Search

Background Geriatric depression is a severe mental illness distinct from depression in other age groups, characterized by significant heterogeneity. Subclinical hypothyroidism (SCH) is a state of hypothyroidism with subtle clinical signs. The impact of SCH on elderly depression is easily overlooked, and the association between SCH and elderly depression is not well understood. Objective To explore the clinical characteristics of hospitalized elderly depression patients with SCH. Methods Depressed patients hospitalized in the Fourth People's Hospital of Hefei from April 2019 to March 2023 were included in the study and divided into the subclinical hypothyroidism depression (SCHD) group (n=108) and control depression (CD) group (n=110). General data of the subjects was collected, fasting venous blood samples were collected for testing biochemical markers, and the Hamilton Depression Rating Scale (HAMD-24) was used to assess depressive symptoms. Results The SCHD group showed a higher number of antipsychotic drug use, comorbid somatic diseases, days of hospitalization, and duration of the disease than the CD group (P

An ontology is a structured framework that categorizes entities, concepts, and relationships within a domain to facilitate shared understanding, and it is important in computational linguistics and knowledge representation. In this paper, we propose a novel framework to automatically extend an existing ontology from streaming data in a zero-shot manner. Specifically, the zero-shot ontology extension framework uses online and hierarchical clustering to integrate new knowledge into existing ontologies without substantial annotated data or domain-specific expertise. Focusing on the medical field, this approach leverages Large Language Models (LLMs) for two key tasks: Symptom Typing and Symptom Taxonomy among breast and bladder cancer survivors. Symptom Typing involves identifying and classifying medical symptoms from unstructured online patient forum data, while Symptom Taxonomy organizes and integrates these symptoms into an existing ontology. The combined use of online and hierarchical clustering enables real-time and structured categorization and integration of symptoms. The dual-phase model employs multiple LLMs to ensure accurate classification and seamless integration of new symptoms with minimal human oversight. The paper details the framework's development, experiments, quantitative analyses, and data visualizations, demonstrating its effectiveness in enhancing medical ontologies and advancing knowledge-based systems in healthcare.

Abstract Patients with ischemic cerebrovascular disease (ICVD) frequently develop concomitant peripheral artery disease (PAD) or renal artery stenosis (RAS), and multiterritorial atherosclerotic patients usually have a worse prognosis. We aimed to evaluate the status of peripheral atherosclerosis (AS) and cervicocephalic AS (CAS) in ICVD patients with AS, their correlation, and related risk factors contributing to coexisting cervicocephalic-peripheral AS (CPAS). Based on the severity and extent of AS evaluated by computed tomography angiography and ultrasound, the degree of AS was triple categorized to assess the correlation between CAS and PAD/RAS. CAS and PAD/RAS were defined as the most severe stenosis being ≥ 50% luminal diameter in cervicocephalic or lower limb arteries, and a peak systolic velocity at the turbulent site being ≥ 180 cm/s in the renal artery. Among 403 patients with symptom onset within 30 days, CAS, PAD, and RAS occurrence rates were 68.7%, 25.3%, and 9.9%, respectively. PAD was independently associated with the degree of extracranial and intracranial CAS (p = 0.042, OR = 1.428, 95% CI 1.014–2.012; p = 0.002, OR = 1.680, 95% CI 1.206–2.339), while RAS was independently associated with the degree of extracranial CAS (p = 0.001, OR = 2.880, 95% CI 1.556–5.329). Independent CPAS risk factors included an ischemic stroke history (p = 0.033), increased age (p

Objective Low bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover. Methods A total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X‐ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score

Abstract Background Colorectal cancer (CRC) is the third most prevalent cancer globally, and liver metastasis (CRLM) is the primary cause of death. Hence, it is essential to discover novel prognostic biomarkers and therapeutic drugs for CRLM. Methods This study developed two liver metastasis-associated prognostic signatures based on differentially expressed genes (DEGs) in CRLM. Additionally, we employed an interpretable deep learning model utilizing drug sensitivity databases to identify potential therapeutic drugs for high-risk CRLM patients. Subsequently, in vitro and in vivo experiments were performed to verify the efficacy of these compounds. Results These two prognostic models exhibited superior performance compared to previously reported ones. Obatoclax, a BCL-2 inhibitor, showed significant differential responses between high and low risk groups classified by prognostic models, and demonstrated remarkable effectiveness in both Transwell assay and CT26 colorectal liver metastasis mouse model. Conclusions This study highlights the significance of developing specialized prognostication approaches and investigating effective therapeutic drugs for patients with CRLM. The application of a deep learning drug response model provides a new drug discovery strategy for translational medicine in precision oncology.

The digestion and retrogradation performance of chestnut starch constrains the development of chestnut food industry. It is of great significance to select reasonable processing methods to regulate the digestion and retrogradation properties for the development of nutritious and healthy chestnut foods with high quality. Therefore, the effects of pullulanase enzymatic hydrolysis coupled with hydrothermal treatment on digestibility, long-term retrogradation and multi-scale structure of chestnut starch were investigated. Results showed that enzymatic hydrolysis increased amylose content, and changed chain length distribution. Short-range ordered and crystalline structures were also improved, and the starch digestibility were also reduced. Hydrothermal treatment promoted starch chain interactions, and improved short-range ordered, crystalline and nano-aggregate structures of starch, leading to the lower starch digestibility. During long-term retrogradation, due to the increase of shorter A chains and the decrease of B1 chains which are easy to rearrange, starch crystalline and nano-aggregate structures decreased, which retarded starch retrogradation. Hydrothermal treatment promoted the interactions among A chains and other molecules, and further inhibited the degree of starch molecule rearrangement, which could lead to the lower degree of retrogradation. Therefore, enzymatic hydrolysis coupled with hydrothermal treatment can be used as an effective method to regulate the digestion and retrogradation performance of starch, which could promote the development of chestnut starch-based foods with slower digestion rate and lower retrogradation degree.

ObjectivesThe aim of this study is to explore the expression of inflammatory cytokines (ICs) in Fabry disease (FD), the correlation between ICs and FD phenotypes, and the impact of enzyme replacement therapy (ERT) on IC expression.MethodsWe recruited 67 FD patients and 44 healthy controls (HCs) and detected concentrations of the following ICs: interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-β. We also analyzed the impact of ERT on IC expression in FD patients and the relationship between IC expression and sex, genotype, phenotype, disease burden, and biomarkers.ResultsMost ICs were significantly higher in FD patients than in HCs. A number of ICs were positively correlated with clinical aspects, including disease burden (Mainz Severity Score Index [MSSI]) and cardiac and renal markers. IL-8 was higher in the high MSSI (P-adj=0.026*) than in the low MSSI.ConclusionsICs were upregulated in FD patients, indicating the role of the innate immune process in FD etiology. ERT ameliorated FD-related inflammatory activation, at least to some extent. IC expression was positively correlated with disease burden and clinical markers in FD. Our findings indicated that the inflammatory pathway may be a promising therapeutic target for FD.

