Structural Alterations Research Articles

Cereal type and conditioning temperature altered protein and carbohydrate molecular structure, nutrient retention and performance in broilers fed pellet diets during starter and grower period

ABSTRACT 1. Effects of cereal type and conditioning temperature (CT) on protein and carbohydrate (CHO) molecular structures, nutrient retention, carcass and blood characteristics, caecal microbial population and growth criteria of broilers fed pellet diet were evaluated for a total period of 35 d. 2. In total, 336-day-old Cobb 500 broiler chicks were randomly allotted into a 2 × 2 factorial arrangement with two different cereal types (maize or wheat) processed in two different temperatures (CT; 68°C or 90°C) with seven pen replicates containing 12 birds each. 3. Chicks fed the maize-based diets significantly gained higher body weight (BW) and lower feed conversion ratio (FCR) in comparison to the chicks fed wheat-based diets during the whole grow-out period (p < 0.01). Overall, the highest BW and feed intake (FI) were seen in birds fed wheat-based diets conditioned at 68°C, but the lowest FCR was observed in maize-based diet conditioned at 90°C at 7, 14 and 21 d of age (p < 0.01). However, BW was higher and FCR lower in chicks fed maize-based diets conditioned at 90°C in the grower period (28 and 35 d; p < 0.01). 4. The α-helix height was higher in wheat-based starter diets in comparison to the maize-based diet (p < 0.01). Ratio of amide I to II area and total CHO peak height were increased when diets were processed at 90°C in both maize and wheat-based starter diet (p < 0.05). Increasing the CT from 68°C to 90°C reduced CHO peak 1 and 2 height by 11.6% and 3.95%, respectively, in maize-based starter diets, while increasing the CT from 68°C to 90°C reduced CHO peak 1 and 2 height by 54.3% and 57.2%, respectively, in wheat-based starter diets. In the grower diets, increasing the CT from 68°C to 90°C increased CHO peak 1 by 23% in maize-based diets, but reduced CHO peak 1 by 24.5% in wheat-based diets. 5. Calcium and phosphorous retention were highest in chicks fed wheat-based diets conditioned at 90°C and lowest in chicks fed maize-based diets conditioned at 90°C (p < 0.01). Salmonella, E. coli and coliforms in the caeca reduced significantly (p < 0.05) in chicks fed wheat-based diets conditioned at 90°C on d 11 and increased with the same diet at 35 d of age compared to the chicks fed maize-based diets conditioned at both 68°C and 90°C or wheat-based diets conditioned at 68°C. 6. Conditioning the wheat-based diets at 68°C improved production responses without causing any adverse effects on protein and CHO molecular structures, however increasing the conditioning temperature to 90°C impaired performance due to alteration of protein and CHO molecular structures. In contrast, conditioning of the maize-based diets at 90°C had the opposite effect, and improved production performance compared to diets conditioned at 68°C.

CUPPING THERAPY

Traditional cupping therapy (CT) has been around for a long time and is still used today to treat many different kinds of medical issues. Still, researchers have yet to pin down exactly how (CT) works. Looking at CT through the lens of contemporary medicine, this review set out to determine how it might work and provide some explanations for its effects. A search was conducted using keywords in the English publications in PubMed, Cochrane Library, and Google Scholar. From the 223 articles that were found, 149 records were reviewed and 74 articles were deemed irrelevant and removed. Of the 75 full-text publications that were considered for this review, 64 were ultimately included. There are six competing explanations for the benefits of cupping therapy. Nitric Oxide theory may provide an explanation for the calming effects on muscles, alterations in local tissue structures, and improvements in blood circulation. The Activation of immune system theory may explain the hormonal changes and immunological effects. According to the "Blood Detoxification Theory" heavy metals and waste are eliminated while toxins are released. These theories can complement one another or even be used interchangeably to treat different diseases and ailments. It would appear that the many impacts of cupping cannot be adequately explained by a single theory. The aforementioned theories require further investigation to either confirm or disprove them, and future research should also aim to develop novel conceptualizations of CT.

