Search

Abstract The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu5.4O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu5.4O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu5.4O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.

Abstract Contractile rings are formed from cytoskeletal filaments during cell division. Ring formation is induced by specific crosslinkers, while contraction is typically associated with motor protein activity. Here, we engineer DNA nanotubes and peptide-functionalized starPEG constructs as synthetic crosslinkers to mimic this process. The crosslinker induces bundling of ten to hundred DNA nanotubes into closed micron-scale rings in a one-pot self-assembly process yielding several thousand rings per microliter. Molecular dynamics simulations reproduce the detailed architectural properties of the DNA rings observed in electron microscopy. Theory and simulations predict DNA ring contraction – without motor proteins – providing mechanistic insights into the parameter space relevant for efficient nanotube sliding. In agreement between simulation and experiment, we obtain ring contraction to less than half of the initial ring diameter. DNA-based contractile rings hold promise for an artificial division machinery or contractile muscle-like materials.

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

Abstract Mutations in a Plasmodium de-ubiquitinase UBP1 have been linked to antimalarial drug resistance. However, the UBP1-mediated drug-resistant mechanism remains unknown. Through drug selection, genetic mapping, allelic exchange, and functional characterization, here we show that simultaneous mutations of two amino acids (I1560N and P2874T) in the Plasmodium yoelii UBP1 can mediate high-level resistance to mefloquine, lumefantrine, and piperaquine. Mechanistically, the double mutations are shown to impair UBP1 cytoplasmic aggregation and de-ubiquitinating activity, leading to increased ubiquitination levels and altered protein localization, from the parasite digestive vacuole to the plasma membrane, of the P. yoelii multidrug resistance transporter 1 (MDR1). The MDR1 on the plasma membrane enhances the efflux of substrates/drugs out of the parasite cytoplasm to confer multidrug resistance, which can be reversed by inhibition of MDR1 transport. This study reveals a previously unknown drug-resistant mechanism mediated by UBP1 through altered MDR1 localization and substrate transport direction in a mouse model, providing a new malaria treatment strategy.

Aiming at the propagation of asymmetric vortex beam, we investigate the spreading and wander characteristics of asymmetric Bessel-Gaussian beam in oceanic turbulence. Based on the cross-spectral density and Wigner distribution function of beam field, the theoretical expressions of spreading factor and beam center displacement are established to evaluate spreading and wander. The anisotropic turbulent condition is adopted to analyze turbulence impacts with more generality. The turbulence dominated by salinity fluctuation with lower anisotropy, larger temperature dissipation and smaller kinetic energy dissipation induces more beam spreading and wander. As for asymmetric Bessel-Gaussian beam, the increment of asymmetry can improve beam directionality. Besides, smaller beam scale but larger Gaussian waist radius, vortex order and beam wavelength also mitigate spreading and wander. The investigations are instructive for the underwater applications of asymmetric vortex beams.

Abstract Background Milk synthesis in lactating animals demands high energy metabolism, which results in an increased production of reactive oxygen metabolites (ROM) causing an imbalance between oxidants and antioxidants thereby inducing oxidative stress (OS) on the animals. To mitigate OS and postpartum disorders in dairy goats and gain insight into the impact of dietary choices on redox status during lactation, a feeding trial was conducted using alfalfa silage inoculated with a high-antioxidant strain of Lactiplantibacillus plantarum. Methods Twenty-four Guanzhong dairy goats (38.1 ± 1.20 kg) were randomly assigned to two dietary treatments: one containing silage inoculated with L. plantarum MTD/1 (RSMTD-1), and the other containing silage inoculated with high antioxidant activity L. plantarum 24-7 (ES24-7). Results ES24-7-inoculated silage exhibited better fermentation quality and antioxidant activity compared to RSMTD-1. The ES24-7 diet elevated the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in milk, serum, and feces of lactating goats (with the exception of T-AOC in milk). Additionally, the diet containing ES24-7 inoculated silage enhanced casein yield, milk free fatty acid (FFA) content, and vitamin A level in the goats’ milk. Furthermore, an increase of immunoglobulin (Ig)A, IgG, IgM, interleukin (IL)-4, and IL-10 concentrations were observed, coupled with a reduction in IL-1β, IL-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α concentrations in the serum of lactating goats fed ES24-7. Higher concentrations of total volatile fatty acid (VFA), acetate, and propionate were observed in the rumen fluid of dairy goats fed ES24-7 inoculated silage. Moreover, the diet containing ES24-7 inoculated silage significantly upregulated the expression of nuclear factor erythroid 2 like 2 (NFE2L2), beta-carotene oxygenase 1 (BCO1), SOD1, SOD2, SOD3, GPX2, CAT, glutathione-disulfide reductase (GSR), and heme oxygenase 1 (HMOX1) genes in the mammary gland, while decreased the levels of NADPH oxidase 4 (NOX4), TNF, and interferon gamma (IFNG). Conclusions These findings indicated that feeding L. plantarum 24-7 inoculated alfalfa silage not only improved rumen fermentation and milk quality in lactating dairy goats but also boosted their immunity and antioxidant status by modulating the expression of several genes related to antioxidant and inflammation in the mammary gland.

AbstractContext Danggui Buxue Decoction (DBD) is an effective complementary medicine in alleviating myelosuppression after chemotherapy (MAC). However, its mechanism of action is elusive.Objective To illustrate that regulating β-hydroxybutyric acid (β-OHB) metabolism and suppressing oxidative stress could be a potential mechanism of action for DBD in alleviating MAC.Materials and methods After HPLC quantification and dose testing (3, 6 and 10 g/kg, gavage) of DBD, Sprague-Dawley rats were divided into control, cyclophosphamide (CTX) (30 mg/kg CTX for 5 days, intraperitoneal administration) and CTX + DBD groups (6 g/kg DBD for 14 days, gavage). Blood cell counts, thigh bone histological examination, β-OHB levels, oxidative stress indices and HDAC1 activity were tested. The biological function of β-OHB was verified in vitro (hBMSC cells were incubated in culture mediums that contained 40 μM CTX and β-OHB in 0, 1, 2.5, 5, 10 mM) and in vivo (MAC rat model, 3 g/kg β-OHB for 14 days, gavage).Results Rats in the CTX + DBD group showed upregulated blood cell counts (118–243%), β-OHB levels (495 nmol/mL in blood, 122 nmol/mg in marrow supernatant) and downregulated HDAC1 activity (59%), and oxidative stress indices (60–85%). In vitro, 5 mM β-OHB improved hBMSC cell migration (123%) and proliferation (131%). In vivo, rats treated with 3 g/kg β-OHB showed upregulated blood cell counts (121–182%) and downregulated HDAC1 activity (64%) and oxidative stress indices (65–83%).Discussion and conclusions DBD, a traditional Chinese medicine, alleviates MAC by intervening in β-OHB metabolism and oxidative stress.

