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1.
Ecotoxicol Environ Saf ; 278: 116400, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38718725

RESUMEN

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

2.
Rev Sci Instrum ; 95(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38727574

RESUMEN

A pulsed power supply with a short rise time and high repetition frequency is favorable to driving diffusive plasma for strongly oxidizing radical (O3, OH) generation and increasing the system's energy efficiency. In this paper, a 10-stage solid-state linear transformer driver (LTD) with a nanosecond rise time is developed to drive plasma for wastewater treatment. To decrease the rise time, a control system with low jitter is developed to improve the synchronization of pulses using an optocoupler isolation chip. A 10-stage LTD with a rise time of 6.2 ns is realized in the case that the rise time of the single-stage LTD is 5.4 ns. The results show that the LTD can generate pulses on a 300 Ω resistive load with a repetition frequency of 10 kHz, an amplitude of 8.80 kV, an overshoot less than 3.97%, and a reverse overshoot less than 4.82%. The rise time (6.2-33.0 ns), the pulse width (35.9-200.0 ns), and the fall time (10.5-27.6 ns) can be adjusted flexibly and independently by controlling the drive signals of metal oxide semiconductor field effect transistors. The pulsed generator is utilized to drive plasma in the needle-water electrode system. The preliminary experimental results show that the plasma includes abundant oxygen atoms and hydroxyl radicals with high activity, and it is suitable for wastewater treatment.

3.
Org Biomol Chem ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695833

RESUMEN

The K2CO3-mediated one-pot reaction of 1,3-acetonedicarboxylates with 2 equiv. of substituted 2-fluoro-1-nitrobenzenes has been developed to synthesize various 2,3-dicarboxylate indoles via a tandem annulation pathway. In the effective reaction, one carbon-carbon double bond, one carbon-carbon single bond and one carbon-nitrogen single bond are formed under open-vessel conditions. DFT calculations are used to rationalize the plausible mechanisms.

4.
Food Funct ; 15(9): 4862-4873, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38587236

RESUMEN

Intestinal infections are strongly associated with infant mortality, and intestinal immunoglobulin A (IgA) is important to protect infants from intestinal infections after weaning. This study aims to screen probiotics that can promote the production of intestinal IgA after weaning and further explore their potential mechanisms of action. In this study, probiotics promoting intestinal IgA production were screened in weanling mouse models. The results showed that oral administration of Bifidobacterium bifidum (B. bifidum) FL228.1 and Bifidobacterium bifidum (B. bifidum) FL276.1 significantly enhanced IgA levels in the small intestine and upregulated the expression of a proliferation-inducing ligand (APRIL) and its upstream regulatory factor toll-like receptor 4 (TLR4). Furthermore, B. bifidum FL228.1 upregulated the relative abundance of Lactobacillus, while B. bifidum FL276.1 increased the relative abundance of Marvinbryantia and decreased Mucispirillum, further elevating intestinal IgA levels. In summary, B. bifidum FL228.1 and B. bifidum FL276.1 can induce IgA production in the intestinal tract of weanling mice by promoting intestinal APRIL expression and mediating changes in the gut microbiota, thus playing a significant role in enhancing local intestinal immunity in infants.


Asunto(s)
Bifidobacterium bifidum , Microbioma Gastrointestinal , Inmunoglobulina A , Probióticos , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Animales , Probióticos/farmacología , Probióticos/administración & dosificación , Ratones , Bifidobacterium bifidum/fisiología , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Destete , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Masculino , Intestinos/inmunología , Intestinos/microbiología , Femenino , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Ratones Endogámicos BALB C
5.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1028-1043, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621910

RESUMEN

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500_29_marine_group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500_29_marine_group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.


