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1.
Environ Res ; 252(Pt 3): 118982, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697598

RESUMO

The surge in non-grain production on farmland (NGPF) poses significant threats to food security and land sustainability, particularly in hilly regions. However, there remains a lack of clarity on how to effectively balance grain and non-grain production in relation to land remediation. Using Wannian County as a case study, we investigate the evolution of this by leveraging high-precision land surveys and satellite imagery. Through the application of bootstrapped partial linear regression models, we identify key influencers behind each type of NGPF. In proposing land remediation solutions, we integrate the results of NGPF and land quality evaluations to identify mismatches between non-grain production and land attributes (i.e., topography, geology, soil, and land use). Our findings reveal a substantial growth in NGPF, expanding from 3838.72 ha to 5659.64 ha (2010-2020), and predominantly occurring on farmland with favorable natural conditions and connected locations such as proximity to roads, town centers, and industrial plants. Surprisingly, the basic farmland protection policy shows limited effectiveness in curbing NGPF, except for garden operations. We identify 1674 NGPF patches suitable for conversion to grain production and provide land remediation suggestions tailored to low-quality farmland with specific natural barriers, thus complementing the demand for regional non-grain production. This study thereby innovatively proposes nature-based land remediation strategies to address the non-grain production dilemma by tailoring NGPF and land quality, offering valuable insights for sustainable farmland management in China and beyond.

2.
World J Psychiatry ; 14(5): 678-685, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38808091

RESUMO

BACKGROUND: Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum depression. AIM: To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum women. METHODS: Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September 2023. The patients were divided into the Group S (35 cases, biomimetic electrical stimulation treatment) and Group L (35 cases, biomimetic electrical stimulation combined with manual massage treatment). Baseline data, the edinburgh postpartum depression scale (EPDS) score, and the visual analog scale (VAS) scores for rectus abdominis distance, waist circumference, and lower back pain before and after treatment were compared. RESULTS: No significant differences were found in the baseline data, rectus abdominis distance, waist circumference, and VAS and EPDS scores between the two groups before treatment (P > 0.05). After treatment, the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S (P < 0.05). Furthermore, lower back pain (VAS score) and the EPDS score in Group L were significantly lower than those in Group S (P < 0.05). CONCLUSION: Manual massage can significantly reduce early postpartum DRA, waist circumference, and back pain and improve the patient's mental state and postpartum depression.

3.
Dalton Trans ; 53(21): 8980-8987, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38717188

RESUMO

Octanuclear polyoxomolybdenum-based porous materials, Na8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·26H2O (1, 3-Hapz = 3-aminopyrazole), K8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·7H2O (2) and (NH4)4[Mo8O8(µ2-O)8(µ2-OH)4(3-apz)8]·20.5H2O (3), have been successfully synthesized by a hydrothermal method and fully characterized. X-ray structural analyses show that microporous materials 1-3 contain round pores formed by octanuclear molybdenum-oxygen groups connected sequentially with pore sizes of 4.0, 4.0, and 4.8 Å, respectively. Both 1 and 2 are composed of two {Mo8} rings, which are connected by strong intramolecular hydrogen bonds between bridging hydroxy groups and oxygen atoms to form dimeric structures. The central pores in 1 and 2 are occupied by Na+ and K+, respectively, while they are empty in 3. This reflects the structural expansion and contraction effects induced by different cations. Through intermolecular stacking, 1-3 also exhibit channels with sizes of 14.0 × 6.4, 4.6 × 2.6, and 5.4 × 5.4 Å, respectively, which were used for the studies of gas adsorption. The results show that 1-3 can selectively adsorb CO2 and O2, including the empty hole in 3, while they show little or no affinity for gases H2, N2, and CH4. Moreover, an additional polyoxomolybdenum-based species (Mo8O26)n·4n(3-H2apz) (4) has been obtained with protonated 3-aminopyrazole in the absence of a reducing agent, which can serve as an intermediate for the polyoxomolybdenum-based porous products.