BackgroundPredicting flap viability benefits patients by reducing complications and guides flap design by reducing donor areas. Due to varying anatomy, obtaining individual vascular information preoperatively is fundamental for designing safe flaps. Although indocyanine green angiography (ICGA) is a conventional tool in intraoperative assessment and postoperative monitoring, it is rare in preoperative prediction.MethodsICGA was performed on 20 male BALB/c mice under five wavelengths (900/1,000/1,100, /1,250/1,450 nm) to assess vascular resolution after ICG perfusion. A “mirrored-L” flap model with three angiosomes was established on another 20 male BALB/c mice, randomly divided into two equal groups. In Group A, a midline between angiosomes II and III was used as a border. In Group B, the points of the minimized choke vessel caliber marked according to the ICG signal at 1,450 nm wavelength (ICG1450) were connected. Necrotic area calculations, pathohistological testing, and statistical analysis were performed.ResultsThe vascular structure was clearly observed at 1,450 nm wavelength, while the 900 to 1,100 nm failed to depict vessel morphology. Necrosis was beyond the borderline in 60% of Group A. Conversely, 100% of Group B had necrosis distal to the borderline. The number of choke vessels between angiosomes II and III was positively correlated with the necrotic area (%). The pathohistological findings supported the gross observation and analysis.ConclusionICG1450 can delineate the vessel structure in vivo and predict the viability of pedicled skin flaps using the choke vessel as the border between angiosomes.

Plant synthetic biology research requires diverse bioparts that facilitate the redesign and construction of new-to-nature biological devices or systems in plants. Limited by few well-characterized bioparts for plant chassis, the development of plant synthetic biology lags behind that of its microbial counterpart. Here, we constructed a web-based Plant Synthetic BioDatabase (PSBD), which currently categorizes 1677 catalytic bioparts and 384 regulatory elements and provides information on 309 species and 850 chemicals. Online bioinformatics tools including local BLAST, chem similarity, phylogenetic analysis, and visual strength are provided to assist with the rational design of genetic circuits for manipulation of gene expression in planta. We demonstrated the utility of the PSBD by functionally characterizing taxadiene synthase 2 and its quantitative regulation in tobacco leaves. More powerful synthetic devices were then assembled to amplify the transcriptional signals, enabling enhanced expression of flavivirus non-structure 1 proteins in plants. The PSBD is expected to be an integrative and user-centered platform that provides a one-stop service for diverse applications in plant synthetic biology research.

Abstract Background Therapeutic options for ulcerative colitis (UC) have increased since the introduction of biologics a few decades ago. Due to the wide range of biologics available, physicians have difficulty in selecting biologics and do not know how to balance the best drug between clinical efficacy and safety. This study aimed to compare the efficacy and safety of biologics in treating ulcerative colitis. Methods In this study, eight electronic databases (PubMed, Web of Science, Cochrane, Embase, Sinomed, China National Knowledge Infrastructure, Chongqing VIP Information, and WanFang Data) were searched to collect eligible studies without language restrictions. Retrieved 1 June 2023, from inception. All articles included in the mesh analysis are randomised controlled trials (RCTs). The inclusion of drugs for each outcome was ranked using a curved surface under cumulative ranking (SUCRA). Higher SUCRA scores were associated with better outcomes, whereas lower SUCRA scores were associated with better safety. This study has registered with PROSPERO, CRD42023389483. Results Induction Therapy: Among the biologic therapies evaluated for induction therapy, vedolizumab demonstrated the highest efficacy in achieving clinical remission (OR vs daclizumab, 9.09; 95% CI, 1.01–81.61; SUCRA 94.1) and clinical response. Guselkumab showed the lowest risk of recurrence of UC (SUCRA 94.9%), adverse events resulting in treatment discontinuation (SUCRA 94.8%), and serious infections (SUCRA 78.0%). Maintenance Therapy: For maintenance therapy, vedolizumab ranked highest in maintaining clinical remission (OR vs mesalazine 4.36; 95% CI, 1.65–11.49; SUCRA 89.7) and endoscopic improvement (SUCRA 92.6). Infliximab demonstrated the highest efficacy in endoscopic improvement (SUCRA 92.6%). Ustekinumab had the lowest risk of infections (SUCRA 92.9%), serious adverse events (SUCRA 91.3%), and serious infections (SUCRA 67.6%). Conclusion Our network meta-analysis suggests that vedolizumab is the most effective biologic therapy for inducing and maintaining clinical remission in UC patients. Guselkumab shows promise in reducing the risk of recurrence and adverse events during induction therapy. Infliximab is effective in improving endoscopic outcomes during maintenance therapy. Ustekinumab appears to have a favorable safety profile. These findings provide valuable insights for clinicians in selecting the most appropriate biologic therapy for UC patients.

Abstract Gastric cancer (GC) is the one of the most commonly solid cancer worldwide. Although under the aggressive treatment, the poor clinical outcomes of patients with GCs have not been improved. Current studies emphasized that targeting therapies or immune response-based therapeutic strategy may be a potential approach to improve the clinical outcomes. Moreover, accumulative evidence has reported the increasing expression of PD-L1 expression in GC cells and highlighted its role in the tumor progression. Currently, great development has been established in the immune checkpoint inhibitors (ICIs) and further changed the clinical practice of GC treatment and prognosis. In addition, the combination therapies with targeting therapy or traditional therapies are expected to push the development of immunotherapies. In our present review, we predominantly focus on the biomarkers and molecular profiles for immunotherapies in GCs and highlight the role and administration of ICIs-based immunotherapeutic strategies against the GCs.

