Diagnostic value of new biliary biopsy cannulae for malignant bile duct strictures by endoscopic retrograde cholangiopancreatography pathway.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the diagnosis of malignant biliary strictures. ERCP fluoroscopy-guided biliary biopsy is more sensitive than brushing, but it is more difficult to perform and less successful. Therefore, a new technique of biliary biopsy using a new biliary biopsy cannula via the ERCP route was developed in our center with the aim of improving the diagnosis rate of malignant biliary strictures. METHODS: This is a retrospective study that included 42 patients who underwent ERCP-guided biliary brushing and biliary biopsy for biliary strictures using a new biliary biopsy cannula in our department from January 2019 to May 2022. The final diagnosis was determined after brushing, biliary biopsy under the new biliary biopsy cannula or adequate follow-up. Diagnostic rates were calculated and analyzed for relevant factors. RESULTS: The satisfactory rates of pathological specimens of 42 patients who underwent bile duct biopsy with bile duct brush and new bile duct biopsy cannula were 57.14% and 95.24% respectively. Cholangiocarcinoma was diagnosed in 45.23% and 83.30% of the samples by biliary brush examination and biliary biopsy using the new biliary biopsy cannula, respectively (p < 0.001). CONCLUSIONS: The ERCP route using a new biliary biopsy cannula for biliary biopsy technique can improve pathology positivity and benefit ratio. It provides a new approach in the diagnosis of malignant stenosis in the bile duct.

Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury.

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.

[Effects of Long-term Sod Cultivation on Chinese Hickory Plantation Soil Fungal Community and Enzyme Activities].

A long-term field experiment was conducted at a Chinese hickory (Carya cathayensis) plantation from 2011 to 2021, with the purpose of researching the effects of long-term sod cultivation on hickory plantation soil fungal communities and enzyme activities and providing experience for ecological management in other plantations. Sod cultivation included oilseed rape (Brassica chinensis, BR), Chinese milk vetch (Astragalus sinicus, AS), and oilseed rape+Chinese milk vetch (BA), and clear tillage (CT) served as a contrast. The soil fertility, fungal community composition and diversity, and soil enzyme activities were determined. The results showed that:① long-term sod cultivation significantly increased soil nutrient contents and availability, and pH increased variably from different sod cultivation treatments (P<0.05). ②The soil fungal community composition was changed by long-term sod cultivation. The relative abundance of Ascomycota, which utilized the readily decomposed organic matter, was increased, whereas the relative abundance of Basidiomycota, which degraded stubborn organic matter, decreased. Long-term sod cultivation shifted the soil dominant genera, as BR and BA increased the relative abundance of somemycorrhizal fungi that could form mutually beneficial structures with dominant plant genera after sod cultivation,whereas AS increased the relative abundance of saprophytic fungi that could decompose the remains of dead plants and animals. The soil fertility factors including pH, available nitrogen, microbial biomass nitrogen, and water-soluble organic carbon were revealed to have a significant influence on the soil fungal composition (P<0.05). ③ Moreover, long-term sod cultivation stimulated the activities of soil enzymes involved in the carbon and nitrogen cycle. Apart from BA, sod cultivation treatments decreased the activities of alkaline phosphatase, which was involved in the soil P turnover. The correlation analysis demonstrated that the correlations between activities of enzymes decomposing carbon and nitrogen and soil fertility were significant (P<0.05 or P<0.01). The activities of phosphatase were positively correlated with soil microbial biomass carbon and nitrogen. Long-term sod cultivation could improve soil nutrient content and availability, optimized soil fungal community structure, and promoted soil nutrient turnover enzyme activities.

Effect of end-stage kidney disease on the return of spontaneous circulation in Taiwanese adults with out-of-hospital cardiac arrest.

