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Abstract The genome is intricately folded into chromatin compartments, topologically associating domains (TADs) and loops unique to each cell type. How this higher-order genome organization regulates cell fate transition remains elusive. Here we show how a single non-neural progenitor transcription factor, PTF1A, reorchestrates the 3D genome during fibroblast transdifferentiation into neural stem cells (NSCs). Multiomics analyses integrating Hi-C data, PTF1A and CTCF DNA-binding profiles, H3K27ac modification, and gene expression, demonstrate that PTF1A binds to subTAD boundaries subsequently associated with elevated CTCF binding and enhanced boundary insulation, and reorganizes chromatin loops, leading to gene expression changes that drive transdifferentiation into NSCs. Moreover, PTF1A activates enhancers and super-enhancers near low-insulation boundaries and modulates H3K27ac deposition, promoting cell fate transitions. Together, our data implicate an involvement of 3D genome in transcriptional and cell fate alterations, and highlight an essential role for PTF1A in gene expression control and multiscale 3D genome remodeling during cell reprogramming.

Abstract The contradiction between high piezoelectricity and uniquely poor temperature stability generated by polymorphic phase boundary is a huge obstacle to high-performance (K, Na)NbO3 -based ceramics entering the application market as Pb-based substitutes. We possess the phase boundary by mimicking Pb(Zr, Ti)O3’s morphotropic phase boundary structure via the synergistic optimization of diffusion phase boundary and crystal orientation in 0.94(Na0.56K0.44)NbO3−0.03Bi0.5Na0.5ZrO3−0.03(Bi0.5K0.5)HfO3 textured ceramics. As a result, a prominent comprehensive performance is obtained, including giant d 33 of 550 ± 30 pC/N and ultrahigh temperature stability (d 33 change rate less than 1.2% within 25-150 °C), representing a significant breakthrough in lead-free piezoceramics, even surpassing the Pb-based piezoelectric ceramics. Within the same temperature range, the d 33 change rate of the commercial Pb(Zr, Ti)O3−5 ceramics is only about 10%, and more importantly, its d 33 (~ 350 pC/N) is much lower than that of the (K, Na)NbO3-based ceramics in this work. This study demonstrates a strategy for constructing the phase boundary with MPB feature, settling the problem of temperature instability in (K, Na)NbO3-based ceramics.

Abstract Social and technical networks undergo constant evolution driven by both existing entities and newcomers. In academia, research papers are continually cited by new papers, while senior researchers integrate newly arrived junior researchers into their academic networks. Moreover, social systems can be influenced by external factors that could indirectly impact their growth patterns. For instance, systematic discrimination against certain groups in academia or managerial positions can impede their long-term growth, especially when combined with group-level preferences in hiring or adoption, as observed in our study. To address this, we introduce a network growth and adoption model where generalised preferential attachment and asymmetric mixing act as the two fundamental mechanisms of growth and adoption. We show analytically and numerically that these mechanisms can recover the empirical properties of citation and collaboration growth, as well as the inequalities observed in the growth dynamics of groups. This model can be used to investigate the effect of intervention in group mixing preferences to overcome the cumulative disparities in the group-level dynamics.

Abstract Background This study aimed to investigate the epidemiological changes in scarlet fever before, during and after the COVID-19 pandemic (2005–2023) and predict the incidence of the disease in 2024 and 2025 in Chongqing Municipality, Southwest China. Methods Descriptive analysis was used to summarize the characteristics of the scarlet fever epidemic. Spatial autocorrelation analysis was utilized to explore the distribution pattern of the disease, and the seasonal autoregressive integrated moving average (SARIMA) model was constructed to predict its incidence in 2024 and 2025. Results Between 2005 and 2023, 9,593 scarlet fever cases were reported in Chongqing, which resulted in an annual average incidence of 1.6694 per 100,000 people. Children aged 3–7 were the primary victims of this disease, with the highest average incidence found among children aged 6 (5.0002 per 100,000 people). Kindergarten children were the dominant infected population, accounting for as much as 54.32% of cases, followed by students (34.09%). The incidence for the male was 1.51 times greater than that for the female. The monthly distribution of the incidence showed a bimodal pattern, with one peak occurring between April and June and another in November or December. The spatial autocorrelation analysis revealed that scarlet fever cases were markedly clustered; the areas with higher incidence were mainly concentrated in Chongqing’s urban areas and its adjacent districts, and gradually spreading to remote areas after 2020. The incidence of scarlet fever increased by 106.54% and 39.33% in the post-upsurge period (2015–2019) and the dynamic zero-COVID period (2020–2022), respectively, compared to the pre-upsurge period (2005–2014) (P

Abstract To explore computed tomography (CT) findings and pathological features of intestinal inflammatory myofibroblastic tumors (IMT). A retrospective review was conducted on the CT features of five patients with pathologically confirmed IMT, which were then compared with the corresponding pathological findings. The study included four female and one male patients. The tumors were located in the rectum (n = 1), small intestine (n = 2), or cecum (n = 2). One patient exhibited a cystic solid mass with exophytic growth and the solid components showed moderate enhancement. Additionally, flaky low‐density, marginal line‐like calcified shadows were observed around the lesions. Two cases presented as solid masses within the lumen of the intestinal tract, showing obvious non‐uniform enhancement along with visible enhancement shadows of small blood vessels. One patient had a metastasis. In two other cases, solid masses grew outside the lumen of the intestinal tract, demonstrating progressive and delayed enhancement on enhanced scans, as well as local nodular enhancement and ring enhancement. These two cases also exhibited focal sarcomatoid lesions, along with their respective IMTs. Histologically, these tumors mainly consist of proliferating spindle myofibroblast cells accompanied by variable infiltration by interstitial inflammatory cells, such as fibroblasts. Immunohistochemical analysis revealed positive staining for smooth muscle actin (SMA) in ~80% of the cells tested, while vimentin staining was positive in ~60% of the cells. Intestinal IMT is an extremely rare tumor with imaging features that can reflect the underlying pathological characteristics to some extent, thus aiding diagnosis.

