Biological Characteristics Research Articles

Tensor Completion for Alzheimer's Disease Prediction From Diffusion Tensor Imaging.

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder with insidious onset. Accurate prediction of the disease progression has received increasing attention. Cognitive scores that reflect patients' cognitive status have become important criteria for predicting AD. Most existing methods consider the relationship between neuroimages and cognitive scores to improve prediction results. However, the inherent structure information in interrelated cognitive scores is rarely considered. In this article, we propose a relation-aware tensor completion multitask learning method (RATC-MTL), in which the cognitive scores are represented as a third-order tensor to preserve the global structure information in clinical scores. We combine both tensor completion and linear regression into a unified framework, which allows us to capture both inter and intra modes correlations in cognitive tensor with a low-rank constraint, as well as incorporate the relationship between biological features and cognitive status by imposing a regression model on multiple cognitive scores. Compared to the single-task and state-of-the-art multi-task algorithms, our proposed method obtains the best results for predicting cognitive scores in terms of four commonly used metrics. Furthermore, the overall performance of our method in classifying AD progress is also the best. Our results demonstrate the effectiveness of the proposed framework in fully exploring the global structure information in cognitive scores. This study introduces a novel concept of leveraging tensor completion to assist in disease diagnoses, potentially offering a solution to the issue of data scarcity encountered in prolonged monitoring scenarios.

Phenotypic Trait Analysis for Registered Cultivars of Camellia sasanqua

Based on the International Camellia Register (ICR), an analysis of 1616 cultivars of Sasanqua that were registered in 2022 and earlier was conducted. This analysis focused on the resource and biological characteristics of the cultivars. Additionally, a trait diversity analysis, principal component analysis, and cluster analysis of 118 cultivars that had complete morphological records were performed. The findings revealed a rich diversity of Sasanqua cultivars, with Japan, the United States, and Australia being the main sources. The primary flower color was red, followed by multiple colors, white, and rare colors. The predominant flower forms were single-petal and semi-double-petal, with a limited number of formal double-petal forms. Elliptical leaf shapes were the most common, and the predominant leaf colors were green and deep green. The flowering period mainly corresponded to early flowering cultivars. The phenotypic diversity index (H) of the 118 cultivars ranged from 0.31 to 1.84. The flower diameter exhibited the highest H value (1.84), whereas leaf shape had the lowest H value (0.31). The coefficient of variation (CV) ranged from 21.67% to 71.81%, with the flower diameter having the smallest CV (21.67%) and petal number having the largest CV (71.81%). The first three principal components, which accounted for a cumulative contribution rate of 62.49%, effectively represented most of the information regarding the seven trait indicators of the different cultivars. Furthermore, a cluster analysis was conducted based on the flower form, diameter, petal numbers, and other characteristics of the various cultivars. The 118 cultivars were divided into three groups. The first group could be used for breeding single-petal flower cultivars, whereas the third group exhibited a larger number of petals and could be used for breeding double-petal flower cultivars.

Wild goose in the traditional worldview of the Buryats

The purpose of this study is to identify the image of the wild goose in the traditional worldview of the Buryats. The timeframe of this research covers the end of the 19th — middle of the 20th c., the period when the Buryats overall retained their set of mythological views. Geographically, the survey is focused on south-eastern Siberia, which includes ethnic Buryatia. The research is based on a variety of sources, including folklore, linguistic and ethnographic information. The structural-semiotic method has been chosen as the main technique of study, which allows determination of the symbolism that conveys the ideas about wild goose. It has been revealed that in minor genres of the Buryat folklore, the feminine nature of the wild goose is emphasized, and their anthroponymy mani-fests its gender differences. It has been found that, for the Buryats, the individual biological and behavioral char-acteristics of the goose were of a particular importance. It has also been determined that natural rhythms (the start of spring and the middle of autumn) were associated with the wild goose, as well as the first snowfall. At the same time, significant importance was attributed to its cry. Its image symbolized long distances and time. The motive of shapeshifting was also linked to it. This bird, both in shamanic and Buddhist traditions, was considered to be an assistant to the deity (the supreme celestial being among shamanists, and the White Elder among Bud-dhists). In the Buryat epics, it was endowed with a negative connotation. According to the traditional perceptions of some of the Cis-Baikal Buryats, the wild goose had a sacred status, and the interchangeability of images of a goose and another sacred bird — a swan — has been noted. The goose (precisely, the female goose) acted as a totem for a number of Cis-Baikal kins.

