Structural Alterations Research Articles

An Overview of Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a myocardial disorder that is characterised by structural and functional abnormalities of the heart muscle in the absence of hypertension, valvular heart disease, congenital heart defects, or coronary artery disease (CAD). After witnessing a particular form of cardiomyopathy in diabetic individuals, Rubler et al. came up with the moniker diabetic cardiomyopathy in 1972. Four stages of DCM are documented, and the American College of Cardiology/American Heart Association Stage and New York Heart Association Class for HF have some overlap. Diabetes is linked to several distinct forms of heart failure. Around 40% of people with heart failure with preserved ejection fraction (HFpEF) have diabetes, which is thought to be closely associated with the pathophysiology of HFpEF. Diabetes and HF are uniquely associated in a bidirectional manner. When compared to the general population without diabetes, those with diabetes have a risk of heart failure that is up to four times higher. A biomarker is a trait that is reliably measured and assessed as a predictor of healthy biological activities, pathological processes, or pharmacologic responses to a clinical treatment. Several biomarker values have been discovered to be greater in patients with diabetes than in control subjects among those who have recently developed heart failure. Myocardial fibrosis and hypertrophy are the primary characteristics of DCM, and structural alterations in the diabetic myocardium are often examined by non-invasive, reliable, and reproducible procedures. An invasive method called endomyocardial biopsy (EMB) is most often used to diagnose many cardiac illnesses.

Distinct features of the regenerating heart uncovered through comparative single-cell profiling.

Adult humans respond to heart injury by forming a permanent scar, yet other vertebrates are capable of robust and complete cardiac regeneration. Despite progress towards characterizing the mechanisms of cardiac regeneration in fish and amphibians, the large evolutionary gulf between mammals and regenerating vertebrates complicates deciphering which cellular and molecular features truly enable regeneration. To better define these features, we compared cardiac injury responses in zebrafish and medaka, two fish species that share similar heart anatomy and common teleost ancestry but differ in regenerative capability. We used single-cell transcriptional profiling to create a time-resolved comparative cell atlas of injury responses in all major cardiac cell types across both species. With this approach, we identified several key features that distinguish cardiac injury response in the non-regenerating medaka heart. By comparing immune responses to injury, we found altered cell recruitment and a distinct pro-inflammatory gene program in medaka leukocytes, and an absence of the injury-induced interferon response seen in zebrafish. In addition, we found a lack of pro-regenerative signals, including nrg1 and retinoic acid, from medaka endothelial and epicardial cells. Finally, we identified alterations in the myocardial structure in medaka, where they lack primordial layer cardiomyocytes and fail to employ a cardioprotective gene program shared by regenerating vertebrates. Our findings reveal notable variation in injury response across nearly all major cardiac cell types in zebrafish and medaka, demonstrating how evolutionary divergence influences the hidden cellular features underpinning regenerative potential in these seemingly similar vertebrates.

Mapping of Prion Structures in the Yeast Rnq1.

The Rnq1 protein is one of the best-studied yeast prions. It has a large potentially prionogenic C-terminal region of about 250 residues. However, a previous study indicated that only 40 C-terminal residues form a prion structure. Here, we mapped the actual and potential prion structures formed by Rnq1 and its variants truncated from the C-terminus in two [RNQ+] strains using partial proteinase K digestion. The location of these structures differed in most cases from previous predictions by several computer algorithms. Some aggregation patterns observed microscopically for the Rnq1 hybrid proteins differed significantly from those previously observed for Sup35 prion aggregates. The transfer of a prion from the full-sized Rnq1 to its truncated versions caused substantial alteration of prion structures. In contrast to the Sup35 and Swi1, the terminal prionogenic region of 72 residues was not able to efficiently co-aggregate with the full-sized Rnq1 prion. GFP fusion to the Rnq1 C-terminus blocked formation of the prion structure at the Rnq1 C-terminus. Thus, the Rnq1-GFP fusion mostly used in previous studies cannot be considered a faithful tool for studying Rnq1 prion properties.