4.
Sci Total Environ ; 931: 172567, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38643871

RESUMO

Microalgal polysaccharides have received much attention due to their potential value in preventing and regulating oxidative damage. This study aims to reveal the mechanisms of regulating oxidative stress and the differences in the yield, structure, and effect of polysaccharides extracted from three microalgae: Golenkinia sp. polysaccharides (GPS), Chlorella sorokiniana polysaccharides (CPS), and Spirulina subsalsa polysaccharides (SPS). Using the same extraction method, GPS, CPS, and SPS were all heteropoly- saccharides composed of small molecular fraction: the monosaccharides mainly comprised galactose (Gal). Among the three, SPS had a higher proportion of small molecular fraction, and a higher proportion of Gal; thus it had the highest yield and antioxidant activity. GPS, CPS, and SPS all showed strong antioxidant activity in vitro, and showed strong ability to regulate oxidative stress, among which SPS was slightly higher. From the analysis of gene expression, the Nrf2-ARE signalling pathway was an important pathway for GPS, CPS, and SPS to regulate cellular oxidative stress. This study provides a theoretical foundation for further research on the utilization of microalgae polysaccharides and product development.


Assuntos
Antioxidantes , Chlorella , Microalgas , Estresse Oxidativo , Polissacarídeos , Polissacarídeos/farmacologia , Polissacarídeos/química , Estresse Oxidativo/efeitos dos fármacos , Spirulina/química
5.
Cell Stem Cell ; 31(5): 694-716.e11, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38631356

RESUMO

Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium. This disturbance limits nuclear protein availability and hinders polymerase initiation and engagement, reducing gene transcription. Concurrently, it promptly disrupts nucleolar transcription, ribosomal processes, and nuclear exporting, resulting in a translational shutdown. Prolonged exosome depletion induces nuclear structural changes resembling senescent cells, including aberrant chromatin compaction, chromocenter disassembly, and intensified heterochromatic foci. These effects suggest that the dynamic turnover of nuclear RNA orchestrates crosstalk between essential processes to optimize cellular function. Disruptions in nuclear RNA homeostasis result in systemic functional decline, altering the cell state and promoting senescence.


Assuntos
Senescência Celular , Homeostase , RNA Nuclear , Animais , RNA Nuclear/metabolismo , Camundongos , Diferenciação Celular , Linhagem da Célula , Núcleo Celular/metabolismo , Transcriptoma/genética , Humanos
6.
Acad Radiol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38653598

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) accumulation plays a key role in the progression myocardial infarction (MI) and diabetes. Diabetic patients have elevated risk of major adverse cardiac events (MACEs) compared to non-diabetic patients. We aimed to investigate the prognostic value of EAT volume in MI patients with and without diabetes. METHODS: This study included 458 MI patients who underwent cardiac computed tomography (CT) imaging and received successful stent implantation. EAT volume was quantified with cardiac CT imaging. Sub-study stratification of patients by diabetes status was further analyzed. Cox proportional hazards regression models were applied to evaluate the association between EAT volume and MACEs. RESULTS: Diabetes was identified in 135 of the 458 patients (29.5%). EAT volume was significantly higher in diabetes than non-diabetes. During a median follow-up of 1154 days, MACEs occurred more frequently in patients with versus without diabetes. EAT volume was independent predictor of MACEs in all MI patients after adjustment for risk factors, and showed good predictive value in the evaluation of MACEs. Moreover, EAT volume was also significantly associated with MACEs after adjustment for risk factors in diabetes and non-diabetes in the subgroup analysis. CONCLUSION: MI patients with diabetes had higher EAT volume and experienced higher rate of MACEs compared to non-diabetes. EAT volume is an independent risk of prognosis of MI, regardless of the diabetes status.

