical user interface facilitates the non-target analysis of industrial samples. It has bundled machine learning models for the prediction of retention indices and mass spectra. A critical analysis of whether a combination of several methods of chromatography and mass spectrometry allows us to elucidate the structure of an unknown UDMH transformation product was provided. It was demonstrated that the use of gas chromatographic retention indices for two stationary phases (polar and non-polar) allows for the rejection of false candidates in many cases when only one retention index is not enough. The structures of five previously unknown UDMH transformation products were proposed, and four previously proposed structures were refined. [ABSTRACT FROM AUTHOR]

Membrane proteins play an important role in key cellular functions, such as signal transduction, apoptosis, and metabolism. Therefore, structural and functional studies of these proteins are essential in fields such as fundamental biology, medical science, pharmacology, biotechnology, and bioengineering. However, observing the precise elemental reactions and structures of membrane proteins is difficult, despite their functioning through interactions with various biomolecules in living cells. To investigate these properties, methodologies have been developed to study the functions of membrane proteins that have been purified from biological cells. In this paper, we introduce various methods for creating liposomes or lipid vesicles, from conventional to recent approaches, as well as techniques for reconstituting membrane proteins into artificial membranes. We also cover the different types of artificial membranes that can be used to observe the functions of reconstituted membrane proteins, including their structure, number of transmembrane domains, and functional type. Finally, we discuss the reconstitution of membrane proteins using a cell-free synthesis system and the reconstitution and function of multiple membrane proteins. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with the small molecule CP2 induces an adaptive stress response, activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, Aβ and pTau accumulation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD. Here, using serial block-face scanning electron microscopy (SBFSEM) and three-dimensional (3D) EM reconstructions combined with Western blot analysis and next-generation RNA sequencing, we demonstrate that CP2 treatment also restores mitochondrial morphology and mitochondria-endoplasmic reticulum (ER) communication, reducing ER and unfolded protein response (UPR) stress in the APP/PS1 mouse brain. Using 3D EM volume reconstructions, we show that in the hippocampus of APP/PS1 mice, dendritic mitochondria primarily exist as mitochondria-on-a-string (MOAS). Compared to other morphological phenotypes, MOAS have extensive interaction with the ER membranes, forming multiple mitochondria-ER contact sites (MERCS) known to facilitate abnormal lipid and calcium homeostasis, accumulation of Aβ and pTau, abnormal mitochondrial dynamics, and apoptosis. CP2 treatment reduced MOAS formation, consistent with improved energy homeostasis in the brain, with concomitant reductions in MERCS, ER/UPR stress, and improved lipid homeostasis. These data provide novel information on the MOAS-ER interaction in AD and additional support for the further development of partial MCI inhibitors as a disease-modifying strategy for AD. [ABSTRACT FROM AUTHOR]

With the rapid development of autonomous driving technology, future road traffic must be composed of autonomous vehicles and artificial vehicles. Although autonomous vehicles have greatly improved road capacity, few studies have involved capacity at signal-controlled intersections, and most of the studies are based on experimental simulation. As such, there is a need to more scientifically analyze the impact of autonomous vehicles on road and intersection capacity. Based on three theories of flow-density relationships, traffic flow equilibrium analysis, and the following model, this paper firstly deduces the flow-density relationship of different vehicle types in a single environment. Secondly, flow-density relationships under different proportions of self-driving vehicles are derived. Through the derivation of these two models, the basic road saturation flow rates under different permeabilities of self-driving vehicles, can be obtained. Based on these results, a revised calculation model for the capacity of signalized intersections with different proportions of autonomous vehicles is proposed, which is essentially to revise the basic saturation flow rate under different permeabilities of autonomous vehicles. By using SUMO 1.15.0 traffic simulation software, the theoretical models are individually tested. The results show that the error rate between the theoretical calculation results and the SUMO simulation results, is less than 16%. This study can provide a basis for the calculation of basic capacity of roads and intersections in a future man-machine hybrid driving environment, and provide theoretical guidance for traffic management and control. [ABSTRACT FROM AUTHOR]

