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1.
Biol Direct ; 19(1): 36, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715141

ABSTRACT

Epidermal growth factor receptor (EGFR)-targeted therapy is an important treatment for RAS wild-type metastatic colorectal cancer (mCRC), but the resistance mechanism remains unclear. Here, the differential expression of circRNAs between Cetuximab sensitive and resistant cell lines was analyzed using whole-transcriptome sequencing. We identified that the expression of circHIF1A was significantly higher in LIM1215-R than in LIM1215. When treated with Cetuximab, downregulation of circHIF1A level weakened the proliferation and clonal formation ability of LIM1215-R, caused more cells to enter G0-G1 phase, and significantly reduced the basal respiration, ATP production, and maximal respiration, as well as the glycolytic capacity and glycolytic reserve. The response rate and prognosis of circHIF1A-positive patients were inferior to those of negative patients. Mechanistically, circHIF1A can upregulate the level of hypoxia-inducible factor 1 A (HIF1A) by competitively binding to miR-361-5p, inducing the overexpression of enzymes such as glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). In a xenograft model, inhibition of circHIF1A expression increased the sensitivity to Cetuximab treatment. In conclusion, circHIF1A can promote HIF1α-mediated glycometabolism alteration to induce Cetuximab resistance in CRC. It has the potential to become a screening indicator for the Cetuximab beneficial population in mCRC and a new therapeutic target for enhancing treatment efficacy.


Subject(s)
Cetuximab , Colorectal Neoplasms , Drug Resistance, Neoplasm , Hypoxia-Inducible Factor 1, alpha Subunit , Cetuximab/pharmacology , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Cell Line, Tumor , Mice , Animals , RNA, Circular/genetics , RNA, Circular/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Regulation, Neoplastic , Mice, Nude , Antineoplastic Agents, Immunological/pharmacology , Glycolysis , Cell Proliferation/drug effects
2.
Article in English | MEDLINE | ID: mdl-38806048

ABSTRACT

Recently, signatures of superconductivity with critical temperature from 20 to 30 K have been reported in pressured trilayer nickelate La$_4$Ni$_3$O$_{10}$ through a pressure-induced structure transition. Here we explore the evolution of electronic structures and electronic correlations in different phases of La$_4$Ni$_3$O$_{10}$ under corresponding pressure regions, by using density functional theory (DFT) combined with dynamical mean-field theory (DMFT). Similar to bilayer superconductor La$_3$Ni$_2$O$_{7}$, the electronic bands in superconducting La$_4$Ni$_3$O$_{10}$ are dominated by Ni-3$d_{x^2-y^2}$ and 3$d_{z^2}$ orbits near the Fermi level, in contrast, the inner Ni-O plane in La$_4$Ni$_3$O$_{10}$ generates a doublet hole-pocket Fermi surfaces around the Brillouin-zone corner, meanwhile one branch of the Ni-$3d_{z^2}$ bands is pushed very close above the Fermi level, which can induce an electron pocket through small electron doping. The DFT+DMFT simulations suggest that the electronic correlations only give minor modification to the Fermi surfaces, meanwhile the Ni-$3d_{z^2}$ and 3$d_{x^2-y^2}$ states on outer Ni-O layers have considerable greater mass enhancements than on the inner layer. The sensitiveness of electronic structure under doping and unique layer dependence of correlation suggest a distinct superconducting mechanism with respect to bilayer La$_3$Ni$_2$O$_{7}$. Based on the DFT and DFT+DMFT simulations, we eventually derive a trilayer effective tight-binding model, which can produce rather precise electronic bands and Fermi surfaces, hence can serve as an appropriate model to further study the superconducting mechanism and paring symmetry in trilayer La$_4$Ni$_3$O$_{10}$.