Patient-specific radiation dose for Chinese pediatric patients undergoing whole-body PET/CT examinations

Objective. To assess potential variations in the absorbed dose between Chinese and Caucasian children exposed to 18F-FDG PET scan and to investigate the factors contributing to dose differences, this work employed patient-specific phantoms and our compartment model for calculating the patient-specific absorbed dose in Chinese children. Approach. Data of 29 Chinese pediatric patients undergoing whole-body 18F-FDG PET/CT studies were retrospectively collected, including PET images for activity distributions and corresponding CT images for organ segmentation and phantom construction. A biokinetic compartment model was implemented to obtain cumulated activities. Absorbed radiation dose for both CT and PET component were calculated using Monte Carlo simulations. Regression models were fitted to time integrated activity coefficient (TIAC) and organ absorbed dose for each patient. Main results. TIACs of all the organs in our compartment model and the organ dose for 12 organs were correlated with patients’ weight. Young children have significantly large uptake in brain compared to adults. The distinctions of anatomical and biological characteristics between Chinese and Caucasian children contribute to variations in the absorbed dose of 18F-FDG PET scans. PET contributed more in organ dose than CT did in most organs, especially in brain and bladder. The average effective dose (± SD) was 4.5 mSv (± 1.12 mSv), 7.8 mSv (± 3.2 mSv) and 12.3 mSv (± 3.5 mSv) from CT, PET and their sum respectively. PET contributed 1.7 times higher than CT. Significance. To the best of our knowledge, this work represents the first attempt to estimate patient-specific radiation doses from PET/CT for Chinese pediatric patients. TIACs derived from our methodology in both age groups exhibited significant differences from the that reported in ICRP 128. Substantial differences in absorbed and effective doses were observed between Chinese and Caucasian children across all age groups. These disparities are attributed to markedly distinct anatomical and pharmacokinetic characteristics among adults and pediatric patients, and different racial groups. The application of data derived from adults to pediatric patients introduces considerable uncertainty. Our methodology offers a valuable approach not only for estimating pharmacokinetic characteristics and patient-specific radiation doses in pediatric patients undergoing 18F-FDG studies but also for other cohorts with similar characteristics.

Pretreatment with inflammatory factors altered the secretome of human amniotic epithelial cells.

Human amniotic epithelial cells (hAECs) are novel and promising therapeutic agents for patients suffering from degenerative diseases. Studies have demonstrated that the therapeutic effects of hAECs mainly depend on their paracrine components. Currently, appropriate pretreatment is a widely confirmed strategy for enhancing the repair potential of stem cells; however, the effect of proinflammatory factor pretreatment on hAECs and their secretome is still unclear. In this study, we used the well-characterized proinflammatory factors tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) to stimulate hAECs and analyzed the effect of TNF-α and IFN-γ on hAECs, including gene expression profile, paracrine proteins and miRNAs in exosomes. Results showed that TNF-α and IFN-γ pretreatment improved the viability of hAECs, but inhibited the proliferation of hAECs. TNF-α and IFN-γ pretreatment altered the gene expression profile of hAECs, and upregulated differentially expressed genes (DEGs) were predominantly enriched in biological adhesion, antioxidant activity and response to IFN-beta. In addition, TNF-α and IFN-γ pretreatment enhanced the paracrine secretion of cytokines by hAECs. The upregulated differentially expressed proteins (DEPs) were mainly enriched in tissue remodeling proteins and cytokine-cytokine receptor. Notably, the expression of miRNAs in exosomes from hAECs was also changed by TNF-α and IFN-γ pretreatment. The target genes of upregulated exosomal miRNAs substantially contributed to the response to stimulus, metabolic pathways and PI3K-Akt signaling pathway. Our findings improve our understanding of the biological characteristics of hAECs after proinflammatory factor pretreatment and provide novel insights to strengthen and optimize the therapeutic potential of hAECs and their secretome in regenerative medicine.