Understanding the petrophysical properties of reservoir rocks is crucial for hydrocarbon exploration and production. The evolution of digital rock physics (DRP) in recent years has led to vital improvements in core characterization and in high-quality special core analysis (SCAL) measurements. DRP can estimate petrophysical properties in sandstone reservoirs using digital models. For heterogeneous carbonates, it is difficult to capture the full range of the pore structure with a single imaging technique due to pore sizes ranging from nm to cm. This study aims to accurately characterize sandstone and carbonate core plugs permeability using DRP. In addition, effective and total porosity was evaluated for establishing trends with a variable range of permeability. Six representative sandstone outcrop samples were chosen for this study to cover different lithology types, and five carbonate samples from Middle Eastern reservoirs were selected. A multi-scale imaging approach using an X-ray computer tomography CT, a 3D X-ray microtomographic CT, an X-ray diffraction (XRD), and a quantitative evaluation of minerals using scanning electron microscopy (QEMSCAN) were performed on the samples. After laboratory measurements, the samples were scanned using an X-ray CT with a 1-mm resolution to evaluate the heterogeneity of the rock structure. A sub-plug was then extracted for high-resolution scanning at a resolution of 4 µm using an X-ray micro-CT. At this scale, pore connectivity can be revealed from top to bottom. The 3D images were analyzed using the PerGeos software. The connected porosity of the segmented pores was obtained using the PerGeos software, and flow characteristics were simulated with the Lattice-Boltzmann method (LBM) and compared with laboratory measurements. The porosity obtained using the PerGeos software was comparable to laboratory measurements. The permeability obtained using LBM was in good agreement with experimental results. For high-permeability samples, the difference between total and effective porosity was observed to be lower than in low-permeability samples. This study forms the basis for accurate porosity–permeability evaluation using LBM and conventional laboratory measurements. It also shows the importance and application of DRP for flow characterization of reservoir rock. The accurate estimation of flow characteristics contributes to a better understanding of reservoir evaluation and management and mastering the usage of DRP as a non-destructive tool to evaluate rock characteristics and compare them to standard laboratory practices. [ABSTRACT FROM AUTHOR]

The ability to associate neutral stimuli with valence information and to store these associations as memories forms the basis for decision making. To determine the underlying computational principles, we build a realistic computational model of a central decision module within the Drosophila mushroom body (MB), the fly's center for learning and memory. Our model combines the electron microscopy-based architecture of one MB output neuron (MBON-α3), the synaptic connectivity of its 948 presynaptic Kenyon cells (KCs), and its membrane properties obtained from patch-clamp recordings. We show that this neuron is electrotonically compact and that synaptic input corresponding to simulated odor input robustly drives its spiking behavior. Therefore, sparse innervation by KCs can efficiently control and modulate MBON activity in response to learning with minimal requirements on the specificity of synaptic localization. This architecture allows efficient storage of large numbers of memories using the flexible stochastic connectivity of the circuit. [ABSTRACT FROM AUTHOR]

Chromatographic retention data collected on immobilized keratin (KER) or immobilized artificial membrane (IAM) stationary phases were used to predict skin permeability coefficient (log Kp) and bioconcentration factor (log BCF) of structurally unrelated compounds. Models of both properties contained, apart from chromatographic descriptors, calculated physico-chemical parameters. The log Kp model, containing keratin-based retention factor, has slightly better statistical parameters and is in a better agreement with experimental log Kp data than the model derived from IAM chromatography; both models are applicable primarily to non-ionized compounds.Based on the multiple linear regression (MLR) analyses conducted in this study, it was concluded that immobilized keratin chromatographic support is a moderately useful tool for skin permeability assessment.However, chromatography on immobilized keratin may also be of use for a different purpose—in studies of compounds' bioconcentration in aquatic organisms. [ABSTRACT FROM AUTHOR]

Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers. [ABSTRACT FROM AUTHOR]

Chronic use of antihistamines can induce abnormalities in lipid absorption with potential excessive accumulation of lipids in the mesentery that can lead to the development of obesity and a metabolic syndrome. The focus of the present work was to develop a transdermal gel formulation of desloratadine (DES) to prevent/reduce obesity and metabolic syndromes. Nine formulations were prepared to contain hydroxypropyl methylcellulose (2–3%), DES (2.5–5.0%), and Transcutol® (15–20%). The formulations were evaluated for cohesive and adhesive properties, viscosity, drug diffusion through synthetic and pig ear skin, and pharmacokinetics in New Zealand white rabbits. Drug permeation was faster through the skin compared to synthetic membranes. The drug had good permeation, as indicated by very short lag time (0.08–0.47 h) and high flux (59.3–230.7 μg/cm2.h). The maximum plasma concentration (Cmax) and area under the curve (AUC) of transdermal gel formulations were 2.4 and 3.2 fold that of the Clarinex tablet formulation. In conclusion, as indicated by the higher bioavailability, transdermal gel formulation of DES may decrease the dose of the drug, compared to commercial formulation. It has the potential to reduce or eliminate metabolic syndromes associated with oral antihistamine therapy. [ABSTRACT FROM AUTHOR]