Abstract Purpose This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. Methods This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. Results The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract. Biomolecular aggregation within cellular environments via liquid–liquid phase separation (LLPS) spontaneously forms droplet-like structures, which play pivotal roles in diverse biological processes. These structures are closely associated with a range of diseases, including neurodegenerative disorders, cancer and infectious diseases, highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis, and exploring potential therapeutic interventions. In this review, we delineate recent advancements in LLPS research, emphasizing its pathological relevance, therapeutic considerations, and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations. Additionally, we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability. By providing comprehensive insights into current LLPS-related bioinformatics resources, this review highlights its implications for human health and disease.

Abstract Recent advancements in machine learning (ML) have revolutionized the field of high-performance materials design. However, developing robust ML models to decipher intricate structure-property relationships in materials remains challenging, primarily due to the limited availability of labeled datasets with well-characterized crystal structures. This is particularly pronounced in materials where functional properties are closely intertwined with their crystallographic symmetry. We introduce a self-supervised probabilistic model (SSPM) that autonomously learns unbiased atomic representations and the likelihood of compounds with given crystal structures, utilizing solely the existing crystal structure data from materials databases. SSPM significantly enhances the performance of downstream ML models by efficient atomic representations and accurately captures the probabilistic relationships between composition and crystal structure. We showcase SSPM’s capability by discovering shape memory alloys (SMAs). Amongst the top 50 predictions, 23 have been confirmed as SMAs either experimentally or theoretically, and a previously unknown SMA candidate, MgAu, has been identified.

Abstract Background Alzheimer’s disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. Methods The differentiated human neural cells were induced by Aβ1–42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aβ1–42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. Results The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. Conclusions Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aβ-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.

Abstract The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3−/− (Shn3 −/− ) mice with augmented osteoblast activity, we show Shn3 −/− mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3 −/− mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome.

Abstract Purpose Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. Methods We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. Results In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. Conclusions Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

Abstract It has been shown that the formation of filopodia is a key step in tumor cell metastasis, but there is limited research regarding its mechanism. In this study, we demonstrated that fatty acid synthase (FASN) promoted filopodia formation in liver cancer cells by regulating fascin actin-bundling protein 1 (FSCN1), a marker protein for filopodia. Mechanistically, on the one hand, the accumulation of FASN is caused by the enhanced deubiquitination of FASN mediated by UCHL5 (ubiquitin c-terminal hydrolase L5). In this pathway, low expression of SIAH1 (Seven in absentia homolog 1) can decrease the ubiquitination and degradation of ADRM1 (adhesion regulating molecule 1) thereby increasing its protein level, which will recruit and activate the deubiquitination enzyme UCHL5, leading to FASN undergo deubiquitination and escape from proteasomal degradation. On the other hand, the accumulation of FASN is related to its weakened ubiquitination, where SIAH1 directly acts as a ubiquitin ligase toward FASN, and low expression of SIAH1 reduces the ubiquitination and degradation of FASN. Both the two pathways are involved in the regulation of FASN in liver cancer. Our results reveal a novel mechanism for FASN accumulation due to the low expression of SIAH1 in human liver cancer and suggest an important role of FASN in filopodia formation in liver cancer cells.

Abstract Objective In this study, we investigated the efficacy of percutaneous poking reduction and Kirschner wire fixation in older children with irreducible supracondylar flexion-type fractures of the humerus. Methods This retrospective investigation included 27 children, comprising 15 males and 12 females, aged between 10 years and 3 months to 14 years and 11 months, all diagnosed with a flexion-type supracondylar fracture of the humerus within one week of trauma. All patients underwent surgery under general anesthesia. Following unsuccessful manual reduction, percutaneous poking reduction with Kirschner wires was performed under C-arm fluoroscopy to achieve fracture reduction. Following successful reduction, three 2.0 mm Kirschner wires were inserted in a cross pattern to secure the fracture ends. Postoperatively, the elbow joint was immobilized in a functional position with a plaster cast for four weeks. Results Follow-up in the outpatient department ranged from 9 to 36 months. Clinical functional assessment using Flynn’s criteria rated 24 cases as excellent, 2 as good, and 1 as fair, yielding an overall efficacy of 96.3%. No cases of fracture re-displacement, fracture fragment necrosis, or other complications such as nonunion, iatrogenic nerve injury, myositis ossificans, or long-term elbow joint dysfunction were observed during the postoperative follow-up. Conclusion The percutaneous poking reduction and Kirschner wire fixation technique is a simple and reliable procedure for treating irreducible flexion-type supracondylar fractures of the humerus in older children, with minimal trauma. This technique offers substantial stability for the fracture and results in excellent long-term recovery of joint function.

Abstract In thermoelectric, phase interface engineering proves effective in reducing the lattice thermal conductivity via interface scattering and amplifying the density-of-states effective mass by energy filtering. However, the indiscriminate introduction of phase interfaces inevitably leads to diminished carrier mobility. Moreover, relying on a singular energy barrier is insufficient for comprehensive filtration of low-energy carriers throughout the entire temperature range. Addressing these challenges, we advocate the establishment of a composite phase interface using atomic layer deposition (ALD) technology. This design aims to effectively decouple the interrelated thermoelectric parameters in ZrNiSn. The engineered coherent dual-interface energy barriers substantially enhance the density-of-states effective mass across the entire temperature spectrum while preser carrier mobility. Simultaneously, the strong interface scattering on phonons is crucial for curtailing lattice thermal conductivity. Consequently, a 40-cycles TiO2 coating on ZrNi1.03Sn0.99Sb0.01 achieves an unprecedented zT value of 1.3 at 873 K. These findings deepen the understanding of coherent composite-phase interface engineering.

