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Abstract Heat shuttling phenomenon is characterized by the presence of a non-zero heat flow between two bodies without net thermal bias on average. It was initially predicted in the context of nonlinear heat conduction within atomic lattices coupled to two time-oscillating thermostats. Recent theoretical works revealed an analog of this effect for heat exchanges mediated by thermal photons between two solids having a temperature dependent emissivity. In this paper, we present the experimental proof of this effect using systems made with composite materials based on phase change materials. By periodically modulating the temperature of one of two solids we report that the system akin to heat pumping with a controllable heat flow direction. Additionally, we demonstrate the effectiveness of a simultaneous modulation of two temperatures to control both the strength and direction of heat shuttling by exploiting the phase delay between these temperatures. These results show that this effect is promising for an active thermal management of solid-state technology, to cool down solids, to insulate them from their background or to amplify heat exchanges.

Abstract Background Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. Methods Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. Results Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. Conclusions The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

In the process of constructional backfilling coal mining (CBCM), the demand for the strength of cemented gangue backfill (CGB) samples varies with different backfill rates. It is planned to adjust the strength of CGB samples by changing the proportion of fly ash in the dosage of cement-fly ash binary cementitious material (hereinafter referred to as the proportion of fly ash), and conduct uniaxial compression tests on CGB samples with different proportions of fly ash (0−90%) to explore the range of strength control of CGB samples, and analyze the failure morphology of the samples using digital image correlation technology, and analyze the brittle ductile failure mode of the samples using AE events. The strength of coal gangue and the strength of cement-fly ash binary cementitious material with different fly ash proportions are measured using the pressure cylinder method and uniaxial compression test, respectively, and the mechanism of strength formation of CGB samples is revealed based on the relationship between the strength of coal gangue and the strength of cement-fly ash binary cementitious material. The research results indicate that the strength of CGB decreases with the increase of proportion of fly ash, achieving a larger range of strength control for CGB: 1.77−30.04 MPa. The failure morphology and the brittle ductile failure mode of samples with different replacement rates of CGB samples are different, and the corresponding strength range of the samples is also different, Material properties have undergone fundamental changes. As the proportion of fly ash increases, in terms of the failure morphology, CGB samples transition from shear failure (0−50% proportion of fly ash) to tensile shear composite failure (60%−80% proportion of fly ash) and then to tensile failure (90% proportion of fly ash), corresponding to the strength ranges are 20.8−30.04 MPa, 5.63−12.35 MPa, and 1.77 MPa; In terms of the brittle ductile failure mode, the samples transition from brittle-ductile failure (0−40% proportion of fly ash) to ductile failure (50%−90% proportion of fly ash), corresponding to the strength ranges are 24.64−30.04 MPa and 1.77−20.8 MPa. The strength of CGB is determined by the strength of the cement-fly ash binary cementitious material (1.43−55.5 MPa) and the strength of coal gangue (with an average strength of 4.43 MPa). Cement-fly ash binary cementitious material contributes significantly to the strength of CGB, while coal gangue limits the strength of CGB. The obtained experimental results provide a certain reference for the strength selection of filling materials in CBCM.

Abstract There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.

Abstract Biowaste fermentation is a promising technology for low‐carbon print bioenergy and biochemical production. Although it is believed that the microbiome determines both the fermentation efficiency and the product profiles of biowastes, the explicit mechanisms of how microbial activity controls fermentation processes remained to be unexplored. The current study investigated the microbiome dynamics and fermentation product profiles of biowaste fermentation under different organic loads (5, 20, and 40 g‐VS/L) and with additives that potentially modulate the fermentation process via methanogenesis inhibition (2‐bromoethanesulfonate) or electron transfer promotion (i.e., reduced iron, magnetite iron, and activated carbon). The overall fermentation products yields were 440, 373 and 208 CH4‐eq/g‐VS for low‐, medium‐ and high‐load fermentation. For low‐ and medium‐load fermentation, volatile fatty acids (VFAs) were first accumulated and were gradually converted to methane. For high‐load fermentation, VFAs were the main fermentation products during the entire fermentation period, accounting for 62% of all products. 16S rRNA‐based analyses showed that both 2‐bromoethanesulfonate addition and increase of organic loads inhibited the activity of methanogens and promoted the activity of distinct VFA‐producing bacterial microbiomes. Moreover, the addition of activated carbon promoted the activity of H2‐producing Bacteroides, homoacetogenic Eubacteriaceae and methanogenic Methanosarcinaceae, whose activity dynamics during the fermentation led to changes in acetate and methane production. The current results unveiled mechanisms of microbiome activity dynamics shaping the biowaste fermentation product profiles and provided the fundamental basis for the development of microbiome‐guided engineering approaches to modulate biowaste fermentation toward high‐value product recovery.

