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IntroductionAorto-left ventricular tunnel (ALVT) accounts for

The cell wall is an indispensable element of bacterial cells and a long-known target of many antibiotics. Penicillin, the first discovered beta-lactam antibiotic inhibiting the synthesis of cell walls, was successfully used to cure many bacterial infections. Unfortunately, pathogens eventually developed resistance to it. This started an arms race, and while novel beta-lactams, either natural or (semi)synthetic, were discovered, soon upon their application, bacteria were developing resistance. Currently, we are facing the threat of losing the race since more and more multidrug-resistant (MDR) pathogens are emerging. Therefore, there is an urgent need for developing novel approaches to combat MDR bacteria. The cell wall is a reasonable candidate for a target as it differentiates not only bacterial and human cells but also has a specific composition unique to various groups of bacteria. This ensures the safety and specificity of novel antibacterial agents that target this structure. Due to the shortage of low-molecular-weight candidates for novel antibiotics, attention was focused on peptides and proteins that possess antibacterial activity. Here, we describe proteinaceous agents of various origins that target bacterial cell wall, including bacteriocins and phage and bacterial lysins, as alternatives to classic antibiotic candidates for antimicrobial drugs. Moreover, advancements in protein chemistry and engineering currently allow for the production of stable, specific, and effective drugs. Finally, we introduce the concept of selective targeting of dangerous pathogens, exemplified by staphylococci, by agents specifically disrupting their cell walls.

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson's disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD.

Theories suggest that representational gestures depicting properties of referents in accompanying speech could facilitate language production and comprehension. In order to shed light on how gesture and speech are coordinated during production, we investigate whether representational gestures are time-locked to the onset of utterances (hence planned when full events are encoded) or Lexical Affiliates (LAs; words most closely aligned with the gesture meaning; hence planned when individual concepts are encoded) in a large corpus of naturalistic conversation (n = 1803 gestures from n = 24 speakers). Our data shows that representational gestures are more tightly tied to LA onsets than utterance onsets, which is consistent with theories of multimodal communication in which gestures aid conceptual packaging or retrieval of individual concepts rather than events. We also demonstrate that in naturalistic speech, representational gestures tend to precede their LAs by around 370ms, which means that they could plausibly allow for an addressee to predict upcoming words (ter Bekke, Drijvers & Holler, 2021; Ferré, 2010; Habets et al., 2011).

Abstract In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6‐min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group‐Performance Status [ECOG‐PS]) or patient‐reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ‐C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise‐based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG‐PS (16 vs. 9 trials), and patient‐reported EORTC QLQ‐C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.

Abstract Nanohydroxyapatite (nanoHAP) is widely used in bone regeneration, but there is a need to enhance its properties to provide stimuli for cell commitment and osteoconduction. This study examines the effect of calcination at 1200 °C on the physicochemical and biological properties of nanoHAP doped with magnesium (Mg2+), strontium (Sr2+), and zinc (Zn2+). A synergistic effect of dual modification on nanoHAP biological properties was investigated. The materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), BET analysis, Fourier-transform spectroscopy, and thermal analysis methods. Furthermore, ion release tests and in vitro biological characterization, including cytocompatibility, reactive oxygen species production, osteoconductive potential and cell proliferation, were performed. The XRD results indicate that the ion substitution of nanoHAP has no effect on the apatite structure, and after calcination, β-tricalcium phosphate (β-TCP) is formed as an additional phase. SEM analysis showed that calcination induces the agglomeration of particles and changes in surface morphology. A decrease in the specific surface area and in the ion release rate was observed. Combining calcination and nanoHAP ion modification is beneficial for cell proliferation and osteoblast response and provide additional stimuli for cell commitment in bone regeneration.

Abstract Recently, materials revealing the upconversion (UC) phenomenon, which is a conversion of low-energy photons to higher-energy ones, have attracted considerable attention in luminescence thermometry due to the possibility of precise and remote optical thermal sensing. The most widely studied type of luminescent thermometry uses a ratiometric approach based on changes in the UC luminescence intensity, mainly of lanthanide ions’ thermally coupled energy levels. In this work, NaYF4:Ho3+@NaYF4, and NaYF4:Ho3+, Er3+@NaYF4 nanoparticles (NPs) were synthesized by the controlled reaction in oleic acid and octadecene at 573 K. The obtained nanoparticles had hexagonal structures, oval shapes, and average sizes of 22.5 ± 2.2 nm and 22.2 ± 2.0 nm, respectively. The spectroscopic properties of the products were investigated by measurements of the UC emission under 1151 nm laser excitation in the temperature range between 295 to 378 K. The sample doped with Ho3+ and Er3+ ions showed unique behavior of enhancing emission intensity with the temperature. The relative sensitivity determined for the NPs containing Ho3+ and Er3+ ions, reached the maximum value of 1.80%/K at 378 K. Here, we prove that the NaYF4:Ho3+, Er3+@NaYF4 system presents unique and excellent optical temperature sensing properties based on the luminescence intensity ratios of the near-infrared bands of both Ho3+ and Er3+ ions.

