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Diamonds possess exceptional properties such as high mechanical strength, thermal conductivity, and electrical resistance, making them suitable for various applications, including high-power electronics and optoelectronics. However, fabricating conductive structures in diamond remains a significant technological challenge. In this publication, we present a controlled process for fabricating precise amorphous conductive paths in a monocrystalline diamond using a focused ion beam (FIB) technique. The resistivity and thickness of the fabricated structures were determined, and their morphology was carefully characterized. The results showed that the optimal charge dose for achieving the lowest resistance was found to be 10 17 ions/cm 2 . The fabricated structures exhibited amorphous morphology. Elemental analysis confirmed the presence of gallium ions in the modified material. The resistivity of the conductive paths was determined to be 30 μΩm, which is remarkably low compared to previous studies and only 1-2 orders of magnitude higher than in metals. Additionally, it is shown that this technology has potential applications in high-pressure chambers and the development of high-pressure sensors within diamond anvils. Overall, this study provides valuable insights into fabricating conductive structures on diamonds using FIB and opens up possibilities for diamond electronics.

Three new spirostan glycosides, dracochinosides A-C (1-3), and four known steroidal glycosides (4-7) were isolated from the aerial parts of Dracaena cochinchinensis (Lour.) S.C.Chen. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-3, 6 and 7 inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 57.5 to 92.8 µM. In addition, all the isolated compounds exhibited at least one of seven tested microbial strains with the MIC values ranging from 0.016 to 0.128 mg/mL. This is the first report of compounds 5-7 from the genus Dracaena., (© 2024 Wiley‐VCH GmbH.)

Presumptive drug screening enables timely procurement of search and arrest warrants and represents a crucial first step in crime scene analysis. Screening also reduces the burden on forensic laboratories which often face insurmountable backlogs. In most scenarios, on-site presumptive drug screening relies on chemical field tests for initial identification. However, even when used appropriately, these test kits remain limited to subjective colorimetric analysis, produce false positive or negative results with excessive sample quantities, and are known to cross-react with numerous innocuous substances. Previous efforts to develop microfluidic devices that incorporate these chromogenic indicator reagents address only a few of the many challenges associated with these kits. This is especially true for samples where the drug of interest is present as a lacing agent. This work describes the development of a centrifugal microfluidic device capable of integrating facile sample preparation, by way of a 3D printed snap-on cartridge amenable to microwave assisted extraction, followed by chromatographic separation and chromogenic detection on-disc. As cannabis is among the most widely used controlled substance worldwide, and displays strong interference with these indicator reagents, mock samples of laced marijuana are used for a proof-of-concept demonstration. Post extraction, the microdevice completes high throughput metering just prior to simultaneous reaction with four of the most commonly employed microchemical tests, followed by objective image analysis in CIELAB (a device-independent color model). Separation and recovery of a representative controlled substance with 93% efficiency is achieved. Correct identification, according to hierarchical cluster analysis, of three illicit drugs ( e.g. , heroin, phencyclidine, and cocaine) in artificially laced samples is also demonstrated on-disc. The cost effective microdevice is capable of complete automation post-extraction, with a total analysis time (including extraction) of <8 min. Finally, sample consumption is minimized, thereby preventing the complete destruction of forensic evidence.

Phytochemical study on the methanol extract of the leaves of Phyllanthus reticulatus led to the isolation of two new compounds, phyllanreticosides A (1) and B (2) together with ten known ones (3-12). Their chemical structures were determined by HR-ESI-MS, NMR, and ECD spectra in comparison with the literature. Three ellagitannins, phyllanreticoside A (1), corilagin (3), and phyllanthusiin C (4) inhibited lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values of 63.2, 83.2, and 5.6 µM, respectively. In addition, compounds 1, 3, and 4 exhibited significantly antimicrobial activity (MICs: 16-128 µg/mL) towards some of seven microbial strains, including Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Candida albicans., (© 2024 Wiley‐VCH GmbH.)

The successful development of an amorphous form of a drug demands the use of process conditions and materials that reduce their thermodynamic instability. For the first time, we have prepared amorphous ibrutinib using the quench-cooling method with very high process efficiency. In the presented study, different formulations of amorphous active pharmaceutical ingredient (API) with Soluplus (SOL) in various weight ratios 1:9, 3:7, and 1:1 were prepared. The obtained samples were stored under long-term (25 ± 2 °C/60%RH ± 5% RH, 12 months) and accelerated (40 ± 2 °C/75%RH ± 5% RH, 6 months) storage conditions. The physical stability of amorphous ibrutinib and ibrutinib-Soluplus formulations was analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction analysis (XRPD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The lack of significant interactions between the ingredients of the formulation was confirmed by FTIR analysis. An increase in moisture content with an increasing SOL weight ratio was observed under accelerated aging and long-term conditions. Additionally, a slight increase in the moisture content of the stored sample compared to that at the initial time was observed. The results revealed the physical strength of the polymeric systems in the presence of high humidity and temperature. The observed high thermal stability allows the use of various technological processes without the risk of thermal degradation.

