Effect of quantitative consciousness index on seizure parameters during electroconvulsive therapy in patients with major depressive disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is both an effective treatment for patients with major depressive disorder (MDD) and a noxious stimulus. Although some studies have explored the effect of sedation depth on seizure parameters in ECT, there is little research on the noxious stimulation response to ECT. In this study, we used two electroencephalography (EEG)-derived indices, the quantitative consciousness (qCON) index and quantitative nociceptive (qNOX) index, to monitor sedation, hypnosis, and noxious stimulation response in patients with MDD undergoing acute ECT. AIM: To evaluate the effect of anesthesia depth based on the qCON and qNOX indices on seizure parameters. METHODS: Patients with MDD (n = 24) underwent acute bilateral temporal ECT under propofol anesthesia. Before ECT, the patients were randomly divided into three groups according to qCON scores (qCON60-70, qCON50-60, and qCON40-50). Continuous qCON monitoring was performed 3 minutes before and during ECT, and the qCON, qNOX, vital signs, EEG seizure parameters, and complications during the recovery period were recorded. The 24-item Hamilton Rating Scale for Depression, Zung's Self-rating Depression Scale, and Montreal Cognitive Assessment scores were evaluated before the first ECT session, after the fourth ECT session, and after the full course of ECT. RESULTS: A total of 193 ECT sessions were performed on 24 participants. The qCON index significantly affected the EEG seizure duration, peak mid-ictal amplitude, and maximum heart rate during ECT (P < 0.05). The qNOX index significantly affected the post-ictal suppression index (P < 0.05). Age, number of ECT sessions, and anesthetic-ECT time intervals also had a significant effect on EEG seizure parameters (P < 0.05). However, there were no significant differences in complications, 24-item Hamilton Rating Scale for Depression scores, Zung's Self-rating Depression Scale scores, or Montreal Cognitive Assessment scores among the three groups (P > 0.05). CONCLUSION: Electrical stimulation at a qCON index of 60-70 resulted in better EEG seizure parameters without increasing complications in patients with MDD undergoing bilateral temporal ECT under propofol anesthesia.

A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections and has become increasingly resistant to multiple antibiotics. However, development of novel classes of antibacterial agents against multidrug-resistant P. aeruginosa is extremely difficult. Herein we develop a semisynthetic oligomannuronic acid-based glycoconjugate vaccine that confers broad protection against infections of both mucoid and nonmucoid strains of P. aeruginosa. The well-defined glycoconjugate vaccine formulated with Freund's adjuvant (FA) employing a highly conserved antigen elicited a strong and specific immune response and protected mice against both mucoid and nonmucoid strains of P. aeruginosa. The resulting antibodies recognized different strains of P. aeruginosa and mediated the opsonic killing of the bacteria at varied levels depending on the amount of alginate expressed on the surface of the strains. Vaccination with the glycoconjugate vaccine plus FA significantly promoted the pulmonary and blood clearance of the mucoid PAC1 strain of P. aeruginosa and considerably improved the survival rates of mice against the nonmucoid PAO1 strain of P. aeruginosa. Thus, the semisynthetic glycoconjugate is a promising vaccine that may provide broad protection against both types of P. aeruginosa.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Rationally Integrating Charge-Transfer Cocrystal and Ni(II) Organometallics for Visualized Photo/Thermochromic Sensors.

Smart materials demonstrate fascinating responses to environmental physical/chemical stimuli, including thermal, photonic, electronic, humidity, or magnetic stimuli, which have attracted intensive interest in material chemistry. However, their limited/harsh stimuli-responsive behavior or sophisticated postprocessing leads to enormous challenges for practical applications. Herein, we rationally designed and synthesized thermochromic Ni(II) organometallic [(C2H5)2NH2]2NiCl4-xBrx via a facile mechanochemical strategy, which demonstrated a reversible switch from yellow to blue color with a tunable phase-transition temperature from 75.6 to 61.7 °C. The simple electrospinning technology was applied to fabricate thermochromic Ni(II) organometallic-based nanofiber membranes for temperature monitoring. Furthermore, the organic charge-transfer cocrystal with a wide spectral absorption of 300-1950 nm and a high-efficiency photothermal conversion was combined with thermochromic Ni(II) organometallics for the desired dual-stimuli photo/thermochromism. This work supplies a new strategy for realizing multiple stimuli-responsive applications, such as thermal/light sensor displays and information storage.

