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1.
Science ; 385(6704): 68-74, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38963855

RESUMO

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

2.
Proc Natl Acad Sci U S A ; 121(28): e2322972121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968116

RESUMO

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteína 1 de Ligação à Proteína Supressora de Tumor p53 , Ubiquitina-Proteína Ligases , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Humanos , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Ubiquitina/metabolismo , Histonas/metabolismo , Histonas/genética , Poliubiquitina/metabolismo
3.
Chin J Integr Med ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900227

RESUMO

The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.

4.
Chemistry ; : e202401693, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837262

RESUMO

The serious dendrite growth and H2O-induced side reactions on the Zn electrode lead to a significant fading in the cycling performance, hindering the development of commercial applications of aqueous Zn-ion batteries (AZIBs). Herein, a novel bifunctional network coating of dynamically cross-linking sodium alginate with trehalose has been rationally constructed on the Zn anode (Zn@AT). Firstly, the AT coating possesses abundant zinophilic oxygen-containing functional groups, which are able to induce uniform Zn2+ ion flux. Secondly, the AT coating as a solid barrier can effectively inhibit H2O-induced side reactions by lowering the activity of H2O molecules. More specially, based on the dynamic cross-linking, AT network coating is endowed with self-healing capacity during cycling for durable battery operation. Consequentially, Zn@AT anodes in symmetric cells can cycle stably for 2787 h at 2 mA cm-2/2 mAh cm-2, and even achieve a significantly long cycle performance of 1087 h at large charge/discharge depths of 10 mA cm-2/10 mAh cm-2. Moreover, the Zn@AT//MnO2 full cell shows excellent specific capacity of 175 mAh g-1 after 400 cycles. This study lights an effective strategy to enhance the durability of Zn electrodes in AZIBs.

5.
Int J Antimicrob Agents ; 64(2): 107223, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38810940

RESUMO

OBJECTIVES: Mycobacterium abscessus is a non-tuberculous mycobacterial pathogen that causes pulmonary and skin infections globally. Clarithromycin plays a pivotal role in treating M. abscessus infections, with resistance often leading to treatment failure. While canonical mutations in the 23S rRNA residue 2270/2271 are recognized as the primary mechanism for acquired clarithromycin resistance, resistant isolates lacking these mutations have been widely reported. This study aims to identify new mechanisms of clarithromycin resistance in M. abscessus. METHODS: We selected spontaneous resistant mutants derived from two parental strains characterized by erm(41) T28 and C28 sequevars, respectively. Whole-genome sequencing was performed on mutants lacking the 23S rRNA 2270/2271 mutations. Site-directed mutagenesis was used to confirm the resistance phenotypes of newly identified mutations. Bioinformatic analysis of publicly available genomes was conducted to evaluate the presence of these mutations in clinical isolates. The spatial localization of these mutations in the ribosome was analyzed to investigate potential mechanisms of resistance. RESULTS: A total of 135 resistant mutants were selected from the parental strains. Sequencing of the 78 mutants lacking the 23S rRNA 2270/2271 mutations identified mutations within the peptidyl-transferase center and hairpin loops 35, 49, and 74 of the 23S rRNA. These noncanonical mutations were identified in 57 of 1875 genomes of clinical isolates. Thirteen representative mutations were introduced into the bacterial genome, and their contributions to macrolide resistance were confirmed. The newly identified mutations all localized at the entrance of the nascent peptide exit tunnel, potentially contributing to resistance by disrupting the macrolide binding pocket. CONCLUSION: Several noncanonical 23S rRNA mutations conferring clarithromycin resistance were identified. These mutations enhance our understanding of macrolide resistance in M. abscessus and could serve as important markers for diagnosing clarithromycin resistance.