ABSTRACT Objective: Tibial plateau fractures are common intra-articular fractures that pose classification and treatment challenges for orthopedic surgeons. Objective: This study examines the value of 3D printing for classifying and planning surgery for complex tibial plateau fractures. Methods: We reviewed 54 complex tibial plateau fractures treated at our hospital from January 2017 to January 2019. Patients underwent preoperative spiral CT scans, with DICOM data processed using Mimics software. 3D printing technology created accurate 1:1 scale models of the fractures. These models helped subdivide the fractures into seven types based on the tibial plateau's geometric planes. Surgical approaches and simulated operations, including fracture reduction and plate placement, were planned using these models. Results: The 3D models accurately depicted the direction and extent of fracture displacement and plateau collapse. They facilitated the preoperative planning, allowing for precise reconstruction strategies and matching intraoperative details with the pre-printed models. Post-surgery, the anatomical structure of the tibial plateau was significantly improved in all 54 cases. Conclusion: 3D printing effectively aids in the classification and preoperative planning of complex tibial plateau fractures, enhancing surgical outcomes and anatomical restoration. Level of Evidence IV, Prospective Study.

We identified that distal 10 nucleotides in the D-sequence in AAV2 inverted terminal repeat (ITR) share partial sequence homology to 1/2 binding site of glucocorticoid receptor-binding element (GRE). Here, we describe that (1) purified GR binds to AAV2 D-sequence, and the D-sequence competes with GR binding to its cognate binding site; (2) dexamethasone-mediated activation of GR pathway significantly increases the transduction efficiency of AAV2 vectors in human cells; (3) human osteosarcoma cells, U2OS, which lack expression of GR, are poorly transduced by AAV2 vectors, but stable transfection with a GR expression plasmid restores vector-mediated transgene expression; (4) replacement of the distal 10 nucleotides in the D-sequence of the AAV2 ITR with a full-length GRE consensus sequence significantly enhances transgene expression in human cells in vitro and in murine hepatocytes in vivo; and (5) none of the ITRs in AAV1, AAV3, AAV4, AAV5, and AAV6 genomes contains the GRE 1/2 binding site, and insertion of a full-length GRE consensus sequence in the AAV6-ITR also significantly enhances transgene expression from AAV6 vectors, both in vitro and in vivo. These novel vectors, termed generation Y AAV vectors, which are serotype, transgene, or promoter agnostic, should be useful in human gene therapy.

BackgroundQuality of life， as a major criterion for judging the clinical outcome of ovarian cancer patients， can be affected by adverse psychological symptoms of patients. Meanwhile， fear of disease progression， as a frequent psychological symptom among cancer survivors， is significantly influenced by metacognition， while there is a paucity of research into the specific correlation among the three in patients with ovarian cancer.ObjectiveTo explore the correlation among fear of disease progression， metacognition and quality of life in patients with ovarian cancer， and to test the role of fear of disease progression in the relationship between metacognition and quality of life， so as to provide references for improving the quality of life in patients with ovarian cancer.MethodsA total of 135 patients with ovarian cancer hospitalized in Cangzhou People's Hospital of Hebei Province from January 2019 to December 2022 were selected. All subjects were requested to complete the Functional Assessment of Cancer Therapy-Ovarian Cancer （FACT-O）， Fear of Progression Questionnaire-Short Form （FoP-Q-SF） and Metacognition Questionnaire （MCQ） to assess their quality of life， fear of disease progression and metacognitive level. Pearson correlation analysis was adopted to examine the correlation among the above scales. Process v3.5 macro program was utilized to determine the mediating effect of fear of disease progression on the relationship between metacognition and quality of life， and nonparametric Bootstrap with bias-correction was used to test the mediating effect.ResultsA total of 122 patients （90.37%） with ovarian cancer completed the effective questionnaire survey. Patients scored （90.52±17.13） on FACT-O， （68.52±16.31） on MCQ， and （37.72±8.91） on FoP-Q-SF. Pearson correlation analysis denoted that FoP-Q-SF score was negatively correlated with FACT-O score （r=-0.412， P

Abstract Background Breastfeeding is essential for infants and mothers. Epidural labor analgesia is used frequently to alleviate pain during vaginal delivery. Studies have found that epidural labor analgesia potentially have negative effects on postpartum breastfeeding. However, the efficacy of epidural labor analgesia on early breastfeeding after vaginal delivery is unclear. Therefore, a retrospective analysis was performed to illuminate the efficacy of epidural labor analgesia on postpartum breast feeding. Methods A total of 392 women who received vaginal delivery in the Second People’s Hospital of Foshan from July 2022 to June 2023 were selected for this study, and all women received epidural labor analgesia and were divided into three groups according to the efficacy of labor analgesia. There were three groups: parturients with VAS scores 7 were divided into Group P (n = 73). The labor process, lactation initiation time, and incidence of delayed onset of lactation were analyzed. The lactation volume and time and LATCH score at 24, 48 and 72 h after vaginal delivery were also analyzed. Results There was no significant difference in labor process times among the three groups (P > 0.05). The cases of prolactin use in Group M were less than those in Group E and Group P, with a significant difference (all P 0.05). The lactation initiation time in Group M was significantly shorter than those in Group E and Group P (all P>0.05). There was no significant difference in lactation initiation time after vaginal delivery between Group E and Group P (P>0.05). The incidence of delayed onset of lactation in Group M was significantly lower those that in Group E and Group P (all P 0.05). The lactation volumes at 24, 48 and 72 h after vaginal delivery in Group M were significantly higher than those in Group E and Group P (all P 0.05). The lactation times at 24, 48 and 72 h after vaginal delivery in Group M were significantly higher than those in Group E and Group P (all P 0.05). There was no significant difference in LATCH scores at 24, 48 and 72 h after vaginal delivery among the three groups (all P > 0.05). Conclusions Compared with labor analgesia with excellent and poor analgesia efficacy, labor analgesia with moderate analgesia efficacy has fewer cases of prolactin use, more lactation volume and time, a shorter lactation initiation time, a lower incidence of delayed onset of lactation and no effect on the LATCH score of breastfeeding.

