Online LC-ESI-MS/MS comparative analysis of N/O-glycopatterns in human colostrum from different ethnic groups in Northwest China.

Human milk oligosaccharides, including free oligosaccharides and glycoconjugates, exert a key role in neonatal health and development. Changes in free oligosaccharides of milk from different ethnic groups have been documented. In this study, human milk was collected from Han, Hui, and Tibetan populations in northwest China, and differences in N/O-glycome among these three ethnic groups were systematically compared using online high-performance liquid chromatography-tandem mass spectrometry. Among the 63 detected N-glycans, 35 showed significant differences between the three ethnic groups (p < 0.05). Among the 70 detected O-glycans, four neutral O-glycans and six acidic O-glycans exhibited significant differences among the three ethnic groups (p < 0.05), with six acidic O-glycans reported for the first time. Overall, the extent of milk N/O-glycosylation was higher in the Han population than in the Hui or Tibetan groups. This trend was particularly pronounced for the main sialylated N/O-glycans. Except for sulfated O-glycans, which were higher in the milk from Tibetan mothers, the other types of N/O-glycans were present in similar proportions across all ethnic groups. Understanding the composition of N/O-glycans in human milk can help research on the structure-function relationship of glycans.

Tannins in Phyllanthus emblica L. improves cisplatin efficacy in lung cancer cells by boosting endoplasmic reticulum stress to trigger immunogenic cell death.

BACKGROUND: Lung cancer is one of the deadliest cancers world-wide and immunotherapy has been considered as a promising therapeutic strategy. Previously, our study found that tannins in Phyllanthus emblica L. (PTF) could inhibit the growth of tumor by activating the immune response in liver cancer, and also exhibited a cytotoxicity on human lung cancer cells A549, H460, H1703 in vitro. OBJECTIVE: To explore whether PTF inhibited the growth of lung cancer through its immune-regulating function and to clarify underlying mechanisms. METHODS: The induction of immunogenic cell death (ICD) were characterized by calreticulin exposure, extracellular ATP secretion, and High Mobility Group Box 1(HMGB1) release both in vivo using LLC-derived xenograft tumor model and in vitro using both mouse LLC and human A549 cancer cells. RESULTS: PTF inhibited lung cancer cells growth and tumorigenesis in vivo/vitro and promoted anti-tumor immune responses. We further found that PTF could induce ICD, which then activated Type I interferon responses and CXCL9/10-mediated chemotaxis. Mechanistically, PTF induced the formation of intracellular protein aggregates and following activation of PERK/ATF4/CHOP-dependent endoplasmic reticulum stress-related ICD. Moreover, PTF improved the antitumor efficacy of cisplatin by inducing ICD both in vitro and in vivo. Finally, we screened out 5 components from PTF, including gallocatechin, gallic acid, methyl gallate, ethyl gallate and ellagic acid, which could induce ICD in vitro and might be considered as the potential antitumor pharmacodynamic substances. CONCLUSION: In conclusion, PTF inhibits the growth of lung cancer by triggering ICD and remodeling the tumor microenvironment, suggesting that PTF may have promising prospects as an adjacent immunotherapy for cancers.

Impact of structurally diverse polysaccharides on colonic mucin O-glycosylation and gut microbiota.

Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of the colonic mucosa and gut microbiome were investigated in C57BL/6J mice fed six structurally diverse dietary polysaccharides and a mixture of six fibers. Dietary polysaccharides increased total O-glycans, mainly by stimulating neutral glycans. Highly branched arabinogalactan promoted terminally fucosylated core 1 O-glycans; whereas linear polysaccharides, including pectin, konjac glucomannan, inulin, and the fiber mixture, favored terminally di-fucosylated O-glycans. The last three polysaccharides also lowered the level of sulfated O-glycans and sialylated mono-fucosylated O-glycans. Varied monosaccharide composition in mixed polysaccharides had a synergistic beneficial effect, boosting fucosylated neutral glycans, decreasing acidic glycans, and stimulating microbial richness and diversity. Dietary polysaccharides containing arabinose and sulfate groups enhanced the relative abundances of Akkermansia and Muribaculaceae, respectively. The present comparison reveals the relationship between dietary polysaccharide structure, mucin O-glycan composition, and intestinal microorganisms.

