Search

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvβ3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.

This study analyzes the effects of traditional Chinese medicine fumigation and washing combined with Western medical care on resting pain in elderly males with lower extremity arterial occlusion (LEAO). A total of 200 elderly males with resting pain from LEAO who were treated at our hospital between January 2021 and January 2023 were randomly assigned to an experimental group (n = 100) and a control group (n = 100) using a computer-generated number table. Both groups underwent percutaneous transluminal angioplasty after admission. Following surgery, the control group received Western medical nursing. In contrast, the experimental group received a combination of traditional Chinese medicine fumigation and washing with Western medicine nursing. Both nursing approaches were then compared regarding resting pain in patients. After surgery, the experimental group had a significantly shorter recovery time and hospital stay than the control group (p < 0.05). After intervention, the experimental group had a significantly higher Fugl-Meyer score and Ankle-brachial index (ABI) (p < 0.05). Moreover, significant increases in quality of life scores across all dimensions were achieved in the experimental group than in the control group after intervention (p < 0.05). A significant higher satisfaction rate for nursing care (p < 0.05) and a lower incidence of complications (p < 0.05) were found in the experimental group compared to the control group. A combination of traditional Chinese medicine fumigation and washing with Western medical care can improve blood flow in lower limbs, facilitate functional recovery, enhance quality of life, improve patient satisfaction with nursing care, and facilitate postoperative recovery, which is worth promoting clinically.

A method to optimize the thermal deformation of an indirectly cryo-cooled silicon crystal monochromator exposed to intense X-rays at a low-emittance diffraction-limited synchrotron radiation source is presented. The thermal-induced slope error of the monochromator crystal has been studied as a function of heat transfer efficiency, crystal temperature distribution and beam footprint size. A partial cooling method is proposed, which flattens the crystal surface profile within the beam footprint by modifying the cooling contact area to optimize the crystal peak temperature. The optimal temperature varies with different photon energies, which is investigated, and a proper cooling strategy is obtained to fulfil the thermal distortion requirements over the entire photon energy range. At an absorbed power up to 300 W with a maximum power density of 44.8 W mm−2 normal incidence beam from an in-vacuum undulator, the crystal thermal distortion does not exceed 0.3 µrad at 8.33 keV. This method will provide references for the monochromator design on diffraction-limited synchrotron radiation or free-electron laser light sources.

Abstract Background Quantitative computed tomography (QCT)-based lumbar bone mineral density (LBMD) has been used to diagnose osteoporosis. This study explored the value of lower thoracic BMD (TBMD) in diagnosing osteoporosis in older adults during CT lung cancer screening. Methods This study included 751 subjects who underwent QCT scans with both LBMD and TBMD. 141 of them was selected for a validation. Osteoporosis was diagnosed based on LBMD using the ACR criteria (gold standard). TBMD thresholds were obtained using receiver operating characteristic curve. TBMD was also translated into LBMD (TTBMD) and osteoporosis was defined based on TTBMD using ACR criteria. The performance of TBMD and TTBMD in identifying osteoporosis was determined by Kappa test. The associations between TBMD- and TTBMD-based osteoporosis and fracture were tested in 227 subjects with followed up status of spine fracture. Results The performance of TBMD in identifying osteoporosis was low (kappa = 0.66) if using the ACR criteria. Two thresholds of TBMD for identifying osteopenia (128 mg/cm3) and osteoporosis (91 mg/cm3) were obtained with areas under the curve of 0.97 and 0.99, respectively. The performance of the identification of osteoporosis/osteopenia using the two thresholds or TTBMD both had good agreement with the gold standard (kappa = 0.78, 0.86). Similar results were observed in validation population. Osteoporosis identified using the thresholds (adjusted hazard ratio (HR) = 18.72, 95% confidence interval (CI): 5.13–68.36) or TTBMD (adjusted HR = 10.28, 95% CI: 4.22–25.08) were also associated with fractures. Conclusion Calculating the threshold of TBMD or normalizing TBMD to LBMD are both useful in identifying osteoporosis in older adults during CT lung cancer screening.

Highlights γ-MnO2 loaded on N-doped biomass carbon from grapefruit peel is firstly developed. The splendid cathodic properties (e.g., coulombic efficiency: ~ 100%, energy density: 553.12 Wh kg−1) are gained. The biomass strategy guaranteed via cytotoxicity test shows a clinical potential. Zn-ion storage efficiency is boosted mainly by regulating Mn–O bond and Mn domains.

Summary: Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

BackgroundPsychological distress is highly prevalent and has a severe impact on the quality of life among breast cancer survivors. This type of distress is associated with cognitive failure. However, previous studies have focused solely on the total scale scores of these two concepts while ignoring the unique relationship between specific components. In the present study, we utilized network analysis to explore the relationship between psychological distress and cognitive failure in breast cancer survivors.MethodsThe network analysis approach was adopted to estimate the regularized partial correlation network in a cross-sectional sample of 409 breast cancer survivors. All participants were assessed using the Depression Anxiety Stress Scale and the Cognitive Failure Questionnaire. The Gaussian Graphical Model was employed to estimate the network, centrality indices, and edge weights, providing a description of the characteristics of the network.ResultsThe results indicated that anxiety–stress and depression–stress were the strongest edges in the community of psychological distress. Distractibility–memory was the strongest edge in the community of cognitive failure. Distractibility and memory were the most central nodes, with the highest expected influence in the network. Depression and motor coordination acted as important bridge nodes with the highest bridge expected influence.ConclusionDistractibility and memory in cognitive failure played important roles in activating and maintaining the relationship network. Motor coordination was identified as the crucial pathway for the impact of cognitive failure on psychological distress. Interventions targeting these specific issues might be more effective in improving cognitive failure and reducing psychological distress among breast cancer survivors.

Background/objectiveWhile Physical Literacy has been highlighted as a determinant in health in recent study, there is a dearth of studies examining its effect on physical health, and there is a little in the way of empirical data linking Physical Literacy to health outcomes. Accordingly, further empirical research is needed to clarify the mechanisms by which Physical Literacy affects physical health. The purpose of this study was to verify the role of medical students’ Physical Literacy on Health-related quality of life as well as to explore the chain mediating role of Physical Activity and Subjective Well-being in it.MethodsThis study utilized a cross-sectional study design. The Physical Literacy, Health-related Quality of Life, Physical Activity ratings, and Subjective Well-being of students at Shanxi Medical University were all measured using an online survey administered in September 2023. A total of 1968 valid questionnaires were returned. First, descriptive statistics and correlation analysis were performed using SPSS software. Second, PROCESS was used to test the mediating role. Finally, we used structural equation modeling (Amos) to test the model fit.ResultsThere is a significant correlation between all variables. After mediation effects analysis, we found that there were three indirect pathways of physical literacy on health-related quality of life: a single mediating effect of physical activity, a single mediating effect of subjective well-being, and a chained mediating effect of physical activity-subjective well-being.ConclusionThe mediating role of physical activity and subjective well-being on the relationship between physical literacy and health-related quality of life has been confirmed. Our research results support the integration of physical literacy into physical education teaching and the modification of curriculum content by physical education teachers as part of efforts to enhance students’ physical activity levels, subjective well-being levels, and overall health. This study provides a new perspective for intervention in improving the health of medical students.