Alteration of chromosome structure impacts gene expressions implicated in pancreatic ductal adenocarcinoma cells

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a five-year survival rate of approximately 10%. Genetic mutations are pivotal drivers in PDAC pathogenesis, but recent investigations also revealed the involvement of non-genetic alterations in the disease development. In this study, we undertook a multi-omics approach, encompassing ATAC-seq, RNA-seq, ChIP-seq, and Hi-C methodologies, to dissect gene expression alterations arising from changes in chromosome accessibility and chromatin three-dimensional interactions in PDAC.ResultsOur findings indicate that chromosomal structural alterations can lead to abnormal expressions on key genes during PDAC development. Notably, overexpression of oncogenes FGFR2, FOXA2, CYP2R1, and CPOX can be attributed to the augmentation of promoter accessibility, coupled with long-range interactions with distal elements. Additionally, our findings indicate that chromosomal structural alterations caused by genomic instability can lead to abnormal expressions in PDACs. As an example, by analyzing chromosomal changes, we identified a putative oncogenic gene, LPAR1, which shows upregulated expression in both PDAC cell lines and clinical samples. The overexpression is correlated with alterations in LPAR1-associated 3D genome structure and chromatin state. We further demonstrated that high LPAR1 activity is required for enhanced PDAC cell migration in vitro.ConclusionsCollectively, our findings reveal that the chromosomal conformational alterations, in addition to the well-known genetic mutations, are critical for PDAC tumorigenesis.

Unraveling Meso-Substituent Steric Effects on the Mechanism of Hydrogen Evolution Reaction in NiII Porphyrin Hydrides Using DFT Method.

Substituents at the meso-site of metalloporphyrins profoundly influence the hydrogen evolution reaction (HER) mechanism. This study employs density functional theory (DFT) to computationally analyze NiII-porphyrin and its hydrides derived from tetrakis(pentafluorophenyl)porphyrin molecules, presenting stereoisomers in ortho- or para-positions. The results reveal that the spatial resistance effect of meso-substituted groups at the ortho- and para-positions induces significant changes in Ni-N bond lengths, angles, and reaction dynamics. For ortho-position substituents forming complex I, a favorable 88.88 ų spherical space was created, facilitating proton coordination and the formation of H2 molecules; conversely, para-position substituents forming complex II impeded H2 formation until bimolecular complexes arose. Molecular dynamics (MD) analysis and comparison were conducted on the intermediation products of I-H2 and (II-H)2, focusing on the configuration and energy changes. In the I-H2 products, H2 molecules underwent separation after 150 fs and overcame the 2.2 eV energy barrier. Subsequently, significant alterations in the spatial structure were observed as complex I deformed. In the case of (II-H)2, it was influenced by the distinctive "sandwich" configuration; the spatial structure necessitated overcoming a 6.7 eV energy barrier for H2 detachment and a process observed after 2400 fs.

Motivation levels and white matter microstructure in children living with HIV

Central nervous system involvement in HIV infection leads to neurobehavioural sequelae. Although apathy is a well-recognised symptom in adults living with HIV linked to alterations in brain structure, there is scarce research examining motivation in children living with HIV (CLWH). We used the Children’s Motivation Scale (CMS; normative mean = 50, SD = 10) to assess motivation levels in 76 CLWH aged 6–16 years (63 on antiretroviral therapy [ART]; 13 ART-naïve slow progressors) in South Africa. Overall, CLWH scored low on the CMS (mean = 35.70 [SD = 5.87]). Motivation levels were significantly reduced in children taking ART compared to ART-naïve slow progressors (p = 0.02), but were not correlated with markers of HIV disease (CD4 + cell count or viral load), or neurocognitive function (p > 0.05). CMS scores were correlated with diffusion tensor imaging metrics of white matter microstructure in specific frontostriatal brain regions (p < 0.05). On multiple regression, associations with the anterior limb of the internal capsule, a subcortical white matter region, remained significant after adjusting for potential confounders. These findings suggest that reduced motivation may be an important neurobehavioural symptom in CLWH and may reflect changes in white matter microstructure of frontostriatal brain regions.

Post-Stroke Depression in Older Adults: An Overview.

