[Effects of Grazing on Plant Diversity and Their Carbon Stocks in Different Types of Grasslands].

With the drying and warming of the climate and irrational grazing, various types of grasslands in Inner Mongolia have been degraded to different degrees, and different management modes will inevitably affect the plant diversity and vegetation carbon stock of soil grasslands. To clarify the changes and influencing factors of plant diversity and carbon stock in different types of grasslands under different management modes, plant species composition, aboveground biomass, and vegetation carbon were analyzed based on 18 sentinel monitoring stations across three different types of grasslands in Inner Mongolia. The results showed that grazing increased the dominance of typical grassland and desert grassland, whereas meadow grassland decreased, and the evenness index and Shannon Wiener diversity index increased less in meadow grassland and desert grassland. Grazing decreased graminaceous biomass in meadow grassland and typical grassland, whereas it increased in desert grassland. Above-ground vegetation and below-ground root carbon stocks were much higher than those in grazing areas, 1.5 and 1.2 higher, respectively, but vegetation carbon stocks in long-term grazing sites were significantly lower than those in short-term grazing. Further, the structural equations showed that the effects of geographic location, climatic factors, and soil factors on the biomass and vegetation carbon stocks of the three grassland types differed significantly. The results can provide a reference for the ecologically sustainable development of grassland and the optimization of management mode.

Blood cadmium concentration and pulmonary function injury: potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients.

BACKGROUND: Exposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown. METHODS: The cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models. RESULTS: Each 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively. CONCLUSION: Blood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

Efficacy and prognostic factors of stereotactic body radiotherapy combined with immunotherapy for pulmonary oligometastases: a preliminary retrospective cohort study.

Background: Stereotactic body radiotherapy (SBRT) combined immunotherapy has a synergistic effect on patients with stage IV tumors. However, the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with pulmonary oligometastases have rarely been reported in the studies. The purpose of this study is to explore the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with oligometastatic lung tumors. Methods: A retrospective analysis was conducted on 43 patients with advanced tumors who received SBRT combined with immunotherapy for pulmonary oligometastases from October 2018 to October 2021. Local control (LC), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses of OS were performed using the Cox regression model, and the P value <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve of neutrophil-to-lymphocyte ratio (NLR) after SBRT was generated. Spearman correlation analysis was used to determine the relationship of planning target volume (PTV) with absolute lymphocyte count (ALC) before and after SBRT and with neutrophil count (NE) after SBRT. Additionally, linear regression was used to examine the relationship between ALC after SBRT and clinical factors. Results: A total of 43 patients with pulmonary oligometastases receiving SBRT combined with immunotherapy were included in the study. The change in NLR after SBRT was statistically significant (P<0.001). At 1 and 2 years, respectively, the LC rates were 90.3% and 87.5%, the OS rates were 83.46% and 60.99%, and the PFS rates were 69.92% and 54.25%, with a median PFS of 27.00 (17.84-36.13) months. Univariate and multivariate Cox regression analyses showed that a shorter interval between radiotherapy and immunization [≤21 days; hazard ratio (HR) =1.10, 95% confidence interval (CI): 0.06-0.89; P=0.02] and a low NLR after SBRT (HR =0.24, 95% CI: 1.01-1.9; P=0.03) were associated with improved OS. The ROC curve identified 4.12 as the cutoff value for predicting OS based on NLR after SBRT. NLR after SBRT ≤4.12 significantly extended OS compared to NLR after SBRT >4.12 (log-rank P=0.001). Spearman correlation analysis and linear regression analysis showed that PTV was negatively correlated with ALC after SBRT. Conclusions: Our preliminary research shows that SBRT combined with immunotherapy has a good effect, and NLR after SBRT is a poor prognostic factor for OS. Larger PTV volume is associated with decreased ALC after SBRT.

BRCC36 regulates ß-catenin ubiquitination to alleviate vascular calcification in chronic kidney disease.

BACKGROUND: The prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC. METHODS: The association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/ß-catenin pathway. RESULTS: BRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/ß-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/ß-catenin pathway by decreasing the K63-linked ubiquitination of ß-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression. CONCLUSIONS: Our research results emphasize the critical role of the BRCC36-ß-catenin axis in VC, suggesting that BRCC36 or ß-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients.