Central nervous system (CNS) damage is usually irreversible owing to the limited regenerative capability of neurons. Following CNS injury, astrocytes are reactively activated and are the key cells involved in post-injury repair mechanisms. Consequently, research on the reprogramming of reactive astrocytes into neurons could provide new directions for the restoration of neural function after CNS injury and in the promotion of recovery in various neurodegenerative diseases. This review aims to provide an overview of the means through which reactive astrocytes around lesions can be reprogrammed into neurons, to elucidate the intrinsic connection between the two cell types from a neurogenesis perspective, and to summarize what is known about the neurotranscription factors, small-molecule compounds and MicroRNA that play major roles in astrocyte reprogramming. As the malignant proliferation of astrocytes promotes the development of glioblastoma multiforme (GBM), this review also examines the research advances on and the theoretical basis for the reprogramming of GBM cells into neurons and discusses the advantages of such approaches over traditional treatment modalities. This comprehensive review provides new insights into the field of GBM therapy and theoretical insights into the mechanisms of neurological recovery following neurological injury and in GBM treatment.

The significance of point-of-care testing (POCT) in early clinical diagnosis and personalized patient care is increasingly recognized as a crucial tool in reducing disease outbreaks and improving patient survival rates. Within the realm of POCT, biosensors utilizing magnetic nanoparticles (MNPs) have emerged as a subject of substantial interest. This review aims to provide a comprehensive evaluation of the current landscape of POCT, emphasizing its growing significance within clinical practice. Subsequently, the current status of the combination of MNPs in the Biological detection has been presented. Furthermore, it delves into the specific domain of MNP-based biosensors, assessing their potential impact on POCT. By combining existing research and spotlighting pivotal discoveries, this review enhances our comprehension of the advancements and promising prospects offered by MNP-based biosensors in the context of POCT. It seeks to facilitate informed decision-making among healthcare professionals and researchers while also promoting further exploration in this promising field of study.

Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile, there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C. amabile, including botanical characteristics, geographical distribution, traditional applications, phytochemistry, pharmacological activities, toxicology, and clinical applications. The results have shown that C. amabile has been traditionally used for medicinal, edible, and ornamental purposes in China for many centuries. The whole plant, root, and leaf of C. amabile are used by different ethnic groups, such as Lisu, Bai, Naxi, Yi, Jinuo, and Han, to treat malaria, hepatitis, dysentery, leucorrhea, tuberculosis cough, fracture, joint dislocation, trauma bleeding, and skin carbuncle abscess. A total of 47 chemical components, including alkaloids (pyrrolizidine alkaloids, PAs), sterols, organic acids, and saccharides, were isolated from C. amabile. Pharmacological studies show that the chemical extracts of C. amabile possess various biological activities, such as anti-inflammatory, anti-tumor, anti-microbial, cardiovascular effects, ganglionic action, and acetylcholinesterase inhibition. However, it is important to note that C. amabile exhibits hepatotoxicity, with its toxicity being linked to its primary PAs components. Although preliminary studies suggest potential applications in the treatment of prostate diseases and alopecia, further research is needed to validate these clinical uses. Our review highlights the traditional uses, phytochemistry, biological activity, toxicity, and clinical applications of C. amabile. It emphasizes the essential guiding role of the indigenous medicinal knowledge system in developing new drugs. Previous studies have shown that the phytochemical and pharmacological characteristics of C. amabile are significantly related to its traditional medicinal practices. Cynoglossum amabile has excellent market potential and can be further analyzed in terms of phytochemistry, pharmacology, and toxicology, which are critical for its clinical drug safety, quality evaluation, and resource development.

Objectives: This study aimed to assess the diagnostic, risk stratification, and prognostic capabilities of apelin-13 and APJ in comparison to procalcitonin (PCT) for septic patients presenting to the emergency department (ED). Methods: Two hundred and thirty-eight patients meeting the Third International Consensus Definition (Sepsis-3) criteria were enrolled from Beijing Chaoyang Hospital's ED, along with a control group of forty healthy individuals. Patients were categorized into two groups based on disease severity: those with sepsis or septic shock. Plasma levels of apelin-13, CD4+ Th cells, and PCT were measured. The expression levels of plasma APJ mRNA were quantified using real-time fluorescence quantitative PCR (RT-qPCR) methodology. The Sequential Organ Failure Assessment (SOFA) score was determined at the time of enrollment. The prognostic values of apelin-13 and APJ was evaluated in comparison to that of PCT and the SOFA score. All patients were followed up for a duration of 28 days. Results: The plasma concentrations of apelin-13 and APJ exhibited a positive correlation with the severity of sepsis, while the number of CD4+ T cells decreased in septic patients. The areas under the receiver operating characteristic (AUC) curves for apelin-13 and APJ in the diagnosis and prediction of 28-day mortality were greater than that of PCT. In non-survivors at the 28-day follow-up, the plasma levels of apelin-13 and APJ were significantly higher compared to survivors. Furthermore, apelin-13 levels were notably higher in cases of sepsis-induced cardiomyopathy (SICM) than in those without SICM. Apelin-13 and APJ emerged as independent predictors of 28-day mortality among septic patients. Conclusions: Apelin-13 and APJ demonstrate value in the assessment of risk stratification, early diagnosis, and prognosis of sepsis in the ED. Apelin-13 also proves to be an effective biomarker for assessing the prognosis of SICM in the ED. Sepsis may lead to immune function suppression.

Objective This study aimed to systematically investigate the relationship between immune-inflammatory indexes with lower urinary tract symptoms (LUTSs).Design Cross-sectional study.Setting National Health and Nutrition Examination Survey (NHANES) (2005–2008).Participants A total of 2709 men with complete information for immune-inflammatory indexes and LUTSs were included from NHANES 2005–2008.Outcomes and analyses Automated haematology analysing devices are used to measure blood cell counts, and LUTSs were presented by standard questionnaires. Non-linear and logistic regression analyses were used to estimate their association after adjustment for confounders.Results Multivariate logistic regression showed that pan-immune-inflammation value (OR (95% CI)=1.60 (1.14 to 2.23)), systemic inflammation response index (SIRI) (OR (95% CI)=1.82 (1.21 to 2.73)), neutrophil/lymphocyte ratio (NLR) (OR (95% CI)=1.81 (1.31 to 2.49)), derived NLR (dNLR) (OR (95% CI)=1.91 (1.35 to 2.70)) and C reactive protein (CRP) (OR (95% CI)=1.71 (1.05 to 2.79)) was positively associated with LUTS. Additionally, composite immune-inflammation markers exhibited a stronger association with LUTS than any single index, with the ORs for high SIRI+high CRP, high NLR+high CRP and high dNLR+high CRP being 2.26, 2.44 and 2.16, respectively (all p

