Structure and pharmacokinetics/pharmacodynamics of the anticoagulant tetradecasaccharide oHG-14 as an intrinsic tenase inhibitor.

The intrinsic tenase complex (iXase) is an attractive antithrombotic target to treat or prevent pathological thrombosis with negligible bleeding risk. Fucosylated glycosaminoglycan (FG) is a promising anticoagulant by inhibiting iXase. A depolymerized FG (dHG-5) as an anticoagulant has been approved for clinical trials. Given that dHG-5 is a multi-component drug candidate consisting of a homologous series of oligosaccharides, it is difficult to predict a clear pharmacokinetics. Here, as a major oligosaccharide component, the tetradecasaccharide (oHG-14) was purified from dHG-5 and its structure was defined as L-Fuc3S4S-α(1,3)-L-Δ4,5GlcA-α(1,3)-{D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ß(1,3)-}3-D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ol. oHG-14 showed potent iXase inhibitory activity in vitro and antithrombotic effect in vivo comparable to dHG-5. After single subcutaneous administration of oHG-14 at 8, 14.4 and 32.4 mg/kg to rats, the absolute bioavailability was 71.6 %-80.9 % determined by the validated bioanalytical methods. The maximum concentration (Cmax) was 3.73, 8.07, and 11.95 µg/mL, respectively, and the time reaching Cmax (Tmax) was about 1 h. oHG-14 was mainly excreted by kidney as the parent compound with the elimination kinetics of first-order linear model. Anticoagulant activity of oHG-14 was positively correlated with its concentration in rat plasma. The pharmacokinetics/pharmacodynamics (PK/PD) of oHG-14 is similar to that of dHG-5. This study could provide supportive data for the clinical trial of dHG-5 and further development of pure oligosaccharide as an antithrombotic drug candidate.

Surface-Enhanced Raman Spectroscopy: Current Understanding, Challenges, and Opportunities.

While surface-enhanced Raman spectroscopy (SERS) has experienced substantial advancements since its discovery in the 1970s, it is an opportunity to celebrate achievements, consider ongoing endeavors, and anticipate the future trajectory of SERS. In this perspective, we encapsulate the latest breakthroughs in comprehending the electromagnetic enhancement mechanisms of SERS, and revisit CT mechanisms of semiconductors. We then summarize the strategies to improve sensitivity, selectivity, and reliability. After addressing experimental advancements, we comprehensively survey the progress on spectrum-structure correlation of SERS showcasing their important role in promoting SERS development. Finally, we anticipate forthcoming directions and opportunities, especially in deepening our insights into chemical or biological processes and establishing a clear spectrum-structure correlation.

Risk factors for post-operative portal vein stenosis in pediatric liver transplantation: a single center case-control study.

PURPOSE: The incidence of post-transplant poral vein stenosis (PVS) is higher in pediatric liver transplantation, probably resulting from various portal vein (PV) reconstruction methods or other factors. METHODS: 332 patients less than 12 years old when receiving liver transplantation (LT) were enrolled in this research. Portal vein reconstruction methods include anastomosis to the left side of the recipient PV trunk (type 1, n = 170), to the recipient left and right PV branch patch (type 2, n = 79), using vein graft interposition (type 3, n = 32), or end-to-end PV anastomosis (type 4, n = 50). The incidence of PVS was analyzed in terms to different PV reconstruction methods and other possible risk factors. RESULTS: PVS occurred in 35 (10.5%) patients. Of the 32 patients using vein graft, 20 patients received a cryopreserved vein graft, 11 (55%) developed PVS, while the remaining 12 patients received a fresh iliac vein for PV interposition and none of them developed PVS. 9 patients whose liver donor was under 12 years old developed PVS, with an incidence of 18.8%. CONCLUSION: Cryopreserved vein graft interposition and a liver donor under 12 are independent risk factors for PVS in pediatric LT.

Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Exploring Genetic Associations of 3 Types of Risk Factors With Ischemic Stroke: An Integrated Bioinformatics Study.