7.
J Exerc Sci Fit ; 22(2): 145-151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38435333

RESUMO

Background: This study examined sedentary volume and bouts of Chinese primary and middle school students during different segments of a school day and determined whether gender and school level are associated with their sedentary volume and bouts. Methods: A total of 472 students participated in this study. Accelerometers were used to measure the sedentary volume and sedentary bouts of different durations (i.e., 1-4 min, 5-9 min and ≥10 min) during all segments. Results: The participants spent the majority of their time in sitting (61.7%) and sitting bouts of ≥10 min (37.3%). They spent higher percentages of time in sitting during regular classes (76.7%) and out-of-school time (54.5%), and lower during physical education (PE) classes (32.2%), lunch break (35.4%) and recess (38.0%). The highest proportions of time were in sedentary bouts of ≥10 min during regular classes (50.2%), out-of-school time (28.0%) and lunch break (18.8%), while the greatest percentages occurred in sitting bouts of 1-4 min during PE class (16.4%) and recess (18.6%). Girls and middle school students had higher percentages of sedentary volume than boys and primary school students during most segments. They spent greater proportions of time in sitting bouts of ≥10 min during regular classes, lunch break, and out-of-school time, and higher proportions in sedentary bouts of 1-4 min than boys and primary students during PE classes. Conclusion: Regular class and out-of-school time were identified as key segments for reducing sedentary volume and breaking up prolonged sitting. Interventions on interrupting prolonged sitting during lunch break should also be explored. Girls and middle school students should receive more attention in future interventions.

8.
Bioresour Technol ; 398: 130512, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437960

RESUMO

The reuse of wastewater after seawater cultivation is critically important. In this study, a phosphorus-supplemented seawater-wastewater cyclic system (PSSWCS) based on Chlorella pyrenoidosa SDEC-35 was developed. With the addition of phosphorus, the algal biomass and the ability to assimilate nitrogen and carbon were improved. At the nitrogen to phosphorus ratio of 20:1, the biomass productivity per mass of nitrogen reached 3.6 g g-1 (N) day-1 in the second cycle. After the third cycle the protein content reached 35.7% of dry mass, and the major metabolic substances in PSSWCS reached the highest content level of 89.5% (35.7% protein, 38.3% lipid, and 15.5% carbohydrate). After the fourth cycle the lipid content maintained at 40.1%. Furthermore, 100.0% recovery of wastewater in PSSWCS increased the nitrogen and carbon absorption to 15.0 and 396.8 g per tonne of seawater. This study achieved seawater-wastewater recycle and produced high-lipid and high-protein algae by phosphorus addition.


Assuntos
Chlorella , Microalgas , Águas Residuárias , Chlorella/metabolismo , Microalgas/metabolismo , Biomassa , Nitrogênio/metabolismo , Água do Mar , Fósforo/metabolismo , Lipídeos , Carbono/metabolismo
9.
Org Lett ; 26(10): 2108-2113, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38440974

RESUMO

A metal-free photosensitized 1,2-imino-sulfamoylation of olefins by employing a tailor-made sulfamoyl carbamate as the difunctionalization reagent has been established. This protocol exhibits versatility across a broad substrate scope, including aryl and aliphatic alkenes, leading to the synthesis of diverse ß-imino sulfonamides in moderate to good yields. This method is characterized by its metal-free reaction system, mild reaction conditions, excellent regioselectivity, and high atom economy, serving as a promising platform for the preparation of ß-amino sulfonamide-containing molecules, particularly in the context of drug discovery.