Asunto(s)
Microbioma Gastrointestinal , Bazo , Humanos , Ratones , Animales , Factor de Necrosis Tumoral alfa/farmacología , ARN Ribosómico 16S/genética , Interleucina-2/farmacología , Serotonina , Inmunoglobulina A/farmacología
6.
J Colloid Interface Sci ; 665: 1079-1090, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38581719

RESUMEN

Directly capturing CO2 in ambient air and converting it into value-added fuels using photocatalysis is a potentially valuable technology. In this study, Cu-porphyrin (tetrakis-carboxyphenyl porphyrin copper, CuTCPP) was innovatively anchored on the surface of TiO2 (titanium dioxide) nanosheets to form an S-scheme heterojunction. Based on this, a photocatalytic reaction system for stably converting CO2 in ambient air into value-added fuels at the gas-solid interface was constructed without addition of sacrificial agents and alkaline liquids. Under the illumination of visible light and sunlight, the evolution rate of CO is 56 µmol·g-1·h-1 and 73 µmol·g-1·h-1, respectively, with a potential CO2 conversion rate of 35.8 % and 50.4 %. The enhanced of photocatalytic performance is attributed to the introduction of CuTCPP, which provides additional active sites, significantly improves capture capacity of CO2 and the utilization of electrons. Additionally, the formation of S-scheme heterojunction expands the redox range and improves the separation efficiency of photo-generated charges.

7.
J Adv Res ; 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38614215

RESUMEN

INTRODUCTION: Senescence refers to a state of permanent cell growth arrest and is regarded as a tumor suppressive mechanism, whereas accumulative evidence demonstrate that senescent cells play an adverse role during cancer progression. The scarcity of specific and reliable markers reflecting senescence level in cancer impede our understanding of this biological basis. OBJECTIVES: Senescence-related genes (SRGs) were collected for integrative analysis to reveal the role of senescence in hepatocellular carcinoma (HCC). METHODS: Consensus clustering was used to subtype HCC based on SRGs. Several computational methods, including single sample gene set enrichment analysis (ssGSEA), fuzzy c-means algorithm, were performed. Data of drug sensitivities were utilized to screen potential therapeutic agents for different senescence patients. Additionally, we developed a method called signature-related gene analysis (SRGA) for identification of markers relevant to phenotype of interest. Experimental strategies consisting quantitative real-time PCR (qRT-PCR), ß-galactosidase assay, western blot, and tumor-T cell co-culture system were used to validate the findings in vitro. RESULTS: We identified three robust prognostic clusters of HCC patients with distinct survival outcome, mutational landscape, and immune features. We further extracted signature genes of senescence clusters to construct the senescence scoring system and profile senescence level in HCC at bulk and single-cell resolution. Senescence-induced stemness reprogramming was confirmed both in silico and in vitro. HCC patients with high senescence were immune suppressed and sensitive to Tozasertib and other drugs. We suggested that MAFG, PLIN3, and 4 other genes were pertinent to HCC senescence, and MAFG potentially mediated immune suppression, senescence, and stemness. CONCLUSION: Our findings provide insights into the role of SRGs in patients stratification and precision medicine.

8.
J Org Chem ; 89(8): 5560-5572, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38564232

RESUMEN

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

9.
Front Neurol ; 15: 1379801, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606274

RESUMEN

Growing evidence has demonstrated that peripapillary hyperreflective ovoid mass-like structures (PHOMS) are novel structures rather than a subtype of optic disc drusen. They correspond to the laterally bulging herniation of optic nerve fibers and are believed to be the marker of axoplasmic stasis. PHOMS present in a broad spectrum of diseases, including optic disc drusen, tilted disc syndrome, papilloedema, multiple sclerosis, non-arteritic anterior ischemic optic neuropathy, optic neuritis, Leber hereditary optic neuropathy, and so on. We focus on the multimodal imaging features, pathophysiological mechanisms of PHOMS, and their association with multiple diseases and healthy people in this review to deepen the ophthalmologists' understanding of PHOMS. Additionally, we provide some new directions for future research.