PtCo nanoalloy embedded nitrogen-doped carbon nanotube for rechargeable Zn-air batteries.

The large-scale application of metal-air batteries strongly depends on the development of cost-effective, highly efficient, and durable bifunctional oxygen catalysts. In this work, a facile approach for preparing the monodisperse PtCo nanoalloy anchored the nitrogen-doped carbon nanotubes (PtCo/NCNT) for zinc-air batteries is reported. The nitrogen-doped carbon shell prevents PtCo nanoalloy from exfoliation, dissolution, and aggregation and enables the accessibility of electrolytes to the alloy surface and the electron transfer. Besides, the strong interaction between PtCo nanoalloy and nitrogen-doped carbon can efficiently modulate the electronic structure of the formed active sites. When used as a cathode catalyst, the constructed rechargeable zinc-air battery presents higher power density (268 mW cm-2), specific capacity (840 mAh g-1), and excellent stability. More importantly, the PtCo/NCNT catalyst allows the all-solid-state cell to exhibit remarkable flexibility and high round-trip efficiency at various bending states, demonstrating a potential possibility to replace the conventional Pt/C and RuO2 catalysts.

Application of genome tagging technology in elucidating the function of sperm-specific protein 411 (Ssp411).

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

Poly[[µ3-2-(benzotriazol-1-yl)acetato-κ3 O:O':N 3]chlorido-(ethanol-κO)cobalt(II)].

In the title compound, [Co(C8H6N3O2)Cl(C2H5OH)] n , the CoII atoms adopt octa-hedral trans-CoN2O4 and tetra-hedral CoCl2O2 coordination geometries (site symmetries and m, respectively). The bridging µ3-O:O:N 2-(benzotriazol-1-yl)acetato ligands connect the octa-hedral cobalt nodes into (010) sheets and the CoCl2 fragments link the sheets into a tri-periodic network. The structure displays O-H⋯O hydrogen bonding and the ethanol mol-ecule is disordered over two orientations.

Comparisons of clinical scoring systems among suspected pulmonary embolism patients presenting to emergency department.

Introduction: Pulmonary embolism (PE) is among the most severe cardiovascular disorders worldwide. Timely and appropriate diagnosis of PE remains an important step in reducing PE related mortality and morbidity. Methods: In this retrospective single-center cohort study, we comprehensively compared the screening performances of several clinical scoring systems (Wells score [WS], Revised Geneva score [RGS], WS + d-Dimer [D-D], RGS + D-D, WS + PE rule-out criteria [PERC] and RGS + PERC) among PE suspected patients. Failure rates across different PE severity grades as well as overall sensitivity/specificity were considered in evaluating each screening strategy. Results: A total of 3437 patients were included in this study and 698 of them were diagnosed with PE. Patients with and without PE were similar in demographics, while significantly different in respiration-related characteristics. Compared with WS or RGS alone, Integrating PERC or D-D with WS or RGS significantly decreased the failure rates across all PE severity grades, and increased the overall sensitivity from 88.5% and 87.2% to 96.3% and 94.8% (D-D) to 99.4% and 99.6% (PERC), respectively. However, compared with other four scoring approaches, using WS or RGS alone increased the specificity from 8.3% and 7.2%, 38.3% and 21.3%, to 63.5% and 34.8%, respectively, and increased the AUC from 0.54 to 0.54, 0.70 and 0.69, to 0.8 and 0.76, respectively. In general, all screening approaches achieved better performances among PE patients with respiratory distress compared to those without respiratory distress. Conclusion: Combining PERC or D-D with WS or RGS, and the presence of respiratory distress provide significantly better PE rule-out performances.

Genetically Determined Circulating Saturated and Unsaturated Fatty Acids and the Occurrence and Exacerbation of Chronic Obstructive Pulmonary Disease-A Two-Sample Mendelian Randomization Study.

