Preterm birth is the leading cause of death in children under five years of age worldwide. The association between preterm birth and long-term outcomes is vaguely known. In very preterm infants, the gut microbiome is highly variable and impacted by the neonatal intensive care unit environment. Our objective was to better understand the crosstalk between the gut microbiome and the host at one month of age in very preterm infants and its impact on neurological outcomes at two years of age. We performed a multi-omics analysis of fecal samples collected in 2011 from 73 very preterm French infants at one month of age, grouped according to their neurodevelopment assessed at two years of age using the Ages & Stages questionnaire. Multi-omics profiling and integrative analyses were performed between 2022 and 2023, including fecal microbiome, metabolome, and host transcriptome characterization using 16S rRNA gene sequencing, LC-MS, and mRNA sequencing, respectively. The gut microbiome of very preterm infants at one month is mostly driven by either Escherichia or Staphylococcus, which are differentially associated with host immune markers (CAMP), metabolomic pathways, notably the energy pathway due to the presence of various nicotinamide adenine dinucleotides (NAD+) and two-year neurodevelopmental outcomes. The gut microbiome at one month of age could be a noninvasive biomarker of gut immaturity and metabolic defects. Escherichia and Staphylococcus proportions were found to be the best indicators of physiological maturity and immaturity, respectively. Escherichia may help the process of intestinal maturation in preterm infants through specific metabolites production and is associated with a better neurodevelopment.

Attributes required for soccer performance may be developed through involvement in pitch-based training and its interaction with growth and maturation processes even in the absence of specific strength, speed, and power training. This study was designed to investigate the effects of training stimuli and its interaction with growth and maturation on changes in physical performance over a 7−8-month period. Highly-trained youth soccer players affiliated to a professional soccer club (PSA; age: 13.8 ± 0.53, stature: 162.8 ± 8.3 cm, body mass: 52.2 ± 7.1 kg) exposed to both pitch-based training and strength, speed, and power training, were compared to amateur (ASA; age: 14.3 ± 0.53, stature: 166.8 ± 8.9 cm, body mass: 55.4 ± 7.7 kg) players that undertook pitch-based training alone. Two age groups from each club completed an isometric squat test (ISqT), countermovement jump (CMJ), 10 m, 20 m, and 30 m sprint tests. PSA players improved ( p = < 0.001 and 0.023, respectively) CMJ and ISqT relative peak force (rPF) scores by 3.53 cm and 6.75 N/kg respectively, compared to the ASA players. Maturation improved ( p < 0.05) performance in all physical tests and metrics apart from ISqT rPF. The results suggest that maturation combined with pitch- and specific training results in greater improvements in muscle force production and CMJ height compared to maturation pitch-based training alone. Although maturation processes likely contributed towards a significant proportion of the improvements in aforementioned characteristics, practitioners should consider programming additional tailored training strategies to optimise these effects.

Variations in the prostate of Molossus molossus during the processes of testicular maturation, regression, and recrudescence: Morphophysiology and hormonal control.

Since their discovery over 90 years ago, neutrons have become one of the premier tools in the study of the structure and dynamics of matter and materials. The main nuclear processes to generate a large number of free neutrons are fusion, fission, and spallation, which have been well established for using neutrons in broad areas of physics, material science, engineering, life sciences, and elsewhere. The vast majority of experiments that use neutrons as a probe require a directional, well-collimated beam of neutrons. Over the years, methods have been developed to deliver such neutron beams sufficiently, but it is still much desired to improve the efficiency of neutron sources. With the advent of high-powered lasers, laser-driven neutron sources suggest an attractive possibility. Laser photons can be converted to neutrons by accelerating particles (electrons, protons, and deuterons) and then either utilize hard x rays from, for example, electron acceleration to create photoneutrons or nuclear reactions, such as deuteron break-up. The maturity of such processes in recent years might have reached a state where such neutron sources are becoming useful and beneficial to the neutron community. In the present report, the current state-of-the-art of a laser-driven neutron source and its future development for neutron applications are presented, and existing sources are described. The basic physical principles of laser-driven neutron production and the current state-of-the-art of production techniques are outlined. The potential developments and the role of such sources in the landscape of neutron sources in the future are critically commented on.

Depletion of CX3CR1+ macrophages results in disrupted functionality and immune surveillance within epididymis and testis.