Detailed data on post-stroke depression (PSD) in older adults are limited in spite of the high vulnerability of this population to stroke. In fact, PSD prevalence in older adults ranges from 16.0 to 43.9%; however, timing and instruments of evaluation often differ significantly across all available studies. The etiology, genetic and inflammatory factors, as well as structural brain alterations, are claimed as part of a multifaceted mechanism of action in PSD onset. Thus, the aim of this narrative review was to further elaborate on the prevalence, etiology, diagnosis, consequences and treatment of PSD in older adults. The consequences of PSD in older adults may be devastating, including a poor functional outcome after rehabilitation and lower medication adherence. In addition, lower quality of life and reduced social participation, higher risk of new stroke, rehospitalization, and mortality have been reported. In this scenario, treating PSD represents a crucial step to prevent these complications. Both pharmacological and non-pharmacological therapies are currently available. The pharmacological treatment utilizes antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TAs) and new multimodal antidepressants (NMAs). Non-pharmacological therapies include psychological interventions and non-invasive brain stimulation techniques, while excluding drug administration. In the general population experiencing PSD, SSRIs (sertraline in particular) are the most prescribed, whereas the combination of antidepressants and psychotherapy is underused. Furthermore, about one-third of patients do not receive treatment for PSD. In regard to older adults with PSD, the possibility of more adverse effects or contraindications to antidepressant prescription due to comorbidities may limit the therapeutic window. Although drugs such as citalopram, escitalopram, sertraline, venlafaxine, and vortioxetine are usually well tolerated by older patients with PSD, the few randomized controlled trials (RCTs) specifically considering older adults with PSD have been conducted with fluoxetine, fluvoxamine, reboxetine, citalopram and nortriptyline, often with very small patient samples. Furthermore, data regarding the results of non-pharmacological therapies are scarce. High-quality RCTs recruiting large samples of older adults are needed in order to better manage PSD in this population. In addition, adequate screening and diagnosis instruments, with reliable timing of evaluation, should be applied.

Elucidating the mechanisms of formononetin in modulating atherosclerotic plaque formation in ApoE-/- mice

BackgroundAtherosclerosis(AS) poses a pressing challenge in contemporary medicine. Formononetin (FMN) plays a crucial role in its prevention and treatment. However, the detailed impact of FMN on the stability of atherosclerotic plaques and its underlying mechanisms remain to be elucidated.MethodsAn intervention consisting of FMN was given along with a high-fat food regimen in the ApoE-/- mouse model. The investigation included the evaluation of the degree of atherosclerotic lesion, the main components of the plaque, lipid profiles, particular markers indicating M1/M2 macrophage phenotypes, the quantities of factors related to inflammation, the infiltration of macrophages, and the identification of markers linked to the α7nAChR/JAK2/STAT3 axis effect molecules.ResultsThe evaluation of aortic morphology in ApoE-/-mice revealed that FMN significantly improved the plaque area, fibrous cap protrusion, lipid deposition, and structural alterations on the aortic surface, among other markers of atherosclerosis,and there is concentration dependence. Furthermore, the lipid content of mouse serum was assessed, and the results showed that the low-, medium-, and high-dosage FMN groups had significantly lower levels of LDL-C, ox-LDL, TC, and TG. The results of immunohistochemical staining indicated that the low-, medium-, and high-dose FMN therapy groups had enhanced CD206 expression and decreased expression of CD68 and iNOS. According to RT-qPCR data, FMN intervention has the potential to suppress the expression of iNOS, COX-2, miR-155-5p, IL-6, and IL-1β mRNA, while promoting the expression of IL-10, SHIP1, and Arg-1 mRNA levels. However, the degree of inhibition varied among dosage groups. Western blot investigation of JAK/STAT signaling pathway proteins and cholinergic α7nAChR protein showed that p-JAK2 and p-STAT3 protein expression was suppressed at all dosages, whereas α7nAChR protein expression was enhanced.ConclusionsAccording to the aforementioned findings, FMN can reduce inflammation and atherosclerosis by influencing macrophage polarization, blocking the JAK/STAT signaling pathway, and increasing α7nAChR expression.