Detecting deep-sea megabenthic organisms is of foremost importance for seabed resource surveys, typical habitat protection, and biodiversity surveys. However, the complexity of the deep-sea environment, uneven illumination, and small biological targets that are easily obscured all increase target detection difficulty significantly. To address these, this paper proposes a deep-sea megabenthic detection algorithm, DS-YOLO, based on YOLOv5s. To improve the detection ability of the model for deep-sea megabenthic organisms, the space-to-depth module and the spatial pyramid pooling cross stage partial channel module are introduced in the Backbone layer to enlarge the receptive field and enhance the retention of small-scale features. Then, the space-to-depth and normalization-based attention modules and the Add and Concat functions of the bidirectional feature pyramid network are introduced in the Neck layer to increase the multiscale fusion ability of the model and highlight the insignificant features. Finally, the two branches of the decoupling header output the category and location of the target, which causes the model to utilize the feature information to the maximum extent. Experiments showed that DS-YOLO improved mAP0.5 from 89.6% to 92.4% and mAP0.5:0.95 from 65.7% to 72.3% compared to the original YOLOv5s on the homemade dataset and outperformed other algorithms in the YOLO series. DS-YOLO reaches 84.7 FPS for deployment on mobile platforms. In addition, the combined DS-YOLO and DeepSORT algorithm can be used to calculate the abundance and community structure of deep-sea megabenthos. The model outperforms general target detection models for deep-sea megabenthos detection and is suitable for use in complex deep-sea environments.

IntroductionRapid and accurate detection of food-borne pathogens on mutton is of great significance to ensure the safety of mutton and its products and the health of consumers.ObjectivesThe feasibility of short-wave infrared hyperspectral imaging (SWIR-HSI) in detecting the contamination status and species of Escherichia coli (EC), Staphylococcus aureus (SA) and Salmonella typhimurium (ST) contaminated on mutton was explored.Materials and methodsThe hyperspectral images of uncontaminated and contaminated mutton samples with different concentrations (108, 107, 106, 105, 104, 103 and 102 CFU/mL) of EC, SA and ST were acquired. The one dimensional convolutional neural network (1D-CNN) model was constructed and the influence of structure hyperparameters on the model was explored. The effects of different spectral preprocessing methods on partial least squares-discriminant analysis (PLS-DA), support vector machine (SVM) and 1D-CNN models were discussed. In addition, the feasibility of using the characteristic wavelength to establish simplified models was explored.Results and discussionThe best full band model was the 1D-CNN model with the convolution kernels number of (64, 16) and the activation function of tanh established by the original spectra, and its accuracy of training set, test set and external validation set were 100.00, 92.86 and 97.62%, respectively. The optimal simplified model was genetic algorithm optimization support vector machine (GA-SVM). For discriminating the pathogen species, the accuracies of SVM models established by full band spectra preprocessed by 2D and all 1D-CNN models with the convolution kernel number of (32, 16) and the activation function of tanh were 100.00%. In addition, the accuracies of all simplified models were 100.00% except for the 1D-CNN models. Considering the complexity of features and model calculation, the 1D-CNN models established by original spectra were the optimal models for pathogenic bacteria contamination status and species. The simplified models provide basis for developing multispectral detection instruments.ConclusionThe results proved that SWIR-HSI combined with machine learning and deep learning could accurately detect the foodborne pathogen contamination on mutton, and the performance of deep learning models were better than that of machine learning. This study can promote the application of HSI technology in the detection of foodborne pathogens on meat.

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid β-peptide (Aβ) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aβ oligomer deposited and ganglioside GM1 could be formed as “seed” from insoluble GAβ polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aβ, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aβ, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.

Abstract Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA‐loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA‐ loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L‐type hydrogels are found to have preferable drug penetration over D‐type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration.

Summary: Plasma proteins are promising biomarkers and potential drug targets in lung cancer. To evaluate the causal association between plasma proteins and lung cancer, we performed proteome-wide Mendelian randomization meta-analysis (PW-MR-meta) based on lung cancer genome-wide association studies (GWASs), protein quantitative trait loci (pQTLs) of 4,719 plasma proteins in deCODE and 4,775 in Fenland. Further, causal-protein risk score (CPRS) was developed based on causal proteins and validated in the UK Biobank. 270 plasma proteins were identified using PW-MR meta-analysis, including 39 robust causal proteins (both FDR-q

The multiple global environments have triggered changes in the international environment, leading to a sharp decline of foreign direct investment (FDI) compared to pre-pandemic level. To evaluate the investment risk of FDI and make optimal investment decision becomes the most important issue for investors. This paper focuses on the evaluation of investment risk for FDI. First, an index system for risk evaluation of FDI is constructed. Then, we introduce the probabilistic linguistic entropy and cross entropy measures, based on which, a programming model is developed to identify the objective attribute weights. A composite weight derivation method, which takes both the objective attribute weights and the subjective attribute weights into account, is further introduced. In view of attributes' uncertainty and fuzziness and the conflicting characteristics of some attributes, the VIKOR (the Serbian name: VlseKriterijumska Optimizacija I Kompromisno Resenje, means multi-criteria optimization and compromise solution) method is used to evaluate the risk of FDI under the probabilistic linguistic environment. Furthermore, a case study is presented to illustrate the proposed method. The comparative analysis and some further discussions verify the validity of the proposed method for the FDI risk evaluation.

Repairing defects in alveolar bone is essential for regenerating periodontal tissue, but it is a formidable challenge. One promising therapeutic approach involves using a strategy that specifically recruits periodontal ligament cells (PDLCs) with high regenerative potential to achieve in situ regeneration of alveolar bone. In this study, we have created a new type of microsphere conjugated with an antibody to target p75 neurotrophin receptor (p75NTR), which is made of nano-hydroxyapatite (nHA) and chitosan (CS). The goal of this design is to attract p75NTR+hPDLCs selectively and promote osteogenesis. In vitro experiments demonstrated that the antibody-conjugated microspheres attracted significantly more PDLCs compared to non-conjugated microspheres. Incorporating nHA not only enhances cell adhesion and proliferation on the surface of the microsphere but also augments its osteoinductive properties. Microspheres effectively recruited p75NTR+ cells at bone defect sites in SD rats, as observed through immunofluorescent staining of p75NTR antibodies. This p75NTR antibody-conjugated nHA/CS microsphere presents a promising approach for selectively recruiting cells and repairing bone defects.