Neuropathologic Validation and Diagnostic Accuracy of Presynaptic Dopaminergic Imaging in the Diagnosis of Parkinsonism.

Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism. Retrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism. All of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%). DAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations. This study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.

Multiomics analysis of platelet-rich plasma promoting biological performance of mesenchymal stem cells

Mesenchymal Stem Cells are ideal seed cells for tissue repair and cell therapy and have promising applications in regenerative medicine and tissue engineering. Using Platelet-Rich Plasma as an adjuvant to create and improve the microenvironment for Mesenchymal Stem Cells growth can enhance the biological properties of Mesenchymal Stem Cells and improve the efficacy of cell therapy. However, the mechanism by which Platelet-Rich Plasma improves the biological performance of Mesenchymal Stem Cells is still unknown. In this study, by examining the effects of Platelet-Rich Plasma on the biological performance of Mesenchymal Stem Cells, combined with multiomics analysis (Transcriptomics, Proteomics and Metabolomics) and related tests, we analyzed the specific pathways, related mechanisms and metabolic pathways of Platelet-Rich Plasma to improve the biological performance of Mesenchymal Stem Cells. In an in vitro cell culture system, the biological performance of Mesenchymal Stem Cells was significantly improved after replacing Foetal Bovine Serum with Platelet-Rich Plasma, and the genes (ESM1, PDGFB, CLEC7A, CCR1 and ITGA6 et al.) related to cell proliferation, adhesion, growth, migration and signal transduction were significantly upregulated. Platelet-Rich Plasma can enhance the secretion function of MSC exosomes, significantly upregulate many proteins related to tissue repair, immune regulation and anti-infection, and enhance the repair effect of exosomes on skin injury. After replacing Foetal Bovine Serum with Platelet-Rich Plasma, Mesenchymal Stem Cells underwent metabolic reprogramming, the metabolism of amino acids and fatty acids and various signaling pathways were changed, the anabolic pathways of various proteins were enhanced. These results provide a theoretical and technical reference for optimizing the Mesenchymal Stem Cells culture system, improving the biological characteristics and clinical application effects of Mesenchymal Stem Cells.

Free Salivary Amino Acid Profile in Breast Cancer: Clinicopathological and Molecular Biological Features.

The study of salivary amino acid profiles has attracted the attention of researchers, since amino acids are actively involved in most metabolic processes, including breast cancer. In this study, we analyzed the amino acid profile of saliva in a sample including all molecular biological subtypes of breast cancer to obtain a more complete picture and evaluate the potential utility of individual amino acids or their combinations for diagnostic purposes. This study included 116 patients with breast cancer, 24 patients with benign breast disease, and 25 healthy controls. From all patients, strictly before the start of treatment, saliva samples were collected, and the quantitative content of 26 amino acids was determined. Statistically significant differences between the three groups are shown in the content of Asp, Gly, Leu + Ile, Orn, Phe, Pro, Thr, and Tyr. To differentiate the three groups from each other, a decision tree was built. To construct it, we selected those amino acids for which the change in concentrations in the subgroups was multidirectional (GABA, Hyl, Arg, His, Pro, and Car). For the first time, it is shown that the amino acid profile of saliva depends on the molecular biological subtype of breast cancer. The most significant differences are shown for the luminal B HER2-positive and TNBC subgroups. In our opinion, it is critically important to consider the molecular biological subtype of breast cancer when searching for potential diagnostic markers.

Deciphering tertiary lymphoid structure heterogeneity reveals prognostic signature and therapeutic potentials for colorectal cancer: a multicenter retrospective cohort study.

Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. We collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multi-omics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. We subsequently employed a regularization algorithm to construct the TLSscore based on 9 core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy. We identified distinct TLS patterns in CRC and characterized their heterogeneity through multi-omics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.

Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants that Confer Risk for Breast Cancer.

Breast cancer includes several subtypes with distinct characteristic biological, pathological, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate development of improved prevention and treatment approaches. Here, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case GWAS (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared to luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to 2-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among breast cancer patients. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC.

Case series: Management and outcomes of five cases of blunt and open pancreatic trauma

Introduction Pancreatic trauma is notably less frequent than injuries affecting other solid organs, such as the liver or spleen. Despite their infrequency, pancreatic injuries can pose significant risks, with mortality rates ranging from 5 to 30% and morbidity rates reaching 50%. Managing such injuries remains contentious because of the anatomical complexity, lesion extent, and close proximity to neighboring organs. Methods Our study aimed to delineate the clinical and biological characteristics of pancreatic trauma and specify diagnostic and therapeutic modalities. This study was conducted retrospectively from 2010 to 2021 at Mahmoud El Matri Hospital’s General Surgery Department in Ariana, TUNISIA, and included five cases of blunt and open pancreatic trauma. Results Although rare, pancreatic injuries can lead to serious consequences, prompting the development of a diverse array of therapeutic options. Pancreatic trauma presents a complex clinical challenge, necessitating a comprehensive approach that considers various factors, such as injury severity, anatomical location, and patient condition. Advanced imaging techniques, including computed tomography (CT) scanning, Wirsung-MRI, and ERCP, aid in the accurate diagnosis and assessment of canal involvement. Conservative management was considered for cases with limited canal rupture, whereas endoscopic treatments showed promise for hemodynamically stable cases. Surgical interventions, such as duodenopancreatectomy, are reserved for exceptional cases with severe injuries. Conclusion Pancreatic trauma requires a comprehensive approach that considers factors such as injury severity, anatomical location, and patient condition. Ongoing research and collaboration are vital for refining pancreatic trauma management and proposing guidelines for facilitating decision-making.

Suppressing mitochondrial inner membrane protein (IMMT) inhibits the proliferation of breast cancer cells through mitochondrial remodeling and metabolic regulation

Metabolic reprogramming is widely recognized as a hallmark of malignant tumors, and the targeting of metabolism has emerged as an appealing approach for cancer treatment. Mitochondria, as pivotal organelles, play a crucial role in the metabolic regulation of tumor cells, and their morphological and functional alterations are intricately linked to the biological characteristics of tumors. As a key regulatory subunit of mitochondria, mitochondrial inner membrane protein (IMMT), plays a vital role in degenerative diseases, but its role in tumor is almost unknown. The objective of this research was to investigate the roles that IMMT play in the development and progression of breast cancer (BC), as well as to elucidate the underlying biological mechanisms that drive these effects. In this study, it was confirmed that the expression of IMMT in BC tissues was significantly higher than that in normal tissues. The analysis of The Cancer Genome Atlas (TCGA) database revealed that IMMT can serve as an independent prognostic factor for BC patients. Additionally, verification in clinical specimens of BC demonstrated a positive association between high IMMT expression and larger tumor size (> 2 cm), Ki-67 expression (> 15%), and HER-2 status. Furthermore, in vitro experiments have substantiated that the suppression of IMMT expression resulted in a reduction in cell proliferation and alterations in mitochondrial cristae, concomitant with the liberation of cytochrome c, but it did not elicit mitochondrial apoptosis. Through Gene Set Enrichment Analysis (GSEA) analysis, we have predicted the associated metabolic genes and discovered that IMMT potentially modulates the advancement of BC through its interaction with 16 metabolic-related genes, and the changes in glycolysis related pathways have been validated in BC cell lines after IMMT inhibition. Consequently, this investigation furnishes compelling evidence supporting the classification of IMMT as prognostic marker in BC, and underscoring its prospective utility as a novel target for metabolic therapy.

