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Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for “cell-free therapy” in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Objective To investigate the key elements for model establishment and determine the evaluation indicators of animal models for pelvic inflammatory disease (PID), providing a reference for improving modelling methods and optimizing the application of PID animal models. Methods The search query "Pelvic Inflammatory Disease" AND "Animal Model" OR "Rat" OR "Mouse" OR" Guinea Pig" OR "Rabbit" OR "Dog" OR "Pig" was used to retrieve relevant literature on PID animal models published from 2013 to 2023 in China Knowledge Network Infrastructure (CNKI), Wanfang, and PubMed databases. The studies were analyzed and categorized based on experimental animal types, modelling methods, modelling cycles, detection indicators, positive control drugs, and administration duration. A database was established for statistical analysis. Results A total of 214 research articles on PID animal models meeting the inclusion criteria were identified. The most commonly used model animals are Sprague Dawley (SD) rats, followed by Wistar rats. The most frequently employed modelling method is a combination of mechanical injury and bacterial infection, followed by the phenol mucilage method. The most common modelling cycles for acute pelvic inflammatory disease (APID) and chronic pelvic inflammatory disease (CPID)/sequelae of pelvic inflammatory disease (SPID) are 8 to 14 days, while for PID models without specific staging, the cycles are 7 days. High-frequency detection methods and indicators include histopathological observation using hematoxylin-eosin staining, enzyme-linked immunosorbent assay (ELISA) for serum-related indicators, morphological changes of tissues observed with the naked eye, and immunohistochemical detection of related protein expression in uterine tissues, and pathological scoring. The most frequently used positive control drugs are Fuke Qianjin Tablets, followed by Jingangteng Capsules. The most common administration duration for APID is 7 days, and for CPID/SPID models, it ranges from 15 to 21 days. Conclusion Currently, SD rats and Wistar rats are commonly used as experimental animals for PID models. The dual modelling method of mechanical injury combined with mixed bacterial infection aligns closely with clinical pathogenesis and can be used to establish a PID model that simulates postoperative uterine cavity infection. Depending on the research objectives, different positive drugs and detection indicators should be selected for comprehensive evaluation. Most existing PID animal model studies are based on western medical diagnosis, with fewer studies focusing on Traditional Chinese Medicine (TCM) syndromes. There is a need to integrate TCM theories of etiology and pathogenesis to construct PID animal models that are more in line with TCM clinical symptoms.

The effect of La treatment on the transformation of inclusions in H13 steel was investigated by subjecting H13 die steel to vacuum induction melting and subsequently treating the molten steel with La under an argon atmosphere protection.The results demonstrate that La has a beneficial effect on inclusions in H13 steel， the number of inclusions increases with the increase of La content， while the average size of inclusions initially decreases and then increases. The inclusions in H13 steel without the rare earth La additions are primarily Al₂O₃ and MnS. However， with a La content of 0.016% in H13 steel， the dominant inclusions shift to La2O2S. When the La content in H13 steel is 0.016%， the inclusions in the steel are mainly La2O2S；Furthermore， when the La content reaches 0.045% and 0.073%， the predominant inclusions in steel become LaP and La2O2S. Thermodynamic calculations show that the transformation process of La-treated inclusions is Al2O3→LaAlO3→La2O2S in molten steel at 1 600 ℃. During the solidification process， La2S3 is initially precipitated in the molten steel. As the temperature continues to decline， LaP begins to precipitate on the surface of La2S3 and La2O2S， ultimately forming the composite inclusions La2O2S-LaP and La2S3-LaP.

Abstract Background This study aimed to investigate the potential risk factors associated with postoperative infectious complications following laparoscopic hysterectomy for cervical cancer and to develop a prediction model based on these factors. Methods This study enrolled patients who underwent selective laparoscopic hysterectomy for cervical cancer between 2019 and 2024. A multivariate regression analysis was performed to identify independent risk factors associated with postoperative infectious complications. A nomogram prediction model was subsequently constructed and evaluated using R software. Results Out of 301 patients were enrolled and 38 patients (12.6%) experienced infectious complications within one month postoperatively. Six variables were independent risk factors for postoperative infectious complications: age ≥ 60 (OR: 3.06, 95% confidence interval (CI): 1.06–8.79, P = 0.038), body mass index (BMI) ≥ 24.0 (OR: 3.70, 95%CI: 1.4–9.26, P = 0.005), diabetes (OR: 2.91, 95% CI: 1.10–7.73, P = 0.032), systemic immune-inflammation index (SII) ≥ 830 (OR: 6.95, 95% CI: 2.53–19.07, P