Unveiling the evolution of phytoplankton communities: Decades-long insights into the southern Yellow Sea, China (1959–2023)

We obtained historical and observational data on phytoplankton communities from 1959 to 2023 to explore the responses of the phytoplankton community structure to long-term environmental changes in the southern Yellow Sea (SYS), China. The results revealed a decrease in the proportions of diatom cell abundance within the phytoplankton community by 8 %, accompanied by a corresponding increase in that of dinoflagellates. Dominant phytoplankton species were mainly chain-forming diatoms before 2000, and large dinoflagellate species from the genera Tripos and Noctiluca increased their dominance after 2000. Warm-water phytoplankton species have increased in dominance over the study period. Correlation analysis revealed that the ocean warming and alterations in nutrient structure (N/P and Si/N ratios) were mostly responsible for the long-term evolution trend, and these changes may result in an increase in dinoflagellate harmful algal blooms, reduced efficiency of the biological carbon pump, and heightened hypoxia in the future, which should draw our attention.

Different biological responses of Skeletonema costatum and Prorocentrum donghaiense to polymetallic nodules from seawaters

The negative impacts of polymetallic nodules mining on deep-sea benthic organisms have been widely established, but there is still a lack of understanding of the environmental impact on the surface ocean scenario. Phytoplankton growth experiment was conducted to determine the biological effect of polymetallic nodules on Prorocentrum donghaiense and Skeletonema costatum. The results showed that regardless of concentration and particle size, polymetallic nodules show a promoting effect on P. donghaiense (p < 0.05), the cell density in the experimental group increased by 35.2%-46.5% compared to the control at the end of the experiment. While fine particles significantly inhibited the growth of S. costatum (p < 0.05), the maximum inhibition rate on cell density reached 63.1%. Polymetallic nodules significantly enhance the Fv/Fm and the maximum electron transport rate of photosystem II in P. donghaiense, thereby increasing its growth rate. However, polymetallic nodules particles stimulated the antioxidant activity and extracellular polymeric substances secretion of S. costatum, resulting in phytoplankton flocculation and sedimentation, which inhibits its growth. Thus, these discriminatory impacts may cause alterations in biomass and community structure, ultimately affecting the ecological function.

Thermal annealing induced graphite/diamond structure processed by high-voltage hydroxide ion treatments

Ohmic contacts with low specific contact resistance are necessary for fabrication of diamond electronic devices. This work reports that graphite/diamond ohmic contacts can be obtained by thermal annealing of diamond, patterned by hydroxide ion treatment. Surface graphitization of diamond is achieved through rapid thermal annealing at 1050 °C in vacuum. The thickness of graphite layer is found to be dependent on the duration of annealing with an approximate rate of 3.3 ∼ 3.6 nm/minute. The alteration in surface structure is analyzed using Raman spectra, showing a continuously enhanced G peak with increasing annealing time. Early stages of graphitization are discovered by X-ray photoelectron spectroscopy, after annealing diamond samples for merely 0.5 ∼ 2 min. Additionally, a distinct atomic interface between graphite and diamond is observed via cross-sectional transmission electron microscopy. Further, the surface graphite is selectively etched by hydroxide ion treatments, protected by gold patterns. In the end, the specific contact resistance of the graphite/diamond contact is determined to be 2.53 × 10-4 Ω cm2 employing the transmission line model.

Histological analysis of neuronal changes in the olfactory cortex during pregnancy

Fluctuations in olfactory sensitivity are widely known to occur during pregnancy and may be responsible for hyperemesis gravidarum. These changes are thought to be caused by structural and functional alterations in neurons in response to marked changes of the hormonal milieu. In this study, we examined changes in neurons in the olfactory cortex during pregnancy and after delivery in rats. Dendritic spine densities were measured in the piriform cortex (PIR) and posterolateral cortical amygdala (COApl), which are involved in olfaction. The results showed increased numbers of dendritic spines in the PIR in mid-pregnancy and in the COApl during early and late pregnancy, but not in the motor area of the cerebral cortex, indicating a correlation with changes in olfactory sensitivity during pregnancy. Immunohistochemical analysis of expression of ovarian hormone receptors in these brain regions revealed a decrease in the number of estrogen receptor α-positive cells during pregnancy in the PIR and during pregnancy and the postpartum period in the COApl. Regarding pregnancy-related peptide hormones, oxytocin receptors were expressed in the PIR and COApl, while prolactin receptors were not found in these regions. Accordingly, oxytocin-containing neurites were distributed in both regions. These results suggest that the balance of these hormonal signals has an effect on olfactory sensitivity in pregnant females.

