Search

Fulminant myocarditis (FM) is characteristically associated with rapid progressive decline in cardiac function and high mortality, with rapid onset of hemodynamic dysfunction and severe arrhythmias. In this report, we describe a case concerning a patient clinically diagnosed with FM, marked by rapid progression leading to intractable ventricular fibrillation and subsequent cardiac arrest. Conventional cardiopulmonary resuscitation (CCPR) was performed 120 min before extracorporeal membrane oxygenation (ECMO) was initiated. This critical situation was effectively addressed through the utilization of extracorporeal cardiopulmonary resuscitation (ECPR). By providing sustained cardiopulmonary support, effective hemodynamics were obtained. Eventually, the patient made a full recovery, and discharged without neurologic complications on hospital day 13.

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

Pear anthracnose, caused by Colletotrichum bacteria, is a severe infectious disease that significantly impacts the growth, development, and fruit yield of pear trees. Early detection of pear anthracnose before symptoms manifest is of great importance in preventing its spread and minimizing economic losses. This study utilized hyperspectral imaging (HSI) technology to investigate early detection of pear anthracnose through spectral features, vegetation indices (VIs), and texture features (TFs). Healthy and diseased pear leaves aged 1 to 5 days were selected as subjects for capturing hyperspectral images at various stages of health and disease. Characteristic wavelengths (OWs1 and OWs2) were extracted using the Successive Projection Algorithm (SPA) and Competitive Adaptive Reweighted Sampling (CARS) algorithm. Significant VIs were identified using the Random Forest (RF) algorithm, while effective TFs were derived from the Gray Level Co-occurrence Matrix (GLCM). A classification model for pear leaf early anthracnose disease was constructed by integrating different features using three machine learning algorithms: Support Vector Machine (SVM), Extreme Learning Machine (ELM), and Back Propagation Neural Network (BPNN). The results showed that: the classification identification model constructed based on the feature fusion performed better than that of single feature, with the OWs2-VIs-TFs-BPNN model achieving a highest accuracy of 98.61% in detection and identification of pear leaf early anthracnose disease. Additionally, to intuitively and effectively monitor the progression and severity of anthracnose in pear leaves, the visualization of anthracnose lesions was achieved using Successive Maximum Angle Convex Cone (SMACC) and Spectral Information Divergence (SID) techniques. According to our research results, the fusion of multi-source features based on hyperspectral imaging can be a reliable method to detect early asymptomatic infection of pear leaf anthracnose, and provide scientific theoretical support for early warning and prevention of pear leaf diseases.

BackgroundDespite advances in neuro-oncology, treatments of glioma and tools for predicting the outcome of patients remain limited. The objective of this research is to construct a prognostic model for glioma using the Homologous Recombination Deficiency (HRD) score and validate its predictive capability for glioma.MethodsWe consolidated glioma datasets from TCGA, various cancer types for pan-cancer HRD analysis, and two additional glioma RNAseq datasets from GEO and CGGA databases. HRD scores, mutation data, and other genomic indices were calculated. Using machine learning algorithms, we identified signature genes and constructed an HRD-related prognostic risk model. The model’s performance was validated across multiple cohorts. We also assessed immune infiltration and conducted molecular docking to identify potential therapeutic agents.ResultsOur analysis established a correlation between higher HRD scores and genomic instability in gliomas. The model, based on machine learning algorithms, identified seven key genes, significantly predicting patient prognosis. Moreover, the HRD score prognostic model surpassed other models in terms of prediction efficacy across different cancers. Differential immune cell infiltration patterns were observed between HRD risk groups, with potential implications for immunotherapy. Molecular docking highlighted several compounds, notably Panobinostat, as promising for high-risk patients.ConclusionsThe prognostic model based on the HRD score threshold and associated genes in glioma offers new insights into the genomic and immunological landscapes, potentially guiding therapeutic strategies. The differential immune profiles associated with HRD-risk groups could inform immunotherapeutic interventions, with our findings paving the way for personalized medicine in glioma treatment.