A catalyst- and additive-free synthesis of 2-benzyl N-substituted anilines from (E)-2-arylidene-3-cyclohexenones and primary amines has been reported. The reaction proceeds smoothly through a sequential imine condensation–isoaromatization pathway, affording a series of synthetically useful aniline derivatives in acceptable to high yields. Mild reaction conditions, no requirement of metal catalysts, operational simplicity and the potential for scale-up production are some of the highlighted advantages of this transformation.

Abstract Background Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. Methods Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. Results The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. Conclusion This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.

Abstract To improve the understanding of potential pathological mechanisms of macular edema (ME), we try to discover biomarker candidates related to ME caused by diabetic retinopathy (DR) and retinal vein occlusion (RVO) in spectral-domain optical coherence tomography images by means of deep learning (DL). 32 eyes of 26 subjects with non-proliferative DR (NPDR), 77 eyes of 61 subjects with proliferative DR (PDR), 120 eyes of 116 subjects with branch RVO (BRVO), and 17 eyes of 15 subjects with central RVO (CRVO) were collected. A DL model was implemented to guide biomarker candidate discovery. The disorganization of the retinal outer layers (DROL), i.e., the gray value of the retinal tissues between the external limiting membrane (ELM) and retinal pigment epithelium (RPE), the disrupted and obscured rate of the ELM, ellipsoid zone (EZ), and RPE, was measured. In addition, the occurrence, number, volume, and projected area of hyperreflective foci (HRF) were recorded. ELM, EZ, and RPE are more likely to be obscured in RVO group and HRFs are observed more frequently in DR group (all P ≤ 0.001). In conclusion, the features of DROL and HRF can be possible biomarkers related to ME caused by DR and RVO in OCT modality.

Abstract Limited studies have triangulated the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and systolic blood pressure (SBP), diastolic blood pressure (DBP) or hypertension risk utilizing both observational and Mendelian randomization (MR) approaches. We employed data from the Norwegian Trøndelag Health Study (HUNT) to conduct cross-sectional (n = 5854) and prospective (n = 3592) analyses, as well as one-sample MR (n = 86,324). We also used largest publicly available data for two-sample MR. Our cross-sectional analyses showed a 25 nmol/L increase in 25(OH)D was associated with a 1.73 mmHg decrease in SBP (95% CI − 2.46 to − 1.01), a 0.91 mmHg decrease in DBP (95% CI − 1.35 to − 0.47) and 19% lower prevalence of hypertension (OR 0.81, 95% CI 0.74 to 0.90) after adjusting for important confounders. However, these associations disappeared in prospective analyses. One-sample and two-sample MR results further suggested no causal relationship between serum vitamin D levels and blood pressure or hypertension risk in the general population.

BackgroundUnhealthy lifestyles may constitute significant risk factors for dyslipidemia. However, limited studies focus on the association mentioned above among railway workers undertaking frequent shift work. ObjectiveTo understand the status of dyslipidemia and lifestyles among railway workers, and to investigate the association between the lifestyles of workers involved in different shift work schedules and dyslipidemia, aiming to provide a reference for the development of targeted intervention strategies against dyslipidemia in this occupational group. MethodsThe participants were selected from the in-service staff of a railway unit in 2021. A quota sampling approach was used to ensure the participation of at least 50% of employees from each department. Demographic and lifestyle information of the railway workers in 2021 was collected through self-administered questionnaires, while physiological and biochemical indicators were obtained through health examinations. Chi-square tests were employed to analyze the distribution of dyslipidemia among railway workers with different characteristics. Binary logistic regression was utilized to examine the associations between selected variables and dyslipidemia, and additive model was used to investigate the interaction between lifestyle and different shift work schedules on dyslipidemia. ResultsA total of 17392 railway workers were included in the study, and the total prevalence of dyslipidemia was 31.3%, with a higher prevalence reported among workers undertaking rotating night shifts (33.5%) and permanent night shifts (34.3%) than those with regular day work. The main adverse lifestyles among the railway workers were physical inactivity (59.6%), alcohol consumption (40.0%), and smoking (35.7%), and only 13.6% reported a healthy lifestyle. Furthermore, significant statistical differences in the prevalence of dyslipidemia were reported among workers with different lifestyles (P