BACKGROUND: Ischemic stroke (IS) is a major cause of disability and mortality worldwide. Increasing evidence suggests a strong association between blood pressure, blood glucose, circulating lipids, and IS. Nonetheless, the genetic association of these 3 risk factors with IS remains elusive. METHODS: We screened genetic instruments related to blood pressure, blood glucose, and circulating lipids and paired them with IS genome-wide association study data to conduct Mendelian randomization analysis. Positive Mendelian randomization findings were then subjected to colocalization analysis. Subsequently, we utilized the Gene Expression Omnibus data set to perform differential expression analysis, aiming to identify differentially expressed associated genes. We determined the importance scores of these differentially expressed associated genes through 4 machine learning models and constructed a nomogram based on these findings. RESULTS: The combined results of the Mendelian randomization analysis indicate that blood pressure (systolic blood pressure: odds ratio [OR], 1.02 [95% CI, 1.01-1.02]; diastolic blood pressure: OR, 1.03 [95% CI, 1.03-1.04]) and some circulating lipids (low-density lipoprotein cholesterol: OR, 1.06 [95% CI, 1.01-1.12]; apoA1: OR, 0.95 [95% CI, 0.92-0.98]; apoB: OR, 1.05 [95% CI, 1.01-1.09]; eicosapentaenoic acid: OR, 2.36 [95% CI, 1.41-3.96]) have causal relationships with the risk of IS onset. We identified 73 genes that are linked to blood pressure and circulating lipids in the context of IS, and 16 are differentially expressed associated genes. FURIN, MAN2A2, HDDC3, ALDH2, and TOMM40 were identified as feature genes for constructing the nomogram that provides a quantitative prediction of the risk of IS onset. CONCLUSIONS: This study indicates that there are causal links between blood pressure, certain circulating lipids, and the development of IS. The potential mechanisms underlying these causal relationships involve the regulation of lipid metabolism, blood pressure, DNA repair and methylation, cell apoptosis and autophagy, immune inflammation, and neuronal protection, among others.

Universal antifungal prophylaxis effectively prevents fungal bloodstream infection in pediatric liver transplant recipients: a retrospective real-world study.

OBJECTIVES: Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. METHODS: We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. RESULTS: Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P <0.001). CONCLUSIONS: Universal prophylaxis strategy for fBSI in pediatrics after liver transplantation is desirable as it could markedly decrease the occurrence of fBSI. Pediatric patients with deceased donors and high-volume intraoperative transfusion should be paid more attention to preventing fBSI.

Complete genome sequence of a novel Prescottella sp. R16 isolate from deep-sea sediments in the western Pacific.

Prescottella, a distinct genus separate from Rhodococcus, has garnered attention for its adaptability and ecological versatility. In this study, a Gram-stain positive and ovoid-rod shaped the actinobacterium strain R16 was isolated from deep-sea sediment (with a depth of 6,310 m) in the Western Pacific. On the basis of 16S rRNA gene sequence analysis, average nucleotide identity and phylogenomic analysis, strain R16 clearly represents a novel species within the genus Prescottella. Genomic analyses indicate Prescottella sp. R16 contains a circular chromosome of 4,531,251 bp with an average GC content of 68.9%, 4,208 protein-coding genes, 51 tRNA genes, and 12 rRNA operons. Additionally, four CRISPRs and 24 genomic islands are also identified. The presence of rich categories related to catalytic activity, membrane part and metabolic process highlights their involvement in cellular component, biological process, and molecular function. The genome sequence of strain R16 also revealed the presence of 13 putative biosynthetic gene clusters for secondary metabolites, including those for ε-Poly-L-lysine, ectoine, heterobactin, isorenieratene and corynecin, suggesting its potential for antibiotic production and warranting further exploration.

The tolerance of two marine diatoms to diurnal pH fluctuation under dynamic light condition and ocean acidification scenario.

