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1.
J Inorg Biochem ; 262: 112766, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39476503

RESUMO

The histamine (HA) in tumors plays critical roles in promoting metastasis. Herein, a series of cetirizine (CTZ) platinum(IV) complexes with antihistamine properties were developed as antimetastatic agents. Dual CTZ platinum(IV) complex with cisplatin core was screened out as a candidate displaying potent antiproliferative activities. More importantly, it exerted promising antimetastatic properties both in vitro and in vivo. Investigation of the mechanism revealed that serious DNA damage was induced, which further led to the upregulation of histone H2AX (γ-H2AX) and P53. The mitochondria-mediated apoptosis was ignited through the B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax)/caspase3 pathway. Moreover, the HA-histamine receptor H1 (HRH1) axis was inhibited, then the key signaling phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) was suppressed. Subsequently, the angiogenesis in tumors was restrained by suppressing the inflammatory and hypoxic microenvironment. Then, the antitumor immunity was reinforced by increasing the CD3+ and CD8+ T cells and promoting the polarization of macrophages from M2- to M1-type, which was associated with the blockade of programmed cell death ligand-1 (PD-L1) expression in tumors.

2.
Proc Natl Acad Sci U S A ; 121(39): e2404395121, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39292743

RESUMO

Adult central nervous system (CNS) neurons down-regulate growth programs after injury, leading to persistent regeneration failure. Coordinated lipids metabolism is required to synthesize membrane components during axon regeneration. However, lipids also function as cell signaling molecules. Whether lipid signaling contributes to axon regeneration remains unclear. In this study, we showed that lipin1 orchestrates mechanistic target of rapamycin (mTOR) and STAT3 signaling pathways to determine axon regeneration. We established an mTOR-lipin1-phosphatidic acid/lysophosphatidic acid-mTOR loop that acts as a positive feedback inhibitory signaling, contributing to the persistent suppression of CNS axon regeneration following injury. In addition, lipin1 knockdown (KD) enhances corticospinal tract (CST) sprouting after unilateral pyramidotomy and promotes CST regeneration following complete spinal cord injury (SCI). Furthermore, lipin1 KD enhances sensory axon regeneration after SCI. Overall, our research reveals that lipin1 functions as a central regulator to coordinate mTOR and STAT3 signaling pathways in the CNS neurons and highlights the potential of lipin1 as a promising therapeutic target for promoting the regeneration of motor and sensory axons after SCI.


Assuntos
Axônios , Neurônios Motores , Regeneração Nervosa , Fosfatidato Fosfatase , Fator de Transcrição STAT3 , Transdução de Sinais , Traumatismos da Medula Espinal , Serina-Treonina Quinases TOR , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Animais , Axônios/metabolismo , Axônios/fisiologia , Regeneração Nervosa/fisiologia , Fator de Transcrição STAT3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatidato Fosfatase/metabolismo , Fosfatidato Fosfatase/genética , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , Camundongos , Ácidos Fosfatídicos/metabolismo , Células Receptoras Sensoriais/metabolismo , Feminino , Tratos Piramidais/metabolismo , Tratos Piramidais/patologia
3.
Angew Chem Int Ed Engl ; : e202414128, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39243205

RESUMO

Electron-withdrawing molecules (EWMs) have exhibited remarkable efficacy in boosting the performance of perovskite solar cells (PSCs). However, the underneath mechanisms governing their positive attributes remain inadequately understood. Herein, we conducted a comprehensive study on EWMs by comparing 2,2'-(2,5-cyclohexadiene-1,4-diylidene) bismalononitrile (TCNQ) and (2,3,5,6-tetrafluoro-2,5-cyclohexadiene-1,4-diylidene) dimalononitrile (F4TCNQ) employed at the perovskite/hole transport layer (HTL) interfaces. Our findings reveal that EWMs simultaneously enhance chemical passivation, interface dipole effect, and chemically binding of the perovskite to the HTL. Notably, F4TCNQ, with its superior electron-withdrawing properties, demonstrates a more pronounced impact. Consequently, PCSs modified with F4TCNQ achieved an impressive power conversion efficiency (PCE) of 25.21%, while demonstrating excellent long-term stability. Moreover, the PCE of a larger-area perovskite module (14.0 cm2) based on F4TCNQ reached 21.41%. This work illuminates the multifaceted mechanisms of EWMs at the interfaces in PSCs, delivering pivotal insights that pave the way for the sophisticated design and strategic application of EWMs, thereby propelling the advancement of perovskite photovoltaic technology.