Correction: Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Correction for 'Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration' by Shukai Wang et al., Food Funct., 2023, 14, 4607-4620, https://doi.org/10.1039/D2FO03685A.

Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Tumor-associated macrophages (TAMs) participate in tumorigenesis, growth, invasion as well as metastasis by facilitating an immunosuppressive tumor microenvironment. Reversing the pro-tumoral M2 phenotype of TAMs has become a hot spot in advancing cancer immunotherapy. In the current study, the content of Moringa oleifera leaf polysaccharides (MOLP) was determined and characterized, along with the anti-cancer mechanism of MOLP studied in a Lewis lung cancer (LLC) tumor-bearing mouse model and bone marrow-derived macrophages. The monosaccharide composition and gel permeation chromatography analyses show that MOLP are mainly composed of galactose, glucose, and arabinose, with approximately 17.35 kDa average molecular weight (Mw). In vivo studies demonstrate that MOLP convert TAMs from the immunosuppressive M2 phenotype to the antitumor M1 phenotype, thus inducing CXCL9 and CXCL10 expression and increasing T-cell infiltration in the tumor. Furthermore, macrophage depletion and T cell suppression demonstrated that the tumor suppressive effect of MOLP was reliant on reprogramming macrophage polarization and T cell infiltration. In vitro studies revealed that MOLP could induce the phenotypic switch from M2 macrophages to M1 by targeting TLR4. The current study highlights that MOLP are promising anticancer plant-derived polysaccharides with potential in modulating the immune microenvironment and have a bright application prospect in the immunotherapy of lung cancer.

Enhanced TSG stability through co-assembly with C3G: the mechanism behind processing Polygonum multiflorum Thunb with black beans via supramolecular analysis.

Elucidating the underlying mechanism of the processing of Chinese herbal medicine (CHM) is crucial and also challenging for the modernization of Traditional Chinese Medicine (TCM). Herein, inspired by the traditional method for processing the Chinese herb Polygonum multiflorum (PM) Thunb with excipient black beans, the representative herbal components trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-D-glucopyranoside (TSG) and cyanidin-3-O-ß-glucoside (C3G) from each herbal medicine were selected to investigate the processing mechanism at the supramolecular level. The co-assemblies of TSG/C3G were found to be formed, and their structure was characterized by electronic microscopy and a small angle X-ray scattering (SAXS) technique. In addition, the supramolecular interactions between TSG and C3G were fully probed with UV-Vis, fluorescence, XRD, and NMR spectroscopy. Molecular dynamics were further performed to simulate the assembly processes of TSG and C3G. Notably, the formation of TSG/C3G co-assemblies was found to significantly enhance the stability of TSG against light, Fe3+, and simulated intestinal fluids. The co-assembly of TSG and C3G that leads to supramolecular aggregates discovered here may imply the underlying mechanism of processing PM with black beans. Our results may also suggest that a new effective form of TCM is supramolecular aggregates rather than each component.

The Therapeutic Effect and the Potential Mechanism of Flavonoids and Phenolics of Moringa oleifera Lam. Leaves against Hyperuricemia Mice.

The aim of this study is to evaluate the anti-hyperuricemia effect and clarify the possible mechanisms of flavonoids and phenolics of MOL (MOL-FP) in mice. Hyperuricemia mice were generated via intraperitoneal (i.p.) administration of potassium oxonate (PO) and oral gavage (p.o.) of hypoxanthine (HX). Serum uric acid (UA), weight, serum XO activity, hepatic XO activity, urea nitrogen (BUN), creatinine (CRE), serum AST level, serum ALT level, mRNA expression of renal urate-anion transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), organic anion transporters 3 (OAT3), and ATP-binding cassette transporter G2 (ABCG2) were determined. The molecular docking was conducted using AutoDock Vina 1.2.0 to screen potential XO inhibitors in MOL-FP. Serum metabolomics was established to collect the metabolic profiles of mice and explore the metabolic changes that occurred after MOL-FP treatment. MOL-FP could notably reduce the serum UA level of hyperuricemia mice by inhibiting XO activity and regulating renal urate transporters. Molecular docking studies indicated that 5-p-coumaroylquinic acid, 3-p-coumaroylquinic acid, and catechin could be potential XO inhibitors. Besides, MOL-FP prevented the pathological process of hyperuricemia by regulating biomarkers associated with purine metabolism, amino acid metabolism, and lipid metabolism.