10.
PeerJ ; 12: e16934, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529304

RESUMO

Background: Ischemic stroke (IS) is the main cause of death and adult disability. However, the pathogenesis of this complicated disease is unknown. The present study aimed to assess the relationship between ITLN1 single nucleotide polymorphisms (SNPs) and the susceptibility to IS in Xi'an population, Shaanxi province. Methods: In this study, we designed polymerase chain reaction (PCR) primers located at -3,308 bp upstream of the transcription initiation site within promoter region of the ITLN1 gene. The target fragment was amplified by PCR and identified by agarose gel electrophoresis. Sanger sequencing was then performed in the samples extracted from a cohort comprising 1,272 participants (636 controls and 636 cases), and the obtained sequences were compared with the reference sequences available on the National Center for Biotechnology Information (NCBI) website to detect SNPs in the ITLN1 gene promoter region. Logistic regression analysis was employed to assess the relationship between ITLN1 polymorphisms and IS risk, with adjustments for age and gender. Significant positive results were tested by false-positive report probability (FPRP) and false discovery rate (FDR). The interaction among noteworthy SNPs and their predictive relationship with IS risk were explored using the Multi-Factor Dimensionality Reduction (MDR) software. Results: The results of Sanger sequencing were compared with the reference sequences on the NCBI website, and we found 14 SNPs in ITLN1 gene promoter satisfied Hardy-Weinberg equilibrium (HWE). Logistic regression analysis showed that ITLN1 was associated with a decreased risk of IS (rs6427553: Homozygous C/C: adjusted OR: 0.69, 95% CI [0.48-0.97]; Log-additive: adjusted OR: 0.83, 95% CI [0.70-0.98]; rs7411035: Homozygous G/G: adjusted OR: 0.66, 95% CI [0.47-0.94]; Dominant G/T-G/G: adjusted OR: 0.78, 95% CI [0.62-0.98]; Log-additive: adjusted OR: 0.81, 95% CI [0.69-0.96]; rs4656958: Heterozygous G/A: adjusted OR: 0.74, 95% CI [0.59-0.94]; Homozygous A/A: adjusted OR: 0.51, 95% CI [0.31-0.84]; Dominant G/A-A/A: adjusted OR: 0.71, 95% CI [0.57-0.89]; Recessive A/A: adjusted OR: 0.59, 95% CI [0.36-0.96]; Log-additive: adjusted OR: 0.73, 95% CI [0.61-0.88]), especially in people aged less than 60 years and males. Conclusions: In short, our study revealed a correlation between ITLN1 variants (rs6427553, rs7411035 and rs4656958) and IS risk in Xi'an population, Shaanxi province, laying a foundation for ITLN1 gene as a potential biomarker for predicting susceptibility to IS.


Assuntos
AVC Isquêmico , Polimorfismo de Nucleotídeo Único , Adulto , Humanos , Biomarcadores , Predisposição Genética para Doença/genética , Heterozigoto , AVC Isquêmico/genética , Polimorfismo de Nucleotídeo Único/genética , Citocinas/genética , Lectinas/genética , Proteínas Ligadas por GPI/genética
11.
J Mol Neurosci ; 74(1): 24, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386166

RESUMO

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.


Assuntos
Glutationa Transferase , Acidente Vascular Cerebral Hemorrágico , Animais , Camundongos , Antioxidantes , Hemorragia Cerebral/genética , Modelos Animais de Doenças , Glutationa , Glutationa Transferase/genética , Hemina/farmacologia , Neurônios , RNA Mensageiro
12.
Microb Pathog ; 188: 106562, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307370

RESUMO

Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/fisiologia , Infecções por Pseudomonas/microbiologia , Imunidade Inata , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Interações Hospedeiro-Patógeno , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Asian J Surg ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38342723

RESUMO

BACKGROUND: This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. METHOD: This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. RESULTS: This study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. CONCLUSION: LR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

14.
Dalton Trans ; 53(15): 6529-6536, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38299993

RESUMO

The electronic structures of FeFe-cofactors (FeFe-cos) in resting and turnover states, together with their PN clusters from iron-only nitrogenases, have been calculated using the bond valence method, and their crystallographic data were reported recently and deposited in the Protein Data Bank (PDB codes: 8BOQ and 8OIE). The calculated results have also been compared with those of their homologous Mo- and V-nitrogenases. For FeFe-cos in the resting state, Fe1/2/4/5/6/7/8 atoms are prone to Fe3+, while the Fe3 atom shows different degrees of mixed valences. The results support that the Fe8 atom at the terminal positions of FeFe-cos possesses the same oxidation states as the Mo3+/V3+ atoms of FeMo-/FeV-cos. In the turnover state, the overall oxidation state of FeFe-co is slightly reduced than those in the resting species, and its electronic configuration is rearranged after the substitution of S2B with OH, compatible with those found in CO-bound FeV-co. Moreover, the calculations give the formal oxidation states of 6Fe2+-2Fe3+ for the electronic structures of PN clusters in Fe-nitrogenases. By the comparison of Mo-, V- and Fe-nitrogenases, the overall oxidation levels of 7Fe atoms (Fe1-Fe7) for both FeFe- and FeMo-cos in resting states are found to be higher than that of FeV-co. For the PN clusters in MoFe-, VFe- and FeFe-proteins, they all exhibit a strong reductive character.

