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1.
Adv Ophthalmol Pract Res ; 4(3): 112-119, 2024.
Article En | MEDLINE | ID: mdl-38846623

Background: Intraocular malignant tumors represent a severe disease that threatens vision as well as life. To better extend the life of the patient, preserve visual function, and maintain ocular aesthetics, selecting the appropriate timing and methods of treatment becomes crucial. Main text: With the continuous advancement of medical technology, the techniques and methods for treating intraocular malignant tumors are constantly evolving. While surgery was once considered the optimal method to prolong patient survival and prevent local recurrence, the discovery and application of various treatments such as radiotherapy, laser therapy, chemotherapy, cryotherapy, and monoclonal antibodies have led to a greater diversity of treatment options. This diversity offers more possibilities to develop personalized treatment plans, and thereby maximize patient benefit. This article reviews the various treatment methods for intraocular malignant tumors, including indications for treatment, outcomes, and potential complications. Conclusions: Differentiating small intraocular malignant tumors from pigmented lesions is challenging, and ongoing monitoring with regular follow-up is required. Small to medium-sized tumors can be treated with radiotherapy combined with transpupillary thermotherapy. Depending on the tumor's distance from the optic disc, surgery with partial resection may be considered for distant tumors, while proximal tumors may require complete enucleation. Systemic chemotherapy has been widely applied to patients with retinal tumors, lymphomas, and intraocular metastatic cancers, but has limited efficacy in patients with choroidal melanoma. Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) drugs can improve patient vision and quality of life, while the efficacy of immunotherapy and molecular targeted therapy is still under research.

2.
Nat Chem ; 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844638

Ganglioside glycans are ubiquitous and complex biomolecules that are involved in a wide range of biological functions and disease processes. Variations in sialylation and sulfation render the structural complexity and diversity of ganglioside glycans, and influence protein-carbohydrate interactions. Structural and functional insights into the biological roles of these glycans are impeded due to the limited accessibility of well-defined structures. Here we report an integrated chemoenzymatic strategy for expeditious and systematic synthesis of a comprehensive 65-membered ganglioside glycan library covering all possible patterns of sulfation and sialylation. This strategy relies on the streamlined modular assembly of three common sialylated precursors by highly stereoselective iterative sialylation, modular site-specific sulfation through flexible orthogonal protecting-group manipulations and enzymatic-catalysed diversification using three sialyltransferase modules and a galactosidase module. These diverse ganglioside glycans enable exploration into their structure-function relationships using high-throughput glycan microarray technology, which reveals that different patterns of sulfation and sialylation on these glycans mediate their unique binding specificities.

3.
Front Microbiol ; 15: 1398919, 2024.
Article En | MEDLINE | ID: mdl-38690359

Introduction: Adequate crude protein (CP) content in diets plays a crucial role in the intestinal health of the animal. This study investigated the impacts of CP content in diets on the intestinal microbiome and metabolome profiles in growing Huanjiang mini-pigs. Methods: A total of 360 pigs with similar body weight (BW) were allocated for three independent feeding trials based on three different BW stages, including (i) 5-10 kg BW, diets consisting of 14, 16, 18, 20, and 22% CP content; (ii) 10-20 kg BW, diets consisting of 12, 14, 16, 18, and 20% CP content; and (iii) 20-30 kg BW, diets consisting of 10, 12, 14, 16, and 18% CP content. These experiments lasted 28, 28, and 26 days, respectively. Results: The results showed that the Shannon and Simpson indices were decreased (p < 0.05) in the ileum of pigs in response to the 14-18% CP compared with the 20% CP content at 5-10 kg BW stage, while diets containing 12 and 14% CP had higher Chao1 (p < 0.05) and Shannon (p = 0.054) indices compared with 18% CP at 20-30 kg BW stage. Compared with the 20% CP, the diet containing 16% CP displayed an increasing trend (p = 0.089) of Firmicutes abundance but had decreased (p = 0.056) Actinobacteria abundance in the jejunum at 5-10 kg BW stage. In addition, a diet containing 16% CP had higher Lactobacillus abundance in the jejunum and ileum compared with the 18, 20, and 22% CP, while had lower Sphingomonas and Pelomonas abundances in the jejunum and Streptococcus abundance in the ileum compared with the diet containing 22% CP (p < 0.05). Diets containing lower CP content altered differential metabolites in the small intestine at the early stage, while higher CP content had less impact. Conclusion: These findings suggest that a diet containing lower CP content (16% CP) may be an appropriate dietary CP content for 5-10 kg Huanjiang mini-pigs, as 16% CP content in diet has shown beneficial impacts on the intestinal microbiome and metabolome profiles at the early growth stage of pigs.