Characterization and Fine Mapping of qRPR1-3 and qRPR3-1, Two Major QTLs for Rind Penetrometer Resistance in Maize.

Stalk strength is one of the most important traits in maize, which affects stalk lodging resistance and, consequently, maize harvestable yield. Rind penetrometer resistance (RPR) as an effective and reliable measurement for evaluating maize stalk strength is positively correlated with stalk lodging resistance. In this study, one F2 and three F2:3 populations derived from the cross of inbred lines 3705I (the low RPR line) and LH277 (the high RPR line) were constructed for mapping quantitative trait loci (QTL), conferring RPR in maize. Fourteen RPR QTLs were identified in four environments and explained the phenotypic variation of RPR from 4.14 to 15.89%. By using a sequential fine-mapping strategy based on the progeny test, two major QTLs, qRPR1-3 and qRPR3-1, were narrowed down to 4-Mb and 550-kb genomic interval, respectively. The quantitative real-time PCR (qRT-PCR) assay was adopted to identify 12 candidate genes responsible for QTL qRPR3-1. These findings should facilitate the identification of the polymorphism loci underlying QTL qRPR3-1 and molecular breeding for RPR in maize.

Comparative Analysis of Transcriptomes of Diploid and Tetraploid Miscanthus lutarioriparius under Drought Stress.

Miscanthus lutarioriparius is a species of bioenergy crop unique to China. It is widely distributed in the south of China with high resistance to drought and salt stress. To date, the molecular mechanism of the adaption to drought stress in M. lutarioriparius is little known. In this study, RNA-seq technology was employed to analyze the transcriptome changes of diploid and tetraploid M. lutarioriparius after drought treatment. It was found that the number of differentially expressed genes in diploid M. lutarioriparius was much higher than tetraploid, whereas the tetraploid M. lutarioriparius may require fewer transcriptional changes. While the transcriptional changes in drought-tolerant tetraploid M. lutarioriparius are less than that of diploid, more known drought-tolerant pathways were significantly enriched than drought-sensitive diploid M. lutarioriparius. In addition, many drought-tolerance-related genes were constitutively and highly expressed in tetraploid under either normal condition or drought stress. These results together demonstrated that drought-tolerant tetraploid M. lutarioriparius, on the one hand, may preadapt to drought by constitutively overexpressing a series of drought-tolerant genes and, on the other hand, may adapt to drought by actively inducing other drought-tolerant-related pathways. Overall, this study could deepen our understanding of the molecular mechanism of drought-tolerance in bioenergy plants.

Comprehensive Characterization of the Function of Metabolic Genes and Establishment of a Prediction Model in Breast Cancer.

Background: Breast cancer (BC) is a highly heterogeneous disease with high morbidity and mortality. Its subtypes may have distinctly different biological behaviors, clinical outcomes, and therapeutic responses. The metabolic status of BC tissue is closely related to its progress. Therefore, we comprehensively characterized the function of metabolic genes in BC and identified new biomarkers to predict BC patients' prognoses. Methods: Metabolic genes were identified by intersecting genes obtained from two published pieces of literature. The function of metabolic genes in BC was determined by extracting differentially expressed genes (DEGs), performing functional enrichment analyses, analyzing the infiltrating proportion of immune cells, and conducting metabolic subgroup analyses. A risk score model was constructed to assess the prognoses of BC patients by performing the univariate Cox regression, LASSO algorithm, multivariate Cox regression, Kaplan-Meier survival analyses, and ROC curve analyses in the training set. The prognostic model was then validated on the testing dataset, external dataset, the whole TCGA-BC database, and our clinical specimens. Finally, a nomogram was constructed for clinical prognostic prediction based on the risk score model and other clinicopathological parameters. Results: 955 metabolic genes were obtained. Among these, 157 metabolic DEGs were identified between BC and normal tissues for subsequent GO and KEGG pathway enrichment analyses. 5 metabolic genes were negatively correlated with CD8+ T cells, while 49 genes were positively correlated with CD8+ T cells. Furthermore, 5 metabolic subgroups with varying proportions of PAM50 subtypes, TNM classification, and immune cell infiltration were obtained. Finally, a risk score model was constructed to predict the prognoses of BC patients, and a nomogram incorporating the risk score model was established for clinical application. Conclusion: In this study, we elucidated tumor heterogeneity from metabolite profiling of BC. The roles of metabolic genes in the occurrence of BC were comprehensively characterized, clarifying the relationship between the tumor microenvironment (TME) and metabolic genes. Meanwhile, a concise prediction model was also constructed based on metabolic genes, providing a convenient and precise method for the individualized diagnosis and treatment of BC patients.