3.
Discov Med ; 36(184): 992-1001, 2024 May.
Article in English | MEDLINE | ID: mdl-38798258

ABSTRACT

BACKGROUND: Diabetic neuropathic pain (DNP) is a complication of diabetes mellitus (DM). Hyperbaric lidocaine (HL), a local anesthetics drug, has neurotoxicity. The present study aims to study the effect and molecular mechanisms of HL on spinal nerve injury in DNP. METHODS: The DNP rat model was established through a high-fat-glucose diet in combination with Streptozotocin (STZ) administration. SB203580 and PD98059 were utilized to inhibit p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK). The mechanical paw withdrawal threshold (PWT) and the thermal paw withdrawal latency (PWL) were tested to evaluate rats' mechanical allodynia and thermal hyperalgesia. Hematoxylin-eosin (H&E) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end Labeling (TUNEL) staining were performed to evaluate the pathological changes and neuron apoptosis in spinal cord tissues of L4-5. Western blotting analysis and reverse transcription-polymerase chain reaction (RT-qPCR) assay were used to measure the levels of proteins and mRNAs, respectively. RESULTS: PWT and PWL were decreased in DNP rats with serious spinal nerve injury. HL administration downregulated the PWT and PWL and aggravated spinal nerve injury in DNP rats, but isobaric lidocaine had no effects on these changes. Meanwhile, p38 MAPK/ERK signaling and PTEN-induced kinase 1 (PINK1)-mediated mitophagy were activated in DNP, which was enhanced by HL but not isobaric lidocaine. Blocking p38 MAPK/ERK signaling could effectively attenuate HL-induced spinal nerve injury and inhibit mitophagy. CONCLUSION: In summary, HL can aggravate spinal cord tissue damage in DNP rats by inducing PINK1-mediated mitophagy via activating p38 MAPK/ERK signaling. Our data provide a novel insight that supports the potential role of p38 MAPK/ERK signaling in acting as a therapeutic target for HL-induced neurotoxicity.


Subject(s)
Diabetic Neuropathies , Lidocaine , Mitophagy , Protein Kinases , Rats, Sprague-Dawley , Ubiquitin-Protein Ligases , p38 Mitogen-Activated Protein Kinases , Animals , Lidocaine/pharmacology , Rats , Diabetic Neuropathies/pathology , Diabetic Neuropathies/metabolism , Diabetic Neuropathies/etiology , p38 Mitogen-Activated Protein Kinases/metabolism , Mitophagy/drug effects , Male , Protein Kinases/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , MAP Kinase Signaling System/drug effects , Signal Transduction/drug effects
4.
J Phys Chem Lett ; : 5761-5769, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38776132

ABSTRACT

Metal-free diradicals based on polycyclic aromatic hydrocarbons are promising candidates for organic spintronics due to their stable magnetism and tunable spin coupling. However, distinguishing and elucidating the origins of ferromagnetic and antiferromagnetic interactions in these systems remain challenging. Here, we investigate the 2-OS diradical molecule sandwiched between gold electrodes using a combined density functional theory and hierarchical equations of motion approach. We find that the dihedral angle between the radical moieties controls the nature and strength of the intramolecular spin coupling, transitioning smoothly from antiferromagnetic to ferromagnetic as the angle increases. Distinct features in the inelastic electron tunneling spectra are identified that can discern the two coupling regimes, including spin excitation steps whose energies directly reveal the exchange coupling constant. Mechanical stretching of the junction is predicted to modulate the spectral line shapes by adjusting the hybridization of the molecular radicals with the electrodes. Our work elucidates the electronic origin of tunable spin interactions in 2-OS and provides spectroscopic fingerprints for characterizing magnetism in metal-free diradicals.

5.
Nat Commun ; 15(1): 4336, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773100

ABSTRACT

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures and potent biological activities. A vast majority of RiPP gene clusters remain unexplored in microbial genomes, which is partially due to the lack of rapid and efficient heterologous expression systems for RiPP characterization and biosynthesis. Here, we report a unified biocatalysis (UniBioCat) system based on cell-free gene expression for rapid biosynthesis and engineering of RiPPs. We demonstrate UniBioCat by reconstituting a full biosynthetic pathway for de novo biosynthesis of salivaricin B, a lanthipeptide RiPP. Next, we delete several protease/peptidase genes from the source strain to enhance the performance of UniBioCat, which then can synthesize and screen salivaricin B variants with enhanced antimicrobial activity. Finally, we show that UniBioCat is generalizable by synthesizing and evaluating the bioactivity of ten uncharacterized lanthipeptides. We expect UniBioCat to accelerate the discovery, characterization, and synthesis of RiPPs.


Subject(s)
Cell-Free System , Protein Processing, Post-Translational , Ribosomes , Ribosomes/metabolism , Ribosomes/genetics , Peptides/metabolism , Peptides/genetics , Peptides/chemistry , Biosynthetic Pathways/genetics , Multigene Family , Biocatalysis
6.
Front Public Health ; 12: 1375533, 2024.
Article in English | MEDLINE | ID: mdl-38756891

ABSTRACT

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.