Background: Toxoplasma gondii is an opportunistic parasitic protozoan that can cause highly fatal toxoplasmic encephalitis when the host immune system is compromised. However, the transition from chronic to acute infection remains poorly understood. In this study, we conducted a 180-day observation of tissue damage and inflammation in the brains of mice infected with T. gondii. Subsequently, we investigated the inflammatory factors that T. gondii infection may alter using two-sample Mendelian randomization (MR) analysis. Methods: We first established a mouse model of T. gondii infection. Subsequently, the mice were euthanized, the brain tissue collected, and immunohistochemistry and hematoxylin and eosin staining performed to observe tissue damage and inflammatory conditions at various time points. Our study also included a published large-scale genome-wide association study meta-analysis that encompassed the circulating concentrations of 41 cytokines. This dataset included 8293 individuals from three independent population cohorts in Finland. Genetic association data for T. gondii were sourced from the Integrative Epidemiology Unit and European Bioinformatics Institute datasets, which included 5010 and 559 individuals of European ancestry, respectively. To assess the causal relationship between T. gondii infection and inflammatory biomarkers, we applied a two-sample MR. Results: Inflammation and damage resulting from T. gondii infection varied among the distinct regions of the mouse brain. Based on the MR analysis results, three inflammatory biomarkers were chemically assigned to Chemokines and Others, including IP10 (interferon gamma inducible protein-10), MCP1 (monocyte chemoattractant protein-1), and TRAIL (TNF-related apoptosis-inducing ligand). Conclusion: Our study commenced with the assessment of tissue damage and progression of inflammation in distinct regions of the mouse brain after T. gondii infection. Subsequently, using MR analysis, we detected potential alterations in inflammatory factors associated with this infection. These findings offer valuable insights into the mechanisms underlying toxoplasmic encephalitis and suggest directions for the prevention and treatment of T. gondii infections.

ABSTRACTCerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection with acute brain lesions. Genetic variations in both host and parasite have been associated with susceptibility to CM, but the underlying molecular mechanism remains unclear. Here, we demonstrate that variants of human apolipoprotein E (hApoE) impact the outcome of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). Mice carrying the hApoE2 isoform have fewer intracerebral hemorrhages and are more resistant to ECM than mice bearing the hApoE3, hApoE4, or endogenous murine ApoE (mApoE). hApoE2 mice infected with PbA showed increased splenomegaly and IFN-γ levels in serum but reduced cerebral cell apoptosis that correlated with the survival advantage against ECM. In addition, upregulated expression of genes associated with lipid metabolism and downregulated expression of genes linked to immune responses were observed in the brain tissue of hApoE2 mice relative to ECM-susceptible mice after PbA infection. Notably, serum cholesterol and the cholesterol content of brain-infiltrating CD8+ T cells are significantly higher in infected hApoE2 mice, which might contribute to a significant reduction in the sequestration of brain CD8+ T cells. Consistent with the finding that fewer brain lesions occurred in infected hApoE2 mice, fewer behavioral deficits were observed in the hApoE2 mice. Finally, a meta-analysis of publicly available data also showed an increased hApoE2 allele in the malaria-endemic African population, suggesting malaria selection. This study shows that hApoE2 protects mice from ECM through suppression of CD8+ T cell activation and migration to the brain and enhanced cholesterol metabolism.IMPORTANCECerebral malaria (CM) is the deadliest complication of malaria infection with an estimated 15%–25% mortality. Even with timely and effective treatment with antimalarial drugs such as quinine and artemisinin derivatives, survivors of CM may suffer long-term cognitive and neurological impairment. Here, we show that human apolipoprotein E variant 2 (hApoE2) protects mice from experimental CM (ECM) via suppression of CD8+ T cell activation and infiltration to the brain, enhanced cholesterol metabolism, and increased IFN-γ production, leading to reduced endothelial cell apoptosis, BBB disruption, and ECM symptoms. Our results suggest that hApoE can be an important factor for risk assessment and treatment of CM in humans.

BackgroundResidential green spaces (RGS) are a crucial aspect of urban life, which provide residents with a positive living environment both for mental and physical well-being. However, extreme heat events caused by global warming and local urban heat island effects are threatening the public health of rapidly growing populations. This is especially true for mental health. Depression is a mental illness that can be impacted by extreme heat events, i.e., heatwaves.ObjectiveThis study aimed to investigate the potential for residential green spaces (RGS) to alleviate depression by reducing heat stress sensitivity during extreme heat events.MethodsWe conducted a literature review using scientometric analysis with CiteSpace to summarize existing research on the relationships between RGS, depression, and heatwaves. We proposed a conceptual framework for the relationship between RGS and depression, and that extreme heat events may be an important contributor to depression.ResultsOur review found that RGS can provide ecosystem services that lower ambient temperatures through evaporative cooling, radiation reflection, humidity regulation, and shading. Different types of RGS, i.e., small green spaces, green roofs, green walls, and street trees, have varying cooling capacities. The mechanisms by which RGS alleviate depression during heatwaves involve green space composition, exposure, physical activity, social contacts, and cohesion. And we proposed a conceptual framework for the relationship between RGS and depression, and that extreme heat events may be an important contributor to depression.ConclusionWe present a multidimensional RGS evaluation roadmap to inform green space design for reducing depression during heatwaves. Establishing RGS multidimensional evaluation can guide future research on leveraging RGS to build resilience against extreme heat and improve public mental health.

The progressive collapse of flat plate structures due to brittle punching shear failure of reinforced concrete (RC) slab-column connections is a major concern in structural engineering. This paper proposed an innovative star-shaped steel plates (SSPs) system to achieve an effective yet practical enhancement of the punching and post-punching performance of RC slab-column connections. SSPs were fabricated from thin steel plates, welded together, and placed in the centre of the joint. Engineering cementitious composite (ECC) was also adopted to replace the joint core concrete and work with the SSPs further to improve the punching shear behaviour of the joint. To evaluate the effectiveness of the proposed system, five large-scale RC slab-column connections with different SSPs configurations and concrete materials were tested under monotonic load. The results showed that the initial stiffness of the joint was minimally affected by the presence of SSPs, but the system significantly improved the punching shear strength, post-punching load-bearing capacity, and deformation capacity of the joint. Specimens with ECC and SSPs exhibited an even higher punching shear strength and more ductile post-punching behaviour. The study also found that the optimum enhancement of the punching shear behaviour of the slab-column joint can be realised when the SSPs yield just before the joint experiences punching shear damage. Finally, formulas were developed to reasonably predict the punching shear strength and post-punching load-carrying capacity of the SSPs reinforced slab-column connections.