ABSTRACTFusobacterium nucleatum (Fn), as a conditional pathogen, can cause a range of oral and gastrointestinal diseases. However, existing clinical detection methods require expensive equipment and complex procedures, which are inconvenient for large-scale screening in epidemiological research. The purpose of this study was to establish a reliable, rapid, and inexpensive detection method based on CRISPR/Cas12a technology for the detection of Fn. Specific recombinase polymerase amplification (RPA) primer sequences and crRNA sequences were designed based on the nusG gene of Fn. Subsequently, a fluorescence assay and a lateral flow immunoassay were established using the RPA and CRISPR-Cas12a system (RPA-CRISPR-Cas12a). Sensitivity validation revealed a limit of detection of 5 copies/µL. This method could distinguish Fn from other pathogens with excellent specificity. Furthermore, the RPA-CRISPR-Cas12a assay was highly consistent with the classical quantitative real-time PCR method when testing periodontal pocket samples. This makes it a promising method for the detection of Fn and has the potential to play an increasingly important role in infectious disease testing.IMPORTANCEFusobacterium nucleatum (Fn) naturally exists in the microbial communities of the oral and gastrointestinal tracts of healthy individuals and can cause inflammatory diseases in the oral and gastrointestinal tracts. Recent studies have shown that Fn is closely associated with the occurrence and development of gastrointestinal cancer. Therefore, the detection of Fn is very important. Unlike the existing clinical detection methods, this study established a fluorescence-based assay and lateral flow immunoassay based on the RPA and CRISPR-Cas12a system (RPA-CRISPR-Cas12a), which is fast, reliable, and inexpensive and can complete the detection within 30–40 minutes. This makes it a promising method for the detection of Fn and has the potential to play an increasingly important role in infectious disease testing.

The biotoxicity and chemotherapeutic resistance of cisplatin (CDDP) pose a challenge for tumor therapy. Practically, the change in the therapeutic response of tumor from resistance to sensitivity are impressive but challenging. To this end, we propose a strategy of “one stone, three birds” by designing a CuPt nanoalloy to simultaneously eliminate GSH, relieve hypoxia, and promote ROS production for effectively reversing the platinum (IV) (Pt(IV), (c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)2)) resistance. Notably, the CuPt nanoalloy exhibits ternary catalytic capabilities including mimicking GSH oxidase, catalase and peroxidase. With the subsequent disguise of tumor cell membrane, the CuPt nanoalloy is conferred with homologous targeting ability, making it actively recognize tumor cells and then effectively internalized by tumor cells. Upon entering tumor cell, it gives rise to GSH depletion, hypoxia relief, and oxidative stress enhancement by catalyzing the reaction of GSH and H2O2, which mitigates the vicious milieu and ultimately reinforces the tumor response to Pt(IV) treatment. In vivo results prove that combination therapy of mCuPt and Pt(IV) realizes the most significant suppression on A549 cisplatin-resistant tumor. This study provides a potential strategy to design novel nanozyme for conquering resistant tumor.

Abstract Optical thermometry based on the upconversion (UC) luminescence intensity ratio (LIR) has attracted considerable attention because of its feasibility for achievement of accurate non-contact temperature measurement. Compared with traditional UC phosphors, optical thermometry based on UC single crystals can achieve faster response and higher sensitivity due to the stability and high thermal conductivity of the single crystals. In this study, a high-quality 5 at% Yb3+ and 1 at% Ho3+ co-doped Gd0.74Y0.2TaO4 single crystal was grown by the Czochralski (Cz) method, and the structure of the as-grown crystal was characterized. Importantly, the UC luminescent properties and optical thermometry behaviors of this crystal were revealed. Under 980 nm wavelength excitation, green and red UC luminescence lines at 550 and 650 nm and corresponding to the 5F4/5S2 → 5I8 and 5F5 → 5I8 transitions of Ho3+, respectively, were observed. The green and red UC emissions involved a two-photon mechanism, as evidenced by the analysis of power-dependent UC emission spectra. The temperature-dependent UC emission spectra were measured in the temperature range of 330–660 K to assess the optical temperature sensing behavior. At 660 K, the maximum relative sensing sensitivity (S r) was determined to be 0.0037 K−1. These results highlight the significant potential of Yb,Ho:GYTO single crystal for optical temperature sensors. Graphical abstract

Abstract Background Functioning as a competing endogenous RNA (ceRNA) is the main action mechanism of most cytoplasmic lncRNAs. However, it is not known whether this mechanism of action also exists in the nucleus. Results We identified four nuclear lncRNAs that are presented in granulosa cells (GCs) and were differentially expressed during sow follicular atresia. Notably, similar to cytoplasmic lncRNAs, these nuclear lncRNAs also sponge miRNAs in the nucleus of GCs through direct interactions. Furthermore, NORSF (non-coding RNA involved in sow fertility), one of the nuclear lncRNA acts as a ceRNA of miR-339. Thereby, it relieves the regulatory effect of miR-339 on CYP19A1 encoding P450arom, a rate-limiting enzyme for E2 synthesis in GCs. Interestingly, miR-339 acts as a saRNA that activates CYP19A1 transcription and enhances E2 release by GCs through altering histone modifications in the promoter by directly binding to the CYP19A1 promoter. Functionally, NORSF inhibited E2 release by GCs via the miR-339 and CYP19A1 axis. Conclusions Our findings highlight an unappreciated mechanism of nuclear lncRNAs and show it acts as a ceRNA, which may be a common lncRNA function in the cytoplasm and nucleus. We also identified a potential endogenous saRNA for improving female fertility and treating female infertility.

Testicular germ cell tumors (TGCT) are the most common type of testicular cancer, comprising 90–95% of cases and representing the most prevalent solid malignancy in young adult men. Immune infiltrates play important regulatory roles in tumors, but their role in TGCT remains unclear. Molecular subtyping is a promising way to provide precisely personalized treatment and avoid unnecessary toxicities. This study investigated immune infiltrates, key biomarkers, and immune subtyping of TGCT. In GSE3218, 24 differentially expressed immune genes (immDEGs) were identified. A new risk signature consisting of six immDEGs was developed using these genes. Individuals in the high‐risk group had poor overall survival (OS; hazard ratio of 4.61 and P‐value

Abstract Background Bacterial meningitis is a central nervous system (CNS) infection disease of the meninges and brain parenchyma caused by the bacteria. Few cases of meningitis related to oral anaerobes have been reported in the literature. Here, we report a case of meningitis in a middle-aged woman, caused by oral anaerobes. Case presentation A 58-year-old woman was admitted to hospital with fever, headache for 21 days and left limb weakness for 2 days. The blood cell counts (11.73 × 109/L), neutrophil counts (9.22 × 109/L) and high-sensitivity C-reactive protein levels (> 5.00 mg/L) were elevated. The brain computerized tomography (CT) scanning indicated the new right thalamus infarct. The brain cranial-enhanced magnetic resonance imaging (MRI) showed the right lateral paraventricular and right thalamic infarct, and abnormal signal in occipital horns of bilateral lateral ventricles were increased. In addition, the brain enhanced nuclear magnetic resonance (NMR) scanning suggested that meninges were thickened and enhanced at the base of the brain, with meningitis changes. The neck CT angiography (CTA) revealed arteriosclerotic changes. The metagenomic next-generation sequencing (mNGS) revealed Eubacterium brachy, Porphyromonas gingivalis, Fusobacterium nucleatum and Torque teno virus in her cerebrospinal fluid (CSF). The patient was diagnosed with purulent meningitis caused by infection of oral anaerobes, and treated with mannitol, ceftriaxone and vancomycin. Her symptoms alleviated. Subsequently, she was transferred to the infectious department and treated with ceftriaxone plus metronidazole (anti-anaerobes) and mannitol (reduce intracranial pressure). Her symptoms improved and currently received rehabilitation treatment. Conclusion We herein report a rare case involving meningitis caused by infection of oral anaerobes. The mNGS can accurately detect the pathogens of infectious diseases.