4.
Dalton Trans ; 53(33): 13890-13905, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39092626

RESUMO

Protective autophagy is a promising target for antitumor drug exploration. A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI rate of 44.2% against 4T1 tumors in vivo and exhibited a rather lower toxicity than cisplatin. Notably, it exhibited satisfactory antimetastatic activities toward lung pulmonary metastasis models with an inhibition rate of 49.6% and was obviously more potent than CDDP, which has an inhibition rate of 21.6%. Mechanism detection revealed that it caused serious DNA damage and upregulated the expression of γ-H2AX and p53. More importantly, the incorporation of an autophagy inhibitor HCQ endowed the platinum(IV) complex with potent autophagy impairing properties by perturbing the lysosomal function in tumor cells, which promoted apoptosis synergistically with DNA injury. Then, the impaired autophagy further led to the suppression of hypoxia and inflammation in the tumor microenvironment by downregulating ERK1/2, HIF-1α, iNOS, caspase1 and COX-2. Adaptive immune response was improved by inhibiting the immune checkpoint PD-L1 and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.


Assuntos
Antineoplásicos , Autofagia , Hidroxicloroquina , Microambiente Tumoral , Hidroxicloroquina/farmacologia , Hidroxicloroquina/química , Autofagia/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Platina/química , Platina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose/efeitos dos fármacos
5.
J Inorg Biochem ; 260: 112696, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39142055

RESUMO

Mitophagy is an important target for antitumor drugs development. A series of ciclopirox (CPX) platinum(IV) hybrids targeting PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitophagy were designed and prepared as antitumor agents. The dual CPX platinum(IV) complex with cisplatin core was screened out as a candidate, which displayed promising antitumor activities both in vitro and in vivo. Mechanistically, it caused serious DNA damage in tumor cells. Then, remarkable mitochondrial damage was induced accompanied by the mitochondrial membrane depolarization and reactive oxygen species generation, which further promoted apoptosis through the Bcl-2/Bax/Caspase3 pathway. Furthermore, mitophagy was ignited via the PINK1/Parkin/P62/LC3 axis, and exhibited positive influence on promoting the apoptosis of tumor cells. The antitumor immunity was boosted by the block of immune check point programmed cell death ligand-1 (PD-L1), which further increased the density of T cells in tumors. Subsequently, the metastasis of tumor cells was inhibited by inhibiting angiogenesis in tumors.


Assuntos
Antineoplásicos , Ciclopirox , Mitofagia , Ciclopirox/farmacologia , Humanos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos , Mitofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Platina/química , Platina/farmacologia , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/imunologia , Neoplasias/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo
6.
J Med Chem ; 67(15): 12868-12886, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39069665

RESUMO

Epithelial-mesenchymal transition (EMT) is a critical process for cancer progression, which is crucial in inhibiting the immunity in tumors and further boosting tumor metastasis. The suppression of EMT represents a promising strategy for inhibiting metastatic tumors. Herein, a series of new canadine platinum(IV) conjugates with potent antiproliferative and antimetastatic activities were developed, which activated by suppressing EMT and provoking immune response in tumors besides causing DNA injury. The complexes could covalently conjugate to DNA and induce mitochondria-mediated apoptosis via Bcl-2/Bax/caspase3 signaling. The EMT process was remarkably inhibited by suppressing the Wnt/ß-catenin pathway, reversing the inflammatory tumor microenvironment, and inhibiting the HIF-1α pathway, which further resulted in the inhibited angiogenesis in tumors. Moreover, the antitumor immunity was elevated by blocking immune checkpoints PD-L1 and CD47 accompanied by the improvement of CD3+ and CD8+ T lymphocytes and the macrophage polarization from M2- toward M1-type simultaneously in tumors.


Assuntos
Antineoplásicos , Proliferação de Células , Transição Epitelial-Mesenquimal , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Animais , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/química , Microambiente Tumoral/efeitos dos fármacos , Metástase Neoplásica , Feminino , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais
7.
Anim Nutr ; 18: 1-16, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38989011