Abstract Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

To date, the exploration of multi-principal element alloys (MPEAs) has rarely ventured into the realm of hexagonal close-packed (HCP) structures. In this research, we embarked on a pioneering systematic comparison between a single-phase Ti-Zr-Hf HCP-MPEA and Ti regarding their dislocation activities and mesoscale deformation homogeneity. Through large-area high-resolution quasi-in-situ slip trace analysis and crystal plasticity finite element modeling, we identified HCP-MPEA’s significantly enhanced pyramidal slip activities—resulted from minimized disparities among different deformation modes—notably improve the material’s intragranular deformation homogeneity. Alongside MPEA’s intrinsically high slip resistance, it renders HCP-MPEA an outstanding strength-toughness combination relative to its conventional HCP counterparts.

Abstract Background Femoral neck system (FNS) has exhibited some drawbacks, such as non-fit of the plate with the lateral femoral cortex, postoperative pain, and the potential risk of subtrochanteric fractures. We have developed a low-profile FNS system that addresses some compatibility issues in FNS. In this study, we conducted finite element analysis on the 1-hole FNS (1 H-FNS), 2-holes FNS (2 H-FNS), and low-profile FNS (LP-FNS) and compared their biomechanical performance. Methods After the mesh convergence analysis, we established three groups of 1 H-FNS, 2 H-FNS, and LP-FNS. The interfragmentary gap, sliding distance, shear stress, and compressive stress and the bone-implant interface compression stress, stiffness, and displacement were determined under the neutral, flexion, or extension conditions of the hip joint, respectively. The stress and displacement of the femur after the implant removal were also investigated. Results (1) There were no obvious differences among the three FNS groups in terms of the IFM distance. However, the LP-FNS group showed less rotational angle compared with conventional FNS (neutral: 1 H-FNS, -61.64%; 2 H-FNS, -45.40%). Also, the maximum bone-implant interface compression stress was obviously decreased under the neutral, flexion, or extension conditions of the hip joint (1 H-FNS: -6.47%, -20.59%, or -4.49%; 2 H-FNS: -3.11%, 16.70%, or -7.03%; respectively). (2) After the implant removal, there was no notable difference in the maximum displacement between the three groups, but the maximum von Mises stress displayed a notable difference between LP-FNS and 1 H-FNS groups (-15.27%) except for the difference between LP-FNS and 2 H-FNS groups (-4.57%). Conclusions The LP-FNS may not only provide the same biomechanical stabilities as the 1 H-FNS and 2 H-FNS, but also have more advantages in rotational resistance especially under the neutral condition of the hip joint, in the bone-implant interface compression stress, and after the implant removal. In addition, the 1 H-FNS and 2 H-FNS have similar biomechanical stabilities except for the maximum von Mises stress after the implant removal. The femur after the LP-FNS removal not only is subjected to relatively little stress but also minimizes stress concentration areas.

The cellular carbon content and chlorophyll a (Chl a) concentration are two of the most significant indices for assessing phytoplankton biomass. Recording and monitoring these biomasses are essential tasks in phytoplankton research, and the carbon-to-chlorophyll a (C:Chl a) ratio serves as a crucial conversion tool between them. Although the C:Chl a ratio varies widely, it is influenced by external environmental factors, making modeling studies of C:Chl a particularly important. This paper provides an overview of the historical development of the C:Chl a model, beginning with early empirical models and progressing to the development of mechanistic models. This discussion is followed by an examination of existing gaps and future challenges in current C:Chl a modeling, particularly the potential underestimation of carbon biomass in existing C:Chl a models for dinoflagellates exhibiting multiple growth strategies. Finally, it is suggested that future C:Chl a models should strive to achieve a balance between reliability and applicability.

Abstract Postbiotics is a novel category of biotics that encompasses dead cells, metabolites, and derivatives from gut microbiota. These substances can exhibit their effects without containing cells, such as in cell‐free supernatants and spent media. Examples of widely studied postbiotics include short‐chain fatty acids, exopolysaccharides, cell wall fragments, and bacterial lysates. Evidence suggests that postbiotics have numerous benefits for human health, including antiaging, and anti‐inflammatory properties, and participation in immune and lipid metabolism regulation. Specifically, postbiotics can improve intestinal health by strengthening the intestinal barrier, reducing inflammation, and promoting antibacterial activity. These findings may pave the way for the development of postbiotic functional foods in the future. This review provides an overview of the components, health effects, and industrial applications of postbiotics, aiming to consolidate existing research conclusions and serve as a reference for future studies.

BackgroundHigher sedentary behavior (SB) and lower physical activity (PA) are associated with negative physical and mental health outcomes. SB and PA can be objectively assessed using inertial sensors to evaluate body movements. This study aimed to quantify the association between instrumented measures of SB (i-SB) and PA (i-PA) and depression among children and adolescents using a systematic review and meta-analysis of observational studies.MethodsAn electronic search was conducted on six databases up to May 12, 2024. A dose–response meta-analysis was conducted to determine the association between i-SB and i-PA and depression, expressed as odds ratios (ORs) and 95% confidence intervals (CIs).ResultsFive cross-sectional and 11 longitudinal studies comprising 26,109 participants met the inclusion criteria. Comparing the most sedentary with the least sedentary groups of participants resulted in a pooled ORs of 1.05 (95% CI 0.94–1.16). Comparing the least active with the most active groups of participants resulted in pooled ORs of 0.93 (95% CI 0.84–1.07), 0.89 (95% CI 0.79–1.00), 0.83 (95% CI 0.66–0.99), and 0.73 (95% CI 0.58–0.89) for light, moderate-to-vigorous (MV), vigorous, and total PA, respectively. Robust error meta-regression analyses showed clear dose–response relationships between i-SB and i-MVPA and depression.ConclusionBoth i-SB and i-PA were significantly associated with risk of depression in children and adolescents, which may become non-significant after mutual adjustment for i-PA and i-SB.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=546666], identifier [CRD42024546666].

