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1.
Artigo em Inglês | MEDLINE | ID: mdl-38949261

RESUMO

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs). SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures. METHODS: We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors. RESULTS: Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively. CONCLUSION: Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach. LEVEL OF EVIDENCE: 3.

2.
Chem Commun (Camb) ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946539

RESUMO

Designing electrocatalysts for seawater splitting remains challenging. A Ru-Co alloy supported by an N-doped carbon substrate catalyst has been designed using etching and a low-temperature treatment method. Studies show that the superior performance of this catalyst is related to the hollow-structured N-doped carbon frame and surface reconstruction of the Ru-Co alloy.

4.
Fitoterapia ; 177: 106096, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936672

RESUMO

Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, ß-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC50 values ranging from 2.35 to 17.06 µM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC50 values of 15.12 ± 0.53 and 12.92 ± 0.60 µM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC50 values of 23.56 ± 0.99 µM, compared to the positive control L-NMMA with an IC50 value of 41.11 ± 1.34 µM.

5.
Mol Biochem Parasitol ; 260: 111637, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901801

RESUMO

The protozoan protein kinase calcium-dependent protein kinase 1 (CDPK1) has emerged as a potential therapeutic target for the treatment of cryptosporidiosis. A focused screen of known kinase inhibitors identified a pyridopyrimidinone as a new chemotype of Cryptosporidium parvum (Cp) CDPK1 inhibitors. Structural comparison of CpCDPK1 to two representative human kinases, RIPK2 and Src, revealed differences in the positioning of the αC-helix that was used in the design of a potent pyridopyrimidinone-based CpCDPK1 inhibitor 7 (a.k.a. UH15-16, IC50 = 10 nM), which blocked the growth of three C. parvum strains (EC50 = 12-40 nM) as well as C. hominis (EC50 = 85 nM) in HCT-8 host cells. Pharmacokinetic and tissue distribution analyses indicated that 7 had low systemic exposure after oral administration, but high gastrointestinal concentration, as well as good Caco-2 cell permeability. Finally, 7 demonstrated partial efficacy in an IL-12 knock-out mouse model of acute cryptosporidiosis.

6.
Alcohol ; 120: 25-33, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38843962

RESUMO

Alcohol use disorder (AUD) is recognized as a chronic relapsing disorder. Alcohol Relapse Risk Scale (ARRS), a multidimensionally self-rating scale, was developed initially by the Japanese to assess the risk of alcohol reuse. The study aimed to validate the reliability and factor structure of the Chinese version of the ARRS (C-ARRS) for patients with AUD. A total of 218 patients diagnosed with AUD according to DSM-5 were recruited for self-administering C-ARRS. We assessed the internal consistency of C-ARRS using Cronbach's α coefficients and examined the factor structure through confirmatory factor analysis (CFA). Additionally, we investigated the concurrent validity by correlating C-ARRS with the Visual Analog Scale of Alcohol Craving (VAS), Penn Alcohol Craving Score (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores. CFA demonstrated inadequate data fit for the original 32-item C-ARRS, prompting the development of a revised 27-item version consisting of 6 subscales with satisfactory model fit estimates. The 27-item C-ARRS exhibited favorable internal consistency, with Cronbach's α ranging from 0.611 to 0.798, along with adequate factor loadings. The 27-item C-ARRS scores displayed significant correlations with the scores of VAS, PACS, BDI and BAI (p < .001). Our results indicated favorable reliability and factor structure of the 27-item C-ARRS. The significant correlation between the 27-item C-ARRS and clinical measures (such as depression, anxiety, and craving) demonstrates satisfactory concurrent validity. These observations collectively support the feasibility of using 27-item C-ARRS to assess the risk of alcohol relapse in patients with AUD.

7.
J Sports Sci ; 42(8): 751-762, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38864405

RESUMO

Few studies have reported the cardiovascular health effects of different high-intensity interval training (HIIT) protocols among sedentary young women. We investigated the impact of a traditional HIIT programme and a high-intensity circuit training (HICT) programme on lipid profiles and inflammatory cytokine levels in sedentary young women. Forty-two women were randomly assigned to HICT (body weight-based training), HIIT (cycling-based training), or control groups (n = 14 each). HICT and HIIT participants completed an 8-week training programme of three sessions per week. Total cholesterol (TC), triglyceride, high- and low-density lipoprotein, leptin, resistin, tumour necrosis factor-alpha (TNF-α), interleukin-8, and interferon-gamma levels were measured before and after the intervention. Post-intervention, TC and leptin were decreased in the HICT group. The HICT group also demonstrated increased lean mass, upper and lower limb strength, and balance, while the HIIT group displayed improved lower limb strength. Additionally, the control group showed significant increases in triglyceride levels, weight, body mass index, and fat mass. In conclusion, although both HICT and HIIT interventions showed improvements in cardiovascular health and physical fitness, participants in the HICT group experienced more health benefits.