Coastal waters undergo dynamic changes in seawater carbonate chemistry due to natural and anthropogenic factors. Despite this, our current understanding of how coastal phytoplankton respond to fluctuating pH is limited. In the present study, we investigated the physiological responses of two coastal diatoms Thalassiosira pseudonana and Thalassiosira weissflogii to seawater acidification and diurnally fluctuating pH under natural solar irradiance. Seawater acidification did not significantly impact the growth, maximum and effective quantum yield of PSII, and photosynthetic rates of the two species. However, it did increase the maximum relative electron transport rate of T. weissflogii by 11%. Overall, fluctuating pH had neutral or positive effects on both species. It enhanced the light-saturated photosynthetic rate of T. weissflogii by 20% compared to cells grown under seawater acidification condition. Results from the short-term pH exposure experiment revealed that the photosynthetic rates of both species remained unaffected by acute pH changes, indicating their tolerance to varying pH. Nevertheless, it is crucial to consider dynamic pH when predicting changes in primary production in coastal waters, given the interplay of various environmental drivers.

Identification of KU-55933 as an anti-atherosclerosis compound by using a hemodynamic-based high-throughput drug screening platform.

Several compounds have been used for atherosclerosis treatment, including clinical trials; however, no anti-atherosclerotic drugs based on hemodynamic force-mediated atherogenesis have been discovered. Our previous studies demonstrated that "small mothers against decapentaplegic homolog 1/5" (Smad1/5) is a convergent signaling molecule for chemical [e.g., bone morphogenetic proteins (BMPs)] and mechanical (e.g., disturbed flow) stimulations and hence may serve as a promising hemodynamic-based target for anti-atherosclerosis drug development. The goal of this study was to develop a high-throughput screening (HTS) platform to identify potential compounds that can inhibit disturbed flow- and BMP-induced Smad1/5 activation and atherosclerosis. Through HTS using a Smad1/5 downstream target inhibitor of DNA binding 1 (Id-1) as a luciferase reporter, we demonstrated that KU-55933 and Apicidin suppressed Id-1 expression in AD-293 cells. KU-55933 (10 µM), Apicidin (10 µM), and the combination of half doses of each [1/2(K + A)] inhibited disturbed flow- and BMP4-induced Smad1/5 activation in human vascular endothelial cells (ECs). KU-55933, Apicidin, and 1/2(K + A) treatments caused 50.6%, 47.4%, and 73.3% inhibitions of EC proliferation induced by disturbed flow, respectively, whereas EC inflammation was only suppressed by KU-55933 and 1/2(K + A), but not Apicidin alone. Administrations of KU-55933 and 1/2(K + A) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in ECs in athero-susceptible regions, thereby suppressing endothelial proliferation and inflammation, with the attenuation of atherosclerotic lesions in these mice. A unique drug screening platform has been developed to demonstrate that KU-55933 and its combination with Apicidin are promising therapeutic compounds for atherosclerosis based on hemodynamic considerations.

Extended application of PGT-M strategies for small pathogenic CNVs.

PURPOSE: The preimplantation genetic testing for aneuploidy (PGT-A) platform is not currently available for small copy-number variants (CNVs), especially those < 1 Mb. Through strategies used in PGT for monogenic disease (PGT-M), this study intended to perform PGT for families with small pathogenic CNVs. METHODS: Couples who carried small pathogenic CNVs and underwent PGT at the Reproductive and Genetic Hospital of CITIC-Xiangya (Hunan, China) between November 2019 and April 2023 were included in this study. Haplotype analysis was performed through two platforms (targeted sequencing and whole-genome arrays) to identify the unaffected embryos, which were subjected to transplantation. Prenatal diagnosis using amniotic fluid was performed during 18-20 weeks of pregnancy. RESULTS: PGT was successfully performed for 20 small CNVs (15 microdeletions and 5 microduplications) in 20 families. These CNVs distributed on chromosomes 1, 2, 6, 7, 13, 15, 16, and X with sizes ranging from 57 to 2120 kb. Three haplotyping-based PGT-M strategies were applied. A total of 89 embryos were identified in 25 PGT cycles for the 20 families. The diagnostic yield was 98.9% (88/89). Nineteen transfers were performed for 17 women, resulting in a 78.9% (15/19) clinical pregnancy rate after each transplantation. Of the nine women who had healthy babies, eight accepted prenatal diagnosis and the results showed no related pathogenic CNVs. CONCLUSION: Our results show that the extended haplotyping-based PGT-M strategy application for small pathogenic CNVs compensated for the insufficient resolution of PGT-A. These three PGT-M strategies could be applied to couples with small pathogenic CNVs.

Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics.

Organic fluorescent molecules with emission in the second near-infrared (NIR-II) biological window have aroused increasing investigation in cancer phototheranostics. Among these studies, Benzobisthiadiazole (BBT), with high electron affinity, is widely utilized as the electron acceptor in constructing donor-acceptor-donor (D-A-D) structured fluorophores with intensive near-infrared (NIR) absorption and NIR-II fluorescence. Until now, numerous BBT-based NIR-II dyes have been employed in tumor phototheranostics due to their exceptional structure tunability, biocompatibility, and photophysical properties. This review systematically overviews the research progress of BBT-based small molecular NIR-II dyes and focuses on molecule design and bioapplications. First, the molecular engineering strategies to fine-tune the photophysical properties in constructing the high-performance BBT-based NIR-II fluorophores are discussed in detail. Then, their biological applications in optical imaging and phototherapy are highlighted. Finally, the current challenges and future prospects of BBT-based NIR-II fluorescent dyes are also summarized. This review is believed to significantly promote the further progress of BBT-derived NIR-II fluorophores for cancer phototheranostics.

Deleterious variants in X-linked RHOXF1 cause male infertility with oligo- and azoospermia.

Oligozoospermia and azoospermia are two common phenotypes of male infertility characterized by massive sperm defects owing to failure of spermatogenesis. The deleterious impact of candidate variants with male infertility is to be explored. In our study, we identified three hemizygous missense variants (c.388G>A: p.V130M, c.272C>T: p.A91V, and c.467C>T: p.A156V) and one hemizygous nonsense variant (c.478C>T: p.R160X) in the Rhox homeobox family member 1 gene (RHOXF1) in four unrelated cases from a cohort of 1201 infertile Chinese men with oligo- and azoospermia using whole-exome sequencing and Sanger sequencing. RHOXF1 was absent in the testicular biopsy of one patient (c.388G>A: p.V130M) whose histological analysis showed a phenotype of Sertoli cell-only syndrome. In vitro experiments indicated that RHOXF1 mutations significantly reduced the content of RHOXF1 protein in HEK293T cells. Specifically, the p.V130M, p.A156V, and p.R160X mutants of RHOXF1 also led to increased RHOXF1 accumulation in cytoplasmic particles. Luciferase assays revealed that p.V130M and p.R160X mutants may disrupt downstream spermatogenesis by perturbing the regulation of doublesex and mab-3 related transcription factor 1 (DMRT1) promoter activity. Furthermore, ICSI treatment could be beneficial in the context of oligozoospermia caused by RHOXF1 mutations. In conclusion, our findings collectively identified mutated RHOXF1 to be a disease-causing X-linked gene in human oligo- and azoospermia.

Positively Charged Silver and Gold Nanoparticles with Controllable Size Distribution for SERS Detection of Negatively Charged Molecules.

