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1.
Bioresour Technol ; : 130686, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599351

RESUMO

Although there are many microorganisms in nature, the limitations of isolation and cultivation conditions have restricted the development of artificial enhanced remediation technology using functional microbial communities. In this study, an integrated technology of Magnetic Nanoparticle-mediated Enrichment (MME) and Microfluidic Single Cell separation (MSC) that breaks through the bottleneck of traditional separation and cultivation techniques and can efficiently obtain more in situ functional microorganisms from the environment was developed. MME technology was first used to enrich rapidly growing active bacteria in the environment. Subsequently, MSC technology was applied to isolate and incubate functional bacterial communities in situ and validate the degradation ability of individual bacteria. As a result, this study has changed the order of traditional pure culture methods, which are first selected and then cultured, and provided a new method for obtaining non-culturable functional microorganisms.

2.
Cell Death Differ ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654072

RESUMO

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.

3.
ACS Sens ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642064

RESUMO

Gas sensors play a crucial role in various industries and applications. In recent years, there has been an increasing demand for gas sensors in society. However, the current method for screening gas-sensitive materials is time-, energy-, and cost-consuming. Consequently, an imperative exists to enhance the screening efficiency. In this study, we proposed a collaborative screening strategy through integration of density functional theory and machine learning. Taking zinc oxide (ZnO) as an example, the responsiveness of ZnO to the target gas was determined quickly on the basis of the changes in the electronic state and structure before and after gas adsorption. In this work, the adsorption energy and electronic and structural characteristics of ZnO after adsorbing 24 kinds of gases were calculated. These computed features served as the basis for training a machine learning model. Subsequently, various machine learning and evaluation algorithms were utilized to train the fast screening model. The importance of feature values was evaluated by the AdaBoost, Random Forest, and Extra Trees models. Specifically, charge transfer was assigned importance values of 0.160, 0.127, and 0.122, respectively, ranking as the highest among the 11 features. Following closely was the d-band center, which was presumed to exert influence on electrical conductivity and, consequently, adsorption properties. With 5-fold cross-validation using the Extra Tree accuracy, the 24-sample data set achieved an accuracy of 88%. The 72-sample data set achieved an accuracy of 78% using multilayer perceptron after 5-fold cross-validation, with both data sets exhibiting low standard deviations. This verified the accuracy and reliability of the strategy, showcasing its potential for rapidly screening a material's responsiveness to the target gas.

4.
Food Chem ; 450: 139285, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38631203

RESUMO

Theaflavins are beneficial to human health due to various bioactivities. Biosynthesis of theaflavins using polyphenol oxidase (PPO) is advantageous due to cost effectiveness and environmental friendliness. In this review, studies on the mechanism of theaflavins formation, the procedures to screen and prepare PPOs, optimization of reaction systems and immobilization of PPOs were described. The challenges associated with the mass biosynthesis of theaflavins, such as poor enzyme activity, undesirable subproducts and inclusion bodies of recombinant PPOs were presented. Further strategies to solve these challenges and improve theaflavins production, including enzyme engineering, immobilization enzyme technology, water-immiscible solvent-water biphasic systems and recombinant enzyme technology, were proposed.

5.
Materials (Basel) ; 17(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38541473

RESUMO

To reduce the damage to reinforced concrete shear walls in earthquakes and repair costs, a self-centering wall with sloped plane friction dampers (SPFDs) is proposed. In addition to the SPFDs, the proposed wall includes a precast composite wall, steel wall toes, and post-tensioned (PT) tendons. The steel wall toes embedded in the base of the precast wall were used to improve its strength, and the SPFDs installed in the steel toes were used to increase its energy dissipation capacity. To investigate the effect of the initial PT force and prestressing clamping force of the friction bolt on the seismic performance of the wall, quasistatic cyclic loading tests were carried out on three precast wall specimens. The damage to the self-centering walls was slight, the residual drift was small, and the energy dissipation met the specification requirements. The wall with the greater initial PT force showed higher self-centering and bearing capacity, and the wall with higher prestressing clamping forces showed greater energy dissipation capacity. Additionally, a calculation method for the bearing capacity of the precast wall, which was verified by comparison with the test results, is suggested.

