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1.
BMC Microbiol ; 24(1): 237, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961326

ABSTRACT

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.


Subject(s)
Bacteroidetes , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Immunotherapy , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/microbiology , Animals , Humans , Mice , Immunotherapy/methods , Bacteroidetes/genetics , Bacteroidetes/immunology , Female , Male , RNA, Ribosomal, 16S/genetics , Feces/microbiology , Middle Aged , Aged , Mice, Inbred C57BL
2.
J Environ Manage ; 365: 121683, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38963968

ABSTRACT

Ammonia recovery from wastewater has positive environmental benefits, avoiding eutrophication and reducing production energy consumption, which is one of the most effective ways to manage nutrients in wastewater. Specifically, ammonia recovery by membrane distillation has been gradually adopted due to its excellent separation properties for volatile substances. However, the global optimization of direct contact membrane distillation (DCMD) operating parameters to maximize ammonia recovery efficiency (ARE) has not been attempted. In this work, three key operating factors affecting ammonia recovery, i.e., feed ammonia concentration, feed pH, and DCMD running time, were identified from eight factors, by a two-level Plackett-Burman Design (PBD). Subsequently, Box-Behnken design (BBD) under the response surface methodology (RSM) was used to model and optimize the significant operating parameters affecting the recovery of ammonia though DCMD identified by PBD and statistically verified by analysis of variance (ANOVA). Results showed that the model had a high coefficient of determination value (R2 = 0.99), and the interaction between NH4Cl concentration and feed pH had a significant effect on ARE. The optimal operating parameters of DCMD as follows: NH4Cl concentration of 0.46 g/L, feed pH of 10.6, DCMD running time of 11.3 h, and the maximum value of ARE was 98.46%. Under the optimized conditions, ARE reached up to 98.72%, which matched the predicted value and verified the validity and reliability of the model for the optimization of ammonia recovery by DCMD process.

3.
World J Clin Cases ; 12(16): 2869-2875, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38899294

ABSTRACT

BACKGROUND: Vascular malformations (VMs) arise as a result of errors in the process of angiogenesis and are usually present at birth, but may not become apparent until after birth. However, giant VMs of the head and face are uncommon, with few reported cases, and the prognosis for their surgical intervention is unclear. CASE SUMMARY: A 12-year-old girl was admitted to the hospital with findings of an enlarged right temporal scalp. After admission, computed tomography (CT) angiography of cerebral ateries showed a right occlusal gap and a right temporal artery venous malformation. Furthermore, cerebral angiography showed a right temporal lobe VM with multiple vessels supplying blood. The patient underwent surgery to remove the malformed vessels and the eroded skull. Two hours after the surgery, the patient's right pupil was dilated, and an urgent CT scan of the skull showed a right subdural haematoma under the incision, which was urgently removed by a second operation. After surgery, we gave continuous antibiotic anti-infection treatment, and the patient recovered well and was discharged two weeks later. CONCLUSION: Surgical removal of giant haemangiomas is risky and adequate preoperative (including interventional embolisation) and intraoperative preparations should be made.

4.
Adv Sci (Weinh) ; : e2402380, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837633

ABSTRACT

Simultaneously achieving high-energy-density and high-power-density is a crucial yet challenging objective in the pursuit of commercialized power batteries. In this study, atomic layer deposition (ALD) is employed combined with a coordinated thermal treatment strategy to construct a densely packed, electron-ion dual conductor (EIC) protective coating on the surface of commercial LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode material, further enhanced by gradient Al doping (Al@EIC-NCM523). The ultra-thin EIC effectively suppresses side reactions, thereby enhancing the stability of the cathode-electrolyte interphase (CEI) at high-voltages. The EIC's dual conduction capability provides a potent driving force for Li+ transport at the interface, promoting the formation of rapid ion deintercalation pathways within the Al@EIC-NCM523 bulk phase. Moreover, the strategic gradient doping of Al serves to anchor the atomic spacing of Ni and O within the structure of Al@EIC-NCM523, curbing irreversible phase transitions at high-voltages and preserving the integrity of its layered structure. Remarkably, Al@EIC-NCM523 displays an unprecedented rate capability (114.7 mAh g-1 at 20 C), and a sustained cycling performance (capacity retention of 74.72% after 800 cycles at 10 C) at 4.6 V. These findings demonstrate that the proposed EIC and doping strategy holds a significant promise for developing high-energy-density and high-power-density lithium-ion batteries (LIBs).