6.
Nat Commun ; 15(1): 3820, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744833

RESUMO

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

7.
Adv Sci (Weinh) ; 11(22): e2400336, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38605606

RESUMO

The practical application of aqueous Zn-ion batteries (AZIBs) is hindered by the crazy Zn dendrites growth and the H2O-induced side reactions, which rapidly consume the Zn anode and H2O molecules, especially under the lean electrolyte and Zn anode. Herein, a natural disaccharide, d-trehalose (DT), is exploited as a novel multifunctional co-solvent to address the above issues. Molecular dynamics simulations and spectral characterizations demonstrate that DT with abundant polar -OH groups can form strong interactions with Zn2+ ions and H2O molecules, and thus massively reconstruct the coordination structure of Zn2+ ions and the hydrogen bonding network of the electrolyte. Especially, the strong H-bonds between DT and H2O molecules can not only effectively suppress the H2O activity but also prevent the rearrangement of H2O molecules at low temperature. Consequently, the AZIBs using DT30 electrolyte can show high cycling stability even under lean electrolyte (E/C ratio = 2.95 µL mAh-1), low N/P ratio (3.4), and low temperature (-12 °C). As a proof-of-concept, a Zn||LiFePO4 pack with LiFePO4 loading as high as 506.49 mg can be achieved. Therefore, DT as an eco-friendly multifunctional co-solvent provides a sustainable and effective strategy for the practical application of AZIBs.

8.
J Phys Condens Matter ; 36(25)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38457831

RESUMO

Cyclo-pentazolate salts (CPSs) as a new type of high-energy-density materials (HEDMs) with high nitrogen content have attracted considerable research attention. In contrast to the extensive studies on their energy properties, the thermal transport process in CPSs has been less studied which relates closely to the thermal safety of this material. Concerning the hydrazinium cyclo-pentazolate (HCP), we conduct a computational study to estimate the thermal conductivity of HCP by means of the non-equilibrium molecular dynamics (NEMD) simulation. To achieve that, we have customized interaction parameters based on the default OPLS force field for the HCP, as benchmarked by its crystal structure. Our simulations have revealed surprisingly anisotropic thermal conductivity for the HCP, while the thermal conductivity becomes highest roughly in the direction perpendicular tocyclo-N5-with its value notably higher than common high explosives. By modulating the interaction parameters within the HCP molecule, we have further captured a dominant role of the interaction betweencyclo-N5-in regulating the thermal conductivity of the HCP. The attractive Lennard-Jones (LJ) potential may restrict the relative motion betweencyclo-N5-, which forms a long-range order thus enhances thermal transport in the direction perpendicular tocyclo-N5-. Our simulations result on the effect of (cyclo-N5-)-(cyclo-N5-) interaction provide insights to engineer thermal transport in CPSs at the molecular level.

9.
Parasites Hosts Dis ; 62(1): 53-63, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38443770

RESUMO

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 µg/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0 ± 3.0%, and 48.0 ± 2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.


Assuntos
Babesia microti , Babesiose , Gastrópodes , Humanos , Animais , Camundongos , Antígenos de Superfície , Grupos Controle , Contagem de Eritrócitos
10.
Sci Data ; 11(1): 280, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459039

RESUMO

The flower thrips Frankliniella intonsa (Thysanoptera: Thripidae) is a common insect found in flowers of many plants. Sometimes, F. intonsa causes damage to crops through direct feeding and transmission of plant viruses. Here, we assembled a chromosomal level genome of F. intonsa using the Illumina, Oxford Nanopore (ONT), and Hi-C technologies. The assembled genome had a size of 209.09 Mb, with a contig N50 of 997 bp, scaffold N50 of 13.415 Mb, and BUSCO completeness of 92.5%. The assembled contigs were anchored on 15 chromosomes. A set of 14,109 protein-coding genes were annotated in the genome with a BUSCO completeness of 95.0%. The genome contained 491 non-coding RNA and 0.57% of interspersed repeats. This high-quality genome provides a valuable resource for understanding the ecology, genetics, and evolution of F. intonsa, as well as for controlling thrips pests.