The gelling properties and flavor quality of preserved eggs are affected by temperature reached during pickling. In response, this study investigates the effects of different temperature-controlled techniques on the gelling properties and flavor quality of preserved eggs. The results show that compared with an overall constant temperature and a two-stage temperature-controlled technique, the P-12–18–30 °C three-stage temperature-controlled pickling model produced the best texture properties of the preserved egg white gel, as further verified by LF NMR and SEM analysis. The results of amino acid analysis also show that the taste intensity of free amino acids in the P-12–18–30 °C group was significantly increased, especially for umami amino acids. In addition, the results of the electronic noise show that the volatile components of preserved eggs subjected to different temperature-controlled pickling techniques were similar, mainly consisting of short-chain alkanes; alcohols, aldehydes, ketones, and some aromatic compounds; long-chain alkane aliphatic groups; and inorganic sulfides, and there was no significant difference in the content of each flavor substance. In conclusion, this study offers theoretical basis for temperature-controlled pickling of preserved egg with better gel quality.

BackgroundEpidemiological and experimental evidence suggests that chronic inflammation plays an important role in the onset and progression of sarcopenia. However, there is inconsistent data on the inflammatory cytokines involved in the pathogenesis of sarcopenia. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between circulating cytokines and sarcopenia-related traits.MethodsThe MR analysis utilized genetic data from genome-wide association study that included genetic variations in 41 circulating cytokines and genetic variant data for appendicular lean mass (ALM), hand grip strength, and usual walking pace. Causal associations were primarily explored using the inverse variance-weighted (IVW) method, supplemented by MR-Egger, simple mode, weighted median, and weighted mode analyses. Additionally, sensitivity analyses were also performed to ensure the reliability and stability of the results.ResultsThree cytokines [hepatocyte growth factor (HGF), interferon gamma-induced protein 10 (IP-10), and macrophage colony-stimulating factor (M-CSF)] were positively associated with ALM (β: 0.0221, 95% confidence interval (CI): 0.0071, 0.0372, P= 0.0039 for HGF; β: 0.0096, 95%CI: 4e-04, 0.0189, P= 0.0419 for IP-10; and β: 0.0100, 95%CI: 0.0035, 0.0165, P= 0.0025 for M-CSF). Conversely, higher levels of interleukin-7 (IL-7), monocyte chemotactic protein 3 (MCP-3), and regulated on activation, normal T cell expressed and secreted (RANTES) were associated with decreased hand grip strength (β: -0.0071, 95%CI: -0.0127, -0.0014, P= 0.0140 for IL-7; β: -0.0064, 95%CI: -0.0123, -6e-04, P= 0.0313 for MCP-3; and β: -0.0082, 95%CI: -0.0164, -1e-04, P= 0.0480 for RANTES). Similarly, interleukin 1 receptor antagonist (IL-1RA) was negatively correlated with usual walking pace (β: -0.0104, 95%CI: -0.0195, -0.0013, P= 0.0254). Sensitivity analysis confirmed the robustness of these findings.ConclusionsOur study provides additional insights into the pivotal role of specific inflammatory cytokines in the pathogenesis of sarcopenia. Further research is required to determine whether these cytokines can be used as targets for the prevention and treatment of sarcopenia.

BackgroundPulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored.MethodsNetwork analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-β1 (TGF-β1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2’s effects against PF.ResultsNetwork analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway.ConclusionLG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

Eukaryotic microorganisms were the key components of marine microecosystems and were involved in biogeochemical cycling processes. Although oceanographers have emphasized their importance in open oceans, the current understanding was not comprehensive enough about the assembly processes and co-occurrence network of different fraction eukaryotic microbial communities in the coastal China sea. We used co–occurrence networks and ecological process model to investigate possible ecological interactions in two fractions (small fraction 0.22–3 μm; large fraction 3–200 μm) of eukaryotes throughout different depths and geographical regions of coastal China sea. We found that environmental distance shapes the diversity of the two fractions eukaryotic microorganisms. Dispersal limitation and homogeneous selection processes were the key drivers of eukaryotic microbial community assembly. Co-occurrence network analysis showed that the networks of the 0.2–3 μm eukaryotes more nodes and edges, with more complex interactions between microorganisms, and higher network stability than that of 3–200 μm eukaryotic microorganisms. Temperature, oxygen, salinity, and nutrients play the crucial role in the abundance of two fractions eukaryotic microorganisms. These results crystallize the knowledge of eukaryotic microbes in the coastal China sea, which was essential for addressing the challenges posed by global change.