Using ultrasound radiomics to forecast adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

OBJECTIVE: Exploring the performance of ultrasound-based radiomics in forecasting major adverse cardiovascular events (MACE) within 1 year following percutaneous coronary intervention (PCI) of acute coronary syndrome (ACS) patients. METHODS: In this research, 161 ACS patients who underwent PCI were included (114 patients were randomly assigned to the training set and 47 patients to the validation set). Every patient received echocardiography 3-7 days after PCI and followed up for 1 year. The radiomics features related to MACE occurrence were extracted and selected to formulate the RAD score. Building ultrasound personalized model by incorporating RAD score, LVEF, LVGLS, and NT-ProBNP. The model's capacity to predict was tested using ROC curves. RESULTS: Multifactorial logistic regression analysis of RAD score with clinical data and echocardiographic parameters indicated RAD score and LVGLS as independent risk factors for the occurrence of MACE. The RAD score predicted MACE, with AUC values of 0.85 and 0.86 in the training and validation sets. The ultrasound personalized model had a superior ability to predict the occurrence of MACE, with AUC values of 0.88 and 0.92, which were higher than those of the clinical model (with AUC of 0.72 and 0.80) without RAD score (Z = 3.711, 2.043, P < .001, P = .041). Furthermore, DCA indicated that the ultrasound personalization model presented a more favorable net clinical benefit. CONCLUSIONS: Ultrasound radiomics can be a reliable tool to predict the incidence of MACE after PCI in patients with ACS and provides quantifiable data for personalized clinical treatment.

Sub-regional Radiomics Analysis for Predicting Metastasis Risk in Clear Cell Renal Cell Carcinoma: A Multicenter Retrospective Study.

RATIONALE AND OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm affecting the kidney, exhibiting a dismal prognosis in metastatic instances. Elucidating the composition of ccRCC holds promise for the discovery of highly sensitive biomarkers. Our objective was to utilize habitat imaging techniques and integrate multimodal data to precisely predict the risk of metastasis, ultimately enabling early intervention and enhancing patient survival rates. MATERIAL AND METHODS: A retrospective analysis was performed on a cohort of 263 patients with ccRCC from three hospitals between April 2013 and March 2021. Preoperative CT images, ultrasound images, and clinical data were comprehensively analyzed. Patients from two campuses of Qilu Hospital of Shandong University were assigned to the training dataset, while the third hospital served as the independent testing dataset. A robust consensus clustering method was used to classify the primary tumor space into distinct sub-regions (i.e., habitats) using contrast-enhanced CT images. Radiomic features were extracted from these tumor sub-regions and subsequently reduced to identify meaningful features for constructing a predictive model for ccRCC metastasis risk assessment. In addition, the potential value of radiomics in predicting ccRCC metastasis risk was explored by integrating ultrasound image features and clinical data to construct and compare alternative models. RESULTS: In this study, we performed k-means clustering within the tumor region to generate three distinct tumor subregions. We quantified the Hounsfiled Unit (HU) value, volume fraction, and distribution of high- and low-risk groups in each subregion. Our investigation focused on 252 patients with Habitat1 + Habitat3 to assess the discriminative power of these two subregions. We then developed a risk prediction model for ccRCC metastasis risk classification based on radiomic features extracted from CT and ultrasound images, and clinical data. The Combined model and the CT_Habitat3 model showed AUC values of 0.935 [95%CI: 0.902-0.968] and 0.934 [95%CI: 0.902-0.966], respectively, in the training dataset, while in the independent testing dataset, they achieved AUC values of 0.891 [95%CI: 0.794-0.988] and 0.903 [95%CI: 0.819-0.987], respectively. CONCLUSION: We have identified a non-invasive imaging predictor and the proposed sub-regional radiomics model can accurately predict the risk of metastasis in ccRCC. This predictive tool has potential for clinical application to refine individualized treatment strategies for patients with ccRCC.

Development and validation of a patient-centered communication scale for nurses.