Background/Objectives: Smith–Magenis syndrome (SMS) is a rare neurogenetic disorder caused by a microdeletion in chromosome region 17p11.2 or by pathogenic variants in the RAI1 gene. The syndrome is characterized by a distinctive neurobehavioral profile, including cognitive deficits, sleep disturbances, self-injurious behavior, and typical dysmorphic features. A characteristic diagnostic hallmark is paradoxical melatonin secretion, with increased daytime levels instead of the normal nocturnal peak. This article aims to summarize current knowledge on the etiology, diagnostics, EEG findings, therapy, and prognosis of SMS from a neuropediatric perspective. Methods: A narrative review of the literature on Smith–Magenis syndrome was conducted, focusing on genetic background, clinical features, diagnostic approaches, EEG characteristics, therapeutic strategies, and prognosis. In addition, a detailed clinical case of a 16-year-old female patient with SMS is presented. Results: The reviewed data confirm that SMS is associated with characteristic neurobehavioral abnormalities and sleep–wake rhythm disturbances. EEG findings may include epileptiform activity without overt epilepsy. In the presented case, “Rolandic-type” spike–sharp wave complexes were observed on EEG and are interpreted as an expression of congenital disturbances in brain maturation processes. Therapeutic recommendations addressing behavioral symptoms and sleep regulation are discussed. Conclusions: Smith–Magenis syndrome represents a complex neurodevelopmental disorder with distinctive clinical, neurophysiological, and genetic features. Early recognition of characteristic signs, including sleep disturbances and EEG abnormalities, is essential for appropriate management. A multidisciplinary, individualized therapeutic approach may improve quality of life and long-term outcomes.

The selection of graft remains a subject of ongoing debate in anterior cruciate ligament (ACL) reconstruction, with distinct maturation processes having been observed among different graft types. A thorough understanding of these differences in graft maturation is crucial for optimizing rehabilitation protocols and ensuring a safe return to sports. This study aimed to systematically review the differences in graft maturation among different graft types following ACL reconstruction. A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included only if they compared intra-articular ACL graft maturity across different graft types. Twenty-one studies met the inclusion criteria. Graft maturity was assessed using magnetic resonance imaging (MRI) in 15 studies, second-look arthroscopy in 4 studies, and histological biopsy in 1 study; one additional study utilized both MRI and second-look arthroscopy. Hamstring tendon (HT) and bone-patellar tendon-bone (BPTB) autografts showed similar maturity, as assessed by MRI signal intensity (SI) and histological findings, after ACL reconstruction. However, results from second-look arthroscopy were inconclusive. HT autografts exhibited MRI SI comparable to soft-tissue allografts within the first postoperative year, but demonstrated superior maturity and graft appearances at approximately 2years postoperatively. Quadriceps tendon (QT) autografts, both with and without a patellar bone block, revealed lower MRI SI compared to HT autografts, suggesting better graft maturity. HT autografts with preserved tibial insertion maintained relatively lower SI during the early maturation phase (6 and 12months) than free HT autografts, though no significant differences were observed at later stages (24 and 60months). MRI, second-look arthroscopy, and histological biopsy analysis indicated distinct graft maturation levels following ACL reconstruction. No conclusive evidence established whether HT or BPTB autografts are superior in terms of graft maturity. Compared to free HT autografts and soft-tissue allografts, QT autografts and HT autografts with preserved tibial insertion may mature earlier, which may allow for consideration of an earlier return to sports in clinical decision-making. These grafts may therefore represent viable alternatives to HT and BPTB grafts, particularly in young and active patients. III, systematic review of level Ⅰ-Ⅲ investigation.

Unlike mRNA surveillance, ncRNA quality control is less well understood. While mRNA maturation is monitored by guard proteins that allow nuclear export of correctly processed transcripts or retention and degradation of faulty RNAs, such surveillance system is unknown for ncRNAs. This study investigates the maturation process of the snRNA U6 in Saccharomyces cerevisiae, revealing that this RNAPIII transcript undergoes quality control by established guard proteins and the novel factor Lhp1 (human La), which ensures proper loading of the Lsm-ring in the nucleus. Subsequent Mex67 binding facilitates the nuclear export of pre-U6. In the cytoplasm, pre-U6 associates with Prp24 which assists in annealing with pre-U4. Defects in di-snRNP formation are identified by the guard proteins Npl3, Gbp2, and Hrb1. These proteins retain the RNA in the cytoplasm and recruit Dcp1 and Dcp2 for de-capping, along with Xrn1 for degradation of faulty pre-U6. Correctly assembled U4/U6 complexes are released from the guard proteins and imported back into the nucleus. This guard protein-mediated surveillance mechanism prevents faulty di-snRNPs to torpedo the spliceosome, underscoring the significance of the compartmented maturation and quality control of ncRNA. Additionally, the study illustrates that RNA surveillance mechanisms extend beyond coding RNAs and involve similar quality control mechanisms and proteins.