15.
Microb Cell Fact ; 23(1): 34, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273342

RESUMO

BACKGROUND: Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids. RESULT: In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. The sgRNA were designed based on the active site residues. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. The results showed that deletion of PcSE inhibited triterpene synthesis. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach. CONCLUSION: The findings from this study provide a foundation for further studies on heterologous biosynthesis of P. cocos secondary metabolites.


Assuntos
Fitosteróis , Triterpenos , Wolfiporia , Espectrometria de Massas em Tandem/métodos , Esqualeno Mono-Oxigenase/genética , Esqualeno Mono-Oxigenase/metabolismo , Wolfiporia/genética , Wolfiporia/metabolismo , Simulação de Acoplamento Molecular , Esqualeno , Sistemas CRISPR-Cas , Edição de Genes , RNA Guia de Sistemas CRISPR-Cas , Triterpenos/metabolismo
16.
Cancer Lett ; 581: 216485, 2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-38008394

RESUMO

Oncolytic viruses are multifaceted tumor killers, which can function as tumor vaccines to boost systemic antitumor immunity. In previous study, we rationally designed a synthetic oncolytic adenovirus (SynOV) harboring a synthetic gene circuit, which can kill tumors in mouse hepatocellular carcinoma (HCC) models. In this study, we demonstrated that SynOV could sense the tumor biomarkers to lyse tumors in a dosage-dependent manner, and killed PD-L1 antibody resistant tumor cells in mouse model. Meanwhile, we observed SynOV could cure liver cancer and partially alleviate the liver cancer with distant metastasis by activating systemic antitumor immunity. To understand its high efficacy, it is essential to explore the cellular and molecular features of the remodeled tumor microenvironment (TME). By combining spatial transcriptome sequencing and single-cell RNA sequencing, we successfully depicted the remodeled TME at single cell resolution. The state transition of immune cells and stromal cells towards an antitumor and normalized status exemplified the overall cancer-suppressive TME after SynOV treatment. Specifically, SynOV treatment increased the proportion of CD8+ T cells, enhanced the cell-cell communication of Cxcl9-Cxcr3, and normalized the Kupffer cells and macrophages in the TME. Furthermore, we observed that SynOV could induce distant responses to reduce tumor burden in metastatic HCC patient in the Phase I clinical trial. In summary, our results suggest that SynOV can trigger systemic antitumor immunity to induce CD8+ T cells and normalize the abundance of immune cells to remodel the TME, which promises a powerful option to treat HCC in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia Viral Oncolítica , Vírus Oncolíticos , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Adenoviridae/genética , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Vírus Oncolíticos/genética , Terapia Viral Oncolítica/métodos , Modelos Animais de Doenças , Análise de Célula Única , Microambiente Tumoral
17.
Glia ; 72(2): 227-244, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37650384

RESUMO

Microglia are the resident phagocytes of the brain, where they primarily function in the clearance of dead cells and the removal of un- or misfolded proteins. The impaired activity of receptors or proteins involved in phagocytosis can result in enhanced inflammation and neurodegeneration. RNA-seq and genome-wide association studies have linked multiple phagocytosis-related genes to neurodegenerative diseases, while the knockout of such genes has been demonstrated to exert protective effects against neurodegeneration in animal models. The failure of microglial phagocytosis influences AD-linked pathologies, including amyloid ß accumulation, tau propagation, neuroinflammation, and infection. However, a precise understanding of microglia-mediated phagocytosis in Alzheimer's disease (AD) is still lacking. In this review, we summarize current knowledge of the molecular mechanisms involved in microglial phagocytosis in AD across a wide range of pre-clinical, post-mortem, ex vivo, and clinical studies and review the current limitations regarding the detection of microglia phagocytosis in AD. Finally, we discuss the rationale of targeting microglial phagocytosis as a therapeutic strategy for preventing AD or slowing its progression.