Assuntos
Genoma de Inseto , Tisanópteros , Animais , Cromossomos , Flores , Tisanópteros/genética
11.
RSC Adv ; 14(11): 7490-7498, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38440281

RESUMO

In this work, we report a novel high-pressure solid-state metathesis (HSM) reaction to produce spherical bulk (diameters 2-4 mm) Co-C alloys (Co3C and Co1-xCx). At 2-5 GPa and 1300 °C, C atoms preferentially occupy the interstitial sites of the face-centered cubic (fcc) Co lattice, leading to the formation of metastable Pnma Co3C. The Co3C decomposes above 1400 °C at 2-5 GPa, C atoms infiltrate the interstitial sites of the fcc Co lattice, saturating the C content in Co, forming an fcc Co1-xCx solid solution while the C atoms in excess are found to precipitate in the form of graphite. The Vickers hardness of the Co-C alloys is approximately 6.1 GPa, representing a 19.6% increase compared to hexagonal close-packed (hcp) Co. First-principles calculations indicate that the presence of C atoms in the Pnma Co3C structure leads to a relative decrease in the magnetic moments of the two distinct Co atom occupancies. The Co-C alloys exhibited a soft magnetic behavior with saturation magnetization up to 93.71 emu g-1 and coercivity of 74.8 Oe; coercivity increased as the synthesis pressure rises.

12.
Int J Biol Macromol ; 265(Pt 2): 131091, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521319

RESUMO

Acetaldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme in alcohol metabolism, and oral administration of ALDH2 is a promising method for alcohol detoxification. However, recombinant ALDH2 is susceptible to hydrolysis by digestive enzymes in the gastrointestinal tract and is expressed as inactive inclusion bodies in E. coli. In this study, we performed three rounds of rational design to address these issues. Specifically, the surface digestive sites of pepsin and trypsin were replaced with other polar amino acids, while hydrophobic amino acids were incorporated to reshape the catalytic cavity of ALDH2. The resulting mutant DE2-852 exhibited a 45-fold increase in soluble expression levels, while its stability against trypsin and pepsin increased by eightfold and twofold, respectively. Its catalytic efficiency (kcat/Km) at pH 7.2 and 3.2 improved by more than four and five times, respectively, with increased Vmax and decreased Km values. The enhanced properties of DE2-852 were attributed to the D457Y mutation, which created a more compact protein structure and facilitated a faster collision between the substrate and catalytic residues. These results laid the foundation for the oral administration and mass preparation of highly active ALDH2 and offered insights into the oral application of other proteins.


Assuntos
Aldeído Desidrogenase , Pepsina A , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/química , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Tripsina , Escherichia coli/genética , Escherichia coli/metabolismo , Aminoácidos
13.
Front Cell Infect Microbiol ; 14: 1301089, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435308

RESUMO

Bacteriophages (phages) represent promising alternative treatments against multidrug-resistant Acinetobacter baumannii (MDRAB) infections. The application of phages as antibacterial agents is limited by their generally narrow host ranges, so changing or expanding the host ranges of phages is beneficial for phage therapy. Multiple studies have identified that phage tail fiber protein mediates the recognition and binding to the host as receptor binding protein in phage infection. However, the tail tubular-dependent host specificity of phages has not been studied well. In this study, we isolated and characterized a novel lytic phage, vB_Ab4_Hep4, specifically infecting MDRAB strains. Meanwhile, we identified a spontaneous mutant of the phage, vB_Ab4_Hep4-M, which revealed an expanded host range compared to the wild-type phage. A single mutation of G to C was detected in the gene encoding the phage tail tubular protein B and thus resulted in an aspartate to histidine change. We further demonstrated that the host range expansion of the phage mutant is driven by the spontaneous mutation of guanine to cytosine using expressed tail tubular protein B. Moreover, we established that the bacterial capsule is the receptor for phage Abp4 and Abp4-M by identifying mutant genes in phage-resistant strains. In conclusion, our study provided a detailed description of phage vB_Ab4_Hep4 and revealed the tail tubular-dependent host specificity in A. baumannii phages, which may provide new insights into extending the host ranges of phages by gene-modifying tail tubular proteins.


