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Abstract Aims Despite being commonly found in patients with various etiologies of liver cirrhosis, cirrhotic cardiomyopathy (CCM) is often overlooked, and its mechanism remains unknown. This study aimed to illuminate the epidemiological data and risk factors of CCM and to explore its potential mechanisms through a bioinformatics analysis. Methods Clinical data were collected from January 2008 to December 2022 retrospectively, and patients were divided into the CCM and non‐CCM groups based on the criteria proposed by the 2005 World Congress of Gastroenterology. Independent risk factors for CCM were identified through a multivariate logistic regression analysis. CCM‐related genes were explored using the GeneCards database, and enrichment analysis was performed. Protein–protein interaction analysis was conducted using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes were identified using Cytoscape software. The Transcriptional Regulatory Relationships Unraveled by Sentence‐based Text Mining (TRRUST) database was utilized to explore transcription factors (TFs), and a network regulatory diagram of TF‐gene pathways was constructed. Finally, potential drugs were predicted using the Drug Gene Interaction Database. Results A total of 965 patients with liver cirrhosis were included, among whom 563 (58.3%) were diagnosed with CCM. Portal hypertension (PHT) was identified as the only independent risk factor for CCM. The hub genes included IL6, TNF, TGFB1, IL1B, MMP9, and IL10. Enrichment analysis revealed that Forkhead box O (FoxO), mitogen‐activated protein kinase (MAPK), hypoxia‐inducible factor (HIF‐1), phosphoinositide 3‐kinase‐protein kinase B (PI3K‐AKT), interleukin (IL)‐17, tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), Janus kinase/signal transducers and activators of transcription (JAK‐STAT), and transforming growth factor (TGF)‐beta pathways were enriched. TFs such as CEBPB, NFKB1, STAT1, STAT3, and SP1 were also implicated. Potential drugs included pravastatin and atorvastatin. Conclusions The morbidity associated with CCM was high, and PHT was the only independent risk factor. The mechanism may be related to inflammation, and statins may hold therapeutic promise.

Introduction: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. Objectives: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. Results: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. Conclusion: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes.

Objective This study investigates the relationship between hypertension, dysregulation of the autonomic nervous system, heart rate variability (HRV), and chronic inflammation.Methods We analysed a cohort of 50 hypertensive patients treated at the affiliated Hospital of Jianghan University. The average systolic and diastolic blood pressures (BPs) in this group were 155.26 and 95.32 mmHg, respectively. A control group of 50 healthy volunteers, undergoing routine physical examinations at the same hospital, was also analysed.Results The average systolic BP of the control group was 115.64 ± 10.27 mmHg, and the average diastolic BP was 75.33 ± 8.25 mmHg. In contrast, the experimental group exhibited an average systolic BP of 155.26 ± 20.13 mmHg and an average diastolic BP of 95.32 ± 12.16 mmHg. Both systolic and diastolic BPs were significantly higher in the hypertensive group (p

Abstract The challenge of ensuring reliability for high‐efficiency technology, multiple‐input‐multiple‐output orthogonal‐frequency‐division‐multiplexing (MIMO‐OFDM), in wireless frequency‐selective fading environments persists. In this article, the concept of spreading a symbol's energy is proposed as a viable solution to enhance transmission reliability for MIMO‐OFDM systems. And an energy‐spreading‐transform (EST)‐based MIMO‐OFDM transceiver is developed. Following the Inverse Fast Fourier Transform (IFFT) performed by the conventional MIMO‐OFDM transmitter, an orthogonal transformation called the EST is introduced. This transform spreads the energy of a symbol across the entire frequency domain and all time slots. The EST is coupled with the improved iterative detection algorithm named EST‐partial decision (PD)‐iterative‐interference‐cancellation (EST‐PD‐IIC) to maximize and leverage the potential diversity gain. Numerical simulation results demonstrate that the proposed scheme approaches the performance bound when signal‐to‐noise ratio (SNR) is about 21dB for 16‐ary quadrature amplitude modulation (16‐QAM). Complexity analysis illustrates that the computational complexity of the evolved EST‐PD‐IIC algorithm is lower than that of the famous vertically Bell laboratory layered space‐time detector (V‐BLAST) when the antenna array size is greater than 3×3. In summary, the proposed scheme is practical for providing high‐quality communication in multi‐path fading environments and can even enable a reliable communication without channel encoding when Eb/N0 exceeds a threshold in 5G‐Advanced.

Abstract Background The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). Methods Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1−4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. Results This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values

Abstract Background Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. Methods Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. Results The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p

Abstract Background RNA–DNA hybrids or R-loops are associated with deleterious genomic instability and protective immunoglobulin class switch recombination (CSR). However, the underlying phenomenon regulating the two contrasting functions of R-loops is unknown. Notably, the underlying mechanism that protects R-loops from classic RNase H-mediated digestion thereby promoting persistence of CSR-associated R-loops during CSR remains elusive. Results Here, we report that during CSR, R-loops formed at the immunoglobulin heavy (IgH) chain are modified by ribose 2′-O-methylation (2′-OMe). Moreover, we find that 2′-O-methyltransferase fibrillarin (FBL) interacts with activation-induced cytidine deaminase (AID) associated snoRNA aSNORD1C to facilitate the 2′-OMe. Moreover, deleting AID C-terminal tail impairs its association with aSNORD1C and FBL. Disrupting FBL, AID or aSNORD1C expression severely impairs 2′-OMe, R-loop stability and CSR. Surprisingly, FBL, AID’s interaction partner and aSNORD1C promoted AID targeting to the IgH locus. Conclusion Taken together, our results suggest that 2′-OMe stabilizes IgH-associated R-loops to enable productive CSR. These results would shed light on AID-mediated CSR and explain the mechanism of R-loop-associated genomic instability.