Phytochemical study on the roots of Achyranthes bidentata Blume led to the isolation of sixteen compounds including three new ones ( 1-3 ). Their chemical structures were determined as oleanolic acid 28- O - β -D-glucopyranoside-3- O -[ β -D-glucopyranosyl-(1→3)- β -D-galactopyranoside) ( 1 ), methyl (8 Z ,11 Z )-5,6,7-trihydroxytetradeca-8,11-dienoate ( 2 ), methyl (6 E ,11 Z )-5,8,9-trihydroxytetradeca-6,11-dienoate ( 3 ), fulgidic acid ( 4 ), (9 E ,11 E )-13-oxooctadeca-9,11-dienoic acid ( 5 ), (9 Z ,11 E ,15 Z )-13-hydroxyoctadeca-9,11,15-trienoic acid ( 6 ), oleanolic acid 28- O - β -D-glucopyranoside-3- O - α -L-rhamnopyranosyl-(1→4)- β -D-glucuronopyranoside ( 7 ), oleanolic acid 28- O - β -D-glucopyranoside-3- O - β -D - glucopyranosyl-(1→2)-[ α -L-rhamnopyranosyl-(1→3)]- β -D-glucuronopyranoside ( 8 ), oleanolic acid 3- O - β -D - glucopyranosyl-(1→2)-[ α -L-rhamnopyranosyl-(1→3)]- β -D-glucuronopyranoside ( 9 ), oleanolic acid 3- O - α -L-rhamnopyranosyl-(1→3)- β -D-glucuronopyranoside ( 10 ), blumenol C glucoside ( 11 ), citroside A ( 12 ), 6 S ,9 S -roseoside ( 13 ), ginsenoside Rg1 ( 14 ), 20-hydroxyecdysone ( 15 ), and benzyl α -L-rhamnopyranosyl-(1→6)]- β -D-glucopyranoside ( 16 ) by spectroscopic analysis. Compounds 1 , 7 and 11-16 inhibited NO production in LPS-activated RAW264.7 cells with IC 50 values in the range from 28.03 to 54.23 µM (positive control, L-NMMA: IC 50 = 35.52 µM). Compounds 14 and 15 showed anti α -glucosidase activity with IC 50 values of 176.24 and 156.92 µM, respectively, compared with the positive control, acarbose, IC 50 = 160.99 μM.

This study revisits a (001)-oriented layered lead chloride templated by 1,2,4-triazolium, Tz 2 PbCl 4 , which recently has been an object of intense research but still suffers from gaps in characterization. Indeed, the divergent reports on the crystal structures of Tz 2 PbCl 4 at various temperatures, devoid of independent verification of chiral phases through second harmonic generation (SHG), have led to an unresolved debate regarding the existence of a low-temperature phase transition (PT) and the noncentrosymmetric nature of the low-temperature phase. Now, by combining differential scanning calorimetry, single-crystal X-ray diffraction, dielectric, as well as linear and nonlinear optical spectroscopies on Tz 2 PbCl 4 , we reveal a sequence of reversible PTs at T 1 = 361 K (phase I-II), T 2 = 339 K (phase II-III), and T 3 = 280 K (phase III-IV). No SHG activity could be registered for any of the four crystal phases, as checked by wide-temperature range SHG screening, supporting their centrosymmetry. The dipole relaxation processes indicate a decrease in activation energy with increasing temperature, from 0.60, 0.38, to 0.24 eV observed for phase IV (space group P 2 1 / c ), phase III ( Pnma ), and phase II ( Cmcm ), respectively. This change is interpreted as a result of the diminishing strength of H-bonds as the system transforms from phase IV to III and subsequently to II. The weaker H-bonds facilitate the reorientation of Tz + cations in the presence of an external electric field. The photoluminescence spectra of Tz 2 PbCl 4 reveal an intriguing interplay of narrow and broadband emission, linked respectively to free excitons and excitons trapped on defects. Notably, as the temperature decreases from 300 K to 16 K, both the emission bands exhibit distinctive blue and red shifts, indicative of increased in-plane octahedral distortion. This dynamic behaviour transforms the photoluminescence of Tz 2 PbCl 4 from greenish-blue at 300 K to yellowish-green at 13 K, enriching our understanding of 2D lead halide perovskites and highlighting the optoelectronic potential of Tz 2 PbCl 4 .