Assuntos
Biomarcadores , Treinamento Intervalado de Alta Intensidade , Leptina , Comportamento Sedentário , Humanos , Treinamento Intervalado de Alta Intensidade/métodos , Feminino , Biomarcadores/sangue , Leptina/sangue , Adulto Jovem , Triglicerídeos/sangue , Índice de Massa Corporal , Fator de Necrose Tumoral alfa/sangue , Lipídeos/sangue , Força Muscular/fisiologia , Composição Corporal , Resistina/sangue , Citocinas/sangue , Colesterol/sangue , Adulto , Interferon gama/sangue , Interleucina-8/sangue
8.
Inj Prev ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844338

RESUMO

OBJECTIVE: The USA has higher rates of fatal motor vehicle collisions than most high-income countries. Previous studies examining the role of the built environment were generally limited to small geographic areas or single cities. This study aims to quantify associations between built environment characteristics and traffic collisions in the USA. METHODS: Built environment characteristics were derived from Google Street View images and summarised at the census tract level. Fatal traffic collisions were obtained from the 2019-2021 Fatality Analysis Reporting System. Fatal and non-fatal traffic collisions in Washington DC were obtained from the District Department of Transportation. Adjusted Poisson regression models examined whether built environment characteristics are related to motor vehicle collisions in the USA, controlling for census tract sociodemographic characteristics. RESULTS: Census tracts in the highest tertile of sidewalks, single-lane roads, streetlights and street greenness had 70%, 50%, 30% and 26% fewer fatal vehicle collisions compared with those in the lowest tertile. Street greenness and single-lane roads were associated with 37% and 38% fewer pedestrian-involved and cyclist-involved fatal collisions. Analyses with fatal and non-fatal collisions in Washington DC found streetlights and stop signs were associated with fewer pedestrians and cyclists-involved vehicle collisions while road construction had an adverse association. CONCLUSION: This study demonstrates the utility of using data algorithms that can automatically analyse street segments to create indicators of the built environment to enhance understanding of large-scale patterns and inform interventions to decrease road traffic injuries and fatalities.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38910476

RESUMO

INTRODUCTION: Diffuse Large B-Cell Lymphoma (DLBCL) is the most common Bcell lymphoma type. Detoxification and tumor elimination formula, a herbal compound, can potentially treat lymphoma. In this study, network pharmacology and molecular docking approaches were utilized to reveal the potential mechanism of the Jiedu Xiaoliu formula (JDXLF) against DLBCL. METHODS: Active compounds and targets of JDXLF were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to DLBCL were retrieved from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Protein- Protein Interaction (PPI) networks were established to screen core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R 4.2.2. Model interactions between potential disease targets and pharmacologically active compounds were determined by molecular docking. RESULTS: Screening of 14 herbal active ingredients yielded 129 active compounds and 1414 disease targets for DLBCL. GO annotations showed that the effects of JDXLF were related to protein phosphorylation and reactive oxygen species response. KEGG pathway enrichment analysis indicated that the detoxification and elimination of tumors formula mainly regulated apoptosis pathways. Nobiletin showed good interaction with AKT1, TP53, and CASP3, and the cell counting kit-8 (CCK-8) assay confirmed that nobiletin inhibited the proliferation of SU-DHL-4 cells. Western blot analysis showed that nobiletin downregulated the expressions of p-PI3K, p- AKT, and BCL-2 proteins and upregulated those of cleaved-caspase3 and BAX. CONCLUSION: Our findings preliminarily suggested that the active ingredient of JDXLF, nobiletin, may induce apoptosis in Diffuse Large B-Cell Lymphoma SU-DHL-4 cells by regulating the PI3K/AKT signaling pathway.