Visualizing the bibliometrics of the inflammatory mechanisms in intervertebral disc degeneration

ObjectiveIntervertebral disc degeneration (IVDD) constitutes a crucial pathological foundation for spinal degenerative diseases (SDD) and stands as a primary contributor to both low back pain (LBP) and disability. The progression of IVDD is linked to structural and functional alterations in tissues, where an imbalance in the inflammatory microenvironment can induce extracellular matrix (ECM) degradation, senescence, and apoptosis. This imbalance is a key pathomechanism in the disease's development, gaining considerable attention in recent years. This study aims to conduct a bibliometric analysis of publications pertaining to the inflammatory mechanisms of IVDD to quantitatively assess current research hotspots and directions. MethodsIn this study, we queried the Web of Science Core Collection (WOSCC) database covering the period from January 1, 2001, to November 7, 2023. Content in this area was analyzed and visualized using software such as Citespace, Vosviewer, and the bibliometrix package. ResultsFindings indicate a consistent annual increase in the number of publications, highlighting the widespread attention garnered by research on the inflammatory mechanisms of IVDD. In terms of journal research, Spine emerged with the highest number of publications, along with significantly elevated total citations and average citations compared to other journals. Regarding country analysis, China led in the number of publications, while the USA claimed the highest number of citations and total link strength. Institutional analysis revealed Sun Yat-sen University as having the highest number of publications and total link strength, with Thomas Jefferson University securing the highest total citations. Author analysis identified Ohtori, S. with the highest number of publications, Risbud, M.V. with the highest number of citations, and Inoue, G. with the highest total link strength, all of whom have made significant contributions to the field's development. Citation and co-citation analyses indicated that highly cited documents primarily focused on classical studies exploring inflammatory mechanisms in IVDD pathogenesis. Keyword analysis showcased the ongoing research hotspot as the further investigation of mechanisms and treatment studies. Recent years have seen a shift towards exploring pyroptosis, necrotic apoptosis, autophagy, ferroptosis, oxidative stress, and bacterial infection, among other mechanisms. In terms of treatment, alongside traditional monomer, drug, and compound therapies for IVDD, research is increasingly concentrating on stem cell therapy, exosomes, hydrogels, and scaffolds. ConclusionThis bibliometric analysis of research on inflammatory mechanisms in IVDD provides insights into the current status, hotspots, and potential future trends. These findings can serve as a valuable reference and guide for researchers in the field.

Epidermal barrier impairment predisposes for excessive growth of the allergy-associated yeast Malassezia on murine skin.

The skin barrier is vital for protection against environmental threats including insults caused by skin-resident microbes. Dysregulation of this barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While Malassezia is the most abundant commensal fungus of the skin, little is known about the host control of this fungus in inflammatory skin diseases. In this experimental study, MC903-treated mice were colonized with Malassezia spp. to assess the host-fungal interactions in atopic dermatitis. Additional murine models of AD and ichthyosis, including tape stripping, K5-Nrf2 overexpression and flaky tail mice, were employed to confirm and expand the findings. Skin fungal counts were enumerated. High parameter flow cytometry was used to characterize the antifungal response in the AD-like skin. Structural and functional alterations in the skin barrier were determined by histology and transcriptomics of bulk skin. Finally, differential expression of metabolic genes in Malassezia in atopic and control skin was quantified. Malassezia grows excessively in AD-like skin. Fungal overgrowth could, however, not be explained by the altered immune status of the atopic skin. Instead, we found that by upregulating key metabolic genes in the altered cutaneous niche, Malassezia acquired enhanced fitness to efficiently colonise the impaired skin barrier. This study provides evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. Our findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders.