Abstract Objective In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. Methods All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. Results A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P

Abstract Objectives To compare the iatrogenic radial nerve injury (iRNI) rate of different implant (plate vs. intramedullary nail) and surgical approaches during humeral shaft fracture surgery. Methods The online PubMed database was used to search for articles describing iRNI after humeral fracture with a publication date from Jan 2000 to October 2023. The following types of articles were selected: (1) case series associating with adult humeral shaft fracture, preoperative radial nerve continuity, non-pathological fracture and non-periprosthetic fracture; (2) involving humeral shaft (OTA/AO 12) fractures. Articles where we were unable to judge surgical approach or fracture pattern (OTA/AO 12) were excluded. The data were analyzed by SPSS 27.0 and Chi-square test was performed to identify incidence of iRNI associated with different implant and surgical approaches. Results Fifty-four articles with 5063 cases were included, with 3510 cases of the plate, 830 cases of intramedullary nail and 723 cases of uncertain internal fixation. The incidences of iRNI with plate and intramedullary nail were 5.95% (209/3510) and 2.77% (23/830) (p 0.05). The iRNI rates were 2.87% (21/732) for anterograde intramedullary nail and 2.04% (2/98) for retrograde intramedullary nail (p > 0.05). In humeral bone nonunion surgery, the rate of iRNI was 15.00% (9/60) for anterolateral approach, 16.7% (2/12) for lateral approach and 18.2% (6/33) for posterior approach (p > 0.05). Conclusion Intramedullary nailing is the preferred method of internal fixation for humeral shaft fractures that has the lowest rate of iRNI. Compared with anterolateral and posterior approaches, the lateral surgical approach had a higher incidence of iRNI. The rate of iRNI in MIPO was lower than that in open reduction and internal fixation. Level of evidence Level IV.

In-situ thermal upgrading aids recovery from low-maturity oil shales where low permeability is the rate-limiting feature. We use machine leaning classified pore and pore network morphological descriptions recovered at elevated temperatures to define the dynamic thermal evolution of permeability. These descriptions define key factors influencing permeability evolution, in particular the development of anisotropy and its implication for recovery. Heating enhances permeability by increasing both the number and total cross-sectional area (SEM) of pores. Fractal dimensions indicate that the pore microstructure is anisotropic in the bedding-parallel and bedding-perpendicular directions and is upgraded by elevated temperature. The permeability anisotropy endures throughout the entire heating process and fluctuates at elevated temperature, quantified by the index called anisotropic coefficient of permeability. A newly proposed “aggregation degree” indexes the relative contribution of minority pores to overall permeability – 50 % of the permeability (K) is sourced from

BackgroundPrimary hepatic neuroendocrine tumors (PHNETs) are an utterly rare entity. The diagnosis of PHNETs could legitimize when an extrahepatic primary NET must always be excluded. PHNETs can achieve a high survival rate after complete surgical resection, however, most patients still have an 18% risk of recurrence within 5 years after surgery. In our case, the recurrence occurred 8 years after the first hepatectomy, which is relatively rare in the current literature. Therefore, rigorous postoperative follow-up is necessary for early detection and timely treatment of recurrent PHNETs.Case informationWe report a case of PHNET in a 24-year-old previously healthy female patient who relapsed 8 years after hepatectomy. This case focuses on the importance of diagnosis of primary and recurrent PHNETS in young patients, rare pathological types, and post-operative follow-up.ConclusionThis case report detailed the rare pathological morphology and characteristic immunohistochemical markers in our case for PHNETS, which enhanced the new understanding of the diagnosis of this entity. In addition, we also highlighted the variable duration of recurrence after treatment of PHNETs. The 8-year recurrent period in our case suggests the importance of regular examination in patients with PHNETs by following the doctor’s instructions.

IntroductionThis study aimed to investigate the relationship between athletes' training satisfaction and competitive state anxiety, by examining the mediating roles of psychological resilience and coping strategies. The findings provide a theoretical foundation and practical recommendations for enhancing athletes' training and mental health services.MethodsA questionnaire was utilized to assess training satisfaction, psychological resilience, coping strategies, and Competitive State Anxiety among a sample of 447 athletes. The data was examined through descriptive statistics, correlation analysis, and structural equation modeling, employing SPSS and the Process 3.5 plug-in.ResultsTraining satisfaction had a significant positive effect on psychological resilience (β = 0.726, p

Abstract Background Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. Methods 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. Results The plateau rats showed more lower left ventricular GLS and GRS (P 0.05). Conclusions After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Exploring plant behavior at the cellular scale in a minimally invasive manner is critical to understanding plant adaptation to the environment. Phytohormones play vital regulatory roles in multiple aspects of plant growth and development and acclimation to environmental changes. Since the biosynthesis, modification, transportation, and degradation of plant hormones in plants change with time and space, their content level and distribution are highly dynamic. To monitor the production, transport, perception, and distribution of phytohormones within undamaged tissues, we require qualitative and quantitative tools endowed with remarkably high temporal and spatial resolution. Fluorescent probes are regarded as excellent tools for widespread plant imaging because of their high sensitivity and selectivity, reproducibility, real-time in situ detection, and uncomplicated mechanism elucidation. In this review, we provide a systematical overview of the progress in the sensing and imaging of phytohormone fluorescent probes and fluorescently labeled phytohormones to their receptors in plants. Moreover, forthcoming viewpoints and possible applications of these fluorescent probes within the realm of plants are also presented. We hold the conviction that the new perspective brought by this paper can promote the development of fluorescent probes, enabling them to have better detection performance in plant hormone imaging.

Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic loss within the eel aquaculture sector. To date, no vaccines are available against AngHV-1. Recently, we developed a safe and efficacious live attenuated recombinant vaccine against Cyprinid herpesvirus 3 (CyHV-3). This CyHV-3 recombinant vaccine encodes a deletion of ORF57. Orthologues of CyHV-3 ORF57 exist in Cyprinid herpesvirus 2 (CyHV-2, ORF57) and AngHV-1 (ORF35). Methods: In the present study, using recombinant strains and bioluminescent in vivo imaging, we investigated the effect of AngHV-1 ORF35 deletion on virus replication in vitro, virulence in vivo, and the potential of an AngHV-1 ORF35-deleted recombinant as a vaccine candidate for the mass vaccination of eels by immersion. With this goal in mind, we produced ORF35-deleted recombinants using two parental strains: a UK strain and a recombinant derived from the former strain by insertion of a Luciferase–GFP reporter cassette into a non-coding intergenic region. Results: Analyses of ORF35-deleted recombinants led to the following observations: (i) AngHV-1 ORF35 is not essential for viral growth in cell culture, and its deletion does not affect the production of extracellular virions despite reducing the size of viral plaque. (ii) In contrast to what has been observed for CyHV-3 ORF57 and CyHV-2 ORF57, in vivo bioluminescent analyses revealed that AngHV-1 ORF35 is an essential virulence factor and that its deletion led to abortive infection in vivo. (iii) Inoculation of the AngHV-1 ORF35-deleted recombinant by immersion induced a protective immune response against a wild-type challenge. This protection was shown to be dose-dependent and to rely on the infectivity of AngHV-1 ORF35-deleted virions. Conclusions: This study suggests that the AngHV-1 ORF35 protein has singular properties compared to its orthologues encoded by CyHV-2 and CyHV-3. It also supports the potential of AngHV-1 ORF35-deleted recombinants for the mass vaccination of eels by immersion.

More than 619 million people in the world suffer from low back pain (LBP). As two potential inducers of LBP, intervertebral disc degeneration (IVDD) and fat infiltration of paraspinal muscles (PSMs) have attracted extensive attention in recent years. So far, only one review has been presented to summarize their relationship and relevant mechanisms. Nevertheless, it has several noticeable drawbacks, such as incomplete categorization and discussion, lack of practical proposals, etc. Consequently, this paper aims to systematically summarize and classify the interaction between IVDD and fat infiltration of PSMs, thus providing a one-stop search handbook for future studies. As a result, four mechanisms of IVDD leading to fat infiltration of PSMs and three mechanisms of fat infiltration in PSMs causing IVDD are thoroughly analyzed and summarized. The typical reseaches are tabulated and evaluated from four aspects, i.e., methods, conclusions, benefits, and drawbacks. We find that IVDD and fat infiltration of PSMs is a vicious cycle that can promote the occurrence and development of each other, ultimately leading to LBP and disability. Finally, eight perspectives are proposed for future in-depth research.

Objective To establish and verify a new nucleic acid extraction method for OBI detection with large volume and high sensitivity, and apply it in the quantitative determination of OBI samples with low viral load. Methods The method for nucleic acid extraction with large volume was established based on the method of Roche nucleic acid detection kit. HBV standards were configured into 10 000 IU/mL, 1 000 IU/mL, 100 IU/mL, 10 IU/mL and 1 IU/mL respectively, and nucleic acid was extracted from the 10 mL standards by magnetic beads. CT values of each concentration were detected by fluorescence quantitative PCR and each concentration gradient was detected in parallel duplicates. The logarithm of virus concentration was taken as the X-axis and the average CT values of two tests were taken as the Y-axis to construct the fluorescence quantitative standard curve and regression equation. Three repeated experiments were conducted to verify the stability of the method. This method was used to extract nucleic acid from OBI samples with low viral load, and fluorescence quantification was performed. Results The amplification efficiency of fluorescence quantitative standard curves ranged from 90% to 105%, and the regression equation was greater than 0.99. The variation coefficients of variation of CT values were 0.63%, 0.78%, 1.52%, 1.36% and 0.78%, respectively. This method can extract nucleic acid from OBI samples with viral load of 1 IU/mL for quantification. Conclusion The detection limit of HBV nucleic acid quantitative detection system can reach 1 IU/mL, and it has strong stability and high sensitivity, which can be used for the quantitative detection of OBI with low viral load.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

Abstract Background Mesothelin (MSLN) has been implicated in cancer migration, invasion, and prognosis, making it a potential tumor marker. However, the precise role of MSLN in the migration and invasion of malignant pleural mesothelioma (MPM) remains elusive, and effective noninvasive methods for assessing MSLN status are currently lacking. In this study, we focused on MSLN expression and elucidated the underlying mechanisms by which MSLN regulates migration and invasion in MPM. Building upon this knowledge, we developed an MRI nanoprobe that targets MSLN to assess its status in vitro and in vivo by comparing T2 signal intensity and T2 values on magnetic resonance imaging examinations. This nanoprobe combines the anatomical information obtained from MRI with biological information obtained from MSLN for comprehensive evaluation of MPM. Results Notably, we observed that MSLN expression in the epithelial type of MPM was higher and increased continuously with tumor growth than that in other types. In addition, MSLN upregulation promoted N-cadherin, matrix metalloproteinase-7, and MMP9 expression and resulted in higher migration/invasion ability and shorter survival. We synthesized MSLN-targeted nanoprobes (Fe3O4@SiO2-PEG-MSLN, FSPM) to assess MSLN expression by comparing the T2 signal intensity and T2 value of different cell lines and mice after 14, 28, and 42 days of modeling. Remarkably, MSLN-targeted nanoprobes demonstrated excellent targeting capabilities. In vitro studies revealed a pronounced reduction in T2 signal intensity and T2 values of the epithelial type as the probe concentration increased. In addition, in vivo experiments demonstrated a gradual decline in these parameters over time, particularly in the epithelial type as compared to the biphasic type, corresponding to the dynamic expression patterns of MSLN during different growth stages. Conclusion Our comprehensive research succeeded in confirming the regulatory mechanisms by which MSLN influences migration and invasion. Moreover, we introduced a promising method for monitoring MSLN expression that may help in facilitating the early detection, histological subtype identification, and assessment of migration, invasion, and prognosis in MPM.