AbstractMagnetic Fe3O4 nanoparticles were prepared via a simple hydrothermal method and utilized to load paclitaxel. The average particle size of Fe3O4 nanoparticles was found to be 20.2 ± 3.0 nm, and the calculated saturation magnetization reached 129.38 emu/g, verifying superparamagnetism of nanomaterials. The specific surface area and pore volume were 84.756 m2/g and 0.265 cm3/g, respectively. Subsequently, Fe3O4@mSiO2 nanoparticles were successfully fabricated using the Fe3O4 nanoparticles as precursors with an average size of 27.81 nm. The relevant saturation magnetization, zeta potential, and specific surface area of Fe3O4@mSiO2-NH2-FA were respectively 76.3 emu/g, −14.1 mV, and 324.410 m2/g. The pore volume and average adsorption pore size were 0.369 cm3/g and 4.548 nm, respectively. Compared to free paclitaxel, the solubility and stability of nanoparticles loaded with paclitaxel were improved. The drug loading efficiency and drug load of the nanoformulation were 44.26 and 11.38%, respectively. The Fe3O4@mSiO2-NH2-FA nanocomposites were easy to construct with excellent active targeting performance, pH sensitivity, and sustained-release effect. The nanoformulation also showed good biocompatibility, where the cell viability remained at 73.8% when the concentration reached 1200 μg/mL. The nanoformulation induced cell death through apoptosis, as confirmed by AO/EB staining and flow cytometry. Western blotting results suggested that the nanoformulation could induce iron death by inhibiting Glutathione Peroxidase 4 (GPX4) activity or decreasing Ferritin Heavy Chain 1 (FTH1) expression. Subsequently, the expression of HIF-1α was upregulated owing to the accumulation of reactive oxygen species (ROS), thus affecting the expression of apoptosis-related proteins regulated by p53, inducing cell apoptosis.

Uncovering genes associated with muscle growth and body size will benefit the molecular breeding of meat Hu sheep. HMGA2 has proven to be an important gene in mouse muscle growth and is associated with the body size of various species. However, its roles in sheep are still limited. Using sheep myoblast as a cell model, the overexpression of HMGA2 significantly promoted sheep myoblast proliferation, while interference with HMGA2 expression inhibited proliferation, indicated by qPCR, EdU, and CCK-8 assays. Furthermore, the dual-luciferase reporter system indicated that the region NC_056056.1: 154134300-154134882 (-618 to -1200 bp upstream of the HMGA2 transcription start site) was one of the habitats of the HMGA2 core promoter, given the observation that this fragment led to a ~3-fold increase in luciferase activity. Interestingly, SNP rs428001129 (NC_056056.1:g.154134315 C>A) was detected in this fragment by Sanger sequencing of the PCR product of pooled DNA from 458 crossbred sheep. This SNP was found to affect the promoter activity and was significantly associated with chest width at birth and two months old, as well as chest depth at two and six months old. The data obtained in this study demonstrated the phenotypic regulatory role of the HMGA2 gene in sheep production traits and the potential of rs428001129 in marker-assisted selection for sheep breeding in terms of chest width and chest depth.

In recent years, analyzing the explanation for the prediction of Graph Neural Networks (GNNs) has attracted increasing attention. Despite this progress, most existing methods do not adequately consider the inherent uncertainties stemming from the randomness of model parameters and graph data, which may lead to overconfidence and misguiding explanations. However, it is challenging for most of GNN explanation methods to quantify these uncertainties since they obtain the prediction explanation in a post-hoc and model-agnostic manner without considering the randomness of graph data and model parameters. To address the above problems, this paper proposes a novel uncertainty quantification framework for GNN explanations. For mitigating the randomness of graph data in the explanation, our framework accounts for two distinct data uncertainties, allowing for a direct assessment of the uncertainty in GNN explanations. For mitigating the randomness of learned model parameters, our method learns the parameter distribution directly from the data, obviating the need for assumptions about specific distributions. Moreover, the explanation uncertainty within model parameters is also quantified based on the learned parameter distributions. This holistic approach can integrate with any post-hoc GNN explanation methods. Empirical results from our study show that our proposed method sets a new standard for GNN explanation performance across diverse real-world graph benchmarks.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that can interfere with the endocrine system and cause liver damage. However, the molecular mechanism of DEHP-induced liver injury is unclear. This study aimed to investigate the effects of DEHP on liver function and its relationship with thioredoxin-interacting protein (TXNIP) and mitochondrial oxidative stress pathway. We used C57BL/6 J mice and THLE-2 liver cells as in vivo and in vitro models, respectively, and treated them with different doses of DEHP, and measured the relevant biochemical indicators and molecular markers. We found that DEHP significantly increased the expression of TXNIP and NLRP3, while decreasing the expression of mitochondrial functional proteins, such as PGC-1α, TFAM, NRF1, NDUHA9, SDHA, MFN1. This resulted in mitochondrial dysfunction, manifested by reduced ATP generation, increased inflammatory factor release, elevated liver enzyme indicators, decreased mitochondrial membrane potential and increased oxidative stress. We further demonstrated that TXNIP upregulation activated NF-κB and MAPK signaling pathways, such as NF-κB, IκB, TAB2, TRAF6, ERK1, JNK, p38 MAPK, MEK1, which exacerbated oxidative stress and inflammation, leading to liver damage. Additionally, we found that treatment with the antioxidant MitoQ partially alleviated DEHP-induced liver toxicity, while silencing TXNIP more effectively restored mitochondrial function. Our study supports the hypothesis that DEHP induces mitochondrial oxidative stress through the TXNIP signaling pathway, resulting in liver dysfunction in mice, and suggests possible links between endocrine-disrupting chemicals and human diseases.

The in vivo absorption of nanocarriers is a complex process, which is affected by the bioabsorption barrier. It is doubtful whether nanopreparations can promote the absorption and utilization of bioactive molecules. In this study, soy protein isolate (SPI) was used to prepare plant-based nanocarriers encapsulating β-carotene, and an in vitro digestion model was employed to investigate the structural changes of β-carotene loaded soy protein isolate nanoparticles (BC-SPIs) during digestion. Additionally, the Caco2 cell transport model was used to explore the impact mechanism of digestion conditions on the transmembrane transport of BC-SPIs after digestion. Furthermore, a Caco2-HT29 co-culture model containing a mucus layer was used to investigate the permeability of BC-SPIs through the mucus layer before and after digestion. This study found that before digestion, BC-SPIs could be directly absorbed by the Caco-2 cell monolayer through clathrin- and caveolin-dependent endocytosis. After in vitro simulated digestion, the size of BC-SPIs increased, and they could be directly absorbed by cells through clathrin-dependent endocytosis, caveolin-dependent endocytosis and macropinocytosis. The digested nanoparticles carried more negative charge, resulting in a 1.48-fold enhancement in the ability to cross the mucus layer and a 1.56-fold increase in the transmembrane transport efficiency of β-carotene. This study clarified the different absorption pathways of BC-SPIs before and after digestion and revealed the interaction between BC-SPIs and bile salts under simulated digestion conditions and the contribution of increasing the size of BC-SPIs to their transport and absorption efficiency by cells. These findings lay a theoretical foundation for further improving the application potential of nanocarriers in bioavailability enhancement, which will help advance the development of nanotechnology in several fields such as pharmaceuticals and health products.