Theoretical Design of Novel Boron-Based Nanowires via Inverse Sandwich Clusters.

Borophene has important application value, boron nanomaterials doped with transition metal have wondrous structures and chemical bonding. However, little attention was paid to the boron nanowires (NWs). Inspired by the novel metal boron clusters Ln2B n - (Ln = La, Pr, Tb, n = 7-9) adopting inverse sandwich configuration, we examined Sc2B8 and Y2B8 clusters in such novel structure and found that they are the global minima and show good stability. Thus, based on the novel structural moiety and first-principles calculations, we connected the inverse sandwich clusters into one-dimensional (1D) nanowires by sharing B-B bridges between adjacent clusters, and the 1D-Sc4B24 and 1D-Y2B12 were reached after structural relaxation. The two nanowires were identified to be stable in thermodynamical, dynamical and thermal aspects. Both nanowires are nonmagnetic, the 1D-Sc4B24 NW is a direct-bandgap semiconductor, while the 1D-Y2B12 NW shows metallic feature. Our theoretical results revealed that the inverse sandwich structure is the most energy-favored configuration for transition metal borides Sc2B8 and Y2B8, and the inverse sandwich motif can be extended to 1D nanowires, providing useful guidance for designing novel boron-based nanowires with diverse electronic properties.

The reference genome of Miscanthus floridulus illuminates the evolution of Saccharinae.

Miscanthus, a member of the Saccharinae subtribe that includes sorghum and sugarcane, has been widely studied as a feedstock for cellulosic biofuel production. Here, we report the sequencing and assembly of the Miscanthus floridulus genome by the integration of PacBio sequencing and Hi-C mapping, resulting in a chromosome-scale, high-quality reference genome of the genus Miscanthus. Comparisons among Saccharinae genomes suggest that Sorghum split first from the common ancestor of Saccharum and Miscanthus, which subsequently diverged from each other, with two successive whole-genome duplication events occurring independently in the Saccharum genus and one whole-genome duplication occurring in the Miscanthus genus. Fusion of two chromosomes occurred during rediploidization in M. floridulus and no significant subgenome dominance was observed. A survey of cellulose synthases (CesA) in M. floridulus revealed quite high expression of most CesA genes in growing stems, which is in agreement with the high cellulose content of this species. Resequencing and comparisons of 75 Miscanthus accessions suggest that M. lutarioriparius is genetically close to M. sacchariflorus and that M. floridulus is more distantly related to other species and is more genetically diverse. This study provides a valuable genomic resource for molecular breeding and improvement of Miscanthus and Saccharinae crops.

A super stable assembled P nanowire with variant structural and magnetic/electronic properties via transition metal adsorption.

By means of first-principles calculations, we systematically investigated the structure, stability and magnetic and electronic properties of one-dimensional P nanowire (1D-P10 NW) assembled by Pn subunits (n = 2, 8) and transition metal doped 1D-P10 NW. Our calculations showed that the assembled 1D-P10 NW is super stable in thermodynamic, dynamic, thermal and chemical perspectives. Moreover, when the assembled 1D-P10 NW is decorated with transition metals (TM = Ti ∼ Zn, Zr ∼ Mo), structural transformation occurs (to sandwich or quasi-sandwich chains), and various magnetic and electronic characteristics are introduced to the nanowire. Particularly, the sandwich chains 1D-Mn2@P10 and 1D-V1@P5 are a ferromagnetic semiconductor and a ferromagnetic half-metal, respectively, and the magnetic anisotropy energies are both ∼0.3 meV per Mn/V atom. Our theoretical studies proposed a super stable 1D P nanowire and also offer a feasible approach to reach P5-TM-P5-TM chains with diverse magnetic and electronic properties, as well as ferromagnetic vdW-type 2D systems, which are promising in nanoelectronic devices and spintronics.

Prognostic value of preoperative hematological markers combined with molecular pathology in patients with diffuse gliomas.