The Effect of Microwaves on Protein Structure: Molecular Dynamics Approach.

The impact of microwave (MW) irradiation on protein folding, potentially inciting misfolding, was investigated by employing molecular dynamics (MD) simulations. Twenty-nine proteins were subjected to MD simulations under equilibrium (300 K) and MW conditions, where the rotational temperature was elevated to 700 K. The utilized replacement model captures the microwave effects of δ- and γ-relaxation processes (frequency range of ∼300 MHz to ∼20 GHz). The results disclosed that MW heating incited a shift toward more compact protein conformations, as indicated by decreased root-mean-square deviations, root-mean-square fluctuations, head-to-tail distances, and radii of gyration. This compaction was attributed to the intensification of intramolecular electrostatic interactions and hydrogen bonds within the protein caused by MW-destabilized hydrogen bonds between the protein and solvent. The solvent-accessible surface area (SASA), particularly that of polar amino-acid residues, shrank under MW conditions, corresponding to a reduced polarity of the water solvent. However, MW irradiation produced no significant alterations in protein secondary structures; hence, MW heating was observed to primarily affect the protein tertiary structures.

Research progress of mechanism of acupuncture for migraine.

The literature regarding the action mechanism of acupuncture for migraine published from 2013 to 2023 was searched in China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Science and Technology Periodical Database, PubMed, Medline, and Cochrane Library. The pathogenesis of migraine and potential mechanisms of acupuncture treatment were summarized from the aspects of trigeminovascular system (TGVS), metabolic-related mechanisms, genetic factors, and alterations in brain structure and function. The results revealed that current research on the mechanisms of acupuncture for migraine predominantly centered around the TGVS, with studies confirming the specific regulatory effects of acupuncture on trigeminal system-related components, such as cortical spreading depression (CSD), astrocytes, and neurogenic kinin. While metabolic-related mechanisms and genetic factors are gaining attention, further in-depth exploration is needed to fully understand their roles in the mechanism of acupuncture for migraine. The study of brain structure and function in migraine has advanced, albeit with some controversies. Future research should prioritize larger sample sizes and standardized study designs to delve deeper into the mechanisms of acupuncture in treating migraine.

The neurobiological effects of childhood maltreatment on brain structure, function, and attachment.

Childhood maltreatment is a risk factor for psychopathologies, and influences brain development at specific periods, particularly during early childhood and adolescence. This narrative review addresses phenotypic alterations in sensory systems associated with specific types of childhood maltreatment exposure, periods of vulnerability to the neurobiological effects of maltreatment, and the relationships between childhood maltreatment and brain structure, function, connectivity, and network architecture; psychopathology; and resilience. It also addresses neurobiological alterations associated with maternal communication and attachment disturbances, and uses laboratory-based measures during infancy and case-control studies to elucidate neurobiological alterations in reactive attachment disorders in children with maltreatment histories. Moreover, we review studies on the acute effects of oxytocin on reactive attachment disorder and maltreatment and methylation of oxytocin regulatory genes. Epigenetic changes may play a critical role in initiating or producing the atypical structural and functional brain alterations associated with childhood maltreatment. However, these changes could be reversed through psychological and pharmacological interventions, and by anticipating or preventing the emergence of brain alterations and subsequent psychopathological risks.

Molecular interaction of human serum albumin with gemini surfactant, 1,6 bis (N,N-hexadecyl dimethyl ammonium) bromide: Influence of micelles and pH