Abstract Background Increasing evidence shows that bone turnover markers (BTMs) and vitamin D can affect human cognitive function. However, there are few studies that have investigated the association between BTMs and cognitive function in chronic schizophrenia patients. The aim of this study was to investigate the relationship between BTMs and cognitive function in chronic schizophrenia patients with or without vitamin D insufficiency (VDI). Methods In all, 118 chronic schizophrenia patients were enrolled in this cross-sectional study. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was applied to evaluate the cognitive function of the subjects. Blood analysis included bone turnover markers, vitamin D levels, and glycolipid levels. Results Relative to 72 vitamin D-sufficient (VDS) patients, 46 VDI patients had higher bone resorption markers levels and lower bone formation markers levels. Regression analysis showed that, in the total sample, CTX and language function exhibited independent positive correlation (p = 0.027, R2 change = 0.042), and in the VDS group, procollagen type I N-terminal propeptide (PINP) was independently negatively correlated with language function (p = 0.031, R2 change = 0.065), while the positive correlation between osteopontin (OPN) and delayed memory remained in the VDI group (p = 0.036, R2 change = 0.083). Conclusion Our study showed an association between the levels of BTMs and cognitive function among chronic schizophrenia patients. This correlation may have different mechanisms of action at different vitamin D levels.

Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease with various immune system manifestations, showing a global trend of increased prevalence. AIH is diagnosed through histological abnormalities, clinical manifestations, and biochemical indicators. The biochemical markers involve interfacial hepatitis, transaminase abnormalities, positive autoantibodies, etc. Although AIH pathogenesis is unclear, gene mutations and immunological factors could be the leading factors. AIH usually presents as a chronic liver disease and sometimes as acute hepatitis, making it challenging to distinguish it from drug-related hepatitis due to similar clinical symptoms. Normalizing transaminases and serum IgG levels is essential in assessing the remission status of AIH treatment. Glucocorticoids and azathioprine are the first-line AIH treatment, with lifelong maintenance therapy in some patients. The quality of life and survival can be improved after appropriate treatment. However, certain limitations jeopardize the quality of treatment, including long treatment cycles, side effects, poor patient compliance, and inability to inhibit liver fibrosis and cirrhosis. Accurate AIH animal models will help us understand the pathophysiology of the disease while providing fresh perspectives for avoiding and treating AIH. This review will help us understand AIH better, from the cellular and molecular causes to the clinical features, and will provide insight into new therapy techniques with fewer side effects.

Objective The proper selection of the lower instrumented vertebra (LIV) remains controversial in the surgical treatment of Scheuermann's disease and there is a paucity of studies investigating the clinical outcomes of fusion surgery when selecting the vertebra one level proximal to the sagittal stable vertebra (SSV‐1) as LIV. The purpose of this study is to investigate whether SSV‐1 could be a valid LIV for Scheuermann kyphosis (SK) patients with different curve patterns. Methods This was a prospective study on consecutive SK patients treated with posterior surgery between January 2018 and September 2020, in which the distal fusion level ended at SSV‐1. The LIV was selected at SSV‐1 only in patients with Risser >2 and with LIV translation less than 40 mm. All of the patients had a minimum of 2‐year follow‐up. Patients were further grouped based on the sagittal curve pattern as thoracic kyphosis (TK, n = 23) and thoracolumbar kyphosis (TLK, n = 13). Radiographic parameters including global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis (SVA), LIV translation, pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured preoperatively, postoperatively, and at the latest follow‐up. The intraoperative and postoperative complications were recorded. The Scoliosis Research Society (SRS)‐22 scores were performed to evaluate clinical outcomes. Results A total of 36 patients were recruited in this study, with 23 in the TK group and 13 in the TLK group. In TK group, the GK was significantly decreased from 80.8° ± 10.1° to 45.4° ± 7.7° after surgery, and was maintained at 45.3° ± 8.6° at the final follow‐up. While in the TLK group, GK was significantly decreased from 70.7° ± 9.2° to 39.1° ± 5.4° after surgery (p 2 and LIV translation less than 40 mm.

Researching and developing a new type of diaphragm wall foundation can solve the probl em that the traditional diaphragm wall structure may not meet the high standards of safety and stability of underground structures in some specific engineering environments. This paper focuses on the horizontal bearing characteristic of a new form of foundation, a strip-walled underground diaphragm wall, through a series of model tests. In the tests, nine plexiglass models with different section sizes, wall spacings and wall heights, as well as loading strategies (horizontal loads along and against the wall in the model), were conducted. The influence of the above factors on the horizontal bearing performance of the foundation and the soil resistance distribution around the wall was studied. The results show that when the horizontal load applied along the wall is greater than 50 N, the growth rate of total displacement at the top of the wall gradually decreases; when a horizontal load is applied against the wall, with a uniform change in wall height, the optimal wall spacing is 11 cm. When the same displacement occurs, the bearing performance of the model under the former loading strategy is generally 10% higher than that under the later loading strategy. In addition, the depth where the maximum bending moment along the wall occurred gradually moves downward with the increase in horizontal load, and the increase in wall spacing and wall height has a positive effect on the horizontal bearing characteristic. With the application of load, the maximum bending moment of the wall will gradually decrease along the depth. The increase in wall spacing and wall height can improve the overall flexural stiffness and horizontal bearing performance of the foundation. Lastly, the group wall effect coefficient, β, is put forward, and a simplified formula for calculating the horizontal bearing capacity of a strip wall foundation is proposed. In the formula, β is negatively correlated with the buried depth of the wall and positively correlated with the distance between the walls, and its coefficient is greater than 1.

Starch and protein are two important components in food system. The interactions between starch and protein have important influence on the structure, physicochemical properties of starch and the texture and digestibility of starch-based food. In recent years, the effect of exogenous protein on starch-protein interaction in mixed system and its application have become a hot research topic in the field of food. This article reviews the interaction mode between starch and protein, the effect of protein on physicochemical properties （gelatinization properties, retrogradation properties, rheological properties, thermal properties and texture properties） and microstructure of starch-protein mixed system, summarizes the regulation effect of protein on digestibility of starch in mixed system and its mechanism, and presents the application of the mixed system in food processing, aiming to clarify the mechanism of interactions between starch and protein and provide theoretical reference for the research and development of starch-based food.

Abstract Background White matter hyperintensities, a neuroimaging marker of small-vessel cerebrovascular disease and apolipoprotein ε4 (APOE4) allele, are important dementia risk factors. However, APOE4 as a key effect modifier in the relationship between white matter hyperintensities and grey matter volume needs further exploration. Methods One hundred ninety-two early-stage dementia (including mild cognitive impairment and mild dementia) and 259 cognitively unimpaired participants from a neurocognitive research cohort with neuroimaging data, APOE genotyping, and neuropsychological assessments were studied. We investigated independent and interactive effects of white matter hyperintensities and APOE4 on whole-brain voxel-wise grey matter volume using voxel-based morphometry (uncorrected p

The membrane frizzled-related protein (Mfrp) and C1-tumor necrosis factor related protein 5 (Ctrp5) genes are transcribed as a bicistronic unit and dysregulation of either gene is associated with retinal degeneration in the retinal pigment epithelium (RPE) cells. However, the mechanisms that regulate the expression of the bicistronic transcript remain controversial. Here, we identified a microRNA-based negative feedback loop that helps maintain a normal expression level of the bicistronic Mfrp and Ctrp5 transcript. Specifically, miR-149-3p, a conserved microRNA, binds to the 3′UTR of the Mfrp gene. In MFRP-deficient rd6 mice, the miR-149-3p levels were compromised compared with those in WT mice, resulting in an increase in the bicistronic transcript. We also report a capsid-modified rAAVDJ-3M vector that is capable of robustly and specifically transducing RPE cells following subretinal delivery. Compared with the parental vector, the modified vector elicited similar levels of serum anti-rAAV antibodies, but recruited fewer microglial infiltrations. Most significantly, we also demonstrate that simultaneous overexpressing of MFRP and knockdown of the bicistronic transcript was more effective in rescuing vision than MFRP overexpression alone. Our findings offer new insights into the function of MFRP and provide a promising therapeutic strategy for the treatment of MFRP-associated ocular diseases.