Assuntos
Acinetobacter baumannii , Bacteriófagos , Mutação , Acinetobacter baumannii/genética , Antibacterianos , Bacteriófagos/genética , Especificidade de Hospedeiro
14.
Biosystems ; 238: 105190, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492628

RESUMO

A primary objective of biology is the development of universal laws that define how organic form develops and how it evolves as a function of size, both ontogenetically and across evolutionary time. Scaling theory has been essential in reaching this goal by giving a complete perspective point, particularly in illuminating the fundamental biological features produced within scaling exponents defining families of equations. Nonetheless, the theoretical basis of the allometric equation within scaling theory are inadequately explained, particularly when it comes to establishing links between micro-level processes at the cellular level and macro-level phenomena. We proposed an unlimited cell bipartition, resulting in an exponential growth in cell numbers during an individual's lifespan, to bridge this conceptual gap between cellular processes and allometric scaling. The power-law scaling between body mass and organ weight was produced by the synchronous exponential increments and the allometric exponent is rate of logarithmic cell proliferation rate. Substituting organ weight for erythrocyte weight aided in the development of a power-law scaling relationship between body mass and metabolic rate. Furthermore, it is critical to understand how cell size affects the exponent in power-law scaling. We find that a bigger exponent will result from an increase in the average weight of organ cells or a decrease in the average weight of all cells. Furthermore, cell proliferation dynamics showed a complex exponential scaling between body mass and longevity, defying the previously reported power-law scaling. We discovered a quadratic link between longevity and logarithmic body mass. Notably, all of the parameters included in these relationships are explained by indices linked to cell division and embryonic development. This research adds to our understanding of the complex interaction between cellular processes and overarching scaling phenomena in biology.


Assuntos
Evolução Biológica , Modelos Biológicos , Tamanho Corporal , Divisão Celular , Tamanho Celular
15.
J Clin Neurosci ; 121: 119-128, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38394955

RESUMO

BACKGROUND: Total/near-total resection (TR/NTR) of complex lumbosacral lipomas (CSL) is reported to be associated with better long-term functional outcomes and lower symptomatic re-tethering rates. We report our institutional experience for CSL resection in affected children. METHODS: This is a single-institution, retrospective study. Inclusion criteria consist of patients with CSL with dorsal, transitional and chaotic lipomas based on Pang et al's classification. The study population is divided into 2 groups: asymptomatic patients with a normal preoperative workup referred to as 'prophylactic intent' and 'therapeutic intent' for those with pre-existing neuro-urological symptoms. Primary aims are to review factors that affect post-operative clean intermittent catheterization (CIC), functional outcomes based on Necker functional score (NFS), and re-tethering rates. RESULTS: 122 patients were included from 2000 to 2021. There were 32 dorsal lipomas (26.2 %), 74 transitional lipomas (60.7 %), and 16 chaotic lipomas (13.1 %). 82 % patients achieved TR/NTR. Favourable NFS at 1-year was 48.2 %. The re-tethering rate was 6.6 %. After multivariable analysis, post-operative CIC was associated with median age at surgery (p = 0.026), lipoma type (p = 0.029), conus height (p = 0.048) and prophylactic intent (p < 0.001). Next, extent of lipoma resection (p = 0.012) and the post-operative CSF leak (p = 0.004) were associated with re-tethering. Favourable NFS was associated with lipoma type (p = 0.047) and prophylactic intent surgery (p < 0.001). CONCLUSIONS: Our experience shows that TR/NTR for CSL is a feasible option to prevent functional deterioration and re-tethering. Efforts are needed to work on factors associated with post-operative CIC.


Assuntos
Lipoma , Neoplasias da Medula Espinal , Criança , Humanos , Lactente , Estudos Longitudinais , Estudos Retrospectivos , Resultado do Tratamento , Singapura/epidemiologia , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Medula Espinal , Lipoma/cirurgia , Hospitais , Região Lombossacral/cirurgia
16.
Protein Cell ; 15(8): 594-611, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38366188

RESUMO

The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in-depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.


