Astrocyte-derived lactoferrin inhibits neuronal ferroptosis by reducing iron content and GPX4 degradation in APP/PS1 transgenic mice.

Increased astrocytic lactoferrin (Lf) expression was observed in the brains of elderly individuals and Alzheimer's disease (AD) patients. Our previous study revealed that astrocytic Lf overexpression improved cognitive capacity by facilitating Lf secretion to neurons to inhibit ß-amyloid protein (Aß) production in APP/PS1 mice. Here, we further discovered that astrocytic Lf overexpression inhibited neuronal loss by decreasing iron accumulation and increasing glutathione peroxidase 4 (GPX4) expression in neurons within APP/PS1 mice. Furthermore, human Lf (hLf) treatment inhibited ammonium ferric citrate (FAC)-induced ferroptosis by chelating intracellular iron. Additionally, machine learning analysis uncovered a correlation between Lf and GPX4. hLf treatment boosted low-density lipoprotein receptor-related protein 1 (LRP1) internalization and facilitated its interaction with heat shock cognate 70 (HSC70), thereby inhibiting HSC70 binds to GPX4, and eventually attenuating GPX4 degradation and FAC-induced ferroptosis. Overall, astrocytic Lf overexpression inhibited neuronal ferroptosis through two pathways: reducing intracellular iron accumulation and promoting GPX4 expression via inhibiting chaperone-mediated autophagy (CMA)-mediated GPX4 degradation. Hence, upregulating astrocytic Lf expression is a promising strategy for combating AD.

Structural identification, rheological properties and immunological receptor of a complex galacturonoglucan from fruits of Schisandra chinensis (Turcz.) Baill.

A complex heteropolysaccharide SCP-2 named schisanan B (Mw = 1.005 × 105 g/mol) was obtained from water extracts of Schisandra chinensis fruits, and its planar structure was finally deduced as a galacturonoglucan by a combination of monosaccharide compositions, methylation analysis, partial acid hydrolysis, enzymatic hydrolysis and 1D/2D-nuclear magnetic resonance spectroscopy. The conformation of SCP-2 exhibited a globular shape with branching in ammonium formate aqueous solutions. The rheological properties of SCP-2 were investigated on concentrations, temperature, pH and salts. The in vitro immunomodulatory activity assay demonstrated that SCP-2 significantly enhanced the production of nitric oxide (NO) and stimulated the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in macrophages. Through a combination of high-resolution live-cell imaging, surface plasmon resonance, and molecular docking techniques, SCP-2 exhibited a strong binding affinity with the Toll-like receptor 4 (TLR4). Moreover, western blot analysis revealed that SCP-2 effectively induced downstream signaling proteins associated with TLR4 activation, thereby promoting macrophage activation. The evidence strongly indicates that TLR4 functions as a membrane protein target in the activation of macrophages and immune regulation induced by SCP-2.

The complete chloroplast genome of Dryas octopetala var. asiatica (Dryadoideae, Rosaceae) and phylogenetic analysis.

Dryas octopetala L. var. asiatica (Nakai) Nakai 1918 is a dwarf shrub that mainly grow in alpine and arctic zones of the Northern Hemisphere, representing an endemic variety in Asia. In the present study, the complete chloroplast (cp) genome of D. octopetala var. asiatica was first characterized and used for its phylogenetic analysis. The cp genome span 158,271 bp with an overall GC content of 36.5%. A total of 129 genes were identified, including 84 protein-coding genes (PCGs), 37 tRNA genes, and 8 rRNA genes. In addition, repetitive sequences and microsatellites were detected within this species. Phylogenetic analysis involving 39 cp genomes from Rosaceae family indicated that D. octopetala var. asiatica was sister to the clade of Amygdaloideae. This study contributes fundamental insights into the cp genome of Dryas octopetala var. asiatica, which will have expanded its use in photosynthesis and evolutionary study.

Identification of AS1842856 as a novel small-molecule GSK3α/ß inhibitor against Tauopathy by accelerating GSK3α/ß exocytosis.