Abstract Background Laparoscopic radical resection of gastrointestinal cancer is associated with a high incidence of postoperative catheter-related bladder discomfort (CRBD). Studies on the benefits of magnesium sulfate intravenous infusion during the perioperative period post-laparoscopic surgery are yet lacking. Methods A total of 88 gastrointestinal cancer male patients scheduled for laparoscopic radical resection were randomly divided into two groups: normal saline (control) and magnesium. In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min just after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery; the control group was administered the same dose of normal saline. Subsequently, 2 μg/kg sufentanil was continuously infused intravenously by a postoperative patient-controlled intravenous analgesia (PCIA) device. The primary outcome was the incidence of CRBD at 0 h after the surgery. The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the postoperative numerical rating scale (NRS) score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement were also assessed. Results The incidence of CRBD at 0, 1, 2, and 6 h postoperatively was lower in the magnesium group than the control group (0 h: P = 0.01; 1 h: P = 0.003; 2 h: P = 0.001; 6 h: P = 0.006). The incidence of moderate to severe CRBD was higher in the control group at postoperative 0 and 1 h (0 h: P = 0.002; 1 h: P = 0.028), remifentanil requirement during surgery were significantly lower in the magnesium group than the control group. Sufentanil requirements during the 24 h postoperative period were significantly lower in the magnesium group than the control group. The NRS score was reduced in the magnesium group compared to the control group in the early postoperative period. Magnesium-related side effects and rescue medication (morphine) did not differ significantly between the two groups. Conclusions Intravenous magnesium sulfate administration reduces the incidence and severity of CRBD and remifentanil requirement in male patients undergoing radical resection of gastrointestinal cancer. Also, no significant side effects were observed. Trial registration Chictr.org.cn ChiCTR2100053073. The study was registered on 10/11/2021.

Antibiotic resistance is an escalating global health concern, exacerbated by the pervasive presence of antibiotic resistance genes (ARGs) in natural environments. The Yangtze River, the world's third-longest river, traversing areas with intense human activities, presents a unique ecosystem for studying the impact of these genes on human health. Here, we explored ARGs in the Yangtze River, examining 204 samples from six distinct habitats of approximately 6000 km of the river, including free-living and particle-associated settings, surface and bottom sediments, and surface and bottom bank soils. Employing shotgun sequencing, we generated an average of 13.69 Gb reads per sample. Our findings revealed a significantly higher abundance and diversity of ARGs in water-borne bacteria compared to other habitats. A notable pattern of resistome coalescence was observed within similar habitat types. In addition, we developed a framework for ranking the risk of ARG and a corresponding method for calculating the risk index. Applying them, we identified water-borne bacteria as the highest contributors to health risks, and noted an increase in ARG risks in particle-associated bacteria correlating with heightened anthropogenic activities. Further analysis using a weighted ARG risk index pinpointed the Chengdu–Chongqing and Yangtze River Delta urban agglomerations as regions of elevated health risk. These insights provide a critical new perspective on ARG health risk assessment, highlighting the urgent need for strategies to mitigate the impact of ARGs on human health and to preserve the ecological and economic sustainability of the Yangtze River for future human use.

Sophocarpine is a natural compound that belongs to the quinolizidine alkaloid family, and has a long history of use and widespread distribution in traditional Chinese herbal medicines such as Sophora alopecuroides L., Sophora flavescens Ait., and Sophora subprostrata. This article aims to summarize the pharmacology, pharmacokinetics, and toxicity of sophocarpine, evaluate its potential pharmacological effects in various diseases, and propose the necessity for further research and evaluation to promote its clinical application. A large number of studies have shown that it has anti-inflammatory, analgesic, antiviral, antiparasitic, anticancer, endocrine regulatory, and organ-protective effects as it modulates various signaling pathways, such as the NF-κB, MAPK, PI3K/AKT, and AMPK pathways. The distribution of sophocarpine in the body conforms to a two-compartment model, and sophocarpine can be detected in various tissues with a relatively short half-life. Although the pharmacological effects of sophocarpine have been confirmed, toxicity and safety assessments and reports on molecular mechanisms of its pharmacological actions have been limited. Given its significant pharmacological effects and potential clinical value, further research and evaluation are needed to promote the clinical application of sophocarpine.