4.
Sci Rep ; 14(1): 11153, 2024 05 15.
Article En | MEDLINE | ID: mdl-38750224

The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients' perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach's α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P < 0.001). Confirmatory factor analysis (CFA) indicated a good model fit, with indices of χ2/df (2.602), IFI (0.960), and RMSEA (0.067). The Average Variance Extracted (AVE) values for the seven dimensions of PROMIS-29 V2.1, ranging from 0.500 to 0.910, demonstrated satisfactory convergent validity. Discriminant validity was confirmed by ideal √AVE values. The Chinese version of the PROMIS-29 V2.1 profile has been validated as an effective instrument for assessing symptoms and functions in patients with hematological malignancy, underscoring its reliability and applicability in this specific patient group.


Hematologic Neoplasms , Psychometrics , Humans , Hematologic Neoplasms/psychology , Psychometrics/methods , Male , Female , Middle Aged , Adult , China , Cross-Sectional Studies , Reproducibility of Results , Patient Reported Outcome Measures , Quality of Life , Surveys and Questionnaires , Aged , Young Adult , Adolescent
5.
J Med Chem ; 67(10): 8420-8444, 2024 May 23.
Article En | MEDLINE | ID: mdl-38718180

Faced with increasingly serious fungal infections and drug resistance issues, three different series of novel dual-target (programmed death ligand 1/14 α-demethylase) compounds were constructed through the fragment combination pathway in the study. Their chemical structures were synthesized, characterized, and evaluated. Among them, preferred compounds 10c-1, 17b-1, and 18b-2 could efficiently exert their antifungal and antidrug-resistant fungal ability through blocking ergosterol biosynthesis, inducing the upregulation of reactive oxygen species level, and triggering apoptosis. Especially, compound 18b-2 exhibited the synergistic function of fungal inhibition and immune activation. Moreover, the covalent organic framework carrier was also generated based on the acidic microenvironment of fungal infection to improve the bioavailability and targeting of preferred compounds; this finally accelerated the body's recovery rate.


Antifungal Agents , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Humans , Animals , Microbial Sensitivity Tests , Structure-Activity Relationship , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , 14-alpha Demethylase Inhibitors/pharmacology , 14-alpha Demethylase Inhibitors/chemistry , 14-alpha Demethylase Inhibitors/chemical synthesis , Mycoses/drug therapy , Mice , Candida albicans/drug effects , Ergosterol/metabolism , Molecular Structure
6.
PLoS One ; 19(5): e0304551, 2024.
Article En | MEDLINE | ID: mdl-38814895

Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to reduced endothelium-derived relaxing factor nitric oxide (NO) generation, causing and accelerating CMD. Endoplasmic reticulum stress (ER stress) has been shown to reduce NO production in umbilical vein endothelial cells. Oxidized low-density lipoprotein (ox-LDL) damages endothelial cell function. However, the relationship between ox-LDL and coronary microcirculation has yet to be assessed. Short-chain fatty acid (SCFA), a fermentation product of the gut microbiome, could improve endothelial-dependent vasodilation in human adipose arterioles, but the effect of SCFA on coronary microcirculation is unclear. In this study, we found ox-LDL stimulated expression of ER chaperone GRP78. Further, we activated downstream PERK/eIF2a, IRE1/JNK, and ATF6 signaling pathways, decreasing eNOS phosphorylation and NO production in human cardiac microvascular endothelial. Furthermore, SCFA-propionate can inhibit ox-LDL-induced eNOS phosphorylation reduction and raise NO production; the mechanism is related to the inhibition of ER stress and downstream signaling pathways PERK/eIF2a, IRE1/JNK, and ATF6. In summary, we demonstrate that ox-LDL induced CMD by activating ER stress, propionate can effectively counteract the adverse effects of ox-LDL and protect coronary microcirculation function via inhibiting ER stress.


Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Lipoproteins, LDL , Nitric Oxide Synthase Type III , Nitric Oxide , Propionates , Signal Transduction , Humans , Endoplasmic Reticulum Stress/drug effects , Lipoproteins, LDL/metabolism , Nitric Oxide Synthase Type III/metabolism , Propionates/pharmacology , Nitric Oxide/metabolism , Signal Transduction/drug effects , Phosphorylation/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Coronary Vessels/drug effects , Coronary Vessels/metabolism , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/pharmacology , eIF-2 Kinase/metabolism , Activating Transcription Factor 6/metabolism , Microcirculation/drug effects , Heat-Shock Proteins/metabolism
7.
PLoS One ; 19(5): e0303626, 2024.
Article En | MEDLINE | ID: mdl-38787901

Green development is an important component of China's new development concept. Pilot Free Trade Zones (PFTZs), as "experimental fields" for promoting reform, deepening opening-up, and raising the level of an open economy, are important open areas for China to promote green development. However, existing related research is not extensive. This article takes PFTZs as quasi-natural experiments, with the Yangtze River Economic Belt (YREB) as the research area. Based on urban panel data from 2006 to 2020, using multi-period differences-in-differences and spatial differences-in-differences models, it explores the impact effects of PFTZs on urban green development and their potential mechanisms. The research findings indicate: (1) Overall, PFTZs significantly promote urban green development, with variations in impact effects due to different batches and locations of establishment. (2) Mechanism tests show that PFTZs mainly promote urban green development by stimulating technological innovation, industrial upgrading, and reducing government intervention. (3) From the perspective of spatial spillover effects, the establishment of PFTZs not only promotes the green development process in the host cities but also has a promoting effect on the green development of surrounding cities.


Cities , Rivers , China , Commerce , Conservation of Natural Resources/economics , Humans , Pilot Projects , Economic Development , Sustainable Development
8.
Ophthalmologie ; 121(5): 366-373, 2024 May.
Article De | MEDLINE | ID: mdl-38700760

Orbital and periocular metastatic tumors used to be considered very rare; however, with the constant updating of drugs and detection methods for cancer treatment, new chemotherapies and radiation treatments are being used. The life expectancy of cancer patients has become longer and periocular metastases are becoming easier to detect. Our knowledge of this rare disease of metastases also needs to be updated. This article reviews the incidence, symptomatic presentation, clinical features, diagnostic approaches and current treatment of metastatic tumors of the orbit and ocular adnexa in these patients.


Orbital Neoplasms , Humans , Orbital Neoplasms/secondary , Orbital Neoplasms/therapy , Eyelid Neoplasms/therapy , Eyelid Neoplasms/pathology , Eyelid Neoplasms/epidemiology , Eyelid Neoplasms/secondary , Eye Neoplasms/secondary , Eye Neoplasms/therapy , Eye Neoplasms/pathology
9.
Cancer Cell Int ; 24(1): 145, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38654331

Lung adenocarcinoma is a major public health problem with the low 5-year survival rate (15%) among cancers. Aberrant alterations of meiotic genes, which have gained increased attention recently, might contribute to elevated tumor risks. However, systematic and comprehensive studies based on the relationship between meiotic genes and LUAD recurrence and treatment response are still lacking. In this manuscript, we first confirmed that the meiosis related prognostic model (MRPM) was strongly related to LUAD progression via LASSO-Cox regression analyses. Furthermore, we identified the role of PPP2R1A in LUAD, which showed more contributions to LUAD process compared with other meiotic genes in our prognostic model. Additionally, repression of PPP2R1A enhances cellular susceptibility to nelfinavir-induced apoptosis and pyroptosis. Collectively, our findings indicated that meiosis-related genes might be therapeutic targets in LUAD and provided crucial guidelines for LUAD clinical intervention.