BackgroundThere is limited knowledge regarding the association between heart rate (HR) during different exercise phases and coronary artery disease (CAD). This study aimed to evaluate the relationship between four exercise-related HR metrics detected by cardiopulmonary exercise testing (CPET) and CAD. These metrics include HR at the anaerobic threshold (HRAT), HR at respiratory compensatory point (HRRCP), maximal HR (HRmax), and HR 60 s post-exercise (HRRec60s).MethodsThe 705 participants included 383 with CAD and 322 without CAD in Beijing Hospital, who underwent CPET between January 2021 and December 2022. The Logistic regression analysis was applied to estimate the odds ratio and the 95% confidence interval. Additionally, the multivariable Logistic regression analyses with restricted cubic splines were conducted to characterize the dose-response association and explore whether the relationship was linear or nonlinear.ResultsOur primary finding indicates that for each one-beat increase in HRAT, there is a 2.8% reduction in the adjusted risk of CAD in the general population. Similarly, a one-beat increase in HRRCP corresponds to a 2.6% reduction in the adjusted risk of CAD. Subgroup analyses revealed significant interactions between HRAT and factors such as sex, hypertension, and lung cancer, as well as between HRRCP and sex and hypertension, in relation to CAD. The dose-response analysis further confirmed that higher HRAT and HRRCP are associated with a reduced risk of CAD.ConclusionThese results are suggestive of a good association between HRAT, HRRCP, and CAD. The lower HRAT, and HRRCP are signs of poor HR response to exercise in CAD. HRAT and HRRCP are potentially good indicators of poor HR response to exercise without considering maximal effort.

Achaete-Scute Complex Homolog 1 (ASCL1) is a key regulator in the development and function of the nervous system, particularly in the process of neuronal and neuroendocrine cell differentiation. By employing the CRISPR/Cas9 system, we successfully established an ASCL1-mCherry knock-in human embryonic stem cell (hESC) line by inserting a P2A-mCherry fragment at the ASCL1 locus. The mCherry reporter effectively demonstrated the expression level of endogenous ASCL1 during the process of inducing pulmonary neuroendocrine cells (PNECs) from hESC. This reporter cell line holds significant value as a research tool for investigating the process of lung neuroendocrine cell differentiation, conducting drug screening, and exploring the underlying mechanisms of lung diseases associated with PNECs dysfunction.

Hybridization can substantially improve growth performance. This study used metagenomics and metabolome sequencing to examine whether the rumen microbiota and its metabolites contributed to this phenomenon. We selected 48 approximately 3 month-old male ♂Hu × ♀Hu (HH, n = 16), ♂Poll Dorset × ♀Hu (DH, n = 16), and ♂Southdown × ♀Hu (SH, n = 16) lambs having similar body weight. The sheep were fed individually under the same nutritional and management conditions for 95 days. After completion of the trial, seven sheep close to the average weight per group were slaughtered to collect rumen tissue and content samples to measure rumen epithelial parameters, fermentation patterns, microbiota, and metabolite profiles. The final body weight (FBW), average daily gain (ADG), and dry matter intake (DMI) values in the DH and SH groups were significantly higher and the feed-to-gain ratio (F/G) significantly lower than the value in the HH group; additionally, the papilla height in the DH group was higher than that in the HH group. Acetate, propionate, and total volatile fatty acid (VFA) concentrations in the DH group were higher than those in the HH group, whereas NH3-N concentration decreased in the DH and SH groups. Metagenomic analysis revealed that several Prevotella and Fibrobacter species were significantly more abundant in the DH group, contributing to an increased ability to degrade dietary cellulose and enrich their functions in enzymes involved in carbohydrate breakdown. Bacteroidaceae bacterium was higher in the SH group, indicating a greater ability to digest dietary fiber. Metabolomic analysis revealed that the concentrations of rumen metabolites (mainly lysophosphatidylethanolamines [LPEs]) were higher in the DH group, and microbiome-related metabolite analysis indicated that Treponema bryantii and Fibrobacter succinogenes were positively correlated with the LPEs. Moreover, we found methionine sulfoxide and N-methyl-4-aminobutyric acid were characteristic metabolites in the DH and SH groups, respectively, and are related to oxidative stress, indicating that the environmental adaptability of crossbred sheep needs to be further improved. These findings substantially deepen the general understanding of how hybridization promotes growth performance from the perspective of rumen microbiota, this is vital for the cultivation of new species and the formulation of precision nutrition strategies for sheep.

