Mitochondrial Function and Resistance to Oxidative Stress in the Kidney during Pregnancy.

We demonstrated that the serum of pregnant rats increases viability of kidney epithelial cells and promotes their proliferation. The intensity of oxidative stress in the kidneys was also reduced during pregnancy, but only in rats that were not exposed to acute ischemic kidney injury. This decrease in oxidative stress was not associated with changes in transmembrane mitochondrial potential, the size of mitochondria, time of opening of mitochondrial permeability transition pore (mPTP), mitochondrial respiration rate, antioxidant activity, or nitric oxide level.

"Association between caries in anterior teeth and bullying victimization in Brazilian schoolchildren aged 6 to 10 years.: a cross sectional study".

AIM: To investigate the association between presence of caries in anterior teeth and bullying victimization in schoolchildren. METHODS: A cross-sectional study was conducted in Brazil with a sample of 387 schoolchildren aged 6 to 10 years. The presence of moderate/extensive dental caries was assessed using the International System for the Evaluation and Detection of Dental Caries (ICDAS-II). The children answered the "Olweus Bullying" (QBO). Descriptive analyses were performed, and the associations between bullying victimization and independent variables collected were determined by univariate and multivariate Poisson regression. RESULTS: The prevalence of bullying victimization was 66.4%. Bullying victimization was higher among children who had moderate/extensive caries in some anterior teeth (p = 0.010). 8-year-old (p = 0.048), 9-year-old (p = 0.001), and 10-year-old (p = 0.002) children reported greater bullying victimization when compared to 6-year-olds. CONCLUSION: The presence of moderate/extensive dental caries in anterior teeth is associated with bullying victimization in schoolchildren.

Collagen and collagenases in mare's endometrium with endometrosis.

Equine endometrosis is a degenerative and predominantly fibrotic condition resulting from progressive and irreversible multifactorial causes that influence the endometrium of mare. Tissue remodeling in the equine endometrium occurs as part of the pathogenesis of endometrosis, a process characterized by a shift in extracellular matrix (ECM) components. The relationship between matrix metalloproteinases and their specific inhibitors is crucial for the remodeling process. Collagen play a significant role in maintaining a healthy uterus and may promote fibrotic processes. The aim of this study was to quantify endometrial collagen deposition using picrosirius 25 red (PSR) staining, and to evaluate gene expression of collagen type 2 (COL-2) and 3 (COL-3), matrix metalloproteinases 1 (MMP-1) and 2 (MMP-2), their tissue inhibitor (TIMP-2), and tumor necrosis factor (TNF-α) in the endometrium of mares with different grades of fibrosis. The samples (n = 34) were classified into three categories based on the frequency and distribution of fibrosis-related changes in the endometrium: Category I (healthy endometrium, n = 12), Category II (moderate fibrosis, n = 12), and Category III (severe fibrosis, n = 10). Collagen quantification demonstrate a substantial proportional increase (P < 0.0001) in collagen deposition across Category I (11.72 ± 1.39 %), Category II (17.76 ± 1.29 %), and Category III (24.15 ± 1.87 %). In transcript evaluations, higher COL-2 expression was found in Category II than in mares classified as Category I or III. MMP-1 showed increased transcript expression in Category II compared to Category III endometrial samples. Higher expression of MMP-2 was detected in Category III than in Category I and II. TIMP-2 showed lower mRNA expression in Category III vs Category I and II. However, TNF-α gene expression was higher in Category II than in Categories I and III. This study demonstrates that endometrial evaluation using PSR can play an important role in routine analyses for the detection and objective quantification of collagen in endometrial tissues. Additionally, this study demonstrated through gene expression analysis that MMP-1 may be linked to physiological endometrial remodeling. In contrast, MMP-2 could be associated with fibrogenesis in the endometrium, which is regulated by the inhibitor TIMP-2. Furthermore, COL-2 and TNF-α could be considered as biological markers involved in the progression endometrosis in mares. As such, the results of this study may contribute to the development of future antifibrotic therapies that aim to delay or even reverse the pathological remodeling of the extracellular matrix in the uterus, in addition to optimizing the diagnosis and prognosis of endometrial fibrosis in mares.

Black hole jets on the scale of the cosmic web.