Tannic acid modified keratin/sodium alginate/carboxymethyl chitosan biocomposite hydrogels with good mechanical properties and swelling behavior

Natural polymer-based hydrogels have demonstrated great potential as wound-healing dressings. They help to maintain a moist wound environment as well as promote faster healing. In this work, a multifunctional hydrogel was prepared using keratin, sodium alginate, and carboxymethyl chitosan with tannic acid modification. Micro-morphology of hydrogels has been performed by scanning electron microscopy. Fourier Transform Infrared Spectroscopy reveals the presence of hydrogen bonding. The mechanical properties of the hydrogels were examined using a universal testing machine. Furthermore, we investigated several properties of the modified hydrogel. These properties include swelling rate, water retention, anti-freezing properties, antimicrobial and antioxidant properties, hemocompatibility evaluation and cell viability test in vitro. The modified hydrogel has a three-dimensional microporous structure, the swelling rate was 1541.7%, the elastic modulus was 589.74 kPa, the toughness was 211.74 kJ/m3, and the elongation at break was 75.39%, which was similar to the human skin modulus. The modified hydrogel also showed inhibition of S. aureus and E. coli, as well as a DPPH scavenging rate of 95%. In addition, the modified hydrogels have good biological characteristics. Based on these findings, the K/SA/CCS hydrogel holds promise for applications in biomedical engineering.

A review of ultrasound contrast media

Efforts have been made over the last five decades to create effective ultrasonic contrast media (UCM) for cardiac and noncardiac applications. The initial UCM was established in the 1980s, following publications from the 1960s that detailed the discovery of ultrasonic contrast enhancement using small gaseous bubbles in echocardiographic examinations. An optimal contrast agent for echography should possess the following characteristics: non-toxicity, suitability for intravenous injection, ability to traverse pulmonary, cardiac, and capillary circulations, and stability for recirculation. Definity, Optison, Sonazoid, and SonoVue are examples of current commercial contrast media. These contrast media have shown potential for various clinical reasons, both on-label and off-label. Several possible UCMs have been developed or are in progress. Advancements in comprehending the physical, chemical, and biological characteristics of microbubbles have significantly improved the visualization of tumor blood vessels, the identification of areas with reduced blood supply, and the enhanced detection of narrowed blood vessels. Innovative advances are expected to enhance future applications such as ultrasonic molecular imaging and therapeutic utilization of microbubbles.

Role of the transient receptor potential melastatin 4 in inhibition effect of arsenic trioxide on the tumor biological features of colorectal cancer cell

Background To investigate the effects of arsenic trioxide (ATO) on human colorectal cancer cells (HCT116) growth and the role of transient receptor potential melastatin 4 (TRPM4) channel in this process. Methods The viability of HCT116 cells was assessed using the CCK-8 assay. Western blot analysis was employed to examine the protein expression of TRPM4. The apoptosis of HCT116 cells was determined using TUNEL and Flow cytometry. Cell migration was assessed through the cell scratch recovery assay and Transwell cell migration assay. Additionally, Transwell cell invasion assay was performed to determine the invasion ability of HCT116 cells. Results ATO suppressed the viability of HCT116 cells in a dose-dependent manner, accompanied by a decline in cell migration and invasion, and an increase in apoptosis. 9-phenanthroline (9-Ph), a specific inhibitor of TRPM4, abrogated the ATO-induced upregulation of TRPM4 expression. Additionally, blocking TRPM4 reversed the effects of ATO on HCT116 cells proliferation, including restoration of cell viability, migration and invasion, as well as the inhibition of apoptosis. Conclusion ATO inhibits CRC cell growth by inducing TRPM4 expression, our findings indicate that ATO is a promising therapeutic strategy and TRPM4 may be a novel target for the treatment of CRC.

Reduced Protein Import via TIM23 SORT Drives Disease Pathology in TIMM50-Associated Mitochondrial Disease.