10.
Heliyon ; 10(8): e29655, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38655365

Background: The major facilitator superfamily glucose transporters (GLUTs), encoded by solute carrier 2A (SLC2A) genes, mediate the transmembrane movement and uptake of glucose. To satisfy the improved energy demands, glycolysis flux is increased in cancers compared with healthy tissues. Multiple diseases, including cancer, have been associated with GLUTs. Nevertheless, not much research has been done on the functions of SLC2As in pan-cancer prognosis or their clinical treatment potential. Methods: The SLC2A family genes' level of expression and prognostic values were analyzed in relation to pan-cancer. We then examined the association among SLC2As expression and TME, Stemness score, clinical characteristics, immune subtypes, and drug sensitivity. We merged bioinformatics analysis techniques with up-to-date public databases. Additionally, SLC2As from the KOBAS database were subjected to enrichment analysis. Results: We discovered that SLC2As' gene expression differed significantly between normal tissues and many malignancies. A number of tumors from various databases demonstrate a relationship between prognosis and SLC2A family gene expression. For instance, SLC2A2 and SLC2A5 were associated with the overall survival (OS) of hepatocellular carcinoma. SLC2A1 was associated with the OS of lung adenocarcinoma and pancreatic adenocarcinoma. Moreover, the SLC2A family gene expression is significantly correlated with the pan-cancer stromal and immune scores, and the RNA and DNA stemness scores. Furthermore, we found that the majority of SLC2As had a strong correlation with the tumor stages in KIRC. The immunological subtypes and all members of the SLC2A gene family exhibited a substantial correlation. Moreover, pathways containing insulin resistance and adipocytokine signaling pathway may influence the progression of some cancers. Finally, there is a significant positive or negative connection between drug sensitivity and SLC2A1 expression. Conclusion: Our research highlights the significant promise of SLC2As as prognostic indicators and offers insightful approaches for upcoming exploration of SLC2As as putative therapeutic targets in malignancies.

11.
Toxins (Basel) ; 16(3)2024 Mar 20.
Article En | MEDLINE | ID: mdl-38535825

Toad Venom (TV) is the dried product of toxic secretions from Bufo bufo gargarizans Cantor (BgC) or B. melanostictus Schneider (BmS). Given the increasing medical demand and the severe depletion of wild toads, a number of counterfeit TVs appeared on the market, posing challenges to its quality control. In order to develop an efficient, feasible, and comprehensive approach to evaluate TV quality, a thorough analysis and comparison of chemical compounds among legal species BgC and BmS, as well as the main confusion species B. andrewsi Schmidt (BaS) and B. raddei Strauch (BrS), were conducted by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), high performance liquid chromatography (HPLC), sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Nano LC-MS/MS analyses. We identified 126 compounds, including free or conjugated bufadienolides, indole alkaloids and amino acids, among the four Bufo species. The content of main bufadienolides, such as gamabufotalin, bufotalin, bufalin, cinobufagin, and resibufogenin, and the total protein contents varied widely among 28 batches of TV due to their origin species. The sum of the five bufadienolides within the BgC, BmS, BaS, and BrS samples were 8.15-15.93%, 2.45-4.14%, 11.15-13.50%, and 13.21-14.68%, respectively. The total protein content of BgC (6.9-24.4%) and BaS (19.1-20.6%) samples were higher than that of BmS (4.8-20.4%) and BrS (10.1-13.7%) samples. Additionally, a total of 1357 proteins were identified. There were differences between the protein compositions among the samples of the four Bufo species. The results indicated that BgC TV is of the highest quality; BaS and BrS TV could serve as alternative resources, whereas BmS TV performed poorly overall. This research provides evidence for developing approaches to evaluate TV quality and selecting the proper Bufo species as the origin source of TV listed in the Chinese pharmacopoeia.


Bufanolides , Tandem Mass Spectrometry , Animals , Amino Acids , Bufonidae
12.
ACS Appl Mater Interfaces ; 16(12): 14467-14473, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38491944

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H2S detection. The PB shell degraded quickly upon contact with endogenous H2S, generating a unique Raman signal response in the Raman silent region (1800-2800 cm-1). By taking advantage of the high SERS-activity of Au NBPs and H2S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 µM to 250 µM and a limit of detection (LOD) of 0.34 µM, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H2S concentrations in human serum samples with satisfied results.