Phytochemical study on the rhizomes of Kaempferia parviflora led to the isolation of twenty-three compounds including six phenolic glycosides ( 1 - 6 ), thirteen flavones ( 7 - 19 ), and five phenolic compounds ( 20 - 23 ). Of these, the new compounds were determined to be 2,4-dihydroxy-6-methoxyacetophenone-2 -β- D-apiofuranosyl-(1→6) -β- D-glucopyranoside ( 1 ), 2-hydroxy-4-propionyl-phenyl O-β- D-glucopyranoside ( 2 ), and 4-hydroxy-3,5-dimethoxyacetophenone 8- O-α- L-rhamnopyranosyl-(1→6) -β- D-glucopyranoside ( 3 ) and named as kaempanosides A-C, respectively. Their chemical structures were established based on HR-ESI-MS, 1D and 2D NMR spectra. All compounds 1 - 23 exhibited acetylcholinesterase inhibitory activity with IC 50 values ranging from 57.76 to 253.31 µM.

Buds of poplar trees ( Populus species) are often covered with sticky, usually polyphenol-rich, exudates. Moreover, accessible data showed that some Populus bud extracts may be excellent antibacterial agents, especially against Gram-positive bacteria. Due to the fragmentary nature of the data found, we conducted a systematic screening study. The antimicrobial activity of two extract types (semi-polar-ethanolic and polar-ethanolic-water (50/50; V / V )) from 27 bud samples of different poplar taxons were compared. Antimicrobial assays were performed against Gram-positive (five strains) and Gram-negative (six strains) bacteria as well as fungi (three strains) and covered the determination of minimal inhibitory, bactericidal, and fungicidal concentrations. The composition of extracts was later investigated by ultra-high-performance liquid chromatography coupled with ultraviolet detection (UHPLC-DAD) and with electrospray-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-ESI-qTOF-MS). As a result, most of the extracts exhibited good (MIC ≤ 62.5 µg/mL) or moderate (62.5 < MIC ≤ 500 µg/mL) activity against Gram-positives and Helicobacter pylori , as well as fungi. The most active were ethanolic extracts from P . trichocarpa , P . trichocarpa clone 'Robusta', and P . tacamahaca × P . trichocarpa . The strongest activity was observed for P . tacamahaca × P . trichocarpa . Antibacterial activity was supposedly connected with the abundant presence of flavonoids (pinobanksin, pinobanksin 3-acetate, chrysin, pinocembrin, galangin, isosakuranetin dihydrochalcone, pinocembrin dihydrochalcone, and 2',6'-dihydroxy-4'-methoxydihydrochalcone), hydroxycinnamic acids monoesters ( p -methoxycinnamic acid cinnamyl ester, caffeic acid phenethylate and different isomers of prenyl esters), and some minor components (balsacones).

Osteosarcoma is a malignant osseous neoplasm. Osteosarcoma is a primary bone malignancy capable of producing osteoid tissue or immature bones. A subsequent malignant degeneration of the primary bone pathology occurs less frequently in adults. The over-expression of several proteins, including Heat shock proteins, Cofilin, Annexins, Insulin-like growth factor, transforming growth factor-β, Receptor tyrosine kinase, Ezrin, Runx2, SATB2, ATF4, Annexins, cofilin, EGFR, VEGF, retinoblastoma 1 (Rb1) and secreted protein, has been associated to the development and progression of osteosarcoma. These proteins are involved in cell adhesion, migration, invasion, and the control of cell cycle and apoptosis. In genomic studies, osteosarcoma has been associated with several genetic abnormalities, including chromosomal rearrangements, gene mutations, and gene amplifications. These differentially expressed proteins could be used as early identification biomarkers or treatment targets. Proteomics and genomics play significant parts in enhancing our molecular understanding of osteosarcoma, and their integration provides essential insights into this aggressive bone cancer. This review will discuss the tumour biology that has assisted in helping us better understand the causes of osteosarcoma and how they could potentially be used to find new treatment targets and enhance the survival rate for osteosarcoma patients., (Copyright © 2024. Published by Elsevier Inc.)

Globally, there is a growing concern about air pollution due to rapid industrialization and urbanization. Therefore, in this study, an experimental study was conducted to evaluate the performance of reducing nitrogen oxides, a precursor to fine dust, in mortars coated with a titanium dioxide (TiO 2 ) photocatalyst, which has the effect of decomposing pollutants. In particular, in this study, zeolite and activated red clay were used as cement substitutes to improve the fine dust reduction performance of the TiO 2 photocatalyst. A total of 14 different mixtures were designed, considering the substitution rates of zeolite and activated red clay (30%, 40%, and 50%) and the cement-fine aggregate ratio (1:2 and 1:3) as experimental variables. A TiO 2 photocatalyst was employed in this study to evaluate the NO x reduction performance. As zeolite and activated red clay were added, the compressive strength and flexural strength of the mortars decreased by 15% to 60%, while the absorption rate increased by 5% to 16%. The NO x reduction efficiency of up to 67.4% was confirmed in the H50-3 specimen with the TiO 2 catalyst. The NO x reduction performance of mortars with the TiO 2 photocatalyst sprayed on their surface improved as the substitution ratio of zeolite and activated red clay increased. Additionally, it was confirmed that the NO x reduction effect of specimens using activated red clay was superior to those using zeolite. Therefore, through this study, it was confirmed that the NO x reduction performance of the TiO 2 photocatalyst can be improved when zeolite and activated red clay are used as cement substitutes.