ABSTRACTBacterial secondary metabolites serve as an important source of molecules for drug discovery. They also play an important function in mediating the interactions of microbial producers with their living environment and surrounding organisms. However, little is known about the genetic novelty, distribution, and community-level impacts of soil bacterial biosynthetic potential on a large geographic scale. Here, we constructed the first catalog of 11,149 biosynthetic gene clusters (BGCs) from agricultural soils across China and unearthed hidden biosynthetic potential for new natural product discovery from the not-yet-cultivated soil bacteria. Notably, we revealed soil pH as the strongest environmental driver of BGC biogeography and predicted that soil acidification and global climate change could damage the biosynthetic potential of the soil microbiome. The co-occurrence network of bacterial genomes revealed two BGC-rich species, i.e., Nocardia niigatensis from Actinobacteriota and PSRF01 from Acidobacteriota, as the module hub and connector, respectively, indicating their keystone positions in the soil microbial communities. We also uncovered a dominant role of BGC-inferred biotic interactions over environmental drivers in structuring the soil microbiome. Overall, this study achieved novel insights into the BGC landscape in agricultural soils of China, substantially expanding our understanding of the diversity and novelty of bacterial secondary metabolism and the potential role of secondary metabolites in microbiota assembly.IMPORTANCEBacterial secondary metabolites not only serve as the foundation for numerous therapeutics (e.g., antibiotics and anticancer drugs), but they also play critical ecological roles in mediating microbial interactions (e.g., competition and communication). However, our knowledge of bacterial secondary metabolism is limited to only a small fraction of cultured strains, thus restricting our comprehensive understanding of their diversity, novelty, and potential ecological roles in soil ecosystems. Here, we used culture-independent metagenomics to explore biosynthetic potentials in agricultural soils of China. Our analyses revealed a high degree of genetic diversity and novelty within biosynthetic gene clusters in agricultural soil environments, offering valuable insights for biochemists seeking to synthesize novel bioactive products. Furthermore, we uncovered the pivotal role of BGC-rich species in microbial communities and the significant relationship between BGC richness and microbial phylogenetic turnover. This information emphasizes the importance of biosynthetic potential in the assembly of microbial communities.

IntroductionClostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.MethodsIn this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.ResultsThe results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge.ConclusionBased on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

This article proposes a flexible surgical robot featuring strong magnetic steering achieved by a hemispherical magnet array actuation, and high‐accuracy ultrasonic position sensing achieved by a beacon total focusing method (b‐TFM). The hemispherical magnet array with magnetic focusing is described and its array parameters are optimized through finite element analysis to increase the magnetic field for actuation. The magnetic field strength at 100 mm for the array with the same mass as the cylindrical magnet is about 1.8 times higher than that of the cylindrical magnet. Using the magnet array actuation, the flexible robot exhibits the capability of agile steering to navigate along a predefined trajectory. In addition, a 1 mm × 1 mm lead zirconate titanate (PZT) patch is embedded into the tip of the flexible robot as a beacon for b‐TFM ultrasonic imaging to detect the position of the robot. Therefore, the entire navigation process can be executed under the supervision of the ultrasonic position sensing system, and the maximum error is 0.8 mm when the steering radius is 100 mm.

Dominant native plants are crucial for vegetation reconstruction and ecological restoration of mining areas, though their adaptation mechanisms in stressful environments are unclear. This study focuses on the interactions between dominant indigenous species in antimony (Sb) mining area, Artemisia lavandulaefolia and Betula luminifera, and the microbes in their rhizosphere. The rhizosphere microbial diversity and potential functions of both plants were analyzed through the utilization of 16S, ITS sequencing, and metabarcoding analysis. The results revealed that soil environmental factors, rather than plant species, had a more significant impact on the composition of the rhizosphere microbial community. Soil pH and moisture significantly affected microbial biomarkers and keystone species. Actinobacteria, Proteobacteria and Acidobacteriota, exhibited high resistance to Sb and As, and played a crucial role in the cycling of carbon, nitrogen (N), phosphorus (P), and sulfur (S). The genes participating in N, P, and S cycling exhibited metabolic coupling with those genes associated with Sb and As resistance, which might have enhanced the rhizosphere microbes’ capacity to endure environmental stressors. The enrichment of these rhizosphere functional microbes is the combined result of dispersal limitations and deterministic assembly processes. Notably, the genes related to quorum sensing, the type III secretion system, and chemotaxis systems were significantly enriched in the rhizosphere of plants, especially in B. luminifera, in the mining area. The phylogenetic tree derived from the evolutionary relationships among rhizosphere microbial and chloroplast whole-genome resequencing results, infers both species especially B. luminifera, may have undergone co-evolution with rhizosphere microorganisms in mining areas. These findings offer valuable insights into the dominant native rhizosphere microorganisms that facilitate plant adaptation to environmental stress in mining areas, thereby shedding light on potential strategies for ecological restoration in such environments.