When sustained for megayears (refs. 1,2), high-power jets from supermassive black holes (SMBHs) become the largest galaxy-made structures in the Universe3. By pumping electrons, atomic nuclei and magnetic fields into the intergalactic medium (IGM), these energetic flows affect the distribution of matter and magnetism in the cosmic web4-6 and could have a sweeping cosmological influence if they reached far at early epochs. For the past 50 years, the known size range of black hole jet pairs ended at 4.6-5.0 Mpc (refs. 7-9), or 20-30% of a cosmic void radius in the Local Universe10. An observational lack of longer jets, as well as theoretical results11, thus suggested a growth limit at about 5 Mpc (ref. 12). Here we report observations of a radio structure spanning about 7 Mpc, or roughly 66% of a coeval cosmic void radius, apparently generated by a black hole between 4.4 - 0.7 + 0.2 and 6.3 Gyr after the Big Bang. The structure consists of a northern lobe, a northern jet, a core, a southern jet with an inner hotspot and a southern outer hotspot with a backflow. This system demonstrates that jets can avoid destruction by magnetohydrodynamical instabilities over cosmological distances, even at epochs when the Universe was 7 to 1 5 - 2 + 6 times denser than it is today. How jets can retain such long-lived coherence is unknown at present.

Acute normobaric hypoxia causes a rightward shift in the torque-frequency relationship, but has no effect on post-activation potentiation.

Low fractions of inspired oxygen (FIO2; i.e., hypoxia) affect aspects of skeletal muscle contractility in humans, but it remains unclear if post-activation potentiation (PAP) and the torque-frequency (T-F) relationship are altered. We investigated the effects of two (H2) and four hours (H4) of normobaric hypoxia (FIO2=0.11±0.47) on the magnitude of PAP of the knee extensors (KE) and the T-F relationship of the dorsiflexors (DF) in 13 and 12 healthy participants, respectively. To assess PAP, a resting twitch was evoked via femoral nerve stimulation before, and 2-300 s following a 10-s maximal voluntary contraction (MVC). A T-F relationship was obtained by stimulating the common fibular nerve with a single pulse and 1-s trains between 5-100 Hz. During hypoxia, peripheral oxygen saturation decreased by ~18% from 98.0±0.8% at baseline (P<0.001). MVC force and voluntary activation (VA) of the KE were lower than baseline throughout hypoxia (e.g., ~8 and ~5%, respectively at H2; P≤0.027); however, the magnitude of PAP was not altered by hypoxia (P≥0.711). Surprisingly, PAP did increase with time across the control day (P≤0.012). MVC torque and VA of the DF were unaffected by hypoxia (P≥0.127), but the estimated frequency required to evoke 50 % of 100-Hz torque increased by ~1.2 Hz at H2 (P≤0.021). These results imply that two hours of normobaric hypoxia were sufficient to: i) impair neural drive to the KE but not the mechanism(s) responsible for PAP, and ii) lead to a rightward shift of the T-F relationship for the DF.

[Adaptation of the 12-item medication adherence scale ( the Questionnaire for assessment of adherence to Medication) on a Russian-speaking sample of patients with type 1 and type 2 diabetes mellitus].

BACKGROUND: Poor adherence to treatment among patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) hinders the effective use of antidiabetic agents and the achievement of optimal glycemic control, reducing their quality of life and outcomes. Assessing adherence to treatment using a questionnaire can help identify and eliminate factors and barriers that negatively affect adherence to medical recommendations and satisfaction with treatment. AIM: To conduct linguistic and cultural adaptation of the 12-item Medication Adherence Scale (MAS-12) questionnaire and evaluate the psychometric properties of the Russian version of the MAS-12 questionnaire among patients suffering from T1DM and T2DM. MATERIALS AND METHODS: A survey of 198 patients with T1DM and T2DM was carried out, including self-completion of the MAS-12 questionnaire in Russian. Average age: 47.1±18.62 years, proportion of women - 76%. Average duration of the disease: 13.08±10.05 years. The construct validity of the MAS-12 questionnaire was assessed using confirmatory factor analysis. As an external criterion for assessing convergent validity, the KOP-25 method was used - the Russian Questionnaire for Quantitative Assessment of Treatment Adherence (KOP-25). Reliability of the MAS-12 was assessed using Cronbach's α internal consistency and participant retest after 1 to 4 months. RESULTS: The factor structure of the MAS-12 questionnaire is reproduced for the first time on a Russian sample of patients with diabetes. Recommended fit indicators for the measurement model (CFI=0.983, RMSEA=0.049, TLI=0.968) were achieved by excluding two items (9 and 12) that did not demonstrate statistically significant contributions to their respective subscales. The internal consistency of the subscales (α ϵ [0.522; 0.857]) and the questionnaire as a whole (α=0.766) was assessed as sufficient. Significant correlations of the adapted methodology and its subscales with the scales of the KOP-25 questionnaire were obtained. The closest connections (r ϵ [0.333; 0.431], p<0.010) are observed with the COP-25 scales related to drug therapy, which indicates good external validity of the adapted methodology. CONCLUSION: The Russian version of the MAS-12 questionnaire "Questionnaire for assessing adherence to medication treatment" (PML-10), consisting of 10 questions, has good psychometric properties, is a valid and reliable tool for assessing medication adherence among patients with T1DM and T2DM and can be recommended for use in clinical practice, including for monitoring treatment adherence in Russia.