Surface-enhanced Raman spectroscopy (SERS) has been demonstrated as an ultrasensitive tool for various molecules. However, for the negatively charged molecules, the widely used SERS substrate [negatively charged Ag and Au nanoparticles (Ag or Au NPs (-)] showed either low sensitivity or poor stability. The best solution is to synthesize positively charged silver or gold nanoparticles [Ag or Au NPs (+)] with high stability and excellent SERS performance, which are currently unavailable. To this end, we revitalized the strategy of "charge reversal and seed growth". By selection of ascorbic acid as the reductant and surfactant, the surface charge of Ag or Au NP (-) seeds is adjusted to a balanced state, where the surface charge is negative enough to satisfy the stabilization of the NPs (-) but does not hinder the subsequent charge reversal. By optimization of the chain length and electric charge of polyamine molecules, the highly stable and size-controllable uniform Ag NPs (+) and Au NPs (+) were seed-growth synthesized with high reproducibility. More importantly, the SERS performance of both Ag NPs (+) and Au NPs (+) achieved the trace detection of negatively charged molecules at the level of 1 µg/L, demonstrating an improved SERS sensitivity of up to 3 orders of magnitude compared to the previously reported sensitivity. Promisingly, the introduction of polyamine-capped Ag NPs (+) and Au NPs (+) as SERS substrates with high stability (1 year shelf life) will significantly broaden the application of SERS.

On practicing magicine, from wonder to care: A systematic review of studies that apply magic in healthcare.

RATIONALE: Magic, traditionally perceived as entertainment, has been increasingly employed in healthcare to enhance health and well-being. Despite its potential benefits across various dimensions of health, including biological, psychological, and social, a comprehensive review highlighting its broad applications in healthcare remains unexplored. OBJECTIVE: This study aims to explore the diverse uses of magic within healthcare, progressing from entertainment to integral medical care, termed "magicine." METHODS: This systematic review adopted a narrative synthesis approach, and an extensive database search was conducted including Embase Classic & Embase, MEDLINE (Ovid), Scopus, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and CINAHL (EBSCOhost), from the earliest records to 22 June 2023. Potential applications of magic in healthcare were explored with an unrestricted search strategy. A quality assessment was conducted using the Mixed Methods Appraisal Tool. (Registration: PROSPERO number CRD42023417122.) RESULTS: This review identified 82 journal articles, including 11 randomized controlled trials, four quasi-experimental designs, 10 pre-experimental designs, five qualitative studies, three mixed methods studies, two observational studies, five review articles, and 42 commentaries. The review resulted in the conception of "magicine ennead" - nine diverse areas where magic can be applied in healthcare including physical rehabilitation, cognitive training, psychotherapy, humor therapy, distraction therapy, social skills, health education, doctor-patient relationships, and surgical techniques. These applications demonstrate the potential of magic to enhance health outcomes for the general population and improve the clinical practice of healthcare professionals. CONCLUSIONS: Magic in healthcare shows potential for varied applications, and a deeper understanding of these applications could lead to optimized and cost-efficient intervention programs. Given the heterogeneity and varied methodological quality of the current research, future studies necessitate the adoption of rigorous designs with active controls.

Clinical characteristics and outcomes of liver transplant recipients infected by Omicron during the opening up of the dynamic zero-coronavirus disease policy in China: A prospective, observational study.

We analyzed the characteristics, risk factors, outcomes, and post-coronavirus disease 2019 (COVID-19) symptoms in liver transplant recipients in China's late 2022 COVID-19 wave. Recipients with COVID-19 were enrolled from December 1, 2022, to January 31, 2023, and followed up until May 31, 2023. Baseline and characteristic data were collected. A total of 930 recipients were included, with a vaccination rate (non-mRNA) of 40.0%. Among 726 (78.1%) recipients with COVID-19, 641 (88.3%) patients were treated at home, 81 (11.2%) patients required hospitalization in general wards, 4 (0.6%) patients required intensive care, and 1 (0.1%) patient died because of COVID-19. Severe acute respiratory syndrome coronavirus 2 infection was related to close contact with confirmed cases (P < .001) and the condition of end-stage kidney disease (P < .046). Older age, male sex, less vaccination, and hypertension were independent risk factors for hospitalization. Fatigue (36.9%) was the most common symptom post-COVID-19, followed by memory loss (35.7%) and sleep disturbance (23.9%). Two doses of vaccines had a protective effect against these post-COVID-19 symptoms (P < .05). During this Omicron outbreak, liver transplant recipients were susceptible to COVID-19, with frequent hospitalization but low mortality. Two doses of non-mRNA COVID-19 vaccines could protect against liver transplant recipient hospitalization and post-COVID-19 symptoms.