The interaction between human seram albumin (HSA) and a cationic gemini (dimeric) surfactant, 1,6 bis (N,N-hexadecyl dimethyl ammonium) bromide (16–6-16) has been investigated. Various analytical techniques, including UV–vis spectroscopy, fluorescence spectroscopy, lifetime fluorescence measurement, circular dichroism (CD), and atomic force microscope (AFM), were employed to investigate these interaction studies. The experiments were conducted in aqueous environments at three distinct pH levels (viz., below (4.0), at (4.7), and above (7.0) the isoelectric point (IP)), as well as both above and below the critical micellar concentration (CMC) of the surfactant (16–6-16). In these experimental conditions, HSA experiences conformational changes, leading to unfolding and denaturation as a result of its interaction with the gemini surfactant molecules (16–6-16). The extent of these conformational changes is found to be associated with both the degree of surfactant partial intercalation and the characteristics (size and charge) of the surfactant aggregates formed. The AFM microscopy studies provide insights into the topographical structural alterations occurring above, at, and below the CMC. Molecular docking analysis further validates the interaction between the protein (HSA) and the gemini surfactant (16–6-16) at a molecular level.

Investigating Dynamic Changes in 3D‐Printed Covalent Adaptable Polymer Networks

Abstract3D printing technologies have matured to produce complex structures, still they are often limited to static materials. Introducing alkoxyamine bonds into 3D printed structures offers unprecedented possibilities for post‐synthetic modification through nitroxide exchange reaction and nitroxide‐mediated polymerization. This study provides a comprehensive molecular and macroscopic characterization of 3D‐printed alkoxyamine‐containing dynamic covalent adaptable networks. The study provides new insights into their dynamic structural and mechanical alterations, making them promising candidates for advanced applications ranging from biomedical engineering to flexible electronics.

Phylogenetic position and genetic features of HIV-1 in CNS

Background. Due to the wide coverage with antiretroviral therapy, the life expectancy of HIV infected people has significantly increased. Against the background of a decrease in mortality from HIV infection, HIV-associated neurocognitive disorders, which develop even during effective treatment, are of high importance. The overall prevalence of this pathology among HIV-infected people reaches 42.6%.
 The objective of the study was to research the genetic features and phylogenetic position of HIV-1 persisting in the central nervous system.
 Materials and methods. The clinical study group consisted of 38 patients with severe neurocognitive disorders against the background of HIV infection in stage 4B. The viral load of HIV-1 in blood plasma and cerebrospinal fluid (CSF) was measured using the "AmpliSens HIV Monitor-FRT" reagents kit. Sanger sequencing was performed using the AmpliSens HIV-Resist-Seq assay kit on an Applied Biosystems 3500 analyzer. Phylogenetic analysis of the pol gene fragments of HIV-1 strains (the site encoding the viral protease and part of the reverse transcriptase) was carried out using maximum likelihood method with the GTR+G nucleotide substitution model. Comparisons of the tertiary structure of viral proteins were performed according to three-dimensional models of the protease and p51 and p66 reverse transcriptase subunits obtained by homologous reconstruction using the SWISS-MODEL tools.
 Results. The viral load in the sample of patients with severe CNS lesions in blood plasma was 6.27 times higher than in CSF and amounted to 4.67 and 3.87 lg copies/ml respectively by median (p = 0,004).
 Phylogenetic analysis with the use of all available HIV-1 genomes from GenBank, which differed from the studied ones by less than 5% showed close genetic relations of viruses circulating in Chelyabinsk region, apart from strains circulating in Russian Federation, with viruses circulating in neighboring countries, in most abundance — from Ukraine and Kyrgyzstan, slightly less — from Belarus, Tajikistan, Kazakhstan and Armenia and also with strains from certain foreign countries: Poland and Germany. Phylogenetic analysis of 38 HIV-1 genomes revealed significant genetic distances between HIV isolates from blood plasma and CSF in 5 patients, 4 of whom were PWID, which may indicate an event of superinfection.
 The amount of independent amino acid substitutions in protease in isolates from blood plasma ranged from 1 to 3, in isolates from CSF — from 1 to 2. An amount of such substitutions in a fragment of reverse transcriptase in isolates from blood plasma ranged from 1 to 6, while in isolates from CSF, it ranged from 1 to 7. HIV isolates from blood plasma and CSF from 5 patients had differences in the tertiary structure of HIV-1 reverse transcriptase p51 subunit in amino acid positions 16–20 and 210–235. Isolates from 3 other patients differed in the tertiary structure only in amino acid positons 210–235. Isolates from 3 patients differed in the structure of HIV-1 RT p66 subunit in a non-nucleoside reverse transcriptase inhibitor binding pocket (NNRTI) region. Fixed differences in the tertiary structure of p51 subunit required at minimum only 1 amino acid substitution to emerge. Alterations in the tertiary structure of p66 subunit required at least 3 amino acid substitutions.
 Conclusion. Microevolution of HIV-1 proceeds in parallel within the same patient, in different compartments, which is reflected in the accumulation of amino acid substitutions different from another compartment in the conserved pol gene. There is a weak correlation between the viral load level in plasma and in CSF. The genetic heterogeneity of HIV strains from patients of the Chelyabinsk region indicates a high frequency of reintroduction of HIV infection in the region from other countries. Differences in the tertiary structure of HIV-1 reverse transcriptase between blood plasma and CSF isolates are regularly fixed in certain domens, which also confirms the presence of parallel HIV microevolution during virus persistence in tissues separated by the blood-brain barrier which allows a better understanding of the fixation trends of individual amino acid substitutions during HIV-induced damage to central nervous system.