NVL2-interacting protein CWF19L2 is required for debranching of intron-derived lariat RNAs.

Doublecortin-expressing cells are selectively altered in the piriform cortex but not in neurogenic areas of symptomatic Mecp2-heterozygous mice.

Small-scale siRNA screen reveals WWC2 as a novel regulator of cardiomyocyte mitosis.

Tin dioxide (SnO2) has emerged as an ideal premier electron transport layer (ETL) material for perovskite solar cells (PSCs) due to its exceptional optical transparency and high electron mobility. Among all of the deposition techniques, magnetron sputtering represents as one of the most mature mass productive processes. This work reports a cost-effective method for fabricating a SnO2 ETL via direct current (DC) sputtering metallic Sn target followed by thermal oxidation in ambient air, which simultaneously enhanced deposition rates for industrial-scale production and reduced target poisoning risks associated with reactive sputtering. Furthermore, we implemented an industrially compatible ultraviolet-ozone (UV-O3) treatment strategy to further reduce surface oxygen vacancies (VO) defects at the SnO2 surface while optimizing the ETL/perovskite interface through improving energy level alignment, promoting preferential crystal orientation of perovskite films, and enhancing charge extraction efficiency. As a result, the UV-O3-treated SnO2-based device delivered a power conversion efficiency (PCE) of 21.17%, which is among the top-performing devices utilizing DC magnetron-sputtered SnO2 as the ETL. In addition, the unencapsulated devices retained approximately 90% of initial PCE after 1300 h of storage at ∼20% relative humidity, demonstrating their excellent environmental stability. This work provides a straightforward, economical, and effective approach to advance SnO2 ETL implementation for commercial PSC applications.

Acute lymphoblastic leukemia (ALL) is a critical type of cancer affecting white blood cell development. It is characterized by the disruption of normal stem cell maturation processes or the excessive proliferation of leukemic cells. As the most common childhood cancer, ALL is a significant health problem requiring continuous clinical monitoring. A major challenge in diagnosing the disease stems from the non-specific nature of the initial symptoms. Common symptoms, such as fever, fatigue, headache, weight loss, and musculoskeletal disorders, can mimic many diseases, making diagnostic accuracy challenging. This ambiguity leads to delayed diagnosis and negatively impacts treatment success. Although the incidence of leukemia has increased in recent years, advances in medical technology have shown promising results in reducing mortality rates. Health information systems play a significant role in this success by facilitating early disease diagnosis. In our research, two different image enhancement methods were developed to highlight the characteristics of blast cells, a critical indicator for the diagnosis of ALL. Three image groups were evaluated: unprocessed original images and two different processed image sets (versions 1 and 2). Classification performed using the MobileNetv2 transfer learning framework achieved accuracy rates of 85%, 90%, and 89% on the test dataset, respectively. To enhance diagnostic reliability beyond single-model performance, an ensemble architecture combining eight different transfer learning networks was created. This optimized ensemble model, using images enhanced with the high-performing version 1 filter, achieved approximately 90% classification accuracy. This result represents a significant advancement in AI-assisted hematological image interpretation.

During the germinal centre (GC) reaction, mature B cells undergo rapid and reversible phenotypic shifts that are essential for adaptive immunity. Here we report that GC B cells, unlike other mature B cells, transiently acquire a unique epigenetic plasticity, demonstrated by their enhanced capacity to reprogram to induced pluripotent stem cells. This plasticity depends on T follicular helper (TFH) cells and is not due to increased proliferation or MYC activation. Instead, it involves weakening of B-cell identity and derepression of stem and progenitor programs driven by NF-κB and other TFH-derived signals. Thus, physiological GC plasticity is tightly constrained by the affinity maturation process of positive selection. Loss of histone 1, a chromatin compaction regulator restricting the accessibility of embryonic stem cell programs, further enhances GC plasticity by bypassing this gatekeeping mechanism. Importantly, patients with B-cell lymphoma enriched for GC plasticity signatures had worse outcomes, suggesting that this mechanism may also contribute to lymphomagenesis.