Research on dietary fatty acids (FAs) and lung health has reported skeptical findings. This study aims to examine the causal relationship between circulating FAs and Chronic Obstructive Pulmonary Disease (COPD) onset and exacerbation, using a two-sample Mendelian Randomization (MR) analysis. Strong and independent genetic variants of FAs were obtained from the UK Biobank of European ancestry. The exposure traits included saturated FA (SFA), poly- and mono-unsaturated FA (PUFA and MUFA), omega-3 and omega-6 PUFA, docosahexaenoic acid (DHA), and linoleic acid (LA), all expressed as total FA (TFA) percentages. Summary statistics for COPD outcomes were obtained from the FinnGen consortium including COPD, COPD hospitalization, COPD/asthma-related infections, COPD-related respiratory insufficiency, and COPD/asthma/interstitial lung disease (ILD)-related pneumonia. The inverse-variance weighted (IVW) was the primary MR approach. MR-Egger regression and MR-PRESSO were utilized to evaluate heterogeneity and pleiotropy. MR-PRESSO tests suggested no obvious horizontal pleiotropy. MR results by the IVW approach indicated that the genetically high SFA/TFA levels were associated with an increased risk of COPD/asthma/ILD-related pneumonia (OR: 1.275, 95%CI: 1.103-1.474, p for FDR = 0.002). No significant relationship was observed between other types of FAs and COPD outcomes. Our MR analysis suggests that there is weak evidence that the genetically predicted high SFA/TFA was associated with an increased risk of pneumonia.

Systematic analysis of the expression profiles and prognostic significance of the MED gene family in renal clear cell carcinoma.

The mediator complex (MED) family is a contributing factor in the regulation of transcription and proliferation of cells, and is closely associated with the development of various types of cancer. However, the significance of the expression levels and prognostic value of MED genes in kidney renal clear cell carcinoma (KIRC) have rarely been reported. The present study analyzed the expression and prognostic potential of MED genes in KIRC. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network (PPI), the Assistant for Clinical Bioinformatics database was used to perform correlation analysis, GEPIA 2 was utilized to draw the Kaplan-Meier plot and analyze prognostic significance and the Tumor Immune Estimation Resource was used to assess the association of MED genes with the infiltration of immune cells in patients with KIRC. A total of 30 MED genes were identified, and among these genes, 11 were selected for the creation of a prognostic gene signature based on the results of a LASSO Cox regression analysis. Furthermore, according to univariate and multivariate analyses, MED7, MED16, MED21, MED25 and MED29 may be valuable independent predictive biomarkers for the prognosis of individuals with KIRC. Furthermore, there were significant differences in the expression levels of MED7, MED21 and MED25 in KIRC among different tumor grades. Additionally, patients with KIRC with high transcription levels of MED7, MED21 and MED29 had considerably longer overall survival times. The expression levels of MED genes were also linked to the infiltration of several immune cells. Overall, MED genes may have potential significance in predicting the prognosis of patients with KIRC.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Pan-cancer single-cell dissection reveals phenotypically distinct B cell subtypes.

Characterizing the compositional and phenotypic characteristics of tumor-infiltrating B cells (TIBs) is important for advancing our understanding of their role in cancer development. Here, we establish a comprehensive resource of human B cells by integrating single-cell RNA sequencing data of B cells from 649 patients across 19 major cancer types. We demonstrate substantial heterogeneity in their total abundance and subtype composition and observe immunoglobulin G (IgG)-skewness of antibody-secreting cell isotypes. Moreover, we identify stress-response memory B cells and tumor-associated atypical B cells (TAABs), two tumor-enriched subpopulations with prognostic potential, shared in a pan-cancer manner. In particular, TAABs, characterized by a high clonal expansion level and proliferative capacity as well as by close interactions with activated CD4 T cells in tumors, are predictive of immunotherapy response. Our integrative resource depicts distinct clinically relevant TIB subsets, laying a foundation for further exploration of functional commonality and diversity of B cells in cancer.

A novel polyp retrieval bag reduces the polyp fragmentation rate in colon polypectomy: a single-blind randomized controlled study.