Abstract Background Edible flowers (EFs) represent valuable sources of both food and medicinal resources, holding the promise to enhance human well-being. Unfortunately, their significance is often overlooked. Ethnobotanical studies on the EFs are lacking in comparison with their botanical and phytochemical research. The practice of consuming flowers as food has a rich culture and long history in China, especially among different linguistic groups in Xishuangbanna, Yunnan. However, economic activities have led to a decline of this tradition. Consequently, preserving the traditional knowledge and culture tied to the EFs in Xishuangbanna becomes both essential and pressing. Methods The field ethnobotanical survey was conducted in Xishuangbanna during five visits in April 2021 and May 2023, covering 48 villages and 19 local markets of all three county-level areas and 9 different linguistic groups. By conducting a comprehensive literature review and on-site field surveys, relevant information regarding the EFs of Xishuangbanna was systematically collected and documented. Additionally, the relative frequency of citation (RFC) values were calculated from the survey data. Results A total of 212 taxa (including species and varieties) of EFs from 58 families and 141 genera were documented in the study area. The edible parts of flowers were classified into 13 categories including peduncle, petal, flower buds, inflorescence as a whole, and etc. They were consumed in 21 ways and as 8 types of food. The inflorescence was the most commonly consumed category, accounting for 85 species (40.1%) of the total categories. They always eat flowers as vegetables (184 species, 86.8%). The preparing form of stir-frying was the preferred food preparation method (138, 65.1%). The Xishuangbanna locals had profound knowledge of which EFs required specific processing to remove their toxicity or bitterness. The dishes can be made from either exclusively from the flowers themselves or by incorporating them alongside other plant parts like stems and leaves. Some EFs with high RFC value, such as Musa acuminata and Bauhinia variegata var. candida, showed significant cultural meanings. These edible flowers occupy specific positions in local traditional culture. Conclusion Traditional knowledge regarding edible flowers holds substantial significance and serves as a representative element of the flower-eating culture in Xishuangbanna. Nevertheless, this knowledge and cultural practice are currently decreasing. Serving as a bridge between tradition and modernity, the flower-eating culture, which derives from local people’s practical experience, shows the potential of EFs and can be applied to the conservation of biocultural diversity, healthy food systems, and sustainable development.

Optimizing soil carbon content is essential for mitigating climate change. Understanding the soil organic carbon (SOC) contents and their relationship with plantation age is important for enhancing SOC in tea plantations. However, there is still a lack of studies in quantifying the SOC–age curve of the whole life cycle in tea plantations. Thus, in this study, we collected 140 soil samples aged 3 to 60 years in the four representative regions (Anxi, Datian, Qingliu, and Fuzhou) in Fujian Province to quantify the SOC contents and their relationship with plantation age. We found that the average SOC was 14.6 ± 6.1 g/kg in the four sampling regions. Nitrogen (N) emerged as having a highly significant positive correlation with SOC (R2 = 0.9). We also found a significant negative correlation between SOC and mean annual temperature (MAT) (R2 = 0.6), and a significant positive correlation with mean annual precipitation (MAP) (R2 = 0.6). The SOC increased with plantation age at 3–20 years old and peaked at 16–20 years old. After 35 years, the SOC decreased gradually with the aging of the plantation. The results indicated that tea plantations could be renewed after the age of 35. These results showed that optimizing age structure is important in enhancing SOC in tea plantations and is meaningful in achieving carbon neutrality.

2-naphthylamine (NAP) was classified as a group I carcinogen associated with bladder cancer. The daily exposure is mostly from cigarette and E-cigarette smoke. NAP can lead to testicular atrophy and interstitial tissue hyperplasia; however, the outcomes of NAP treatment on spermatogenesis and the associated mechanisms have not been reported. The study aimed to investigate the effect of NAP on spermatogenesis and sperm physiologic functions after being persistently exposed to NAP at 5, 20, and 40 mg/kg for 35 days. We found that sperm motility, progressive motility, sperm average path velocity, and straight-line velocity declined remarkably in the NAP (40 mg/kg) treated group, and the sperm deformation rate rose upon NAP administration. The testis immunity- and lipid metabolism-associated processes were enriched from RNA-sequence profiling. Plvap, Ccr7, Foxn1, Trim29, Sirpb1c, Cfd, and Lpar4 involved in testis immunity and Pnliprp1 that inhibit triglyceride and cholesterol absorption were confirmed to rise dramatically in the NAP-exposed group. The increased total cholesterol and CD68 levels were observed in the testis from the NAP-exposed group. Gpx5, serving as an antioxidant in sperm plasma, and Semg1, which contributes to sperm progressive motility, were both down-regulated. We concluded that the short-term exposure to NAP caused reproductive toxicity, primarily due to the inflammatory abnormality in the testis.

This study aimed to prepare an o/w mitiglinide microemulsion (MTGME) to improve the drug solubility and bioavailability. The formulation of o/w MTGME was optimized by the solubility study of drug, pseudo-ternary phase diagram and Box-Behnken design successively. MTGME was characterized by dynamic laser light scattering (DLS), zeta potential and transmission electron microscopy (TEM), moreover, the storage stability, pharmacodynamics and pharmacokinetics were investigated. The optimal prescription for MTGME consisted of Maisine 35–1 (oil), Cremophor EL (surfactant) and propylene glycol (PG, cosurfactant). MTGME with a spherical dimension of 58.1 ± 5.86 nm was stable when stored at 4 °C for 3 months. The blood glucose levers (BGL) of diabetic mice were uniformly and significantly decreased by intragastric (i.g.) administration of 1–4 mg/kg MTGME, in which BGL (i.g. 4 mg/kg MTGME) was reduced by 69% during 24 h. The pharmacokinetics study of MTGME (i.g., 20 mg/kg) in Wistar rats showed higher plasma drug concentration (Cmax, 2.9 folds), larger area under curve (AUC, 4.6 folds) and oral bioavailability than those of MTG suspensions. Generally, the MTGME (o/w) showed good effect on controlling hyperglycemia. Therefore, microemulsion can be used as an effective oral drug delivery system to improve the bioavailability of MTG.