Background: Sepsis-induced cardiomyopathy (SIC) is a severe myocardial dysfunction secondary to septicemia. It is a major concern owing to the high mortality and morbidity, which are greatly influenced by ferroptosis. Resveratrol (RSV) is a naturally existing agonist of the silent information regulator 1 (Sirt1). It has cardioprotective effects against sepsis-induced myocardial injury, However, the detailed mechanism is unknown. Methods: In this study, cecal ligation and puncture (CLP)-induced septic rats were employed to assess the changes in ferroptosis with RSV administration. According to the different treatments the rats were divided into the following groups: (1) the Sham, (2) CLP, (3) CLP + RSV at various doses (10, 30, and 50 mg/kg), and (4) CLP + Fer-1(a ferroptotic inhibitor) groups. After 24 h, the structure and function of the cardiac system in rats were evaluated, and mitochondrial morphology, ferroptosis-related biomarkers, and the levels of Sirt1/Nrf2 were assessed. Results: The rats that underwent CLP had suffered cardiac dysfunction, accompanied with myocardial damage, impaired mitochondria, elevated lipid peroxidation, and reduced Sirt1/Nrf2 expression in the myocardium. High-dose RSV successfully improved heart function, reversing the abnormalities in a dose-dependent manner. We then used EX527, a selective Sirt1 inhibitor, to further identify the intermediate signaling targets of RSV that regulate ferroptosis. EX527 diminished the curative effects of high-doses RSV. Conclusions: Summarily, our findings suggest a novel mechanism of RSV in reducing SIC: ferroptosis inhibition via upregulation of Sirt1/Nrf2 signaling pathways. This may be an effective therapeutic approach against organ failure in sepsis, particularly SIC.

The study aimed to evaluate the value of cancer-directed surgery (CDS) in improving the prognosis of patients with stage IVB endometrial cancer (EC) and under which kind of conditions could maximise its value. The Surveillance, Epidemiology, and End Results database was used to analyse patients diagnosed with stage IVB EC who received chemotherapy between 2004 and 2016. Among 1978 patients were enrolled following propensity score matching (PSM). We found that CDS was closely associated with prolonged overall survival. Moreover, CDS can effectively improve the survival rate of patients with protective or unfavourable factors and should be considered in a range of circumstances. Almost all patients (96.15%) who received surgery were operated on primary tumours of the reproductive organs and obtained favourable surgical outcomes. In conclusion, surgery can improve the survival of patients with stage IVB EC, palliative hysterectomy is worth considering in such patients.IMPACT STATEMENT What is already known on this subject? Patients with stage IVB EC account for a small proportion, so previous researches usually had an insufficient sample size. And it is still controversial whether to perform surgery on patients with stage IVB EC. What do the results of this study add? We verified the value of CDS in improving prognosis of patients with stage IVB EC. We also found that surgery outcomes were better in patients aged ˂ 60 years, and with T1 and T2 invasion. Moreover, resection of the primary site played an important role in prolonging survival time. What are the implications of these findings for clinical practice and/or further research? Surgical treatment can prolong the overall survival of patients with stage IVB EC, even if only primary site resection is performed. Surgery should be more aggressive in patients aged ˂ 60 years, and with lesions confined in the pelvis (with T1 and T2 invasion). The survival rate of patients with brain metastasis may also be improved by surgery. However, because of the small sample size, the surgical benefit needs further confirmation.

Surfactants were proposed to be added into magnesium sulfate solution to improve the leaching process of weathered crust elution-deposited rare earth ores (WREOs). Effects of surfactants and their concentration on the seepage of leaching solutions and the leaching efficiency of rare earth (RE) and aluminum (Al) were investigated, and the leaching kinetics, the mass transfer process, the adhesion work and the adhesion work reduction factor were analyzed to reveal its strengthening leaching mechanism. The results show that cetyltrimethylammonium bromide (CTAB) has a better strengthening effect on the leaching process than dodecyl trimethyl ammonium bromide (DTAB), sodium dodecyl sulfate (SDS), sodium oleate and oleic acid. In the presence of 0.04% CTAB in 0.2 mol/L solution, the permeability coefficient of WREOs increases from 0.945×10−5 to 1.640×10−5 cm·s−1, and the leaching efficiency of RE increases from 80% to 90%, confirming the promotion of surfactants on the leaching process of WREOs. Kinetic analysis shows that the leaching process conforms to the inner diffusion control model, and the leaching kinetics equations of RE and Al related to CTAB content are obtained. Mass transfer discussion shows a smaller height equivalent to theoretical plate (HETP) of RE and Al at CTAB content of 0.04%, suggesting the higher mass transfer efficiency here. According to the interfacial properties of leaching solutions, the calculated adhesion work and the adhesion work reduction factor further demonstrate the strengthening leaching effect of CTAB on the leaching process of WREOs.

Abstract Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI primarily manifests as ovarian function decline and endocrine disorders in women prior to age 40 and is an established cause of female infertility. It is crucial to elucidate the causative factors of POI, not only to expand the understanding of ovarian physiology, but also to provide genetic counselling and fertility guidance to affected patients. Factors leading to POI are multifaceted with genetic factors accounting for 7% to 30%. In recent years, an increasing number of DNA damage-repair-related genes have been linked with the occurrence of POI. Among them, DNA double-strand breaks (DSBs), one of the most damaging to DNA, and its main repair methods including homologous recombination (HR) and non-homologous end joining (NHEJ) are of particular interest. Numerous genes are known to be involved in the regulation of programmed DSB formation and damage repair. The abnormal expression of several genes have been shown to trigger defects in the overall repair pathway and induce POI and other diseases. This review summarises the DSB-related genes that may contribute to the development of POI and their potential regulatory mechanisms, which will help to further establish role of DSB in the pathogenesis of POI and provide theoretical guidance for the study of the pathogenesis and clinical treatment of this disease.

Abstract Background Prior clinical studies suggest a shared mechanism between vestibular symptoms and migraine headache. However, the specific neuroanatomical substrate connecting vestibular symptoms with migraine remains to be largely unknown. Thus, the aim of this study was to further investigate the mechanisms that whether and how trigeminovestibular neurons produce effects on neuronal activation in vestibular nucleus (VN). Methods A chronic-NTG rat model was established by recurrent intermittent administration of nitroglycerin (NTG). Pain- and vestibular-related behaviors were assessed. To selectively inhibit the glutamatergic neurons and trigeminal nucleus caudalis (TNC) to VN projection neurons, the AAVs encoding engineered Gi-coupled hM4D receptor were administered in the TNC or VN area. Results We identify a glutamatergic projection from TNC to VN that mediates vestibular dysfunction in a chronic-NTG rat model. Inhibition of the GlutamateTNC neurons alleviates vestibular dysfunction in the chronic-NTG rat. Calcitonin gene-related peptide (CGRP)-expressing neurons in the VN received glutamatergic projections from TNC neurons. Silencing the glutamatergic TNC-VN projection neurons attenuates vestibular dysfunction in the chronic-NTG rat. Conclusions Together, we reveal a modulatory role of glutamatergic TNC-VN projection neurons in vestibular dysfunction of migraine. Graphical Abstract

In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.