Subject(s)
Cost-Benefit Analysis , Markov Chains , Nasopharyngeal Carcinoma , Humans , China/epidemiology , Middle Aged , Male , Adult , Female , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/genetics , Aged , Nasopharyngeal Neoplasms/diagnosis , Early Detection of Cancer/economics , Mass Screening/economics , Multifactorial Inheritance , Risk Factors , Risk Assessment
7.
J Neurosurg Spine ; : 1-8, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38759244

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion (OLIF) with or without posterior internal fixation. METHODS: The authors retrospectively reviewed the records of patients who underwent OLIF between 2017 and 2022. Endplate bone quality (EBQ), mean vertebral bone quality (MVBQ), and vertebral bone quality (VBQ) scores were measured using preoperative non-contrast-enhanced T1-weighted MRI of the lumbar spine. Logistic regression analysis was used to identify factors associated with cage subsidence. Receiver operating characteristic curve analysis was used to evaluate the value of different site-specific MRI-based assessments of bone quality in predicting cage subsidence. RESULTS: Of the 124 patients who underwent OLIF, subsidence was found in 42 (33.9%). The VBQ, MVBQ, and EBQ scores were higher in the subsidence group than in the no-subsidence group. In the stand-alone OLIF (SA-OLIF) group, logistic regression analysis showed that the EBQ score was significantly associated with subsidence (OR 13.656, 95% CI 2.561-72.806; p = 0.002). Furthermore, the areas under the curve (AUCs) for using the VBQ, MVBQ, and EBQ scores and T-score to predict cage subsidence were 0.684, 0.683, 0.745, and 0.685, respectively. In the OLIF with posterior internal fixation (OLIF-PF) group, logistic regression analysis showed that the MVBQ score was significantly associated with subsidence (OR 8.301, 95% CI 2.064-33.385; p = 0.003). The AUCs for using the VBQ score, MVBQ score, and T-score to predict cage subsidence were 0.757, 0.774, and 0.685, respectively. CONCLUSIONS: There are significant differences in the predictive value of different site-specific bone quality assessments for cage subsidence among patients undergoing OLIF. For SA-OLIF, the EBQ score is recommended, while for OLIF-PF, the VBQ score is preferable.

8.
Proc Natl Acad Sci U S A ; 121(21): e2313797121, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38709948

ABSTRACT

During 2010 to 2020, Northeast Pacific (NEP) sea surface temperature (SST) experienced the warmest decade ever recorded, manifested in several extreme marine heatwaves, referred to as "warm blob" events, which severely affect marine ecosystems and extreme weather along the west coast of North America. While year-to-year internal climate variability has been suggested as a cause of individual events, the causes of the continuous dramatic NEP SST warming remain elusive. Here, we show that other than the greenhouse gas (GHG) forcing, rapid aerosol abatement in China over the period likely plays an important role. Anomalous tropospheric warming induced by declining aerosols in China generated atmospheric teleconnections from East Asia to the NEP, featuring an intensified and southward-shifted Aleutian Low. The associated atmospheric circulation anomaly weakens the climatological westerlies in the NEP and warms the SST there by suppressing the evaporative cooling. The aerosol-induced mean warming of the NEP SST, along with internal climate variability and the GHG-induced warming, made the warm blob events more frequent and intense during 2010 to 2020. As anthropogenic aerosol emissions continue to decrease, there is likely to be an increase in NEP warm blob events, disproportionately large beyond the direct radiative effects.

9.
Nat Prod Res ; : 1-7, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752778

ABSTRACT

The fungus Penicillium egyptacum has been reported as a producer of the 16-membered macrolide antibiotic A26771B. In this study, two new berkeleylactone analogues, berkeleylactones S-T (1-2), were isolated from P. egyptiacum. Their structures were determined by the analyses of 1D- and 2D-NMR data, HRESIMS, and chemical derivatization. 1 is the first example of berkeleylactone analogue possessing a glucose moiety, whose absolute configuration was elucidated by acid hydrolysis followed by derivatization and LC-MS analysis. No antibacterial activity against Bacillus subtilis and Streptococcus salivarius was found within the range of 0-100 µM for compounds 1-2.

