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Abstract Background The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE. Methods A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed. Results A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P

Abstract O6-methylguanine-DNA methyltransferase (MGMT) has been demonstrated to be an important prognostic and predictive marker in glioblastoma (GBM). To establish a reliable radiomics model based on MRI data to predict the MGMT promoter methylation status of GBM. A total of 183 patients with glioblastoma were included in this retrospective study. The visually accessible Rembrandt images (VASARI) features were extracted for each patient, and a total of 14676 multi-region features were extracted from enhanced, necrotic, “non-enhanced, and edematous” areas on their multiparametric MRI. Twelve individual radiomics models were constructed based on the radiomics features from different subregions and different sequences. Four single-sequence models, three single-region models and the combined radiomics model combining all individual models were constructed. Finally, the predictive performance of adding clinical factors and VASARI characteristics was evaluated. The ComRad model combining all individual radiomics models exhibited the best performance in test set 1 and test set 2, with the area under the receiver operating characteristic curve (AUC) of 0.839 (0.709–0.963) and 0.739 (0.581–0.897), respectively. The results indicated that the radiomics model combining multi-region and multi-parametric MRI features has exhibited promising performance in predicting MGMT methylation status in GBM. The Modeling scheme that combining all individual radiomics models showed best performance among all constructed moels.

Abstract The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1–4 (L1–L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P

Abstract Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Backgrounds: The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved. Materials and methods: In animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L4-5 DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth. Results: Three days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L4-6 DRG and the lumbosacral enlargement (P

Abstract Background Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. Methods This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. Results No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483–3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987–1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999–1.011, P-value = 0.132). Conclusion This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Abstract Quantum information is often carried in the frequency and polarization degrees of freedom (DoFs) in single photons and entangled photons. We demonstrate an approach to couple and decouple the frequency and polarization DoFs of broadband biphotons. Our approach is based on a nonlinear interferometer consisting of a linear dispersive medium and a polarization controller in between the two biphoton sources (nonlinear media). When the two DoFs are decoupled, maximally polarization-entangled biphotons are observed in the polarization DoF, while interference fringes are observed in the spectrum of the biphotons. When the two DoFs are coupled, by adjusting the polarization controller, interference fringes disappear from the spectrum and instead appear in the degree of polarization entanglement, varying between 0 and 1, depending on the signal and idler frequencies. Our approach offers a convenient means of tuning the polarization entanglement and can be employed for arbitrary biphoton polarization state generation.

Abstract Background Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. Methods A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways’ activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein–protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. Results In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. Conclusion We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

Abstract Purpose This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. Methods Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). Results A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p

Crucian carp (Carassius auratus gibelio), an extensively cultivated freshwater fish, was one of the model species for the study of fish immunology. Polyclonal antibodies were advantageous molecular tools for studying teleost immune system. Specifically, polyclonal antibodies reacting with immunoglobulins (Ig) were used successfully in studies of the teleost fishes. In the present study, we produced polyclonal antibody against CH2 domains of crucian carp IgM, and measured the in vivo dynamics of IgM mRNA caused by CyHV-2 infection. The recombinant protein IgM with relative molecular weight about 53 KD was correctly expressed in prokaryotic cells. The specificity of the polyclonal antibody was evaluated by Western blotting and results revealed that the antibody not only specifically recognized crucian carp serum but also cross-reacted with grass carp serum. Quantitative RT-PCR analysis demonstrated the expression of IgM mRNA changed significantly after CyHV-2 infection. The expression of IgM in the kidney increased and reached a maximum at 6 h post-infection (hpi), while dropped to a low level at 5 days post-infection (dpi). In conclusion, the expression of IgM was significantly upregulated in the kidney of crucian carp infected with CyHV-2, indicating that IgM played a potential role in systemic immunity against viral infection. Polyclonal antibody against crucian carp IgM had certain clinical relevance, which might provide insight into the early stage of virus infection and prevention of the disease.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

Summary: In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear. Single cell RNA sequencing (scRNA-seq) suggested that Ace2 involved the proliferation of the stem/eTA cells. Ace2 was reduced following corneal injury. Such reduction enhanced limbal epithelial proliferation and downregulated LCN2, a negative regulator of proliferation in a variety of tissues, via upregulating TGFA and consequently activating epidermal growth factor receptor (EGFR). Inhibition of EGFR or overexpression of LCN2 reversed the increased proliferation in limbal epithelial cells lacking ACE2. Our findings demonstrate that after corneal injury, ACE2 is downregulated, which activates limbal epithelial cell proliferation via a TGFA/EGFR/LCN2 pathway.

Acute kidney injury (AKI) is in high prevalence worldwide but with no therapeutic strategies. Programmed cell death in tubular epithelial cells has been reported to accelerate a variety of AKI, but the major pathways and underlying mechanisms are not defined. Herein, we identified that pyroptosis was responsible for AKI progression and related to ATP depletion in renal tubular cells. We found that FAM3A, a mitochondrial protein that assists ATP synthesis, was decreased and negatively correlated with tubular cell injury and pyroptosis in both mice and patients with AKI. Knockout of FAM3A worsened kidney function decline, increased macrophage and neutrophil cell infiltration, and facilitated tubular cell pyroptosis in ischemia/reperfusion injury model. Conversely, FAM3A overexpression alleviated tubular cell pyroptosis, and inhibited kidney injury in ischemic AKI. Mechanistically, FAM3A promoted PI3K/AKT/NRF2 signaling, thus blocking mitochondrial reactive oxygen species (mt-ROS) accumulation. NLRP3 inflammasome sensed the overload of mt-ROS and then activated Caspase-1, which cleaved GSDMD, pro-IL-1β, and pro-IL-18 into their mature forms to mediate pyroptosis. Of interest, NRF2 activator alleviated the pro-pyroptotic effects of FAM3A depletion, whereas the deletion of NRF2 blocked the anti-pyroptotic function of FAM3A. Thus, our study provides new mechanisms for AKI progression and demonstrates that FAM3A is a potential therapeutic target for treating AKI.