Rescuing patients with out-of-hospital cardiac arrest (OHCA), especially those with end-stage kidney disease (ESKD), is challenging. This study hypothesizes that OHCA patients with ESKD undergoing maintenance hemodialysis have (1) higher rates of return of spontaneous circulation (ROSC) during cardio-pulmonary resuscitation (CPR) and (2) lower rates of hyperkalemia and less severe acidosis than those without ESKD. OHCA patients who received CPR between 2011 and 2020 were dichotomized into ESKD and non-ESKD groups. The association of ESKD with "any" and "sustained" ROSC were examined using logistic regression analysis. Furthermore, the effect of ESKD on hospital outcomes for OHCA patients who survived to admission was evaluated using Kaplan-Meier analysis. ESKD patients without "any" ROSC displayed lower potassium and higher pH levels than non-ESKD patients. ESKD was positively associated with "any" ROSC (adjusted-OR: 4.82, 95% CI 2.70-5.16, P < 0.01) and "sustained" ROSC (adjusted-OR: 9.45, 95% CI 3.83-24.13, P < 0.01). Kaplan-Meier analysis demonstrated ESKD patients had a non-inferior hospital survival than non-ESKD patients. OHCA patients with ESKD had lower serum potassium level and less severe acidosis compared to the general population in Taiwan; therefore, should not be treated under the stereotypical assumption that hyperkalemia and acidosis always occur.

Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.

Phenolic components from the fruits of Solanum xanthocarpum with anti-inflammatory activity.

Two new compounds (1 and 2), along with thirty-one known compounds (3-33) were isolated from the fruits of Solanum xanthocarpum. The structure of isolates was elucidated by analysis of spectroscopic data and the physicochemical methods. Meanwhile, the anti-inflammatory activity of isolates was determined using LPS-induced RAW 264.7 cells. The results of anti-inflammatory assays indicated that most isolated compounds (3, 4, 6, 8-14, 17-20, and 30) possessed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 cells with IC50 values ranging from 14.33 to 48.55 µM.

Machine learning for the prediction of postoperative nosocomial pulmonary infection in patients with spinal cord injury.

PURPOSE: The purpose of this study was to establish the best prediction model for postoperative nosocomial pulmonary infection through machine learning (ML) and assist physicians to make accurate diagnosis and treatment decisions. METHODS: Patients with spinal cord injury (SCI) who admitted to a general hospital between July 2014 and April 2022 were included in this study. The data were segmented according to the ratio of seven to three, 70% were randomly selected to train the model, and the other 30% were used for testing. We used LASSO regression to screen the variables, and the selected variables were used in the construction of six different ML models. Shapley additive explanations and permutation importance were used to explain the output of the ML models. Finally, sensitivity, specificity, accuracy and area under receiver operating characteristic curve (AUC) were used as the evaluation index of the model. RESULTS: A total of 870 patients were enrolled in this study, of whom 98 (11.26%) developed pulmonary infection. Seven variables were used for ML model construction and multivariate logistic regression analysis. Among these variables, age, ASIA scale and tracheotomy were found to be the independent risk factors for postoperative nosocomial pulmonary infection in SCI patients. Meanwhile, the prediction model based on RF algorithm performed best in the training and test sets. (AUC = 0.721, accuracy = 0.664, sensitivity = 0.694, specificity = 0.656). CONCLUSION: Age, ASIA scale and tracheotomy were the independent risk factors of postoperative nosocomial pulmonary infection in SCI. The prediction model based on RF algorithm had the best performance.

Dynamic changes in circulating EBV-DNA load during treatment have prognostic values in EBV+ DLBCL-NOS: a Chinese cohort study.

EBV-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL-NOS), is an EBV-positive clonal B-cell lymphoid proliferation and circulating EBV-DNA is a great indicator for prognosis among EBV associated disease. In this retrospective study, we report 66 EBV+ DLBCL cases among 2137 DLBCL-NOS cases diagnosed from 2013 to 2021 (prevalence of 6.0%). After a median follow-up of 27 months, progression-free survival (PFS) and overall survival (OS) at 2 years were 39.5% ± 6.2% and 53.6% ± 6.4%, respectively. Multivariate analysis showed that only the biomarker of the positivity of post treatment EBV-DNA had a borderline correlation with shorter PFS and OS (PFS: P = 0.053; OS: P = 0.065). Patients were divided into three subgroups according to dynamic changes of EBV-DNA status: EBV-DNA persistently negative group, EBV-DNA persistently positive group, and EBV-DNA transformed from positive to negative group; among the three groups, patients of the persistently positive group had worst PFS and OS (P = 0.0527 and P = 0.0139, respectively). Decline in EBV copies correlated significantly with treatment response as well. In conclusion, circulating EBV-DNA level played a vital role in prognostic and monitoring marker for EBV+ DLBCL-NOS.