[Analysis of learning curves for mini-gastric bypass in 341 patients with obesity]. / Izuchenie opyta osvoeniya mini-gastroshuntirovaniya metodom postroeniya krivykh obucheniya u 341 patsienta s ozhireniem.

OBJECTIVE: To analyze learning curves and appropriate experience on the features of mini-bypass surgery in 341 obese patients. MATERIAL AND METHODS: A total of 341 laparoscopic mini-gastric bypass surgeries performed by one surgeon were studied. The median age of patients was 40.5 [34; 48.3] years. There were 284 (83.2%) women and 57 (16.8%) men. The median BMI was 45 [40;52] kg/m2. RESULTS: The period of MGB development consisted of 138 interventions. Surgery time was 120 [100; 130] min and 90 [82.5; 100] mins after development of this technique (p=0.001). Complications occurred in 5 (1.5%) patients (1 patient with Clavien Dindo grade IIIA and 4 ones with grade IIIB). Of these, there were 3 patients with stapler suture defects. There were no complications only in the 4th quartile of surgeries. Surgical experience significantly affects postoperative outcomes. Surgery time was more influenced by surgical skill rather technique of anastomosis imposing. CONCLUSION: Polynomial regression objectively characterizes development of surgical skills lasting 138 interventions. MGB is safe for morbid obesity with a complication rate of 1.5% and no mortality.

Antibacterial properties of photo-crosslinked chitosan/methacrylated hyaluronic acid nanoparticles loaded with bacitracin.

The current treatments for wounds often fail to induce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. Photo-crosslinked HAMA/CS nanoparticles loaded with BC demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.

The effects of four hours of normobaric hypoxia on the vestibular control of balance.

Whole-body vestibular-evoked balance responses decrease following ~ 55 min of normobaric hypoxia. It is unclear how longer durations of hypoxia affect the vestibular control of balance at the muscle and whole-body levels. This study examined how four hours of normobaric hypoxia influenced the vestibular control of balance. Fifteen participants (4 females; 11 males) stood on a force plate with vision occluded and head rotated rightward while subjected to three blocks of binaural, bipolar stochastic electrical vestibular stimulation (EVS; 0-25 Hz, root mean square amplitude = 1.1 mA) consisting of two, 90-s trials. The relationship between EVS and anteroposterior (AP) forces or medial gastrocnemius (MG) electromyography (EMG) was estimated in the time and frequency domains at baseline (BL; 0.21 fraction of inspired oxygen-FIO2) and following two (H2) and four (H4) hours of normobaric hypoxia (0.11 FIO2). The EVS-MG EMG short-latency peak and peak-to-peak amplitudes were smaller than BL at H2 and H4, but the medium-latency peak amplitude was only lower at H4. The EVS-AP force medium-latency peak amplitude was lower than BL at H4, but the short-latency peak and peak-to-amplitudes were unchanged. The EVS-MG EMG coherence and gain were reduced compared to BL at H2 and H4 across multiple frequencies ≥ 7 Hz, whereas EVS-AP force coherence was blunted at H4 (≤ 4 Hz), but gain was unaffected. Overall, the central nervous system's response to vestibular-driven signals during quiet standing was decreased for up to four hours of normobaric hypoxia, and vestibular-evoked responses recorded within postural muscles may be more sensitive than the whole-body response.

Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR.

. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here, we present 1-year efficacy and safety data of the SOLAR study. OBJECTIVES: . To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA. MATERIALS AND METHODS: : The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18 years with confirmed diagnosis of RA1 were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued to  receive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152). RESULTS: : Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred. CONCLUSIONS: : Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24.

Real-World Retention Rate, Effectiveness, and Safety of Netakimab in the Treatment of Patients with Ankylosing Spondylitis: First Year Results of the LIBRA Post-Registration Safety Study.

Netakimab has shown high efficacy in controlled clinical trials in the treatment of AS patients. This article presents results of an observational study of netakimab using in routine clinical practice. OBJECTIVE: : To evaluate retention rates and safety of netakimab in patients with AS in real-world clinical practice. Additionally, the efficacy of netakimab was evaluated at 1-year follow-up. MATERIALS AND METHODS: : Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, and 52 weeks of therapy were collected within the study. Drug survival rate was calculated according to Kaplan-Meier analysis. RESULTS: : The study included 137 (93 men and 44 women) patients with AS. The average age of patients was 42.3 (11.9) years, 34.3% of patients had previously received therapy with bDMARD, mainly TNF inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% (95% CI, 85.4-95.7) of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; AEs, related to therapy according to the investigator's opinion, were reported in 7 (5.1%) patients. Two patients stopped taking netakimab due to AEs (terminal ileitis and chronic colitis). CONCLUSIONS: : In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

Grb2 Y160F mutant mimics the wild-type monomeric state dynamics and the monomer-dimer equilibrium.

The Growth factor receptor-bound protein 2 (Grb2) participates in early signaling complexes and regulates tyrosine kinase-mediated signal transduction through a monomer-dimer equilibrium. Grb2 dimeric state inhibits signal transduction whereas the monomer promotes signaling downstream. Since Grb2 dimer KD is ∼0.8 µM, studies focused on the monomer are still challenging and require mutations or interaction with phosphotyrosine peptides. However, these mutants were never characterized considering their effects on protein structure and dynamics in solution. Here, we present the biophysical characterization of Grb2Y160F, the first Grb2 mutant to induce protein monomerization without disrupting its native behavior in solution due to net charge modifications or interaction with peptides. We also identified that Grb2Y160F exists in a monomer-dimer equilibrium. Grb2Y160F ability to dimerize implies that different dimerization interfaces might regulate signaling pathways in distinct ways and raises an important question about the role of the Y160 residue in other dimerization interfaces.

Study of the N1-(2,3,4-Trimethoxybenzyl)-N2-{2-[(2,3,4-Trimethoxybenzyl)Amine]Ethyl}-1,2-Ethandiamine Compound Effect on the Physical Performance of Animals.

We studied the effect of N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (compound ALM-802) on the physical performance of mice after acute fatigue. The animals' performance was assessed on a treadmill. The criterion for assessing exercise tolerance was the length of the distance passed when running on a treadmill until complete fatigue. To assess the actoprotective activity of compound ALM-802, we used a method of stepwise increase in load with an initial running speed of 42 cm/sec and its subsequent increase by 5 cm/sec every 5 min. The maximum speed of movement of the treadmill belt is 77 cm/sec. Animals that received compound ALM-802 (2 mg/kg intraperitoneally), 1 day after acute fatigue, ran a distance to complete fatigue that exceeded that of control mice by 68% (387.9±60.5 and 230.6±29.6 m, respectively, p=0.023). The reference drug trimetazidine (30 mg/kg, intraperitoneally) did not have a significant effect on the distance traveled. Compound ALM-802 helps restore physical performance, i.e. exhibits significant actoprotective activity.

[Artificial ventilation in patients with stroke: main results of the Russian multicenter observational clinical trial RETAS]. / Iskusstvennaya ventilyatsiya legkikh u patsientov s ostrym narusheniem mozgovogo krovoobrashcheniya: osnovnye rezul'taty Rossiiskogo mnogotsentrovogo observatsionnogo klinicheskogo issledovaniya RETAS.