BACKGROUND. When preparing flax straw using the dew retting method, uniformity of the raw material’s technological parameters along the length of the stems is not ensured, which reduces the yield and quality of the fiber. The excessive spread of values is due to differences in the mechanical properties of the stems along the length of freshly pulled plants. The middle and upper parts of the plant, when in contact with the working parts of flax harvesting machines, receive microdamage to their structure and dry out faster, activating tissue maceration in these areas of the stem. The lower part of the plants, having no such contacts, retains the integrity of their structure and remains viable, delaying the maturation process in this zone and increasing the heterogeneity of the parameters along the stem length. Maximum heterogeneity is observed during two-phase flax harvesting due to a long gap between the effects of the working parts on individual sections of the stems. The most effective solution to the problem is flattening the lower part of the plants when pulling flax. Many scientific studies are known that confirm the high efficiency of this technique. At the same time, flattening weakens the flexural rigidity of the stems, which can complicate layer formation before processing the flax straw and reduce the yield of long fiber. AIM: investigation of the effect of flattening working bodies of flax harvesters on the bending stiffness of plants. METHODS: For the practical implementation of the two-phase harvesting technology, a flax pulling machine TLP-1.5K (P) with a two-roll flattening apparatus and a pick-up stripper POL-1.5K with a comb stripping apparatus were used. A special device has been developed that allows one to estimate the flexural rigidity of the stem by measuring the force of its fracture and the corresponding deflection. RESULTS: It has been established that flattening of stems during two-phase harvesting does not have a cardinal effect on the distribution of bending rigidity along the technical length of the plant. In all cases, the weakest link in the design of the flattened stem remains its middle part, flattened by the belts of the top-lifting sections. Therefore, the maximum probability of bending of stems during layer formation will be observed in the middle part, and the processes of thinning of the layer of flattened and non-flattened stems will not have significant differences. Processing of experimental lots of flax straw obtained during two-phase flax harvesting with flattening of the butt parts of plants showed an increase in the yield of long fiber by an average of 2.37%. Thus, the categorical hypothesis about the harmful effect of plant flattening on the process of layer thinning and the yield of long fiber was not confirmed. CONCLUSIONS: To ensure high efficiency of the two-phase technology of harvesting flax, all machines intended for pulling plants should be equipped with crushing devices. In addition, it has been established that it is necessary to also process the tops of the stems with crushing rollers.

Vanishing White Matter Disease (VWMD) is a devastating, currently incurable neurodevelopmental disorder primarily affecting white matter. The prevailing view attributes VWMD to the activation of the canonical integrated stress response (c-ISR). However, recent studies have identified a novel, distinct pathway called the split ISR (s-ISR), though its activation has so far only been documented in mouse stem cells harboring a single eIF2B mutation, leaving uncertainty about whether it occurs in human cells, whether other mutations can trigger it, and what role it plays in the disease. Here, we used prime editing (PE) to engineer multiple eIF2B pathogenic mutations into HEK293T and induced pluripotent stem cells (iPSCs), generating human models. We demonstrated PE’s effectiveness and safety, marking the first successful application of PE for modeling VWMD. We found that all modeled mutations activate the s-ISR, indicating that this response is a common feature across VWMD mutations, and that it can be further amplified by stress-induced c-ISR and effectively suppressed by ISRIB. Mechanistically, we show that s-ISR hinders mutant iPSCs from achieving the high protein synthesis levels necessary for proper differentiation, expecially into astrocytes. This impairment disrupts their maturation process, directly linking s-ISR activation to the white matter abnormalities of VWMD.

This article examines the theoretical and applied aspects of conducting a retrospective audit of completed projects to assess the maturity level of the project management (PM) methodology and determine the directions for its further improvement. The emphasis is on the formation of a holistic methodological base for organizing a high-quality retrospective analysis of projects and the subsequent development of recommendations for increasing the maturity of the PM methodology used. Conducting a retrospective audit is analyzed using the example of processes of a modern IT company, however, the experience gained is universal and can be effectively used for projects in various industries. The object of the study are the methods and tools of retrospective audit used to assess the maturity of project management processes, as well as the factors determining the quality and completeness of the final audit report. The subject of the study is the specific stages of conducting a retrospective audit of a project, the criteria for assessing the maturity of the PM methodology used, as well as the mechanisms for formulating practical recommendations for increasing the maturity and optimizing project management. The main objective of the study is to develop a comprehensive approach to conducting a retrospective audit of completed projects, aimed at assessing the current level of project management maturity and developing specific measures for further improvement of the PM methodology in order to increase the overall efficiency and effectiveness of project management in the organization.