Ferrocyanides , Hydrogen Sulfide , Metal Nanoparticles , Humans , Hydrogen Sulfide/analysis , Gold , Reproducibility of Results , Spectrum Analysis, Raman/methods
13.
Phytomedicine ; 128: 155417, 2024 Jun.
Article En | MEDLINE | ID: mdl-38518642

BACKGROUND: The role of the glioblastoma (GBM) microenvironment is pivotal in the development of gliomas. Discovering drugs that can traverse the blood-brain barrier and modulate the tumor microenvironment is crucial for the treatment of GBM. Dioscin, a steroidal saponin derived from various kinds of plants and herbs known to penetrate the blood-brain barrier, has shown its powerful anti-tumor activity. However, little is known about its effects on GBM microenvironment. METHODS: Bioinformatics analysis was conducted to assess the link between GBM patients and their prognosis. Multiple techniques, including RNA sequencing, immunofluorescence staining, Western blot analysis, RNA-immunoprecipitation (RIP) assays, and Chromatin immunoprecipitation (CHIP) analysis were employed to elucidate the mechanism through which Dioscin modulates the immune microenvironment. RESULTS: Dioscin significantly impaired the polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages in vitro and in vivo. A strong correlation between high expression of RBM47 in GBM and a detrimental prognosis for patients was demonstrated. RNA-sequencing analysis revealed an association between RBM47 and the immune response. The inhibition of RBM47 significantly impaired the recruitment and polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages. Moreover, RBM47 could stabilize the mRNA of inflammatory genes and enhance the expression of these genes by activating the NF-κB pathway. In addition, NF-κB acts as a transcription factor that enhances the transcriptional activity of RBM47. Notably, we found that Dioscin could significantly inhibit the activation of NF-κB and then downregulate the expression of RBM47 and inflammatory genes protein. CONCLUSION: Our study reveals that the positive feedback loop between RBM47 and NF-κB could promote immunosuppressive microenvironment in GBM. Dioscin effectively inhibits M2 polarization in GBM by disrupting the positive feedback loop between RBM47 and NF-κB, indicating its potential therapeutic effects in GBM treatment.


Diosgenin , Glioma , NF-kappa B , Animals , Humans , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Cell Line, Tumor , Diosgenin/pharmacology , Diosgenin/analogs & derivatives , Feedback, Physiological/drug effects , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioma/drug therapy , Glioma/metabolism , Macrophages/drug effects , Macrophages/metabolism , NF-kappa B/metabolism , RNA-Binding Proteins/metabolism , Tumor Microenvironment/drug effects
14.
Stem Cells Transl Med ; 13(5): 415-424, 2024 May 14.
Article En | MEDLINE | ID: mdl-38513284

BACKGROUND: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. RESULTS: ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. CONCLUSIONS: ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. TRIAL REGISTRATION: registered with Chictr.org.cn (ChiCTR2100051405).


Transplantation, Autologous , Vitiligo , Humans , Vitiligo/therapy , Male , Female , Retrospective Studies , Transplantation, Autologous/methods , Adult , Adolescent , Young Adult , Middle Aged , Melanocytes/transplantation , Child , Keratinocytes/transplantation , Cells, Cultured , Epithelium
15.
J Phys Chem Lett ; 15(10): 2675-2681, 2024 Mar 14.
Article En | MEDLINE | ID: mdl-38426861

Organic photodetectors (OPDs) have attracted tremendous interest due to their potential applications in wearable electronics. However, due to the nonideal contacts between the electrodes and organic semiconductors, OPDs still suffer from high dark current and slow frequency response. Herein, by inserting potassium aspartic acid (PAA) interlayers between ITO/metal oxides and the metal oxides/active layer, the shunts and hole injections are blocked and the energy levels of the electrodes are aligned. As a result, our dual-interface modified OPDs (ITO/PAA/ZnO/PAA/PTB7-Th:ITIC/MoO3/Ag) exhibit suppressed dark current 550 times lower than the reference device, corresponding to specific detectivity of 2.1 × 1012 Jones, broad linear dynamic range of 113 dB, and quick response time to the nanosecond level. PAA interlayers have also been demonstrated to improve the storage stability of OPDs, leading to 10 times slower degradation for the on/off ratio when compared with the reference and conventional polyethylenimine-modified OPDs.