Abstract Objective The aim of this study was to present an innovative surgical protocol, navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the mandibular ramus. Methods Twelve patients who presented with a large mandibular cystic lesion involving the mandibular ramus were enrolled in this study. Preoperative planning and intraoperative navigation were performed in all 12 patients. Results All patients in this study were treated with navigation-based endoscopic enucleation successfully. The follow-up period ranged from 7 to 10 months. Bone regenerated was found in all patients postoperatively. Three patients experienced temporary mandibular nerve palsy, and all relieved within 2 months. No pathological bone fracture was found during surgery. Conclusions The use of navigation-based endoscopic enucleation (NBEE) for the treatment of large mandibular cystic lesions involving the ramus proved to be an effective method for complete and precise enucleation of the cystic lesion that also preserved the surrounding tissue.

Abstract Background Previous research has reported that prenatal exposure to dexamethasone (PDE) results in organ dysplasia and increased disease susceptibility in offspring. This study aimed to investigate the epigenetic mechanism of metabolic syndrome induced by PDE in offspring. Methods Pregnant Wistar rats were administered dexamethasone, and their offspring’s serum and liver tissues were analyzed. The hepatocyte differentiation model was established to unveil the molecular mechanism. Neonatal cord blood samples were collected to validate the phenomenon and mechanism. Results The findings demonstrated that PDE leads to insulin resistance and typical metabolic syndrome traits in adult offspring rats, which originated from fetal liver dysplasia. Additionally, PDE reduced serum corticosterone level and inhibited hepatic insulin-like growth factor 1 (IGF1) signaling in fetal rats. It further revealed that liver dysplasia and functional impairment induced by PDE persist after birth, driven by the continuous downregulation of serum corticosterone and hepatic IGF1 signaling. Both in vitro and in vivo experiments confirmed that low endogenous corticosterone reduces the histone 3 lysine 9 acetylation (H3K27ac) level of IGF1 and its expression by blocking glucocorticoid receptor α, special protein 1, and P300 into the nucleus, resulting in hepatocyte differentiation inhibition and liver dysplasia. Intriguingly, neonatal cord blood samples validated the link between reduced liver function in neonates induced by PDE and decreased serum cortisol and IGF1 levels. Conclusions This study demonstrated that low endogenous glucocorticoid level under PDE lead to liver dysplasia by downregulating the H3K27ac level of IGF1 and its expression, ultimately contributing to metabolic syndrome in adult offspring.

Abstract As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2′-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state. Increasing overall H3K27 acetylation with GTA and reducing overall DNA methylation with 5-Aza not only elevated the Vitamin D receptor (VDR) expression but also reprogrammed the Vitamin D-responsive genes. Consequently, Vitamin D inhibited cell viability and migration in the epigenetically primed PDAC cells by activating genes involved in apoptosis as well as genes involved in negative regulation of cell proliferation and migration, while the opposite effect of Vitamin D was observed in unprimed cells. Studies in genetically engineered mouse PDAC cells further validated the effects of epigenetic priming for enhancing the anti-tumor activity of Vitamin D. Using gain- and loss-of-function experiments, we further demonstrated that VDR expression was necessary but not sufficient for activating the favorable transcriptomic phenotype in respond to Vitamin D treatment in PDAC, highlighting that both the VDR and Vitamin D-responsive genes were prerequisites for Vitamin D response. These data reveal a previously undefined mechanism in which epigenetic state orchestrates the expression of both VDR and Vitamin D-responsive genes and determines the therapeutic response to Vitamin D in PDAC.

Objective To investigate the condition of confidential unit exclusion(CUE) in Guangzhou, so as to ensure blood safety. Methods The number of CUE donors, demographic characteristics of CUE donors, reasons for CUE, and response time of CUE after blood donation in Guangzhou from 2009 to 2022 were statistically analyzed. Results From 2009 to 2022, the response ratios of CUE was 0.006 2% (260/4 170 984) and the ratios had statistically significant difference between different years(P0.05), but statistically significant differences were found in age, number of blood donations, education background, and marital status (P

Consensus has been widely used in distributed control, where distributed individuals need to share their states with their neighbors through communication links to achieve a common goal. However, the objectives of existing consensus-based control strategies for energy systems seldom address battery degradation cost, which is an important performance indicator to assess the performance and sustainability of battery energy storage (BES) systems. In this paper, we propose a consensus-based optimal control strategy for multi-microgrid systems, aiming at multiple control objectives including minimizing battery degradation cost. Distributed consensus is used to synchronize the ratio of BES output power to BES state-of-charge (SoC) among all microgrids while each microgrid is trying to reach its individual optimality. In order to reduce the pressure of commu-nication links and prevent excessive exposure of local information, this ratio is the only state variable shared between microgrids. Since our complex nonlinear problem might be difficult to solve by traditional methods, we design a compressive sensing-based gradient descent (CSGD) method to solve the control problem. Numerical simulation results show that our control strategy results in a 74.24 % reduction in battery degradation cost on average compared to the control method without considering battery degradation. In addition, the compressive sensing method causes an 89.12 % reduction in computation time cost compared to the traditional Monte Carlo (MC) method in solving the control problem.

In promoting the development of China's digital economy, relevant departments have given full play to the underpinning role of the rule of law, actively promoted the formulation of laws and regulations in the field of data, and put in place a foundational legal system for data that combines vertical and horizontal aspects.Firstly, this paper introduces the basic overview of China's data legal system, including both horizontal system and vertical system.Secondly, it analyzes the vertical system, including data legislation at central and local levels, and covering laws, administrative regulations, departmental rules, local regulations and local administrative rules.Thirdly, it analyzes the horizontal system, including legal systems in the fields of data security and development, personal information protection, commercial data circulation and government data management.Finally, this paper summarizes the achievements of China's data legislation and deficiencies of the current data law system, and puts forward suggestions for improvement.