BackgroundType 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease among children and adolescents. Telemedicine has been widely used in the field of chronic disease management and can benefit patients with T1DM. However, existing studies lack high-level evidence related to the effectiveness of telemedicine for glycemic control in children and adolescents with T1DM. ObjectiveThis study aims to systematically review the evidence on the effectiveness of telemedicine interventions compared with usual care on glycemic control among children and adolescents with T1DM. MethodsIn this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Embase, Web of Science (all databases), and CINAHL Complete from database inception to May 2023. We included randomized controlled trials (RCTs) that evaluated the effectiveness of a telemedicine intervention on glycemic control in children and adolescents with T1DM. In total, 2 independent reviewers performed the study selection and data extraction. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Our primary outcome was glycated hemoglobin (HbA1c) levels. Secondary outcomes were quality of life, self-monitoring of blood glucose, the incidence of hypoglycemia, and cost-effectiveness. A random-effects model was used for this meta-analysis. ResultsOverall, 20 RCTs (1704 participants from 12 countries) were included in the meta-analysis. Only 5% (1/20) of the studies were at high risk of bias. Compared to usual care, telemedicine was found to reduce HbA1c levels by 0.22 (95% CI –0.33 to –0.10; P

IntroductionDiabetic cardiomyopathy (DCM) is predominantly distinguished by impairment in ventricular function and myocardial fibrosis. Previous studies revealed the cardioprotective properties of C1q/tumor necrosis factor-related protein 9 (CTRP9). However, whether CTRP9 affects diabetic myocardial fibrosis and its underlying mechanisms remains unclear.MethodsWe developed a type 1 diabetes (T1DM) model in CTRP9-KO mice via streptozotocin (STZ) induction to examine cardiac function, histopathology, fibrosis extent, Yes-associated protein (YAP) expression, and the expression of markers for autophagy such LC3-II and p62. Additionally, we analyzed the direct impact of CTRP9 on high glucose (HG)-induced transdifferentiation, autophagic activity, and YAP protein levels in cardiac fibroblasts.ResultsIn diabetic mice, CTRP9 expression was decreased in the heart. The absence of CTRP9 aggravated cardiac dysfunction and fibrosis in mice with diabetes, alongside increased YAP expression and impaired autophagy. In vitro, HG induced the activation of myocardial fibroblasts, which demonstrated elevated cell proliferation, collagen production, and α-smooth muscle actin (α-SMA) expression. CTRP9 countered these adverse effects by restoring autophagy and reducing YAP protein levels in cardiac fibroblasts. Notably, the protective effects of CTRP9 were negated by the inhibition of autophagy with chloroquine (CQ) or by YAP overexpression through plasmid intervention. Notably, the protective effect of CTRP9 was negated by inhibition of autophagy caused by chloroquine (CQ) or plasmid intervention with YAP overexpression.DiscussionOur findings suggest that CTRP9 can enhance cardiac function and mitigate cardiac remodeling in DCM through the regulation of YAP-mediated autophagy. CTRP9 holds promise as a potential candidate for pharmacotherapy in managing diabetic cardiac fibrosis.

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that targets pig intestines to cause disease. It is globally widespread and causes huge economic losses to the pig industry. PEDV N protein is the protein that constitutes the core of PEDV virus particles, and most of it is expressed in the cytoplasm, and a small part can also be expressed in the nucleus. However, the role of related proteins in host nucleotide metabolic pathways in regulating PEDV replication have not been fully elucidated. In this study, PEDV-N-labeled antibodies were co-immunoprecipitated and combined with LC-MS to screen for host proteins that interact with N proteins. Bioinformatics analyses showed that the selected host proteins were mainly enriched in metabolic pathways. Moreover, co-immunoprecipitation and confocal microscopy confirmed that the second-largest subunit of RNA polymerase II (RPB2) and uridine phosphorylase 1 (UPP1) interacted with the N protein. RPB2 is the main subunit of RNA polymerase II and plays an important role in eukaryotic transcription. UPP1 is an enzyme that catalyzes reversible phosphorylation of uridine to uracil and ribo-1-phosphate to promote catabolism and bio anabolism. RPB2 overexpression significantly promoted viral replication, whereas UPP1 overexpression significantly inhibited viral replication. Studies on interactions between the PEDV N and host proteins are helpful in elucidating the pathogenesis and immune escape mechanism of PEDV.

Meteorological disasters along highways significantly reduce road traffic efficiency. Low visibility caused by heavy fog is a severe meteorological disaster that greatly increases highway traffic accidents. Accurately predicting highway visibility and taking timely response measures can reduce the impact of meteorological disasters and improve traffic safety. We proposed an Attention-based BiLSTM-CNN (ABCNet) model, which synergized attention mechanisms with BiLSTM and CNN technologies to forecast atmospheric visibility more accurately. First, the Bi-LSTM module processed information both forward and backward, capturing intricate temporal dependencies in the model. Second, the multi-head attention mechanism following the Bi-LSTM distilled and prioritized salient features from multiple aspects of the sequence data. Third, the CNN module recognized local spatial features, and a singular attention mechanism refined the feature map after the CNN module, further enhancing the model's accuracy and predictive capability. Experiments showed that the model was accurate, effective, and significantly advanced compared to conventional models. It could fully extract the spatiotemporal characteristics of meteorological elements. The model was integrated into practical systems with positive results. Additionally, this study provides a self-collected meteorological dataset for highways in high-altitude mountainous areas.

Abstract Objective We aimed to explore the heterogeneity of neurons in heart failure with dilated cardiomyopathy (DCM). Methods Single-cell RNA sequencing (scRNA-seq) data of patients with DCM and chronic heart failure and healthy samples from GSE183852 dataset were downloaded from NCBI Gene Expression Omnibus, in which neuron data were extracted for investigation. Cell clustering analysis, differential expression analysis, trajectory analysis, and cell communication analysis were performed, and highly expressed genes in neurons from patients were used to construct a protein-protein interaction (PPI) network and validated by GSE120895 dataset. Results Neurons were divided into six subclusters involved in various biological processes and each subcluster owned its specific cell communication pathways. Neurons were differentiated into two branches along the pseudotime, one of which was differentiated into mature neurons, whereas another tended to be involved in the immune and inflammation response. Genes exhibited branch-specific differential expression patterns. FLNA, ITGA6, ITGA1, and MDK interacted more with other gene-product proteins in the PPI network. The differential expression of FLNA between DCM and control was validated. Conclusion Neurons have significant heterogeneity in heart failure with DCM, and may be involved in the immune and inflammation response to heart failure.