10.
Front Pharmacol ; 15: 1407435, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910891

RESUMO

Objective: Anaprazole, an innovative drug, has shown promise in initial clinical trials for patients with duodenal ulcers (DU) in China. This study aimed to evaluate the potential effects, safety, and cost-effectiveness of Anaprazole compared to Ilaprazole in the treatment of DU and the budgetary impact on the healthcare system. Methods: Two multicentre, randomized controlled trials were used as data sources. The efficacy and safety of Anaprazole and Ilaprazole were compared using an anchored matching-adjusted indirect comparison (MAIC). A cost-utility analysis (CUA) was performed using a Markov model. A budget impact analysis (BIA) was conducted to evaluate the impact on the expenditure of the Chinese healthcare system. Deterministic and probabilistic sensitivity analyses were undertaken to test the uncertainty. Results: The study findings indicated that Anaprazole and Ilaprazole have similar efficacy and safety in treating DU (OR = 1.05; 95% CI, 0.94-1.01; p = 0.35; OR = 0.63; 95% CI, 0.39-1.08; p = 0.12). The ICUR was 2,995.41¥/QALY, which is below the WTP threshold. The CUA results showed that Anaprazole is a cost-effective intervention with a probability of 85% at a given threshold. The results demonstrated strong robustness in the sensitivity analysis. Anaprazole imposed a low burden on the Chinese healthcare budget in the BIA. Conclusion: Compared with Ilaprazole, Anaprazole has similar efficacy, safety, and high cost-effectiveness, while also impacting the total expenditure of the healthcare system. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04215653 and NCT02847455.

11.
Circulation ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934130

RESUMO

BACKGROUND: Proximity to urban blue and green spaces has been associated with improved cardiovascular health; however, few studies have examined the role of race and socioeconomic status in these associations. METHODS: Data were from the CARDIA study (Coronary Artery Risk Development in Young Adults). We included longitudinal measurements (1985-1986 to 2010-2011) of blue and green spaces, including percentage of blue space cover, distance to the nearest river, green space cover, and distance to the nearest major park. Presence of coronary artery calcification (CAC) was measured with noncontrast cardiac computed tomography in 2010 to 2011. The associations of blue and green spaces with CAC were assessed with generalized estimating equation regression with adjustment for demographics, individual and neighborhood socioeconomic status, health-related behaviors, and other health conditions. We conducted stratified analyses by race and neighborhood deprivation score to investigate whether the association varied according to social determinants of health. RESULTS: The analytic sample included 1365 Black and 1555 White participants with a mean±SD age of 50.1±3.6 years. Among Black participants, shorter distance to a river and greater green space cover were associated with lower odds of CAC (per interquartile range decrease [1.45 km] to the river: odds ratio [OR], 0.90 [95% CI, 0.84-0.96]; per 10%-point increase of green space cover: OR, 0.85 [95% CI, 0.75-0.95]). Among participants in deprived neighborhoods, greater green space cover was associated with lower odds of CAC (per a 10%-point increase: OR, 0.89 [95% CI, 0.80-0.99]), whereas shorter distance to the park was associated with higher odds of CAC (per an interquartile range decrease [5.3 km]: OR, 1.07 [95% CI, 1.00-1.15]). Black participants in deprived neighborhoods had lower odds of CAC with shorter distance to a river (per an interquartile range decrease: OR, 0.90 [95% CI, 0.82-0.98]) and greater green space cover (per a 10%-point increase: OR, 0.85 [95% CI, 0.75-0.97]). There was no statistical interaction between the blue and green spaces and race or neighborhood characteristics in association with CAC. CONCLUSIONS: Longitudinally, shorter distance to a river and greater green space cover were associated with less CAC among Black participants and those in deprived neighborhoods. Shorter distance to a park was associated with increased odds of CAC among participants in deprived neighborhoods. Black participants residing in more deprived neighborhoods showed lower odds of CAC in association with greater exposure to river and green space cover.

12.
Front Physiol ; 15: 1389113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803365

RESUMO

Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of the symptoms may vary. The exact mechanism of action of thyroid hormones on gastrointestinal motility is not completely understood, however, a clue lies in the fact that muscle cell receptors can be directly acted upon by thyroxines. Both hypo- and hyperthyroidism can cause impairment of gastrointestinal motility, modifying structure and function of pharynx and esophagus, and regulating esophageal peristalsis through neuro-humoral interaction. In hyperthyroid patients, alterations of postprandial and basic electric rhythms have been observed at gastro-duodenal level, often resulting in slower gastric emptying. Gastric emptying may also be delayed in hypothyroidism, but an unrelated gastric mucosa-affecting chronic modification may also cause such pattern. Hyperthyroidism commonly show malabsorption and diarrhoea, while hypothyroidism frequently show constipation. In summary, it can be stated that symptoms of gastrointestinal motility dysfunction can be related to thyroid diseases, affecting any of the gastrointestinal segment. Clinically, the typical thyroid disease manifestations may be missing, borderline, or concealed because of intercurrent sicknesses. Motility-linked gastrointestinal problems may easily conceal a misdetected, underlying dysthyroidism that should be carefully analyzed. Here, we aim to elaborate on the associations between thyroid disorders and GI dysmotility and the common clinical manifestations associated with GI dysmotility.