Assuntos
Envelhecimento , Análise de Célula Única , Malha Trabecular , Transcriptoma , Animais , Envelhecimento/genética , Malha Trabecular/metabolismo , Malha Trabecular/citologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Movimento Celular/genética , Macaca , Apoptose/genética
18.
World J Hepatol ; 16(1): 91-102, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38313249

RESUMO

BACKGROUND: Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma (HCC), the dismal overall prognosis still envelops HCC patients. Several comparative trials have been conducted to study whether transarterial chemoembolization (TACE) could improve clinical outcomes in patients receiving sorafenib for advanced HCC; however, the findings have been inconsistent. AIM: To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC, by performing a systematic review and meta-analysis. METHODS: This study was conducted following the PRISMA statement. A systematic literature search was conducted using the Cochrane Library, Embase, PubMed, and Web of Science databases. Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone. Data synthesis and meta-analysis were conducted using Review Manager software. RESULTS: The present study included 2780 patients from five comparative clinical trials (1 was randomized control trial and 4 were retrospective studies). It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival (OS), with a combined hazard ratio (HR) of 0.65 [95% confidence interval (95%CI): 0.46-0.93, P = 0.02, n = 2780]. Consistently, progression free survival (PFS) and time to progression (TTP) differed significantly between the sorafenib plus TACE arm and sorafenib arm (PFS: HR = 0.62, 95%CI: 0.40-0.96, P = 0.03, n = 443; TTP: HR = 0.73, 95%CI: 0.64-0.83, P < 0.00001, n = 2451). Disease control rate (DCR) was also significantly increased by combination therapy (risk ratio = 1.36, 95%CI: 1.02-1.81, P = 0.04, n = 641). Regarding safety, the incidence of any adverse event (AE) was increased due to the addition of TACE; however, no significant difference was found in grade ≥ 3 AEs. CONCLUSION: The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy, as evidenced by prolonged OS, PFS, and TTP, as well as increased DCR. Additional high-quality trials are essential to further validate the clinical benefit of this combination in the treatment of advanced HCC.

19.
iScience ; 27(3): 109055, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38375231

RESUMO

In an unchanging environment, natural selection always selects species with high fitness. In this study, we build a co-evolutionary system to study the interaction between stochasticity in finite populations and environmental feedback. Positive feedback between species and environment is detrimental to the invasion success, whereas negative feedback is beneficial to invasion since feedback makes population size important enough to revise natural selection's preference. In competition scenario, positive and negative feedback will benefit the initially inferior species. When selection intensity is high, negative feedback may even cause natural selection to favor the initially inferior species. All of these effects are caused by feedback that allows the initially inferior species to have greater fitness than the initially dominant species. Our results emphasize that the effects of stochasticity in evolutionary path can be reinforced by feedback with environment and then reverse the preference of natural selection.

20.
J Asian Nat Prod Res ; 26(6): 765-771, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38373226

RESUMO

To clarify the chemical basis of the total alkaloids of Uncaria rhynchophylla, HPLC-VWD chromatogram of total alkaloids was established. Under its guidance, modern chromatographic and spectroscopic techniques were used to track, isolate and identify the representative principal components. As a result, one new monoterpenoid indole alkaloid, 3S,15S-N4-methoxymethyl-geissoschizine methyl ether (1), together with 20 known alkaloids (2-21), and 5 other known compounds (22-26) were obtained. Meanwhile, sixteen characteristic peaks were identified from the total alkaloids using HPLC analysis. Then, the anti-neuroinflammatory effect of compounds 1-21 was assessed through inhibiting nitric ---oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among them, compounds 1, 3, 7, 8, 11, 12, 19 and 21 showed potent inhibitory activities with IC50 values of 5.87-76.78 µM.


Assuntos
Alcaloides , Anti-Inflamatórios , Alcaloides Indólicos , Lipopolissacarídeos , Microglia , Óxido Nítrico , Uncaria , Uncaria/química , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Animais , Camundongos , Cromatografia Líquida de Alta Pressão , Alcaloides de Triptamina e Secologanina/farmacologia , Alcaloides de Triptamina e Secologanina/química
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