Development and validation of a prognostic nomogram for patients with laryngeal cancer with synchronous or metachronous lung cancer.

BACKGROUND: The objective of this study was to examine the independent prognostic factors of laryngeal cancer with synchronous or metachronous lung cancer (LCSMLC), and to generate and verify a clinical prediction model. METHODS: In this study, laryngeal cancer alone and LCSMLC were defined using the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors of patients with LCSMLC were analyzed through univariate and multivariate logistic regression analysis. Independent prognostic factors were selected by Cox regression analyses, on the basis of which a nomogram was constructed using R code. Kaplan-Meier survival analyses were applied to test the application of a risk stratification system. Finally, we conducted a comparison of the American Joint Committee on Cancer (AJCC) staging system of laryngeal cancer with the new model of nomogram and risk stratification. For further validation of the nomogram, data from patients at two Chinese independent institutions were also analyzed. RESULTS: According to the eligibility criteria, 32 429 patients with laryngeal cancer alone and 641 patients with LCSMLC from the SEER database (the training cohort) and additional 61 patients from two Chinese independent institutions (the external validation cohort) were included for final analyses. Compared with patients with laryngeal cancer who did not have synchronous or metachronous lung cancer, age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC, while marriage, surgery, radiation therapy, and chemotherapy are not their risk factors. Age, two cancers' interval, pathological type, stage, surgery, radiation, primary lung site, and primary throat site were independent prognostic predictors of LCSMLC. The risk stratification system of high-, medium-, and low-risk groups significantly distinguished the prognosis in different patients with LCSMLC, regardless of the training cohort or the validation cohort. Compared with the 6th AJCC TNM stage of laryngeal cancer, the new model of nomogram and risk stratification showed an improved net benefit. CONCLUSIONS: Age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC. An individualized clinical prognostic predictive model by nomogram was generated and validated, which showed superior prediction ability for LCSMLC.

Structural Characterization and Anticoagulant Activities of a Keratan Sulfate-like Polysaccharide from the Sea Cucumber Holothuria fuscopunctata.

A sulfated polysaccharide (AG) was extracted and isolated from the sea cucumber H. fuscopunctata, consisting of GlcNAc, GalNAc, Gal, Fuc and lacking any uronic acid residues. Importantly, several chemical depolymerization methods were used to elucidate the structure of the AG through a bottom-up strategy. A highly sulfated galactose (oAG-1) and two disaccharides labeled with 2,5-anhydro-D-mannose (oAG-2, oAG-3) were obtained from the deaminative depolymerized product along with the structures of the disaccharide derivatives (oAG-4~oAG-6) identified from the free radical depolymerized product, suggesting that the repeating building blocks in a natural AG should comprise the disaccharide ß-D-GalS-1,4-D-GlcNAc6S. The possible disaccharide side chains (bAG-1) were obtained with mild acid hydrolysis. Thus, a natural AG may consist of a keratan sulfate-like (KS-like) glycosaminoglycan with diverse modifications, including the sulfation types of the Gal residue and the possible disaccharide branches α-D-GalNAc4S6S-1,2-α/ß-L-Fuc3S linked to the KS-like chain. Additionally, the anticoagulant activities of the AG and its depolymerized products (dAG1-9) were evaluated in vitro using normal human plasma. The AG could prolong activated partial thromboplastin time (APTT) in a dose-dependent manner, and the activity potency was positively related to the chain length. The AG and dAG1-dAG3 could prolong thrombin time (TT), while they had little effect on prothrombin time (PT). The results indicate that the AG could inhibit the intrinsic and common coagulation pathways.

Exploring the potential mechanisms of Tongmai Jiangtang capsules in treating diabetic nephropathy through multi-dimensional data.