16.
ACS Cent Sci ; 10(2): 417-425, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38435515

Disialosyl globopentaosylceramide (DSGb5) is a tumor-associated complex glycosphingolipid. However, the accessibility of structurally well-defined DSGb5 for precise biological functional studies remains challenging. Herein, we describe the first total synthesis of DSGb5 glycolipid by an efficient chemoenzymatic approach. A Gb5 pentasaccharide-sphingosine was chemically synthesized by a convergent and stereocontrolled [2 + 3] method using an oxazoline disaccharide donor to exclusively form ß-anomeric linkage. After investigating the substrate specificity of different sialyltransferases, regio- and stereoselective installment of two sialic acids was achieved by two sequential enzyme-catalyzed reactions using α2,3-sialyltransferase Cst-I and α2,6-sialyltransferase ST6GalNAc5. A unique aspect of the approach is that methyl-ß-cyclodextrin-assisted enzymatic α2,6-sialylation of glycolipid substrate enables installment of the challenging internal α2,6-linked sialoside to synthesize DSGb5 glycosphingolipid. Surface plasmon resonance studies indicate that DSGb5 glycolipid exhibits better binding affinity for Siglec-7 than the oligosaccharide moiety of DSGb5. The binding results suggest that the ceramide moiety of DSGb5 facilitates its binding by presenting multivalent interactions of glycan epitope for the recognition of Siglec-7.

17.
Virus Res ; 342: 199334, 2024 04.
Article En | MEDLINE | ID: mdl-38325524

Tomato spotted wilt virus (TSWV) is ranked among the top 10 most destructive viruses globally. It results in abnormal leaf growth, stunting, and even death, significantly affecting crop yield and quality. Phytohormones play a crucial role in regulating plant-virus interactions. However, there is still limited research on the effect of TSWV on phytohormone levels, particularly growth hormones and genes involved in the phytohormone pathway. In our study, we combined phytohormone metabolomics and transcriptomics to examine the impact of TSWV infection on phytohormone content and gene expression profile. Metabolomic results showed that 41 metabolites, including major phytohormones and their precursors and derivatives were significantly altered after 14 days of TSWV inoculation tobacco plants cvK326, with 31 being significantly increased and 10 significantly reduced. Specifically, the levels of abscisic acid (ABA) and jasmonoyl-isoleucine (JA-Ile) were significantly reduced. The levels of indole-3-acetic acid (IAA) have remained unchanged. However, the levels of cytokinin isopentenyladenine (iP) and salicylic acid (SA) significantly increased. The transcriptome analysis revealed 2,746 genes with significant changes in expression. Out of these, 1,072 genes were significantly downregulated, while 1,674 genes were significantly upregulated. Among them, genes involved in ABA synthesis and signaling pathways, such as 9-cis-epoxycarotenoid dioxygenase (NCED), protein phosphatase 2C (PP2C), serine/threonine-protein kinase (SnRK2), and abscisic acid responsive element binding factor (ABF), exhibited significant downregulation. Additionally, expression of the lipoxygenase gene LOX, Jasmonate ZIM domain-containing protein gene JAZ, and transcription factor gene MYC were significantly down-regulated. In the cytokinin pathway, while there were no significant changes in the expression of the cytokinin synthesis genes, a significant downregulation of transcriptionally active factor type-B response regulators (type-B RRs) was observed. In terms of SA synthesis and signaling pathways, the isochorismate synthase gene ICS1 and the pathogenesis-related gene PR1 were significantly upregulated. These results can strengthen the theoretical foundation for understanding the interaction between TSWV and tobacco and provide new insights for the future prevention and control of TSWV.


Plant Growth Regulators , Tospovirus , Nicotiana , Tospovirus/genetics , Abscisic Acid , Gene Expression Profiling , Cytokinins
18.
BMC Cancer ; 24(1): 263, 2024 Feb 24.
Article En | MEDLINE | ID: mdl-38402391