Abstract Background Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-β-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. Methods To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. Results We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. Conclusions Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.

Abstract Parnassius glacialis is a typical “Out of the QTP” alpine butterfly that originated on the Qinghai-Tibet Plateau (QTP) and dispersed into relatively low-altitude mountainous. Here we assemble a chromosome-level genome of P. glacialis and resequence 9 populations in order to explore the genome evolution and local adaptation of this species. These results indicated that the rapid accumulation and slow unequal recombination of transposable elements (TEs) contributed to the formation of its large genome. Several ribosomal gene families showed extensive expansion and selective evolution through transposon-mediated processed pseudogenes. Additionally, massive structural variations (SVs) of TEs affected the genetic differentiation of low-altitude populations. These low-altitude populations might have experienced a genetic bottleneck in the past and harbor genes with selective signatures which may be responsible for the potential adaptation to low-altitude environments. These results provide a foundation for understanding genome evolution and local adaptation for “Out of the QTP” of P. glacialis.

The traditional computer with von Neumann architecture has the characteristics of separate storage and computing units, which leads to sizeable time and energy consumption in the process of data transmission, which is also the famous “von Neumann storage wall” problem. Inspired by neural synapses, neuromorphic computing has emerged as a promising solution to address the von Neumann problem due to its excellent adaptive learning and parallel capabilities. Notably, in 2016, researchers integrated light into neuromorphic computing, which inspired the extensive exploration of optoelectronic and all-optical synaptic devices. These optical synaptic devices offer obvious advantages over traditional all-electric synaptic devices, including a wider bandwidth and lower latency. This review provides an overview of the research background on optoelectronic and all-optical devices, discusses their implementation principles in different scenarios, presents their application scenarios, and concludes with prospects for future developments.

Abstract The vibration controlled transient elastography (VCTE) technique was used to assess the effectiveness of a Biejia Decoction pill in combination with Entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis. We randomly selected 120 patients to receive entecavir and 119 patients to receive both entecavir and Biejia Decoction Pill, which both with hepatitis B liver fibrosis/cirrhosis visited the Second Affiliated Hospital of Nanchang University between January 2019 and February 2022. The observation group got ETV (entecavir) and Biejia Decoction pills, whereas the control group received only standard ETV antiviral medication. Based on the grading of the VCTE detection value (LSM) initially diagnosed for patients with hepatitis B liver fibrosis/cirrhosis, we divided the patients into two subgroups of liver fibrosis and cirrhosis. In addition, patients with liver fibrosis were divided into mild and moderate subgroups according to their VCTE values. Patients were measured for liver hardness after three, six, nine, and twelve months of treatment with VCTE. Biejia Decoction Pill combined with ETV on HBV liver fibrosis/cirrhosis was evaluated by comparing patients' changes in liver hardness and HBV-DNA negative conversion rates before and after treatment in each group at the same baseline. The LSM (liver elasticity value) of the observation group and the control group after treatment was lower than that before treatment, and the difference was statistically significant (P

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Abstract Distant metastasis remains a leading cause of mortality among patients with colorectal cancer (CRC). Organotropism, referring to the propensity of metastasis to target specific organs, is a well-documented phenomenon in CRC, with the liver, lungs, and peritoneum being preferred sites. Prior to establishing premetastatic niches within host organs, CRC cells secrete substances that promote metastatic organotropism. Given the pivotal role of organotropism in CRC metastasis, a comprehensive understanding of its molecular underpinnings is crucial for biomarker-based diagnosis, innovative treatment development, and ultimately, improved patient outcomes. In this review, we focus on metabolic reprogramming, tumor-derived exosomes, the immune system, and cancer cell-organ interactions to outline the molecular mechanisms of CRC organotropic metastasis. Furthermore, we consider the prospect of targeting metastatic organotropism for CRC therapy.

Objective To explore the pathogenesis of fetal edema caused by CD36 antibody in fetal/neonatal alloimmune thrombocytopenia (FNAIT), and to provide reference for clinical prevention and treatment. Methods The established CD36 monoclonal antibody was incubated with human peripheral blood mononuclear cells (PBMC), and the concentrations of cytokines (TNF-α and IL-1β) in the supernatant of cell culture were detected by ELISA. The permeability of endothelial cells were investigated by detecting the fluorescence intensity of FITC-albumin by incubating cytokine-rich cell supernatant with human umbilical vein endothelial cells (HUVEC). Results Flow cytometry showed that CD36 monoclonal antibody could bind to human monocytes. Compared with isotype IgG control, increased cytokine TNF-α (pg/mL) (407.73±20.40 vs 29.38 ±4.72, P

Abstract Insects harbor a remarkable diversity of gut microbiomes critical for host survival, health, and fitness, but the mechanism of this structured symbiotic community remains poorly known, especially for the insect group consisting of many closely related species that inhabit the Qinghai‐Tibet Plateau. Here, we firstly analyzed population‐level 16S rRNA microbial dataset, comprising 11 Parnassius species covering 5 subgenera, from 14 populations mostly sampled in mountainous regions across northwestern‐to‐southeastern China, and meanwhile clarified the relative importance of multiple factors on gut microbial community structure and evolution. Our findings indicated that both host genetics and larval host plant modulated gut microbial diversity and community structure. Moreover, the effect analysis of host genetics and larval diet on gut microbiomes showed that host genetics played a critical role in governing the gut microbial beta diversity and the symbiotic community structure, while larval host plant remarkably influenced the functional evolution of gut microbiomes. These findings of the intimate insect–microbe–plant interactions jointly provide some new insights into the correlation among the host genetic background, larval host plant, the structure and evolution of gut microbiome, as well as the mechanisms of high‐altitude adaptation in closely related species of this alpine butterfly group.