6.
Oncol Rep ; 51(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456536

RESUMO

Definitive concurrent chemoradiotherapy has been the main standard treatment method for unresectable locally advanced esophageal squamous cell cancer (ESCC) since 1999. However, several disadvantages continue to be associated with this type of treatment, including a high local failure rate (reaching ~50% within 3 years) and a median overall survival (OS) time of 16.9 months. In addition, the 5­year overall survival rate of patients remains relatively low, at only ~21% for patients with ESCC with TNM stage T1­3N0­1M0. Burgeoning clinical trials and continually updating treatment modalities are currently in the process of being developed for the treatment of unresectable locally advanced ESCC. Compared with definitive concurrent chemoradiotherapy alone, clinical trials that have examined the efficacy of induction therapy, consolidation therapy, immunotherapy and targeted therapy have observed a prolonged median progression­free survival and OS. Salvage surgery can also bring benefits to some patients. Therefore, the present review aimed to provide a comprehensive overview on the latest progress that is being made in the development of treatment strategies for unresectable locally advanced ESCC, taking into account the several new challenges that need to be overcome.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Quimiorradioterapia/métodos , Células Epiteliais
7.
Am J Cancer Res ; 14(1): 73-85, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323293

RESUMO

This study aimed to construct nomograms for predicting the likelihood of clinically significant prostate cancer (csPCa) in patients with lesions rated as Prostate Imaging Reporting and Data System (PI-RADS) 3 on biparametric magnetic resonance imaging (bpMRI). We retrospectively analyzed a cohort of 457 patients from the Peking Union Medical College Hospital (January 2017-July 2021) to develop the model and externally validated it with a cohort of 238 patients from the Second Hospital of Tianjin Medical University (September 2017-September 2021). Univariate and multivariate logistic regression analyses identified significant predictors of csPCa, defined by tumor volumes ≥ 0.5 cm3, Gleason score ≥ 7, or presence of extracapsular extension. Diagnostic performance for the peripheral zone (PZ) and transitional zone (TZ) was compared using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Through univariate and multivariate logistic regression analyses, we identified age, prostate-specific antigen (PSA), and prostate volume (PV) as predictors of csPCa for the PZ, and age, serum-free to total PSA ratio (f/t PSA), and PSA density (PSAD) for the TZ. The nomograms demonstrated robust discriminative ability, with an area under the ROC curve (AUC) of 0.819 for PZ and 0.804 for TZ. The external validation corroborated the model's high predictive accuracy (AUC of 0.831 for PZ and 0.773 for TZ). Calibration curves indicated excellent agreement between predicted and observed outcomes, and DCA underscored the nomogram's clinical utility for both PZ and TZ. Overall, the nomograms offer high predictive accuracy for csPCa at initial biopsy, potentially reducing unnecessary biopsies in clinical settings.

8.
J Vis Exp ; (203)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38314772

RESUMO

With the advancement of multi-photon microscopy and molecular technologies, fluorescence imaging is rapidly growing to become a powerful approach for studying the structure, function, and plasticity of living brain tissues. In comparison to conventional electrophysiology, fluorescence microscopy can capture the neural activity as well as the morphology of the cells, enabling long-term recordings of the identified neuron populations at single-cell or subcellular resolution. However, high-resolution imaging typically requires a stable, head-fixed setup that restricts the movement of the animal, and the preparation of a flat surface of transparent glass allows visualization of neurons at one or more horizontal planes but is limited in studying the vertical processes running across different depths. Here, we describe a procedure to combine a head plate fixation and a microprism that gives multilayer and multimodal imaging. This surgical preparation not only gives access to the entire column of the mouse visual cortex but allows two-photon imaging in a head-fixed position and one-photon imaging in a freely moving paradigm. Using this approach, one can sample identified cell populations across different cortical layers, register their responses under head-fixed and freely moving states, and track the long-term changes over months. Thus, this method provides a comprehensive assay of the microcircuits, enabling direct comparison of neural activities evoked by well-controlled stimuli and under a natural behavioral paradigm.