People with upper limb disabilities or high quadriplegia have extremely high requirements for the maneuverability and functionality of power wheelchairs. Normal wheelchairs cannot meet travel tasks, while smart customized wheelchairs are expensive and cannot be popularized. Therefore, a novel extension control instrument for power wheelchairs with low cost, strong scalability, and convenient usage is proposed, which can realize the control of the wheelchair by sensing a change of head posture. The device is divided into a head motion sensing unit (HMSU) and a wheelchair assistance control unit (WACU). The mapping relationship between the head attitude and the subject’s motion intention is established. The inertial measurement module in the HMSU collects the head attitude data and uses the Kalman filtering method to obtain the accurate Euler angle. The WACU is fixed on the original controller of the wheelchair. The joystick is inserted into the extended control mechanism and controlled, instead of the hand, through a 2-degree-of-freedom servo system combined with the pinion and rack push rod structure, thus controlling the movement of the wheelchair. In proceeding, the system can also detect the distance of objects in the environment in real time through the three-direction (front, left, right) ultrasonic ranging sensors installed on the WACU, with a certain obstacle avoidance function. The prototype experiments prove that the extension control instrument developed in this paper based on the Kalman filter can quickly and accurately identify head motion and accurately control the movement of the wheelchair. It is easy to operate and has strong universality, which presents a new low-cost solution for the travel of patients with disabilities.

As the main organic materials, straw and manure play a critical role in soil organic carbon (SOC) sequestration and crop yield in China. This meta-analysis evaluated the impact of straw and manure amendments, both individually and combined, on crop yield, SOC, and soil nutrients in China by collecting 173 studies. The findings of this study revealed that straw return and manure application increased crop yields by 14.4% and 70.4%, respectively, overall. Combined straw and manure application gained a better improvement effect than straw alone but was less effective than manure alone. Regarding the straw return results, rice straw and a 3000–6000 kg ha−1 returning quantity improved crop yield, SOC, available phosphorus (AP), available potassium (AK), and total nitrogen (TN) the most; regarding the straw return form, straw incorporated into soil and biochar increased crop yield and SOC more, respectively; and

CeO2 is an outstanding support commonly used for the CuO-based CO oxidation catalysts due to its excellent redox property and oxygen storage–release property. However, the inherently small specific surface area of CeO2 support restricts the further enhancement of its catalytic performance. In this work, the novel mesoporous CeO2 nanosphere with a large specific surface area (~190.4 m2/g) was facilely synthesized by the improved hydrothermal method. The large specific surface area of mesoporous CeO2 nanosphere could be successfully maintained even at high temperatures up to 500 °C, exhibiting excellent thermal stability. Then, a series of CuO-based CO oxidation catalysts were prepared with the mesoporous CeO2 nanosphere as the support. The large surface area of the mesoporous CeO2 nanosphere support could greatly promote the dispersion of CuO active sites. The effects of the CuO loading amount, the calcination temperature, mesostructure, and redox property on the performances of CO oxidation were systematically investigated. It was found that high Cu+ concentration and lattice oxygen content in mesoporous CuO/CeO2 nanosphere catalysts greatly contributed to enhancing the performances of CO oxidation. Therefore, the present mesoporous CeO2 nanosphere with its large specific surface area was considered a promising support for advanced CO oxidation and even other industrial catalysts.

The circadian clock plays a critical role in dentomaxillofacial development. Tooth biomineralization is characterized by the circadian clock; however, the mechanisms underlying the coordination of circadian rhythms with tooth development and biomineralization remain unclear. The p75 neurotrophin receptor (p75NTR) is a clock factor that regulates the oscillatory components of the circadian rhythm. This study aims to investigate the impact of p75NTR on the rhythmic mineralization of teeth and elucidate its underlying molecular mechanisms. We generated p75NTR knockout mice to examine the effects of p75NTR deficiency on tooth mineralization. Ectomesenchymal stem cells (EMSCs), derived from mouse tooth germs, were used for in vitro experiments. Results showed a reduction in tooth mineral density and daily mineralization rate in p75NTR knockout mice. Deletion of p75NTR decreased the expression of DMP1, DSPP, RUNX2, and ALP in tooth germ. Odontogenic differentiation and mineralization of EMSCs were activated by p75NTR. Histological results demonstrated predominant detection of p75NTR protein in odontoblasts and stratum intermedium cells during rapid formation phases of dental hard tissue. The mRNA expression of p75NTR exhibited circadian variations in tooth germs and EMSCs, consistent with the expression patterns of the core clock genes Bmal1 and Clock. The upregulation of BMAL1/CLOCK expression by p75NTR positively regulated the mineralization ability of EMSCs, whereas BMAL1 and CLOCK exerted a negative feedback regulation on p75NTR by inhibiting its promoter activity. Our findings suggest that p75NTR is necessary to maintain normal tooth biomineralization. Odontogenic differentiation and mineralization of EMSCs is regulated by the p75NTR-BMAL1/CLOCK signaling axis. These findings offer valuable insights into the associations between circadian rhythms, tooth development, and biomineralization.

Abstract Background Type 2 diabetes mellitus (T2DM), which has a high incidence and several harmful consequences, poses a severe danger to human health. Research on the function of ferroptosis in T2DM is increasing. This study uses bioinformatics techniques identify new diagnostic T2DM biomarkers associated with ferroptosis. Methods To identify ferroptosis‐related genes (FRGs) that are differentially expressed between T2DM patients and healthy individuals, we first obtained T2DM sequencing data and FRGs from the Gene Expression Omnibus (GEO) database and FerrDb database. Then, drug‐gene interaction networks and competitive endogenous RNA (ceRNA) networks linked to the marker genes were built after marker genes were filtered by two machine learning algorithms (LASSO and SVM‐RFE algorithms). Finally, to confirm the expression of marker genes, the GSE76895 dataset was utilized. The protein and RNA expression of some marker genes in T2DM and nondiabetic tissues was also examined by Western blotting, immunohistochemistry (IHC), immunofluorescence (IF) and quantitative real‐time PCR (qRT‐PCR). Results We obtained 58 differentially expressed genes (DEGs) associated with ferroptosis. GO and KEGG enrichment analyses showed that these DEGs were significantly enriched in hypoxia and ferroptosis. Subsequently, eight marker genes (SCD, CD44, HIF1A, BCAT2, MTF1, HILPDA, NR1D2, and MYCN) were screened by LASSO and SVM‐RFE machine learning algorithms, and a model was constructed based on these eight genes. This model also has high diagnostic power. In addition, based on these eight genes, we obtained 48 drugs and constructed a complex ceRNA network map. Finally, Western blotting, IHC, IF, and qRT‐PCR results of clinical samples further confirmed the results of public databases. Conclusions The diagnosis and aetiology of T2DM can be greatly aided by eight FRGs, providing novel therapeutic avenues.