Unveiling Alterations of Epigenetic Modifications and Chromatin Architecture Leading to Lipid Metabolic Reprogramming during the Evolutionary Trastuzumab Adaptation of HER2-Positive Breast Cancer.

Secondary trastuzumab resistance represents an evolutionary adaptation of HER2-positive breast cancer during anti-HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their associated genetic and epigenetic mechanisms. Here, transcriptome data is not only characterized but also examined epigenomic and 3D genome architecture information in both trastuzumab-sensitive and secondary-resistant breast cancer cells. The findings reveal that the global metabolic reprogramming associated with trastuzumab resistance may stem from genome-wide alterations in both histone modifications and chromatin structure. Specifically, the transcriptional activities of key genes involved in lipid metabolism appear to be regulated by variant promoter H3K27me3 and H3K4me3 modifications, as well as promoter-enhancer interactions. These discoveries offer valuable insights into how cancer cells adapt to anti-tumor drugs and have the potential to impact future diagnostic and treatment strategies.

Raman–Infrared Spectral Correlation of an Artificially Space-Weathered Carbonaceous Chondrite Meteorite

Raman and infrared measurements of the same locations were conducted on a northwest African (NWA) 10580 CO3 meteorite sample, before and after three proton irradiations (1 keV ion energy using 1011, 1014, and 1017 ion/cm2 fluent values), to simulate space weathering effects. In the case of Raman spectroscopy, both FWHM and peak positions of the major olivine and pyroxene bands changed after the irradiation, and the minor bands disappeared. In the FTIR spectra, the minor bands of olivine and pyroxene also disappeared; meanwhile, major IR bands of pyroxene remained visible, demonstrating both positive and negative peak shifts, and the olivines were characterised only by negative peak shifts. The olivines were characterised by negative FWHM changes for major bands, but positive FWHM changes for minor bands. The pyroxenes were characterised by elevated FWHM changes for minor bands after the irradiation. The disappearance of minor bands both of IR and Raman spectra indicates the amorphization of minerals. The negative peak shift in IR spectra indicates Mg loss for olivine and pyroxene, in agreement with the literature. The Raman spectra are characterised by positive peak shift and positive FWHM changes; the IR spectra are characterised by a negative peak shift. The Mg loss, which was detected by negative peak shifts of FTIR bands, may be caused by distortion of the crystal structure, which could be detected by a positive peak shift in Raman spectra. This joint observation and interpretation has not been formulated in the literature, but indicates further possibilities in the confirmation of mineral changes by different instruments. Shock alteration-based observations by other researchers could be used as a reference for irradiation experiments as irradiation makes a similar structural alteration, like a low-grade shock metamorphism.