This review summarizes the core advantages and limitations of berberine, a naturally derived alkaloid, around three key aspects: synthesis, mechanism of action, and application. In synthesis, its strength lies in mature natural extraction processes that support stable and low-cost production, while its limitation stems from difficult chemical synthesis and reliance on plant sources that bring sustainability concerns. In terms of mechanism, berberine shows value in multi-target regulation that enables diverse therapeutic effects, yet its efficacy is restricted by poor oral bioavailability that requires higher doses. In application, it demonstrates potential in managing metabolic disorders, infections, and inflammatory conditions, but is accompanied by common side effects, drug interaction risks, and insufficient long-term research data.

An ultrastructural morphometric analysis of the postnatal development of the lung in the gray short-tailed opossum (Monodelphis domestica) has been conducted to evaluate the morphofunctional status of this poorly developed marsupial lung immediately following parturition. Allometric scaling of the volumes of the parenchymal components against body mass is carried out. In the parenchymal septa, volume proportions of pulmonary capillaries and solid septal tissue components (type I and type II epithelial cells, capillary endothelium, and interstitium) as well as alveolar and capillary surface densities are determined in transmission electron microscopic images using morphometry. Most parameters show a positive correlation with body mass over postnatal development. The lung of the neonate is at the late canalicular stage and consists of large terminal airspaces. The thick airspace septa are lined by cuboidal epithelium, interspersed with respiratory capillaries, and have a massive interstitial layer. A mature surfactant system is present at birth. The volume density of type II epithelial cells, which contain surfactant producing lamellar bodies, is highest in the late saccular stage, when septal growth is accelerated. The rapid development of the lung is indicated by an increase in the septal proportion of the parenchyma around postnatal day 4 and attainment of the saccular stage between day 4 and 7. The saccular stage, indicated by formation of a double capillary system, is characterized by repetitive steps of septation, increasing the number of saccular generations. By day 28 alveolarization starts and the process of microvascular maturation begins. The reduction of the interstitial tissue causes the two capillary beds to converge; finally, the two capillary layers begin to fuse, leading to a single capillary septum. In adults, capillaries and alveolar epithelia are the predominant septal components; the interstitium is greatly reduced. Despite the immaturity of the gray short-tailed opossum lung, it appears to be structurally and quantitatively sufficient for gas exchange. The structural transformation of the septa is accompanied with an increase in gas exchange surface area and thinning of the diffusion barrier, in order to meet the metabolic requirements of the developing young.

Endocrine infertility is one of the most common forms, the origin of which is directly related to a decrease in ovarian reserve, hormonal imbalance, metabolic changes, and immunological factors. Functional disorders in the endocrine system disrupt the maturation process of egg cells, cause ovulation to fail, and this causes serious problems in restoring fertility in women Objective: In the early diagnosis and prognosis of women with endocrine infertility, the level of expression of epigenetic markers Let-7b-5p, miR-223-3p, and miR-320a was studied, and their pathogenetic relationship with clinical, hormonal, and echographic indicators was proven. Results: This study is distinguished by the fact that it covers biomarker-based approaches in the diagnosis of women with infertility of endocrine genesis, and this algorithm is important for restoring fertility and improving the resultsThe introduction of differentiated, pathogenetically based, and individualized approaches to cases of infertility of endocrine origin not only increased clinical effectiveness, but also provided a wide range of social and economic benefits. According to the results of the study, in women with infertility against the background of hyperprolactinemia, hypothyroidism, and ovarian dysfunction, against the background of targeted therapy (cabergoline, tyramine, ovariamine), the frequency of ovulation and pregnancy significantly increased (56.7-66.7% and 33.3-40.0%, respectively). Conclusions:The introduction of differentiated, pathogenetically based, and individualized approaches to cases of infertility of endocrine origin not only increased clinical effectiveness, but also provided a wide range of social and economic benefits. this study is distinguished by the fact that the diagnosis of women with infertility of endocrine genesis includes individual, biomarker-based approaches, which is important for the restoration of fertility and improvement of results.