Diatoms (> 2 μm) have traditionally been identified as the primary biological agents linking the carbon (C) and silicon (Si) cycles. However, recent research has shown that picophytoplankton species (< 2 μm) also play a crucial role in the intertwined Si-C biogeochemical cycling in marine ecosystems. In this study, we examined the spatial distribution and vertical variation of micro/nano-diatoms and picophytoplankton in the eastern Indian Ocean (EIO), aimed to differentiate the contributions of living carbon and biogenic silica (bSi) stocks between diatoms and picophytoplankton. The study revealed that the abundance of picophytoplankton surpasses that of diatoms by four to seven orders of magnitude. Synechococcus was predominantly presented in the upper layer, while Prochlorococcus, picoeukaryotes, and diatoms were primarily located in the middle layer. Aggregation Boosted Tree (ABT) and Generalized Additive Models (GAM) analyses revealed that temperature and silicate (DSi) levels strongly influenced the diatom and picophytoplankton communities in the EIO. The fractions smaller than 2 μm made substantial contributions of 86.20%, 55.69%, and 96.86% to chlorophyll a (Chl-a), particulate organic carbon (POC), and living carbon biomass, respectively, underscoring the ecological significance of picophytoplankton in the carbon cycle of oligotrophic regions. Picophytoplankton represented a 33.06% of bSi stocks in the area, comparable to the contribution of diatoms (> 20 μm). Moreover, estimated contributions of diatom living carbon and silicon quota averaged 0.47% and 0.66%, respectively, while that of Synechococcus stood at 2.58% and 1.77%, indicating the predominance of Synechococcus as a weakly siliceous organism with high cell abundance in oligotrophic seas. Overall, this study draws on data from diatom and picophytoplankton biomass in the EIO to offer insights into the disproportionate carbon and silicon budgets in oligotrophic oceans from a biological perspective.

Owing to the fragile ecological environment and the prominent human–land conflict relationship, the competition between land multifunctionality in the karst region has increased. In this context, the coordination and stability of production–living–ecological space (PLES) have been severely affected, and the scientific diagnosis of PLES conflict characteristics can provide an important basis for optimizing national land allocation. Using land use data, this study used a spatial conflict measurement model to examine the spatial and temporal variations of PLES conflicts across mountain–basin areas of various geomorphological in karst types. Meanwhile, the factors influencing their evolution were also investigated. The study results showed that the ecological space (ES) area was the largest in the study area and had an increasing trend from 2010 to 2020. PLES conflicts were dominated by stable and controllable, and light conflicts, and the overall conflict level had increased. Influenced by the natural environment, socioeconomics, and policies, there were significant differences in the development of PLES conflicts in the mountain–basin areas. The conflict level in the basin area was higher than in the mountain area. The intensity of PLES conflicts in the mountain–basin areas in the karst valleys geomorphic types and in the mountain areas in the karst fault basin showed a decreasing trend. The level of conflicts in the mountain–basin areas in the karst plateau, karst peak–cluster depression, karst trough valley geomorphic and in the basin area of the karst fault basin geomorphic type showed an increasing trend. There were also common evolutionary characteristics for PLES conflicts in mountain–basin areas. The findings have provided a reference to support differentiated land management and decision-making in karst areas, which can contribute to the strategic sustainable development at the regional level.

【Objective】The study was conducted to investigate the spatial distribution and content differences of asymbiotic nitrogen fixation (ANF) in different ecosystem components of Cunninghamia lanceolata, Eucalyptus, Pinus massoniana plantation forests in different growing seasons.【Method】By using ordinary kriging interpolation, analysis of variance and correlation analysis, we conducted a characterisation study of spatial variability and content differences in ANF of Cunninghamia lanceolata, Eucalyptus, Pinus massoniana plantation forests in Guangxi Gaofeng Forestry by determining the amount of ANF in soil, litter and canopy leaves in the growing season and non-growing season.【Result】In both growing and non-growing seasons, the trends of ANF in each component of plantation forests were different and significant, with strong spatial correlation and heterogeneity. In the growing season, the distribution of soil ANF was low in the northeast and high in the southwest, while the distributions of litter and canopy leaves were high in the northeast and low in the southwest; in the nongrowing season, the spatial distributions of soil and canopy leaves were generally similar to those in the growing season, and that of the litter showed the opposite result. Soil ANF was the highest in plantation forests, at 1.2834 and 0.5668 kg/hm2·y, and the lowest was in canopy leaves, at 0.0009 and 0.0028 kg/hm2·y. ANF in soil differed significantly from that in litter and canopy leaves. In the growing season, the amount of soil ANF was significantly negatively correlated with litter, and the correlation between the other components was not significant; in the non-growing season, the amount of ANF between the components did not have a significant correlation.【Conclusion】The spatial differentiation of ANF in various components of Cunninghamia lanceolata, Eucalyptus, Pinus massoniana plantation forests in different seasons was significant and strong, and ANF mainly existed in the soil fraction. Therefore, the application of a certain amount of nitrogen fertilizer to the soil during the planting of Cunninghamia lanceolata, Eucalyptus and Pinus massoniana can promote the growth of plantation forests.

Abstract The ultrahigh flexibility and elasticity achieved in freestanding single-crystalline ferroelectric oxide membranes have attracted much attention recently. However, for antiferroelectric oxides, the flexibility limit and fundamental mechanism in their freestanding membranes are still not explored clearly. Here, we successfully fabricate freestanding single-crystalline PbZrO3 membranes by a water-soluble sacrificial layer technique. They exhibit good antiferroelectricity and have a commensurate/incommensurate modulated microstructure. Moreover, they also have good shape recoverability when bending with a small radius of curvature (about 2.4 μm for the thickness of 120 nm), corresponding to a bending strain of 2.5%. They could tolerate a maximum bending strain as large as 3.5%, far beyond their bulk counterpart. Our atomistic simulations reveal that this remarkable flexibility originates from the antiferroelectric-ferroelectric phase transition with the aid of polarization rotation. This study not only suggests the mechanism of antiferroelectric oxides to achieve high flexibility but also paves the way for potential applications in flexible electronics.