Sorption Efficacy of Weathered Basalt Rock for Metal Ions of Nuclear Importance

Background:: A safe and long-term isolation of radionuclides is crucial for efficient waste management in the nuclear fuel cycle. Clay minerals of geological origin are considered candidate barrier materials for the sequestration of nuclear waste for geological disposal applications. Objective:: The present study encompasses a systematic characterization of weathered basalt rock and the influence of its constituent clay minerals (formed mainly due to the weathering process) in the uptake of metal ions of nuclear importance, such as cesium (Cs+) and strontium (Sr2+). Method:: The structural profile of the weathered basalt has been investigated using different analytical techniques, including polarizing microscope, XRD, FTIR and EDXRF. The sorption behaviour of the rock sample for Cs+ and Sr2+ has been investigated in a comprehensive batch mode by varying the experimental conditions. The analytical findings for structure and batch sorption performance of the material have been further correlated to understand the influence of different parameters on the uptake of metal ions and the underlying mechanism. Results:: Structural analyses confirmed the presence of clay minerals viz., kaolinite, illite and montmorillonite in the sample. A comprehensive sorption performance assessment carried out in batch mode at different experimental conditions revealed that the uptake of both the metal ions was rapid and dependent on initial metal ion concentration and solution pH. The uptake of Cs+ ions was found to be higher as compared to the Sr2+ ions. EDXRF analysis confirmed the loading of Cs+ and Sr2+ on the weathered basalt. Experimental batch sorption data presented a better agreement with the theoretical Freundlich isotherm pertaining to the heterogeneous nature of the sorbent. Conclusion:: The studies highlight that the clay minerals formed by structural alteration of basalt rock upon intense weathering could be very useful in fixing the nuclear fission waste components such as Cs+ and Sr2+.

Specific protein-RNA interactions are mostly preserved in biomolecular condensates.

Many biomolecular condensates are enriched in and depend on RNAs and RNA binding proteins (RBPs). So far, only a few studies have addressed the characterization of the intermolecular interactions responsible for liquid-liquid phase separation (LLPS) and the impact of condensation on RBPs and RNAs. Here, we present an approach to study protein-RNA interactions inside biomolecular condensates by applying cross-linking of isotope labeled RNA and tandem mass spectrometry to phase-separating systems (LLPS-CLIR-MS). LLPS-CLIR-MS enables the characterization of intermolecular interactions present within biomolecular condensates at residue-specific resolution and allows a comparison with the same complexes in the dispersed phase. We observe that sequence-specific RBP-RNA interactions present in the dispersed phase are generally maintained inside condensates. In addition, LLPS-CLIR-MS identifies structural alterations at the protein-RNA interfaces, including additional unspecific contacts in the condensed phase. Our approach offers a procedure to derive structural information of protein-RNA complexes within biomolecular condensates that could be critical for integrative structural modeling of ribonucleoproteins (RNPs) in this form.

Assessing the Effectiveness of Education Policy in Addressing Skill Gaps and Enhancing Employability

The National Education Policy (NEP) was implemented in India to revamp the education system in order to better cater to the demands of the 21st century, with a focus on holistic development, flexibility, and innovation. Potential outcomes of the NEP may involve alterations in curriculum structure, a heightened emphasis on vocational training and skill enhancement, enhancements in teacher education and professional growth, and initiatives to foster equality and inclusivity in education. Nevertheless, a comprehensive evaluation and analysis would be necessary to fully comprehend the impact of the NEP and how effectively it is being executed, along with its real-world consequences. It is imperative to refer to recent reports, studies, or government updates for a more precise evaluation of the current impact of the NEP. This research seeks to evaluate the efficacy of educational policy interventions in addressing skill gaps and improving employability in the job market. Given the rapid advancements in technology and changes in the global economic scenario, the demand for specific skills is constantly evolving, presenting challenges for educational institutions to keep up. This study utilizes a mixed-methods approach, combining quantitative analysis of education policy data with qualitative assessments of stakeholder viewpoints. Qualitative evaluations will consist of conducting interviews and focus groups with important stakeholders such as policymakers, educators, employers, and recent graduates. These qualitative perspectives will offer detailed viewpoints on the advantages, disadvantages, and obstacles in implementing current education policies to address skill gaps and enhance workforce preparedness. The results of this research are intended to guide data-driven policy suggestions for enhancing education systems to effectively address the needs of the changing labor market, ultimately leading to continuous economic development, decreased unemployment rates, and enhanced prospects for individuals to secure meaningful and satisfying job opportunities. Keywords: National Education Policy, Skill Development, Employability, Bridging Gap