Background: As an inevitable event after kidney transplantation, ischemia‒reperfusion injury (IRI) can lead to a decrease in kidney transplant success. The search for signature genes of renal ischemia‒reperfusion injury (RIRI) is helpful in improving the diagnosis and guiding clinical treatment. Methods: We first downloaded 3 datasets from the GEO database. Then, differentially expressed genes (DEGs) were identified and applied for functional enrichment analysis. After that, we performed three machine learning methods, including random forest (RF), Lasso regression analysis, and support vector machine recursive feature elimination (SVM-RFE), to further predict candidate genes. WGCNA was also executed to screen candidate genes from DEGs. Then, we took the intersection of candidate genes to obtain the signature genes of RIRI. Receiver operating characteristic (ROC) analysis was conducted to measure the predictive ability of the signature genes. Kaplan‒Meier analysis was used for association analysis between signature genes and graft survival. Verifying the expression of signature genes in the ischemia cell model. Results: A total of 117 DEGs were screened out. Subsequently, RF, Lasso regression analysis, SVM-RFE and WGCNA identified 17, 25, 18 and 74 candidate genes, respectively. Finally, 3 signature genes (DUSP1, FOS, JUN) were screened out through the intersection of candidate genes. ROC analysis suggested that the 3 signature genes could well diagnose and predict RIRI. Kaplan‒Meier analysis indicated that patients with low FOS or JUN expression had a longer OS than those with high FOS or JUN expression. Finally, we validated using the ischemia cell model that compared to the control group, the expression level of JUN increased under hypoxic conditions. Conclusions: Three signature genes (DUSP1, FOS, JUN) offer a good prediction for RIRI outcome and may serve as potential therapeutic targets for RIRI intervention, especially JUN. The prediction of graft survival by FOS and JUN may improve graft survival in patients with RIRI.

IntroductionSpeech communication is multi-sensory in nature. Seeing a speaker’s head and face movements may significantly influence the listeners’ speech processing, especially when the auditory information is not clear enough. However, research on the visual-auditory integration speech processing has left prosodic perception less well investigated than segmental perception. Furthermore, while native Japanese speakers tend to use less visual cues in segmental perception than in other western languages, to what extent the visual cues are used in Japanese focus perception by the native and non-native listeners remains unknown. To fill in these gaps, we test focus perception in Japanese among native Japanese speakers and Cantonese speakers who learn Japanese, using auditory-only and auditory-visual sentences as stimuli.MethodologyThirty native Tokyo Japanese speakers and thirty Cantonese-speaking Japanese learners who had passed the Japanese-Language Proficiency Test with level N2 or N3 were asked to judge the naturalness of 28 question-answer pairs made up of broad focus eliciting questions and three-word answers carrying broad focus, or contrastive or non-contrastive narrow focus on the middle object words. Question-answer pairs were presented in two sensory modalities, auditory-only and visual-auditory modalities in two separate experimental sessions.ResultsBoth the Japanese and Cantonese groups showed weak integration of visual cues in the judgement of naturalness. Visual-auditory modality only significantly influenced Japanese participants’ perception when the questions and answers were mismatched, but when the answers carried non-contrastive narrow focus, the visual cues impeded rather than facilitated their judgement. Also, the influences of specific visual cues like the displacement of eyebrows or head movements of both Japanese and Cantonese participants’ responses were only significant when the questions and answers were mismatched. While Japanese participants consistently relied on the left eyebrow for focus perception, the Cantonese participants referred to head movements more often.DiscussionThe lack of visual-auditory integration in Japanese speaking population found in segmental perception also exist in prosodic perception of focus. Not much foreign language effects has been found among the Cantonese-speaking learners either, suggesting a limited use of facial expressions in focus marking by native and non-native Japanese speakers. Overall, the present findings indicate that the integration of visual cues in perception of focus may be specific to languages rather than universal, adding to our understanding of multisensory speech perception.

Abstract Due to its excellent modularity and scalability, the cascaded H‐bridge solid‐state transformer (CHB SST) is a prominent candidate for interconnecting different grids in future hybrid ac/dc distribution systems. However, the CHB SST's large number of power switches are potential sources of faults that can disrupt the system's normal operation. Among other failure modes, a power switch open‐circuit fault (OCF) in a dual active bridge (DAB) module in the SST can result in overcurrent and previously ignored DAB high‐frequency transformer (HFT) saturation issues. The fault is generally addressed by installing redundant modules or additional devices, which would increase the cost, size, and complexity of the system. Based on the OCF analysis presented in this paper, a fault‐tolerant scheme using dc current injection and phase shift ratio adjustment is proposed to maintain the CHB SST operation with maximum remaining bidirectional power transfer capability of the faulty DAB. The overcurrent and HFT saturation issues are also eliminated. The proposed scheme features less cost and volume as compared with module redundancy methods. Moreover, it does not require modifications in the configuration and implementation of the SST. The feasibility and effectiveness of the proposed scheme are verified through a 4.8 kVA CHB SST experimental platform.

Aging research has shifted from studying phenotypes to studying in-depth mechanisms in recent decades. However, extrapolating cellular and molecular bases of aging from studying traditional model systems to humans has been challenging. The advent of organoids holds promise for overcoming the limitations of monolayer cell culture and bridging the gap between animal models and humans. Here, we mainly discuss recent paradigms for using organoid models in studying organ aging. Pluripotent stem cells–derived organoid provides a promising platform for simulating the pathophysiology of several aging-related diseases, especially neurodegenerative diseases, and adult stem cells organoids derived from different age groups have been applied to detect aging-related functional changes. We also assess the value of organoid model systems in understanding human aging and aging-related diseases, and identify challenges to be addressed in the future, such as the immaturity of organoids, and effective methods of inducing aging.