Purpose: Predictors of ‘imminent’ risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals. Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes. Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32–26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25–3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32–3.34). Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration.

Abstract Background Mortality following hip fracture is high and incompletely understood. We hypothesize that hip musculature size and quality are related to mortality following hip fracture. This study aims to investigate the associations of hip muscle area and density from hip CT with death following hip fracture as well as assess the dependence of this association on time after hip fracture. Methods In this secondary analysis of the prospectively collected CT images and data from the Chinese Second Hip Fracture Evaluation, 459 patients were enrolled between May 2015 and June 2016 and followed up for a median of 4.5 years. Muscle cross‐sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur. The Goutallier classification (GC) was used for qualitatively assessing muscle fat infiltration. Separate Cox models were used to predict mortality risk adjusted for covariates. Results At the end of the follow‐up, 85 patients were lost, 81 patients (64% women) had died, and 293 (71% women) survived. The mean age of non‐surviving patients at death (82.0 ± 8.1 years) was higher than that of the surviving patients (74.4 ± 9.9 years). The Parker Mobility Score and the American Society of Anesthesiologists scores of the patients that died were respectively lower and higher compared to the surviving patients. Hip fracture patients received different surgical procedures, and no significant difference in the percentage of hip arthroplasty was observed between the dead and the surviving patients (P = 0.11). The cumulative survival was significantly lower for patients with low G.MaxM area and density and low G.Med/MinM density, independent of age and clinical risk scores. The GC grades were not associated with the mortality after hip fracture. Muscle density of both G.MaxM (adj. HR 1.83; 95% CI, 1.06–3.17) and G.Med/MinM (adj. HR 1.98; 95% CI, 1.14–3.46) was associated with mortality in the 1st year after hip fracture. G.MaxM area (adj. HR 2.11; 95% CI, 1.08–4.14) was associated with mortality in the 2nd and later years after hip fracture. Conclusion Our results for the first time show that hip muscle size and density are associated with mortality in older hip fracture patients, independent of age and clinical risk scores. This is an important finding to better understand the factors contributing to the high mortality in older hip fracture patients and to develop better future risk prediction scores that include muscle parameters.

Human epidermal growth factor 2 (HER2) mutations are uncommon in non-small cell lung cancer (NSCLC), and the lack of established, effective, targeted drugs has resulted in a persistently poor prognosis. Herein, we report the case of a non-smoking, 58-year-old man diagnosed with lung adenocarcinoma (cT3N0M1c, stage IVB) harboring a HER2 mutation (Y772_A775dupYVMA) and PD-L1 (-). The patient’s Eastern Cooperative Oncology Group performance status (PS) score was assessed as 1. He commenced first-line treatment with chemotherapy, followed by immuno-chemotherapy, and with disease progression, he received HER2-targeted therapy and chemotherapy with an anti-angiogenic agent. However, HER2-targeted therapy, including pan-HER tyrosine kinase inhibitors (afatinib, pyrotinib, and pozitinib) and antibody–drug conjugate (T-DM1), produced only stable disease (SD) as the best response. After the previously described treatment, primary tumor recurrence and multiple brain metastases were observed. Despite the patient’s compromised overall physical condition with a PS score of 3-4, he was administered T-DXd in addition to whole-brain radiotherapy (WBRT). Remarkably, both intracranial metastases and primary lesions were significantly reduced, he achieved a partial response (PR), and his PS score increased from 3-4 to 1. He was then treated with T-DXd for almost 9 months until the disease again progressed, and he did not discontinue the drug despite the occurrence of myelosuppression during this period. This is a critical case as it exerted an effective response to T-DXd despite multiple lines therapy, including T-DM1. Simultaneously, despite the occurrence of myelosuppression in the patient during T-DXd, it was controlled after aggressive treatment.

BackgroundIschemic heart disease (IHD) is the leading cause of death among noncommunicable diseases worldwide, but data on current epidemiological patterns and associated risk factors are lacking. ObjectiveThis study assessed the global, regional, and national trends in IHD mortality and attributable risks since 1990. MethodsMortality data were obtained from the Global Burden of Disease 2019 Study. We used an age-period-cohort model to calculate longitudinal age curves (expected longitudinal age-specific rate), net drift (overall annual percentage change), and local drift (annual percentage change in each age group) from 15 to >95 years of age and estimate cohort and period effects between 1990 and 2019. Deaths from IHD attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and theoretical minimum risk exposure level. ResultsIHD is the leading cause of death in noncommunicable disease–related mortality (118.1/598.8, 19.7%). However, the age-standardized mortality rate for IHD decreased by 30.8% (95% CI –34.83% to –27.17%) over the past 30 years, and its net drift ranged from –2.89% (95% CI –3.07% to –2.71%) in high sociodemographic index (SDI) region to –0.24% (95% CI –0.32% to –0.16%) in low-middle–SDI region. The greatest decrease in IHD mortality occurred in the Republic of Korea (high SDI) with net drift –6.06% (95% CI –6.23% to –5.88%), followed by 5 high-SDI nations (Denmark, Norway, Estonia, the Netherlands, and Ireland) and 2 high-middle–SDI nations (Israel and Bahrain) with net drift less than –5.00%. Globally, age groups of >60 years continued to have the largest proportion of IHD-related mortality, with slightly higher mortality in male than female group. For period and birth cohort effects, the trend of rate ratios for IHD mortality declined across successive period groups from 2000 to 2004 and birth cohort groups from 1985 to 2000, with noticeable improvements in high-SDI regions. In low-SDI regions, IHD mortality significantly declined in female group but fluctuated in male group across successive periods; sex differences were greater in those born after 1945 in middle- and low-middle–SDI regions and after 1970 in low-SDI regions. Metabolic risks were the leading cause of mortality from IHD worldwide in 2019. Moreover, smoking, particulate matter pollution, and dietary risks were also important risk factors, increasingly occurring at a younger age. Diets low in whole grains and legumes were prominent dietary risks in both male and female groups, and smoking and high-sodium diet mainly affect male group. ConclusionsIHD, a major concern, needs focused health care attention, especially for older male individuals and those in low-SDI regions. Metabolic risks should be prioritized for prevention, and behavioral and environmental risks should attract more attention to decrease IHD mortality.