5.
Phys Rev Lett ; 132(21): 216903, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38856288

ABSTRACT

Controlling interlayer excitons in Van der Waals heterostructures holds promise for exploring Bose-Einstein condensates and developing novel optoelectronic applications, such as excitonic integrated circuits. Despite intensive studies, several key fundamental properties of interlayer excitons, such as their binding energies and interactions with charges, remain not well understood. Here we report the formation of momentum-direct interlayer excitons in a high-quality MoSe_{2}/hBN/MoSe_{2} heterostructure under an electric field, characterized by bright photoluminescence (PL) emission with high quantum yield and a narrow linewidth of less than 4 meV. These interlayer excitons show electrically tunable emission energy spanning ∼180 meV through the Stark effect, and exhibit a sizable binding energy of ∼81 meV in the intrinsic regime, along with trion binding energies of a few millielectronvolts. Remarkably, we demonstrate the long-range transport of interlayer excitons with a characteristic diffusion length exceeding 10 µm, which can be attributed, in part, to their dipolar repulsive interactions. Spatially and polarization-resolved spectroscopic studies reveal rich exciton physics in the system, such as valley polarization, local trapping, and the possible existence of dark interlayer excitons. The formation and transport of tightly bound interlayer excitons with narrow linewidth, coupled with the ability to electrically manipulate their properties, open exciting new avenues for exploring quantum many-body physics, including excitonic condensate and superfluidity, and for developing novel optoelectronic devices, such as exciton and photon routers.

7.
Colloids Surf B Biointerfaces ; 240: 113998, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823340

ABSTRACT

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Nanocomposites , Staphylococcus aureus , Wound Healing , Nanocomposites/chemistry , Wound Healing/drug effects , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Photochemotherapy , Microbial Sensitivity Tests , Mice , Sterilization/methods , Ferrocyanides/chemistry , Ferrocyanides/pharmacology , Particle Size , Zinc/chemistry , Zinc/pharmacology , Photothermal Therapy , Surface Properties , Nitrogen Compounds/chemistry , Nitrogen Compounds/pharmacology , Graphite
8.
Huan Jing Ke Xue ; 45(6): 3459-3467, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897766

ABSTRACT

Road transport is the primary source of greenhouse gas emissions in China's transportation field. As an important means to achieve the "double carbon" goal in the transportation field, the new energy automobile industry will face a large number of power battery scrapping in the future. In order to quantitatively assess the carbon emission reduction benefits generated by the spent ternary lithium-ion battery waste recycling industry, the carbon footprint accounting model of spent ternary lithium-ion battery waste recycling and utilization was constructed from the life cycle perspective. By optimizing the power structure and transportation structure, the carbon emission reduction potential of spent ternary lithium-ion battery waste recycling was predicted and evaluated. In addition, the uncertainty analysis was conducted using the propagation of uncertainty equation to ensure the reliability and effectiveness of the carbon footprint results. The results showed that the current carbon footprint of Chinese enterprises using wet technology to recover 1 kg waste lithium batteries was -2 760.90 g (directional recycling process) and -3 752.78 g (recycling process), and the uncertainty of the carbon footprint was 16 % (directional recycling process) and 15 % (recycling process), respectively. From the analysis of carbon emission contribution, the regenerated product stage was the primary source of carbon reduction in the wet recycling and utilization of waste ternary lithium batteries, whereas the battery acquisition, disassembly, and end treatment stages were the main sources of carbon increase. Compared to optimizing the transportation structure, optimizing the power structure could effectively achieve greater carbon emission reduction potential. Under the collaborative optimization scenario, compared to that before optimization, 14 %-19 % carbon emission reduction could be achieved. Compared with native products, the directional circulation process and recycling process could achieve 9 % and 11 % emission reduction potential, respectively.

9.
World J Urol ; 42(1): 302, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720010

ABSTRACT

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.


Subject(s)
Contrast Media , Ferric Compounds , Iron , Kidney Neoplasms , Magnetic Resonance Imaging , Oxides , Tomography, X-Ray Computed , Ultrasonography , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Male , Female , Middle Aged , Prospective Studies , Ultrasonography/methods , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging/methods , Aged , Diagnosis, Differential , Adult , Aged, 80 and over
10.
J Org Chem ; 89(11): 8041-8054, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38757188