10.
Angew Chem Int Ed Engl ; 63(21): e202402044, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38469657

RESUMEN

The nuanced role of spin effects remains a critical gap in designing proficient open-shell catalysts. This study elucidates an iron-catalyzed allylic C(sp3)-H silylation/alkyne hydrosilylation reaction, in which the spin state of the open-shell iron catalyst dictates the reaction kinetics and pathway. Specifically, spin crossover led to alkyne hydrosilylation, whereas spin conservation resulted in a novel allylic C(sp3)-H silylation reaction. This chemoselectivity, governed by the spin-crossover efficiency, reveals an unexpected dimension in spin effects and a first in the realm of transition-metal-catalyzed in situ silylation of allylic C(sp3)-H bonds, which had been previously inhibited by the heightened reactivity of alkenes in hydrosilylation reactions. Furthermore, this spin crossover can either accelerate or hinder the reaction at different stages within a single catalytic reaction, a phenomenon scarcely documented. Moreover, we identify a substrate-assisted C-H activation mechanism, a departure from known ligand-assisted processes, offering a fresh perspective on C-H activation strategies.

11.
Adv Sci (Weinh) ; : e2400274, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38520071

RESUMEN

Hydrogen storage in MgH2 is an ideal solution for realizing the safe storage of hydrogen. High operating temperature, however, is required for hydrogen storage of MgH2 induced by high thermodynamic stability and kinetic barrier. Herein, flower-like microspheres uniformly constructed by N-doped TiO2 nanosheets coated with TiN nanoparticles are fabricated to integrate the light absorber and thermo-chemical catalysts at a nanometer scale for driving hydrogen storage of MgH2 using solar energy. N-doped TiO2 is in situ transformed into TiNxOy and Ti/TiH2 uniformly distributed inside of TiN matrix during cycling, in which TiN and Ti/TiHx pairs serve as light absorbers that exhibit strong localized surface plasmon resonance effect with full-spectrum light absorbance capability. On the other hand, it is theoretically and experimentally demonstrated that the intimate interface between TiH2 and MgH2 can not only thermodynamically and kinetically promote H2 desorption from MgH2 but also simultaneously weaken Ti─H bonds and hence in turn improve H2 desorption from the combination of weakened Ti─H and Ti─H bonds. The uniform integration of photothermal and catalytic effect leads to the direct action of localized heat generated from TiN on initiating the catalytic effect in realizing hydrogen storage of MgH2 with a capacity of 6.1 wt.% under 27 sun.

12.
Quant Imaging Med Surg ; 14(3): 2499-2513, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38545035

RESUMEN

Background: Anterior bone loss (ABL) is a common phenomenon after cervical disc replacement (CDR), which can also be observed after anterior cervical discectomy and fusion (ACDF). This study aimed to investigate the incidence and severity of ABL in single-level CDR and ACDF and explore the association of cervical sagittal alignment with ABL. Methods: This is a single-center retrospective cohort study. A total of 113 patients treated with CDR and 99 patients treated with ACDF were retrospectively reviewed from January 2014 to December 2018 in West China Hospital. Radiological data were collected at pre-operation, 1 week, 3 months postoperatively, and the last follow-up. The incidence and severity of ABL after both CDR and ACDF were evaluated. Cervical sagittal alignment parameters, including C0-C2 angle, cervical lordosis (CL), C2-C7 sagittal vertical axis (cSVA), T1 slope, functional spinal unit angle, disc angle, and surgical level slope, were evaluated. Results: ABL was identified in 75 (66.4%) patients in the CDR group and 57 (57.6%) patients in the ACDF group. There were no significant differences in the incidence, severity, and location of ABL between the ACDF and CDR groups. For patients who underwent ACDF, the proportion of females was significantly higher in the ABL group (64.9% vs. 33.3%, P=0.002), whereas the body mass index (BMI) was significantly lower in the ABL group compared to the non-ABL group (22.72±3.09 vs. 24.60±3.04, P=0.002). No effect of ABL on the short-term clinical outcomes of ACDF and CDR was observed. In the ACDF group, patients with ABL had significantly smaller postoperative CL (11.83°±8.24° vs. 15.25°±8.32°, P=0.04) and cSVA (17.77±10.08 vs. 23.35±9.86 mm, P=0.007). In the CDR group, no significant differences were found in the cervical sagittal parameters between patients with and without ABL (CL: 12.58±8.70 vs. 15.46±8.50, P=0.10; cSVA: 20.95±8.54 vs. 19.40±9.43, P=0.38). Conclusions: ABL is common after both CDR and ACDF with comparable incidence and severity. Cervical sagittal alignment was closely related to ABL after ACDF yet had less influence on ABL after CDR.