13.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38711367

RESUMO

Hi-C data are commonly normalized using single sample processing methods, with focus on comparisons between regions within a given contact map. Here, we aim to compare contact maps across different samples. We demonstrate that unwanted variation, of likely technical origin, is present in Hi-C data with replicates from different individuals, and that properties of this unwanted variation change across the contact map. We present band-wise normalization and batch correction, a method for normalization and batch correction of Hi-C data and show that it substantially improves comparisons across samples, including in a quantitative trait loci analysis as well as differential enrichment across cell types.


Assuntos
Locos de Características Quantitativas , Humanos , Biologia Computacional
14.
J Glob Antimicrob Resist ; 38: 83-89, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719186

RESUMO

OBJECTIVES: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. METHODS: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. RESULTS: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. CONCLUSIONS: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

15.
Poult Sci ; 103(7): 103845, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788486

RESUMO

Phage therapy is gaining momentum as an alternative to antibiotics in the treatment of salmonellosis caused by Salmonella. In this study, a novel Salmonella phage, vB_SalS_JNS02, was isolated successfully from poultry farms in Shandong, China. The biological characteristics of vB_SalS_JNS02 were analysed, which revealed a short latent period of approximately 10 min and a burst size of 110 PFU/cell. Moreover, vB_SalS_JNS02 exhibited remarkable stability across a wide pH range (pH 3-12) and temperatures ranging from 30 to 80°C. Genome sequencing analysis provided valuable insights into the genetic composition of vB_SalS_JNS02, which consists of a double-stranded DNA genome that spans 42,450 base pairs and has a G + C content of 49.4%. Of significant importance, the genomic sequence of vB_SalS_JNS02 did not contain any genes related to lysogenicity, virulence, or antibiotic resistance. The phage's efficacy was evaluated in a larval challenge study. Treatment with the phage resulted in increased survival of Galleria mellonella larvae (100, 70, and 85%) (MOI 0.1) in the prophylactic treatment, co-infection treatment, and remedial treatment experiments, respectively. Another in vivo experiment investigated the potential application of the phage in broiler chickens and revealed that a single oral dose of vB_SalS_JNS02 (108 PFU/mL, 100 µL/chick) administered 3 h after S. enteritidis oral administration provided effective protection. The introduction of bacteriophage not only enhances the production of secretory immunoglobulin A (sIgA), but also induces alterations in the composition of the gut microbial community. Phage therapy increases the relative abundance of beneficial bacteria, which helps to maintain intestinal barrier homeostasis. However, it is unable to fully restore the disrupted intestinal microbiome caused by S. enteritidis infection. Importantly, no significant adverse effects were observed in the animal subjects following oral administration of the phage, and our findings highlight vB_SalS_JNS02 is a hopeful candidate as a promising tool to target Salmonella infections in poultry.


Assuntos
Galinhas , Genoma Viral , Terapia por Fagos , Doenças das Aves Domésticas , Salmonelose Animal , Fagos de Salmonella , Animais , Terapia por Fagos/veterinária , Fagos de Salmonella/fisiologia , Fagos de Salmonella/genética , Doenças das Aves Domésticas/terapia , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/virologia , Salmonelose Animal/terapia , Salmonelose Animal/microbiologia , Mariposas/virologia , Mariposas/microbiologia , China , Larva/microbiologia , Larva/virologia
16.
Eur J Med Chem ; 274: 116536, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38805936

RESUMO

G-quadruplexes (G4s) are commonly formed in the G-rich strand of telomeric DNA. Ligands targeting telomeric G4 induce DNA damage and telomere dysfunction, which makes them potential antitumor drugs. New telomeric G4 ligands with drug-likeness are still needed to be exploited, especially with their antitumor mechanisms thoroughly discussed. In this study, a novel series of quinoxaline analogs were rationally designed and synthesized. Among them, R1 was the most promising ligand for its cytotoxic effects on tumor cells and stabilizing ability with telomeric G4. Cellular assays illustrated that R1 stabilized G4 and induced R-loop accumulation in the telomeric regions, subsequently triggering DNA damage responses, cell cycle arrest in G2/M phase, apoptosis and antiproliferation. Moreover, R1 evoked immunogenic cell death (ICD) in tumor cells, which promoted the maturation of bone marrow derived dendritic cells (BMDCs). In breast cancer mouse model, R1 exhibited a significant decrease in tumor burden through the immunomodulatory effects, including the increase of CD4+ and CD8+ T cells in tumors and cytokine levels in sera. Our research provides a new idea that targeting telomeric G4 induces DNA damage responses, causing antitumor effects both in vitro and in vivo, partially due to the enhancement of immunomodulation.