The current trajectory planning methods for multi‐robot systems face challenges due to high computational burden and inadequate adaptability in complex constrained environments, obstructing efficiency improvements in production and logistics. This article presents an innovative solution by integrating model predictive contouring control (MPCC) and long short‐term memory (LSTM) networks for real‐time trajectory planning of multiple mobile robots. Based on the datasets generated by MPCC, a customized LSTM network is constructed to learn the collaborative planning behavior from these datasets offline, subsequently producing smooth and efficient trajectories online with a low computational burden. Moreover, a hybrid control scheme, incorporating a lidar‐based safety evaluator, avoids unexpected collision risks by switching to MPCC when necessary, ensuring the overall safety and reliability of the multi‐robot system. The proposed hybrid LSTM method is implemented and tested in the robot operating system (ROS) within diverse constrained scenarios. Experimental results demonstrate that the hybrid LSTM method achieves ≈6% enhancements in trajectory productivity and a reduced computational burden of roughly 75% compared to MPCC, thereby providing a promising solution for local multi‐robot trajectory planning in logistics transportation tasks.

Abstract Background Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD. Method We used genetic variants associated with inflammatory cytokines from a meta‐analysis of genome‐wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse‐Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR‐Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results. Result We found interferon‐gamma (IFN‐γ, p = 2.14 × 10–6, OR = 0.870, 95% CI = 0.821–0.921), interleukin‐1 beta (IL‐1b, p = 0.012, OR = 0.951, 95% CI = 0.914–0.989), interleukin‐4 (IL‐4, p = 0.034, OR = 0.946, 95% CI = 0.899–0.996), interleukin‐18 (IL‐18, p = 0.028, OR = 0.964, 95% CI = 0.934–0.996), granulocyte colony‐stimulating factor (GCSF, p = 0.010, OR = 0.919, 95% CI = 0.861–0.980), and Stromal cell‐derived factor 1a (SDF1a, p = 0.014, OR = 1.072, 95% CI = 1.014–1.134) were causally associated with risk of IVDD. Conclusion Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN‐γ, IL‐1b, IL‐4, IL‐18, SDF1a, and GCSF) and altered IVDD risk.

Abstract Background Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. Methods Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni–NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. Results In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αβ T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. Conclusion Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Abstract The engineered clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas) system is currently widely applied in genetic editing and transcriptional regulation. The catalytically inactivated CasRx (dCasRx) has the ability to selectively focus on the mRNA coding region without disrupting transcription and translation, opening up new avenues for research on RNA modification and protein translation control. This research utilized dCasRx to create a translation-enhancement system for mammals called dCasRx-eIF4GI, which combined eukaryotic translation initiation factor 4G (eIF4GI) to boost translation levels of the target gene by recruiting ribosomes, without affecting mRNA levels, ultimately increasing translation levels of different endogenous proteins. Due to the small size of dCasRx, the dCasRx-eIF4GI translation enhancement system was integrated into a single viral vector, thus optimizing the delivery and transfection efficiency in subsequent applications. Previous studies reported that ferroptosis, mediated by calcium oxalate (CaOx) crystals, significantly promotes stone formation. In order to further validate its developmental potential, it was applied to a kidney stone model in vitro and in vivo. The manipulation of the ferroptosis regulatory gene FTH1 through single-guide RNA (sgRNA) resulted in a notable increase in FTH1 protein levels without affecting its mRNA levels. This ultimately prevented intracellular ferroptosis and protected against cell damage and renal impairment caused by CaOx crystals. Taken together, this study preliminarily validated the effectiveness and application prospects of the dCasRx-eIF4GI translation enhancement system in mammalian cell-based disease models, providing novel insights and a universal tool platform for protein translation research and future therapeutic approaches for nephrolithiasis.