To synthesise the best available evidence for the effectiveness of interventions delivered in community-based rehabilitation (CBR) centers on physical fitness, for community-dwelling older adults living in Asian countries. This study is a systematic review and meta-analysis. Seven English and two Chinese electronic databases were searched for randomised controlled trials (RCTs) and quasi-experimental studies that were conducted by centers providing CBR. Independent reviewers screened, quality-appraised and extracted data. The primary outcome was physical fitness measured by validated assessment tools, including the Timed Up and Go Test (TUG) gait speed, hand grip strength, Functional Reach Test (FRT), and one-leg standing test. Assessments of activity of daily living and quality of life using tools including the Barthel Index, Short Form (SF)-12, and SF-36 were secondary outcomes. After screening 5,272 studies, 29 studies were included (16 RCTs, 13 quasi-experimental studies) from four countries. Meta-analyses found that CBR programs significantly decreased TUG time (mean difference [MD], -1.89 seconds; 95% confidence interval [95% CI], -2.84 to -0.94; I2=0%; Z=3.90, p

Combining inverse projection and vote accumulation methods, we propose a novel 3-D geometric reconstruction method based on inverse synthetic aperture radar image sequence for triaxially stabilized space targets. Considering that the translation of a triaxially stabilized space target results in a large angular rotation of the radar line-of-sight and an attitude adjustment rotation of the target itself, the projection relationship between the radar imaging plane and a triaxially stabilized space target is constructed first. Subsequently, we perform an inverse projection on the dominant points extracted from each imaging plane to determine the location of the 3-D candidate scatterers and assign a voting value of 1 to each position. By accumulating these vote values, we can obtain the total number of votes for the candidate scatterer position. We treat candidate 3-D scatterers with a large cumulative number of votes as actual scatterers. Thus, the target 3-D geometry can be obtained. Compared with the traditional matrix factorization-based 3-D reconstruction methods, this method is more accurate and ensures that the target pose is consistent with the actual pose. At the same time, compared with 3-D reconstruction methods based on the energy accumulation ideas, this method produces fewer false scatterers and has higher credibility. The experimental results based on the simulated point target and electromagnetic data are presented to validate the effectiveness and robustness of the proposed method.

Multiple-input-multiple-output (MIMO) synthetic aperture radar (SAR) (MIMO-SAR) has numerous potential applications in fields, such as medical diagnosis and security screening. In near-field MIMO-SAR imaging, the virtual array is typically defined as the midpoint of the transceiver array. Based on the virtual array, the multistatic data can be converted to monostatic data for imaging. However, these approaches suffer from low accuracy and cannot reconstruct large scenes, despite their small computational load. In this article, we propose a novel near-field MIMO-SAR imaging algorithm based on range compensation. The convolution between transmitting and receiving elements of the MIMO array defines the positions of virtual array's elements, with the center of the small scene selected as the reference point. The range difference between the transceiver array and the corresponding virtual array to the reference point is calculated. An approximate expression of the range difference is also derived, which can effectively reduce the computational load associated with the range compensation. The conditions for partitioning large scenes are derived by analyzing the range difference between the reference point and other scattered points with respect to the antenna elements. Based on the conditions, the large scenes are divided into blocks. The final image is obtained by a weighted sum of each block scene image. Simulation and experimental results on the designed MIMO radar near-field imaging system demonstrate that the proposed algorithm can effectively reconstruct high-resolution scene images of arbitrary size.

Abstract Visual sentiment analysis is in great demand as it provides a computational method to recognize sentiment information in abundant visual contents from social media sites. Most of existing methods use CNNs to extract varying visual attributes for image sentiment prediction, but they failed to comprehensively consider the correlation among visual components, and are limited by the receptive field of convolutional layers as a result. In this work, we propose a visual semantic correlation network VSCNet, a Transformer-based visual sentiment prediction model. Precisely, global visual features are captured through an extended attention network stacked by a well-designed extended attention mechanism like Transformer. An off-the-shelf object query tool is used to determine the local candidates of potential affective regions, by which redundant and noisy visual proposals are filtered out. All candidates considered affective are embedded into a computable semantic space. Finally, a fusion strategy integrates semantic representations and visual features for sentiment analysis. Extensive experiments reveal that our method outperforms previous studies on 5 annotated public image sentiment datasets without any training tricks. More specifically, it achieves 1.8% higher accuracy on FI benchmark compared with other state-of-the-art methods.

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme (CYP), which plays a crucial role in the metabolism of neurosteroids. The antiepileptic drug phenytoin (PHT) has been observed to induce neuronal side effects in patients, which could be attributed to its induction of CYP expression and testosterone (TES) metabolism in the hippocampus. While pregnane X receptor (PXR) is widely known for its regulatory function of CYPs in the liver, we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile (PCN), a PXR agonist, has differential effects on CYP expression in the liver and hippocampus. Specifically, the PCN treatment resulted in the induction of cytochrome P450, family 3, subfamily a, polypeptide 11 (CYP3A11), and CYP2B10 expression in the liver, while suppressing their expression in the hippocampus. Functionally, the PCN treatment protected mice from PHT-induced hippocampal nerve injury, which was accompanied by the inhibition of TES metabolism in the hippocampus. Mechanistically, we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent, rather than PXR independent, as demonstrated by genetic and pharmacological models. In conclusion, our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR. Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