Due to improper operation of the shield construction process and unknown geological surveys, shield construction faces many risks in passing through complex strata, among which the excavation face instability is the most serious, potentially leading to disastrous accidents. To address these issues, this research focuses on the limit support pressure and the excavation face stability in the soil when crossing the Yangtze River. First, an analytical formula for the limit support pressure of the excavation face is established through the wedge model. The support safety coefficient is used to assess the excavation face stability quantitatively. Then the rough set algorithm is used to analyse the sensitivity of each index to establish the reduced evaluation index system for the excavation face stability. The back propagation (BP) neural network is used to train the learning data, and a neural network evaluation model with a prediction error of 5.7675 × 10 -4 is established. The prediction performance of BP is verified by comparison with the TOPSIS prediction model and the cloud model. The evaluation method proposed in this paper provides an essential reference for evaluating the underwater shield tunnel excavation face stability. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.

Solid-state NMR (ss-NMR) is a powerful tool to investigate noncrystallizable, poorly soluble molecular systems, such as membrane proteins, amyloids, and cell walls, in environments that closely resemble their physical sites of action. Rotational-echo double resonance (REDOR) is an ss-NMR methodology, which by reintroducing heteronuclear dipolar coupling under magic angle spinning conditions provides intramolecular and intermolecular distance restraints at the atomic level. In addition, REDOR can be exploited as a selection tool to filter spectra based on dipolar couplings. Used extensively as a spectroscopic ruler between isolated spins in site-specifically labeled systems and more recently as a building block in multidimensional ss-NMR pulse sequences allowing the simultaneous measurement of multiple distances, REDOR yields atomic-scale information on the structure and interaction of proteins. By extending REDOR to the determination of 1 H-X dipolar couplings in recent years, the limit of measurable distances has reached ~15-20 Å, making it an attractive method of choice for the study of complex biomolecular assemblies. Following a methodological introduction including the most recent implementations, examples are discussed to illustrate the versatility of REDOR in the study of biological systems.

Pseudomonas is a cosmopolitan genus of bacteria found in soil, water, organic matter, plants and animals and known for the production of glycolipid and lipopeptide biosurfactants. In this study bacteria (laboratory collection number 28E) isolated from soil collected in Spitsbergen were used for biosurfactant production. 16S rRNA sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) revealed that this isolate belongs to the species Pseudomonas antarctica . In the present study, crude glycerol, a raw material obtained from several industrial processes, was evaluated as a potential low-cost carbon source to reduce the costs of lipopeptide production. Among several tested glycerols, a waste product of stearin production, rich in nitrogen, iron and calcium, ensured optimal conditions for bacterial growth. Biosurfactant production was evidenced by a reduction of surface tension (ST) and an increase in the emulsification index ( E 24 %). According to Fourier-transform infrared spectroscopy (FTIR) and electrospray ionization mass spectrometry (ESI-MS), the biosurfactant was identified as viscosin. The critical micelle concentration (CMC) of lipopeptide was determined to be 20 mg L -1 . Interestingly, viscosin production has been reported previously for Pseudomonas viscosa , Pseudomonas fluorescens and Pseudomonas libanensis . To the best of our knowledge, this is the first report on viscosin production by a P. antarctica 28E. The results indicated the potential of crude glycerol as a low-cost substrate to produce a lipopeptide biosurfactant with promising tensioactive and emulsifying properties., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Dysfunction of the androgen receptor (AR) signalling axis plays a pivotal role in the development and progression of prostate cancer (PCa). Steroidal and non-steroidal AR antagonists can significantly improve the survival of PCa patients by blocking the action of the endogenous ligand through binding to the hormone receptor and preventing its activation. Herein, we report two synthetic strategies, each utilizing the advantages of microwave irradiation, to modify the A-ring of natural androgen 5α-dihydrotestosterone (DHT) with pyridine scaffolds. Treatment of DHT with appropriate Mannich salts led to 1,5-diketones, which were then converted with hydroxylamine to A-ring-fused 6'-substituted pyridines. To extend the compound library with 4',6'-disubstituted analogues, 2-arylidene derivatives of DHT were subjected to ring closure reactions according to the Kröhnke's pyridine synthesis. The crystal structure of a monosubstituted pyridine product was determined by single crystal X-ray diffraction. AR transcriptional activity in a reporter cell line was investigated for all novel A-ring-fused pyridines and a number of previously synthesized DHT-based quinolines were included to the biological study to obtain information about the structure-activity relationship. It was shown that several A-ring-fused quinolines acted as AR antagonists, in comparison with the dual or agonist character of the majority of A-ring-fused pyridines. Derivative 1d (A-ring-fused 6'-methoxyquinoline) was studied in detail and showed to be a low-micromolar AR antagonist (IC 50 = 10.5 µM), and it suppressed the viability and proliferation of AR-positive PCa cell lines. Moreover, the candidate compound blocked the AR downstream signalling, induced moderate cell-cycle arrest and showed to bind recombinant AR and to target AR in cells. The binding mode and crucial interactions were described using molecular modelling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