Assuntos
Movimento , Neurônios , Camundongos , Animais , Neurônios/fisiologia , Microscopia de Fluorescência , Imagem Óptica
9.
Int J Biol Macromol ; 260(Pt 1): 129435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228205

RESUMO

Caulerpa lentillifera polysaccharide (CLP) has been characterized as a sulfated polysaccharide which can effectively inhibit lipid digestion. However, little information was known regarding its inhibitory mechanisms. In the present study, desulfation and degradation were conducted to prepare the derivatives of CLP, and a series of chemical and spectroscopic methods were used to elucidate the structure-activity relationship of CLP on the inhibitory effect of lipid digestion. Results revealed that CLP possessed excellent binding capacities for sodium cholate, sodium glycocholate, and sodium taurocholate. In addition, CLP can effectively inhibit lipase activity by quenching the fluorescence intensity, changing the secondary structure, and decreasing the UV-Vis absorbance. Of note, sulfate groups in CLP took a vital role in inhibiting lipase activity, while the molecular weight of CLP showed a positive correlation with the binding activities of bile acids. Furthermore, adding CLP into the whey protein isolate (WPI) emulsion system also impeded lipid digestion, indicating that CLP can be a potential reduced-fat nutraceutical used in food emulsion systems.


Assuntos
Caulerpa , 60578 , Lipídeos , Polissacarídeos , Emulsões , Polissacarídeos/química , Relação Estrutura-Atividade , Digestão , Lipase
10.
Mol Clin Oncol ; 20(1): 4, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223404

RESUMO

Compared with postoperative adjuvant therapy, neoadjuvant therapy has more potential advantages, such as decreasing tumor stage, killing micrometastatic cells. Because of these advantages, neoadjuvant therapy is recommended for numerous types of tumor, such as breast, lung and rectal cancer. To determine the role of neoadjuvant therapy on overall survival and adverse for patients with resectable esophageal carcinoma. we summarized clinical studies on 7 types of neoadjuvant therapies in this review. Currently, patients with esophageal cancer (EC) in China mainly receive postoperative treatment with <30% of patients receiving neoadjuvant therapy. One reason for the limited use of neoadjuvant therapy in China is inaccurate staging based on imaging and neoadjuvant treatment may increase difficulties in surgery. After neoadjuvant therapy, there may be tissue edema, blurry surgical field of view and unclear tissue gaps, resulting in greater difficulty in surgical procedures. However, oncologists are interested in neoadjuvant treatment, especially neoadjuvant immunotherapy to treat EC. Concurrent chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) is the most common neoadjuvant treatment regimen and increases the pathological complete response (pCR) and 5- and 10-year survival rates. Preoperative induction chemotherapy and sequential concurrent chemoradiotherapy are currently the most widely treatments used in clinical practice in China. However, this treatment strategy does not yield long-term survival. The pCR rate of neoadjuvant immunotherapy is greater than that of concurrent chemoradiotherapy but, to the best of our knowledge, no evidence of long-term survival benefit has been found in phase I and II clinical trials. Neoadjuvant treatment should be considered for patients with locally advanced ESCC.

11.
Neuron ; 112(5): 821-834.e4, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38134920

RESUMO

Electrical stimulation is an effective tool for mapping and altering brain connectivity, with applications ranging from treating pharmacology-resistant neurological disorders to providing sensory feedback for neural prostheses. Paramount to the success of these applications is the ability to manipulate electrical currents to precisely control evoked neural activity patterns. However, little is known about stimulation-evoked responses in inhibitory neurons nor how stimulation-evoked activity patterns depend on ongoing neural activity. In this study, we used 2-photon imaging and cell-type specific labeling to measure single-cell responses of excitatory and inhibitory neurons to electrical stimuli in the visual cortex of awake mice. Our data revealed strong interactions between electrical stimulation and pre-stimulus activity of single neurons in awake animals and distinct recruitment and response patterns for excitatory and inhibitory neurons. This work demonstrates the importance of cell-type-specific labeling of neurons in future studies.


Assuntos
Neurônios , Vigília , Camundongos , Animais , Vigília/fisiologia , Neurônios/fisiologia , Córtex Cerebral , Estimulação Elétrica , Mamíferos , Inibição Neural/fisiologia
12.
J Clin Invest ; 133(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099497

RESUMO

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies. Activation of the ADORA2A signaling rewires the proline metabolism via an ERK/MYC/PYCR cascade. Increased proline synthesis promotes deacetylases SIRT6/7-mediated deacetylation of histone H3 at lysine 27 (H3K27), and thereby biases a global transcriptional output toward a neuroendocrine lineage profile. Ablation of Adora2a in genetically engineered mouse models inhibits the development and progression of neuroendocrine prostate and lung cancers, and, intriguingly, prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Importantly, pharmacological blockade of ADORA2A profoundly represses neuroendocrine prostate and lung cancer growth in vivo. Therefore, we believe that ADORA2A can be used as a promising therapeutic target to govern the epigenetic reprogramming in neuroendocrine malignancies.