AbstractThe colchicine binding site of tubulin is a promising target for discovering novel antitumour agents. Previously, we identified 2-aryl-4-amide-quinoline derivatives displayed moderate tubulin polymerisation inhibitory activity and broad-spectrum in vitro antitumour activity. In this study, structure based rational design and systematic structural optimisation were performed to obtain analogues C1∼J2 bearing diverse substituents and scaffolds. Among them, analogue G13 bearing a hydroxymethyl group displayed good tubulin polymerisation inhibitory activity (IC50 = 13.5 μM) and potent antiproliferative activity (IC50 values: 0.65 μM∼0.90 μM). G13 potently inhibited the migration and invasion of MDA-MB-231 cells, and displayed potent antiangiogenic activity. It efficiently increased intracellular ROS level and decreased MMP in cancer cells, and obviously induced the fragmentation and disassembly of the microtubules network. More importantly, G13 exhibited good in vivo antitumour efficacy in MDA-MB-231 xenograft model (TGI = 38.2%; i.p., 30 mg/kg).

The skeleton of 2-trifluoromethyl quinoline is the core structure of many natural products and pharmaceutical molecules. The synthesis of this scaffold is limited by metal catalysis, harsh conditions, toxic or hazardous reagents and solvents, and lower atom-economy. Herein, a novel method for the synthesis of 2-trifluoromethyl quinolines via the [4 + 2] cyclization of β-keto esters or 1,3-diketones with various substituted o-aminobenzaldehydes using the metal free catalyst in EtOH is reported. This atom- and step-economical protocol features simple operation, broad substrate scope, and good functional-group compatibility. The synthetic utility of this methodology was highlighted by easy gram-scale synthesis and late-stage functionalization, which would promote the vigorous development of quinoline chemistry. Moreover, the in vitro antifungal activities of the 2-trifluoromethyl quinolines against F. graminearum (from wheat), F. graminearum (from corn), F. moniliforme, F. oxysporum, and R. solani were investigated to further potential utility of these compounds.

BackgroundThe systemic immune-inflammation index (SII) has emerged as a promising marker predicting the prognosis of some cancers, while its role in urothelial carcinoma (UC) remains uncertain, especially in upper urinary tract urothelial carcinoma (UTUC). This meta-analysis aimed to investigate the association of SII with the prognosis of UC and the response to intravesical Bacillus Calmette-Guerin (BCG) therapy of non-muscle invasive bladder cancer (NMIBC).MethodsA systematic search in PubMed, Embase, Web of Science, and the Cochrane Library was performed to identify relevant studies. The extracted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the association between SII and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) of patients with UC. Additionally, we pooled odds ratios (ORs) and 95% CIs to assess the relationship between SII and BCG response in patients with NMIBC. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity.ResultsTwenty studies comprising a total of 12,645 patients were eligible. This meta-analysis revealed that high SII levels independently increased the risk of OS (HR 1.55, 95%CI 1.25–1.92), CSS (HR 1.82, 95%CI 1.36–2.45), and RFS (HR 1.26, 95% CI 1.18–1.35) in patients with UC, including those with upper tract urothelial carcinoma. Additionally, elevated SII levels could predict a lower response to intravesical BCG treatment (OR 0.18, 95%CI 0.07–0.45) and higher disease recurrence (HR 1.61, 95%CI 1.31–1.98) in patients with NMIBC. Furthermore, elevated SII levels were positively associated with advanced age, lymphovascular invasion, hydronephrosis, and high tumor grade and stage (pT ≥ 3).ConclusionsElevated preoperative SII levels are associated with poor survival outcomes in patients with UC, as well as worse response to BCG treatment in patients with NMIBC. Therefore, SII can serve not only as an independent prognostic predictor of patients with UC but also as a guide for BCG therapy in NMIBC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023409077, identifier CRD42023409077.

Abstract A distinct population of skeletal stem/progenitor cells (SSPCs) has been identified that is indispensable for the maintenance and remodeling of the adult skeleton. However, the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined. Here, we established models of premature aging by conditional depletion of Zmpste24 (Z24) in mice and found that Prx1-dependent Z24 deletion, but not Osx-dependent Z24 deletion, caused significant bone loss. However, Acan-associated Z24 depletion caused only trabecular bone loss. Single-cell RNA sequencing (scRNA-seq) revealed that two populations of SSPCs, one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells, were significantly decreased in Prx1-Cre; Z24 f/f mice. Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation. Physical exercise reversed the effects of Z24 depletion on cellular apoptosis, extracellular matrix expression and bone mass. This study identified two populations of SSPCs that are responsible for premature aging-related bone loss. The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging.

An accurate prediction of peak discharge in watersheds is critical not only for water resource management, but also for understanding the complex relationships of hydrological processes. In this study, a modified peak discharge formula based on the Chemicals, Runoff, and Erosion from Agricultural Management Systems (CREAMS) model was developed by introducing rainfall intensity and soil moisture factors. The reliability of the proposed method was tested with data from 1464 storm events in 41 watersheds and was applied to 256 storm events in five remaining typical watersheds using the optimized parameters. The results indicate that the proposed method is highly accurate in terms of model efficiency, as determined by Nash–Sutcliffe efficiencies (NSEs) of 88.60%, 74.04%, and 90.12% during the calibration, validation, and application cases, respectively. Furthermore, it performed better than the original and modified CREAMS methods. Subsequently, using the parameters derived from the initial 41 watersheds and the runoff estimated using the modified Soil Conservation Service curve number (SCS–CN) method, the proposed method was used to predict the peak discharge from the last five typical watersheds. Large NSE (63.88–80.83%) and low root mean square error (RMSE) values (0.31–35.93 m3s-1) were obtained for the five watersheds. Overall, the proposed peak discharge model, combined with the modified SCS-CN method, may accurately predict event-based peak discharge and runoff for general applications under various hydrological and geomorphic conditions in the Loess Plateau region.

Laccases are the key enzymes responsible for plant lignin biosynthesis and responses to environment stress. However, the roles of LAC genes in plant disease resistance are still largely unknown, especially in grapevine, one of the most important horticultural crops in the world. Its quality and yield are very vulnerable to gray mold disease caused by Botrytis cinerea. In total, 30 VvLAC genes were identified and found to be unevenly distributed on seven chromosomes; they were classified into seven groups based on phylogenetic analysis according to the criteria applied in Arabidopsis thaliana. Collinearity and synteny analyses identified some orthologous gene pairs in Vitis vinifera and a few paralogous gene pairs among grape and peach. The VvLAC gene family has diverse gene structures and a highly conserved motif composition. The prominent presence of the MYB cis-elements in each VvLAC promoter highlighted MYB transcriptional factors as the main regulators of VvLAC genes. Furthermore, twenty-five VvLAC genes with functional redundancy are probably implicated in grape lignin biosynthesis. The expression patterns of the LAC genes in grape leaves of Chinese wild V. amurensis ‘Shuangyou’ (SY), a germplasm highly resistant to B. cinerea, were investigated through transcriptomic data and qRT-PCR verification. Combined with the phylogenetic analysis, with AtLACs participating in lignin metabolism, and the cis-element analysis, VaLAC14, VaLAC19, VaLAC24 and VaLAC30 were identified as key candidate genes for lignin biosynthesis in the grape response to B. cinerea. This study supplies a comprehensive understanding of the classification, evolution, structure and responses of the grape LAC genes against B. cinerea. It also provides valuable genetic resources for functional characterization towards enhancing grapevine disease resistance.