BackgroundIntegrin-dependent cell adhesion and migration play important roles in systemic sclerosis (SSc). The roles of integrin activating molecules including talins and kindlins, however, are unclear in SSc.ObjectivesWe aimed to explore the function of integrin activating molecules in SSc.MethodsTranscriptome analysis of skin datasets of SSc patients was performed to explore the function of integrin-activating molecules including talin1, talin2, kindlin1, kindlin2 and kindlin3 in SSc. Expression of talin1 in skin tissue was assessed by multiplex immunohistochemistry staining. Levels of talin1 in serum were determined by ELISA. The effects of talin1 inhibition were analyzed in human dermal fibroblasts by real-time PCR, western blot and flow cytometry.ResultsWe identified that talin1 appeared to be the primary integrin activating molecule involved in skin fibrosis of SSc. Talin1 was significantly upregulated and positively correlates with the modified Rodnan skin thickness score (mRSS) and the expression of pro-fibrotic biomarkers in the skin lesions of SSc patients. Further analyses revealed that talin1 is predominantly expressed in the dermal fibroblasts of SSc skin and promotes fibroblast activation and collagen production. Additionally, talin1 primarily exerts its effects through integrin β1 and β5 in SSc.ConclusionsOverexpressed talin1 is participated in skin fibrosis of SSc, and talin1 appears to be a potential new therapeutic target for SSc.

Background This study aims to examine the relationship between functional movements and golf performance using the Golf Specific Functional Movement Screen (GSFMS). Methods This cross-sectional study included a total of 56 collegiate golfers (aged 20.89 ± 0.99 years, height of 174.55 ± 7.76 cm, and weight 68.48 ± 9.30 kg) who met the criteria, and were recruited from Hainan Normal University in June 2022. The participants’ golf motor skills (1-yard putt, 10-yard putt, 25-yard chip, 130/100-yard set shot, driver, and 9-hole stroke play) were tested and the GSFMS (e.g., pelvic tilt, pelvic rotation, and torso rotation) was used. Results There were significant weak or moderate correlations between the variables. Furthermore, a multiple linear regression analysis found that pelvic rotation and lower-body rotation abilities can significantly predict golf skill levels, which collectively explain 31.2% of the variance in golf skill levels among collegiate golfers (Adjusted R2 = 0.312, F = 2.663, p < 0.05). Standardised β values indicate that pelvic rotation (β = 0.398) has a more substantial impact on golf skill levels than lower-body rotation (β = 0.315). Conclusions This study found the weak to moderate correlations between the GSFMS and golf performance, and pelvic rotation and lower-body rotation abilities, thus predicting golf skills. Our findings provide novel insights into the relationship between functional abilities and comprehensive skill performance within the context of the Gray Cook’s Movement Pyramid model, and provide theoretical support and practical reference for collegiate golf motor-skill learning and sports injury prevention.

Objective: To investigate whether inflammatory indices, including the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), product of platelet and neutrophil count (PPN), and lymphocyte-to-monocyte ratio (LMR), correlate with chronic obstructive pulmonary disease (COPD). Methods: This was a cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) database 2007–2018. The SII, NLR, PLR, PPN and LMR were calculated based on blood cell counts and were log2-transformed. COPD was diagnosed via a questionnaire or spirometry examination. Multivariate logistic regression, sensitivity analysis, subgroup analyses, and interaction tests were performed to evaluate the relationships. Results: 23,875 participants, including 1000 COPD patients (453 diagnosed via spirometry examination, 547 diagnosed via a questionnaire), were enrolled in this study. Positive associations were observed between SII (OR 1.231, 95 % CI 1.081,1.401), NLR (OR 1.223, 95 % CI 1.064,1.405), PLR (OR 1.325, 95 % CI 1.086,1.617), PPN (OR 1.157, 95 % CI 1.031,1.298) and COPD, while a negative association was obtained between LMR and COPD (OR 0.794, 95 % CI 0.666,0.948) after covariate adjustments. When divided COPD patients into spirometry-based and questionnaire-based, only SII (OR 1.310, 95%CI 1.122,1.529), PLR (OR 1.669, 95%CI 1.272,2.191) and PPN (OR 1.218, 95%CI 1.050,1.412) significantly correlated with spirometry-based COPD, while only NLR (OR 1.303, 95%CI 1.055,1.609) and LMR (OR 0.524, 95%CI 0.406,0.677) significantly correlated with questionnaire-based COPD after covariate adjustments. Conclusion: Significant associations are observed between different inflammation indices and COPD. Heterogeneity exists between spirometry-based and questionnaire-based COPD patients. Future studies are needed to verify the results.

Abstract Intrinsic immunosuppressive tumor microenvironment (ITM) and insufficient tumor infiltration of T cells severely impede the progress of glioblastoma (GBM) immunotherapy. In this study, it is identify that inhibiting the expression of glucose transporter 1 (GLUT1) can facilitate the prevention of lactate excretion from tumor glycolysis, which significantly alleviates the lactate‐driven ITM by reducing immunosuppressive tumor‐associated macrophages (TAMs) and regulatory T cells (Tregs). Simultaneously, the findings show that the generated inflammatory cytokine IFN‐γ during immune activation aggravates the immune escape by upregulating immune checkpoint programmed death‐ligand 1 (PD‐L1) in tumor cells and TAMs. Therefore, an injectable thermogel loaded with a GLUT1 inhibitor BAY‐876 and a PD‐1/PD‐L1 blocker BMS‐1 (Gel@B‐B) for dual‐regulation of metabolism and immunity of GBM is developed. Consequently, in situ injection of Gel@B‐B significantly delays tumor growth and prolongs the survival of the orthotopic GBM mouse model. By actively exposing tumor antigens to antigen‐presenting cells, the GBM vaccine combined with Gel@B‐B is found to significantly increase the fraction of effector T cells (Th1/CTLs) in the tumor microenvironment, thereby remarkably mitigating tumor recurrence long‐term. This study may provide a promising strategy for GBM immunotherapy.