In recent years, with the full implementation and steady advancement of the rural revitalization strategy, the topic of young college students and the construction of rural civilization has become a popular research direction. In this paper, we summarize the information collected in the previous period, design a questionnaire for young college students to participate in the construction of rural culture in ethnic areas, and test the reliability of the questionnaire by combining the KMO value and Cronbach’s alpha coefficient. The questionnaire was designed to be distributed to Yulin Normal College to collect relevant data, and the survey data was statistically analyzed using Excel and SPSS software. The survey results showed that only about half of the college students surveyed participated in the construction of rural culture in ethnic areas. The number of young college students who expressed general concern for the construction of rural culture was 264, which indicates that their participation level was not high. The survey and analysis of the influencing factors found that the employment mentality of the personal factors and the extra points or priority admission policy of the institutional factors have a greater influence on the participation of young college students in the construction of rural culture in ethnic areas. The paper establishes a basis for improving the participation of college students in rural culture construction, and the countermeasure program proposed for the survey results serves as a reference for relevant government departments.

BackgroundThere is a growing amount of evidence suggesting that immunity and inflammation play an important role in the pathophysiology of schizophrenia. In this study, we aimed to examine the relationship between hematological and inflammatory markers with symptom severity in Han Chinese patients with drug-free schizophrenia.MethodsThis retrospective study was conducted at Chaohu Hospital of Anhui Medical University and data were extracted from the electronic medical record system over a 5-year period (May 2017 to April 2022), including participants’ general and clinical information as well as Brief Psychiatric Rating Scale (BPRS) scores and hematological parameters.ResultsA total of 2,899 patients with schizophrenia were identified through the initial search. After screening, 91 patients and 141 healthy controls (HCs) were included. The patients had a higher value of neutrophils/lymphocytes ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) than HCs (all P < 0.001). MLR was positively correlated with BPRS total score (r = 0.337, P = 0.001) and resistance subscale score (r = 0.350, P = 0.001). Binary logistic regression analyses revealed that severely ill was significantly associated with being male and a higher value of MLR (Natural Logaruthm, Ln) (all P < 0.05), and the receiver operating characteristic (ROC) analysis showed good performance of a regression model with an area under the curve (AUC) value of 0.787.ConclusionPatients with drug-free schizophrenia have an unbalanced distribution of peripheral blood granulocytes, and elevated NLR, MLR and PLR. Patients with higher value of MLR tend to have more psychotic symptoms, especially those symptoms of hostility, uncooperativeness, and suspiciousness. Our study gives a preliminary indication that MLR is a potential predictor of disease severity in patients with drug-free schizophrenia.

Problem: Unhealthy dietary habits and inadequate existing treatment technologies have led to high morbidity and mortality rates in patients with gastric cancer, and the research shows that curcumin has excellent antitumor properties, however, the non-water-soluble characteristic of curcumin limits its applications. To break the limitation, the targeted drug carriers become the urgent need to treat gastric cancer. Method: The heterogeneous magnetic α-Fe2O3/Fe3O4 nanoparticles were obtained by rapid combustion method with citric acid (CA) and ferric nitrate as raw materials and anhydrous ethanol as solvent and fuel, and then modified with citric acid (CA) and chitosan (CTS), and loaded curcumin (Cur) to form α-Fe2O3/Fe3O4-CA-CTS-Cur nanosystem. Results: The particle sizes of heterogeneous magnetic α-Fe2O3/Fe3O4 nanoparticles and α-Fe2O3/Fe3O4-CA-CTS-Cur nanosystem were 24.9 nm and 35.6 nm, respectively, and their respective saturation magnetization were 70.9 emu/g and 30.3 emu/g. The magnetic α-Fe2O3/Fe3O4-CA-CTS-Cur nanosystem had good stability, excellent drug release rate, and enhanced apoptosis to gastric cancer cells (SGC-7901) through the caspase pathway and ferroptosis of cells. Conclusions: The magnetic drug delivery nanosystem was successfully constructed, and revealed significant inhibitory and killing effects on SGC-7901 cells, and low toxic and side effects on normal cells.

In various analytical models, modeling the behavior of large-diameter monopiles and piles can be challenging due to these foundations with huge body sizes carrying mechanisms of lateral loads to the surrounding soils. In this paper, the transfer matrix method with the Timoshenko beam theory was used to modify the shear rotation of pile sections under different loading stages, including serviceability limit stages and the ultimate loading stage. In this transfer matrix method, a large-diameter pile is considered according to the Timoshenko beam theory, and the recurring variables in the matrix equation are replaced with constants to simplify the calculation steps. Two model test cases were used to verify the accuracy of the method. Then, a series of comparisons between the Timoshenko beam and the Euler–Bernoulli beam theories, with the relative pile–soil stiffness being equal to 0.15, 0.45, and 0.75, was conducted to investigate the differences in pile response after considering the shear deformation. The results show that the effect of shear deformation of large-diameter piles changes with different loading levels. The values of the pile deformation based on the Timoshenko beam theory divided by those of that based on the Euler–Bernoulli beam theory were in the range of 1.0 to 1.10, and they increased slightly with increasing loads, reaching their maximum value, and then rapidly decreased to 1.0 when close to the ultimate lateral load; the maximum value was influenced by the relative pile–soil stiffness. Furthermore, the ratio of the shear rotation of the pile section to the slope of the deflection curve was in the range of 1.0 to 1.10; these also showed similar but more moderate trends compared with the values of pile deformation based on the Timoshenko beam theory divided by those of that based on the Euler–Bernoulli beam theory.

We present a case of 80 years woman chronic smoker (10 cigarettes)/ per day for 50 years diagnosed with adenocarcinoma in the upper left lobe of her lungs in a geriatric clinic. She has no history of diabetes but taking medicine for hypertension and dyslipidemia. She was admitted and operated on for partial pneumonectomy and discharged after 11 days of care with all essential drugs, and instructions. After 4 weeks of treatment, she complained of unusual polyuria, diagnosed in the department of Geriatrics, Zhongnan Hospital of Wuhan University, China.