BACKGROUND: Patient-centered care aims to prevent disease and promote well-being by actively involving patients in treatment and decision-making that is based on respecting the patients and their families. However, no scales have been developed to assess patient-centered care from the nurse's perspective. This study aimed to develop a scale to measure nurses' level of patient-centered communication and confirm its validity and reliability. METHODS: A methodological cross-sectional study was adopted to develop and validate the Patient-Centered Communication Scale (PCCS). The items were developed through a literature review and online interviews with nurses. Content validity was assessed by experts and the content validity index was calculated. A pretest of the questionnaire was conducted with 10 clinical nurses. To evaluate the factor structure and internal consistency reliability, the PCCS was administered online to 325 nurses in South Korea. Data were analyzed using descriptive statistics, explanatory factor analysis (EFA), and confirmatory factor analysis (CFA). RESULTS: The final instrument consisted of 12 items and three factors: (1) information sharing, (2) patient-as-person, and (3) therapeutic alliance. EFA revealed a distinct three-factor structure, explaining 59.0% of the total variance. CFA confirmed the adequacy of the model fit and validated the inclusion of the final items. The Cronbach's alpha values ranged from 0.60 to 0.77, indicating acceptable internal consistency. Convergent validity was evidenced by the correlation between the PCCS and a measure of interpersonal communication competence. CONCLUSIONS: The 12-item PCCS showed good reliability, construct validity, and convergent validity. The scale has utility for measuring the level of patient-centered communication skills in nurses.

Glycolysis and chemoresistance in acute myeloid leukemia.

While traditional high-dose chemotherapy can effectively prolong the overall survival of acute myeloid leukemia (AML) patients and contribute to better prognostic outcomes, the advent of chemoresistance is a persistent challenge to effective AML management in the clinic. The therapeutic resistance is thought to emerge owing to the heterogeneous and adaptable nature of tumor cells when exposed to exogenous stimuli. Recent studies have focused on exploring metabolic changes that may afford novel opportunities to treat AML, with a particular focus on glycolytic metabolism. The Warburg effect, a hallmark of cancer, refers to metabolism of glucose through glycolysis under normoxic conditions, which contributes to the development of chemoresistance. Despite the key significance of this metabolic process in the context of malignant transformation, the underlying molecular mechanisms linking glycolysis to chemoresistance in AML remain incompletely understood. This review offers an overview of the current status of research focused on the relationship between glycolytic metabolism and AML resistance to chemotherapy, with a particular focus on the contributions of glucose transporters, key glycolytic enzymes, signaling pathways, non-coding RNAs, and the tumor microenvironment to this relationship. Together, this article will provide a foundation for the selection of novel therapeutic targets and the formulation of new approaches to treating AML.

Novel goose parvovirus VP1 targets IRF7 protein to block the type I interferon upstream signaling pathway.

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak IFN-ß induction. NGPV impedes the expression of IFN-ß and downstream interferon-stimulated genes, thereby reducing the secretion of IFN-ß induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit IFN-ß expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of IFN-ß, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host's innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein.

Coptisine exerts anti-tumour effects in triple-negative breast cancer by targeting mitochondrial complex I.

BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to limited therapeutic options. Recent studies have shown that TNBC is highly dependent on mitochondrial oxidative phosphorylation. The aim of this study was to investigate the potential of coptisine, a novel compound that inhibits the complex I of the mitochondrial electron transport chain (ETC), as a treatment for TNBC. EXPERIMENTAL APPROACH: In this study, mitochondrial metabolism in TNBC was analysed by bioinformatics. In vitro and in vivo experiments (in mice) were conducted to evaluate the potential of coptisine as an ETC complex I-targeting therapeutic agent and to investigate the molecular mechanisms underlying coptisine-induced mitochondrial dysfunction. The therapeutic effect of coptisine was assessed in TNBC cells and xenograft mouse model. KEY RESULTS: We demonstrated that mitochondrial ETC I was responsible for this metabolic vulnerability in TNBC. Furthermore, a naturally occurring compound, coptisine, exhibited specific inhibitory activity against this complex I. Treatment with coptisine significantly inhibited mitochondrial functions, reprogrammed cellular metabolism, induced apoptosis and ultimately inhibited the proliferation of TNBC cells. Additionally, coptisine administration induced prominent growth inhibition that was dependent on the presence of a functional complex I in xenograft mouse models. CONCLUSION AND IMPLICATIONS: Altogether, these findings suggest the promising potential of coptisine as a potent ETC complex I inhibitor to target the metabolic vulnerability of TNBC.

How health seeking behavior develops in patients with type 2 diabetes: a qualitative study based on health belief model in China.