Identification of three capsule depolymerases in a bacteriophage infecting Klebsiella pneumoniae capsular types K7, K20, and K27 and therapeutic application.

BACKGROUND: Klebsiella pneumoniae capsular types K1, K2, K5, K20, K54, and K57 are prevalent hypervirulent types associated with community infections, and worrisomely, hypervirulent strains that acquired drug resistance have been found. In the search for alternative therapeutics, studies have been conducted on phages that infect K. pneumoniae K1, K2, K5, and K57-type strains and their phage-encoded depolymerases. However, phages targeting K. pneumoniae K20-type strains and capsule depolymerases capable of digesting K20-type capsules have rarely been reported. In this study, we characterized a phage that can infect K. pneumoniae K20-type strains, phage vB_KpnM-20. METHODS: A phage was isolated from sewage water in Taipei, Taiwan, its genome was analyzed, and its predicted capsule depolymerases were expressed and purified. The host specificity and capsule-digesting activity of the capsule depolymerases were determined. The therapeutic effect of the depolymerase targeting K. pneumoniae K20-type strains was analyzed in a mouse infection model. RESULTS: The isolated Klebsiella phage, vB_KpnM-20, infects K. pneumoniae K7, K20, and K27-type strains. Three capsule depolymerases, K7dep, K20dep, and K27dep, encoded by the phage were specific to K7, K20, and K27-type capsules, respectively. K20dep also recognized Escherichia coli K30-type capsule, which is highly similar to K. pneumoniae K20-type. The survival of K. pneumoniae K20-type-infected mice was increased following administration of K20dep. CONCLUSIONS: The potential of capsule depolymerase K20dep for the treatment of K. pneumoniae infections was revealed using an in vivo infection model. In addition, K7dep, K20dep, and K27dep capsule depolymerases could be used for K. pneumoniae capsular typing.

A Medically Assisted Model for Precise Segmentation of Osteosarcoma Nuclei on Pathological Images.

Osteosarcoma is the most common malignant bone tumor with a high degree of malignancy and misdiagnosis rates. Pathological images are crucial for its diagnosis. However, underdeveloped regions currently lack sufficient high-level pathologists, leading to uncertain diagnostic accuracy and efficiency. Existing research on pathological image segmentation often neglects the differences in staining styles and lack of data, without considering medical backgrounds. To alleviate the difficulty in diagnosing osteosarcoma in underdeveloped areas, an intelligent assisted diagnosis and treatment scheme for osteosarcoma pathological images, ENMViT, is proposed. ENMViT utilizes KIN to achieve normalization of mismatched images with limited GPU resources and uses traditional data enhancement methods, such as cleaning, cropping, mosaic, Laplacian sharpening, and other techniques to alleviate the issue of insufficient data. A multi-path semantic segmentation network combining Transformer and CNN is used to segment images, and the degree of edge offset in the spatial domain is introduced into the loss function. Finally, noise is filtered according to the size of the connecting domain. This paper experimented on more than 2000 osteosarcoma pathological images from Central South University. The experimental results demonstrate that this scheme performs well in each stage of the osteosarcoma pathological image processing, and the segmentation results' IoU index is 9.4% higher than the comparative models, demonstrating its significant value in the medical industry.

Modulation of Brain Network Topological Properties in Knee Osteoarthritis by Electroacupuncture in Rats.