RESUMO

The effects of Lactobacillus plantarum in microencapsulation (LPM) on intestinal development in layer chicks were investigated in this study, as well as the colonization of L. plantarum in the gut. A total of 480 healthy Hy-Line Brown layer chicks at 0 d old were randomly divided into 4 groups (8 replicates each treatment), and the diets of these birds were supplemented with nothing (control), L. plantarum (0.02 g/kg feed; 109 CFU/kg feed), LPM (1.0 g/kg feed; 109 CFU/kg feed) and wall material of LPM (WM; 0.98 g/kg feed), respectively. Compared to control, LPM improved growth performance and intestinal development of layer chicks, evidenced by significantly increased body weight, average daily gain, average daily feed intake, villus height, villus height/crypt depth, as well as weight and length of the duodenum, jejunum and ileum (P < 0.05). These results could be attributed to the increased colonization of L. plantarum in the gut, which was verified by significant increases in lactic acid content, viable counts in chyme and mucosa (P < 0.05), as well as a visible rise in number of strains labeled with fluorescein isothiocyanate. Meanwhile, the relative abundances of Lactobacillus and Bifidobacterium significantly increased in response to microencapsulated L. plantarum supplementation (P < 0.05), accompanied by the significant up-regulation of colonization related genes (P < 0.05), encoding solute carrier family, monocarboxylate transporter, activin A receptor, succinate receptor and secretogranin II. To sum up, microencapsulated L. plantarum supplementation promoted intestinal development, which could be attributed to the enhancement of L. plantarum colonization in the intestine through the mutual assistance of Bifidobacterium and interactions with colonization related transmembrane proteins.

8.
J Agric Food Chem ; 72(27): 15376-15386, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38914516

RESUMO

Determination of quantitative compositions of blended oils is an essential but challenging step for the quality control and safety assurance of blended oils. We herein report a method for the quantitative analysis of blended oils based on the intensity ratio of triacylglycerol marker ions, which could be obtained from the highly reproducible spectra acquired by using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to directly analyze blended oils in their oily states. We demonstrated that this method could provide good quantitative results to binary, ternary, and quaternary blended oils, with simultaneous quantitation of multiple compositions, and was applicable for quantitative analysis of commercial blended oil products. Moreover, the intensity ratio-based method could be used to rapidly measure the proportions of oil compositions in blended oils, only based on the spectra of the blended oils and related pure oils, making the method as a high-throughput approach to meet the sharply growing analytical demands of blended oils.


Assuntos
Óleos de Plantas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Triglicerídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Óleos de Plantas/química , Triglicerídeos/análise , Triglicerídeos/química , Íons/análise
10.
Mater Horiz ; 11(9): 2095-2105, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38391254

RESUMO

Solar-driven evaporation is promising to address water scarcity. However, preserving the heat inside evaporators instead of allowing run-off, and synergistically utilizing it to wick water from the bulk, is still underexplored. Herein, a dual-functional bridge of longitudinal orientated channels of Al2O3 fibers (AOFs) embedded in a multi-layered nonwoven evaporator was proposed to create a buffer for spontaneous thermal conduction and anti-gravitational water pumping. As a self-floating system with high porosity and flexibility, benefiting from the strong water transporting ability and high thermal conductivity of the AOFs, a superhigh evaporation rate (2.79 kg m-2 h-1 under 1 sun) can be achieved with great stability and durability. This work highlights the potential of promoting thermal management using a large-scale vapour chamber and mass-producible nonwoven technology to prepare a high-performance evaporator for practical applications.

11.
RSC Adv ; 13(44): 30898-30904, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37869382

RESUMO

The proliferation and differentiation of bone mesenchymal stem cells (BMSCs) in vitro are the key properties of bone tissue engineering for biomaterials. In this study, hydroxyapatite (HA) coated porous carbon nanofibres (PCNFs) were prepared to load dexamethasone (DEX) and further improve the differentiation ability of the BMSCs. Various characterisations were applied to reveal the DEX loading efficacy and biocompatibility, especially the differentiation strength. The results showed that HA could be successfully coated on the PCNFs by pretreating the surface using PEG conjugation. With an increase of HA, the particle diameter increased and the DEX loading decreased. In vitro experiments proved higher cell viability, alkaline phosphatase (ALP) activity, calcium nodule secretion ability and the RUNX2 protein expression, indicating that the as-prepared was of great biocompatibility and optimised osteoconductivity, which was attributed to the componential imitation to natural bone and the accelerated BMSCs differentiation. Consequently, the novel DEX loaded and HA coated PCNFs can provide potential applications in bone tissue regeneration.