One new phenylpropanoid glycoside, tinosinen A ( 1 ) and 13 known compounds, tinosinen ( 2 ), citrusin B ( 3 ), picraquassioside C ( 4 ), erythro -guaiacylglycerol- β - O -4'-coniferyl alcohol ( 5 ), erythro -guaiacylglycerol-8- O -4'-(sinapyl alcohol) ether ( 6 ), erythro -syringylglycerol-8- O -4'-(sinapyl alcohol) ether ( 7 ), seco -isolariciresinol 9- O -D- β -glucopyranoside ( 8 ), tinosposide A ( 9 ), pinoresinol-4'- O-β -D-glucopyranoside ( 10 ), syringaresinol-4'- O - β -D-glucopyranoside ( 11 ), pinoresinol ( 12 ), syringaresinol ( 13 ), and lirioresino- β -dimethyl ether ( 14 ) were isolated from the stems of Tinospora sinensis (Lour.) Merr. Their structures were established by detailed spectroscopic studies and comparisons with those reported in the literature. Compound 13 showed significant inhibitory NO production (IC 50 value of 38.53 ± 1.90 μM) in RAW264.7 macrophages, LPS-stimulated. Compounds 3 - 7 , 11 , 12 , and 14 inhibited NO production with IC 50 values ranging from 38.53 to 99.07 μM.

A new furostane saponin, ramosaponin ( 1 ), and four known furostane saponins, protodioscin ( 2 ), dehydrotomatoside ( 3 ), (25  R )-26- O -( β -D-glucopyranosyl)-furost-5-ene-3 β ,22 α ,26-triol 3- O - β -D-glucopyranosyl-(1→4)- β -D-galactopyranoside ( 4 ), and anguivioside A ( 5 ) were isolated from the methanol extract of Allium ramosum seeds. Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for reduction of lipid accumulation in HepG2 cell line. As a result, compound 1 showed significant lipid accumulation inhibitory activity with an IC 50 value of 64.32 ± 3.87 µM.

Civilization diseases, cancer, frequent mutations of viruses and other pathogens constitute the need to look for new drugs, as well as systems for their targeted delivery. One of the promising way of using drugs is supplying them by linking to nanostructures. One of the solution for the development of nanobiomedicine are metallic nanoparticles stabilized with various polymer structures. In this report, we present the synthesis of gold nanoparticles, their stabilization with polyamidoamine (PAMAM) dendrimers with ethylenediamine core and the characteristics of the obtained product (AuNPs/PAMAM). The presence, size and morphology of synthesized gold nanoparticles were evaluated by ultraviolet-visible light spectroscopy, transmission electron microscopy and atomic force microscopy. The hydrodynamic radius distribution of the colloids was analyzed by dynamic light scattering technique. Additionally, the cytotoxicity and changes in mechanical properties of human umbilical vein endothelial cell line (HUVEC) cells caused by AuNPs/PAMAM were assessed. The results of studies on the nanomechanical properties of cells suggest a two-step changes in cell elasticity as a response to contact with nanoparticles. When using AuNPs/PAMAM in lower concentrations, no changes in cell viability were observed and the cells were softer than untreated cells. When higher concentrations were used, a decrease in the cells viability to about 80 % were observed, as well as non-physiological stiffening of the cells. The presented results may play a significant role in the development of nanomedicine., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Agnieszka Kolodziejczyk reports financial support was provided by National Science Centre Poland., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Regulatory T cells (Treg) play a critical role in controlling immune responses in diseases such as cancer or autoimmunity. Activated Treg express the membrane protein GARP (LRRC32) in complex with the latent form of the immunosuppressive cytokine TGF-β (L-TGF-β). In this study, we confirmed that active TGF-β was generated from its latent form in an integrin-dependent manner and induced TGF-β receptor signaling in activated human Treg. We studied a series of Abs targeting the L-TGF-β/GARP complex with distinct binding modes. We found that TGF-β receptor signaling could be inhibited by anti-TGF-β and by some, but not all, Abs against the L-TGF-β/GARP complex. Cryogenic electron microscopy structures of three L-TGF-β/GARP complex-targeting Abs revealed their distinct epitopes and allowed us to elucidate how they achieve blockade of TGF-β activation. Three different modes of action were identified, including a novel unusual mechanism of a GARP-binding Ab. However, blockade of GARP or TGF-β by Abs did not influence the suppressive activity of human Treg in vitro. We were also not able to confirm a prominent role of GARP in other functions of human Treg, such as FOXP3 induction and Treg stability. These data show that the GARP/TGF-β axis can be targeted pharmacologically in different ways, but further studies are necessary to understand its complexity and to unleash its therapeutic potential., (Copyright © 2023 The Authors.)