With South Korea’s electricity demand expected to grow 30% by 2035, transitioning to clean energyresources will be critical in reducing the electric sector emissions and achieving national climate goals.Rapid technological improvements can help keep costs low and maintain grid reliability, if Korea’sgovernment takes a coordinated approach to the clean energy transition. This policy brief identifieskey barriers to Korea’s shift toward clean energy, based on the authors’ companion report (A CleanEnergy Korea by 2035: Transitioning to 80% Carbon-Free Electricity Generation ), interviews withexperts, and the most recent data and literature. It then explores policy solutions for overcoming thesetechnological, economic, and institutional barriers, and suggests market transformation strategies tospeed the adoption of clean energy technologies. Amid ongoing cost and technological improvementsin wind, solar, and energy storage, advancing this report’s recommended policy actions with maximumcoordination among government officials can meaningfully accelerate Korea’s clean energy transition.

The current global energy crisis has massive implications for the people and economy of South Korea(Korea), where at least 90% of energy use depends on foreign fossil fuels. Clean electricity accountsfor only 39% of total generation, with electricity demand expected to increase 30% by 2035. This studyshows that Korea can achieve 80% clean electricity by 2035 by capitalizing on rapid technologicalimprovements and decreasing costs of solar, wind, and battery technology. Doing so would slightlylower electricity supply costs, significantly reduce dependence on imported natural gas and coal, anddramatically cut power sector emissions. Further, this study finds that Korea’s power grid under a cleanenergy scenario will maintain reliability without coal generation or new natural gas plants. To realizethese significant economic, environmental, and energy security benefits, policies such as an 80% cleanelectricity standard by 2035 and corresponding renewable energy deployment goals are required.

Black carbon is a product of the incomplete combustion of carbonaceous fuels and has significant adverse effects on climate change, air quality, and human health. China has been a major contributor to global anthropogenic black carbon emissions. This study develops a black carbon inventory in China, using 2015 as the base year, and projects annual black carbon emissions in China for the period 2016-2050, under two scenarios: a Reference scenario and an Accelerated Reduction scenario. The study estimates that the total black carbon emissions in China in 2015 were 1100 thousand tons (kt), with residential use being the biggest contributor, accounting for more than half of the total black carbon emissions, followed by coke production, industry, agricultural waste burning, and transportation. This study then projects the total black carbon emissions in China in 2050 to be 278 kt in the Reference scenario and 86 kt in the Accelerated Reduction Scenario. Compared to the Reference scenario, the Accelerated Reduction scenario will achieve much faster and deeper black carbon reductions in all the sectors. The dramatic reductions can be attributed to the fuel switching in the residential sector, faster implementation of high-efficiency emission control measures in the industry, transportation, and coke production sectors, and faster phase-out of agricultural waste open burning. This analysis reveals the high potential of black carbon emission reductions across multiple sectors in China through the next thirty years.

Cesium lead bromide (CsPbBr3) perovskite nanoparticles (NPs) are widely recognized for their high potential for next-generation optoelectronic devices. However, these NPs’ conventional surface-capped organic ligands with high fluidity are frequently shed from particles during separation and purification steps, significantly reducing their stability. Therefore, a simple method to improve the strength of perovskite NPs is essential. Here, we utilized salicylic acid (SA), which acts as a ligand and protective coating of luminescent NPs, to create CsPbBr3@SA crystals using a straightforward standing technique. The CsPbBr3 NPs were perfectly encapsulated and size-limited in the SA hollow space needle-shaped crystals that retain their significant optical intensity. The fluorescence emission intensity of CsPbBr3@SA crystals without additional treatment can be maintained for six weeks under normal ambient conditions, demonstrating the SA ligand’s ability to protect CsPbBr3 NPs better. Furthermore, the green emission CsPbBr3@SA crystals are combined with K2SiF6 red phosphor and packed with a commercially available blue light emitting diode (LED) chip to fabricate a high gamut area white LED device. The highly straightforward standing method successfully enables the high-potential preparation of perovskite nanoparticles for future practical applications.