Glycogen synthase kinase-3α/ß (GSK3α/ß) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/ß inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/ß. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/ß content in a FOXO1-independent manner. Specifically, AS directly bound to GSK3α/ß, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/ß content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood-brain barrier (BBB) using an imaging mass microscope. Long-term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/ß expression in the brain. Altogether, AS represents a novel small-molecule GSK3α/ß inhibitor that facilitates GSK3α/ß exocytosis, holding promise as a therapeutic agent for GSK3α/ß hyperactivation-associated disorders.

Bridging thrombolysis before endovascular therapy is associated with better outcomes in patients with large infarction core.

BACKGROUND: This study investigates the efficacy and safety of bridging intravenous thrombolysis (IVT) before endovascular therapy (EVT) compared with EVT alone in patients with large infarction core. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library from January 2015 to June 2024. Included studies involved patients with acute ischemic stroke with an Alberta Stroke Program Early CT Score of ≤5 or an ischemic core volume of ≥50 mL. Studies were required to provide either 90-day modified Rankin Scale (mRS) score, reperfusion, symptomatic intracranial hemorrhage (sICH), or 90-day mortality. RESULTS: Nine observational studies with 2641 patients were analyzed. The IVT+EVT group had a higher rate of 90-day functional independence (mRS 0-2; OR 1.56, 95% CI 1.31 to 1.87; adjusted OR (aOR) 1.43, 95% CI 1.21 to 1.68) and 90-day functional outcome (mRS 0-3; OR 1.34, 95% CI 1.11 to 1.62; aOR 1.18, 95% CI 1.02 to 1.37) compared with EVT alone. There was no significant difference in successful reperfusion (OR 1.01, 95% CI 0.62 to 1.64; aOR 1.07, 95% CI 0.74 to 1.54) and 90-day mortality (OR 0.86, 95% CI 0.73 to 1.02; aOR 0.89, 95% CI 0.77 to 1.04) between the two groups. Moreover, patients who received IVT+EVT had a higher rate of sICH (OR 1.30, 95% CI 1.03 to 1.64; aOR 2.21, 95% CI 1.22 to 4.01). CONCLUSIONS: In patients with large infarction core, bridging IVT before EVT is associated with favorable functional outcomes compared with EVT, even though bridging therapy entails a higher risk of sICH. Further trials are needed to confirm these findings.

Multiple Stimuli-Responsive Color-Changing Polymer Materials for Reversible Writing and Anti-Counterfeiting.

Polymer materials with multiple stimuli-responsive properties have demonstrated many potential and practical applications. By covalently introducing spiropyran (SP1) and spirothiopyran (STP) into the polyurethane backbone, photochromic, mechanochromic, and thermally discolored polymer materials have been prepared. In this work, we report for the first time that white light (violet, blue, and green light) above a certain intensity can activate STP to green color. Based on the above discovery, the polyurethane with SP1 and STP can exhibit reversible three-color changes (brown, green, and purple) in response to four stimuli: ultraviolet irradiation, white light irradiation, mechanical stress, and heat. The color-changing polymer materials have high color contrast and excellent reversibility, and can be used for reversible writing, anticounterfeiting and information encryption, etc.

Fast Determination of Eleven Food Additives in River Water Using C18 Functionalized Magnetic Organic Polymer Nanocomposite Followed by High-Performance Liquid Chromatography.