PURPOSE: The fragmentation of polyps affects complete resection confirmation. The primary aim of this study was to assess the feasibility of a novel polyp retrieval bag for reducing the fragmentation rate of colon polyps. METHODS: Patients with a 5-15 mm colon polyp were recruited and randomized into two groups at a 1:1 ratio. After polyp resection, polyps obtained from patients in the treatment group were extracted via a novel polyp retrieval bag without traversing the instrument channel, whereas polyps obtained from patients in the control group were collected through the instrument channel, attaching the polyp trap to the instrument channel port, and applying suction. RESULTS: From January to July 2022, 225 patients were assessed for eligibility. The study participants included 204 patients, and seven patients whose samples were not retrieved were excluded. Polyp fragmentation was significantly lower in the treatment group than in the control group (3.0% [3/100] vs. 17.5% [17/97], P = 0.001). The retrieval failure rates in the treatment group and control group were not significantly different (2.0% [2/102] vs. 4.9% [5/102], P = 0.442). There were fewer colonoscope insertions in the treatment group than in the control group (102 vs. 110), but a significant difference was not present (P = 0.065). No significant adverse events were observed during the follow-up. CONCLUSIONS: This study demonstrated that the polyp retrieval bag was safe and feasible for reducing the fragmentation rate of retrieved polyps. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05189912, 1/12/2021).

Predictability of buprenorphine-naloxone treatment retention: A multi-site analysis combining electronic health records and machine learning.

BACKGROUND AND AIMS: Opioid use disorder (OUD) and opioid dependence lead to significant morbidity and mortality, yet treatment retention, crucial for the effectiveness of medications like buprenorphine-naloxone, remains unpredictable. Our objective was to determine the predictability of 6-month retention in buprenorphine-naloxone treatment using electronic health record (EHR) data from diverse clinical settings and to identify key predictors. DESIGN: This retrospective observational study developed and validated machine learning-based clinical risk prediction models using EHR data. SETTING AND CASES: Data were sourced from Stanford University's healthcare system and Holmusk's NeuroBlu database, reflecting a wide range of healthcare settings. The study analyzed 1800 Stanford and 7957 NeuroBlu treatment encounters from 2008 to 2023 and from 2003 to 2023, respectively. MEASUREMENTS: Predict continuous prescription of buprenorphine-naloxone for at least 6 months, without a gap of more than 30 days. The performance of machine learning prediction models was assessed by area under receiver operating characteristic (ROC-AUC) analysis as well as precision, recall and calibration. To further validate our approach's clinical applicability, we conducted two secondary analyses: a time-to-event analysis on a single site to estimate the duration of buprenorphine-naloxone treatment continuity evaluated by the C-index and a comparative evaluation against predictions made by three human clinical experts. FINDINGS: Attrition rates at 6 months were 58% (NeuroBlu) and 61% (Stanford). Prediction models trained and internally validated on NeuroBlu data achieved ROC-AUCs up to 75.8 (95% confidence interval [CI] = 73.6-78.0). Addiction medicine specialists' predictions show a ROC-AUC of 67.8 (95% CI = 50.4-85.2). Time-to-event analysis on Stanford data indicated a median treatment retention time of 65 days, with random survival forest model achieving an average C-index of 65.9. The top predictor of treatment retention identified included the diagnosis of opioid dependence. CONCLUSIONS: US patients with opioid use disorder or opioid dependence treated with buprenorphine-naloxone prescriptions appear to have a high (∼60%) treatment attrition by 6 months. Machine learning models trained on diverse electronic health record datasets appear to be able to predict treatment continuity with accuracy comparable to that of clinical experts.

Transcriptome analysis of East Asian common octopus, Octopus sinensis, paralarvae.