BackgroundTransgelin is a central actin-binding protein of the calponin family and involved in the process of multiple pulmonary diseases. Nevertheless, the role of transgelin in Coronavirus disease 2019 (COVID-19) patients is confusing.MethodsAll 317 COVID-19 patients were recruited from two hospital. Peripheral blood was collected from the fasting patients at the onset and convalescent phases. Demographic data and clinical information were obtained. The expression of serum transgelin was estimated using ELISA.ResultsThe expression of serum transgelin on admission was gradually elevated in parallel with the increased severity scores of COVID-19. After treatment, serum transgelin expression was reduced during the convalescent phase. Spearman correlative analyses found that serum transgelin expression was closely correlated to lots of clinical parameters. Besides, serum transgelin was positively associated with severity scores. Follow-up research found that serum higher transgelin on admission elevated the risks of mechanical ventilation, vasoactive agent utilization, ICU admission, death, and longer hospital stays during hospitalization through a prospective cohort study. Additionally, there were similarly predictive capacities for critical patients and death between serum transgelin on admission and severity scores among COVID-19 patients.ConclusionsThe expression of serum transgelin is positively with the severity and poorly prognostic outcomes among COVID-19 patients, indicating that transgelin is implicated in the pathological process of COVID-19. Transgelin can assist in the risk stratification and revealing the pathological mechanisms of COVID-19.

To investigate the energetic release attributes and damage potential of a specific thermobaric explosive at atmospheric pressure, we had employed a pressure testing system, high-speed camera system, and thermal imager to elucidate the impact of explosive mass on the energetic release characteristics. Our findings underscored that thermobaric explosive can significantly enhance the after-burning effect. We noted a discernible positive relationship among the magnitude of the explosive force, post-detonation combustion effects, and the inherent quality of the given explosive. In addition, the resultant overpressure from the shockwave, positive pressure-area impulse, and the duration of the positive pressure, all markedly exceeded those produced by TNT, exhibiting increases of 38.9 %, 51.48 %, and 7 %, respectively. To quantify their explosive potency, empirical formulae were derived to account for the shock wave parameters of thermobaric explosive. Under equivalent mass conditions, the peak thermal radiation flux per unit area from thermobaric explosive substantially exceeded that of TNT. When the PROBIT (probability unit) model and the overpressure-impulse criteria were utilized to ascertain the damage potential of the respective explosives on human targets and structures, it emerged that TBX imparted superior destructive effects. This analysis underpinned the foundational assessment concerning the blast hazard presented by TBX.

BackgroundConventional white light imaging (WLI) frequently misses gastric cancer, resulting in a high rate of undiagnosed cases. This study compares the effectiveness of linked color imaging (LCI) and WLI in detecting early gastric cancer and gastrointestinal metaplasia, aiming to improve clinical diagnostic practices through evidence-based medical insights.MethodsThe QUADAS-2 tool evaluated the quality of the studies. Additionally, methods like Split Component Synthesis (SCS) were utilized to evaluate the diagnostic performance of LCI and WLI.ResultsEleven studies involving a total of 7836 patients were included in the meta-analysis. Comparative analysis revealed that LCI demonstrated a statistically significant superiority over WLI in terms of the detection rates of EGC and GIM (detection rate of EGC: LCI vs WLI, 85% vs. 56.7%, p=0.004, OR 4.78, 95% CI 2.33-9.82, I2 = 71%; detection rate of GIM: LCI vs WLI, 88.9% vs. 40.1%, p=0.0003, OR 9.94, 95% CI 5.59-17.68, I2 = 71%). Additionally, LCI exhibited better sensitivity and specificity for the diagnosis of EGC and GIM compared to WLI. For the entire cohort, the sensitivity of LCI for EGC detection was 80% (95% CI 71%-86%) with a specificity of 82% (95% CI 63%-92%), while for GIM detection, the sensitivity was 87% (95% CI 81%-92%) with a specificity of 85% (95% CI 77%-91%).ConclusionsThe detection efficiency of LCI for EGC and GIM is better than that of WLI, and LCI is recommended as the main screening method for EGC and GIM.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023452140.