Abstract Background Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI. Results We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation. Conclusion This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair. Graphical Abstract

This study used multi-scale transform and positive pressure perturbation method to simplify the barotropic quasi-geostrophic vorticity equation.For a class of cosine type shear， analyzes the influence of shear westerly on Rossby solitary wave that has nonlinear Shrödinger envelope soliton characteristics， and studied the topology of the westerly with nonlinear Shrödinger envelope soliton wave pattern.The results show that： （1） The key to the formation of cut-off low pressure is the bifurcation of westerly shear.The shear is not only the source of the envelope Rossby solitary wave， but also leads to the change of the structural characteristics of the westerly flow field.The essence of difference between different flow patterns is the structural change that is caused by bifurcation.It indicates that there exists a critical value for shear， which changes the topology of westerly.The topology of westerly has no singular points， only a degenerate central structure， and the corresponding westerly is a zonal flow， when the shear is less than this critical value.There are singular points， and vortices are generated in the westerly， when the shear is greater than this critical value.（2） For the vortices pattern of westerly， it exhibits different flow patterns， if the location of the singular points varies.The westerly presents an Ω shaped blocking flow field， when the singularity point appears only in the northern part of the system.The westerly presents an inverted Ω shaped cut-off flow field， when the singularity point appears only in the southern part of the system.And the westerly presents a dipole blocking flow field， when singular points appear in both the north and south.（3） There are cut-off low-pressure in both the inverted Ω type field and the dipole blocking flow field.It is a Northeast Cold Vortex， if the cut-off low-pressure forms near the Ural Mountains and moves downstream to the northeast region of China.Based on the blocking situation as the source of the Northeast Cold Vortex， the formation mechanism of the Northeast Cold Vortex is discussed with both the board view （westerly shear） and local characteristics （Rossby solitary wave） considered， and thus deepens the understanding of the formation of the Northeast Cold Vortex.

Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1ΔIEC) and Paneth cell (PC; Axin1ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vivo. Axin1ΔIEC and Axin1ΔPC mice became more susceptible to DSS-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1Loxp mice. However, the intestinal proliferative cells in Axin1ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

Abstract An important epigenetic component of tyrosine kinase signaling is the phosphorylation of histones, and epigenetic readers, writers, and erasers. Phosphorylation of protein arginine methyltransferases (PRMTs), have been shown to enhance and impair their enzymatic activity. In this study, we show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates tyrosine residues (Y149 and Y334) in coactivator-associated arginine methyltransferase 1 (CARM1), an important target in hematologic malignancies, increasing its methyltransferase activity and altering its target specificity. While non-phosphorylatable CARM1 methylates some established substrates (e.g. BAF155 and PABP1), only phospho-CARM1 methylates the RUNX1 transcription factor, on R223 and R319. Furthermore, cells expressing non-phosphorylatable CARM1 have impaired cell-cycle progression and increased apoptosis, compared to cells expressing phosphorylatable, wild-type CARM1, with reduced expression of genes associated with G2/M cell cycle progression and anti-apoptosis. The presence of the JAK2-V617F mutant kinase renders acute myeloid leukemia (AML) cells less sensitive to CARM1 inhibition, and we show that the dual targeting of JAK2 and CARM1 is more effective than monotherapy in AML cells expressing phospho-CARM1. Thus, the phosphorylation of CARM1 by hyperactivated JAK2 regulates its methyltransferase activity, helps select its substrates, and is required for the maximal proliferation of malignant myeloid cells.

Abstract The adenosine A3 receptor (A3AR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective A3AR agonists, CF101 and CF102, are clinically significant, yet their recognition mechanisms remained elusive. Here we report the cryogenic electron microscopy structures of the full-length human A3AR bound to CF101 and CF102 with heterotrimeric Gi protein in complex at 3.3-3.2 Å resolution. These agonists reside in the orthosteric pocket, forming conserved interactions via their adenine moieties, while their 3-iodobenzyl groups exhibit distinct orientations. Functional assays reveal the critical role of extracellular loop 3 in A3AR’s ligand selectivity and receptor activation. Key mutations, including His3.37, Ser5.42, and Ser6.52, in a unique sub-pocket of A3AR, significantly impact receptor activation. Comparative analysis with the inactive A2AAR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of A3AR, paving the way for designing subtype-selective adenosine receptor ligands.

Abstract Background Students’ physical fitness, particularly aerobic fitness, has seriously declined during the COVID-19 epidemic. However, in the post-epidemic era, there are few studies on the methods of improving aerobic fitness. Understanding the dose-response relationship between physical activity and aerobic fitness is crucial for developing effective exercise prescriptions. Method This retrospective study reviewed the Fun Running program at Wannan Medical College in China. We conducted a pre-post study design to analyze the impact of 15 weeks of Fun Running training on aerobic fitness. Middle and long-distance running pace (MLDR-P) was used as the primary indicator of aerobic fitness. A paired sample T-test was used to analyze the differences between the two MLDR-Ps. Pearson’s correlation was used to examine the correlation between variables. Multiple linear regression was used to determine the extent to which Fun Running components explain the variance in MLDR-P. Results A total of 3244 college students participated in this study. 15 weeks of Fun Running training can significantly improve the MLDR-P in both females (P

Abstract CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.

Abstract Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors’ feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.

Abstract Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.