Abstract The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Discriminating strong aroma-type Baijiu (SAB) of different origins was significant for product quality control and origin protection. In this study, a 4×3 sensor array was constructed based on the Ag nanoprism (AgNPR) etching mechanism, in which four AgNPRs varying in shape and size were used as sensing materials, and two metal ions and one oxide anion were used as oxidation etchants. With this array, colorimetric reaction was conducted on 41 representative SAB samples from Sichuan, Jianghuai and North China. The obtained colorimetric signal values were subjected to linear discriminant analysis (LDA). Furthermore, some samples of unknown origin were selected to perform external validation on the discrimination model. Based on the results of colorimetric reaction mechanism, the samples could promote the etching effect of AgNPRs, which might be related to various organic acids contained in Baijiu. Sample discrimination showed that single array produced a comparatively low effect on samples of different origins. The combination of three arrays significantly improved the discrimination effect, whose rate of origin discrimination was up to 99% for 41 samples, and was up to 98% for 15 unknown samples. With combined array, the discriminant rates of 21 samples from 5 brands in Sichuan and 13 samples from 3 brands in Jianghuai could reach 99% and 100%, respectively, while all the discriminant rates could reach 100% for different grades of products from various manufacturers in Sichuan with single array. Being simple and fast, the nanocolorimetric sensing method adopted in this study is not only applicable to product identification and anti-counterfeiting, but also be auxiliarily used for quality control in production process, laying a research foundation for intelligent quality monitoring of Baijiu.

Abstract Cellular behavior is regulated by mechanical signals within the cellular microenvironment. Additionally, changes of temperature, blood flow, and muscle contraction also affect cellular state and the development of diseases. In clinical practice, physical therapy techniques such as ultrasound, vibration, exercise, cold therapy, and hyperthermia are commonly employed to alleviate pain and treat diseases. However, the molecular mechanism about how these physiotherapy methods stimulate local tissues and control gene expression remains unknow. Fortunately, the discovery of YAP filled this gap, which has been reported has the ability to sense and convert a wide variety of mechanical signals into cell-specific programs for transcription, thereby offering a fresh perspective on the mechanisms by which physiotherapy treat different diseases. This review examines the involvement of Hippo/YAP signaling pathway in various diseases and its role in different physical therapy approaches on diseases. Furthermore, we explore the potential therapeutic implications of the Hippo/YAP signaling pathway and address the limitations and controversies surrounding its application in physiotherapy.

Abstract Background The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. Methods We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). Results The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. Conclusion These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

Abstract The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Abstract Post-stroke depression (PSD) is regarded as the consequence of multiple contributors involving the process of cognition, mood and autonomic system, with the specific mechanism unclear yet. As a common type of stroke-heart syndromes, post-stroke arrhythmia shared some common pathogenesis with PSD. We presumed that post-stroke arrhythmia might be an early distinguishable marker for the presence of PSD and aimed to verity their association in this study. Patients with first-ever ischemic stroke were enrolled. The presence of post-stroke ectopic arrhythmia and the symptoms of arrhythmia were recorded with anti-arrhythmia drugs prescribed when necessary. Patients were followed up 3 months later to identify their presence and severity of PSD using Hamilton Depression Scale (HAMD) and also presence and severity of arrhythmia. Characteristics including the prevalence of various types of arrhythmias were compared between PSD and non-PSD groups. The HAMD scores were compared between patients with and without arrhythmia in PSD group. Logistic regression was used to identify the independent predictor of PSD. Patients with PSD had higher prevalence of post-stroke arrhythmia especially newly-detected arrhythmia, symptomatic arrhythmia and poor-controlled arrhythmia. In PSD group, patients of post-stroke arrhythmia had higher scores of HAMD than those without arrhythmia. Presence of newly-detected, symptomatic and poor-controlled arrhythmias were independent predictor of PSD. post-stroke arrhythmia especially newly-detected arrhythmia and symptomatic arrhythmia could be an early predictor of PSD. Successful control of arrhythmia was associated with reduced prevalence and severity of PSD.