Objective: This study aimed to control the degree of crosslinking and etherification in the preparation process of crosslinked hydroxypropyl starch and improve the product performance. Methods: Waxy corn starch was used as a raw material to prepare the composite modified starch （hydroxypropyl distarch phosphate, HDP） under alkaline conditions, during which process sodium trimetaphosphate （STMP） and propylene oxide （PO） was used as the cross-linker and etherifying agent, respectively. The effects of the addition level of STMP and PO on the properties of the Brabender viscosity behavior, transparency and freeze-thaw stability of waxy corn starch were investigated. Results: Combined with the preliminary laboratory exploration and the optimization of this study, a HDP with improved thermal stability, transparency and freeze-thaw stability and lowered gelatinization temperature was obtained. The preparation conditions of HDP were as follows: in the case that the amount of sodium trimetaphosphate was 0.30 g/100 g and cross-linking reaction time was 45 minutes, and the amount of propylene oxide added was 6 mL/100 g and the etherification time was 90 minutes. Conclusion: Compared to raw waxy corn starch, the cross-linked and etherified starches with decreased gelatinization temperature and improved freeze-thaw stability, thermal stability and gelling properties are observed.

The occurrence of emerging environmental pollutants brings new challenges to food safety in China, which needs to be systematically researched. This study focused on the distribution, hazard characteristics, and sources of antibiotics, endocrine disrupting chemicals (EDCs), perfluorinated compounds (PFCs), and microplastics (MPs) in major foods such as vegetables, fruits, grains, meat, aquatic products, eggs, and milk. It was found that fluoroquinolones showed a high detection rate in aquatic products, vegetables, and milk. Fluoroquinolones were mainly derived from the use of agricultural and veterinary drugs. Bisphenol A (one of phenolic EDCs) was frequently detected in canned food and aquatic products, and nonylphenol was mostly detected in aquatic products. Both EDCs were mainly from food packages. PFCs possessed a high detection rate in aquatic products, livestock meat, poultry meat, and eggs. PFCs were mainly from wastewater treatment plants and food packages. MPs showed a very high detection rate in aquatic products, which were mainly imported by contaminated environmental media. Ingestion of environmental emerging pollutants through food may lead to disease risk of human. Thus, it is recommended to monitor more types of emerging environmental pollutants in the scope of food safety, systematically plan the scientific rules of usage of the chemicals, and formulate a multi-departmental joint management and control mechanism to better cope with the issue of food safety caused by emerging environmental pollutants and effectively ensure food safety.

Abstract Objectives To study the correlations between facial profile markers and crown-lump length (CRL) in a Chinese population, and to evaluate the clinical value of these markers for abnormal fetuses during the first trimester (11 to 13+6 gestational weeks). Methods The facial profile markers were as followings: inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA), frontal space (FS) distance and profile line (PL) distance. These markers were measured in facial mid-sagittal section through ViewPoint 6 software. The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic (ROC) curves. Results According to the first-trimester scanning (FTS) and follow-up, 31 fetuses were enrolled in the abnormal group, including 14 cases of trisomy 21, 7 cases of trisomy 18, 10 cases with cleft lip and palate (CLP), and 1000 normal fetuses were selected. Among the normal fetuses, the IFA, FS distance and PL distance had negative correlations with CRL. The MNM angle and FMA had positive correlations with CRL. The mean IFA values for fetuses with trisomy 21 and trisomy 18 were 74.11° (standard deviation (SD) 7.48) and 69.88° (SD 7.08), respectively, which were significantly smaller than the normal fetuses (p = 0.013; p = 0.003). The mean MNM angle of fetuses with trisomy 18 and CLP were 6.98° (SD 2.61) and 9.41° (SD 2.57), respectively, which were significantly greater than the normal fetuses (p = 0.005; p

Abstract Objective The objective of this research was to study the clinical features, genetic characteristics, muscle imaging, and muscle pathological changes of a cohort of Chinese patients with mutations in the valosin‐containing protein (VCP) gene. Methods Nine patients from seven Chinese pedigrees were recruited. Variants were detected by next‐generation sequencing and confirmed by Sanger sequencing. Thigh muscle MRIs were performed in five patients. All the patients received muscle biopsies. Results Seven variants in VCP were identified, and two were novel. All the patients presented with adult‐onset muscle weakness. The appearance of “isolated island sign” or “contra‐isolated island sign” was observed in four of the five the patients on muscle MRIs. Muscle biopsies demonstrated the combination of neuropathic and myopathic changes in seven patients and muscle dystrophic changes in two patients. Notably, rimmed vacuoles and cytoplasmic VCP and p62‐positive protein aggregates were observed in all the patients. Conclusion Our finding of novel variants expanded the mutational spectrum of the VCP gene. This cohort of Chinese patients with VCP mutations mainly present with inclusion body myopathy with predominant limb–girdle distribution. The characteristic pattern of fatty infiltration, especially the “isolated island” and “contra‐isolated island” on muscle MRI, along with rimmed vacuoles in muscle biopsy, provides valuable clues for guiding genetic diagnostic workup.

BackgroundBrain atrophy represents a final common pathway for pathological processes in patients with cerebral small vessel disease (CSVD) and is now recognized as a strong independent predictor of clinical status and progression. The mechanism underlying brain atrophy in patients with CSVD is not yet fully comprehended. This study aims to investigate the association of morphologic features of intracranial distal arteries (A2, M2, P2 and more distal) with different brain structures [gray matter volume (GMV), white matter volume (WMV), and cerebrospinal fluid volume (CSFV)]. Furthermore, we also examined whether a correlation existed between these cerebrovascular characteristics and GMV in different brain regions.MethodA total of 39 participants were eventually enrolled. The morphologic features of intracranial distal arteries based on TOF-MRA were extracted and quantified using the intracranial artery feature extraction technique (iCafe). The brain 3D-T1 images were segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using the “Segment” tool in CAT12 for the voxel-based morphometry (VBM) analysis. Univariable and multivariable linear regression models were used to investigate the relationship between these cerebrovascular features and different brain structures. Partial correlation analysis with a one-tailed method was used to evaluate the relationship between these cerebrovascular features and GMV in different brain regions.ResultsOur findings indicate that both distal artery length and density were positively correlated with GM fraction in CSVD patients, regardless of whether univariable or multivariable linear regression analyses were performed. In addition, distal artery length (β = −0.428, p = 0.007) and density (β = −0.337, p = 0.036) were also found to be negative associated with CSF fraction, although this relationship disappeared after adjusting for potential confounders. Additional adjustment for the effect of WMHs volume did not change these results. In subgroup anasysis, we found that participants in the highest distal artery length tertile had significantly higher GM fraction and lower CSF fraction level than participants in the lowest distal artery length tertile. In partial correlation analysis, we also found that these cerebrovascular characteristics associated with regional GMV, especially subcortical nuclear.ConclusionThe morphologic features of intracranial distal arteries, including artery length, density and average tortuosity, measured from 3D-TOF MRA, are associated with generalized or focal atrophy indexes of CSVD.