12.
Chemphyschem ; 24(24): e202300587, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37880197

RESUMO

Studying the characteristics and molecular mechanisms of liquid self-diffusion coefficient and viscosity changes is of great significance for, e. g., chemical and petroleum processing. As examples of highly complex liquid,an asphaltene-free high-acid and high-viscosity crude oil and its extracted fractions were studied by comparing their 1 H DOSY diffusion maps. The crude oil exhibited a polydisperse diffusion distribution, including multiple diffusion portions with diffusion coefficients much smaller than that of any single fraction in independent diffusion. The main mechanism that leads to the decreases in the diffusion coefficients of crude oil is attributed to diffusion resistance enhanced by Dynamical Molecular-Interaction Networks (DMINs), rather than by enlargement of the diffusion species caused by molecular aggregation. Constructed through the synergistic interactions of various polar molecules in crude oil, DMINs dynamically bind polar molecules, trap polarizable molecules, and spatially hinder the free motion of non-polar molecules. Overall, this reduces the mobility of all molecular species, as illustrated by the decreased diffusion coefficients. This study demonstrates that DOSY is a powerful NMR method to investigate molecular motion abilities also in complex mixtures. In addition, the insights in the influence of the interaction matrix on the molecular mobility also help to understand the contribution of "structural viscosity" to the viscosity of heavy oil.

13.
J Am Coll Emerg Physicians Open ; 4(3): e12956, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37223213

RESUMO

Objective: To characterize the burden of illness associated with oral factor Xa (FXa) inhibitor-related bleeding in the US Medicare population. Methods: This retrospective cohort study used the full 20% Medicare random sample claims database to identify patients who experienced their first hospitalization for an FXa inhibitor-related major bleed between October 2013 and September 2017. Bleeding types were classified as intracranial hemorrhage (ICH), gastrointestinal (GI), and other. Associations between risk factors and outcomes (in-hospital and 30-day mortality, 30-day readmission, and discharge to a location other than home) adjusted for patient demographic characteristics, baseline clinical conditions, index event characteristics, treatment with hemostatic/factor replacement agents or transfusion (ie, usual care prereversal agent availability), multicompartment ICH and neurosurgical procedures (ICH cohort), and endoscopy (GI cohort) were assessed using multivariable regression and reported as crude incidences and adjusted odds ratios (ORs) stratified by bleed type. Results: Of the 11,593 patients identified, 2737 (23.6%) had ICH, 8169 (70.5%) had GI bleeds, and 687 (5.9%) had other bleeds. The incidences of in-hospital mortality, 30-day mortality, need for postdischarge out-of-home care, and 30-day readmission were 15.7%, 29.1%, 78.3%, and 20.3% in the single-compartment ICH cohort, respectively; and 1.7%, 6.8%, 41.3%, and 18.8% in the GI bleeds cohort, respectively. Increased odds of both in-hospital mortality and 30-day mortality were significantly associated with: multicompartment ICH (reference, single compartment ICH; OR = 3.35 [95% confidence interval (CI): 2.41-4.66]; 2.18 [95% CI: 1.63-2.91]), loss of consciousness during index hospitalization (yes vs no; OR = 2.03 [95% CI: 1.38-2.97]; 1.49 [95% CI: 1.11-2.02]), receiving usual care (yes vs no; OR = 1.55 [95% CI: 1.22-1.98]; 1.33 [95% CI: 1.09-1.63]) during index hospitalization, and increasing number of Elixhauser comorbidities at baseline (OR = 1.07 [95% CI: 1.03-1.10]; 1.09 [95% CI: 1.06-1.12]) in the ICH cohort; intensive care unit admission (yes vs no; OR = 1.88 [95% CI: 1.32-2.67]; 1.51 [95% CI: 1.26-1.81]), increasing number of Elixhauser comorbidities at baseline (OR = 1.12 [95% CI: 1.07-1.18]; 1.15 [1.12-1.18]), and increasing age on index date (OR = 1.04 [95% CI: 1.02-1.07]; 1.05 [95% CI: 1.04-1.07]) in the GI bleeds cohort. Conclusions: In this large sample of Medicare patients, FXa inhibitor-related major bleeding was associated with substantial burden in terms of adverse clinical outcomes and health care resource use. Incidence of ICH was lower than GI bleeds; however, burden of illness was notably higher with ICH.