Assuntos
Antineoplásicos , Proliferação de Células , Quadruplex G , Quinoxalinas , Telômero , Quadruplex G/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Quinoxalinas/química , Quinoxalinas/farmacologia , Quinoxalinas/síntese química , Animais , Humanos , Telômero/efeitos dos fármacos , Ligantes , Camundongos , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Feminino , Imunomodulação/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Dano ao DNA/efeitos dos fármacos
17.
Science ; 384(6700): 1117-1121, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38753767

RESUMO

Chemical reactions, in which bonds break and form, are highly dynamic quantum processes. A fundamental question is whether coherence can be preserved in chemical reactions and then harnessed to generate entangled products. Here we investigated this question by studying the 2KRb [Formula: see text][Formula: see text] + Rb2 reaction at 500 nanokelvins, focusing on the nuclear spin degrees of freedom. We prepared the initial nuclear spins in KRb (potassium-rubidium) in an entangled state by lowering the magnetic field to where the spin-spin interaction dominates and characterized the preserved coherence in nuclear spin wave function after the reaction. We observed an interference pattern that is consistent with full coherence at the end of the reaction, suggesting that entanglement prepared within the reactants could be redistributed through the atom-exchange process.

18.
Front Immunol ; 15: 1382088, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711525

RESUMO

Objective: To estimate the cost-effectiveness of adding serplulimab to chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC) patients in a first-line setting from a Chinese perspective. Methods: A three-health state partitioned survival model was constructed to simulate disease development. The clinical data used in the model were derived from the ASTRUM-004 clinical trial. Only direct medical costs were included, and the utilities were derived from published literature. The quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were employed to evaluate health outcomes. Additionally, a sensitivity analysis was performed to verify the robustness of the results. Results: Compared with chemotherapy alone, the addition of serplulimab resulted in an increase of 0.63 QALYs with an incremental cost of $5,372.73, leading to an ICER of $8,528.14 per QALY. This ICER was significantly lower than 3 times China's per capita GDP. The one-way sensitivity analysis suggested that the utility of PFS was the most sensitive factor on ICERs, followed by the price of serplulimab. Conclusion: The combination of serplulimab and chemotherapy has been shown to be a cost-effective initial treatment option for patients with metastatic squamous NSCLC with the commonly accepted willingness-to-pay threshold of 3 times the GDP per capita per QALY in China.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Análise Custo-Benefício , Neoplasias Pulmonares , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , China , Feminino , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/administração & dosagem , Metástase Neoplásica , Pessoa de Meia-Idade
19.
Chem Sci ; 15(17): 6522-6529, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38699280

RESUMO

Site selective functionalization of inert remote C(sp3)-H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical ß-C(sp3)-H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical in situ generated allyl C(sp3)-H bond processes have been well developed. However, radical-mediated direct ß-C(sp3)-H arylation of carbonyls remains elusive. Herein, we describe an iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves diethylaminoethyl radical-mediated generation of an aryl radical intermediate via XAT, then directed 1,5-HAT to form the remote alkyl radical intermediate and radical-radical coupling with cyanoarenes, and is applicable to a broad scope of unactivated remote C(sp3)-H bonds like ß-C(sp3)-H bonds of o-iodoaryl-substituted alkanones and α-C(sp3)-H bonds of o-iodoarylamides. Experimental findings are supported by computational studies (DFT calculations), revealing that this method operates via a radical-relay stepwise mechanism involving multiple SET, XAT, 1,5-HAT and radical-radical coupling processes.

20.
Sci Adv ; 10(22): eadk1113, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38809973

RESUMO

Water purification via interfacial solar steam generation exhibits promising potential. However, salt crystallization on evaporators reduces solar absorption and obstructs water supply. To address it, a waffle-shaped solar evaporator (WSE) has been designed. WSE is fabricated via a zinc-assisted pyrolysis route, combining low-cost biomass carbon sources, recyclable zinc, and die-stamping process. This route enables cost-effective production without the need of sophisticated processing. As compared to conventional plane-shaped evaporators, WSE is featured by extra sidewalls for triggering the convection with the synergistic solute and thermal Marangoni effects. Consequently, WSE achieves spontaneous salt rejection and durable evaporation stability. It has demonstrated continuous operation for more than 60 days in brine without fouling.

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