A novel magnetic nanomaterial with Fe3O4 as the core, PS-DVB as the shell layer, and the surface modified with C18 (C18-PS-DVB-Fe3O4) had been synthesized by seeded emulsion polymerization. C18-PS-DVB-Fe3O4 retains the advantages of the chemical stability, large porosity, and uniform morphology of organic polymers and has the magnetic properties of Fe3O4. A simple, flexible, and efficient magnetic dispersive solid phase extraction (Mag-dSPE) method for the extraction of preservatives, sweeteners, and colorants in river water was established. C18-PS-DVB-Fe3O4 was used as an adsorbent for Mag-dSPE and was coupled with high-performance liquid chromatography (HPLC) to detect 11 food additives: acesulfame, amaranth, benzoic acid, tartrazine, saccharin sodium, sorbic acid, dehydroacetic acid, sunset yellow, allura red, brilliant blue, and erythrosine. Under the optimum extraction conditions, combined with ChromCoreTMAQC18 (5 µm, 4.6 × 250 mm), 20 mmol/L ammonium acetate aqueous solution and methanol were used as mobile phases, and the detection wavelengths were 240 nm and 410 nm. The limits of detection (LODs) of 11 food additives were 0.6-3.1 µg/L with satisfactory recoveries ranging from 86.53% to 106.32%. And the material could be reused for five cycles without much sacrifice of extraction efficiency. The proposed method has been used to determine food additives in river water samples, and results demonstrate the applicability of the proposed C18-PS-DVB-Fe3O4 Mag-dSPE coupled with the HPLC method to environment monitoring analysis.

Efficacy and safety of etrolizumab in the treatment of inflammatory bowel disease: a meta-analysis.

Background: To explore the efficacy and safety of etrolizumab in treating inflammatory bowel disease (IBD) through meta-analysis. Method: A comprehensive exploration encompassed randomized controlled trials examining the efficacy of etrolizumab in treating IBD across PubMed, Embase, Cochrane library, and Web of Science, with a search deadline of 1 December 2023. Quality assessment leaned on the Cochrane manual's risk-of-bias evaluation, while Stata 15 undertook the data analysis. Result: Five randomized controlled studies involving 1682 individuals were finally included, Meta-analysis results suggested that compared with placebo, etrolizumab could improve clinical response (RR = 1.26, 95% CI [1.04-1.51]), clinical remission (RR = 1.26, 95% CI [1.04-1.51]) in IBD patients. Endoscopic alleviate (RR = 2.10, 95% CI [1.56-2.82]), endoscopic improvement (RR = 2.10, 95% CI [1.56-2.82]), endoscopic remission (RR = 2.10, 95% CI [1.56-2.82]), Endoscopic improvement (RR = 1.56, 95% CI [1.30-1.89]), histological remission (RR = 1.62, 95% CI [1.26-2.08]), and did not increase any adverse events (RR = 0.95, 95% CI [0.90-1.01]) and serious adverse events (RR = 0.94, 95% CI [0.68-1.31]). Conclusion: According to our current study, etrolizumab is a promising drug in IBD.

[Rapid determination of chlorate and perchlorate in tea by ion exchange chromatography-tandem mass spectrometry].

Ion exchange chromatography-tandem mass spectrometry (IEC-MS/MS) has recently become the preferred method for detecting ionic substances in tea. In this study, an IEC-MS/MS method was developed for the rapid determination of chlorate and perchlorate residues in tea samples. The optimal sample extraction process, pretreatment column, and chromatographic and mass spectrometric conditions were systematically investigated. In the optimal process, the tea samples were ultrasonically extracted with methanol-water (13∶7, v/v), and a PRiME HLB SPE column was used to purify the sample extract. An AceChrom Hybri-A IEC column (150 mm×2.1 mm, 5.0 µm) was used for separation, and 100 mmol/L ammonium acetate-acetonitrile (40∶60, v/v) was used as the mobile phase for isocratic elution. The flow rate was 0.3 mL/min, the column temperature was 40 ℃, and the injection volume was 5.0 µL. The mass spectrometric data were collected in negative electrospray ionization mode combined with multiple reaction monitoring (MRM) mode to achieve the rapid and accurate separation and qualitative analysis of the desired chemical components. Quantification was performed using the internal standard (IS) method. The measurement results showed a good linear relationship when the mass concentrations of chlorate and perchlorate were between 2.00-200 and 1.00-100 µg/L, respectively, with correlation coefficients (r2) greater than 0.9990. The average recoveries of chlorate and perchlorate at three spiked levels of low, medium, and high ranged from 88.54% to 97.25% with relative standard deviations (RSDs, n=7) of 3.2%-5.2%. The limits of detection for chlorate and perchlorate were 12.0 and 8.0 µg/kg, respectively, while the limits of quantification were 40.0 and 26.6 µg/kg, respectively. The results of tests conducted to assess the linearity, specificity, accuracy, precision, and applicability of the method to the analysis of chlorate and perchlorate in 15 tea samples collected from a local market demonstrated its validity for the routine analysis of tea samples. The proposed method is simple, rapid, sensitive, and accurate, and can meet requirements for the rapid screening and quantitative analysis of residual trace chlorate and perchlorate in large quantities of tea samples.