10.
Cancer Control ; 31: 10732748241251580, 2024.
Article in English | MEDLINE | ID: mdl-38712609

ABSTRACT

BACKGROUND: Immune-based therapies are commonly employed to combat hepatocellular carcinoma (HCC). However, the presence of immune-regulating elements, especially regulatory T cells (Tregs), can dramatically impact the treatment efficacy. A deeper examination of the immune-regulation mechanisms linked to these inhibitory factors and their impact on HCC patient outcomes is warranted. METHODS: We employed multicolor fluorescence immunohistochemistry (mIHC) to stain Foxp3, cytokeratin, and nuclei on an HCC tissue microarray (TMA). Leveraging liver cancer transcriptome data from TCGA, we built a prognostic model focused on Treg-associated gene sets and represented it with a nomogram. We then sourced liver cancer single-cell RNA sequencing data (GSE140228) from the GEO database, selectively focusing on Treg subsets, and conducted further analyses, including cell-to-cell communication and pseudo-time trajectory examination. RESULTS: Our mIHC results revealed a more substantial presence of Foxp3+Tregs in HCC samples than in adjacent normal tissue samples (P < .001). An increased presence of Foxp3+Tregs in HCC samples correlated with unfavorable patient outcomes (HR = 1.722, 95% CI:1.023-2.899, P = .041). The multi-factorial prognosis model we built from TCGA liver cancer data highlighted Tregs as a standalone risk determinant for predicting outcomes (HR = 3.84, 95% CI:2.52-5.83, P < .001). Re-analyzing the scRNA-seq dataset (GSE140228) showcased distinctive gene expression patterns in Tregs from varying tissues. Interactions between Tregs and other CD4+T cell types were predominantly governed by the CXCL13/CXCR3 signaling pathway. Communication pathways between Tregs and macrophages primarily involved MIF-CD74/CXCR4, LGALS9/CD45, and PTPRC/MRC1. Additionally, macrophages could influence Tregs via HLA-class II and CD4 interactions. CONCLUSION: An elevated presence of Tregs in HCC samples correlated with negative patient outcomes. Elucidating the interplay between Tregs and other immune cells in HCC could provide insights into the modulatory role of Tregs within HCC tissues.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , T-Lymphocytes, Regulatory , Humans , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/immunology , Liver Neoplasms/pathology , T-Lymphocytes, Regulatory/immunology , Prognosis , Forkhead Transcription Factors/metabolism , Male , Female
11.
Article in English | MEDLINE | ID: mdl-38804626

ABSTRACT

BACKGROUND: The aim of this study was to investigate the relationship between DII and sarcopenia in individuals with ischemic heart disease (IHD). METHODS: This was a retrospective study utilizing data of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. Adults aged ≥50 years diagnosed with IHD, having complete 24-hour dietary recall data, and dual energy X-ray absorptiometry (DEXA)-measured muscle mass were eligible for inclusion. Association between DII and sarcopenia, defined by reduced appendicular skeletal muscle mass, was determined by the logistic regression analyses. RESULTS: Data of 1088 individuals were analyzed, with the mean age of 68.1±0.5 years. Significantly higher DII was observed in the sarcopenic group compared to the non-sarcopenic group (0.24 vs. -0.17, P=0.020). After adjusting for relevant confounders in the multivariable analysis, each unit increase in DII was significantly associated with higher odds of sarcopenia (adjusted odd ratio [aOR]=1.07, 95% confidence interval: 1.00-1.14, P value = 0.040). In stratified analyses, among patients with a Body Mass Index (BMI) ≥30 kg/m2, both DII tertile 2 and tertile 3 were significantly associated with greater odds of sarcopenia (tertile 2 vs. tertile 1: aOR=2.85, 95% CI: 1.56-5.23, P=0.001; tertile 3 vs. tertile 1: aOR=3.11, 95% CI: 1.53-6.31, P=0.002), whereas no significant associations was observed among patients with a BMI<30 kg/m2. CONCLUSIONS: This study has established a significant independent association between a higher DII and an increased risk of sarcopenia in US adults with IHD regardless of type of IHD. BMI appears as a moderating factor in this association.

13.
Clin Transl Oncol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38769216

ABSTRACT

PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

14.
J Phys Chem Lett ; 15(16): 4333-4341, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38619466

ABSTRACT

Magnetic molecules adsorbed on two-dimensional (2D) substrates have attracted broad attention because of their potential applications in quantum device applications. Experimental observations have demonstrated substantial alteration in the spin excitation energy of iron phthalocyanine (FePc) molecules when adsorbed on nitrogen-doped graphene substrates. However, the underlying mechanism responsible for this notable change remains unclear. To shed light on this, we employ an embedding method and ab initio quantum chemistry calculations to investigate the effects of surface doping on molecular properties. Our study unveils an unconventional chemical bonding at the interface between the FePc molecule and the N-doped graphene. This bonding interaction, stronger than non-covalent interactions, significantly modifies the magnetic anisotropy energy of the adsorbed molecule, consistent with experimental observations. These findings provide valuable insights into the electronic and magnetic properties of molecules on 2D substrates, offering a promising pathway for precise manipulation of molecular spin states.