BackgroundPeripheral vascular disease (PVD) is a common complication in patients with type 2 diabetes mellitus (T2DM). Early detection or prediction the risk of developing PVD is important for clinical decision-making.PurposeThis study aims to establish and validate PVD risk prediction models and perform risk factor analysis for PVD in patients with T2DM using machine learning and Shapley Additive Explanation(SHAP) based on electronic health records.MethodsWe retrospectively analyzed the data from 4,372 inpatients with diabetes in a hospital between January 1, 2021, and March 28, 2023. The data comprised demographic characteristics, discharge diagnoses and biochemical index test results. After data preprocessing and feature selection using Recursive Feature Elimination(RFE), the dataset was split into training and testing sets at a ratio of 8:2, with the Synthetic Minority Over-sampling Technique(SMOTE) employed to balance the training set. Six machine learning(ML) algorithms, including decision tree (DT), logistic regression (LR), random forest (RF), support vector machine(SVM),extreme gradient boosting (XGBoost) and Adaptive Boosting(AdaBoost) were applied to construct PVD prediction models. A grid search with 10-fold cross-validation was conducted to optimize the hyperparameters. Metrics such as accuracy, precision, recall, F1-score, G-mean, and the area under the receiver operating characteristic curve (AUC) assessed the models’ effectiveness. The SHAP method interpreted the best-performing model.ResultsRFE identified the optimal 12 predictors. The XGBoost model outperformed other five ML models, with an AUC of 0.945, G-mean of 0.843, accuracy of 0.890, precision of 0.930, recall of 0.927, and F1-score of 0.928. The feature importance of ML models and SHAP results indicated that Hemoglobin (Hb), age, total bile acids (TBA) and lipoprotein(a)(LP-a) are the top four important risk factors for PVD in T2DM.ConclusionThe machine learning approach successfully developed a PVD risk prediction model with good performance. The model identified the factors associated with PVD and offered physicians an intuitive understanding on the impact of key features in the model.

The proportion of patients diagnosed with cancer has been shown to rise with the increasing aging global population. Advanced age is a major risk factor for morbidity and mortality in older adults. As individuals experience varying health statuses, particularly with age, it poses a challenge for medical professionals in the cancer field to obtain standardized treatment outcomes. Hence, relying solely on chronological age and disease-related parameters is inadequate for clinical decision-making for elderly patients. With functional, multimorbidity-related, and psychosocial changes that occur with aging, oncologic diseases may develop and be treated differently from younger patients, leading to unique challenges in treatment efficacy and tolerance. To overcome this challenge, personalized therapy using biomarkers has emerged as a promising solution. Various categories of biomarkers, including inflammatory, hematological, metabolic, endocrine, and DNA modification-related indicators, may display features related to both cancer and aging, aiding in the development of innovative therapeutic approaches for patients with cancer in old age. Furthermore, physical functional measurements as non-molecular phenotypic biomarkers are being investigated for their potential complementary role in structured multidomain strategies to combat age-related diseases such as cancer. This review provides insight into the current developments, recent discoveries, and significant challenges in cancer and aging biomarkers, with a specific focus on their application in advanced age.

In the mining of nearly horizontal open-pit coal mines, transportation flat plates are usually arranged on the end-slope. Reciprocating transport operations of large heavy-duty trucks cause significant cyclic loading and unloading effects on the overburden rock, leading to initial damage to the coal rock body. At the same time, the strong impact load generated by large-scale blasting during open-pit mining further deteriorates the mechanical properties of the coal rock body, thereby inducing large area instability of the end-slope. Therefore, it is crucial to conduct experimental research on the dynamic mechanical properties of coal rock under cyclic loading and unloading damage conditions for the stability of the end-slopes and safe mining in open-pit coal mines. The dynamic mechanical properties of coal samples under the initial damage condition of cyclic loading and unloading and their damage and fracture mechanism were systematically analyzed by using the split Hopkinson pressure bar test system and scanning electron microscope test system. The results show that: ① With the increase of the loading strain rate, the dynamic compressive strength and elastic modulus of the coal sample increase rapidly, and the strengthening effect of the strain rate on the mechanical properties of the sample is significant. The dynamic compressive strength and elastic modulus decrease linearly and rapidly as the initial damage increases under the condition of fixed strain rate, indicating that the initial damage weakens the mechanical properties of the coal sample; ② There exist small-scale primary cracks and pore defects in the natural state of the coal samples, and the occurrence of damage leads to the emergence of new cracks and pores inside the coal sample. With the increase of the damage intensity, the defect scale and number gradually increase and expand rapidly, which is the fundamental reason for the weakening of its mechanical properties; ③ The failure mode of the coal sample changes from tension failure to shear failure with the increase of the initial damage and strain rate, and at the same time, its degree of damage, dissipation energy during the failure process, and energy dissipation capacity show a rapid increasing trend; ④The dynamic failure of the damaged coal sample is mainly brittle failure, but under the condition of high initial damage, significant sliding separation and toughness fracture morphology can be observed locally, which is also the main reason for the high energy dissipation capacity of the coal sample under the condition of high initial damage.