Preparation of Magnetic Spongy Porous Carbon Skeleton Materials for Efficient Removal of BTEX.

Magnetic polymer microspheres have been extensively utilized as separable and highly efficient adsorbents in wastewater treatment. In this study, a series of novel magnetic spongy porous carbon skeleton materials (Mag-SPCS) have been designed and synthesized by acetonitrile suspension precipitation polymerization, which combines the advantages of the acetonitrile precipitation method and the suspension polymerization method. It was demonstrated that the transformation of the material morphology from microspheres to a porous sponge was achieved by a gradual decrease in the usage amount of ethylene glycol. After N,N-dimethyloctadecylamine (C18) was grafted onto the Mag-SPCS materials, the C18-Mag-SPCS materials with a superhigh saturation adsorption capacity and superfast adsorption efficiency were used for the removal of BTEX (toluene, benzene, and para-xylene) in wastewater. Subsequently, the adsorption properties of the composites with different morphologies were evaluated, and the effect of the usage amount of C18 on the adsorption properties of the C18-Mag-SPCS was further investigated. The maximum adsorption capacities of C18-Mag-SPCS for benzene, toluene, and para-xylene were 714.84, 564.32, and 394.48 mg/g, respectively. The adsorption process was conducted in accordance with the proposed secondary and Langmuir models. Finally, the FTIR, XPS, and XRD characterization results before and after adsorption demonstrated that the adsorption mechanism of toluene onto C18-Mag-SPCS was primarily hydrogen bonding, π-π stacking, and van der Waals forces. These findings of the study indicate that the composite material exhibits an ultrahigh saturation adsorption capacity and ultrafast adsorption efficiency, thereby confirming its considerable potential for application in wastewater treatment.

Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics. METHODS: We analyzed human lung single-cell RNA sequencing dataset to discern the association of butyrophilin subfamily 3 member A2 (BTN3A2) expression with COVID-19. The BTN3A2 gene edited cell lines and transgenic mice were infected by live SARS-CoV-2 in a biosafety level 3 (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry and competition ELISA assays were performed in BTN3A2 gene edited cells. We performed quantitative real-time PCR, histological and/or immunohistochemical analyses for tissue samples from mice with or without SARS-CoV-2 infection. FINDINGS: The BTN3A2 mRNA level was correlated with COVID-19 severity. BTN3A2 expression was predominantly identified in epithelial cells, elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same lung cell subtypes. BTN3A2 targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in vivo. INTERPRETATION: These results reveal a key role of BTN3A2 in the fight against COVID-19. Identifying potential monoclonal antibodies which mimic BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19. FUNDING: This study was supported by the National Natural Science Foundation of China (32070569, U1902215, and 32371017), the CAS "Light of West China" Program, and Yunnan Province (202305AH340006).

Association between body mass index and semen quality: a systematic review and meta-analysis.