Abstract Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.

Abstract Heavy metals are one of the components of smog, which is mainly the product of burning fossil fuels in residential buildings. These elements, introduced into the body of cattle by inhalation, may enter the milk. The goal of this study was to assess the impact of particulate pollution in the atmospheric air on the concentration of particulate matter in the air of a dairy cattle barn and on the content of selected heavy metals in milk from cows present in the building. Measurements were taken between November and April (148 measurement days). The calculations carried out showed a high correlation (RS = + 0.95) between the concentrations of particulates measured outside and inside the barn, which is indicative of a significant impact of the atmospheric air on the particulate pollution level of the livestock building. The number of days in excess of the daily standard for PM10 inside was 51. The conducted analysis of the chemical composition of the milk collected under high particulate pollution (February) showed that the permitted lead level had been exceeded—21.93 µg/kg (norm 20.00 µg/kg).

The excessive use of chemicals in plant production, including mineral fertilizers has a harmful effect on the morpho- and physiological state of strawberry plants, their yielding, and the physicochemical properties of the fruit and soil. Increasing the effectiveness of beneficial microorganisms, i.e. filamentous fungi, arbuscular mycorrhizal fungi (AMF) and bacteria, is an essential method of reducing the amount of fertilizers used to fertilize the soil. The aim of the study was to assess the effect of beneficial soil microorganisms (filamentous fungi and bacteria) applied alone or together with mineral fertilizers on the morpho- and physiological state of 'Marmolada' strawberry plants, their yielding, and the physico-chemical properties of the fruit. The experiment included the application of fungi (Aspergillus niger and Purpureocillium lilacinum), bacteria (Bacillus sp., Bacillus amyloliquefaciens and Paenibacillus polymyxa) alone or together with mineral fertilizers (Polifoska 6, Urea, Super Fos Dar 40). The study investigated the number of inflorescences and flowers, the intensity of the green colour of leaves, fruit yield and weight (g and %), pH, extract (°Brix), titratable acidity (g/100 g), fruit firmness (N), as well as the concentrations of macro-and microelements in the leaves of the plants. The obtained results depend on the type of fertilizer and its concentration. Strains of filamentous fungi or bacterial strains only (without fertilizer), increase the fruit yield by 60 and 35%, respectively. Reduced to 60% doses of Polifoska 6, Urea, and Super Fos Dar 40 combined with beneficial soil microorganisms influence the strawberry fruit yield more beneficially than the fertilizers applied in standard doses (100%). The mineral fertilizers enriched with soil beneficial fungi and bacteria increase the mean fruit weight by 25-30%. Both Super Fos Dar 40 enriched with bacterial strains and Polifoska 6 at 100% positively affect the physical and chemical properties of strawberry fruits. The application of reduced to 60% doses of Fos Dar 40 and Polifoska 6 enriched with beneficial bacterial strains increase the nitrogen and potassium contents in the leaves, respectively. Urea and Super Fos Dar 40 at 100% enriched with beneficial bacteria positively affect magnesium content in the leaves. Application of Polifoska 6 and NPK enriched with bacteria beneficially influences the iron content in the leaves. The calcium content in strawberry leaves decreases due to fertilization.

Abstract The aim of this study was to examine whether acute whole-body vibration, a single bout of drop jumps, or a combination of both may enhance countermovement jump (CMJ) and would affect volitional pace 3 km running performance. Twelve healthy and recreationally active males completed 4 conditions in randomized order: (i) 5 sets of 30 s calf raises on the platform but without vibration; (ii) 5 sets of 30 s calf raises on the vibration platform with 30 s rest intervals between sets; (iii) 5 sets of 6 drop jump with a 30 s rest interval between sets; (iv) 5 sets of 30 s calf raises on the vibration platform followed by 6 drop jumps with a 30 s rest interval between sets. Before, 3-min after, and immediately after a 3 km run each participant performed CMJ. No significant difference between conditions (p = 0.327) for the 3 km time trial was found. Whereas CMJ height and relative peak power were significantly improved in post-3 km run than at baseline (p