The material undergoes high temperature and high strain rate deformation process during the cutting process, which may induce the dynamic recrystallization behavior and result in the evolution of dynamic mechanical properties of the material to be machined. In this paper, the modified Johnson-Cook (J-C) model for nickel-based powder metallurgy superalloy considering dynamic recrystallization behavior in high strain rate and temperature is proposed. The dynamic mechanical properties of the material under different strain rates and temperature conditions are obtained by quasi-static compression test and split Hopkinson pressure bar (SHPB) test. The coefficients of the modified J-C model are obtained by the linear regression method. The modified model is verified by comparison with experimental and model prediction results. The results show that the modified J-C model proposed in this paper can accurately describe the mechanical properties of nickel-based powder metallurgy superalloys at high temperatures and high strain rates. This provides help for studying the cutting mechanism and finite element simulation of nickel-based powder metallurgy superalloy.

Muconic acid is a platform chemical with wide industrial applicability. Here, the authors report efficient muconate production from glucose and xylose by engineered Pseudomonas putida strain using adaptive laboratory evolution, metabolic modeling, and rational strain engineering strategies.

Objectives As a new pelvic fixation technique, the dual S2AI screws fixation technique could provide highly stable distal strength, and have wide clinical prospect in the correction of severe kyphoscoliosis. However, the ideal trajectory parameters, indications and clinical outcomes of this technique have not been reported so far. This study aimed to determine the anatomical parameters of dual S2AI screws in the normal Chinese adult population, investigating the indications of this technique and evaluating the feasibility and clinical outcomes. Methods Fifteen males and 15 females with normal pelvis underwent a pelvic CT scan to determine ideal dual S2AI screws trajectories. Sagittal angle (SA), transverse angle (TA), maximal length (ML), sacral length, and skin distance were measured. Subsequently, we retrospectively reviewed the data of 16 patients (seven males and nine females) who underwent dual S2AI screw fixation and 23 patients who underwent single S2AI screw fixation between January 2014 and December 2019. Preoperative, postoperative, and latest follow‐up measurements of Cobb angle, coronal balance (CB), spinal pelvic obliquity (SPO), and regional kyphosis (RK) were obtained. The mean follow‐up time was 16.7 ± 7.1 months (range: 12–30 months). Independent t‐test was used to determine the difference in the analysis of the trajectories. The paired sample non‐parametric Wilcoxon test was performed to assess the changes in radiographic parameters between different time points and different groups. Results For both male and females, the proximal S2AI screws had significantly higher TA and ML, but a lower SA than distal screws. Females showed significantly more caudal (SA: 25.03° ± 2.32° vs. 29.82° ± 2.47°, t = 7.742, P

Abstract COVID-19, caused by SARS-CoV-2, is the most consequential pandemic of this century. Since the outbreak in late 2019, animal models have been playing crucial roles in aiding the rapid development of vaccines/drugs for prevention and therapy, as well as understanding the pathogenesis of SARS-CoV-2 infection and immune responses of hosts. However, the current animal models have some deficits and there is an urgent need for novel models to evaluate the virulence of variants of concerns (VOC), antibody-dependent enhancement (ADE), and various comorbidities of COVID-19. This review summarizes the clinical features of COVID-19 in different populations, and the characteristics of the major animal models of SARS-CoV-2, including those naturally susceptible animals, such as non-human primates, Syrian hamster, ferret, minks, poultry, livestock, and mouse models sensitized by genetically modified, AAV/adenoviral transduced, mouse-adapted strain of SARS-CoV-2, and by engraftment of human tissues or cells. Since understanding the host receptors and proteases is essential for designing advanced genetically modified animal models, successful studies on receptors and proteases are also reviewed. Several improved alternatives for future mouse models are proposed, including the reselection of alternative receptor genes or multiple gene combinations, the use of transgenic or knock-in method, and different strains for establishing the next generation of genetically modified mice.

The tumors of central nervous system refer to a group of benign and malignant diseases originating from tissues or structures within the central nervous system. Common tumors of central nervous system are sporadic, but a few have familial onset. Compared with sporadic brain tumors, the clinical symptoms, diagnostic ideas and follow-up review plans of familial brain tumors are more complicated. The multidisciplinary diagnosis and treatment (MDT) mode usually refers to a treatment mode in which a case involving multiple organs and systems is discussed, and the best treatment plan is formulated for the patient based on the comprehensive opinions of various disciplines. Because familial brain tumors often involve multiple organs, multiple disciplines and multiple systems, and their low incidence leads to less clinical experience for neurosurgeons, the MDT model is more conducive to efficient diagnosis, treatment and management of familial brain tumors. This review elaborates on the neurosurgeon-led MDT model, and introduces the latest research on the epidemiology, genetic characteristics, clinical manifestations, diagnostic ideas and multidisciplinary management of familial brain tumors.

China was the first country suffering from the SARS-CoV-2 pandemic and one of the countries with stringent mother-neonate isolation measure implemented. Now increasing evidence suggests that coronavirus disease 2019 (COVID-19) should not be taken as an indication for formula feeding or isolation of the infant from the mother.

Abstract Background Ring chromosomes can be formed by terminal breaks of two arms of a chromosome and their rejoining, leading to a loss of genetic material. They may also be formed by telomere-telomere fusions with no deletion, resulting in the formation of a complete ring. Mosaic X-ring chromosomes are extremely rare and have highly variable phenotypes. Here, we report a case with a mosaic X-ring chromosome in a patient with Turner syndrome, and we illustrate the unreported complicated mechanism using chromosome analysis and fluorescence in situ hybridization (FISH). Case presentation A 10-year-old girl of short stature presenting Turner syndrome was admitted to our hospital. The patient’s clinical characteristics were subsequently documented. Genetic analysis showed a karyotype of mostly 45,X[140]/46,X,r(X)[60]. The X ring chromosome was cytogenetically characterized as 45,X/46,X,r(X)(p22.32q21.1), with a length of approximately 74 Mb. Conclusions Taken together, we report a rare case with a mosaic X ring chromosome in Turner syndrome and we believe this case expands our collective knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling for Turner syndrome.

Duplication of the genome requires the replication apparatus to overcome a variety of impediments, including covalent DNA adducts, the most challenging of which is on the leading template strand. Replisomes consist of two functional units, a helicase to unwind DNA and polymerases to synthesize it. The helicase is a multi-protein complex that encircles the leading template strand and makes the first contact with a leading strand adduct. The size of the channel in the helicase would appear to preclude transit by large adducts such as DNA: protein complexes (DPC). Here we discuss some of the extensively studied pathways that support replication restart after replisome encounters with leading template strand adducts. We also call attention to recent work that highlights the tolerance of the helicase for adducts ostensibly too large to pass through the central channel.

Abstract Batteries are of paramount importance for the energy storage, consumption, and transportation in the current and future society. Recently machine learning (ML) has demonstrated success for improving lithium-ion technologies and beyond. This in-depth review aims to provide state-of-art achievements in the interdisciplinary field of ML and battery research and engineering, the battery informatics. We highlight a crucial hurdle in battery informatics, the availability of battery data, and explain the mitigation of the data scarcity challenge with a detailed review of recent achievements. This review is concluded with a perspective in this new but exciting field.