Polygoni Cuspidati Rhizoma et Radix ( syn. rhizomes of Reynoutria japonica Houtt.) is a pharmacopoeial raw material in Europe and China. In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). Moreover, the collagen type III expression was examined using immunocytochemical staining. The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. In contrast, high levels of polysaccharides were observed. In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. The results obtained encourage the use of this raw material in its traditional, safe form-decoction.

The combination of statins and fibrates in the treatment of lipid abnormalities effectively regulates individual lipid fraction levels. In this study, the screening and assessment of the physicochemical properties of simvastatin-fenofibrate solid dispersions were performed. Fenofibrate and simvastatin were processed using the kneading method in different weight ratios, and the resulting solid dispersions were assessed using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, as well as dissolution tests. The obtained results confirmed the formation of a simple eutectic phase diagram, with a eutectic point containing 79 wt% fenofibrate and 21 wt% simvastatin, lack of chemical interactions between the ingredients, and simvastatin impact on improving fenofibrate dissolution profile, due to the formation of crystalline solid dispersions by the kneading method.

In this report, red-emitting alumina nanophosphors doped with Mn 4+ and Mg 2+ (Al 2 O 3 :Mn 4+ , Mg 2+ ) are synthesized by a hydrothermal method using a Pluronic surfactant. The prepared samples are ceramic-sintered at various temperatures. X-ray diffraction shows that Al 2 O 3 :Mn 4+ , Mg 2+ annealed at 500 °C exhibits a cubic γ-Al 2 O 3 phase with the space group Fd 3 m -227. The tetragonal δ-Al 2 O 3 and rhombohedral α-Al 2 O 3 phase is obtained at 1000 and 1300 °C, respectively. Cube-like nanoparticles in a size of ∼40 nm are observed for the alumina heated at 500-1000 °C. The size and red-emitting intensity of the phosphors remarkably increased with annealed temperature ∼1300 °C. Emission spectra of the phosphors show strong peaks at 678 and 692 nm due to 2 E g → 4 A 2 transitions of the Mn 4+ ion, under a light excitation of 460 nm. A strong zero-phonon line (ZPL) emission is observed in the luminescence spectra of δ-Al 2 O 3 :Mn 4+ , Mg 2+ at 298 K, whereas a weak one is observed in those of α- and γ-Al 2 O 3 :Mn 4+ , Mg 2+ . The alumina phosphors exhibited an excellent waterproof ability during 60 days in water and good thermal stability in the range of 77-573 K. A warm-white light-emitting diode (WLED) fabricated using In x Ga 1- x N nanowire chips with Al 2 O 3 :Mn 4+ , Mg 2+ red-emitting nanophosphors presents a high color rendering index of ∼95.1 and a low correlated color temperature of ∼4998 K. Moreover, the current-voltage characteristic of the nanowire LEDs could be improved using Al 2 O 3 :Mn 4+ , Mg 2+ nanophosphors which is attributed to the increased heat dissipation in the nanowire LEDs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This study reports the application of hierarchical porous monoliths as carriers for controlled and dose-adjustable release of model pharmaceutical (dexketoprofen, DEX). The synthesis and detailed characterization of the hierarchical porous scaffolds are provided before and after the adsorption of three doses of DEX─a widely used nonsteroidal anti-inflammatory drug. The drug incorporated in the mesopores of silica was stabilized in an amorphous state, while the presence of macropores provided sufficient space for drug crystallization as we demonstrated via a combination of powder X-ray diffraction, differential scanning calorimetry, and imaging techniques (scanning electron microscopy and EDX analysis). Drug release from silica matrices was tested, and a mechanistic model of this release based on the Fick diffusion equation was proposed. The hierarchical structure of the carrier, due to the presence of micrometric macropores and nanometric mesopores, turned out to be critical for the control of the drug phase and drug release from the monoliths. It was found that at low drug content, the presence of an amorphous component in the pores promoted the rapid release of the drug, while at higher drug contents, the presence of macropores favored the crystallization of DEX, which naturally slowed down its release. Both the hierarchical porous structure and the control of the drug phase (amorphous and/or crystalline) were proven important for adjustable (fast or prolonged) release kinetics, desirable for effective pharmacotherapy and patient compliance. Therefore, the developed materials may serve as a versatile formulation platform for the smart manipulation of drug release kinetics.