Carassius auratus herpesvirus (CaHV) is a pathogen isolated from crucian carp (Carassius auratus) associated with high mortality. A diagnosis method that can detect the virus at an early stage, specifically and accurately, is an urgent requirement for the prevention of CaHV transmission. In the present study, a droplet digital PCR (ddPCR) method based on the tumor necrosis factor receptor (TNFR) gene was established to detect and quantify CaHV DNA with high specificity and no cross-reactions with other aquatic viruses. Skin mucus samples were collected from infected crucian carp from Day 1–8 after infection, and positive amplification was detected on the first day by ddPCR (0.54 copies/μL), whereas the presence of CaHV was not detected by routine PCR until Day 6. Tissue DNA was then collected from the head kidney of 20 fishes which were injected with CaHV and died during the experiment. The five negative samples checked by routine PCR were detected by ddPCR and real-time PCR (qPCR), respectively. The results showed that the positive detection rate of ddPCR (100%) was higher than that of qPCR (40%). The detection limit of the ddPCR was found to be 0.52 copies/μL, which was much lower than the 50.12 copies/μL determined by qPCR. Overall, ddPCR offers a highly promising diagnosis method for the absolute quantification of CaHV in carrier fish and samples from the skin mucus and head kidney with low viral concentrations.

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Summary: Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and β-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.

Adeno-associated virus (AAV) vectors have been widely used in therapy to treat hereditary retinal diseases. But its transduction efficiency by intravitreal injection still needs to be improved. In this study, we investigated the transduction efficiency of AAV-DJ (K137R)-GFP in different retinal cells of normal mice, as well as the therapy effection of AAV-DJ (K137R)-Rs1 on retinal function and structure in Rs1-KO mice. The intravitreal injection of AAV-DJ (K137R)-GFP demonstrated that this vector transduced cells in all layers of the retina, including the inner nuclear layer and photoreceptor layer. The intravitreal injection of AAV-DJ (K137R)-Rs1 found that 3 months post-injection of this vector improved retinal function and structure in Rs1-KO mice. Our conclusion is that AAV-DJ (K137R) vector can efficiently and safely penetrate the inner limiting membrane and transduce different layers of retinal cells in the long term, as well as being able to continuously and efficiently express target therapeutic proteins, making it a candidate therapeutic vector for X-linked retinoschisis (XLRS).

Abstract Depth map super resolution has been paid much attention in 3D applications due to the limitation of depth sensors. Few textures in objects with clear contours along them is the most important characteristic of depth map. An efficient image representation should be directional, multiscale and anisotropic. From this we propose a novel multiscale and multidirection depth map super resolution framework with semantic inference to improve the quality of depth maps. In this framework, a multiscale and multidirection depth map contour fusion scheme captures and assembles intrinsic geometrical structures through a multiview non‐subsampled contourlet transform manner. This scheme not only isolates the discontinuities of contours but retains the smoothness along the contours. The semantic inference is also utilized to segment and label the depth map into objects/backgrounds‐level which are coplanar. Furthermore, a semantic‐aware label refinement strategy is introduced to correct the rarely inaccurate labels of the label map for upscaling the target pixel with pixels in the same object or background. Experimental results on benchmark depth map dataset demonstrate that the proposed multiscale and multidirection depth map super resolution framework with semantic inference has a significant improvement than the state‐of‐the‐art algorithms both visually and quantitatively.

Abstract Background Autism spectrum disorder (ASD) has been associated with intrauterine growth restriction (IUGR), but the underlying mechanisms are unclear. Results We found that the IUGR rat model induced by prenatal caffeine exposure (PCE) showed ASD-like symptoms, accompanied by altered gut microbiota and reduced production of indole 3-propionic acid (IPA), a microbiota-specific metabolite and a ligand of aryl hydrocarbon receptor (AHR). IUGR children also had a reduced serum IPA level consistent with the animal model. We demonstrated that the dysregulated IPA/AHR/NF-κB signaling caused by disturbed gut microbiota mediated the hippocampal microglia hyperactivation and neuronal synapse over-pruning in the PCE-induced IUGR rats. Moreover, postnatal IPA supplementation restored the ASD-like symptoms and the underlying hippocampal lesions in the IUGR rats. Conclusions This study suggests that the microbiota-IPA-brain axis regulates ASD susceptibility in PCE-induced IUGR offspring, and supplementation of microbiota-derived IPA might be a promising interventional strategy for ASD with a fetal origin. Video Abstract

Abstract Fusarium head blight (FHB) caused by Fusarium species, seriously threatens the safety of wheat (Triticum aestivum) production. Resistant cultivars and fungicides are frequently used to control these FHB pathogens. However, Fusarium species have been adapting the current FHB control approaches in a manner that raises concern for future FHB control strategies, which could lead to a greater risk of FHB outbreaks. In this study, a total of 521 strains of Fusarium were isolated from Sichuan province of China, to investigate the diversity of Fusarium species and the genes associated with their adaptation. Seven species were identified based on molecular markers and morphological analysis. The virulence assays showed that Fusarium asiaticum (Fa) and Fusarium graminearum (Fg) were the two major causal agents of FHB, with high virulence and more frequent isolates. Fungicide resistance analysis showed that four isolates had developed the resistance to carbendazim, and four isolates had developed the resistance to tebuconazole. Of note, two point-mutation variants (F200Y and E198Q) occurred in the β2-tubulin gene, leading to the carbendazim resistance. The landscape of genomic diversity was analyzed through whole-genome sequencing, revealing a total of 182,811 and 430,733 variants (including: single nucleotide polymorphisms, SNP, insertion and deletion, Indel, and structure variation, SV) among the Fa and Fg isolates, respectively. In addition, potential alterations in gene function (15.22%) were predicted among Fg variants. These alterations offer potential helps for the Fusarium species to adapt to various managements of FHB, which may increase risks in developing fungicide-resistant isolates. However, these annotated genetic variants are valuable resources for further genetic and genomic studies, as well as potential markers to assist disease risk assessment.