One‐Step Synthesis of Metal Oxide Nanoparticles Using Cannabidiol: Characterisation and Cytotoxicity Assessment in Human Keratinocyte Cells

AbstractThis research paper explores the field of nanobiotechnology, focusing on the design, characterisation, and potential dermal applications of metal oxide nanoparticles (MONPs). ZnO and FeO NPs exhibit distinctive properties that are valuable in dermato‐cosmetic applications and transdermal drug delivery. This study investigates Cannabidiol (CBD) as a capping agent for MONPs synthesis. Employing microwave‐assisted techniques, MONPs were synthesised using either CBD or polyvinylpyrrolidone (PVP) as capping agents. The TEM, SEM, FTIR, and XRD characterisation results confirmed the successful formation of CBD‐capped ZnO and FeO NPs exhibiting an average particle size of 90 and 76 nm, respectively. The cytotoxicity of CBD‐capped MONPs was evaluated on HaCaT cells over a concentration range of 100 to 6.25 μg/mL, which revealed that CBD‐capped ZnO NPs exerted a cytotoxic effect on HaCaT cells (IC50 85.34±1.17 μg/mL). In contrast, CBD‐capped FeO NPs and PVP‐capped MONPs exhibited negligible cytotoxicity (IC50 &gt;100 μg/mL). TEM analysis revealed a noticeable structural alteration of ZnO NPs in the supplemented cell culture medium, which could contribute to enhanced NP uptake, thereby explaining the more pronounced cytotoxic effect of ZnO NPs. Therefore, the disparity in cytotoxic responses can be attributed to the protein coating adhering to the NPs surface in a biological medium.

Ionic Liquids as Reconditioning Agents for Paper Artifacts.

This research explores the potential of ionic liquids (ILs) in restoring paper artifacts, particularly an aged book sample. Three distinct ILs-1-ethyl-3-propylimidazolium bis(trifluoromethylsulfonyl)imide, 1-methyl-3-pentylimidazolium bis(trifluoromethylsulfonyl)imide, and 1-methyl-3-heptylimidazolium bis(trifluoromethylsulfonyl)imide -both in their pure form and isopropanol mixtures, were examined for their specific consumption in conjunction with paper, with 1-ethyl-3-propylimidazolium bis(trifluoromethylsulfonyl)imide displaying the highest absorption. Notably, the methyl-3-heptylimidazolium ionic liquid displayed pronounced deacidification capabilities, elevating the paper pH close to a neutral 7. The treated paper exhibited significant color enhancements, particularly with 1-heptyl-3-methylimidazolium and 1-pentyl-3-methylimidazolium ILs, as evidenced by CIE-Lab* parameters. An exploration of ILs as potential UV stabilizers for paper unveiled promising outcomes, with 1-heptyl-3-methylimidazolium IL demonstrating minimal yellowing post-UV irradiation. FTIR spectra elucidated structural alterations, underscoring the efficacy of ILs in removing small-molecular additives and macromolecules. The study also addressed the preservation of inked artifacts during cleaning, showcasing ILs' ability to solubilize iron gall ink, particularly the one with the 1-ethyl-3-propylimidazolium cation. While exercising caution for prolonged use on inked supports is still recommended, ILs are shown here to be valuable for cleaning ink-stained surfaces, establishing their effectiveness in paper restoration and cultural heritage preservation.

Understanding a point mutation signature D54K in the caspase activation recruitment domain of NOD1 capitulating concerted immunity via atomistic simulation

Point mutation D54K in the human N-terminal caspase recruitment domain (CARD) of nucleotide-binding oligomerization domain −1 (NOD1) abrogates an imperative downstream interaction with receptor-interacting protein kinase (RIPK2) that entails combating bacterial infections and inflammatory dysfunction. Here, we addressed the molecular details concerning conformational changes and interaction patterns (monomeric-dimeric states) of D54K by signature-based molecular dynamics simulation. Initially, the sequence analysis prioritized D54K as a pathogenic mutation, among other variants, based on a sequence signature. Since the mutation is highly conserved, we derived the distant ortholog to predict the sequence and structural similarity between native and mutant. This analysis showed the utility of 33 communal core residues associated with structural-functional preservation and variations, concurrently served to infer the cryptic hotspots Cys39, Glu53, Asp54, Glu56, Ile57, Leu74, and Lys78 determining the inter helical fold forming homodimers for putative receptor interaction. Subsequently, the atomistic simulations with free energy (MM/PB(GB)SA) calculations predicted structural alteration that takes place in the N-terminal mutant CARD where coils changed to helices (45 α3- L4-α4-L6- α683) in contrast to native (45T2-L4-α4-L6-T483). Likewise, the C-terminal helices 93T1-α7105 connected to the loops distorted compared to native 93α6-L7105 may result in conformational misfolding that promotes functional regulation and activation. These structural perturbations of D54K possibly destabilize the flexible adaptation of critical homotypic NOD1CARD-CARDRIPK2 interactions (α4Asp42-Arg488α5 and α6Phe86-Lys471α4) is consistent with earlier experimental reports. Altogether, our findings unveil the conformational plasticity of mutation-dependent immunomodulatory response and may aid in functional validation exploring clinical investigation on CARD-regulated immunotherapies to prevent systemic infection and inflammation. Communicated by Ramaswamy H. Sarma

Altered DTI scalars in the hippocampus are associated with morphological and structural changes after traumatic brain injury.