Background: The optimal glycosylated hemoglobin (HbA1c) target in type 2 diabetes mellitus (T2DM) patients remains controversial, especially in patients with concomitant coronary heart disease (CHD). This study aimed to investigate the correlation between baseline HbA1c and long-term prognosis in CHD patients with T2DM. Methods: The study enrolled 6,839 CHD patients with T2DM and measured HbA1c at admission in a multicenter prospective observational cohort. Patients were divided into two groups according to baseline HbA1c levels: optimal glycemic control group (HbA1c

BackgroundThis study aimed to explore the mechanism of action of DiWuYangGan (DWYG) capsule in improving Immunological non-responder (INR) by analyzing the active ingredients of DWYG.MethodsThe study employed a randomized, controlled, double-blind, single-simulation method. Patients were randomly divided into control and trial groups and treated with the primal highly effective antiretroviral therapy. To demonstrate the effect of DWYG on INR, patients in the control group were administered simulated DWYG, whereas patients in the trial group were administered DWYG capsules (ChiCTR1900024673). The chemical composition of DWYG was analyzed using ultra-performance liquid chromatography-high-resolution mass spectrometry. Potential targets of DWYG in the treatment of INR were identified and predicted using network pharmacology and molecular docking. The molecular mechanisms underlying the effects of DWYG were validated using a peripheral blood monocyte model.ResultsThe CD4:CD8 ratio in the trial group was significantly higher than that in the control group (p < 0.01). A total of 210 DWYG compounds were identified and network pharmacology revealed 182 potential therapeutic targets for DWYG and INR. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the toll-like receptor signaling pathway is one of the key pathways. This study demonstrated that DWYG reduced the expression level of TLR4 and the levels of IL-2, IL-10, and TNF-α, which are important cytokines involved in the immune response.ConclusionThe efficacy of DWYG in the treatment of INR confirmed the potential practical components of DWYG. Moreover, the results of network pharmacology and experimental validation showed that DWYG could restore the immune function of acquired immune deficiency syndrome patients by inhibiting the expression of TLR4 and related signaling pathways and the overactivation of immune function.Clinical Trial Registration:https://www.chictr.org.cn/index.html, identifier ChiCTR1900024673.

Objective: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. Methods: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. Results: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination. Conclusions: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

Perinatal depression (PD), which affects about 10–20 percent of women, often goes unnoticed because related symptoms frequently overlap with those commonly experienced during pregnancy. Moreover, identifying PD currently depends heavily on the use of questionnaires, and objective biological indicators for diagnosis has yet to be identified. This research proposes a safe and non-invasive method for diagnosing PD and aims to delve deeper into its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram (EEG) for mothers-to-be and fetuses, we collected the resting-state scalp EEG of pregnant women (with PD/healthy) at the 38th week of gestation. To compensate for the low spatial resolution of scalp EEG, source analysis was first applied to project the scalp EEG to the cortical-space. Afterwards, cortical-space networks and large-scale networks were constructed to investigate the mechanism of PD from two different level. Herein, differences in the two distinct types of networks between PD patients and healthy mothers-to-be were explored, respectively. We found that the PD patients illustrated decreased network connectivity in the cortical-space, while the large-scale networks revealed weaker connections at cerebellar area. Further, related spatial topological features derived from the two different networks were combined to promote the recognition of pregnant women with PD from those healthy ones. Meanwhile, the depression severity at patient level was effectively predicted based on the combined spatial topological features as well. These findings consistently validated that the two kinds of networks indeed played off each other, which thus helped explore the underlying mechanism of PD; and further verified the superiority of the combination strategy, revealing its reliability and potential in diagnosis and depression severity evaluation.