13.
Neuron ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38492574

RESUMEN

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1+/+, Trpv1-/-, and Trpv1T634A/T634A. Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT.

14.
Molecules ; 29(5)2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38474508

RESUMEN

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

15.
J Affect Disord ; 352: 1-9, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38355054

RESUMEN

BACKGROUND: Psychological repurcussions of COVID-19 pandemic has received wide attention, but there's limited attention paid to psychological recovery afterwards. This study focuses on the changes and predictive factors of mental health of Chinese university students post-pandemic. METHODS: This study included 1175 Chinese undergraduate students sampled in May 2022 and May-June 2023, right before and after peaks of infections following the end of lockdown policy in China. The participants completed a survey of demographic variables, and three questionnaires: 12-item General Health Questionnaire, Positive Psychological Capital Questionnaire, and Prosocial Tendencies Measure. RESULTS: The participants sampled in 2023 have significant lower GHQ scores and higher PPQ scores than those sampled in 2022, while there is no significant difference in PTM scores between them. The proportion of participants with GHQ-12 scores exceeding 12 in 2023 showed slightly decrease compared to that in 2022. The infection of significant others, the sense of hope, and PPQ self-efficiency, hope and optimism subscale scores were significantly associated with GHQ-12 scores in 2023, but actual infection or quarantine experience were not. CONCLUSIONS: The mental health and psychological capital of the university students have been significantly improved within a year. It is worthy to pay attention to the infection of significant others, the sense of hope, and psychological capital in a pandemic to improve the mental health of university students. LIMITATIONS: Compared to a cross-sectional study, longitudinal research is the better choice for a two-year comparison.


Asunto(s)
COVID-19 , Humanos , COVID-19/prevención & control , COVID-19/psicología , Salud Mental , Pandemias , Estudios Transversales , Universidades , Control de Enfermedades Transmisibles , Estudiantes/psicología
16.
Mol Genet Genomics ; 299(1): 13, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396305

RESUMEN

Gamma (γ)-ray irradiation is one of the important modern breeding methods. Gamma-ray irradiation can affect the growth rate and other characteristics of plants. Plant growth rate is crucial for plants. In horticultural crops, the growth rate of plants is closely related to the growth of leaves and flowering time, both of which have important ornamental value. In this study, 60Co-γ-ray was used to treat P. equestris plants. After irradiation, the plant's leaf growth rate increased, and sugar content and antioxidant enzyme activity increased. Therefore, we used RNA-seq technology to analyze the differential gene expression and pathways of control leaves and irradiated leaves. Through transcriptome analysis, we investigated the reasons for the rapid growth of P. equestris leaves after irradiation. In the analysis, genes related to cell wall relaxation and glucose metabolism showed differential expression. In addition, the expression level of genes encoding ROS scavenging enzyme synthesis regulatory genes increased after irradiation. We identified two genes related to P. equestris leaf growth using VIGS technology: PeNGA and PeEXPA10. The expression of PeEXPA10, a gene related to cell wall expansion, was down-regulated, cell wall expansion ability decreased, cell size decreased, and leaf growth rate slowed down. The TCP-NGATHA (NGA) molecular regulatory module plays a crucial role in cell proliferation. When the expression of the PeNGA gene decreases, the leaf growth rate increases, and the number of cells increases. After irradiation, PeNGA and PeEXPA10 affect the growth of P. equestris leaves by influencing cell proliferation and cell expansion, respectively. In addition, many genes in the plant hormone signaling pathway show differential expression after irradiation, indicating the crucial role of plant hormones in plant leaf growth. This provides a theoretical basis for future research on leaf development and biological breeding.