ABSTRACT

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

11.
Molecules ; 29(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38731557

ABSTRACT

The supramolecular solvent (SUPRAS) has garnered significant attention as an innovative, efficient, and environmentally friendly solvent for the effective extraction and separation of bioactive compounds from natural resources. However, research on the use of a SUPRAS for the extraction of phenolic compounds from plants, which are highly valued in food products due to their exceptional antioxidant properties, remains scarce. The present study developed a green, ultra-sound-assisted SUPRAS method for the simultaneous determination of three phenolic acids in Prunella vulgaris using high-performance liquid chromatography (HPLC). The experimental parameters were meticulously optimized. The efficiency and antioxidant properties of the phenolic compounds obtained using different extraction methods were also compared. Under optimal conditions, the extraction efficiency of the SUPRAS, prepared with octanoic acid reverse micelles dispersed in ethanol-water, significantly exceeded that of conventional organic solvents. Moreover, the SUPRAS method demonstrated greater antioxidant capacity. Confocal laser scanning microscopy (CLSM) images revealed the spherical droplet structure of the SUPRAS, characterized by a well-defined circular fluorescence position, which coincided with the position of the phenolic acids. The phenolic acids were encapsulated within the SUPRAS droplets, indicating their efficient extraction capacity. Furthermore, molecular dynamics simulations combined with CLSM supported the proposed method's mechanism and theoretically demonstrated the superior extraction performance of the SUPRAS. In contrast to conventional methods, the higher extraction efficiency of the SUPRAS can be attributed to the larger solvent contact surface area, the formation of more types of hydrogen bonds between the extractants and the supramolecular solvents, and stronger, more stable interaction forces. The results of the theoretical studies corroborate the experimental outcomes.


Subject(s)
Antioxidants , Phenols , Plant Extracts , Solvents , Solvents/chemistry , Phenols/chemistry , Phenols/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Plant Extracts/chemistry , Chromatography, High Pressure Liquid/methods , Green Chemistry Technology , Molecular Dynamics Simulation , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification
12.
Nat Chem ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719944

ABSTRACT

Chiral sulfur pharmacophores are crucial for drug discovery in bioscience and medicinal chemistry. While the catalytic asymmetric synthesis of sulfoxides and sulfinate esters with stereogenic-at-sulfur(IV) centres is well developed, the synthesis of chiral sulfinamides remains challenging, which has primarily been attributed to the high nucleophilicity and competing reactions of amines. In this study, we have developed an efficient methodology for the catalytic asymmetric synthesis of chiral sulfinamides and sulfinate esters by the sulfinylation of diverse nucleophiles, including aromatic amines and alcohols, using our bifunctional chiral 4-arylpyridine N-oxides as catalysts. The remarkable results are a testament to the efficiency, versatility and broad applicability of the developed synthetic approach, serving as a valuable tool for the synthesis of sulfur pharmacophores. Mechanistic experiments and density functional theory calculations revealed that the initiation and stereocontrol of this reaction are induced by an acyl transfer catalyst. Our research provides an efficient approach for the construction of optically pure sulfur(IV) centres.

13.
Mol Med Rep ; 30(1)2024 07.
Article in English | MEDLINE | ID: mdl-38757304

ABSTRACT

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8­week 2% NaCl­feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD­associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/ß­catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt­induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/ß­catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.


Subject(s)
Drugs, Chinese Herbal , Gastrointestinal Microbiome , Pueraria , Renal Insufficiency, Chronic , Wnt Signaling Pathway , Gastrointestinal Microbiome/drug effects , Animals , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Wnt Signaling Pathway/drug effects , Mice , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Male , Pueraria/chemistry , Disease Models, Animal , Dysbiosis/drug therapy , Down-Regulation/drug effects , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Mice, Inbred C57BL , Fecal Microbiota Transplantation
14.
Angew Chem Int Ed Engl ; : e202407898, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739536

ABSTRACT

The quest for smart electronics with higher energy densities has intensified the development of high-voltage LiCoO2 (LCO). Despite their potential, LCO materials operating at 4.7 V faces critical challenges, including interface degradation and structural collapse. Herein, we propose a collective surface architecture through precise nanofilm coating and doping that combines an ultra-thin LiAlO2 coating layer and gradient doping of Al. This architecture not only mitigates side reactions, but also improves the Li+ migration kinetics on the LCO surface. Meanwhile, gradient doping of Al inhibited the severe lattice distortion caused by the irreversible phase transition of O3-H1-3-O1, thereby enhanced the electrochemical stability of LCO during 4.7 V cycling. DFT calculations further revealed that our approach significantly boosts the electronic conductivity. As a result, the modified LCO exhibited an outstanding reversible capacity of 230 mAh g-1 at 4.7 V, which is approximately 28 % higher than the conventional capacity at 4.5 V. To demonstrate their practical application, our cathode structure shows improved stability in full pouch cell configuration under high operating voltage. LCO exhibited an excellent cycling stability, retaining 82.33 % after 1000 cycles at 4.5 V. This multifunctional surface modification strategy offers a viable pathway for the practical application of LCO materials, setting a new standard for the development of high-energy-density and long-lasting electrode materials.

15.
MedComm (2020) ; 5(6): e547, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38764726

ABSTRACT

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

16.
Chem Biodivers ; 21(6): e202400507, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38606561

ABSTRACT

Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3 nM.


Subject(s)
Aureobasidium , Nitric Oxide , Animals , Mice , Aureobasidium/chemistry , Aureobasidium/metabolism , Cell Line , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Molecular Conformation , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Nitric Oxide/metabolism , Lactones
17.
Apoptosis ; 29(5-6): 835-848, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38573492

ABSTRACT

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.