Abstract TRK-fused gene (TFG) is known to be involved in protein secretion and plays essential roles in an antiviral innate immune response. However, its function in LPS-induced inflammation and pyroptotic cell death is still unknown. Here, we reported that TFG promotes the stabilization of Unc-51 like autophagy activating kinase (ULK1) and participates in LPS plus nigericin (Ng) induced pyroptotic cell death. Our results showed that TFG-deficient THP-1 macrophages exhibit higher mitochondrial ROS production. LPS/Ng stimulation triggers a much higher level of ROS and induces pyroptotic cell death. ULK1 undergoes a rapid turnover in TFG-deficient THP-1 cells. TFG forms complex with an E3 ligase, tumor necrosis factor receptor-associated factor 3 (TRAF3), and stabilizes ULK1 via disturbing ULK1-TRAF3 interaction. Knockdown of TFG facilitates the interaction of ULK1 with TRAF3 and subsequent K48-linked ULK1 ubiquitination and proteasome degradation. Rescue of ULK1 expression blocks LPS/Ng-induced cell death in TFG-deficient THP-1 macrophages. Taken together, TFG plays an essential role in LPS/Ng-induced pyroptotic cell death via regulating K48-linked ULK1 ubiquitination in macrophages.

Uterine leiomyoma (ULM) is a kind of gene-involved benign tumor, which is located in the front of female reproductive tract. It is one of the most common reproductive tract tumors in women, which leads to abnormal menstruation, repeated pregnancy loss, and other serious gynecological diseases. Recently, microRNAs (miRNAs) have attracted much more attention in the process of exploring the molecular mechanisms of tumorigenesis. Furthermore, the deregulated miRNAs had been reported to play important roles in ULM pathology.

Brain damage caused by small vessel disease (SVD) differs between males and females. We aimed to examine the pure sex-specific neuroanatomical mechanisms of SVD adjusted for voxel-based expected effects of age and sex on healthy brain volume. Thirty-one female and 32 male genetic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL) patients and 55 sex- and age-matched healthy controls (HCs) underwent 7-Tesla MRI examinations. Voxel-based W-score maps were calculated from volumes and deformations of brain tissues, controlling for the expected effects of age and sex in HCs. Significant cognitive declines in working memory and executive function were identified in male CADASIL patients compared to female patients. Greater gray matter (GM) atrophy was found in the bilateral orbitofrontal cortex (OFC), left anterior cingulate cortex (ACC), left entorhinal cortex (EC), and right temporooccipital cortex in male CADASIL patients than in females. Working memory was associated with volumes in the right OFC specific to female CADASIL patients, whereas visuospatial ability was associated with the right hOcl (primary visual area, BA 17) volume specific to males. The current findings indicate that sex affects the pathogenesis of CADASIL, ranging from differences in neuroanatomy to those in behavioral performance, which may facilitate the development of more effective sex-specific therapeutic strategies for CADASIL and SVD.

Abstract Background With the development of tissue engineering, enhanced tendon regeneration could be achieved by exploiting suitable cell types and biomaterials. The accessibility, robust cell amplification ability, superior tendon differentiation potential, and immunomodulatory effects of human periodontal ligament stem cells (hPDLSCs) indicate their potential as ideal seed cells for tendon tissue engineering. Nevertheless, there are currently no reports of using PDLSCs as seed cells. Previous studies have confirmed the potential of silk scaffold for tendon tissue engineering. However, the biomimetic silk scaffold with tendon extracellular matrix (ECM)-like structure has not been systematically studied for in situ tendon regeneration. Therefore, this study aims to evaluate the effects of hPDLSCs and biomimetic silk scaffold on in situ tendon regeneration. Methods Human PDLSCs were isolated from extracted wisdom teeth. The differentiation potential of hPDLSCs towards osteo-, chondro-, and adipo-lineage was examined by cultured in different inducing media. Aligned and random silk scaffolds were fabricated by the controlled directional freezing technique. Scaffolds were characterized including surface structure, water contact angle, swelling ratio, degradation speed and mechanical properties. The biocompatibility of silk scaffolds was evaluated by live/dead staining, SEM observation, cell proliferation determination and immunofluorescent staining of deposited collagen type I. Subsequently, hPDLSCs were seeded on the aligned silk scaffold and transplanted into the ruptured rat Achilles tendon. Scaffolds without cells served as control groups. After 4 weeks, histology evaluation was carried out and macrophage polarization was examined to check the repair effects and immunomodulatory effects. Results Human PDLSCs were successfully isolated, and their multi-differentiation potential was confirmed. Compared with random scaffold, aligned silk scaffold had more elongated and aligned pores and promoted the proliferation and ordered arrangement of hPDLSCs. After implantation into rat Achilles tendon defect, hPDLSCs seeded aligned silk scaffold enhanced tendon repair with more tendon-like tissue formation after 4 weeks, as compared to the scaffold-only groups. Higher expression of CD206 and lower expression of iNOS, IL-1β and TNF-α were found in the hPDLSCs seeded aligned silk scaffold group, which revealed its modulation effect of macrophage polarization from M1 to M2 phenotype. Conclusions In summary, this study demonstrates the efficacy of hPDLSCs as seed cells and aligned silk scaffold as a tendon-mimetic scaffold for enhanced tendon tissue engineering, which may have broad implications for future tendon tissue engineering and regenerative medicine researches.

The major challenge of recombinant adeno-associated virus (rAAV) vectors is host immunological barriers. Compared to the neutralizing antibody and the cytotoxic T lymphocyte response, the host immune responses induced by unsatisfactory rAAV manufacturing were largely ignored previously. rAAV vector production usually requires large amounts of plasmid DNAs. The DNA are commonly isolated from the DH5α bacterial strain, which contains lipopolysaccharide (LPS) contamination. LPS, also named endotoxin, in plasmid DNA is intractable, and residual endotoxin in the subsequent rAAV vectors may result in substantial host immune response. Recently, a ClearColi K12 bacterial strain is commercially available, with genetically modified LPS that does not trigger endotoxic response in mammalian cells. Here, we produced rAAV-DJ vectors by plasmids yielded from either DH5α or ClearColi K12 bacterial strains. Our data indicated that the ClearColi K12 strain had satisfactory protection for the rAAV inverted terminal repeat (ITR) sequence. As expected, the ClearColi K12-derived rAAV-DJ vectors had lower endotoxin levels. The physical and biological equivalency of the purified viral stocks were confirmed by electron micrographs, Coomassie blue staining, and transduction assays. Most importantly, the ClearColi K12-derived rAAV-DJ vectors triggered reduced nuclear factor-kappa B (NF-κB) signaling pathway both in cell cultures in vitro and in C57BL/6 mice retinas in vivo. We believe that the use of the ClearColi K12 bacterial strain could eliminate the LPS in the purified vector stock at the source. Our data indicate its promising use in future clinical development.