Background: Type 2 diabetes(T2DM) is a global health problem which is accompanied with multi-systemic complications, and associated with long-term health burden and economic burden. Effective health seeking behavior (HSB) refers to reasonably utilize health resources, effectively prevent and treat diseases, and maintain health. Effective health seeking behavior (HSB) is vital to mitigate the risk of T2DM complications. However, health seeking behavior for T2DM patients remains sub-optimal worldwide. Objective: The study aimed to explore the internal logic of how health seeking behavior of T2DM patients develops and the influencing factors of health seeking behavior. With a view to provide a reference basis for improving the health seeking behavior situation of T2DM patients. Methods: This study was conducted at an integrated tertiary hospital in China. People who were diagnosed with T2DM, capable of expressing clearly and had no mental illness, were approached based on a purposive sampling. The experience of T2DM and health seeking behavior were collected via in-depth interviews. A theory-driven thematic analysis based on Health Belief Model (HBM) was applied for data analysis. Inductive reasoning was used to identify emerging themes which were not included in HBM. Results: 26 patients with T2DM were included in the current study. Seven themes were identified, including: (1) T2DM diagnosis and severity; (2) T2DM treatment and management; (3) Perceived susceptibility of diabetes progression; (4) Perceived severity of diabetes progression; (5) Perceived benefits of health seeking behavior; (6) Perceived barriers of health seeking behavior; (7) Perception of behavioral cues. Generally, patients with T2DM lacked reliable sources of information, considered T2DM to be slow-progressing and without posing an immediate threat to life. Consequently, they did not fully grasp the long-term risks associated with T2DM or the protective effects of health seeking behavior. Conclusion: This study highlighted the challenges in health seeking behavior for patients with T2DM. It suggested that future interventions and strategies should involve multi-faceted approaches, targeting healthcare providers (HCPs), patients with T2DM, and their support networks. This comprehensive strategy can help patients better understand their condition and the importance of effective health seeking behavior. Ultimately, enhancing their capacity for adopting appropriate health-seeking practices.

Polyamine Anabolism Promotes Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA-based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy-induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF-1 in response to chemotherapy. Genetic inhibition of HIF-1-controlled polyamine anabolism blocks chemotherapy-induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF-1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy-induced HIF-1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.

Ultrasound-Responsive Nanodelivery System of GPC3-Targeting and Sonosensitizer for Visualized Hepatocellular Carcinoma Therapy.

Purpose: The incidence of hepatocellular carcinoma (HCC) is continuously increasing, and the mortality rate remains high. Thus, more effective strategies are needed to improve the treatment of HCC. Methods: In this study, we report the use of a visualized glypican-3 (GPC3)-targeting nanodelivery system (named GC-NBs) in combination with sonodynamic therapy (SDT) to enhance the therapeutic efficacy for treating HCC. The obtained nanodelivery system could actively target hepatocellular carcinoma cells and achieve ultrasound imaging through phase changes into nanobubbles under low-intensity ultrasound irradiation. Meanwhile, the released chlorine e6 (Ce6) after the nanobubbles collapse could lead to the generation of reactive oxygen species (ROS) under ultrasound irradiation to induce SDT. Results: Both in vitro and in vivo experiments have shown that GC-NBs can accumulate in tumour areas and achieve sonodynamic antitumour therapy under the navigation action of glypican-3-antibody (GPC3-Ab). Furthermore, in vitro and in vivo experiments did not show significant biological toxicity of the nanodelivery system. Moreover, GC-NBs can be imaged with ultrasound, providing personalized treatment monitoring. Conclusion: GC-NBs enable a visualized antitumour strategy from a targeted sonodynamic perspective by combining tumour-specific targeting and stimuli-responsive controlled release into a single system.

Evaluating the role of DNA methyltransferases in trophoblast fusion and preeclampsia development: Insights from methylation-regulated genes.

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.

Utilization of blockchain technology in personalized nursing: A scoping review.