In biomedical and optical applications, multifunctional upconverting nanoparticles (UCNPs) play an essential role where non‐invasive temperature sensing and imaging are necessary. UCNPs smaller than 20 nm, which can be excited under 808 nm wavelength, are particularly promising in this area and can be implemented in humans or other mammals. However, new versatile nanoprobes are still needed for biology, especially for challenging studies of small aquatic invertebrates. Such tools allow better monitoring and understanding of their physiology, biochemistry, and ecological responses, which is crucial due to the growing pollution of water reservoirs and climate change. Herein, multifunctional NaYF4:Yb3+, Er3+@NaNdF4:Yb3+ core@shell NPs (15 nm), forming stable aqueous colloids, exhibiting intense emissions under excitation in the first biological window (808 nm), and presenting high thermal sensitivity and resolution related to the thermally coupled energy levels of Er3+ ions, are designed and synthesized. Such properties of UCNPs are further utilized for optical imaging of aquatic invertebrates (Daphnia magna) and temperature detection inside their bodies under 808 nm excitation. This pioneering application of NaYF4:Yb3+, Er3+@NaNdF4:Yb3+ demonstrates the high potential of developed UCNPs for multifunctional applications, especially for bioimaging and temperature sensing within whole organisms. [ABSTRACT FROM AUTHOR]

Two experiments tested the effectiveness of an egotistic trap, a social influence technique based on the premise that people agree to requests that align with their desirable qualities. In the first experiment, people were asked to participate in a survey-based study. In the control conditions (standard request), approx. 32.7% said yes. Yet, when it was mentioned that intelligent individuals were sought after and the subject appeared intelligent, the percentage became 52.4%. The second experiment aimed to persuade car owners to have their cars inspected at an official service station. Of the participants, 56.7% agreed in the standard conditions. However, when the phrase ‘studies show that sensible customers have their cars inspected at official service stations’ was included, it became 71.7%.

The aim of the study described herein was to design, construct and test a demonstrator of a system to control the direction of the resultant thrust vector of a rocket motor to be used in short range anti-tank missiles with a mass of up to 15 kg. The novelty of the system is that the direction of the resultant thrust vector is manipulated by means of moveable jet vanes integrated with a moveable nozzle diffuser through telescopic connectors. The technology demonstrator was built using different materials and different manufacturing processes. The first versions were 3D printed from plastic materials. Minor modifications to the design were made at an early stage. The final version had the main components made of aluminum using CNC machining. The system, with and without jet vanes, was tested on a specially developed test rig equipped with a multi-axis sensor to measure forces and torques. The nozzle performance parameters measured and analyzed in this study were the components of the thrust vector, the moments and the effective vectoring angle. The findings show that the experimental data are in good agreement with the results of earlier simulations and that the demonstrator is fully operational.

In the present study, we investigated the photooxidation of the biomimetic model of C-terminal methionine, N-Acetyl-Methionine (N-Ac-Met), sensitized by a 3-Carboxybenzophenone (3CB) excited triplet in neutral and basic aqueous solutions. The short-lived transient species that formed in the reaction were identified and quantified by laser flash photolysis and the final stable products were analyzed using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS) and tandem mass spectrometry (MSMS). Based on these complementary methods, it was possible to calculate the quantum yields of both competing reactions, and the deprotonation was found to be favored over decarboxylation (for neutral pH: ϕ-H = 0.23 vs. ϕ-CO2 = 0.09, for basic pH: ϕ-H = 0.23 vs. ϕ-CO2 = 0.05). Findings on such a model system, which can possibly mimic the complex protein environment, are important in understanding complicated biological systems, for example, the studied compound, N-Ac-Met, can, to some extent, mimic the methionine in the C-terminal domain of β-amyloid, which is thought to be connected with the pathogenesis of Alzheimer’s disease.

Abstract Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the first step of carbon fixation performed by photosynthetic organisms. Form I of this enzyme found in plants and cyanobacteria is composed of eight large (RbcL) and eight small (RbcS) subunits. To form a functional enzyme, Rubisco subunits need to be properly folded, with the assistance of cellular chaperone machinery, and consecutively assembled in a strictly orchestrated manner, with the help of multiple auxiliary factors. In recent years, multiple Rubisco assembly chaperones and their function in enzyme biogenesis have been extensively characterized. Little is known about the potential specialized factors involved in Rubisco subunits folding at the pre-chaperonin stage, yet this knowledge is greatly needed for the fast and efficient testing of new Rubisco variants. Synechococcus sp. PCC 6803 Rubisco shows limited solubility and a lack of assembly in the Escherichia coli expression system. In this study, we aim to identify which additional chaperones are necessary and sufficient in sustaining the heterologous assembly of native Rubisco. Our findings prove that upon the introduction of Synechocystis DnaK2 to the E. coli system, RbcL is produced in soluble form. The addition of specific DnaJ (Sll1384) enhances this effect. We explain these combined effects based on binding constancies, measured for particular partners in vitro, as well as our analysis of the putative tertiary structure of the proteins. Our results have potential implications for Rubisco engineering.