A Novel Carrier Based on DNA and Exosome to Sustained Release of 5‐Fluorouracil Anticancer Drug

AbstractThe development of effective drug delivery systems is crucial for improving cancer treatment outcomes. A promising carrier using a combination of DNA and exosomes (EXO) was synthesized to sustain the release of the powerful anticancer drug 5‐fluorouracil (5‐FU). The carrier was prepared by encapsulating 5‐FU‐loaded exosomes (5‐FU.EXO) in the heated DNA carriers (5‐FU.EXO@DNA). Alteration of the DNA structure was studied using molecular dynamics. The physicochemical properties of the carriers were characterized using fourier‐transform infrared spectroscopy (FTIR), field‐emission scanning electron microscopy (FESEM), and dynamic light scattering (DLS). The 5‐FU.EXO@DNA carrier exhibited good stability and biocompatibility, with a uniform size distribution (709±269 nm) and a zeta potential of +312 mV. The interaction between 5‐FU and DNA was confirmed using molecular docking. In vitro release studies showed that both 5‐FU@DNA and 5‐FU.EXO@DNA carriers achieved sustained release of 5‐FU for 576 h, with cumulative releases of approximately 83 % and 89 %, respectively. The 5‐FU release profile showed 40 % release over 86 h. The release rate and other kinetic parameters were also determined. Furthermore, the release kinetics followed by the Korsmeyer‐Peppas model and the diffusion mechanism plays a significant role in controlling the release process.

Identification of a Novel Peptide with Alcohol Dehydrogenase Activating Ability from Ethanol-Induced Lactococcus lactis: A Combined In Silico Prediction and In Vivo Validation.

Alcohol dehydrogenase (ADH) is a crucial rate-limiting enzyme in alcohol metabolism. Our previous research found that ethanol-induced intracellular extracts of Lactococcus lactis (L. lactis) could enhance alcohol metabolism in mice, but the responsible compounds remain unidentified. The study aimed to screen potential ADH-activating peptides from ethanol-induced L. lactis using virtual screening and molecular docking calculation. Among them, the pentapeptide FAPEG might bind to ADH through hydrophobic interaction and hydrogen bonds, then enhancing ADH activity. Spectroscopy analysis further investigated the peptide-enzyme interaction between FAPEG and ADH, including changes in the amino acid residue microenvironment and secondary structural alterations. Furthermore, FAPEG could protect against alcoholic liver injury (ALI) in mice by reducing blood alcohol concentration, enhancing the activity of antioxidant and alcohol metabolism enzymes, and attenuating alcohol-induced hepatotoxicity, which was related to the activation of the Nrf2/keap1/HO-1 signaling pathway. The study provided preliminary evidence that the generation of ADH-activating peptides in ethanol-induced L. lactis has the potential in preventing ALI in mice using in silico prediction and in vivo validation approaches.

Unpredictable chronic mild stress shows neuronal remodeling in multipolar projection neurons of hippocampal complex in postnatal chicks.