TIMM50 is a core subunit of the TIM23 complex, the mitochondrial inner membrane translocase responsible for the import of pre-sequence-containing precursors into the mitochondrial matrix and inner membrane. Here we describe a mitochondrial disease patient who is homozygous for a novel variant in TIMM50 and establish the first proteomic map of mitochondrial disease associated with TIMM50 dysfunction. We demonstrate that TIMM50 pathogenic variants reduce the levels and activity of endogenous TIM23 complex, which significantly impacts the mitochondrial proteome, resulting in a combined oxidative phosphorylation (OXPHOS) defect and changes to mitochondrial ultrastructure. Using proteomic data sets from TIMM50 patient fibroblasts and a TIMM50 HEK293 cell model of disease, we reveal that laterally released substrates imported via the TIM23SORT complex pathway are most sensitive to loss of TIMM50. Proteins involved in OXPHOS and mitochondrial ultrastructure are enriched in the TIM23SORT substrate pool, providing a biochemical mechanism for the specific defects in TIMM50-associated mitochondrial disease patients. These results highlight the power of using proteomics to elucidate molecular mechanisms of disease and uncovering novel features of fundamental biology, with the implication that human TIMM50 may have a more pronounced role in lateral insertion than previously understood.

Amyloid-related imaging abnormalities (ARIA) and their radiological, biological and clinical characteristics: a plain language summary

Amyloid-related imaging abnormalities (ARIA) and their radiological, biological and clinical characteristics: a plain language summary

Soil environmental anomalies dominate the responses of net ecosystem productivity to heatwaves in three Mongolian grasslands

Climate change is causing more frequent and intense heatwaves. Therefore, it is important to understand how heatwaves affect the terrestrial carbon cycle, especially in grasslands, which are especially susceptible to climate extremes. This study assessed the impact of naturally occurring, simultaneous short-term heatwaves on CO2 fluxes in three ecosystems on the Mongolia Plateau: meadow steppe (MDW), typical steppe (TPL), and shrub-grassland (SHB). During three heatwaves, net ecosystem productivity (NEP) was reduced by 86 %, 178 %, and 172 % at MDW, TPL, and SHB, respectively. The changes in ecosystem respiration, gross primary production, evapotranspiration, and water use efficiency were divergent, indicating the mechanisms underlying the observed NEP decreases among the sites. The impact of the heatwave in MDW was mitigated by the high soil water content, which enhanced evapotranspiration and subsequent cooling effects. However, at TPL, insufficient soil water led to combined thermal and drought stress and low resilience. At SHB, the ecosystem's low tolerance to an August heatwave was heavily influenced by species phenology, as it coincided with the key phenological growing phase of plants. The potential key mechanism of divergent NEP response to heatwaves lies in the divergent stability and varying importance of environmental factors, combined with the specific sensitivity of NEP to each factor in ecosystems. Furthermore, our findings suggest that anomalies in soil environment, rather than atmospheric anomalies, are the primary determinants of NEP anomalies during heatwaves. This challenges the conventional understanding of heatwaves as a discrete and ephemeral periods of high air temperatures. Instead, heatwaves should be viewed as chronologically variable, compound, and time-sensitive environmental stressors. The ultimate impact of heatwaves on ecosystems is co-determined by a complex interplay of environmental, biological, and heatwave features.

Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics.

The rise of antibiotic resistance and a dwindling antimicrobial pipeline have been recognized as emerging threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria for which effective therapies were rapidly needed. Now, entering the third decade of the twenty-first century, and despite the introduction of several new antibiotics and antibiotic adjuvants, such as novel β-lactamase inhibitors, these organisms continue to represent major therapeutic challenges. These bacteria share several key biological features, including adaptations for survival in the modern health-care setting, diverse methods for acquiring resistance determinants and the dissemination of successful high-risk clones around the world. With the advent of next-generation sequencing, novel tools to track and combat the spread of these organisms have rapidly evolved, as well as renewed interest in non-traditional antibiotic approaches. In this Review, we explore the current epidemiology and clinical impact of this important group of bacterial pathogens and discuss relevant mechanisms of resistance to recently introduced antibiotics that affect their use in clinical settings. Furthermore, we discuss emerging therapeutic strategies needed for effective patient care in the era of widespread antimicrobial resistance.