Sarracenia provide an optimal system for deciphering the host-microbiome interactions at various levels. We analyzed the pitcher microbiomes and metatranscriptomes of the parental species, and F1 and F2 generations from the mapping population (Sarracenia purpurea X Sarracenia psittacina) utilizing high-throughput sequencing methods. This study aimed to examine the host influences on the microbiome structure and function and to identify the key microbiome traits. Our quality datasets included 8,892,553 full-length bacterial 16s rRNA gene sequences and 65,578 assembled metatranscripts with microbial protein annotations. The correlation network of the bacterial microbiome revealed the presence of 3-7 distinct community clusters, with 8 hub and 19 connector genera. The entire microbiome consisted of viruses, bacterial, archaea, and fungi. The richness and diversity of the microbiome varied among the parental species and offspring genotypes despite being under the same greenhouse environmental conditions. We have discovered certain microbial taxa that are genotype-enriched, including the community hub and connector genera. Nevertheless, there were no significant differences observed in the functional enrichment analysis of the metatranscriptomes across the different genotypes, suggesting a functional convergence of the microbiome. We found that the pitcher microcosm harbors both rhizosphere and phyllosphere microbiomes within its boundaries, resulting in a structurally diverse and functionally complex microbiome community. A total of 50,424 microbial metatranscripts were linked to plant growth-promoting microbial proteins. We show that this complex pitcher microbiome possesses various functions that contribute to plant growth promotion, such as biofertilization, bioremediation, phytohormone signaling, stress regulation, and immune response stimulation. Additionally, the pitcher microbiome exhibits traits related to microbe-microbe interactions, such as colonization of plant systems, biofilm formation, and microbial competitive exclusion. In summary, the demonstrated taxonomical divergence and functionally convergence of the pitcher microbiome are impacted by the host genetics, making it an excellent system for discovering novel beneficial microbiome traits.

Ganglioneuroma (GN) is a rare benign neurogenic tumor that originates from the sympathetic nerves. It is extremely uncommon to find a lesion originating from the mediastinum that occupies the entire left hemithorax. In this report, we present the case of a 48-year-old female patient with a large mediastinal GN who presented with cough, sputum, and wheezing. Multislice spiral-enhanced CT and magnetic resonance imaging (MRI) revealed a large oval mass in the left thoracic cavity. The surgical operation completely resected the lesion, and the histopathological examination of the resected specimen confirmed the diagnosis of giant ganglion cell neuroma of the mediastinum. Due to the low incidence of GN and the lack of specific imaging manifestations, many radiologists may lack sufficient knowledge of GN and may be prone to misdiagnosis, resulting in delayed treatment. To enhance radiologists’ awareness of giant ganglion cell neuroma of mediastinal origin occupying the thoracic cavity, we provided detailed CT/MRI imaging information for this case, along with a brief summary of similar previously reported cases, to highlight the specific clinical and radiological features of this condition.

Abstract Ponicidin is a diterpenoid with demonstrated antitumor activity in clinical trials. However, the specific function and mechanism of action against hepatocellular carcinoma (HCC) remain unknown. In this study, it is found that ponicidin significantly inhibited the proliferation and migration of HCC cells. It is shown that ponicidin targets Keap1 and promotes the formation of the Keap1‐PGAM5 complex, leading to the ubiquitination of PGAM5, using biotin‐labeled ponicidin for target fishing and the HuProtTM Human Proteome Microarray V4.0. Ponicidin is found to activate the cysteine‐dependent mitochondrial pathway via PGAM5, resulting in mitochondrial damage and ROS production, thereby promoting mitochondrial apoptosis in HepG2 cells. The first in vitro cocrystal structure of the PGAM5 IE 12‐mer peptide and the Keap1 Kelch domain is obtained. Using molecular dynamics simulations to confirm the binding of ponicidin to the Keap1‐PGAM5 complex. Based on the depth‐based dynamic simulation, it is found that ponicidin can induce the tightening of the Keap1‐PGAM5 interaction pocket, thereby stabilizing the formation of the protein complex. Finally, it is observed that ponicidin effectively inhibited tumor growth and promoted tumor cell apoptosis in a BALB/c nude mouse xenograft tumor model. The results provide insight into the anti‐HCC properties of ponicidin based on a mechanism involving the Keap1‐PGAM5 complex.