Asunto(s)
Orchidaceae , Fitomejoramiento , Perfilación de la Expresión Génica , Genes de Plantas , RNA-Seq , Antioxidantes/metabolismo , Orchidaceae/genética , Orchidaceae/metabolismo , Hojas de la Planta , Regulación de la Expresión Génica de las Plantas , Transcriptoma/genética
17.
Int J Legal Med ; 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416217

RESUMEN

Massively parallel sequencing allows for integrated genotyping of different types of forensic markers, which reduces DNA consumption, simplifies experimental processes, and provides additional sequence-based genetic information. The STRseqTyper122 kit genotypes 63 autosomal STRs, 16 X-STRs, 42 Y-STRs, and the Amelogenin locus. Amplicon sizes of 117 loci were below 300 bp. In this study, MiSeq FGx sequencing metrics for STRseqTyper122 were presented. The genotyping accuracy of this kit was examined by comparing to certified genotypes of NIST standard reference materials and results from five capillary electrophoresis-based kits. The sensitivity of STRseqTyper122 reached 125 pg, and > 80% of the loci were correctly called with 62.5 pg and 31.25 pg input genomic DNA. Repeatability, species specificity, and tolerance for DNA degradation and PCR inhibitors of this kit were also evaluated. STRseqTyper122 demonstrated reliable performance with routine case-work samples and provided a powerful tool for forensic applications.

18.
Natl Sci Rev ; 11(2): nwad324, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38314400

RESUMEN

Iron catalysts are ideal transition metal catalysts because of the Earths abundant, cheap, biocompatible features of iron salts. Iron catalysts often have unique open-shell structures that easily undergo spin crossover in chemical transformations, a feature rarely found in noble metal catalysts. Unfortunately, little is known currently about how the open-shell structure and spin crossover affect the reactivity and selectivity of iron catalysts, which makes the development of iron catalysts a low efficient trial-and-error program. In this paper, a combination of experiments and theoretical calculations revealed that the iron-catalyzed hydrosilylation of alkynes is typical spin-crossover catalysis. Deep insight into the electronic structures of a set of well-defined open-shell active formal Fe(0) catalysts revealed that the spin-delocalization between the iron center and the 1,10-phenanthroline ligand effectively regulates the iron center's spin and oxidation state to meet the opposite electrostatic requirements of oxidative addition and reductive elimination, respectively, and the spin crossover is essential for this electron transfer process. The triplet transition state was essential for achieving high regioselectivity through tuning the nonbonding interactions. These findings provide an important reference for understanding the effect of catalyst spin state on reaction. It is inspiring for the development of iron catalysts and other Earth-abundant metal catalysts, especially from the point of view of ligand development.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38318829

RESUMEN

Immune checkpoint inhibitors (ICIs) offer significant advantages for the treatment of urologic tumors, enhancing the immune function of anti-tumor T cells by inhibiting PD-1 and PDL1 binding. They have been shown to be well tolerated and remarkably effective in clinical practice, offering hope to many patients who are not well treated with conventional drugs. Clinical trials in recent years have shown that anti-PD-1 and PD-L1 antibodies have good efficacy and safety in the treatment of urologic tumors. These antibodies can be applied to a variety of urologic tumors, such as bladder cancer, renal cell carcinoma, and prostate cancer. They have been approved for the first-line treatment or as an option for follow-up therapy. By blocking the PD-1/PD-L1 signaling pathway, ICIs can release immune functions that are suppressed by tumor cells and enhance T-cell killing, thereby inhibiting tumor growth and metastasis. This therapeutic approach has achieved encouraging efficacy and improved survival for many patients. Although ICIs have shown remarkable results in the treatment of urologic tumors, some problems remain, such as drug resistance and adverse effects in some patients. Therefore, further studies remain important to optimize treatment strategies and improve clinical response in patients. In conclusion, PD-1/PD-L1 signaling pathway blockers have important research advances for the treatment of urologic tumors. Their emergence brings new hope for patients who have poor outcomes with traditional drug therapy and provides new options for immunotherapy of urologic tumors. The purpose of this article is to review the research progress of PD-1 and PD-L1 signaling pathway blockers in urologic tumors in recent years.

20.
Zhongguo Zhong Yao Za Zhi ; 49(1): 216-223, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403354

RESUMEN

This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.


Asunto(s)
Medicamentos Herbarios Chinos , Ratas , Ratones , Animales , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-sis , Ratones Endogámicos C57BL , Medicamentos Herbarios Chinos/uso terapéutico , Transducción de Señal , Isquemia/tratamiento farmacológico , Miembro Posterior/metabolismo , ARN Mensajero/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo
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