The incidence of giant cystic meconium peritonitis (GCMP) in pregnancies following artificial reproductive techniques is rare. We report the first case of GCMP following in vitro fertilization and embryo transfer in China. A 32-year-old woman with a history of bilateral salpingectomy due to ectopic pregnancy attended our in vitro fertilization and embryo transfer program. Meconium peritonitis, polyhydramnios, bowel dilatation, and intra-abdominal calcification were detected by ultrasound at 33 weeks of gestation. Cesarean section due to scarred uterus was performed at 35+1 weeks of gestation. A normal female infant with a distended abdomen was delivered. Emergency laparotomy was performed on the female infant because of the presence of a giant abdominal mass. A 0.2-cm perforation was found in the ileum. Enterostomy could not be performed due to the heavy adhesion. Prenatal diagnosis of meconium peritonitis is possible through careful ultrasonographic examination, and prognosis can be improved through early surgical intervention and intensive postoperative support.

Abstract Background Physical activity was believed to be associated with reduced aging among adults, while the competing nature of the physical activity and sedentary behavior has mainly been neglected in studies. We aimed to estimate the association of sleeping, sedentary behavior, and physical activity with aging among adults, considering the competing nature between variables of activity status. Methods A total of 5288 participants who were 20 years or older from the National Health and Nutrition Examination Survey were involved. The questionnaire was used to collect data regarding sociodemographics (age, sex, ethnicity/race, and education), and lifestyle behaviors (smoking, drinking). The Global Physical Activity Questionnaire was used to measure self-reported time for sedentary behavior, walking/bicycling, and moderate-to-vigorous physical activity (MVPA). The sleeping duration was obtained via interview. Phenotypic age acceleration (PhenoAgeAccel) was calculated as an aging index using nine chemistry biomarkers. Isotemporal substitution models using multivariable linear regression to examine the associations of sleeping, sedentary behavior, and physical activity with PhenoAgeAccel, stratified by MVPA (

Abstract Macrophages are involved mainly in the balance between inflammation and tenogenesis during the healing process of tendinopathy. However, etiological therapeutic strategies to efficiently treat tendinopathy by modulating macrophage state are still lacking. In this study, we find that a small molecule compound Parishin-A (PA) isolated from Gastrodia elata could promote anti-inflammatory M2 macrophage polarization by inhibiting gene transcription and protein phosphorylation of signal transducers and activators of transcription 1. Local injection or sustained delivery of PA by mesoporous silica nanoparticles (MSNs) could almost recover the native tendon’s dense parallel-aligned collagen matrix in collagenase-induced tendinopathy by modulating macrophage-mediated immune microenvironment and preventing heterotopic ossification. Especially, MSNs decrease doses of PA, frequency of injection and yield preferable therapeutic effects. Mechanistically, intervention with PA could indirectly inhibit activation of mammalian target of rapamycin to repress chondrogenic and osteogenic differentiation of tendon stem/progenitor cells by influencing macrophage inflammatory cytokine secretion. Together, pharmacological intervention with a natural small-molecule compound to modulate macrophage status appears to be a promising strategy for tendinopathy treatment.

Dual-pharmacophore DNA-Encoded Libraries (DELs) can generate large libraries, but linker optimisation is challenging. Here, the authors report a trio-pharmacophore DEL (T-DEL) for both de novo fragment identification and linker optimization of known fragment pairs.

Encapsulation engineering is an effective strategy to improve the stability of perovskite solar cells. Here, authors design and synthesize self-crosslinked fluorosilicone polymer gel for nondestructive encapsulation at room temperature, and maintain 98% of efficiency after 1000 h in damp heat test.

In this work, to promote the separation of photogenerated carriers, prevent the catalyst from photo-corrosion, and improve the photo-Fenton synergistic degradation of organic pollutants, the coating structure of FeOOH/BiO2−x rich in oxygen vacancies was successfully synthesized by a facile and environmentally friendly two-step process of hydrothermal and chemical deposition. Through a series of degradation activity tests of synthesized materials under different conditions, it was found that FeOOH/BiO2−x demonstrated outstanding organic pollutant degradation activity under visible and near-infrared light when hydrogen peroxide was added. After 90 min of reaction under photo-Fenton conditions, the degradation rate of Methylene Blue by FeOOH/BiO2−x was 87.4%, significantly higher than the degradation efficiency under photocatalysis (60.3%) and Fenton (49.0%) conditions. The apparent rate constants of FeOOH/BiO2−x under photo-Fenton conditions were 2.33 times and 3.32 times higher than photocatalysis and Fenton catalysis, respectively. The amorphous FeOOH was tightly coated on the layered BiO2−x, which significantly increased the specific surface area and the number of active sites of the composites, and facilitated the improvement of the separation efficiency of the photogenerated carriers and the prevention of photo-corrosion of BiO2−x. The analysis of the mechanism of photo-Fenton synergistic degradation clarified that ·OH, h+, and ·O2− are the main active substances involved in the degradation of pollutants. The optimal degradation conditions were the addition of the FeOOH/BiO2−x composite catalyst loaded with 20% Fe at a concentration of 0.5 g/L, the addition of hydrogen peroxide at a concentration of 8 mM, and an initial pH of 4. This outstanding catalytic system offers a fresh approach to the creation and processing of iron-based photo-Fenton catalysts by quickly and efficiently degrading various organic contaminants.

Safety barriers (SBs) are important means of reducing failure risks of process systems. As barriers vary in type and function, their effectiveness needs to be evaluated in order to find a more reasonable configuration strategy. However, in practice, there is often a lack of accurate and complete data relating to SBs, which poses a significant challenge in quantitatively assessing their effectiveness. To address this issue, in this study, we propose a semi-quantitative approach for evaluating the effectiveness of both preventive and protective barriers in process systems by integrating expert elicitation, interval-valued intuitionistic fuzzy numbers (IVIFNs), and a bow-tie model. In this approach, the bow-tie model is first applied to describe the system failure scenarios and the action phases of the barriers, and then IVIFNs with expert judgment are introduced to obtain the failure probabilities of basic events and the effects of SBs. Subsequently, the effectiveness of each barrier is measured by comparing the relative change in failure risk due to the addition of the barrier. To verify the feasibility of this approach, a natural gas storage tank with some barriers was analyzed. The results show that the regular inspection of the deformation or damage of the storage tank has the highest effectiveness, followed by the installation and regular maintenance of safety electrical equipment. Furthermore, compared to a single barrier, multiple barriers can significantly reduce the system risk.