15.
Mol Cancer ; 23(1): 77, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627681

ABSTRACT

Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor activity. PD-1 inhibitors have demonstrated notable therapeutic efficacy in treating hematological and solid tumors; however, more than 50% of patients undergoing this treatment exhibit a poor response. However, ICI-based combination therapies (ICI combination therapies) have been demonstrated to synergistically increase anti-tumor effects and immune response rates. In this review, we compare the clinical efficacy and side effects of BSABs and ICI combination therapies in real-world tumor immunotherapy, aiming to provide evidence-based approaches for clinical research and personalized tumor diagnosis and treatment.


Subject(s)
Antibodies, Bispecific , Neoplasms , Humans , Antibodies, Bispecific/adverse effects , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/drug therapy , Antibodies, Monoclonal/therapeutic use , Immunotherapy/adverse effects , Immunotherapy/methods
16.
Phytochemistry ; 222: 114098, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38648960

ABSTRACT

Nine undescribed compounds, along with eight known compounds, were isolated from the stipes of Lentinus edodes. Their structures were established by extensive spectroscopic and circular dichroism analyses. The protective effects against Aß25-35-induced N9 microglia cells injury of these compounds were tested by MTT method, and the levels of apoptosis and ROS were detected by flow cytometry. In addition, the binding sites and interactions of compound with amyloid precursor protein were revealed using molecular docking simulations. These findings further establish the structural diversity and bioactivity of stipes of L. edodes, and provide an experimental basis for targeting Alzheimer's disease as a potential strategy.


Subject(s)
Amyloid beta-Peptides , Apoptosis , Microglia , Molecular Docking Simulation , Peptide Fragments , Microglia/drug effects , Microglia/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Peptide Fragments/pharmacology , Animals , Apoptosis/drug effects , Mice , Molecular Structure , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Dose-Response Relationship, Drug , Lentinula/chemistry , Cell Line
17.
Phys Chem Chem Phys ; 26(17): 13395-13404, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38647031

ABSTRACT

Carbonaceous materials are promising candidates as anode materials for non-lithium-ion batteries (NLIBs) due to their appealing properties such as good electrical conductivity, low cost, and high safety. However, graphene, a classic two-dimensional (2D) carbon material, is chemically inert to most metal atoms, hindering its application as an electrode material for metal-ion batteries. Inspired by the unique geometry of a four-penta unit, we explore a metallic 2D carbon allotrope C5-10-16 composed of 5-10-16 carbon rings. The C5-10-16 monolayer is free from any imaginary frequencies in the whole Brillouin zone. Due to the introduction of a non-sp2 hybridization state into C5-10-16, the extended conjugation of π-electrons is disrupted, leading to the enhanced surface activity toward metal ions. We investigate the performance of C5-10-16 as the anode for sodium/potassium-ion batteries by using first-principles calculations. The C5-10-16 sheet has high theoretical specific capacities of Na (850.84 mA h g-1) and K (743.87 mA h g-1). Besides, C5-10-16 exhibits a moderate migration barrier of 0.63 (0.32) eV for Na (K), ensuring rapid charging/discharging processes. The average open-circuit voltages of Na and K are 0.33 and 0.62 V, respectively, which are within the voltage acceptance range of anode materials. The fully sodiated (potassiated) C5-10-16 shows tiny lattice expansions of 1.4% (1.3%), suggesting the good reversibility. Moreover, bilayer C5-10-16 significantly affects both the adsorption strength and the mobility of Na or K. All these results show that C5-10-16 could be used as a promising anode material for NLIBs.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 556-560, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660866