Much experimental work has been contributed to all-metal σ, π and δ-aromaticity among transition metals, semimetallics and other metals in the past two decades. Before our focused investigations on the properties of triangular and sandwich-shaped all-metal aromatics, A. I. Boldyrev presented general discussions on the concepts of all-metal σ-aromaticity and σ-antiaromaticity for metallo-clusters. Schleyer illustrated that Nucleus-Independent Chemical Shifts (NICS) were among the most authoritative criteria for aromaticity. Ugalde discussed the earlier developments of all-metal aromatic compounds with all possible shapes. Besides the theoretical predictions, many stable all-metal aromatic trinuclear clusters have been isolated as the metallic analogues of either the σ-aromatic molecule’s [H3]+ ion or the π-aromatic molecule’s [C3H3]+ ion. Different from Hoffman’s opinion on all-metal aromaticity, triangular all-metal aromatics were found to hold great potential in applications in coordination chemistry, catalysis, and material science. Triangular all-metal aromatics, which were theoretically proved to conform to the Hückel (4n + 2) rule and possess the smallest aromatic ring, could also play roles as stable ligands during the formation of all-metal sandwiches. The triangular and sandwich-shaped all-metal aromatics have not yet been specifically summarized despite their diversity of existence, puissant developments and various interesting applications. These findings are different from the public opinion that all-metal aromatics would be limited to further applications due to their overstated difficulties in synthesis and uncertain stabilities. Our review will specifically focus on the summarization of theoretical predictions, feasible syntheses and isolations, and multiple applications of triangular and sandwich shaped all-metal aromatics. The appropriateness and necessities of this review will emphasize and disseminate their importance and applications forcefully and in a timely manner.

The gate-all-around (GAA) nanosheet (NS) field-effect-transistor (FET) is poised to replace FinFET in the 3 nm CMOS technology node and beyond, marking the second seminal shift in device architecture across the extensive 60-plus-year history of MOSFET. The introduction of a new device structure, coupled with aggressive pitch scaling, can give rise to reliability challenges. In this article, we present a review of the key reliability mechanisms in GAA NS FET, including bias temperature instability (BTI), hot carrier injection (HCI), gate oxide (Gox) time-dependent dielectric breakdown (TDDB), and middle-of-line (MOL) TDDB. We aim to not only underscore the unique reliability attributes inherent to NS architecture but also provide a holistic view of the status and prospects of NS reliability, taking into account the challenges posed by future scaling.

Abstract Background Increasing epidemiological studies demonstrated that modifiable risk factors affected the risk of kidney stones. We aimed to systemically assess these causal associations using a bidirectional Mendelian randomization study. Methods We obtained instrumental variables related to each exposure at the genome-wide significant threshold (P

Abstract Background Ammonium (NH4 +) is a key nitrogen source supporting plant growth and development. Proteins in the ammonium transporter (AMT) family mediate the movement of NH4 + across the cell membrane. Although several studies have examined AMT genes in various plant species, few studies of the AMT gene family have been conducted in chili pepper. Results Here, a total of eight AMT genes were identified in chili pepper, and their exon/intron structures, phylogenetic relationships, and expression patterns in response to arbuscular mycorrhizal (AM) colonization were explored. Synteny analyses among chili pepper, tomato, eggplant, soybean, and Medicago revealed that the CaAMT2;1, CaAMT2.4, and CaAMT3;1 have undergone an expansion prior to the divergence of Solanaceae and Leguminosae. The expression of six AMT2 genes was either up-regulated or down-regulated in response to AM colonization. The expression of CaAMT2;1/2;2/2;3 and SlAMT2;1/2;2/2;3 was significantly up-regulated in AM fungi-inoculated roots. A 1,112-bp CaAMT2;1 promoter fragment and a 1,400-bp CaAMT2;2 promoter fragment drove the expression of the β-glucuronidase gene in the cortex of AM roots. Evaluation of AM colonization under different NH4 + concentrations revealed that a sufficient, but not excessive, supply of NH4 + promotes the growth of chili pepper and the colonization of AM. Furthermore, we demonstrated that CaAMT2;2 overexpression could mediate NH4 + uptake in tomato plants. Conclusion In sum, our results provide new insights into the evolutionary relationships and functional divergence of chili pepper AMT genes. We also identified putative AMT genes expressed in AM symbiotic roots.

Abstract Physico-mechanical properties of shale are important parameters in evaluating the stability of potential wellbore and the design of hydraulic fracturing, which are primarily affected by their non-uniform spatial distribution of the microscopic physical–mechanical properties at particle scale. A series of constant strain rate experiments and stress-cycling experiments on shale specimens with different bedding dip angles were conducted to have a comprehensive understanding of the effect of the non-uniform distribution of microscopic failure stress on macroscopic physico-mechanical properties. According to the experimental results and Weibull distribution, we find that bedding dip angle and the dynamic load applying type affect the spatial distributions of microscopic failure stress. The values of crack damage stress (σ cd), σ cd/σ ucs (peak stress), ε cd (strain at crack damage stress), Poissons' ratio (ν), elastic strain energy (U e) and dissipated energy (U irr) of the specimens with more uniform distribution of microscopic failure stress are overall higher, while ε ucs (peak strain)/ε cd and elastic modulus (E) are lower. The dynamic load enables the spatial distributions of microscopic failure stress trend to be more homogeneous prior to the final failure with the increment of σ cd/σ ucs, ν, U e and U irr and the decrement of E.

The effects of age, body weight (BW), and backfat thickness (BF) of replacement gilts at first estrus and first mating on their subsequent reproductive performance and retention of their first 2 parities as sows was evaluated. A total of 3,025 Danish replacement gilts were categorized by farm (allocated to 4 farms), cross combination, age, BW and BF at first estrus and first mating, estrous cycle number at first mating, and flush feeding before first mating. The result shows that all the factors mentioned above were significantly associated with reproductive performance and retention rates of the first 2 parities. Farm 3 had more piglets born alive per litter (BA) (P

Objective Several studies have suggested a potential link between use of proton pump inhibitors (PPIs) and the risk of kidney stones, attributed to alterations in urine mineral levels. Our study aimed to investigate the association between PPI use and kidney stones in US adults.Design Cross-sectional study.Setting National Health and Nutrition Examination Survey (2007–2018).Participants 27 075 individuals with complete information on PPI use and history of kidney stones were included in this study.Outcomes and analyses Non-linear analysis, logistic regression analysis and subgroup analysis were conducted to estimate the relationship between PPI use and the occurrence and recurrence of kidney stones, after adjusting for potential confounding factors.Results Multivariable logistic regression analysis revealed a significant association between PPI use and kidney stones (OR 1.31, 95% CI 1.07 to 1.60), with a 4% increase in the prevalence of kidney stones for each additional year of PPI use (p

A high glucose diet (HGD) is associated with many metabolic diseases including type 2 diabetes, and cardiovascular diseases. Additionally, a HGD increases the oxidative stress resistance of young animals but shortens their lifespan. To investigate the role of HGD feeding on the aging of aged animals, we tested for oxidative stress resistance and changes in lifespan using C. elegans. We showed that a HGD extends the lifespan of aged worms that are dependent on oxidative stress resistance. Furthermore, we measured the lifespan of oxidative stress responding genes of HGD-fed worms. We found that gpdh-1 and col-92 are highly expressed in HGD and paraquat (PQ) treated worms. Further experiments indicated that intestinal gpdh-1 is essential for the HGD induced lifespan extension of aged worms. Our studies provide new insights into understanding the correlation between glucose metabolism, oxidative stress resistance, and aging.