Beta-blockers are a class of medications predominantly used to manage abnormal heart rhythms. They are also widely used to treat high blood pressure. From the liquid chromatography separation point of view, beta-blockers are interesting molecules due to their hydrophobic–hydrophilic properties. Thus, the study aimed to investigate the beta-blocker separation selectivity on four phosphodiester stationary phases in reversed-phase liquid chromatography (RP LC) and hydrophilic interactions liquid chromatography (HILIC). On tested stationary phases, beta-blockers provide retention in both chromatographic systems, RP LC and HILIC. Additionally, it was found that cation-exchange mechanisms have a significant contribution to retention. Separations were enhanced by applying ChromSword software for gradient optimization and Intelligent Peak Deconvolution Analysis to separate unseparated peaks digitally. [ABSTRACT FROM AUTHOR]

A brief review is given of the methods of analysis and the analytical parameters for identifying the components of complex mixtures. Parameters for identification of substances with chromatographic analysis of complex multicomponent mixtures are studied: linear retention indices; and it is shown that in order to ensure the necessary level of reliability of the analysis results, it is necessary to estimate the uncertainty of the measurement of these indices. A general equation for determining the variance of the result of indirect measurements of linear retention indices is obtained. For analysis of mixtures containing both analytes and n-alkanes, and mixtures with a separate content of these components, particular formulations of the general equation are generated. A formula for determining the effective number of degrees of freedom of standard uncertainty is presented, taking into account the correlation of input variables in the measurement equation. Mathematical expressions are derived for calculating the extended uncertainties of an estimate of linear retention indices that take into account correlations of the retention times of adjacent chromatographic peaks. Using methods of interval mathematics, an upper estimate of the standard uncertainty of linear retention indices for the joint presence of analytes and n-alkanes in the analyzed mixture was derived, and a significant decrease in comparison with the specified uncertainty in the analysis of mixtures with a separate content of these components was shown. The correspondence of theoretical and experimental results was established. The results obtained can be used to identify the components of the analyzed mixture when standardizing chromatographic analysis techniques. [ABSTRACT FROM AUTHOR]

The known approaches to the isolation of biopolymers, in particular, nucleic acids (NAs), from biological samples are based on the binding of molecules to a sorbent ("positive selection") with their subsequent elution using a suitable eluent. The review discusses the physicochemical processes underlying the development of methods for isolating NAs from biological samples. It has been shown that methods including the selective solid-phase extraction (i.e., reversible sorption) provide the possibility of miniaturization and automation of the respective processes. The review discusses the advantages of an alternative approach to NA isolation based on the use of special sorbents that bind proteins and other components of biological samples, while these sorbents exhibit sorption inertness towards NAs ("negative selection"). The approaches providing the creation of such composite polymer-containing sorbents, which are designed for the sample preparation during molecular diagnostics, as well as the methods of their effective use, are considered. It has been demonstrated that, due to an interdisciplinary approach using a complex of synthetic and analytical methods, it is possible to combine composite materials that are very different in structure and properties as a single object of study. Such nanostructured composites (based on porous silica, synthetic membranes, glass multicapillaries) contain fluoropolymers and polyanilines. The results of using such composites for selective isolation of NAs and/or proteins from biological samples are discussed. Alternative applications of such composites in molecular diagnostics, in particular, in mass spectrometry, are considered. Directions for expanding the field of application of polymer-containing composites due to simultaneous use of the sorption properties of the surface of composites obtained and the properties of sorbate molecules are outlined. It has been shown that both polymeric and low-molecular-weight modifiers of the same chemical nature are suitable for the technological preparation of such composites. [ABSTRACT FROM AUTHOR]

Mass Spring Systems (MSS) are often used to simulate the behavior of deformable objects, for example in computer graphics (modeling clothes for virtual characters) or in medicine (surgical simulators that facilitate the planning of surgical operations) due to their simplicity and speed of calculation. This paper presents a new, two-parameter method (TP MSS) of determining the values of spring coefficients for this model. This approach can be distinguished by a constant parameter which is calculated once at the beginning of the simulation, and a variable parameter that must be updated at each simulation step. The value of this variable parameter depends on the shape changes of the elements forming the mesh of the simulated object. The considered mesh is built of elements in the shape of acute-angled triangles. The results obtained using the new model were compared to FEM simulations and the Van Gelder model. The simulation results for the new model were also compared with the results of the bubble inflation test. [ABSTRACT FROM AUTHOR]