Introduction: Osteoarthritis is a chronic, ongoing disease that affects patients, and pain is considered a key factor affecting patients, but the brain changes during the development of osteoarthritis pain are currently unclear. In this study, we used electroacupuncture (EA) to intervene the rat model of knee osteoarthritis and analyzed the changes in topological properties of brain networks using graph theory. Methods: Sixteen SD rat models of right-knee osteoarthritis with anterior cruciate ligament transection (ACLT) were randomly divided into electroacupuncture intervention group and control group. The electroacupuncture group was intervened on Zusanli (ST36) and Futu (ST32) for 20 min each time, five times a week for 3 weeks, while the control group was applied sham stimulation. Both groups were measured for pain threshold. The small-world properties and node properties of the brain network between the two groups after the intervention were statistically analyzed by graph theory methods. Results: The differences are mainly in the changes in node attributes between the two groups, such as degree centrality, betweenness centrality, and so on in different brain regions (P<0.05). Both groups showed no small-world characteristics in the brain networks of the two groups. The mechanical thresholds and thermal pain thresholds were significantly higher in the EA group than in the control group (P<0.05). Conclusion: The study demonstrated that electroacupuncture intervention enhanced the activity of nodes related to pain circuit and relieved pain in osteoarthritis, which provides a complementary basis for explaining the effect of electroacupuncture intervention on pain through graphical analysis of changes in brain network topological properties and helps to develop an imaging model for pain affected by electroacupuncture.

Development of an aminotransferase-driven biocatalytic cascade for deracemization of d,l-phosphinothricin.

2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) is the essential precursor keto acid for the asymmetric biosynthesis of herbicide l-phosphinothricin (l-PPT). Developing a biocatalytic cascade for PPO production with high efficiency and low cost is highly desired. Herein, a d-amino acid aminotransferase from Bacillus sp. YM-1 (Ym DAAT) with high activity (48.95 U/mg) and affinity (Km = 27.49 mM) toward d-PPT was evaluated. To circumvent the inhibition of by-product d-glutamate (d-Glu), an amino acceptor (α-ketoglutarate) regeneration cascade was constructed as a recombinant Escherichia coli (E. coli D), by coupling Ym d-AAT, d-aspartate oxidase from Thermomyces dupontii (TdDDO) and catalase from Geobacillus sp. CHB1. Moreover, the regulation of the ribosome binding site was employed to overcome the limiting step of expression toxic protein TdDDO in E. coli BL21(DE3). The aminotransferase-driven whole-cell biocatalytic cascade (E. coli D) showed superior catalytic efficiency for the synthesis of PPO from d,l-phosphinothricin (d,l-PPT). It revealed the production of PPO exhibited high space-time yield (2.59 g L-1 h-1 ) with complete conversion of d-PPT to PPO at high substrate concentration (600 mM d,l-PPT) in 1.5 L reaction system. This study first provides the synthesis of PPO from d,l-PPT employing an aminotransferase-driven biocatalytic cascade.

Facile access to 2-hydroxy-2-substituted indole-3-ones via a copper-catalyzed oxidative cyclization of 2-arylethynylanilines.

This paper reports a practical and versatile oxidative cyclization of 2-arylethynylanilines towards 2-hydroxy-2-substituted indol-3-ones via a copper-catalyzed radical approach in the presence of O2. The transformation of 2-hydroxy-2-arylindol-3-ones to 3-hydroxy-3-arylindol-2-ones proceeds well with good yields and highlights the practicability and utility of this catalytic system. Mechanistic investigations showed that the acetyl substituent on 2-arylaethynylanilines played an important role in the formation of the cyclic products and the reaction proceeded via an N-center radical-based 5-endo-dig aza-cyclization pathway.

Temporal and spatial variations and influencing factors of gross primary productivity in Changbai Mountain Nature Reserve, China.

Changbai Mountain Nature Reserve (CNR) is a typical temperate forest ecosystem, and gross primary production (GPP) of which is closely related to topography and climate change. Research on the spatio-temporal variations and influencing factors of GPP in the CNR is of great significance for assessing growth status of vegetation and the quality of ecological environment. We calculated GPP in CNR using the vegetation photosynthesis model (VPM), and analyzed the influences of slope, altitude, temperature, precipitation, and total radiation. The results showed that the range of annual average GPP in CNR was 63-1706 g C·m-2·a-1 from 2000 to 2020 and that GPP decreased with the increases of altitude. Temperature played the most important role in driving the spatial varia-tion of GPP, with a significant positive correlation with GPP. During the study period, the overall annual GPP showed a significant increase trend in CNR, with an average annual increase of 13 g C·m-2·a-1. The areas with increase of annual GPP accounted for 79.9% of the total area, and the area proportion of annual GPP increase differed in each plant functional type. Annual precipitation was significantly negatively correlated with GPP in 43.2% of CNR, while annual mean temperature and annual total radiation were significantly positively correlated with GPP in 47.2% and 82.4% of CNR. GPP would increase continuously in CNR under the scenario of future global warming.