ObjectivePoly (ADP-ribose) polymerase inhibitors (PARPis) are emerging targeted therapeutic agents in oncology, primarily indicated for ovarian and metastatic breast cancer. Acute kidney injury (AKI) has been observed in patients undergoing PARPi treatment, while there is still a lack of comprehensive comparisons of AKI associated with different PARPis. Our study aimed to extensively characterize the renal adverse effects (RAEs) of PARPi using real-world data.MethodsDisproportionality analysis and Bayesian analysis were employed for data mining to identify suspected RAE cases after different PARPis use within the Food and Drug Administration’s Adverse Event Reporting System from January 2004 to September 2023. The time to onset, fatality, and hospitalization rates of PARPi-related RAEs were also investigated.ResultsWe identified 1,696 PARPi-related RAEs, predominantly affecting patients over 85 (56.31%). Veliparib exhibited a more pronounced association with RAEs compared to others, as indicated by the highest reporting odds ratio (ROR = 29.20, 95% CI = 8.79–96.97), proportional reporting ratio (PRR = 19.80, χ2 = 72.62), and empirical Bayes geometric mean (EBGM = 19.80, the lower 90% one-sided CI = 7.25). The median time to RAEs onset was 15 (interquartile range: 6–55.75) days following the initiation of PARPi therapy. PARPi-related RAEs generally led to a 28.15% hospitalization rate and a 4.34% fatality rate.ConclusionAlthough the majority present with reversible creatinine elevation, PARPi-related RAEs merits broader attention, given its potential for clinical consequences. We should strive to early identify those individuals who may have irreversible kidney damage. The focus should be directed toward monitoring renal function in individuals receiving PARPi, especially in senile people and those with a predisposition to AKI.

BackgroundChronic inflammation is closely linked to Chronic Obstructive Pulmonary Disease (COPD); however, the impact of the Dietaryq Inflammatory Index (DII) on mortality among COPD patients remains uncertain.ObjectiveTo assess the correlation between the DII and all-cause mortality in COPD patients using data from the National Health and Nutrition Examination Survey (NHANES).MethodsWe conducted a retrospective cohort study on 1,820 COPD patients from the NHANES dataset (1999-2018). The influence of DII on mortality was evaluated using multivariate Cox regression, smoothing spline fitting, and threshold effect analysis. Additionally, Kaplan-Meier survival analysis was performed to compare survival curves among different DII groups. Subgroup analyses and E-values identified sensitive cohorts and assessed unmeasured confounding.ResultsOver an average follow-up of 91 months, multivariate Cox regression models revealed a significant positive correlation between DII scores and mortality risk, with each unit increase in DII associated with a 10% higher risk of death (HR: 1.10, 95% CI: 1.03-1.16; P = 0.002). Among the DII tertiles, individuals in the second tertile (T2: 1.23-2.94) experienced a 67% increase in mortality risk compared to those in the lowest tertile (T1: -5.28-1.23) (HR: 1.67, 95% CI: 1.26-2.21; p < 0.001). The third tertile (T3) did not show a statistically significant increase in mortality risk (HR: 1.30, 95% CI: 0.98-1.72; p=0.074). A restricted cubic spline analysis indicated a significant nonlinear association between DII and all-cause mortality (p = 0.021). Threshold effect analysis further revealed that below a DII of 2.19, there was a significant increase in all-cause mortality risk (HR = 1.19, 95% CI: 1.07-1.33; p = 0.002), while at or above this threshold, the risk increase was not statistically significant (HR=0.89, 95% CI: 0.68-1.15; p = 0.380). Kaplan-Meier analysis revealed significant differences in survival curves among DII tertiles (p < 0.001), with the lowest DII tertile showing the highest survival probability. Both subgroup and sensitivity analyses confirmed the robustness of these findings.ConclusionDII is positively correlated with mortality risk in COPD patients, showing nonlinear characteristics and threshold effects, underscoring its prognostic value.

Japan faces a significant energy security risk as it imports nearly all of the fuel used in its power sector, with clean electricity accounting for only 24% of the total. This study shows that, due to the decreasing costs of solar, wind (especially offshore), and battery technology, Japan can achieve a 90% clean electricity share by 2035. This would also result in a 6% reduction in electricity costs, nearly eliminate dependence on imported LNG and coal, as well as dramatically reduce power sector emissions. Additionally, the study finds that Japan’s power grid will remain dependable without the need for new gas capacity or coal generation. To take advantage of these significant economic, environmental, and energy security benefits, strong policies such as a 90% clean electricity target by 2035 and corresponding renewable deployment goals are required.