Assuntos
Neoplasias Pulmonares , Neoplasias da Próstata , Sirtuínas , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Epigênese Genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prolina/metabolismo , Prolina/uso terapêutico , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia , Sirtuínas/metabolismo
13.
Opt Express ; 31(23): 38114-38131, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017926

RESUMO

A differential FMCW LiDAR for high-precision distance measurements of remote non-stationary targets is proposed and demonstrated experimentally. The required positive and negative symmetrically oppositely chirped laser beams are generated synchronously through a fixed-frequency laser by employing externally unified broadband optical phase modulation and symmetrical dual-sideband optical filtering. After coaxial transmission and reception, orthogonally polarized optical beat signals containing target distance and vector velocity data are de-chirped separately by optical in-phase and quadrature demodulations and then synchronously received by four-channel photoelectric balance detectors. After differential processing of the received beat signals and a fast Fourier transform, it is possible to implement real-time simultaneous range and vector velocity measurements. The inherent symmetrically oppositely chirped optical frequency make it possible to measure the target distance immune to the internal random phase noise introduced by the spectral linewidth of the frequency-swept laser and the external random phase noise introduced by atmospheric turbulence, speckle, and vibration. Meanwhile, the measurement of the target velocity is immune to the nonlinearity of the frequency-swept laser. These results encourage an approach to overcome the barriers of coherence length, nonlinearity, and external noise, and implement simultaneous real-time ranging and velocimetry of long-range, rapid-moving targets.

14.
Front Oncol ; 13: 1273719, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023243

RESUMO

Primary cutaneous follicle center lymphoma (PCFCL) differs from follicular lymphoma in biological behavior and molecular profile and is treated as a distinct entity, according to the 5th edition of the World Health Organization classification of hematolymphoid tumors. It is an uncommon cutaneous B-cell lymphoma that is considerably rare in children and adolescents. To date, only 13 cases of individuals younger than 20 years of age have been reported in the literature. The lack of relevant clinical epidemiological data in this population has hampered the investigation of its clinical and diagnostic aspects. Here we report the case of a 17-year-old male with PCFCL, who may be the first PCFCL patient under 20 years of age reported in China. He was admitted to the hospital with a solitary nodule on his face. After complete surgical excision, the patient's facial mass was histologically identified as PCFCL. The patient's prognosis was favorable, with no recurrence at 17 months of follow-up after the surgical resection. We present a case of an adolescent PCFCL patient and systematically review the literature with a view to increase the awareness of the disease and inform the diagnosis and treatment of this age group.

15.
J Environ Manage ; 348: 119386, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37879175

RESUMO

Various activated persulfate (PS) technologies have been investigated and implemented to eliminate antibiotic contaminants from water. The investigation and evaluation of different activation systems are essential for the application of PS techniques. The degradation of amoxicillin (AMX) by heat, light, or heterogeneous catalyst of Fe-AC composite activated PS was investigated, and the kinetics, mechanisms and toxicities were compared in this work. The apparent activation energy of the Fe-AC system was lower than that of the heat system. Hydroxyl and sulfate radicals were demonstrated by electron paramagnetic resonance (EPR) spectroscopy and quenching tests. There were 22, 21 and 13 types of degradation intermediates detected in heat, light and Fe-AC system, respectively. Six pathways of AMX degradation were proposed and compared in the three activated PS systems. The toxicity prediction of degradation intermediates under different treatment processes was estimated by ecological structure-activity relationship model and toxicity estimation software tool. The genotoxicity of the AMX degradation solution was tested by Acinetobacter baylyi ADP1_recA, which indicated that the AMX solution after treatment in the Fe-AC system had almost no genotoxicity. The Fe-AC/PS system shows apparent advantages over the heat or light activated PS system in most cases, demonstrating that the Fe-AC/PS system is suitable for AMX-contaminated remediation in aqueous solution.