Abstract In acute skin injury, healing is impaired by the excessive release of reactive oxygen species (ROS). Melanin, an efficient scavenger of radical species in the skin, performs a key role in ROS scavenging in response to UV radiation and is upregulated in response to toxic insult. In a chemical injury model in mice, we demonstrate that the topical application of synthetic melanin particles (SMPs) significantly decreases edema, reduces eschar detachment time, and increases the rate of wound area reduction compared to vehicle controls. Furthermore, these results were replicated in a UV-injury model. Immune array analysis shows downregulated gene expression in apoptotic and inflammatory signaling pathways consistent with histological reduction in apoptosis. Mechanistically, synthetic melanin intervention increases superoxide dismutase (SOD) activity, decreases Mmp9 expression, and suppresses ERK1/2 phosphorylation. Furthermore, we observed that the application of SMPs caused increased populations of anti-inflammatory immune cells to accumulate in the skin, mirroring their decrease from splenic populations. To enhance antioxidant capacity, an engineered biomimetic High Surface Area SMP was deployed, exhibiting increased wound healing efficiency. Finally, in human skin explants, SMP intervention significantly decreased the damage caused by chemical injury. Therefore, SMPs are promising and effective candidates as topical therapies for accelerated wound healing, including via pathways validated in human skin.

In this paper, a hybrid shoulder friction stir welding (HS-FSW) process was developed combining the advantages of rotational shoulder friction stir welding (RS-FSW) and non-rotational shoulder friction stir welding (NRS-FSW). Both static and fatigue performance of the HS-FSW Al–Mg–Si alloy joints were examined and compared with those of the RS-FSW and NRS-FSW joints. The ultimate tensile strengths of the joints welded by HS-FSW are increased by 17.3 % and 6.7 %, compared with those of RS and NRS FSW, respectively. Besides, fatigue strengths of HS-FSW joints grow by respective 25.4 % and 1.8 %. For a better understanding of the significant improvements, the fatigue crack propagation (FCP) test and residual stress measurement were carried out. FCP test indicates that the advancing side (AS) is the most sensitive zone for FCP. The residual stress measurements suggest that the HS-FSW joint has the lowest distribution amplitude of residual stress compared with that of the RS-FSW and NRS-FSW joints. Based on above evolution, an assessment is firstly conducted, which reveals that the axial force and the lower heat input to mitigate the amplitude and the peak value of tensile stress during welding, jointly contribute to the superior imprisonment of the tensile strength and fatigue strength of the HS-FSW joints.

Abstract Food protein amyloid fibrils have superior technological, nutritional, sensorial, and physical properties compared to native monomers, but there is as yet insufficient understanding of their digestive fate and safety for wide consumption. By combining SDS-PAGE, ELISA, fluorescence, AFM, MALDI-MS, CD, microfluidics, and SAXS techniques for the characterization of β-lactoglobulin and lysozyme amyloid fibrils subjected to in-vitro gastrointestinal digestion, here we show that either no noticeable conformational differences exist between amyloid aggregates and their monomer counterparts after the gastrointestinal digestion process (as in β-lactoglobulin), or that amyloid fibrils are digested significantly better than monomers (as in lysozyme). Moreover, in-vitro exposure of human cell lines and in-vivo studies with C. elegans and mouse models, indicate that the digested fibrils present no observable cytotoxicity, physiological abnormalities in health-span, nor accumulation of fibril-induced plaques in brain nor other organs. These extensive in-vitro and in-vivo studies together suggest that the digested food amyloids are at least equally as safe as those obtained from the digestion of corresponding native monomers, pointing to food amyloid fibrils as potential ingredients for human nutrition.

Abstract Background Adrenal gland is the synthesis and secretion organ of glucocorticoid, which is crucial to fetal development and postnatal fate. Recently, we found that prenatal dexamethasone exposure (PDE) could cause adrenal dysfunction in offspring rats, but its multigenerational genetic effects and related mechanisms have not been reported. Methods The PDE rat model was established, and female filial generation 1 (F1) rats mate with wild males to produce the F2, the same way for the F3. Three generation rats were sacrificed for the related detection. SW-13 cells were used to clarify the epigenetic molecular mechanism. Results This study confirmed that PDE could activate fetal adrenal glucocorticoid receptor (GR). The activated GR, on the one hand, up-regulated Let-7b (in human cells) to inhibit steroidogenic acute regulatory protein (StAR) expression directly; on the other hand, down-regulated CCCTC binding factor (CTCF) and up-regulated DNA methyltransferase 3a/3b (Dnmt3a/3b), resulting in H19 hypermethylation and low expression. The decreased interaction of H19 and let-7 can further inhibit adrenal steroidogenesis. Additionally, oocytes transmitted the expression change of H19/let-7c axis to the next generation rats. Due to its genetic stability, F2 generation oocytes indirectly exposed to dexamethasone also inhibited H19 expression, which could be inherited to the F3 generation. Conclusions This cascade effect of CTCF/H19/Let-7c ultimately resulted in the transgenerational inheritance of adrenal steroidogenesis inhibition of PDE offspring. This study deepens the understanding of the intrauterine origin of adrenal developmental toxicity, and it will provide evidence for the systematic analysis of the transgenerational inheritance effect of acquired traits induced by PDE. Video Abstract

Abstract Background Oculopharyngodistal myopathy (OPDM) is an autosomal dominant adult-onset degenerative muscle disorder characterized by ptosis, ophthalmoplegia and weakness of the facial, pharyngeal and limb muscles. Trinucleotide repeat expansions in non-coding regions of LRP12, G1PC1, NOTCH2NLC and RILPL1 were reported to be the etiologies for OPDM. Results In this study, we performed long-read whole-genome sequencing in a large five-generation family of 156 individuals, including 21 patients diagnosed with typical OPDM. We identified CGG repeat expansions in 5’UTR of RILPL1 gene in all patients we tested while no CGG expansion in unaffected family members. Repeat-primed PCR and fluorescence amplicon length analysis PCR were further confirmed the segregation of CGG expansions in other family members and 1000 normal Chinese controls. Methylation analysis indicated that methylation levels of the RILPL1 gene were unaltered in OPDM patients, which was consistent with previous studies. Our findings provide evidence that RILPL1 is associated OPDM in this large pedigree. Conclusions Our results identified RILPL1 is the associated the disease in this large pedigree.