A Low-Cost Fertilizer Medium Supplemented with Urea for the Lutein Production of Chlorella sp. and the Ability of the Lutein to Protect Cells against Blue Light Irradiation.

This study aimed to investigate the use of organic fertilizers instead of modified f/2 medium for Chlorella sp. cultivation, and the extracted lutein of the microalga to protect mammal cells against blue-light irradiation. The biomass productivity and lutein content of Chlorella sp. cultured in 20 g/L fertilizer medium for 6 days were 1.04 g/L/d and 4.41 mg/g, respectively. These values are approximately 1.3- and 1.4-fold higher than those achieved with the modified f/2 medium, respectively. The cost of medium per gram of microalgal biomass reduced by about 97%. The microalgal lutein content was further increased to 6.03 mg/g in 20 g/L fertilizer medium when supplemented with 20 mM urea, and the cost of medium per gram lutein reduced by about 96%. When doses of ≥1 µM microalgal lutein were used to protect mammal NIH/3T3 cells, there was a significant reduction in the levels of reactive oxygen species (ROS) produced by the cells in the following blue-light irradiation treatments. The results show that microalgal lutein produced by fertilizers with urea supplements has the potential to develop anti-blue-light oxidation products and reduce the economic challenges of microalgal biomass applied to carbon biofixation and biofuel production.

Challenges for the development of mutant isocitrate dehydrogenases 1 inhibitors to treat glioma.

Glioma is one of the most common types of brain tumors, and its high recurrence and mortality rates threaten human health. In 2008, the frequent isocitrate dehydrogenase 1 (IDH1) mutations in glioma were reported, which brought a new strategy in the treatment of this challenging disease. In this perspective, we first discuss the possible gliomagenesis after IDH1 mutations (mIDH1). Subsequently, we systematically investigate the reported mIDH1 inhibitors and present a comparative analysis of the ligand-binding pocket in mIDH1. Additionally, we also discuss the binding features and physicochemical properties of different mIDH1 inhibitors to facilitate the future development of mIDH1 inhibitors. Finally, we discuss the possible selectivity features of mIDH1 inhibitors against WT-IDH1 and IDH2 by combining protein-based and ligand-based information. We hope that this perspective can inspire the development of mIDH1 inhibitors and bring potent mIDH1 inhibitors for the treatment of glioma.

Cytotoxicity sesquiterpenoids from the leaves of Datura stramonium L.

Four new sesquiterpenoids, dstramonins A-D (1-4), and one new natural product (5), together with three known compounds (6-8), were isolated from the leaves of Datura stramonium L. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the literature. The cytotoxicity of isolates against LN229 cells was assessed and compounds 2-4, and 7 displayed cytotoxic activity with IC50 values ranging from 8.03 to 13.83 µM.

Machine Learning Models for the Identification of Prognostic and Predictive Cancer Biomarkers: A Systematic Review.

The identification of biomarkers plays a crucial role in personalized medicine, both in the clinical and research settings. However, the contrast between predictive and prognostic biomarkers can be challenging due to the overlap between the two. A prognostic biomarker predicts the future outcome of cancer, regardless of treatment, and a predictive biomarker predicts the effectiveness of a therapeutic intervention. Misclassifying a prognostic biomarker as predictive (or vice versa) can have serious financial and personal consequences for patients. To address this issue, various statistical and machine learning approaches have been developed. The aim of this study is to present an in-depth analysis of recent advancements, trends, challenges, and future prospects in biomarker identification. A systematic search was conducted using PubMed to identify relevant studies published between 2017 and 2023. The selected studies were analyzed to better understand the concept of biomarker identification, evaluate machine learning methods, assess the level of research activity, and highlight the application of these methods in cancer research and treatment. Furthermore, existing obstacles and concerns are discussed to identify prospective research areas. We believe that this review will serve as a valuable resource for researchers, providing insights into the methods and approaches used in biomarker discovery and identifying future research opportunities.