Valence electron concentration (VEC) is widely accepted as an effective guideline for designing the mechanical properties of Ti-containing refractory high-entropy alloys (RHEAs). In the present work, a series of Ti–Zr–Nb–Ta and Ti–Zr–Nb–Mo RHEAs with body-centered-cubic (bcc) structure are carefully designed by tailoring their VEC through changing the alloying composition. The elastic properties and mechanical properties are systematically calculated by using a first-principles method. Comparison with available experimental data demonstrates that the employed approach accurately describes the VEC dependence of the elastic and mechanical properties of RHEAs. In general, the elastic stability, elastic properties, ideal shear strength, Vickers hardness, and yield strength increase, whereas Zener anisotropy decreases with increasing VEC. Among all the considered RHEAs, the most isotropic RHEA Ti30Zr30Nb20Mo20 has the best strength-ductility trade-off. Mo has a stronger solid solution strengthening effect than Ta. The higher strength associates with larger lattice distortion induced by increasing VEC. Both elastic stability and mechanical properties are related to the electronic density of states of the alloys. The present work sheds deep insight into the design of high-performance RHEAs through tailoring the VEC.

Within the heart’s ventricle walls are where Purkinje fibers (PFs) are located. They are essential for maintaining a steady cardiac beat because they allow the heart’s conduction system to create synchronized contractions of its ventricles. To replicate or treat some of this organ’s ailments and deficits, hardware representation of the various heart sections is necessary. Models that include a series of differential equations can be used to characterize the performance of Purkinje Fibers (PFs) in Cardiac. To develop hardware that mimics the performance of PF of Cardiac system, the Noble model is updated in this study. Due to the requirement for using units like multipliers, the original model contains non-linear components that are slow and expensive in terms of hardware resources. The main novelty of revised model incorporates non-linear components that have been converted into two base-2 terms accompanied by additional factors. These calculations are executed through efficient and economical digital hardware, including logical shift operations, additions, and subtractions, enabling high-speed processing. To validate the precision and practicality of the suggested model, a digital platform, Virtex-7 FPGA, is employed. The findings demonstrate the suggested model’s simplicity of implementation on this board and its capability to generate various PF output patterns at a maximum frequency of 381.42 MHz. The proposed digital circuit can be applied in application-based fields according to high-speed, low-cost, and accurate design. Based on the high-switching speed of neural data transferring in the human brain, other organs that are realized on hardware platforms need to be designed in high-frequency (speed-up) for adaptation with the brain. Due to removing the non-linear terms, the modified model works 1.95 times faster than the original one and saves the FPGA resources up to 35%. In case of real-world applications, an efficient low-cost hardware design for high-frequency, accurate replication of cardiac Purkinje fiber cells has the potential to revolutionize the development of medical devices for diagnosing and treating cardiac conditions. The speed and cost-effectiveness of design make it particularly promising for the creation of advanced cardiac simulation and treatment systems. The high-speed, low-cost, and accurate hardware design has broader implications for biomedical engineering beyond the cardiac system. The ability to efficiently replicate the functions of biological systems using hardware could open doors for developing high-speed, low-cost, and accurate hardware models for simulating and understanding other biological processes, such as neural data processing in the human brain or the function of other vital organs.

Background and purpose The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting.Methods 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan–Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index.Results A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p

Objective Despite revascularization has been proven to be the optimal choice of moyamoya disease (MMD), many complications may occur in this context.. This study aimed to analyse the risk factors for new or expanded symptomatic infarctions of patients with MMD after revascularization.Methods Patients with MMD who received revascularization in our department were retrospectively enrolled, new or expanded cerebral infarction within a month after revascularization was the main concern. Basic and clinical information, and intraoperative conditions were evaluated. Univariate and multivariate analyses were performed to evaluate the risk factors. Receiver operating characteristic curve analysis was conducted to evaluate the efficiency of the risk factors.Results Eventually, 108 consecutive patients received 174 surgeries were enrolled, experienced new or expanded infarction occured in 13 (7.47%) surgeries, which showed higher Suzuki stage on the non-operative side, more posterior cerebral artery (PCA) involvement, and more intraoperative hypotension compared to those without infarction(p

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. The ALS mice expressing human mutant of transactive response DNA binding protein of 43 kDa (hmTDP43) showed intestinal dysfunction before neuromuscular symptoms. We hypothesize that restoring the intestinal and microbial homeostasis with a bacterial metabolite or probiotics delays the ALS disease onset. We investigate the pathophysiological changes in the intestine and neurons, intestinal and blood–brain barriers, and inflammation during the ALS progression. We then cultured enteric glial cells (EGCs) isolated from TDP43 mice for mechanistic studies. TDP43 mice had significantly decreased intestinal mobility, increased permeability, and weakened muscle, compared with the age-matched wild-type mice. We observed increased hmTDP43 and Glial fibrillary acidic protein (GFAP), and decreased expression of α-smooth muscle actin (α-SMA), tight junction proteins (ZO-1 and Claudin-5) in the colon, spinal cord, and brain in TDP43 mice. TDP43 mice had reduced Butyryl-coenzyme A CoA transferase, decreased butyrate-producing bacteria Butyrivibrio fibrisolvens, and increased Bacteroides fragilis, compared to the WT mice. Serum inflammation cytokines (IL-6, IL-17, and IFN-γ) and LPS were elevated in TDP43 mice. EGCs from TDP43 mice showed aggregation of hmTDP43 associated with increased GFAP and ionized calcium-binding adaptor molecule (IBA1, a microglia marker). TDP43 mice treated with butyrate or probiotic VSL#3 had significantly increased rotarod time, increased intestinal mobility and decreased permeability, compared to the untreated group. Butyrate or probiotics treatment decreased the expression of GFAP, TDP43, and increased α-SMA, ZO-1, and Claudin-5 in the colon, spinal cord, and brain. Also, butyrate or probiotics treatment enhanced the Butyryl-coenzyme A CoA transferase, Butyrivibrio fibrisolvens, and reduced inflammatory cytokines in TDP43 mice. The TDP43 EGCs treated with butyrate or probiotics showed reduced GFAP, IBA1, and TDP43 aggregation. Restoring the intestinal and microbial homeostasis by beneficial bacteria and metabolites provide a potential therapeutic strategy to treat ALS.