AIM AND OBJECTIVE: This study aims to scrutinize the interconnected concepts, prevailing landscape and efficacy of personalized nursing within the framework of blockchain technology and to proffer a roadmap for prospective scholarly inquiries. BACKGROUND: The ethos of personalized nursing as a paradigm grounded in human-centered care has been venerated as the pinnacle of nursing practice. Recent years have witnessed the emergence of groundbreaking technologies, notably blockchain, which have set the stage for the actualization of personalized nursing care. Nevertheless, a lacuna persists in the holistic comprehension surrounding the integration of blockchain technology within the domain of personalized nursing. DESIGN AND METHODS: We considered studies published in English from 2018 to the present. Databases searched included CINAHL, Pubmed, MEDLINE, Scopus. Sources of grey literature that were searched included ProQuest Dissertations and Theses. The eligibility of the studies was independently appraised by a pair of researchers. The findings are delineated through narratives and tabular presentations. RESULTS: The narrative findings are stratified into three primary domains: (1) the theoretical underpinnings of personalized nursing vis-à-vis the integration of blockchain technology; (2) delineation of the specific domains within nursing where blockchain applications are germane to personalized nursing; and (3) the demonstrable impact of blockchain technology on the efficacy of personalized nursing. CONCLUSION: Blockchain technology has wrought profound transformations in the landscape of personalized nursing. As blockchain technology continues to evolve, future scholarship necessitates elucidation on the conceptual intricacies of personalized nursing interfaced with blockchain technology, and broadening of the research purview to encompass a comprehensive understanding of the various applications of personalized nursing. REPORTING METHOD: This scoping review adhered to relevant EQUATOR guidelines and used the PRISMA-ScR.

Screening potential antileukemia agents from duckweed: Integration of chemical profiling, network pharmacology, and experimental validation.

INTRODUCTION: The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated. OBJECTIVES: The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation. METHODS: First, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell-xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation. RESULTS: A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z-VAD). CONCLUSION: Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.

Streptomyces albipurpureus sp. nov., a novel actinobacterium with antimicrobial activity isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don.

A novel actinobacterium, designated strain CWNU-1T, was isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don and examined using a polyphasic taxonomic approach. The organism developed pale blue aerial mycelia that was simply branched and terminated in open or closed coils of three or more volutions on International Streptomyces Project 3 agar. Spores were ellipsoidal to cylindrical with wrinkled surfaces. The strain showed high 16S rRNA gene sequence similarity to Streptomyces kurssanovii NBRC 13192T (98.8 %), Streptomyces xantholiticus NBRC 13354T (98.7 %) and Streptomyces peucetius JCM 9920T (98.6 %). The phylogenetic result based on 16S rRNA gene and genome sequences clearly demonstrated that strain CWNU-1T formed an independent phylogenetic lineage. On the basis of orthologous average nucleotide identity, CWNU-1T was most closely related to Streptomyces inusitatus NBRC 13601T with 79.3 % identity. The results of the digital DNA-DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with S. inusitatus NBRC 13601T (25.3 %). With reference to phenotypic characteristics, phylogenetic data, orthologous average nucleotide identity and digital DNA-DNA hybridization results, strain CWNU-1T was readily distinguished from its most closely related strains and classified as representing a novel species, for which the name Streptomyces albipurpureus sp. nov. is proposed. The type strain is CWNU-1T (=CGMCC 4.7758T=MCCC 1K07402T=JCM 35391T).

Microwave-assisted synthesis of highly sulfated mannuronate glycans as potential inhibitors against SARS-CoV-2.

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.

IL-33/NF-κB/ST2L/Rab37 positive-feedback loop promotes M2 macrophage to limit chemotherapeutic efficacy in lung cancer.

IL-33 is a danger signal that binds to its receptor ST2L to promote tumor progression. This study identifies the IL-33/ST2L positive-feedback loop and the trafficking of ST2L membrane presentation in macrophages that contribute to lung tumor progression. Mechanistically, IL-33 induces ST2L upregulation by activating NF-κB, which binds to the promoter region of the ST2L gene. Moreover, Rab37, a small GTPase involved in membrane trafficking, mediates ST2L trafficking to the plasma membrane of M2 macrophages. This IL-33/NF-κB/ST2L/Rab37 axis promotes positive-feedback loops that enhance ST2L expression and membrane trafficking in M2 macrophages. Notably, neutralizing antibodies against IL-33 or ST2L block NF-κB activity, suppress M2 macrophage polarization, and synergistically inhibit tumor growth when combined with cisplatin treatment in vitro/vivo. Clinically, Rab37+/ST2L+/CD206+ tumor-infiltrating M2 macrophages correlate with advanced-stage lung cancer patients with poor response to chemotherapy. These findings unveil a positive-feedback mechanism and provide a basis for IL-33/ST2L-targeting therapy for cancer.