The hippocampal complex of birds is a narrow-curved strip of tissue that plays a crucial role in learning, memory, spatial navigation, and emotional and sexual behavior. This study was conducted to evaluate the effect of unpredictable chronic mild stress in multipolar neurons of 3-, 5-, 7-, and 9-week-old chick's hippocampal complex. This study revealed that chronic stress results in neuronal remodeling by causing alterations in dendritic field, axonal length, secondary branching, corrected spine number, and dendritic branching at 25, 50, 75, and 100µm. Due to stress, the overall dendritic length was significantly retracted in 3-week-old chick, whereas no significant difference was observed in 5- and 7-week-old chick, but again it was significantly retracted in 9-week-old chick along with the axonal length. So, this study indicates that during initial days of stress exposure, the dendritic field shows retraction, but when the stress continues up to a certain level, the neurons undergo structural modifications so that chicks adapt and survive in stressful conditions. The repeated exposure to chronic stress for longer duration leads to the neuronal structural disruption by retraction in the dendritic length as well as axonal length. Another characteristic which leads to structural alterations is the dendritic spines which significantly decreased in all age groups of stressed chicks and eventually leads to less synaptic connections, disturbance in physiology, and neurology, which affects the learning, memory, and coping ability of an individual.

Effects of Perforated Plates on Shock Structure Alteration for NACA0012 Airfoils

This research investigated a passive flow control technique to mitigate the adverse effects of shock wave–boundary layer interaction on a NACA 0012 airfoil. A perforated plate with a strategically positioned cavity beneath the shock wave anchoring spot was employed. Airfoils with perforated plates of varying orifice sizes (ranging from 0.5 to 1.2 mm) were constructed using various manufacturing techniques. Experimental analysis utilized an “Eiffel”-type open wind tunnel and a Z-type Schlieren system for flow visualization, along with static pressure measurements obtained from the bottom wall. Empirical observations were compared with steady 3D density-based numerical simulations conducted in Ansys FLUENT for comprehensive analysis and validation. The implementation of the perforated plate induced a significant alteration in shock structure, transforming it from a strong normal shock wave into a large lambda-type shock. The passive control case exhibited a 0.2% improvement in total pressure loss and attributed to the perforated plate’s capability to diminish the intensity of the shock wave anchored above. Significant fluctuations in shear stress were introduced by the perforated plate, with lower stress observed in the plate area due to flow detachment from cavity blowing. Balancing shock and viscous losses proved crucial for achieving a favorable outcome with this passive flow control method.

Lysosomes in Cancer-At the Crossroad of Good and Evil.

Although it has been known for decades that lysosomes are central for degradation and recycling in the cell, their pivotal role as nutrient sensing signaling hubs has recently become of central interest. Since lysosomes are highly dynamic and in constant change regarding content and intracellular position, fusion/fission events allow communication between organelles in the cell, as well as cell-to-cell communication via exocytosis of lysosomal content and release of extracellular vesicles. Lysosomes also mediate different forms of regulated cell death by permeabilization of the lysosomal membrane and release of their content to the cytosol. In cancer cells, lysosomal biogenesis and autophagy are increased to support the increased metabolism and allow growth even under nutrient- and oxygen-poor conditions. Tumor cells also induce exocytosis of lysosomal content to the extracellular space to promote invasion and metastasis. However, due to the enhanced lysosomal function, cancer cells are often more susceptible to lysosomal membrane permeabilization, providing an alternative strategy to induce cell death. This review summarizes the current knowledge of cancer-associated alterations in lysosomal structure and function and illustrates how lysosomal exocytosis and release of extracellular vesicles affect disease progression. We focus on functional differences depending on lysosomal localization and the regulation of intracellular transport, and lastly provide insight how new therapeutic strategies can exploit the power of the lysosome and improve cancer treatment.

Characteristics of Weathering Reservoirs and Differences in Fracture Formation in the Weathering Crust of the Pre-Cenozoic Basement of Lishui Sag, East China Sea Basin, China

Characteristics of Weathering Reservoirs and Differences in Fracture Formation in the Weathering Crust of the Pre-Cenozoic Basement of Lishui Sag, East China Sea Basin, China