BACKGROUND: The genes involved in cephalopod development and their association with hatching and survival during early life stages have been extensively studied. However, few studies have investigated the paralarvae transcriptome of the East Asian common octopus (Octopus sinen sis). OBJECTIVE: This study aimed to identify the genes related to embryonic development and hatching in O. sinensis using RNA sequencing (RNA-seq) and verify the genes most relevant to different embryonic stages. METHODS: RNA samples from hatched and 25 days post-hatching (dph) O. sinensis paralarvae were used to construct cDNA libraries. Clean reads from individual samples were aligned to the reference O. sinensis database to identify the differentially expressed genes (DEGs) between the 0- and 25-dph paralarvae libraries. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to supplement the RNA-seq data for embryogenic developmental stages. RESULTS: A total of 12,597 transcripts were annotated and 5,468 DEGs were identified between the 0- and 25-dph O. sinensis paralarvae, including 2,715 upregulated and 2,753 downregulated transcripts in the 25-dph paralarvae. Several key DEGs were related to transmembrane transport, lipid biosynthesis, monooxygenase activity, lipid transport, neuropeptide signaling, transcription regulation, and protein-cysteine S-palmitoyltransferase activity during the post-hatching development of O. sinensis paralarvae. RT-qPCR analysis further revealed that SLC5A3A, ABCC12, and NPC1 transcripts in 20 and/or 30 days post-fertilization (dpf) embryos were significantly higher (p < 0.05) than those in 10-dpf embryos. CONCLUSION: Transcriptome profiles provide molecular targets to understand the embryonic development, hatching, and survival of O. sinensis paralarvae, and enhance octopus production.

BPOZ-2-deficient mice exhibit aggravated inflammation-associated tissue damage after acute dextran sodium sulfate or diethylnitrosamine exposure.

An excessive inflammatory response plays an important role in pathological tissue damage associated with pathogen infection and tumorigenesis. Blood POZ-containing gene type 2 (BPOZ-2), an adaptor protein for the E3 ubiquitin ligase scaffold protein CUL3, is a negative regulator of the inflammatory response. In this study, we investigated the pathophysiological functions of BPOZ-2 in dextran sodium sulfate (DSS)-induced colon injury and diethylnitrosamine (DEN)-induced liver damage. Our results indicated that BPOZ-2 deficiency increased IL-1ß induction after DSS and DEN treatment. In addition, BPOZ-2-deficient mice were more susceptible to DSS-induced colitis. Notably, BPOZ-2 deficiency aggravated DEN-induced acute liver injury. These results revealed that BPOZ-2 protected against pathological tissue damage with a dysregulated inflammatory response.

Brunonianines D-F, three new C19-diterpenoid alkaloids from the Delphinium brunonianum, with therapeutic effect on ovarian cancer in vitro and in vivo.

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.

Chemical constituents of Rubia tibetica Hook. f. from Tibetan medicine and cytotoxic activity evaluation.

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC50 value of 8.15 ± 0.20 µM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase.

An esculentin-1 homolog from a dark-spotted frog (Pelophylax nigromaculatus) possesses antibacterial and immunoregulatory properties.

BACKGROUND: Esculentin-1, initially discovered in the skin secretions of pool frogs (Pelophylax lessonae), has demonstrated broad-spectrum antimicrobial activity; however, its immunomodulatory properties have received little attention. RESULTS: In the present study, esculentin-1 cDNA was identified by analysing the skin transcriptome of the dark-spotted frog (Pelophylax nigromaculatus). Esculentin-1 from this species (esculentin-1PN) encompasses a signal peptide, an acidic spacer peptide, and a mature peptide. Sequence alignments with other amphibian esculentins-1 demonstrated conservation of the peptide, and phylogenetic tree analysis revealed its closest genetic affinity to esculentin-1P, derived from the Fukien gold-striped pond frog (Pelophylax fukienensis). Esculentin-1PN transcripts were observed in various tissues, with the skin exhibiting the highest mRNA levels. Synthetic esculentin-1PN demonstrated antibacterial activity against various pathogens, and esculentin-1PN exhibited bactericidal activity by disrupting cell membrane integrity and hydrolyzing genomic DNA. Esculentin-1PN did not stimulate chemotaxis in RAW264.7, a murine leukemic monocyte/macrophage cell line. However, it amplified the respiratory burst and augmented the pro-inflammatory cytokine gene (TNF-α and IL-1ß) expression in RAW264.7 cells. CONCLUSIONS: This novel finding highlights the immunomodulatory activity of esculentin-1PN on immune cells.