The characterization of X-ray focal spots is of great significance for the diagnosis and performance optimization of focusing systems. X-ray free-electron lasers (XFELs) are the latest generation of X-ray sources with ultrahigh brilliance, ultrashort pulse duration and nearly full transverse coherence. Because each XFEL pulse is unique and has an ultrahigh peak intensity, it is difficult to characterize its focal spot size individually with full power. Herein, a method for characterizing the spot size at the focus position is proposed based on coherent diffraction imaging. A numerical simulation was conducted to verify the feasibility of the proposed method. The focal spot size of the Coherent Scattering and Imaging endstation at the Shanghai Soft X-ray Free Electron Laser Facility was characterized using the method. The full width at half-maxima of the focal spot intensity and spot size in the horizontal and vertical directions were calculated to be 2.10 ± 0.24 µm and 2.00 ± 0.20 µm, respectively. An ablation imprint on the silicon frame was used to validate the results of the proposed method.

Abstract In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss.

[Objective] A nonlinear failure criterion of root-soil composites and the nonlinear characteristics of root-soil composites was studied combining with the strength of root-soil composites under three root content conditions (G=0.12%, 0.24%, and 0.36%) and three moisture content conditions (w=13.22%, 16.22%, and 19.22%). [Methods] The GDS triaxial apparatus was used to conduct consolidated-undrained triaxial tests to obtain the stress-strain curves and shear strength parameters of root-soil composites. [Results] Unreinforced soil and root-soil composite stress-strain curves exhibited characteristics of hardening. Additionally, moisture content was negatively correlated with the peak stress of rooted soil, while root content was positively correlated. Under the condition of G=0.36%, 70.1% was the maximum increase of peak strength of the root-soil composite. When w=13.22%, the peak strength of the root-soil composite increased by a maximum of 86.7%. The nonlinear failure criterion of root-soil composites was nonlinear when the normal stress was lower than the critical stress, and linear when the normal stress was higher than the critical stress. The key parameters that described the effect of roots in the nonlinear failure criterion were c and k. c had a positive correlation with root content and moisture content. The contribution of roots in rooted soil shear strength increased with increasing c. Moreover, k was positively correlated with root content and negatively correlated with moisture content. The smaller the value of k, the more obvious the nonlinear characteristic of the strength envelope of the root-soil composite. [Conclusion] The strength of root-soil composites is greatly influenced by root content and moisture content. The stress-strain relationship curves of both unreinforced soil and root-soil composite showed a hardening type, and the hardening degree of the root soil composite is significantly higher than that of unreinforced soil, indicating that the addition of roots can simultaneously increase the strength and stiffness of the soil.

Abstract This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p

The Richards’ equation is widely used in the simulation of unsaturated flow and related fields. In the numerical solution process, the finite difference method can be used to carry out numerical discretization and iterative calculation. However, in order to obtain a more reliable numerical solution, the space step size of a conventional uniform grid is often small. For some unfavorable numerical conditions, such as infiltration into dry soil, iterative calculation is time-consuming and even the accuracy cannot be improved very well. Therefore, an improved method is proposed by using the Chebyshev space grid, which combines the finite difference method to numerically discretize the Richards’ equation to obtain linear equations. Then the classic Picard iterative method is used to iteratively solve the linear equations to obtain the numerical solutions of the Richards’ equations. Through two examples of unsaturated flow under unfavorable conditions for homogeneous soil and layered soil, combined with the analytical solution of the model and the software Hydrus-1D, the accuracy of the numerical solution obtained by the improved grid method and the uniform grid method is compared and examined. The results show that the proposed Chebyshev grid method can obtain higher numerical accuracy with a smaller number of nodes than the traditional uniform grid, and the computational cost is smaller. This method has a good application prospect.

Steady-state visual evoked potential (SSVEP) signal collected from the scalp typically contains other types of electric signals, and it is important to remove these noise components from the actual signal by application of a pre-processing step for accurate analysis. High-pass or bandpass filtering of the SSVEP signal in the time domain is the most common pre-processing method. Because frequency is the most important feature information contained in the SSVEP signal, a technique for frequency-domain filtering of SSVEP was proposed here. In this method, the time-domain signal is extended to multi-dimensional signal by empirical mode decomposition (EMD), where each dimension represents a intrinsic mode function (IMF). The multi-dimensional signal is transformed to a frequency-domain signal by 2-D Fourier transform, the Gaussian high-pass filter function is constructed to perform high-pass filtering, and then the filtered signal is transformed to time domain by 2-D inverse Fourier transform. Finally, the filtered multi-dimensional intrinsic mode function is superimposed and averaged as the frequency-domain filtered signal. Compared with the time-domain filtering method, the experimental results revealed that frequency-domain filtering method effectively removed the baseline drift in signal and effectively suppressed the low-frequency interference component. This method was tested using data from public datasets and the results show that the proposed frequency-domain filtering method can significantly improve the feature recognition performance of canonical correlation analysis (CCA), filter bank canonical correlation analysis (FBCCA), and task-related component analysis (TRCA) methods. Thus, the results suggest that the application of frequency-domain filtering in the pre-processing stage allows improved noise removal. The proposed method extends SSVEP signal filtering from time-domain to frequency-domain, and the results suggest that this analysis tool significantly promotes the practical application of SSVEP systems.