ABSTRACTVisualizations of flood processes require a balance between scientific authenticity and realistic expressions. As the flood area increases, the amounts of time-series data that are produced by flood models often exceed the capacity of computer rendering, leading to poor user experiences and low visualization effectiveness. Therefore, this study carried out visual perception experiments and proposed a multilevel simplification and scheduling method for flood process data based on visual perceptions. This method first simplifies flood data by flood feature point selection according to conclusions related to visual perception, then triangulated irregular networks are built, and finally, flood data scheduling and rendering are achieved through multiple levels of detail combined with visual ranges. An experimental analysis using a 3D visualization prototype system shows that the proposed method can improve the efficiency of visual expressions while preserving flood morphology features.

Abstract Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol‐carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)‐4‐carboxyphenyl porphyrin/polydopamine (FAMxP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near‐infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH‐dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti‐programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF‐FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI‐guided targeted therapeutic pathways for tumors.

Diabetic kidney disease (DKD) is the primary cause of chronic kidney and end-stage renal disease. Glomerular podocyte loss and death are pathological hallmarks of DKD, and programmed cell death (PCD) in podocytes is crucial in DKD progression. PCD involves apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. During DKD, PCD in podocytes is severely impacted and primarily characterized by accelerated podocyte apoptosis and suppressed autophagy. These changes lead to a gradual decrease in podocyte numbers, impairing the glomerular filtration barrier function and accelerating DKD progression. However, research on the interactions between the different types of PCD in podocytes is lacking. This review focuses on the novel roles and mechanisms of PCD in the podocytes of patients with DKD. Additionally, we summarize clinical drugs capable of regulating podocyte PCD, present challenges and prospects faced in developing drugs related to podocyte PCD and suggest that future research should further explore the detailed mechanisms of podocyte PCD and interactions among different types of PCD.

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 ​mg/kg) via gavage from day 1 through day 28. Evaluation of the sciatic function index (SFI) and paw withdrawal threshold revealed that BBR dose-dependently enhanced both motor and sensory functions. Immunofluorescent staining for anti-myelin basic protein (anti-MBP) and anti-neurofilament-200 (anti–NF–200), along with histological staining comprising hematoxylin-eosin (HE), luxol fast blue (LFB), and Masson staining, demonstrated that BBR dose-dependently promoted structural regeneration. Molecular analyses including qRT-PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence confirmed that inactivation of the NLRP3 inflammasome by MCC950 shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, while also impeding macrophage infiltration. Furthermore, BBR significantly downregulated the expression of the NLRP3 inflammasome and its associated molecules in macrophages, thereby mitigating NLRP3 inflammasome activation-induced macrophage M1 polarization and inflammation. In summary, BBR's neuroprotective effects were concomitant with the suppression of inflammation after PNI, achieved through the inhibition of NLRP3 inflammasome activation-induced macrophage M1 polarization.

This study examines the potential impacts of projected atmospheric carbon dioxide (pCO2) levels reaching 800 ppm by the end of the century, focusing on ocean acidification effects on marine ecosystems in the coastal areas of Bohai. We investigated how acidification affects the grazing patterns of microzooplankton using dilution techniques and ecophysiological methods. Our findings indicate that acidic conditions shift the phytoplankton community structure, changing dominant species. Elevated CO2 concentrations reduced grazing pressure on phytoplankton, with less steep declines in growth rates at 800 ppm CO2 (spring: 2.43 d−1 vs. 2.16 d−1, summer: −0.46 d−1 vs. −0.73 d−1, autumn: −0.45 d−1 vs. −0.90 d−1) and significant decreases in grazing pressure percentages (%Pp from 0.84 to 0.58 and %Pi from 0.64 to 0.46). Short-term acid exposure significantly increased superoxide dismutase activity in both microplankton (from 0.03 to 0.08 U mg−1, p

With the proposal of dual carbon goals, enhancing carbon sinks and reducing carbon emissions has become a critical issue. Fisheries, as a component of agriculture, possess the dual attributes of being a “carbon sink” (biological carbon fixation) and a “carbon source” (the carbon emissions from fishing vessels). Therefore, it is necessary to assess the carbon sink and carbon emission levels of fisheries. The northern marine economic circle, which includes Liaoning, Hebei, Tianjin, and Shandong, is an important site for fisheries in China, characterized by abundant aquatic resources. However, a comprehensive assessment of the carbon budget for fisheries in this region is still unclear. This study calculated the carbon sinks, carbon emissions, and net carbon emissions associated with fisheries in the region from 2013 to 2020. Additionally, we used sensitivity analysis and scenario simulation to explore the factors influencing the net carbon emissions. The results revealed that the carbon budget of the northern marine economic circle was in a carbon deficit (the amount of carbon emissions was higher than that of carbon sinks) from 2013 to 2020. However, a downward trend in the net carbon emissions was observed, indicating the potential of achieving carbon neutrality. From the perspective of provinces, significant differences among provinces (cities) were found in terms of carbon sinks, carbon emissions, and net carbon emissions, with Shandong having the largest net carbon emissions. Furthermore, the production of clams and the use of seawater trawl net have a significant impact on the net carbon emissions. Increasing the production of clams while reducing the power of trawling operations can significantly decrease net carbon emissions. Based on these results, this study provides relevant suggestions to enhance the carbon sink capacity and decrease the carbon emissions of fisheries in the northern marine economic circle.