The interaction between miRNAs (microRNAs) and target genes plays an important role in plant pistil development. MiRNAs related to pistils were explored in pomegranate. The differentially expressed miRNAs were screened at different developmental stages of pomegranate pistils, and their target differentially expressed mRNAs were further identified to clarify the regulatory effect of miRNAs on pistil development. In our study, 61 conserved miRNAs were identified in 30 families, including miR395, miR394, miR393, miR161, miR162, and miR168. Among them, miR156, miR157, miR159, miR160, miR164, miR165, miR166, miR167, miR169, and miR172 were involved in the development of flower organs. Eight miRNAs were randomly selected and verified for qRT-PCR analysis. The result analysis indicated that miR160, miR164, and miR172 might be positive factors in the regulation of pomegranate pistil development. MiR156 and miR166 might be involved in regulation of pomegranate pistil development as negative factors.

Evaluating the levels of the biomarker carbohydrate antigen 19-9 (CA19-9) is crucial in early cancer diagnosis and prognosis assessment. In this study, an antifouling electrochemical immunosensor was developed for the label-free detection of CA19-9, in which bovine serum albumin (BSA) and graphene were cross-linked with the aid of glutaraldehyde to form a 3D conductive porous network on the surface of an electrode. The electrochemical immunosensor was characterized through the use of transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscope (AFM), UV spectroscopy, and electrochemical methods. The level of CA19-9 was determined through the use of label-free electrochemical impedance spectroscopy (EIS) measurements. The electron transfer at the interface of the electrode was well preserved in human serum samples, demonstrating that this electrochemical immunosensor has excellent antifouling performance. CA19-9 could be detected in a wide range from 13.5 U/mL to 1000 U/mL, with a detection limit of 13.5 U/mL in human serum samples. This immunosensor also exhibited good selectivity and stability. The detection results of this immunosensor were further validated and compared using an enzyme-linked immunosorbent assay (ELISA). All the results confirmed that this immunosensor has a good sensing performance in terms of CA19-9, suggesting its promising application prospects in clinical applications.

Immobilized enzymes are currently being rapidly developed and are widely used in juice clarification. Immobilized enzymes have many advantages, and they show great advantages in juice clarification. The commonly used methods for immobilizing enzymes include adsorption, entrapment, covalent bonding, and cross-linking. Different immobilization methods are adopted for different enzymes to accommodate their different characteristics. This article systematically reviews the methods of enzyme immobilization and the use of immobilized supports in juice clarification. In addition, the mechanisms and effects of clarification with immobilized pectinase, immobilized laccase, and immobilized xylanase in fruit juice are elaborated upon. Furthermore, suggestions and prospects are provided for future studies in this area.

Abstract Background Studies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC. Materials and methods 220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients’ demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance. Results There were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p

Abstract Background In the present study, we attempted to develop and validate a participatory competency model for medical workers and then evaluate the current status of competency characteristics of Chinese medical workers. Methods The competency model was constructed in a multistage process, including literature review, expert consultation, critical incident and focus group interview. A pilot study was conducted to refine the initial model among 90 participators and the viability and reliability were evaluated by a questionnaire survey among 121 medical workers. Then, the current status of competency characteristics was measured based on the final version of competency model. Results In the pilot study, ten questionnaires were dropped for the poor quality and thus the eligible rate was 92% (138/150). KMO value was 0.785 and Bartlett test showed that the χ2 = 6464.546 (df = 903) and p value

Abstract Background Although cholesterol metabolism is a common pathway for the development of antitumor drugs, there are no specific targets and drugs for clinical use. Here, based on our previous study of sterol O-acyltransferase 1 (SOAT1) in hepatocelluar carcinoma, we sought to screen an effective targeted drug for precise treatment of hepatocelluar carcinoma and, from the perspective of cholesterol metabolism, clarify the relationship between cholesterol regulation and tumorigenesis and development. Methods In this study, we developed a virtual screening integrated affinity screening technology for target protein drug screening. A series of in vitro and in vivo experiments were used for drug activity verification. Multi-omics analysis and flow cytometry analysis were used to explore antitumor mechanisms. Comparative analysis of proteome and transcriptome combined with survival follow-up information of patients reveals the clinical therapeutic potential of screened drugs. Results We screened three compounds, nilotinib, ABT-737, and evacetrapib, that exhibited optimal binding with SOAT1. In particular, nilotinib displayed a high affinity for SOAT1 protein and significantly inhibited tumor activity both in vitro and in vivo. Multi-omics analysis and flow cytometry analysis indicated that SOAT1-targeting compounds reprogrammed the cholesterol metabolism in tumors and enhanced CD8+ T cells and neutrophils to suppress tumor growth. Conclusions Taken together, we reported several high-affinity SOAT1 ligands and demonstrated their clinical potential in the precision therapy of liver cancer, and also reveal the potential antitumor mechanism of SOAT1-targeting compounds. Graphical Abstract

Gentiana rhodantha is a medicinally important perennial herb used as traditional Chinese and ethnic medicines. Secoiridoids are one of the major bioactive compounds in G. rhodantha. To better understand the secoiridoid biosynthesis pathway, we generated transcriptome sequences from four organs (root, leaf, stem and flower), followed by the de novo sequence assembly. We verified 8-HGO (8-hydroxygeraniol oxidoreductase), which may encode key enzymes of the secoiridoid biosynthesis by qRT-PCR. The mangiferin, swertiamarin and loganic acid contents in root, stem, leaf, and flower were determined by HPLC. The results showed that there were 47,871 unigenes with an average length of 1,107.38 bp. Among them, 1,422 unigenes were involved in 25 standard secondary metabolism-related pathways in the KEGG database. Furthermore, we found that 1,005 unigenes can be divided into 66 transcription factor (TF) families, with no family members exhibiting significant organ-specificity. There were 54 unigenes in G. rhodantha that encoded 17 key enzymes of the secoiridoid biosynthetic pathway. The qRT-PCR of the 8-HGO and HPLC results showed that the relative expression and the mangiferin, swertiamarin, and loganic acid contents of the aerial parts were higher than in the root. Six types of SSR were identified by SSR analysis of unigenes: mono-nucleoside repeat SSR, di-nucleoside repeat SSR, tri-nucleoside repeat SSR, tetra-nucleoside repeat SSR, penta-nucleoside repeat SSR, and hexa-nucleoside repeat SSR. This report not only enriches the Gentiana transcriptome database but helps further study the function and regulation of active component biosynthesis of G. rhodantha.