14.
J Med Chem ; 66(5): 3393-3410, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36891739

RESUMO

A series of autophagy-targeted antimetastatic clioquinol (CLQ) platinum(IV) conjugates were designed and prepared by incorporating an autophagy activator CLQ into the platinum(IV) system. Complex 5 with the cisplatin core bearing dual CLQ ligands with potent antitumor properties was screened out as a candidate. More importantly, it displayed potent antimetastatic properties both in vitro and in vivo as expected. Mechanism investigation manifested that complex 5 induced serious DNA damage to increase γ-H2AX and P53 expression and caused mitochondria-mediated apoptosis through the Bcl-2/Bax/caspase3 pathway. Then, it promoted prodeath autophagy by suppressing PI3K/AKT/mTOR signaling and activating the HIF-1α/Beclin1 pathway. The T-cell immunity was elevated by restraining the PD-L1 expression and subsequently increasing CD3+ and CD8+ T cells. Ultimately, metastasis of tumor cells was suppressed by the synergistic effects of DNA damage, autophagy promotion, and immune activation aroused by CLQ platinum(IV) complexes. Key proteins VEGFA, MMP-9, and CD34 tightly associated with angiogenesis and metastasis were downregulated.


Assuntos
Antineoplásicos , Clioquinol , Platina/farmacologia , Clioquinol/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Antineoplásicos/farmacologia , Apoptose , Autofagia , Linhagem Celular Tumoral
15.
Front Microbiol ; 14: 1115300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937304

RESUMO

Soil microbial diversity is important for maintaining ecosystem functions. However, the linkage between microbial diversity, especially rare and abundant bacterial diversity, and carbon decomposition remains largely unknown. In this study, we assessed the establishment and maintenance of rare and abundant bacterial α-diversities at the taxonomic and phylogenetic levels and their linkages with soil carbon decomposition separately in four Chinese woodlands. Compared to abundant bacteria, rare bacteria showed higher community diversity, tighter phylogenetic clustering, wider environmental breadth, stronger phylogenetic signals, and higher functional redundancy. The assembly of the abundant bacterial subcommunity was governed by stochastic (59.2%) and deterministic (41.8%) processes, whereas the assembly of the rare bacterial subcommunity was mainly dominated by deterministic processes (85.8%). Furthermore, total phosphorus, soil pH, and ammonium nitrogen balanced stochastic and deterministic processes in both rare and abundant bacterial subcommunities. Our results reveal that rare bacteria displayed stronger environmental adaptability and environmental constraint. Importantly, the α-diversities of rare taxa, rather than abundant taxa, were significantly related to carbon decomposition. This study provides a holistic understanding of biogeographic patterns of abundant and rare bacteria and their α-diversities in relation to carbon decomposition, thus helping us better predict and regulate carbon dynamics under the background of global climate change.

16.
Front Genet ; 14: 1122212, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741329

RESUMO

Introduction: Spruce spider mite is a primary insect pest of Chinese chestnut in China and seriously influences its yield and quality. However, the current management against this mite is costly and poorly effective. In previous research, we bred several foxtail millet materials for interplanting with chestnut tree, and found that they had high levels of crude protein (CP) in leaves and attracted spruce spider mite to feed on the leaves, thereby reducing chestnut damage. Methods: In this study, four foxtail millet varieties with significant differences in leaf crude protein content were used for high-throughput sequencing and identification of genes associated with leaf crude protein content. Gene enrichment analyses were carried out to comprehend the functions of these genes and the biological processes in which they are involved. In addition, transcription factors (TFs) were evaluated. Results: 435 differentially expressed genes (DEGs) were identified, suggesting their potential role in crude protein accumulation. Some differentially expressed genes were found to be associated with nitrogen metabolism and ubiquitin-mediated proteolysis pathways. Moreover, we identified 40 TF genes categorized into 11 transcription factor families. Discussion: Our findings represent an important resource that clarifies the mechanisms of accumulation and control of leaf crude protein in foxtail millet, and provide an opportunity for suppression of spruce spider mite attack on Chinese chestnut by interplanting with foxtail millet varieties with high concentrations of leaf crude protein.