Abstract Background Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. Methods In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP–RIPK1–NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1β and in the post-traumatic OA model. Results In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. Conclusions These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.

Abstract Background The objective of this study was to detect the urinary levels of chlorpyrifos, paraquat, and cyproconazole in residents living in Fuyang City and to analyze the correlation between these urinary pesticides levels and the severity of fatty liver disease (FLD). Methods All participants’ fat fraction (FF) values were recorded by MRI (Magnetic resonance imaging). First-morning urine samples were collected from 53 participants from Fuyang Peoples’Hospital. The levels of three urinary pesticides were measured using β-glucuronidase hydrolysis followed by a. The results were analyzed by using Pearson correlation analysis and binary logistic regression analysis to reveal the correlation between three urinary pesticides and the severity of fatty liver. Results 53 individuals were divided into 3 groups based on the results from MRI, with 20 cases in the normal control group, 16 cases in the mild fatty liver group, and 17 cases in the moderate and severe fatty liver group. Urinary chlorpyrifos level was increased along with the increase of the severity of fatty liver. Urinary paraquat level was significantly higher both in the low-grade fatty liver group and moderate & serve grade fatty liver group compared with the control group. No significant differences in urinary cyproconazole levels were observed among the three groups. Furthermore, urinary chlorpyrifos and paraquat levels were positively correlated with FF value. And chlorpyrifos was the risk factor that may be involved in the development of FLD and Receiver Operating Characteristic curve (ROC curve) analysis showed that chlorpyrifos and paraquat may serve as potential predictors of FLD. Conclusion The present findings indicate urinary chlorpyrifos and paraquat were positively correlated with the severity of fatty liver. Moreover, urinary chlorpyrifos and paraquat have the potential to be considered as the predictors for development of FLD. Thus, this study may provide a new perspective from the environmental factors for the diagnosis, prevention, and treatment of FLD.

Abstract Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables’ pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p

AbstractPurpose This study aimed to improve the accuracy of brain-computer interface (BCI) systems based on motor imagery (MI) and mental arithmetic (MA) by utilizing functional near-infrared spectroscopy (fNIRS) and an improved dilation CapsuleNet (ID-CapsuleNet) model.Methods The study focused on the characteristics of fNIRS and employed large-kernel dilation convolution to extract hemodynamic features from fNIRS data. Inspired by CapsuleNet’s success in image classification, an ID-CapsuleNet model was designed, combining large-kernel dilation convolution and CapsuleNet. Four publicly available datasets (A, B, C, and D) were utilized for evaluating the proposed model. Datasets A and B were MA type, while datasets C and D were MI type. Ablation experiments were conducted to assess the usefulness of large-kernel convolution, dynamic routing, and dilation convolution.Results The average accuracies for each dataset were 95.01%, 76.88%, 74.03%, and 80.29% respectively. Cross-subject average accuracies were 88.72%, 75.80%, 75.78%, and 80.34%. Ablation experiments confirmed the importance of large-kernel convolution, dynamic routing, and dilation convolution in the ID-CapsuleNet model.Conclusion The developed ID-CapsuleNet model demonstrated promising potential for enhancing the performance of BCI systems based on MI and MA. The findings contribute to the advancement of BCI technology, offering improved assistive tools for disabled individuals.

AbstractOrthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,β-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1β, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

The fluctuations in power output from distributed power sources are rapid and dramatic, causing voltage fluctuations in the distribution network that threaten the safety of electricity consumption. Soft open points (SOPs) can replace traditional contact switches and are expected to suppress voltage fluctuations. However, traditional power regulation methods based on the reference values are unable to address rapid and large voltage fluctuations. Therefore, this paper proposes an adaptive power control method for SOPs based on virtual impedance. The SOP is modeled as a series link of adjustable impedance and a voltage source. Then, the voltage difference component is used to calculate the reference for the DQ domain to regulate the power flow in real time automatically. By doing so, the proposed method can smooth the voltage fluctuations in the distribution network. Additionally, the virtual impedance is also optimized to minimize the power loss. Finally, the method is validated through simulation and experiments, demonstrating that this method can automatically regulate power and significantly reduce voltage fluctuations.

Abstract Glioblastoma multiforme (GBM) is the most aggressive and lethal subtype of gliomas of the central nervous system. The efficacy of sonodynamic therapy (SDT) against GBM is significantly reduced by the expression of apoptosis‐inhibitory proteins in GBM cells. In this study, an intelligent nanoplatform (denoted as Aza‐BD@PC NPs) based on the aza‐boron‐dipyrromethene dye and phenyl chlorothionocarbonate‐modified DSPE‐PEG molecules is developed for synergistic ferroptosis‐enabled gas therapy (GT) and SDT of GBM. Once internalized by GBM cells, Aza‐BD@PC NPs showed effective cysteine (Cys) consumption and Cys‐triggered hydrogen sulfide (H2S) release for ferroptosis‐enabled GT, thereby disrupting homeostasis in the intracellular environment, affecting GBM cell metabolism, and inhibiting GBM cell proliferation. Additionally, the released Aza‐BD generated abundant singlet oxygen (1O2) under ultrasound irradiation for favorable SDT. In vivo and in vitro evaluations demonstrated that the combined functions of Cys consumption, H2S production, and 1O2 production induced significant death of GBM cells and markedly inhibited tumor growth, with an impressive inhibition rate of up to 97.5%. Collectively, this study constructed a cascade nanoreactor with satisfactory Cys depletion performance, excellent H2S release capability, and prominent reactive oxygen species production ability under ultrasound irradiation for the synergistic ferroptosis‐enabled GT and SDT of gliomas.

During the Mesozoic, the North China Craton experienced intense tectonic movements that resulted in the formation of numerous gold deposits on the Liaodong and Jiaodong Peninsulas in northeastern China. To investigate the relationship between deep crustal structure and gold mineralization in the Liaodong Peninsula, we deployed 334 dense seismic stations in the Wulong goldfield (WLGF) with the idea of analysing numerous receiver functions at different array stations. The purpose focused on knowing the potential for gold mineralization in the area. The study revealed the following: (1) The WLGF is characterized by a crustal thickness of approximately 32 km and an average Vp/Vs ratio of 1.76. The high value of the Vp/Vs ratio near the Wulong gold deposit suggests that mantle materials have penetrated into the crust and contributed to the mineralization process. (2) A low-velocity layer located at a depth of 10–18 km below the WLGF seems to support the existence of a potentially brittle-ductile transition zone. Also, hydrothermal magma upwelling channels are observed in the upper crust beneath the Wulong gold deposit. (3) The presence of a discontinuous low-velocity layer in the middle crust beneath the Liaodong Peninsula suggests promising prospects for gold ore exploration. The receiver functions method based on a dense seismic array employed in this study can offer valuable references and guidance for the fine exploration and research of ore deposits in other regions globally.