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

The Use of Solitaire AB Stents in Coil Embolization of Wide-Necked Cerebral Aneurysms.

BACKGROUND: The Solitaire AB stent is one of many assistant stents used for treating wide-necked cerebral aneurysm, and has been used since 2003. However, large sample studies on its safety and effectiveness are lacking. The objective of this study was to evaluate the effectiveness and safety of the Solitaire AB stent in the coil embolization of wide-necked cerebral aneurysms. METHODS: Retrospective review of the clinical and image data of 116 patients with wide-necked cerebral aneurysms who had been enrolled at six interventional neuroradiology centers from February 2010 to February 2014 and had been treated by coil embolization; in total, 120 Solitaire AB stents were used. The degree of aneurysm occlusion was examined using digital subtraction angiography (DSA) immediately after the procedure and during follow-up, and was graded using the modified Raymond classification. We also observed complications to evaluate the safety and effectiveness of this therapy. RESULTS: The 120 Solitaire AB stents (4 mm × 15 mm, four stents; 4 mm × 20 mm, 16 stents; 6 mm × 20 mm, 36 stents; 6 mm × 30 mm, 64 stents) were inserted to treat 120 wide-necked cerebral aneurysms. All stents were inserted successfully. DSA immediately post-surgery revealed 55 cases of complete occlusion, 59 cases of neck remnant, and six cases of aneurysm remnant. Perioperatively, there were four cases of hemorrhage and four cases of stent thrombosis. The follow-up spanned 3-37 months; of 92 patients examined by DSA at the 6-month follow up, 12 had disease recurrence. CONCLUSIONS: The Solitaire AB stent is effective with a good technical success rate and short-term effect for assisting coil embolization of wide-necked cerebral aneurysms.

Clinical features and surgical management of four peculiar cases of intracranial metastases from renal cell carcinoma.

Intracranial metastasis from renal cell carcinoma is rare. In this study, four patients (age range 56-72 years) were treated for intracranial metastases from renal cell carcinoma. The metastasis was solitary in all four patients and was located in the temporoparietal region in two patients, cerebellum in one patient, and bilateral lateral ventricles in one patient. Preoperative magnetic resonance imaging showed hemorrhage and necrosis in the tumor in all four patients, and one patient had edema in the region of the tumor. All patients were treated with craniotomy for tumor resection, and histopathologic examination showed clear cell carcinoma. Marked bleeding occurred in all patients during the operation, but preoperative direct injection of ethanol into epidural metastases (2 patients) was effective in decreasing intraoperative blood loss. Prognosis was poor with limited survival time (range 2 weeks-45 months), but prognosis was best in the two patients who were treated with postoperative radiation therapy and chemotherapy (survival times 26 and 45 months). To our knowledge, this is the largest report of four uncommon intracranial metastases from RCC in Chinese patients. In summary, intracranial metastasis from renal cell carcinoma should be considered in the differential diagnosis of intracranial tumor because of the high risk of bleeding and poor prognosis.

Successful treatment for giant pituitary adenomas through diverse transcranial approaches in a series of 15 consecutive patients.

OBJECT: Giant pituitary adenomas (GPAs) remain a therapeutic challenge with high mortality and morbidity. We described our experience in a consecutive series of GPAs with extensive suprasellar extension. METHODS: A series of 15 consecutive patients with maximum dimension of more than 4cm was enrolled in present study. These cases were microsurgically treated through diverse transcranial approach in our neurosurgical department from January 2006 to January 2011. Four different transcranial microsurgical approaches were selected based on tumor localization and expansion as well as neurosurgeon's experience. RESULTS: Gross total removal (GTR) was achieved in 10 of all patients (67%), subtotal removal was achieved in 5 of 15 (33%). Nine patients experienced visual improvement postoperatively compared with those of preoperative symptom (82%), no intraoperative or postoperative death was observed in present series. The most striking features of this study indicate that an experienced team can reach 67% with no mortality, no panhypopituitarism and no permanent diabetes insipidus dealing with GPAs. No recurrent tumor was found in the GPAs with GTR, adjuvant radiation therapy had been performed in 5 patients and the continuous shrinkage of the residual adenomas was achieved in 2 out of 5 with radiotherapy. CONCLUSIONS: Transcranial approach was still a relatively reliable and safe management for complex GPAs with extensive suprasellar extension.