Blunt and diffuse injury is a highly prevalent form of traumatic brain injury (TBI) which can result in microstructural alterations in the brain. The blunt impact on the brain can affect the immediate contact region but can also affect the vulnerable regions like hippocampus, leading to functional impairment and long-lasting cognitive deficits. The hippocampus of the moderate weight drop injured male rats was longitudinally assessed for microstructural changes using in vivo MR imaging from 4h to Day 30 post-injury (PI). The DTI analysis found a prominent decline in the apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) values after injury. The perturbed DTI scalars accompanied histological changes in the hippocampus, wherein both the microglia and astrocytes showed changes in the morphometric parameters at all timepoints. Along with this, the hippocampus showed presence of Aβ positive fibrils and neurite plaques after injury. Therefore, this study concludes that TBI can lead to a complex morphological, cellular, and structural alteration in the hippocampus which can be diagnosed using in vivo MR imaging techniques to prevent long-term functional deficits.

Influence of ion beam on the surface characteristics and structural properties of PVA/TiO2 films

This work used the solution-casting preparation method to create flexible polymer composite materials including titanium dioxide (TiO2) and poly(vinyl alcohol) (PVA). Then, using a wide-beam homemade cold-cathode ion generator, the samples were irradiated with oxygen fluences of 4 × 1016, 8 × 1016 and 12 × 1016 ions/cm2. Using the energy-dispersive X-ray spectroscopy, contact angle and X-ray diffraction techniques, the successful production of PVA/titanium dioxide composite films was evaluated. The effects of ion exposure on the optical behavior were determined using the ultraviolet–visible spectroscopy technique. The PVA/titanium dioxide dispersion energy was 1.75 eV. It increased to 2.21, 2.66 and 3.12 eV with irradiation of 4 × 1016, 8 × 1016 and 12 × 1016 ions/cm2, respectively. Moreover, the refractive index (n 0) of PVA/titanium dioxide was 1.18, which increased to 1.25, 1.32 and 1.40, respectively. Moreover, the oscillation energy E 0 reduced from 4.24 eV for the PVA/titanium dioxide composite to 3.84, 3.64 and 3.27 eV, respectively. Consequently, PVA/TiO2 films are treated with ions to change their optical and structural properties, which are then used in a variety of optoelectronic applications.

The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice.

To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated cardiomyopathy. We generated 4 mice carrying TTNtv p. Y4370* through CRISPR/Cas-mediated genome engineering. Monthly serological detection, bimonthly echocardiography, and histology evaluation were carried out to observe and compare alterations of cardiac structure and function between 4 TTN+/- mice and 4 wild-type (WT) mice. For the two-month-old TTN+/- mice, serum glutamic-oxalacetic transaminase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) were significantly increased, the diastolic Left Ventricular Systolic Anterior Wall (LVAW), and the LV mass markedly rose, with the left ventricular volume displaying an increasing trend and Ejection Fraction (EF) and Fractional Shortening (FS) showing a decreasing trend. Besides, the histological evaluation showed that cardiac fibrosis level and positive rate of cardiac mast cell of TTN+/- mice were obviously increased compared with WT mice. TTNtv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of TTNtv c.13254T>G pathogenicity in human.

Correlation between Disc Imaging Observations and Clinical Efficacy after Percutaneous Endoscopic Lumbar Discectomy: A 1-Year Follow-up Study.

The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence-based foundation for assessing postoperative efficacy. From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2-weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS-back/VAS-leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow-up appointments 3, 6, and 12 months after the surgery. The follow-up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. Parameters such as area and circumference of intervertebral discs in the cross-section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross-sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short-term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.