A weigh-in-motion (WIM) system continuously and automatically detects an object's weight during transmission. The WIM system is used widely in logistics and industry due to increasing labor and time costs. However, the accuracy and stability of WIM system measurements could be affected by shock and vibration under high speed and heavy load. A novel six degrees-of-freedom (DOF), mass-spring damping-based Kalman filter with time scale (KFTS) algorithm was proposed to filter noise due to the multiple-input noise and its frequency that is highly coupled with the basic sensor signal. Additionally, an attention-based long short-term memory (LSTM) model was built to predict the object's mass by using multiple time-series sensor signals. The results showed that the model has superior performance compared to support vector machine (SVM), fully connected network (FCN) and extreme gradient boosting (XGBoost) models. Experiments showed this improved deep learning model can provide remarkable accuracy under different loads, speed and working situations, which can be applied to the high-precision logistics industry.

In the present study, a hybrid photocatalyst of Zn/Ti layered double hydroxide (LDH) coupled with MXene - Ti 3 C 2 was synthesized for the first time and applied in photocatalytic degradation of acetaminophen and ibuprofen, two commonly present in the natural environment and prone to accumulate in the aquatic ecosystem pharmaceuticals. The effect of MXene content (0.5 wt%, 2.5 wt%, and 5 wt%) on the photocatalytic activity of LDH/MXene composite was investigated. The composite of LDH/MXene containing 2.5 wt% of MXene revealed the highest photocatalytic activity in the degradation of acetaminophen (100% within 40 min) and ibuprofen (99.7% within 60 min). Furthermore, an improvement in acetaminophen and ibuprofen mineralization was observed for the composite material. Meanwhile, the introduction of interfering ions (Na + , Ca 2+ , Mg 2+ , Cl - , SO 4 2- ) in the model seawater did not affect the removal efficiency of both pharmaceuticals. The photocatalytic experiment performed in the four subsequent cycles, as well as FTIR, TEM, and XPS analyses after the photodegradation process confirmed the excellent stability and reusability of the prepared composite material. In order to evaluate the effect of various reactive oxidizing species (ROS) on the photocatalytic process, the trapping experiment was applied. It was noticed that •O 2 mainly affected the degradation of ibuprofen. Finally, based on the results of Mott Schottky analysis, bandgap calculation, and ROS trapping experiment, the possible mechanism for pharmaceuticals degradation was proposed. This research illustrates the feasibility and novelty of the treatment of pharmaceuticals by LDH/MXene composites, implying that MXene plays a significant role in the electron-hole separation and thus high photocatalytic activity.- had the main contribution in photocatalytic degradation of acetaminophen, while •OH and h + mainly affected the degradation of ibuprofen. Finally, based on the results of Mott Schottky analysis, bandgap calculation, and ROS trapping experiment, the possible mechanism for pharmaceuticals degradation was proposed. This research illustrates the feasibility and novelty of the treatment of pharmaceuticals by LDH/MXene composites, implying that MXene plays a significant role in the electron-hole separation and thus high photocatalytic activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Helicobacter pylori (Hp) Gram-negative bacteria cause gastritis or gastric ulcers. They may be involved in the development of systemic diseases i.e. coronary heart disease (CHD). Both Hp infection and CHD are related to inflammation accompanied by C-reactive protein (CRP), tumor necrosis factor alfa (TNF-α) and homocysteine. Low density lipoprotein (LDL) and triglicerides are a classic risk factors of CHD. Infrared spectroscopy has been introduced for monitoring chronic infections or endogenous disorders using specific absorption bands for biocomponents typed as diagnostic markers. In this study we selected specific motives of infrared radiation (IR) spectra for the sera from CHD patients infected with Hp. In total 141 sera were used: 90 from patients with CHD, all Hp positive, and 51 from healthy donors, 32 Hp negative and 21 Hp positive. Hp status was evaluated by anti-Hp IgG antibodies and/or 13 C urea breath testing. IR spectra were measured using FT-IR/FT-NIR Spectrum 400 spectrometer (PerkinElmer) chemometrically analyzed using artificial neural networks and they showed differences in absorption bands corresponding to triglicerides, CRP, homocysteine, LDL and TNF-α, and selected component groups between CHD patients infected with Hp vs healthy uninfected donors (96.15% accuracy). Triglicerides and CRP were the best biomarkers linking Hp infection with CHD., (© 2022. The Author(s).)

Background: Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD., Objectives: To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed., Material and Methods: Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed., Results: The median citrulline level in the study population was 22.5 μM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027)., Conclusions: Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.