Assuntos
Amoxicilina , Poluentes Químicos da Água , Temperatura Alta , Oxirredução , Poluentes Químicos da Água/química , Antibacterianos , Água
16.
J Environ Manage ; 345: 118834, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37659365

RESUMO

Treating wastewater using purple non-sulfur bacteria (PNSB) is an environmentally friendly technique that can simultaneously remove pollutants and lead to the accumulation of high-value cell inclusions. However, no PNSB system for treating heavy oil refinery wastewater (HORW) and recovering high-value cell inclusions has yet been developed. In this study, five batch PNSB systems dominated by Rhodopseudomonas were used to treat real HORW for 186 d. The effects of using different hydraulic retention times (HRT), sludge retention times (SRT), trace element solutions, phosphate loads, and influent loads were investigated, and the bacteriochlorophyll, carotenoid, and coenzyme Q10 concentrations were determined. The community structure and quantity of Rhodopseudomonas in the systems were determined using a high-sequencing technique and quantitative polymerase chain reaction technique. The long-term results indicated that phosphate was the limiting factor for treating HORW in the PNSB reactor. The soluble chemical oxygen demand (SCOD) removal rates were 67.03% and 85.26% without and with phosphate added, respectively, and the NH4+-N removal rates were 32.18% and 89.22%, respectively. The NO3--N concentration in the effluent was stable at 0-3 mg/L with or without phosphate added. Adding phosphate increased the Rhodopseudomonas relative abundance and number by 13.21% and 41.61%, respectively, to 57.35% and 8.52 × 106 gene copies/µL, respectively. The SRT was the limiting factor for SCOD removal, and the bacteria concentration was the limiting factor for nitrogen removal. Once the inflow load had been increased, the total nitrogen (TN) removal rate increased as the HRT increased. Maximum TN removal rates of 64.46%, 68.06%, 73.89%, 82.15%, and 89.73% were found at HRT of 7, 10, 13, 16, and 19 d, respectively. The highest bacteriochlorophyll, carotenoid, and coenzyme Q10 concentrations were 2.92, 4.99, and 4.53 mg/L, respectively. This study provided a simple and efficient method for treating HORW and reutilizing resources, providing theoretical support and parameter guidance for the application of Rhodopseudomonas in treating HORW.


Assuntos
Poluentes Ambientais , Rodopseudomonas , Águas Residuárias , Ubiquinona , Bacterioclorofilas , Esgotos , Carotenoides , Nitrogênio , Indústria de Petróleo e Gás , Fosfatos
17.
Food Res Int ; 172: 113115, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689883

RESUMO

Liquid-state fermentation (LSF) of tea leaves is a promising way to obtain tea-based nutraceutical products rich in various bioactive compounds. In the study, the changes of bioactive compounds, tea pigments and complex metabolites from LSF of primary dark tea, green tea and white tea infusions with Aspergillus cristatus were determined. Chemical analyses revealed that soluble sugars, monosaccharide composition, total polyphenols, total flavonoids, free amino acids, soluble proteins and tea pigments were changed in different ways. An untargeted metabolomic analysis and ribonucleic acid sequencing (RNA-seq) based transcriptomic analysis were performed to investigate the metabolic differentiation and clarify the key differentially expressed genes (DEGs, fold change >2 and p < 0.05), showing that amino acid metabolism, carbohydrate metabolism and lipid metabolism were the most enriched pathways during A. cristatus fermentation of primary dark tea, green tea and white tea infusions. In addition, glycerophospholipid metabolism, linoleic acid metabolism and phenylalanine metabolism were greatly accumulated in the fermentation of primary dark tea and white tea infusions; Pyruvate metabolism, glycolysis/gluconeogenesis, fatty acid degradation, tyrosine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and valine and leucine, isoleucine degradation were greatly accumulated in the fermentation of primary dark tea and green tea infusions; Starch and sucrose metabolism was greatly accumulated in the fermentation of green tea and white tea infusions; Galactose metabolism was significantly enhanced in the fermentation of primary dark tea infusion; Amino sugar and nucleotide sugar metabolism, sphingolipid metabolism and alanine, aspartate and glutamate metabolism were significantly enhanced in the fermentation of green tea infusion. Besides, some other pathways involving aminobenzoate degradation, biosynthesis of cofactors, pyrimidine metabolism, benzoxazinoid biosynthesis and phenazine biosynthesis, tropane, piperidine and pyridine alkaloid biosynthesis and flavone and flavonol biosynthesis also differed from each other. These findings support that A. cristatus plays a vital role in the biochemical and genetic regulation of metabolite profile, and could be considered a potential prospect for better use of A. cristatus on different kinds of tea materials.