OBJECTIVE: To analyze the relationship between the characteristics of respiratory support (RS) for patients with stroke and clinical factors with the number and structure of complications, deaths, and length of stay in the intensive care unit (ICU) and duration of artificial pulmonary ventilation (ALV). MATERIAL AND METHODS: The Russian multicenter observational clinical study «Respiratory Therapy for Acute Stroke¼ (RETAS) that enrolled 1289 patients with stroke requiring RS was conducted under the auspices of the All-Russian public organization «Federation of Anesthesiologists and Resuscitators¼. Indications for ALV, the use of hyperventilation, the maximum level of positive end-expiratory pressure, starting modes of mechanical ventilation, timing of tracheostomy, the incidence of protein-energy malnutrition (PEM) and infectious complications were analyzed. The following scales were used to assess the severity of the condition: the National Institutes of Health Stroke Severity Scale (NIHSS), the Glasgow Coma Scale, the Glasgow Outcome Scale (GOS). RESULTS: For the group of patients with a stroke severity of more than 20 NIHSS points, the mortality increase was associated with initial hypoxia (p=0.004), hyperventilation used to relieve intracranial hypertension (p=0.034), and starting ventilation with volume control (VC) compared with starting pressure-controlled ventilation (PC) (p<0.001). We found that the use of the instrumental monitoring of intracranial pressure was associated with a decrease in mortality (p<0.001). The absence of PEM in patients with stroke is associated with a higher probability of a positive outcome (GOS 4 and 5) for the group with NIHSS less than 14 points (p<0.001). Ventilator-associated tracheobronchitis and ventilator-associated pneumonia were associated with an increase in the duration of ALV, the duration of weaning from the ventilator (for ventilator-associated tracheobronchitis) and the duration of stay in the ICU, and also reduced the chances of favorable outcomes (p<0.05). CONCLUSION: The factors associated with increased mortality in acute stroke are: hypoxemia at the start of ALV, hyperventilation, starting ventilation with VC in comparison with starting ventilation with PC, the use of only clinical methods of monitoring intracranial pressure in comparison with instrumental monitoring. The adverse effect of PEM and infectious complications on the outcome in patients with acute stroke has been proven.

Body Surface Potential Mapping during Atrial Depolarization in Rats with Post-Infarction Chronic Heart Failure against the Background of Fabomotizole Therapy.

Cardiac remodeling in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction leads to an atypical location of areas of positive and negative cardioelectric potentials on the body surface before the onset of the PII-wave on the ECG in the limb leads, which is a sign of increased heterogeneity of atrial depolarization associated with the appearance of additional excitation focus in the left atrium. A course of therapy with fabomotizole leads to a decrease in the heterogeneity of atrial depolarization at the initial stages of the formation of the cardioelectric field of the atria on the body surface before the onset of the PII-wave, thereby producing an antiarrhythmic effect.

Shape-persistent ladder molecules exhibit nanogap-independent conductance in single-molecule junctions.

Molecular electronic devices require precise control over the flow of current in single molecules. However, the electron transport properties of single molecules critically depend on dynamic molecular conformations in nanoscale junctions. Here we report a unique strategy for controlling molecular conductance using shape-persistent molecules. Chemically diverse, charged ladder molecules, synthesized via a one-pot multicomponent ladderization strategy, show a molecular conductance (d[log(G/G0)]/dx ≈ -0.1 nm-1) that is nearly independent of junction displacement, in stark contrast to the nanogap-dependent conductance (d[log(G/G0)]/dx ≈ -7 nm-1) observed for non-ladder analogues. Ladder molecules show an unusually narrow distribution of molecular conductance during dynamic junction displacement, which is attributed to the shape-persistent backbone and restricted rotation of terminal anchor groups. These principles are further extended to a butterfly-like molecule, thereby demonstrating the strategy's generality for achieving gap-independent conductance. Overall, our work provides important avenues for controlling molecular conductance using shape-persistent molecules.

Glucocorticoid Deflazacort Normalizes the Ultrastructure of Skeletal Muscles and the State of the Colon Microbiota in Dystrophin-Deficient Mice.

We studied the effect of enteral administration of the glucocorticoid deflazacort (DFC, 1.2 mg/kg per day, 28 days) on the state of skeletal muscles and tissue ultrastructure, as well as the composition of the colon microbiota in dystrophin-deficient mdx mice. DFC has been shown to reduce the intensity of degeneration/regeneration cycles in muscle fibers of mdx mice. This effect of DFC was accompanied by normalization of the size of sarcomeres of skeletal muscles of mdx mice, improvement of the ultrastructure of the subsarcolemmal population of mitochondria, and an increase in the number of organelles, as well as normalization of the number of contact interactions between the sarcoplasmic reticulum and mitochondria. In addition, DFC had a corrective effect on the colon microbiota of mdx mice, which manifested in an increase in the number of the Bifidobacterium genus microorganisms and a decrease in the level of E. coli with reduced enzymatic activity.