The continuous decline of human semen quality during the past decades has drawn much concern globally. Previous studies have suggested a link between abnormal BMI and semen quality decline, but the results remain inconsistent. This systematic review and meta-analysis aimed to evaluate the association between body mass index (BMI) and semen quality. We searched PubMed, Embase, and Web of Science for eligible studies from inception to April 17, 2022. We considered men with BMI < 25.0 kg/m2 as the reference and calculated the pooled weighted mean difference of men with overweight (BMI 25.0-29.9 kg/m2), obesity (BMI ≥ 30.0 kg/m2), class I obesity (BMI 30.0-34.9 kg/m2), and class II/III obesity (BMI ≥ 35.0 kg/m2). A total of 5070 articles were identified, of which 50 studies were included (71,337 subjects). Compared with men with BMI < 25.0 kg/m2, men with obesity had an average reduction of 0.24 ml in semen volume, 19.56 × 106 in total sperm number, 2.21% in total motility, 5.95% in progressive motility, and 1.08% in normal forms, respectively, while men with overweight had an average reduction of 0.08 ml in semen volume and 2.91% in progressive motility, respectively. The reduction of semen quality was more pronounced among men with obesity than that among men with overweight. Moreover, significant reductions in semen quality were identified in men with different classes of obesity, which were more pronounced in men with class II/III obesity than that in men with class I obesity. Across men from the general population, infertile or subfertile men, and suspiciously subfertile men, we identified significant semen quality reductions in men with obesity/overweight. In conclusion, obesity and overweight were significantly associated with semen quality reductions, suggesting that maintaining normal weight may help prevent semen quality decline.

Reversible ON- and OFF-switch receptors Clec4G and Rab1A reveal the hormetic effects of a pectin polysaccharide in Aralia elata (Miq.) Seem.

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

Preparation and modification of polymer microspheres, application in wastewater treatment: A review.

The removal of various pollutants from water is necessary due to the increasing requirements for the removal of various pollutants from wastewater and the quality of drinking water. Polymer microspheres are regarded as exemplary adsorbent materials due to their high adsorption efficiency, excellent adsorption performance, and ease of handling. Herein, the advantages and disadvantages of different preparation methods, modifications, applications and the current research status of polymer microspheres are summarized at large. Furthermore, the enhanced performance of modified composite microspheres is emphasized, including adsorption efficiency, thermal stability, and significant improvements in physical and chemical properties. Subsequently, the current applications and potential of polymeric microspheres for wastewater treatment, including the removal of inorganic and organic pollutants, heavy metal ions, and other contaminants are summarized. Finally, future research directions for polymer microspheres are proposed, outlining the challenges and solutions associated with the application of polymer microspheres in wastewater treatment.

Occurrence and risk factors for post-stroke delirium: A systematic review and meta-analysis.

OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4 % (95 %CI, 20.4 %-28.9 %, I2=96.2 %). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5 %, 5.7 % and 5.0 %, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.

A Reverse Thinking Based on Partially Methylated Aldononitrile Acetates to Analyze Glycoside Linkages of Polysaccharides Using Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry.

Glycoside linkage analyses of medicine and food homologous plant polysaccharides have always been a key point and a difficulty of structural characterization. The gas chromatography-mass spectrometry (GC-MS) method is one of the commonly used traditional techniques to determine glycoside linkages via partially methylated alditol acetates and aldononitrile acetates (PMAAs and PMANs). Due to the simplicity of derivatization and the highly structural asymmetry of PMANs, reverse thinking is proposed using liquid chromatography-electrospray ionization-multiple reaction monitoring mass spectrometry (LC-ESI-MRM-MS) for the first time to directly determine the neutral and acidic glycosyl linkages of polysaccharides. The complete characterization of glycoside linkages deduced from PMANs was achieved using a combination of tR values, characteristic MRM ion pairs, diagnostic ESI+-MS/MS fragmentation ions (DFIs), and optimal collision energy (OCE). The DFI and OCE parameters were confirmed to be effective for the auxiliary discrimination of some isomers of the PMANs. The practicality of LC-ESI+-MRM-MS was further verified by analyzing the glycoside linkages of polysaccharides in five medicine and food homologous plants. This method can serve as an alternative to GC-MS for the simultaneous determination of neutral and acidic glycosyl linkages in polysaccharides.

Elucidating the role of angiogenesis-related genes in colorectal cancer: a multi-omics analysis.

Background: Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis. Methods: CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay. Results: Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls. Conclusion: This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.