ABSTRACT

OBJECTIVE: To investigate the efficiency and optimal time of stem cell apheresis mobilized by pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in autologous stem cell transplantation (ASCT) for hematological malignancies without monitoring pre-collection CD34+ cells. METHODS: Forty-six patients underwent stem cell mobilization were retrospectively analyzed between August 2017 and January 2022 at the First Affiliated Hospital of Fujian Medical University. 27 patients using high dose chemotherapy combined with PEG-rhG-CSF mobilization were enrolled in the PEG-rhG-CSF group, and other 19 patients mobilized with recombinant human granulocyte colony stimulating factor (G-CSF) were enrolled in G-CSF group. The mobilization and collection effects of the patients in two groups were compared. RESULTS: A total of 46 patients underwent 86 apheresis procedures, the median amount of mononuclear cell (MNC) in the PEG-rhG-CSF group and G-CSF group was 6.54(3.85-12.61)×108/kg and 6.15(1.13-11.58)×108/kg, respectively (P >0.05), the total CD34+ cells of the grafts were 11.44(1.33-65.02)×106/kg and 4.95(0.30-24.02)×106/kg (P < 0.05), with harvest timing of 14(10-20) days and 14(4-22) days, respectively (P >0.05). In the PEG-rhG-CSF group, there was a significant difference between the number of CD34+ cells collected when white blood cells (WBC) ≥10×109/L and WBC<10×109 /L, 19.04(2.85-65.02)×106/kg and 6.22(0.81-34.86)×106/kg, respectively (P < 0.05). CONCLUSION: Stem cells mobilization with PEG-rhG-CSF was highly efficient with a median mobilization time of 14 days. In the absence of peripheral blood CD34 monitoring, peripheral blood WBC≥10×109/L can be considered as a threshold for a single stem cell apheresis to collect sufficient stem cells.


Subject(s)
Granulocyte Colony-Stimulating Factor , Hematologic Neoplasms , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Polyethylene Glycols , Recombinant Proteins , Transplantation, Autologous , Humans , Granulocyte Colony-Stimulating Factor/administration & dosage , Retrospective Studies , Hematologic Neoplasms/therapy , Antigens, CD34 , Hematopoietic Stem Cells/cytology , Female , Male
19.
Nano Lett ; 24(17): 5324-5331, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38624236

ABSTRACT

Phase transformation offers an alternative strategy for the synthesis of nanomaterials with unconventional phases, allowing us to further explore their unique properties and promising applications. Herein, we first observed the amorphization of Pt nanoparticles on the RuO2 surface by in situ scanning transmission electron microscopy. Density functional theory calculations demonstrate the low energy barrier and thermodynamic driving force for Pt atoms transferring from the Pt cluster to the RuO2 surface to form amorphous Pt. Remarkably, the as-synthesized amorphous Pt/RuO2 exhibits 14.2 times enhanced mass activity compared to commercial RuO2 catalysts for the oxygen evolution reaction (OER). Water electrolyzer with amorphous Pt/RuO2 achieves 1.0 A cm-2 at 1.70 V and remains stable at 200 mA cm-2 for over 80 h. The amorphous Pt layer not only optimized the *O binding but also enhanced the antioxidation ability of amorphous Pt/RuO2, thereby boosting the activity and stability for the OER.

20.
Surg Endosc ; 38(5): 2788-2794, 2024 May.
Article in English | MEDLINE | ID: mdl-38587640

ABSTRACT

AIM: To analyze efficacy of endoscopic lithotripsy combined with drug lithotripsy as compared with drug lithotripsy for the treatment of phytobezoars. METHODS: We collected and evaluated case records of 165 patients with phytobezoars from 2014 to 2023. And we analyzed demographic and clinical characteristics, imaging features, endoscopic features, complications of phytobezoars, and compared efficacy between endoscopic lithotripsy combined with drug lithotripsy (Group A) and drug lithotripsy (sodium bicarbonate combined with proton pump inhibitor) (Group B). RESULTS: The median age of patients with phytobezoars was 67.84 ± 4.286 years old. Abdominal pain was the most common symptom and peptic ulcers (67.5%) were the most common complication. Bezoar-induced ulcers were more frequent in the gastric angle. The success rate of phytobezoars vanishing in Group A and Group B were similar (92.3% vs. 85.1% within 48 h, 98.7% vs. 97.7% within a week), while the average hospitalization period, average hospitalization cost, second endoscopy rate, and average endoscopic operation time were significantly lower in patients in Group B than in Group A. CONCLUSION: Drug lithotripsy is the preferred effective and safe treatment option for phytobezoars. We advise that an endoscopy should be completed after 48 h for drug lithotripsy.


Subject(s)
Bezoars , Lithotripsy , Humans , Bezoars/therapy , Male , Female , Lithotripsy/methods , Aged , Middle Aged , Retrospective Studies , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Treatment Outcome , Sodium Bicarbonate/administration & dosage , Sodium Bicarbonate/therapeutic use , Combined Modality Therapy , Abdominal Pain/etiology , Abdominal Pain/therapy
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