BACKGROUND: Whether Transanal drainage tubes (TDTs) placement reduces the occurrence of anastomotic leakage (AL) after rectal cancer (RC) surgery remains controversial. Most existing meta-analyses rely on retrospective studies, while the prospective studies present an inadequate level of evidence. METHODS: A systematic review and meta-analysis of prospective studies on TDTs placement in RC patients after surgery was conducted. The main analysis index was the incidence of AL, Grade B AL, and Grade C AL, while secondary analysis index was the incidence of anastomotic bleeding, incision infection, and anastomotic stenosis. A comprehensive literature search was performed utilizing the databases Cochrane Library, Embase, PubMed, and Web of Science. We recorded Risk ratios (RRs) and 95% confidence intervals (CI) for each included study, and a fixed-effect model or random-effect model was used to investigate the correlation between TDTs placement and four outcomes after RC surgery. RESULTS: Seven studies (1774 participants, TDT 890 vs non-TDT 884) were considered eligible for quantitative synthesis and meta-analysis. The meta-analysis revealed that the incidence of AL was 9.3% (83/890) in the TDT group and 10.2% (90/884) in the non-TDT group. These disparities were found to lack statistical significance (P = 0.58). A comprehensive meta-analysis, comprising four studies involving a cumulative sample size of 1259 participants, revealed no discernible disparity in the occurrence of Grade B AL or Grade C AL between the TDT group and the non-TDT group (Grade B AL: TDT 34/631 vs non-TDT 26/628, P = 0.30; Grade C AL: TDT 11/631 vs non-TDT 27/628, P = 0.30). Similarly, the incidences of anastomotic bleeding (4 studies, 876 participants), incision infection (3studies, 713 participants), and anastomotic stenosis (2studies, 561 participants) were 5.5% (24/440), 8.1% (29/360), and 2.9% (8/280), respectively, in the TDT group, and 3.0% (13/436), 6.5% (23/353), and 3.9% (11/281), respectively, in the non-TDT group. These differences were also determined to lack statistical significance (P = 0.08, P = 0.43, P = 0.48, respectively). CONCLUSION: The placement of TDTs does not significantly affect the occurrence of AL, Grade B AL, and Grade C AL following surgery for rectal cancer. Additionally, TDTs placement does not be associated with increased complications such as anastomotic bleeding, incision infection, or anastomotic stenosis. TRIAL REGISTRATION: PROSPERO: CRD42023427914.


Anastomotic Leak , Rectal Neoplasms , Humans , Anastomotic Leak/epidemiology , Anastomotic Leak/etiology , Incidence , Retrospective Studies , Prospective Studies , Constriction, Pathologic , Anal Canal/surgery , Rectal Neoplasms/surgery , Rectal Neoplasms/complications , Drainage
19.
Heliyon ; 10(3): e25265, 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38327452

Objectives: To evaluate myocardial work in peritoneal dialysis patients by pressure-strain loop. To analyze the factors influencing myocardial work in peritoneal dialysis patients with preserved ejection fraction. Methods: We collected clinical data on possible effects on myocardial work in 105 maintenance peritoneal dialysis patients with preserved ejection fraction and applied ultrasonic pressure-strain loops to obtain the left ventricular global constructive work (GCW), Global work index (GWI), global work waste (GWW), and global work efficiency (GWE) of the patients. Then, the clinical data and myocardial work indices were statistically described and correlated. Results: Left ventricular hypertrophy was observed in 78 % of peritoneal dialysis patients with left ventricular ejection fraction preservation. There is a correlation between the left ventricular mass index and myocardial work indices (P < 0.05). On multiple linear regression analysis, systolic blood pressure (SBP), IL-6, and hemoglobin correlated with GCW(P < 0.05); SBP and IL-6 correlated with GWI(P < 0.05); homocysteine, SBP, TNF-α, and hemoglobin correlated with GWW(P < 0.05); homocysteine, TNF-α and hemoglobin correlated with GWE (P < 0.05). Conclusions: Using noninvasive pressure-strain loops to assess left ventricular myocardial work can provide information on cardiac function more consistent with pathophysiological changes than conventional ejection fraction. Hypertension, anemia, hyperhomocysteinemia, and inflammation influence left ventricular myocardial work in peritoneal dialysis patients, and they selectively affect one or more myocardial work indices.

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RSC Adv ; 14(8): 5594-5599, 2024 Feb 07.
Article En | MEDLINE | ID: mdl-38352688

A turn-on fluorescence nanoprobe was constructed for the determination of adenosine 5'-triphosphate (ATP) based on DNA-templated silver nanoclusters (DNA-AgNCs). The significant enhancement fluorescence intensity of DNA-AgNCs in the presence of ATP is due to the high special binding affinity between ATP and the aptamer, resulting in the environment of DNA-AgNCs with darkish fluorescence lying at one terminus of DNA slightly altering owing to the change of ATP aptamer conformation. A good linear range runs from 9 to 24 mM with a satisfactory detection limit of 3 µM. Furthermore, the proposed nanoprobe exhibited good performance for ATP detection in diluted fetal bovine serum.

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