The rise and development of the metaverse have brought challenges to legal regulation.The metaverse is not a place outside the law, it also needs to abide by the law and ensure the correct operation in the legal orbit.Firstly, the development characteristics of the metaverse were summarized, such as technological, commercial, social as well as transnational, and the risks and responses were analyzed.Secondly, the main legal conundrums of the metaverse were analyzed including cybersecurity, personal information and privacy protection, data governance, virtual property, ecological governance, platform liability, and cybercrime.Finally, the idea of regulating metaverse development according to law was put forward, it was suggested to adhere to the principle of safe and controllable development, the appropriately advanced layout of legislation of metaverse, promote regulations in main areas through legislative means such as enactment, reform, abolition, and interpretation, and achieved good governance through good laws.

This paper proposes a prediction strategy for the hydrodynamic performance of bionic fish. The major challenges are meshing and building prediction model. The NACA0012 airfoil is used to replace the fish driven by the body and/or caudal fin (BCF), and a two-dimensional swimming geometric model is constructed. The geometric model is divided into hybrid meshes using the overset mesh method. The classical traveling wave model is studied using Matlab, and an improved self-propelled motion model is established. The hydrodynamic performance of the self-propelled model is numerically simulated based on computational fluid dynamics (CFD). In this strategy, the geometric model and the self-propelled motion model are integrated with user defined functions (UDF). The influences of the parameters such as inflow velocity, frequency, wavelength, and head fluctuation amplitude on the motion performance are studied. The results show that when inflow velocity is uniform, the self-propelled motion will eventually reach a quasi-steady state. According to the numerical simulation results, a hydrodynamic performance prediction model is established based on multilayer perceptron (MLP). The model is used to predict the performance of the optimized traveling wave parameters, and the error is within 3[Formula: see text]. The accuracy and generalization ability of the MLP prediction model is verified.

AbstractThere are few studies on denitrification related to the nitrogen cycle in Ebinur Lake wetland. This study aimed to explore the response of the diversity and composition of denitrifying bacteria to the environmental factors in wetland, so as to obtain more information about the community structure of denitrifying bacteria driven by environmental factors. Using the genes encoding nitrite reductase (nirS and nirK) as molecular markers, we analysed the seasonal changes in the diversity of denitrifying bacteria in halophyte soils by high-throughput sequencing technology. The results showed that the diversity of denitrifying bacteria was higher in July and lower in April, showing seasonal changes. The diversity index of denitrifying bacteria in rhizosphere soil was higher than that in non-rhizosphere soil. The diversity of denitrifying bacteria in the Phragmites australis rhizosphere soil was the highest. The diversity of nirK denitrifying bacteria was higher than that of nirS denitrifying bacteria, but the relative abundance was lower than that of nirS denitrifying bacteria. Three-way ANOVA showed that soil types, vegetation types and season had significant effects on the diversity of denitrifying bacteria. Furthermore, redundancy analysis indicated that nitrate was the environmental factor that significantly affected the community structure of nirS denitrifying bacteria in wetland, and electric conductivity, total nitrogen, ammonium and nitrate were the environmental factors that significantly affected the community structure of nirK denitrifying bacteria. These results provide data basis and theoretical support for the dynamic change of diversity of denitrifying bacteria in wetland.

4-Hydrophenylpyruvate dioxygenase (HPPD), a key enzyme involved in tyrosine catabolism, has long been considered a promising target for herbicides and drugs. Several types of HPPD inhibitors have been developed as high-potency drugs or herbicides. Understanding the structural basis of the binding of these inhibitors with HPPD will be beneficial for the development of inhibitors containing novel scaffolds. However, only limited structural information regarding the binding of triketone and pyrazole derivatives with HPPD has been reported. Here, the crystal structures of HPPD complexed with inhibitors containing different scaffolds, including triketone, pyrazole, isoxazole, heterocyclic amide, and quinazolindione derivatives, were comprehensively analyzed. Detailed binding modes of isoxazole and heterocyclic amide derivatives with HPPD were first revealed, facilitating further structural optimization. The binding mode of compound 2 with HPPD suggests that both oxygen and nitrogen atoms can mediate coordination with the metal ion. These results will provide the structure-based rational design of novel HPPD inhibitors.

Background: Severe sarcopenia may result in severe disability. Early diagnosis is currently the key to enhancing the treatment of sarcopenia, and there is an urgent need for a highly sensitive and dependable tool to evaluate the course of early sarcopenia in clinical practice. This study aims to investigate longitudinally the early diagnosability of magnetic resonance imaging (MRI)-based fat infiltration and blood flow perfusion technology in sarcopenia progression. Methods: 48 Sprague-Dawley rats were randomly assigned into six groups that were based on different periods of dexamethasone (DEX) injection (0, 2, 4, 6, 8, 10 days). Multimodal MRI was scanned to assess muscle mass. Grip strength and swimming exhaustion time of rats were measured to assess muscle strength and function. Immunofluorescence staining for CD31 was employed to assess skeletal muscle capillary formation, and western blot was used to detect vascular endothelial growth factor-A (VEGF-A) and muscle ring finger-1 (MuRF-1) protein expression. Subsequently, we analyzed the correlation between imaging and histopathologic parameters. A receiver operating characteristic (ROC) analysis was conducted to assess the effectiveness of quantitative MRI parameters for discriminating diagnosis in both pre- and post-modeling of DEX-induced sarcopenic rats. Results: Significant differences were found in PDFF, R2* and T2 values on day 2 of DEX-induction compared to the control group, occurring prior to the MRI-CSA values and limb grip strength on day 6 of induction and swimming exhaustion time on day 8 of induction. There is a strong correlation between MRI-CSA with HE-CSA values (r = 0.67; p