Assuntos
Doença de Alzheimer , Animais , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Microglia/metabolismo , Estudo de Associação Genômica Ampla , Fagocitose , Encéfalo/metabolismo
18.
Org Lett ; 25(50): 9014-9019, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38063439

RESUMO

Photoinduced generation of phosphoranyl radicals offers a versatile strategy to access a variety of synthetically valuable radicals. A long-standing challenge remains in the regulation of phosphoranyl radical to undergo α-scission pathway, although the ß-scission mode has been intensively studied. We herein developed an unprecedented protocol for selective α-scission of the P(OH)R3 radical intermediate under photocatalytic conditions. This efficient P-C bond cleavage via α-scission of the P(OH)R3 radicals has been successfully utilized in the alkylation/fluoroalkylation of alkenes.

19.
Nat Prod Res ; : 1-7, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38058102

RESUMO

One new lycopodine-type alkaloid (1), one new natural product (2), and eight known analogs (3-10) were isolated from the whole plants of Lycopodium japonicum Thunb. The structures of 1-10 were determined based on extensive comprehensive spectroscopic analyses, including UV, IR, NMR, and HRESIMS. Moreover, the isolated alkaloids were evaluated for their neuroprotective activity against Hemin-induced HT22 cell damage. Notably, compounds 1 and 10 exhibited potential neuroprotective activities, with 21.45% and 20.55% increase in cell survival at 20 µM, respectively. Moreover, compounds 1 and 10 revealed protective effects on Hemin-induced apoptosis in HT22 cells.

20.
BMC Geriatr ; 23(1): 872, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114905

RESUMO

BACKGROUND: Pemphigus and pemphigoid are rare autoimmune skin disorders caused by autoantibodies against structural proteins and characterized by blistering of the skin and/or mucous membranes. Associations have been noted between skin diseases and Alzheimer's dementia (AD). Dementia is a neurological disorder of progressive cognitive impairment with increasing incidence among older adults. This study aimed to assess the potential associations between pemphigus, pemphigoid and AD in a large, nationally representative US cohort. METHODS: All data of hospitalized patients aged 60 years or older were extracted from the US Nationwide Inpatient Sample (NIS) database 2016-2018. Patients with a history of head trauma, diagnosis of vascular dementia, history of cerebrovascular disease, or malformation of cerebral vessels were excluded. The study population was divided into those with and without pemphigus (cohort 1) and with and without pemphigoid (cohort 2). RESULTS: Pemphigus was independently associated with a 69% increased risk of AD. Adults ≥80 years old with pemphigus were 72% more likely to develop AD than adults without pemphigus. Women with pemphigus were 78% more likely to develop AD than women without pemphigus. On the other hand, pemphigoid was independently associated with a 39% increased risk for AD and subjects ≥80 years with pemphigoid were 40% more likely to have AD than those without pemphigoid. Females with pemphigoid were 63% more likely to have AD than those without pemphigoid. Moreover, Hispanic older adults with pemphigus were 3-times more likely to have AD than those without pemphigoid. CONCLUSIONS: Pemphigus and pemphigoid were both independently associated with AD in older adults, especially among females and octogenarians. Further studies addressing the etiology and mechanisms underlying these associations are highly warranted.


Assuntos
Doença de Alzheimer , Penfigoide Bolhoso , Pênfigo , Idoso de 80 Anos ou mais , Humanos , Feminino , Idoso , Pênfigo/diagnóstico , Pênfigo/epidemiologia , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/epidemiologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Pacientes Internados , Causalidade
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