Background: Diabetic nephropathy (DN) is a prevalent and debilitating disease that represents the leading cause of chronic kidney disease which imposes public health challenges Tongmai Jiangtang capsule (TMJT) is commonly used for the treatment of DN, albeit its underlying mechanisms of action are still elusive. Methods: This study retrieved databases to identify the components and collect the targets of TMJT and DN. Target networks were constructed to screen the core components and targets. Samples from the GEO database were utilized to perform analyses of targets and immune cells and obtain significantly differentially expressed core genes (SDECGs). We also selected a machine learning model to screen the feature genes and construct a nomogram. Furthermore, molecular docking, another GEO dataset, and Mendelian randomization (MR) were utilized for preliminary validation. We subsequently clustered the samples based on SDECG expression and consensus clustering and performed analyses between the clusters. Finally, we scored the SDECG score and analyzed the differences between clusters. Results: This study identified 13 SDECGs between DN and normal groups which positively regulated immune cells. We also identified five feature genes (CD40LG, EP300, IL1B, GAPDH, and EGF) which were used to construct a nomogram. MR analysis indicated a causal link between elevated IL1B levels and an increased risk of DN. Clustering analysis divided DN samples into four groups, among which, C1 and CI were mainly highly expressed and most immune cells were up-regulated. C2 and CII were the opposite. Finally, we found significant differences in SDECG scores between C1 and C2, CI and CII, respectively. Conclusion: TMJT may alleviate DN via core components (e.g. Denudatin B, hancinol, hirudinoidine A) targeting SDECGs (e.g. SRC, EGF, GAPDH), with the involvement of feature genes and modulation of immune and inflammation-related pathways. These findings have potential implications for clinical practice and future investigations.

In Vitro Anti-Tumor and Hypoglycemic Effects of Total Flavonoids from Willow Buds.

Salix babylonica L. is a species of willow tree that is widely cultivated worldwide as an ornamental plant, but its medicinal resources have not yet been reasonably developed or utilized. Herein, we extracted and purified the total flavonoids from willow buds (PTFW) for component analysis in order to evaluate their in vitro anti-tumor and hypoglycemic activities. Through Q-Orbitrap LC-MS/MS analysis, a total of 10 flavonoid compounds were identified (including flavones, flavan-3-ols, and flavonols). The inhibitory effects of PTFW on the proliferation of cervical cancer HeLa cells, colon cancer HT-29 cells, and breast cancer MCF7 cells were evaluated using an MTT assay. Moreover, the hypoglycemic activity of PTFW was determined by investigating the inhibitory effects of PTFW on α-amylase and α-glucosidase. The results indicated that PTFW significantly suppressed the proliferation of HeLa cells, HT-29 cells, and MCF7 cells, with IC50 values of 1.432, 0.3476, and 2.297 mg/mL, respectively. PTFW, at different concentrations, had certain inhibitory effects on α-amylase and α-glucosidase, with IC50 values of 2.94 mg/mL and 1.87 mg/mL, respectively. In conclusion, PTFW at different doses exhibits anti-proliferation effects on all three types of cancer cells, particularly on HT-29 cells, and also shows significant hypoglycemic effects. Willow buds have the potential to be used in functional food and pharmaceutical industries.

Characterization of genes involved in micronutrients and toxic metals detoxification in Brassica napus by genome-wide cDNA library screening.

Stresses caused by deficiency/excess of mineral nutrients or of pollution of toxic metals have already become a primary factor in limiting crop production worldwide. Genes involved in minerals and toxic metals accumulation/tolerance could be potential candidates for improving crop plants with enhanced nutritional efficiency and environmental adaptability. In this study, we first generated a high-quality yeast expression cDNA library of Brassica napus (Westar), and 46 genes mediating excess micronutrients and toxic metals detoxification were screened using the yeast genetic complementation system, including 11, 5, 6, 14, 6, and 5 genes involved in cadmium (Cd), zinc (Zn), iron (Fe), manganese (Mn), boron (B), and copper (Cu) tolerance, respectively. Characterization of genes mediating excess ions stress resistance in this study is beneficial for us to further understand ions homeostasis in B. napus.