The fragmentation of the functional brain network has been identified through the functional connectivity (FC) analysis in studies investigating anesthesia-induced loss of consciousness (LOC). However, it remains unclear whether mild sedation of anesthesia can cause similar effects. This paper aims to explore the changes in local–global brain network topology during mild anesthesia, to better understand the macroscopic neural mechanism underlying anesthesia sedation. We analyzed high-density EEG from 20 participants undergoing mild and moderate sedation of propofol anesthesia. By employing a local–global brain parcellation in EEG source analysis, we established binary functional brain networks for each participant. Furthermore, we investigated the global-scale properties of brain networks by estimating global efficiency and modularity, and examined the changes in meso-scale properties of brain networks by quantifying the distribution of high-degree and high-betweenness hubs and their corresponding rich-club coefficients. It is evident from the results that the mild sedation of anesthesia does not cause a significant change in the global-scale properties of brain networks. However, network components centered on SomMot L show a significant decrease, while those centered on Default L, Vis L and Limbic L exhibit a significant increase during the transition from wakefulness to mild sedation (p

Summary: Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30–70 years with an office blood pressure (BP) of

Biliary tract neoplasms, which originate from the intrahepatic or extrahepatic biliary epithelium, are relatively rare but diagnostically challenging types of tumours, and their morbidity and mortality have increased in recent years. Due to ineffective early diagnostic methods, once detected, patients are in an advanced stage with a poor prognosis and few treatment options. With the development of omics technologies, the associations between microorganisms, bile acid and salts, noncoding RNAs and biliary tract malignancies have been gradually revealed, providing new methods for the discovery of diagnostic biomarkers. Here, we review the research advances in microbiomics, transcriptomics, metabolomics, and proteomics in the discovery of diagnostic biomarkers for biliary tract malignancies.

Forkhead box protein J1 (FOXJ1), a member of the forkhead family, is an important transcription factor regulating multiciliated cell differentiation and motile ciliogenic program. Here, we established a FOXJ1- EGFP knock-in human embryonic stem cell (hESC) line by inserting a P2A-EGFP gene cassette of FOXJ1 using CRISPR/Cas9 system. The reporter cell line retained a normal karyotype, expressed comparable pluripotent marker genes, and maintained differentiation potential. This reporter cell line enables live identification of multiciliated cells during the general lung differentiation and will be a valuable tool for studying the multiciliated cell differentiation, ciliogenesis and mechanism of related pulmonary diseases.

The left-lateral Altyn Tagh Fault (ATF) system is the northern boundary of the Qinghai-Xizang Plateau, separating the Tarim Basin and the Qaidam Basin. The middle section of ATF has not recorded any large earthquakes since 1598 AD, so the potential seismic hazard is unclear. We develope an earthquake catalog using continuous waveform data recorded by the Tarim-Altyn-Qaidam dense nodal seismic array from September 17 to November 23, 2021 in the middle section of ATF. With the machine learning-based picker, phase association, location, match and locate workflow, we detecte 233 earthquakes with ML -1–3, far more than 6 earthquakes in the routine catalog. Combining with focal mechanism solutions and the local fault structure, we find that seismic events are clustered along the ATF with strike-slip focal mechanisms and on the southern secondary faults with thrusting focal mechanisms. This overall seismic activity in the middle section of the ATF might be due to the northeastward transpressional motion of the Qinghai-Xizang Plateau block at the western margin of the Qaidam Basin.

Abstract Extracellular vesicles (EVs) have emerged as a promising tool for clinical liquid biopsy. However, the identification of EVs derived from blood samples is hindered by the presence of abundant plasma proteins, which impairs the downstream biochemical analysis of EV‐associated proteins and nucleic acids. Here, we employed optimized asymmetric flow field‐flow fractionation (AF4) combined with density cushion ultracentrifugation (UC) to obtain high‐purity and intact EVs with very low lipoprotein contamination from human plasma and serum. Further proteomic analysis revealed more than 1000 EV‐associated proteins, a large proportion of which has not been previously reported. Specifically, we found that cell‐line‐derived EV markers are incompatible with the identification of plasma‐EVs and proposed that the proteins MYCT1, TSPAN14, MPIG6B and MYADM, as well as the traditional EV markers CD63 and CD147, are plasma‐EV markers. Benefiting from the high‐purity of EVs, we conducted comprehensive miRNA profiling of plasma EVs and nanosized particles (NPs), as well as compared plasma‐ and serum‐derived EVs, which provides a valuable resource for the EV research community. Overall, our findings provide a comprehensive assessment of human blood EVs as a basis for clinical biopsy applications.