Surface-Enhanced Raman Spectroscopy (SERS) is a powerful analytical technique for detecting trace analytes using noble metal nanoparticles. In this paper, we present a novel approach to construct a high-performance SERS sensing platform using self-assembled gold nanoparticles on aminated glass capillaries. The surface self-assembly technology ensures uniformity and repeatability of the SERS substrate, addressing the challenges of poor reproducibility observed in conventional methods. The 30 nm gold nanoparticles exhibit excellent plasmonic properties and biocompatibility, making them ideal candidates for SERS applications. We conducted SERS detection using Rhodamine 6G (R6G) as probe molecules, achieving a minimum detectable concentration of 0.1 nM for the AuNPs/GS substrate and 0.1 pM for the S-AuNPs/GC substrate. The S-AuNPs/GC substrate demonstrated commendable uniformity and repeatability, with a relative standard deviation of 12.1 %. Machine learning techniques, including baseline correction, normalization, and smoothing, were employed for data processing, enhancing the accuracy and reliability of the SERS analysis. By employing the K-means clustering algorithm, we identified three distinct groups of spectral characteristics. Additionally, Principal Component Analysis (PCA) allowed visualization and understanding of the clustering results in a two-dimensional space, capturing approximately 86.74 % of the data's variance. The successful construction of a high-performance SERS sensing platform with enhanced sensitivity, accuracy, and reliability, assisted by machine learning, holds great potential for various applications in chemical sensing, environmental monitoring, and biomedical diagnostics.

Abstract Background The eight phenotypically distinguishable indigenous chicken breeds in Guizhou province of China are great resources for high-quality development of the poultry industry in China. However, their full value and potential have yet to be understood in depth. To illustrate the genetic diversity, the relationship and population structure, and the genetic variation patterns shaped by selection in Guizhou indigenous chickens, we performed a genome-wide analysis of 240 chickens from 8 phenotypically and geographically representative Guizhou chicken breeds and 60 chickens from 2 commercial chicken breeds (one broiler and one layer), together with 10 red jungle fowls (RJF) genomes available from previous studies. Results The results obtained in this present study showed that Guizhou chicken breed populations harbored higher genetic diversity as compared to commercial chicken breeds, however unequal polymorphisms were present within Guizhou indigenous chicken breeds. The results from the population structure analysis markedly reflected the breeding history and the geographical distribution of Guizhou indigenous chickens, whereas, some breeds with complex genetic structure were ungrouped into one cluster. In addition, we confirmed mutual introgression within Guizhou indigenous chicken breeds and from commercial chicken breeds. Furthermore, selective sweep analysis revealed candidate genes which were associated with specific and common phenotypic characteristics evolved rapidly after domestication of Guizhou local chicken breeds and economic traits such as egg production performance, growth performance, and body size. Conclusion Taken together, the results obtained from the comprehensive analysis of the genetic diversity, genetic relationships and population structures in this study showed that Guizhou indigenous chicken breeds harbor great potential for commercial utilization, however effective conservation measures are currently needed. Additionally, the present study drew a genome-wide selection signature draft for eight Guizhou indigenous chicken breeds and two commercial breeds, as well as established a resource that can be exploited in chicken breeding programs to manipulate the genes associated with desired phenotypes. Therefore, this study will provide an essential genetic basis for further research, conservation, and breeding of Guizhou indigenous chickens.

Abstract Heterogeneous structures are ubiquitous in natural organisms. Native heterogeneous structures inspire many artificial structures that are playing important roles in modern society, while it is challenging to identify the relevant factors in forming these structures due to the complexity of living systems. Here, hybrid hydrogels consisting of flexible polymer networks with embedded stiff cellulose nanocrystals (CNCs) are considered an open system to simulate the generalized formation of heterogeneous core-sheath structures. As the result of the modified air drying process of hybrid hydrogels, the formation of heterogeneous core-sheath structure is found to be correlated to the relative evaporation speed. Specifically, the formation of such heterogeneity in xerogel fibers is found to be correlated with the divergence of Deborah number (De). During the transition of De from large to small values with accompanying morphologies, the turning point is around De = 1. The mechanism can be considered a relative humidity-dependent glass transition behavior. These unique heterogeneous structures play a key role in tuning water permeation and water sorption capacity. Insights into these aspects can prospectively contribute to a better understanding of the native heterogeneous structures for bionics design.

Edible fungi were rich in nutrients and were potential sources of high-quality protein. In this study, nutritional components such as moisture, ash, protein, total sugar and L-ergothione in 18 kinds of edible fungi were analyzed, and headspace solid phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used to analyze the fruit-body, mycelium and fermentation broth of 6 edible fungi (Lentinula edodes, Agaricus bisporus, Coprinus comatus, Pleurotus eryngii, Auricularia heimuer and Ganoderma lucidum). The results showed that the water content of 18 edible fungi ranged from 6.7 to 13.77 g/100 g, ash content from 2.24 to 10.9 g/100 g, fat content from 0.3 to 2.92 g/100 g and total sugar content from 2.11 to 10.5 g/100 g. The crude protein content of 18 edible fungi ranged from 7.88 to 35.87 g/100 g, among which the protein content of Agaricus bisporus was as high as 35.87 g/100 g. There was no significant difference in the content of other nutrients. The amino acids were rich and contained 8 kinds of essential amino acids necessary for human body. Principal component analysis showed that the amino acid composition ratio of Lentinula edodes, Auricularia heimuer, Grifola frondosa, Volvariella volvacea, and Flammulina velutipes was most similar to that of egg, but significantly different from that of meat, soybeans and wheat. The results of high performance liquid chromatography showed that Lentinula edodes was rich in ergothioneine, and the content was up to 336 mg/kg. The ergothioneine content of edible fungi such as Grifola frondosa, Morchella, Agaricus bisporus and Coprinus comatus were also higher than 100 mg/kg. A total of 34 volatile compounds, including aldehydes, ketones, esters, alcohols, phenols, ethers, alkanes and heterocyclic compounds, were identified by HS-SPME-GC-MS in 6 edible fungi. Ganoderma lucidum mycelium was rich in hexal, methylnonylketone, trans-2-octenal, 2-n-amylfuran, 2,4-nononadienal and other volatile compounds, which were significantly different from the other 17 samples. The flavor substances of the fermentation broth of the six edible fungi were similar, and all of them had special flavor substances such as ethyl heptanate and 18-crown-6. Pleurotus eryngii mycelium and the fruiting bodies of Ganoderma lucidum and Coprinus comatus contained butylated hydroxytoluene, methyl benzoate and other unique substances. This study provides data basis for the development of high value edible fungi by analyzing the nutritional components and flavor substances of common edible fungi.