Subject(s)
Colorectal Neoplasms , Drug Resistance, Neoplasm , Ferroptosis , Oxaliplatin , PTEN Phosphohydrolase , Animals , Humans , Mice , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Ferroptosis/drug effects , Ferroptosis/genetics , Gene Expression Regulation, Neoplastic/drug effects , Mice, Nude , Oxaliplatin/pharmacology , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Xenograft Model Antitumor Assays , Male
18.
Chem Commun (Camb) ; 60(38): 5018-5021, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38639063

ABSTRACT

Thioglycoside bond formation via an asymmetric sulfa-Michael/aldol reaction of (E)-ß-nucleobase acrylketones and 1,4-dithiane-2,5-diol has been achieved with a cinchona alkaloid-derived bifunctional squaramide chiral catalyst. Diverse purine, benzimidazole, and imidazole substrates are well tolerated and generate 4'-thionucleoside derivatives containing three contiguous stereogenic centers with excellent results (30 examples, up to 97% yield, >20 : 1 dr and up to 99% ee). Moreover, the novel strategy provides an efficient and convenient synthetic route to construct chiral 4'-thionucleosides.

19.
Heliyon ; 10(7): e28458, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601543

ABSTRACT

In managing unique complexities associated with Chinese medicinal quality assessment, metabolomics serves as an innovative tool. This study proposes an analytical approach to assess differing qualities of Scrophularia ningpoensis (S. ningpoensis)Hemsl by identifying potential biomarker metabolites and their activity with the corresponding secondary metabolites. The methodology includes four steps; first, a GC-MS based metabolomics exploration of the Scrophularia ningpoensis Hemsl. Second, a multivariate statistical analysis (PCA, PLS-DA, OPLS-DA) for quality assessment and biomarker identification. Third, the application of ROC analysis and pathway analysis based on identified biomarkers. Finally, validation of the associated active ingredients by HPLC. The analysis showed distinct metabolite profiles across varying grades of S. ningpoensis Hemsl, establishing a grading dependency relationship. Select biomarkers (gluconic Acid, d-xylulose, sucrose, etc.) demonstrated robust grading performances. Further, the Pentose Phosphate Pathway, deemed as most influential in grading, was tied to the synthesis of key constituents (iridoids, phenylpropanoids). HPLC validation tests affirm a decreasing trend in harpagoside and cinnamic acid levels between first and third-grade samples. In conclusion, this GC-MS based metabolomics combined HPLC method offers a sound approach to assess and distinguish quality variations in S. ningpoensis Hemsl samples.

20.
Vaccine ; 42(12): 3091-3098, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38594120

ABSTRACT

BACKGROUND: The study evaluated the protective effect of 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against all-cause hospitalized pneumonia in children in Beijing. METHODS: Based on the vaccination record and inpatient medical record database of Beijing, children born in 2017 in Beijing, matched by age, gender, and district of the children with the ratio of 1:4, were selected as the vaccinated and unvaccinated groups according whether if vaccinated with PCV13. The incidence rate and 95 % confidence interval (95 %CI), vaccine effectiveness (VE) and direct medical costs of all-cause hospitalized pneumonia were calculated and compared within the same period of 12 months, 18 months, 24 months and 30 months after the birth of the child. RESULTS: The decreased incidence rates of all-cause hospitalized pneumonia were observed at the four points in the PCV13 vaccinated group compared to the unvaccinated group, which were significant at the points of 12 months (0.42 % vs. 0.72 %, P = 0.001), 18 months (0.90 % vs. 1.26 %, P = 0.002) and 24 months (1.37 % vs. 1.65 %, P = 0.046). The VE of PCV13 against all-cause hospitalized pneumonia within 12 months was the highest as 41.9 % (95 % CI 19.6 %, 58.0 %), followed by 29.3 % (95 % CI 11.4 %, 43.5 %) within 18 months, 17.1 % (95 % CI 0.3 %, 31.1 %) within 24 months and it almost disappeared within 30 months. The VE of 4-dose vaccination within 18 months and 24 months were 39.9 % (95 % CI 20.3 %, 54.7 %) and 27.2 % (95 % CI 8.6 %, 42.0 %), respectively. The median hospitalization cost of the children in the vaccinated group was higher at the four points but without significance. CONCLUSIONS: PCV13 had a certain protective effect on all-cause hospitalized pneumonia, and the booster immunization strategy had the best protective effect with great public health significance to enter the immunization program.


Subject(s)
Pneumococcal Infections , Pneumonia, Pneumococcal , Child , Humans , Infant , Pneumococcal Infections/prevention & control , Streptococcus pneumoniae , Beijing/epidemiology , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Pneumococcal Vaccines , Hospitalization , Vaccines, Conjugate
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