18.
Curr Med Res Opin ; 38(12): 2201-2208, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36205707

RESUMO

OBJECTIVE: In this study, we examined colorectal cancer (CRC) screening adherence in Medicare beneficiaries and associated healthcare resource utilization (HCRU) and Medicare costs. METHODS: Using 20% Medicare random sample data, the study population included Medicare fee-for-service beneficiaries aged 66-75 years on 1 January 2009, at average risk for CRC and continuously enrolled in Medicare Part A/B from 2008 to 2018. We excluded those who had undergone colonoscopy or flexible sigmoidoscopy during 2007-2008 and assumed everyone was due for screening in 2009; screening patterns were determined for 2009-2018. Based on US Preventive Services Task Force recommendations, individuals were categorized as adherent to screening, inadequately screened or not screened. HCRU and Medicare costs were calculated as mean per patient per year (PPPY). RESULTS: Of 895,846 eligible individuals, 13.2% were adherent to screening, 53.4% were inadequately screened, and 33.4% were not screened. Compared with those not screened, adherent or inadequately screened individuals were more likely to be female, White and have comorbidities. These individuals also used more healthcare services, generating higher Medicare costs. For example, physician visits were 14.6, 22.9 and 25.9 PPPY and total Medicare costs were $6102, $8469 and $9102 PPPY for those not screened, inadequately screened and adherent, respectively. CONCLUSIONS: In Medicare beneficiaries at average risk, adherence to CRC screening was low, although the rate might be underestimated due to lack of early Medicare data. The link between HCRU and screening status suggests that screening initiatives independent of clinical visits may be needed to reach unscreened or inadequately screened individuals.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Humanos , Feminino , Estados Unidos , Masculino , Medicare , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Programas de Rastreamento , Aceitação pelo Paciente de Cuidados de Saúde
19.
BMC Health Serv Res ; 22(1): 1228, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192728

RESUMO

BACKGROUND: While prevalence of up-to-date screening status is the usual reported statistic, annual screening incidence may better reflect current clinical practices and is more actionable. Our main purpose was to examine incident colorectal cancer (CRC) screening rates in Medicare beneficiaries and to explore characteristics associated with CRC screening. METHODS: Using 20% Medicare random sample data, the study population included 2016-2018 Medicare fee-for-service beneficiaries covered by Parts A and B aged 66-75 years at average CRC risk. For each study year, we excluded individuals who had a Medicare claim for a colonoscopy within 9 years, flexible sigmoidoscopy within 4 years, and multitarget stool DNA test (mt-sDNA) within 2 years prior; therefore, any observed screening during study year was considered an "incident screening". Incident screening rates were calculated as number of incident screenings per 1000 Medicare beneficiaries. Overall rates were normalized to 2018 Medicare population distributions of age, sex, and race. RESULTS: Each year, > 1.4 million individuals met the inclusion/exclusion criteria from > 6.5 million Medicare beneficiaries. The overall adjusted incident CRC screening rate per 1000 Medicare beneficiaries increased from 85.2 in 2016 to 94.3 in 2018. Incident screening rates decreased 11.4% (22.9 to 20.3) for colonoscopy and 2.4% (58.3 to 56.9) for fecal immunochemical test/guaiac-based fecal occult blood test; they increased 201.5% (6.5 to 19.6) for mt-sDNA. The 2018 unadjusted rate was 76.0 for men and 110.4 for women. By race/ethnicity, the highest 2018 rate was for Asian individuals and the lowest rate was for Black individuals (113.4 and 72.8, respectively). CONCLUSIONS: The 2016-2018 observed incident CRC screening rate in average-risk Medicare beneficiaries, while increasing, was still low. Our findings suggest more work is needed to improve CRC screening overall and, especially, among male and Black Medicare beneficiaries.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , DNA , Feminino , Guaiaco , Humanos , Masculino , Programas de Rastreamento , Medicare , Sangue Oculto , Aceitação pelo Paciente de Cuidados de Saúde , Estados Unidos/epidemiologia
20.
R Soc Open Sci ; 9(10): 220953, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36249327

RESUMO

A stereo interplanting system with foxtail millet beneath chestnut trees is an effective planting method to raise the utilization of land in chestnut orchards, increase yields and improve quality of chestnut nuts. Consequently, exploration of genes involved in shade tolerance response in foxtail millet and breeding shade-tolerant varieties have become urgent issues. In this study, RNA-seq of leaf samples from two shade-tolerant varieties and three shade-intolerant varieties of foxtail millet at the booting stage was performed. Comparisons between the varieties revealed that 70 genes were commonly differentially expressed. Moreover, the ratio of net photosynthetic rate under shaded environment to that under light environment could be used as an indicator of shade tolerance. Subsequently, weighted gene co-expression network analysis was employed to construct a co-expression network and modules were correlated with this ratio. A total of 375 genes were identified as potentially relevant to shade tolerance, among which nine genes were also present in the 70 differentially expressed genes, which implied that they were good candidates for genes involved in shade tolerance. Our results provide valuable resources for elucidation of the molecular mechanisms underlying shade tolerance and will contribute to breeding of shade-tolerant foxtail millet that are adapted to the shaded environment under chestnut trees.

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