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Abstract Infrared and visible image fusion (IVIF) is an essential branch of image fusion, and enhancing the visible image of IVIF can significantly improve the fusion performance. However, many existing low‐light enhancement methods are unsuitable for the visible image enhancement of IVIF. In order to solve this problem, this paper proposes a new visible image enhancement method for IVIF. Firstly, the colour balance and contrast enhancement‐based self‐calibrated illumination estimation (CCSCE) is proposed to improve the input image's brightness, contrast, and colour information. Then, the method based on Mutually Guided Image Filtering (muGIF) is adopted to design a strategy to extract details adaptively from the original visible image, which can keep details without introducing additional noise effectively. Finally, the proposed visible image enhancement technique is used for IVIF tasks. In addition, the proposed method can be used for the visible image enhancement of IVIF and other low‐light images. Experiment results on different public datasets and IVIF demonstrate the authors’ method's superiority from both qualitative and quantitative comparisons. The authors’ code will be publicly available at https://github.com/yiqiao666/low‐light‐enhancement‐for‐IVIF/tree/master.

For agricultural production, improving the rice harvest index (HI) through agricultural management practices is a major means to enhance water and N utilization efficiency and yield. Both irrigation regimes and nitrogen (N) rates are important aspects of agricultural management practices. However, it is unclear how the rice HI is affected by water and N. This study aimed to clarify the mechanism underlying the response of the rice HI to water and N, and to explore the most suitable water-saving and N reduction management practices to ensure yield. A two-year (2021~2022) field experiment was conducted on Mollisols in Northeast China. In this experiment, nine treatments were performed, involving three irrigation regimes (flooded irrigation, controlled irrigation, and “thin-shallow-wet-dry” irrigation) and three N rates (110, 99, and 88 kg/ha). The rice agronomic traits and transfer of photoassimilates under different water and N management practices were observed and studied; rice HI, WUE, and the NUE of rice was calculated and analyzed. The highest HI was achieved under controlled irrigation with a 99 kg/ha N rate, at values of 0.622 and 0.621 in 2021 and 2022, respectively. Controlled irrigation (CI) with an appropriate reduction in the N rate increased the proportion of productive tillers, the transfer rate of dry matter and non-structural carbohydrates (NSCs), the sugar–spikelet ratio, the grain–leaf ratio, and the leaf area index (LAI) during the heading–flowering stage. A subsequent analysis indicated that the main reason for the increase in the HI was the increase in the sugar–spikelet ratio during the heading–flowering stage. A high HI increased the rice yield by increasing the thousand-grain weight. The present study suggested that water-saving irrigation regimes and appropriate N reduction not only led to water and fertilizer resource savings but also improved agronomic characteristics during rice growth and enhanced transport capacity. Thus, these practices improved the rice HI and have enormous potential for increasing yield. Therefore, regulating the rice HI through water and N management methods should be considered an important strategy for improving rice yield.

Idiopathic multicentric Castleman disease (iMCD) is a rare and cytokine storm-driven inflammatory disorder. The exact cause of iMCD is still unknown, although several hypotheses have been proposed. However, regardless of the underlying cause, the ultimate result is the activation of the inflammatory pathway, which can lead to damage in multiple organs. Currently, there have been several reports highlighting the intricate link between coronavirus disease 2019 (COVID-19) and iMCD. To better understand the impact of COVID-19-induced immune storm on iMCD, we conducted a multicenter retrospective study in three hospitals in China. A total of 28 patients with iMCD were included, among whom 25 had confirmed COVID-19 infection, and we presented 4 cases that showed different disease progression after the infection of COVID-19, including 2 who did not receive any treatment for Castleman disease before. Our findings underscore the necessity of carefully monitoring iMCD patients with COVID-19 and promptly intervening to address any changes in their condition. Besides, this study also summarized the shared cytokines between COVID-19 and iMCD. Recent studies have shown promising results in treating severe COVID-19 and iMCD using tocilizumab, an interleukin-6 receptor antagonist. Therefore, it suggests that other potential cytokine storm therapy targets that have been effective in COVID-19 may also be explored for the treatment of iMCD.

Fecal scores are crucial for assessing the digestive and gastrointestinal status of animals. The Bristol fecal scoring system is a commonly used method for the subjective evaluation of host feces, there is limited research on fecal scoring standards for fattening Hu sheep. In this study, Hu sheep were collected for rumen, rectum, and colon contents for 16S rDNA sequencing. 514 Hu sheep feces were scored based on the Bristol fecal scoring system, and production performance at each stage was measured. Finally, we developed the scoring standard of the manure of Hu sheep in the fattening period (a total of five grades). The result shows that moisture content significantly increased with higher grades (p < 0.05). We analyzed the relationship between fecal scores and production traits, blood indices, muscle nutrients, and digestive tract microorganisms. The growth traits (body weight, body height, body length, average daily gain (ADG), and average daily feed intake (ADFI) during 80–180 days), body composition traits of the F3 group, and the carcass traits were found to be significantly higher (p < 0.05) than those of the F1 and F2 groups. There was no significant difference in gastrointestinal microflora diversity among all groups (p > 0.05). Significant differences were observed in Aspartate aminotransferase, Glucose, Total bilirubin, and Red Blood Cell Count between groups (p < 0.05). The mutton moisture content in group F4 was significantly higher than in the other groups, and the protein content was also the lowest (p < 0.05). The results of the correlation analysis demonstrated that Actinobacteria, Peptostreptococcaceae, Acidaminococcales, Gammaproteobacteria, and Proteobacteria were the significant bacteria affecting fecal scores. In addition, Muribaculaceae and Oscillospiraceae were identified as the noteworthy flora affecting growth performance and immunity. This study highlights the differences in production traits and blood indicators between fecal assessment groups and the complex relationship between intestinal microbiota and fecal characteristics in Hu sheep, suggesting potential impacts on animal performance and health, which suggest strategies for improved management.