Introduction:A. truncatum Bunge (Sapindaceae or formerly Aceraceae) is a tall deciduous tree native to China. Traditionally, the leaves of A. truncatum are decocted and used by Chinese Mongolians, Koreans, and Tibetans to treat skin itching, dry cracks, and other skin ailments, which indicates A. truncatum leaves may have a potential inhibitory effect on various skin inflammations.Methods: To examine the protective effect against skin inflammations of A. truncatum leaf extract (ATLE), an in vitro dermatitis model was established using sodium dodecyl sulfate (SLS)-induced HaCaT cells. The anti-inflammatory effect of ATLE was evaluated by analyzing cell viability, apoptosis, reactive oxygen species (ROS), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) levels.Results: Orthogonal experiments showed that the pretreatment with ATLE can reduce the IL-6 levels, PGE2 levels, and apoptosis increased in SLS-stimulated HaCaT cells, which indicates that ATLE has positive efficacy for dermatitis. Furthermore, three flavonoid compounds kaempferol-3-O-α-L-rhamnoside, quercetin-3-O-α-L-rhamnopyranoside, kaempferol-3,7-di-O-α-L-rhamnoside, and 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG) were isolated and identified. Among them, kaempferol-3,7-di-O-α-L-rhamnoside was isolated from this plant for the first time. These compounds have been proven to have an anti-inflammatory effect. They may contribute to the efficacy of A. truncatumin treating skin inflammation.Discussion: The results revealed that ATLE has the potential to be used as an additive in various skin care products to prevent skin inflammations and may be incorporated in formulations for topical application as a therapeutic approach against dermatitis.

Influenza A viruses (IAVs) can infect a wide variety of bird and mammal species. Their genome is characterized by 8 RNA single stranded segments. The low proofreading activity of their polymerases and the genomic reassortment between different IAVs subtypes allow them to continuously evolve, constituting a constant threat to human and animal health. In 2009, a pandemic of an IAV highlighted the importance of the swine host in IAVs adaptation between humans and birds. The swine population and the incidence of swine IAV is constantly growing. In previous studies, despite vaccination, swine IAV growth and evolution were proven in vaccinated and challenged animals. However, how vaccination can drive the evolutionary dynamics of swine IAV after coinfection with two subtypes is poorly studied. In the present study, vaccinated and nonvaccinated pigs were challenged by direct contact with H1N1 and H3N2 independent swine IAVs seeder pigs. Nasal swab samples were daily recovered and broncho-alveolar lavage fluid (BALF) was also collected at necropsy day from each pig for swine IAV detection and whole genome sequencing. In total, 39 swine IAV whole genome sequences were obtained by next generation sequencing from samples collected from both experimental groups. Subsequently, genomic, and evolutionary analyses were carried out to detect both, genomic reassortments and single nucleotide variants (SNV). Regarding the segments found per sample, the simultaneous presence of segments from both subtypes was much lower in vaccinated animals, indicating that the vaccine reduced the likelihood of genomic reassortment events. In relation to swine IAV intra-host diversity, a total of 239 and 74 SNV were detected within H1N1 and H3N2 subtypes, respectively. Different proportions of synonymous and nonsynonymous substitutions were found, indicating that vaccine may be influencing the main mechanism that shape swine IAV evolution, detecting natural, neutral, and purifying selection in the different analyzed scenarios. SNV were detected along the whole swine IAV genome with important nonsynonymous substitutions on polymerases, surface glycoproteins and nonstructural proteins, which may have an impact on virus replication, immune system escaping and virulence of virus, respectively. The present study further emphasized the vast evolutionary capacity of swine IAV, under natural infection and vaccination pressure scenarios.

Constructed wetlands (CWs) are artificial systems that use natural processes to treat wastewater containing organic pollutants. This approach has been widely applied in both developing and developed countries worldwide, providing a cost-effective method for industrial wastewater treatment and the improvement of environmental water quality. However, due to the large organic carbon inputs, CWs is produced in varying amounts of CH4 and have the potential to become an important contributor to global climate change. Subsequently, research on the mitigation of CH4 emissions by CWs is key to achieving sustainable, low-carbon dependency wastewater treatment systems. This review evaluates the current research on CH4 emissions from CWs through bibliometric analysis, summarizing the reported mechanisms of CH4 generation, transfer and oxidation in CWs. Furthermore, the important environmental factors driving CH4 generation in CW systems are summarized, including: temperature, water table position, oxidation reduction potential, and the effects of CW characteristics such as wetland type, plant species composition, substrate type, CW-coupled microbial fuel cell, oxygen supply, available carbon source, and salinity. This review provides guidance and novel perspectives for sustainable and effective CW management, as well as for future studies on CH4 reduction in CWs.

The park-integrated energy system can achieve the optimal allocation, dispatch, and management of energy by integrating various energy resources and intelligent control and monitoring. Flexible load participation in scheduling can reduce peak and valley load, optimize load curves, further improve energy utilization efficiency, and reduce system costs. Based on this, firstly, a flexible power-load model is established considering the translatable load, transferable load, and reducible load; and a thermal flexible load model is established based on the fuzziness of user perception of temperature in this study; then, the mixed integer linear programming method is adopted, and the sum of the carbon transaction cost, operation and maintenance cost, compensation cost, power purchase cost, gas purchase cost, wind and light abandonment penalty cost and investment cost of the system is minimized as the objective function, and the configuration of the integrated energy system is optimized, and the optimal capacity of each equipment and the output of each period are obtained. Finally, taking an industrial park in Liaoning Province of China as an example, the analysis is carried out. The example results show that by scheduling the flexible electrical load and flexibly adjusting the indoor temperature, renewable energy consumption can be promoted, and electricity load and heat-load curves can be optimized to increase the installed capacity of wind turbines, reduce the capacity of gas turbines, batteries, and heat-storage tanks, improve system economy, and improve the penetration rate of renewable energy.

Activated pancreatic stellate cells (PSCs) are the main cells involved in chronic pancreatitis and pancreatic intraepithelial neoplasia lesion (PanIN). Fine-tuning the precise molecular targets in PSC activation might help the development of PSC-specific therapeutic strategies to tackle progression of pancreatic cancer-related fibrosis. miR-301a is a pro-inflammatory microRNA known to be activated by multiple inflammatory factors in the tumor stroma. Here, we show that miR-301a is highly expressed in activated PSCs in mice, sustained tissue fibrosis in caerulein-induced chronic pancreatitis, and accelerated PanIN formation. Genetic ablation of miR-301a reduced pancreatic fibrosis in mouse models with chronic pancreatitis and PanIN. Cell proliferation and activation of PSCs was inhibited by downregulation of miR-301a via two of its targets, Tsc1 and Gadd45g. Moreover, aberrant PSC expression of miR-301a and Gadd45g restricted the interplay between PSCs and pancreatic cancer cells in tumorigenesis. Our findings suggest that miR-301a activates two major cell proliferation pathways, Tsc1/mTOR and Gadd45g/Stat3, in vivo, to facilitate development of inflammatory-induced PanIN and maintenance of PSC activation and desmoplasia in pancreatic cancer.

Abstract Background Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. Methods In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. Results Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. Conclusions This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.