Immune checkpoint inhibitors (ICIs) are essential for urothelial carcinoma (UC) treatment. Fibroblast growth factor receptor (FGFR) alterations, as common oncogenic drivers in UC, have been reported to drive T cell depletion of UC immune microenvironment via up-regulating FGFR signaling, which indicated FGFR alterations potentially result in reduced response to ICIs. In addition, the selective pan-FGFR inhibitor showed better clinical benefit in clinical trials, indicating FGFR has emerged as critical therapeutic target via inhibiting FGFR signaling. The present study aims to evaluate prognosis and response to ICIs between FGFR-altered UC patients and FGFR-wildtype UC patients via 1963 UC patients and offers new insights into personalized precision therapy and combination therapy for UC.

Earthquake-induced liquefaction is a geological disaster that caused extensive damage to buildings, railways, dams. Due to the construction techniques and economic conditions, the subsurface layers of some buildings must be reinforced to resist seismic loads. Microbial-induced desaturation is a development technique which can be used for existing buildings to mitigate liquefaction. Shaking table tests were conducted to survey the effect of microbial induced desaturation on liquefaction-prone foundations beneath buildings. The test results showed that, lower saturation degree delays the generation of excess pore pressure and reduces its magnitude. It appears that the resistance to excess pressure increases as saturation degree is reduced from 100% to 93.4% or 85.6%. Desaturation prevents the decay of the amplitude of acceleration oscillations, but increases the accelerations of the structure. The settlement of the sandy soil decreases as the saturation degree decreases. Resistance to liquefaction increased by more than twice than that in the saturated sample after induced desaturation to 93.4%. The weight of the building structure contributes to the anti-liquefaction capacity.

The quantitative research on swelling properties of bentonite considering the influence of salt ions under the effect of hydrothermo-mechanical coupling is relatively weak. Based on a calculation model for the swelling characteristics of bentonite from a fractal perspective, this work proposes a novel coupled multifield control equation for unsaturated bentonite considering the influence of salt ions. The numericalization of the coupling control equation was completed by secondary development of a numerical analysis platform. The new theoretical model’s dependability and validity were validated by comparing it to experimental data. The evolution of the related-field quantities under the multifield coupled effect in salt-bearing environments was obtained, and the effect of salt ion concentration was analyzed. The calculation showed that the temperature of bentonite changed periodically with changing ambient temperature. Temperature gradient induces migratory movement of water from high to low temperature regions. The hollow axisymmetric soil sample gradually saturated from outside to inside with increasing water injection rate at the outer cylindrical surface. The swelling pressure of bentonite will increase with an increase in water content, whereas the presence of salt ions weakened the swelling behavior. Temperature and relative humidity were less affected by salt ion concentration.

Abstract Background Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti‐inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro. Methods In vitro, western blotting, real‐time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin‐1 beta (IL‐1β)‐induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture‐induced IVDD rat models. Results In vitro, API played a crucial role in anti‐inflammation and autophagy enhancement in IL‐1β‐induced NPCs. API improved inflammation by inhibiting the nuclear factor‐kappaB and mitogen‐activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3‐kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture‐induced IVDD model. Conclusions API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.

BackgroundThe performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC.MethodsWe searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities.ResultsFourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89–0.94), 0.79 (95% CI 0.72–0.85), and 0.90 (95% CI 0.86–0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists.DiscussionIn conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).