Assuntos
Metabolômica , Transcriptoma , Fermentação , Aspergillus/genética
18.
Bioorg Chem ; 139: 106754, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37536216

RESUMO

Small molecules directly downregulating ß-catenin could potentially offer a more effective therapeutic approach for combating against cancer stem cells, as compared to targeting the downstream components of the Wnt/ß-catenin pathway. The challenge, however, lies in the fact that very few ß-catenin suppressors have proven clinically effective, leaving a significant gap in medical solutions. Given that E-cadherin has a natural affinity for ß-catenin, it stands to reason that agents designed to increase E-cadherin expression might provide an alternative method of regulating ß-catenin levels. In this study, we report our discovery of DSS-C12 and DSS-B8, specific ester-based drugs derived from Dan-Shen-Su (DSS) extracted from the herb Salvia miltiorrhiza. Remarkably, these compounds display a potent ability to downregulate ß-catenin, while also improving overall survival in post-surgery mice. Additionally, when these drugs are used in combination with PD-L1 checkpoint blockade, they stimulate enhanced systemic immune responses leading to significant suppression of primary tumor growth. In-depth mechanistic studies revealed that DSS-B8 functions as a vitamin D receptor agonist without inducing hypercalcemic effects. Collectively, our findings indicate that DSS-derived small molecules have considerable potential as clinically viable therapeutic strategies for ß-catenin deactivation.

19.
Angew Chem Int Ed Engl ; 62(38): e202308704, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37489759

RESUMO

To date, only a few noble metal oxides exhibit the required efficiency and stability as oxygen evolution reaction (OER) catalysts under the acidic, high-voltage conditions that exist during proton exchange membrane water electrolysis (PEMWE). The high cost and scarcity of these catalysts hinder the large-scale application of PEMWE. Here, we report a novel OER electrocatalyst for OER comprised of uniformly dispersed Ru clusters confined on boron carbon nitride (BCN) support. Compared to RuO2 , our BCN-supported catalyst shows enhanced charge transfer. It displays a low overpotential of 164 mV at a current density of 10 mA cm-2 , suggesting its excellent OER catalytic activity. This catalyst was able to operate continuously for over 12 h under acidic conditions, whereas RuO2 without any support fails in 1 h. Density functional theory (DFT) calculations confirm that the interaction between the N on BCN support and Ru clusters changes the adsorption capacity and reduces the OER energy barrier, which increases the electrocatalytic activity of Ru.

20.
Front Immunol ; 14: 1156470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187749

RESUMO

Background: Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there are few clinical studies on RTX for PMN in Asian populations, especially in China. Methods: To observe and analyse the efficacy and safety of RTX treatment, 81 patients with PMN suffering from nephrotic syndrome (NS) were enrolled and divided into an initial therapy group, a conventional immunosuppressive therapy relapse group, and a conventional immunosuppressive therapy ineffective group according to their pre-RTX treatment background. Patients in each group were followed up for 12 months. The primary outcome was clinical remission at 12 months, and the secondary outcomes were safety and the occurrence of adverse events. Results: At 12 months, 65 of 81 (80.2%) patients achieved complete (n=21, 25.9%) or partial (n=44, 54.3%) remission after rituximab treatment. Thirty-two of 36 (88.9%) patients in the initial therapy group, 11 of 12 (91.7%) patients in the relapse group and 22 of 33 (66.7%) patients in the ineffective group achieved clinical remission. All 59 patients with positive anti-PLA2R antibodies showed a decreasing trend in antibody levels after RTX treatment, and 55 (93.2%) of them achieved antibody clearance (<20 U/mL). Logistic regression analysis showed that a high anti-PLA2R antibody titer (OR=0.993, P=0.032) was an independent risk factor for nonremission. Adverse events occurred in 18 (22.2%) patients, of which 5 (6.2%) were serious adverse events, and none were malignant or otherwise fatal. Conclusion: RTX alone can effectively induce remission PMN and maintain stable renal function. It is recommended as the first choice of treatment and is also effective in patients who relapse and have poor responses to conventional immunosuppressive therapy. Anti-PLA2R antibodies can be used as a marker for RTX treatment monitoring, and antibody clearance is necessary to achieve and improve the rates of clinical remission.


Assuntos
Glomerulonefrite Membranosa , Humanos , Rituximab/efeitos adversos , Estudos Retrospectivos , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Imunossupressores/efeitos adversos , Anticorpos/uso terapêutico
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