Superhydrophobic coatings are limited to poor durability and a tedious preparation process. In this work, an efficient, eco-friendly, and cost-effective sol-gel method is developed for preparing superhydrophobic surfaces using an all-in-one suspension composed of methyltrimethoxysilane (MTMS), nano silicon dioxide (SiO 2 ) particles, and micron zinc oxide (ZnO) particles. Superhydrophobic coatings with a contact angle (CA) up to 153.9° and a sliding angle (SA) of about 3.0° are prepared on Q235 steel substrates using MTMS 5 mL, 0.8 g of nano SiO 2 , and 0.2 g of micron ZnO. The morphology of the superhydrophobic coating is characterized by scanning electron microscopy (SEM), and the surface is covered with a micro- and nano-scaled hierarchical rough structure. A series of tests are conducted, including long-term stability tests and thermostability tests. The CAs are all above 150°, and the SAs are below 6.3°, indicating the excellent static stability of the prepared superhydrophobic coatings. Moreover, the CA of the superhydrophobic coating remains above 152° after 120 h of UV exposure, and the time for a water droplet to freeze on the surface of the superhydrophobic coating is 18 times of the bare Q235 steel, indicating that the superhydrophobic coating exhibits good resistance to UV radiation and icing-delay properties.

Reinvestigation of a methanol extract of Uraria crinita afforded a new 3- hydroxyisoflavanone, 3,5,7,2',4'-pentahydroxyisoflavanone ( 1 ), two new monoaryl glucosides, 3,4-dimethoxyphenyl 1- O -(6'- O -acetyl)- β -D-glucopyranoside ( 2) and 3,4,5-trimethoxyphenyl 1- O -(6'- O -acetyl)- β -D-glucopyranoside ( 3 ), in addition to three known compounds, 3'- O -methylorobol ( 4 ), robusflavone B ( 5 ), and apigenin ( 6 ). The structural elucidation of these compounds was achieved by analyses of their spectroscopic data (HR-ESI-MS, 1 D- and 2 D-NMR) and acidic hydrolysis. The U. crinita extracts and compounds 1 - 6 exhibited weak or no cytotoxic activity against KB, HepG2, Lu and MCF7 cell lines.

Arginine-rich cell-penetrating peptides (RRCPPs) exhibit intrinsic neuroprotective effects on neurons injured by acute ischemic stroke. Conformational properties, interaction, and the ability to penetrate the neural membrane are critical for the neuroprotective effects of RRCCPs. In this study, we applied circular dichroism (CD) spectroscopy and coarse-grained molecular dynamics (CG MD) simulations to investigate the interactions of two RRCPPs, Tat(49-57)-NH 2 (arginine-rich motif of Tat HIV-1 protein) and PTD4 (a less basic Ala-scan analog of the Tat peptide), with an artificial neuronal membrane (ANM). CD spectra showed that in an aqueous environment, such as phosphate-buffered saline, the peptides mostly adopted a random coil (PTD4) or a polyproline type II helical (Tat(49-57)-NH 2 ) conformation. On the other hand, in the hydrophobic environment of the ANM liposomes, the peptides showed moderate conformational changes, especially around 200 nm, as indicated by CD curves. The changes induced by the liposomes were slightly more significant in the PTD4 peptide. However, the nature of the conformational changes could not be clearly defined. CG MD simulations showed that the peptides are quickly attracted to the neuronal lipid bilayer and bind preferentially to monosialotetrahexosylganglioside (DPG1) molecules. However, the peptides did not penetrate the membrane even at increasing concentrations. This suggests that the energy barrier required to break the strong peptide-lipid electrostatic interactions was not exceeded in the simulated models. The obtained results show a correlation between the potential of mean force parameter and a peptide's cell membrane-penetrating ability and neuroprotective properties.

Radiation damage is one of the significant factors limiting the operating time of many structural materials working under extreme conditions. One of the promising directions in the development of materials that are resistant to radiation damage and have improved physical and mechanical properties is the creation of nanoscale multilayer coatings (NMCs). The paper is devoted to the experimental comprehension of changes in the defect structure and mechanical properties of nanoscale multilayer coatings (NMCs) with alternating layers of Zr and Nb under irradiation. Series of Zr/Nb NMCs with different thicknesses of individual layers were fabricated by magnetron sputtering and subjected to H+ irradiation. The evolution of structure and phase states, as well as the defect state under proton irradiation, was studied using the methods of high-resolution transmission electron microscopy (HRTEM), X-ray diffraction analysis (XRD), glow discharge optical emission spectroscopy (GDOES), and positron annihilation spectroscopy (PAS). The layer-by-layer analysis of structural defects was carried out by Doppler broadening spectroscopy (DBS) using a variable-energy positron beam. To estimate the binding energy and the energy paths for the hydrogen diffusion in Zr/Nb NMCs, calculations from the first principles were used. When the thickness of individual layers is less than 25 nm, irradiation causes destruction of the interfaces, but there is no significant increase in the defect level, the S parameter (open volume defects amount) before and after irradiation is practically unchanged. After irradiation of NMC Zr/Nb with a thickness of layers 50 and 100 nm, the initial microstructure is retained, and the S parameter is significantly reduced. The GDOES data reveal the irregular H accumulation at the interface caused by significant differences in H diffusion barriers in the bulk of Zr and Nb multilayers as well as near the interface's region.