China's power system is highly regulated and uses an "equal-share" dispatch approach. However, market mechanisms are being introduced to reduce generation costs and improve system reliability. Here, we quantify the climate and human health impacts brought about by this transition, modeling China's power system operations under economic dispatch. We find that significant reductions in mortality related to air pollution (11%) and CO2 emissions (3%) from the power sector can be attained by economic dispatch, relative to the equal-share approach, through more efficient coal-powered generation. Additional health and climate benefits can be achieved by incorporating emission externalities in electricity generation costs. However, the benefits of the transition to economic dispatch will be unevenly distributed across China and may lead to increased health damage in some regions. Our results show the potential of dispatch decision-making in electricity generation to mitigate the negative impacts of power plant emissions with existing facilities in China.

Background and objectivesMyasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG.MethodsIn this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II-Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline). CS doses were increased (based on the current CS dose) in patients who worsened. Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required. The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45). The study results and full protocol are available at clinicaltrials.gov/ct2/show/NCT02473965.ResultsThe primary end point (≥50% reduction in CS dose) showed no significant difference between the IGIV-C treatment (60.0% of patients) and placebo (63.3%). There were no significant differences for secondary end points. Safety data indicated that IGIV-C was well tolerated.DiscussionIn this study, IGIV-C was not more effective than placebo in reducing daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different.Trial registration informationThe trial was registered on clinicaltrialsregister.eu (EudraCT #: 2013-005099-17) and clinicaltrials.gov (identifier NCT02473965).Classification of evidenceThis study provides Class II evidence that IVIG infusions in adult patients with MG do not increase the percentage of patients achieving a ≥50% reduction in corticosteroid dose compared with placebo.

Abstract With the increasing concerns about railway energy efficiency, two typical driving strategies have been used in actual train operation. One includes a sequence of full power traction, cruising, coasting, and full braking (CC). The other uses coasting–remotoring (CR) to replace cruising in CC. However, energy‐saving performance by CC and CR, which can be affected by route parameters of gradients and speed limits, has not been fully compared and studied. This paper analyses the energy distribution of CC and CR considering various route parameters and proposes an improved strategy for different gradients and speed limits. The detailed energy flow of CC and CR is analysed by Cauchy–Bunyakovsky–Schwarz inequality and the generalised Hölder's inequality, and then, a novel driving strategy CC_CR is designed. To verify the theoretical results and the effectiveness of the proposed strategy, three simulators with CC, CR, and CC_CR driving modes have been developed and implemented into case studies of four scenarios as well as a real‐world metro line. Simulation results demonstrate that CR can only outperform CC on routes with steep downhill and CC_CR is always the best strategy. The energy savings of CC_CR can be as much as 15% more than CR and 42% greater than CC.

Abstract It is very important to clarify the reservoir damage characteristics and damage characteristics and damage mechanism of tight sandstone gas reservoirs in Jinhua-Zhongtai mountain area of central SiChuan Basin, and put forward the technical countermeasures of “Double protection” drilling fluid to protect the reservoir and the environment, which is very important for the efficient well construction in this area. Through X-ray diffraction, scanning electron microscopy, casting thin sections and other testing methods, the mineral composition and microstructure characteristics of the block were analyzed, and the potential damage factors of the reservoir were clarified. Based on the sensitivity evaluation, it was revealed that the overall sensitivity damage of the block was weak. The main damage type was salt-sensitive damage, and the critical salinity was 9472.5 mg/L. On the basis of the environmental protection drilling fluid system used in this block, the surfactant which can effectively prevent gas invasion and reduce surface tension is selected, and the “Double protection” drilling fluid system is constructed. Through comprehensive performance test and reservoir protection performance evaluation, the core permeability damage rate of the optimized drilling fluid system is reduced from 88.77 to 18.66%, and the cuttings recovery rate is increased to more than 66%, and the cuttings expansion rate is reduced to less than 3.2%, which can effectively solve the problem of reservoir damage in drilling in Jinhua-Zhongtai mountain block in central Sichuan.