New palladium(II) ß-ketoesterates for focused electron beam induced deposition: synthesis, structures, and characterization.

We report the synthesis and characterization of new palladium(II) ß-ketoesterate complexes [Pd(CH3COCHCO2R)2] with alkyl substituents R = tBu, iPr, Et. These compounds can have potential use in focused electron beam induced deposition (FEBID), which is a direct write method for the growth of structures at the nanoscale. However, it is still a major challenge to obtain deposits with a high metal content, and new precursor molecules are needed to overcome this. Single crystal X-ray diffraction, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and density-functional theory calculations were used to confirm the compounds' composition and structure. Using thermal analysis and sublimation experiments, we investigate their thermal stability and volatility. These studies show that the palladium complexes sublimate over the range 348-353 K under 10-2 mbar pressure. The electron-induced decomposition of the complex molecules in the gas phase and their thin layers on silicon substrates were analysed using electron impact mass spectrometry (EI MS) and microscopy studies (SEM/EDX). They confirm that the precursor electron-induced fragmentation depends on the molecular structure. The obtained results reveal that [Pd(CH3COCHCO2tBu)2] with cis-positioned tert-butyl groups may be a promising FEBID precursor, and we carried out preliminary deposition experiments using this compound.

Analysis of Immunobiological Properties of Recombinant Streptococcus pneumoniae Pneumolysin.

We compared the immunogenicity of recombinant S. pneumoniae pneumolysin (rPly) when administered with and without Al(OH)3 adjuvant, and evaluated the protective properties of recombinant protein in the active defense experiment. It was shown that double immunization with rPly+Al(OH)3 increases the levels of IgG antibodies in comparison with the control (p<0.01), while triple immunization results in a more significant increase in IgG antibody levels (p<0.001). Double immunization with rPly without Al(OH)3 does not induce a significant increase in antibody levels in comparison with the control, while triple immunization results in a slight but significant increase in antibody levels (p<0.05). The active defense test proved the protective activity of rPly against S. pneumoniae serotype 3 at intranasal infection.

Insight into Olfactory Learning, Memory, and Mortality of Apis mellifera jemenitica after Exposure to Acetamiprid Insecticide.

The honey bee, a significant crop pollinator, encounters pesticides through various routes of exposure during foraging and flower visitation. Considering the potential threat of pesticide poisoning, the indigenous Saudi bee Apis mellifera jemenitica is susceptible to the risks associated with acetamiprid, a neonicotinoid insecticide. This study investigates the acetamiprid-induced effects on the survival, olfactory learning, and memory formation of A. m. jemenitica through two exposure routes: topical application and oral ingestion. Field-realistic and serially diluted concentrations (100, 50, 25, and 10 ppm) of acetamiprid led to notable mortality at 4, 12, 24, and 48 h after treatment, with peak mortality observed at 24 h and 48 h for both exposure routes. Bee mortality was concentration-dependent, increasing with the rising concentration of acetamiprid at the tested time intervals. Food consumption following oral exposure exhibited a concentration-dependent pattern, steadily decreasing with increasing concentrations of acetamiprid. Oral exposure resulted in a substantially higher cumulative mortality (55%) compared to topical exposure (15%), indicating a significant disparity in bee mortality between the two exposure routes. The 24 h post-treatment LC50 values for acetamiprid were 160.33 and 12.76 ppm for topical application and oral ingestion, respectively. The sublethal concentrations (LC10, LC20, and LC30) of acetamiprid were 15.23, 34.18, and 61.20 ppm, respectively, following topical exposure, and 2.85, 4.77, and 6.91 ppm, respectively, following oral exposure. The sublethal concentrations of acetamiprid significantly decreased learning during the 2nd-3rd conditioning trials and impaired memory formation at 2, 12, and 24 h following both topical and oral exposure routes, compared to the control bees. Notably, the sublethal concentrations were equally effective in impairing bee learning and memory. Taken together, acetamiprid exposure adversely affected bee survival, hindered learning, and impaired the memory retention of learned tasks.