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1.
Cell ; 170(3): 577-592.e10, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28753431

RESUMO

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.


Assuntos
Neoplasias/genética , Neoplasias/patologia , Interferência de RNA , Linhagem Celular Tumoral , Biblioteca Gênica , Redes Reguladoras de Genes , Humanos , Complexos Multiproteicos/metabolismo , Neoplasias/metabolismo , Oncogenes , RNA Interferente Pequeno , Transdução de Sinais , Fatores de Transcrição/metabolismo
2.
Nano Lett ; 24(3): 966-974, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38206580

RESUMO

Two-dimensional (2D) Fe chalcogenides with their rich structures and properties are highly desirable for revealing the torturous transition mechanism of Fe chalcogenides and exploring their potential applications in spintronics and nanoelectronics. Hydrostatic pressure can effectively stimulate phase transitions between various ordered states, allowing one to successfully plot a phase diagram for a given material. Herein, the structural evolution and transport characteristics of 2D FeTe were systematically investigated under extreme conditions by comparing two distinct symmetries, i.e., tetragonal (t) and hexagonal (h) FeTe. We found that t-FeTe presented a pressure-induced transition from an antiferromagnetic state to a ferromagnetic state at ∼3 GPa, corresponding to the tetragonal collapse of the layered structure. Contrarily, the ferromagnetic order of h-FeTe was retained up to 15 GPa, which was evidently confirmed by electrical transport and Raman measurements. Furthermore, T-P phase diagrams for t-FeTe and h-FeTe were mapped under delicate critical conditions. Our results can provide a unique platform to elaborate the extraordinary properties of Fe chalcogenides and further develop their applications.

3.
J Am Chem Soc ; 146(14): 9688-9696, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38427795

RESUMO

Nearly a decade has passed since the discovery of superconductivity in CrAs, but until now, the discovered structure types of chromium-based superconductors are still scanty. It is urgent to expand this family to decipher the interplay between magnetism and superconductivity penetratingly. Here, we report the observation of superconductivity in ferromagnet CrSbSe3 with a quasi-one-dimensional structure under high pressure. Under compression, CrSbSe3 undergoes an insulator-to-metal transition and sequential isostructural phase transitions accompanied by volume collapse. Superconductivity emerges at 32.8 GPa concomitant with metallization in CrSbSe3. A maximum superconducting transition temperature Tc of 7.7 K is achieved at 57.9 GPa benefiting from both the phonon softening and the enhanced p-d hybridization between Se and Cr in CrSbSe3. The discovery of superconductivity in CrSbSe3 expands the existing chromium-based superconductor family and sheds light on the search for concealed superconductivity in low-dimensional van der Waals materials.

4.
BMC Health Serv Res ; 24(1): 120, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254103

RESUMO

OBJECTIVE: Antimicrobial resistance (AMR) has emerged as a serious global public health crisis. In response, 2016, 14 ministries in China, under the leadership of the National Health Commission, collaboratively issued the National Action Plan (NAP) to Contain Antibacterial Resistance (2016-2020). The NAP outlines strategies for medical institutions to adopt stewardship and implement AMR control. The purpose of this study was to comprehend stakeholders' perceptions of the NAP and explore the factors that influence its implementation in medical institutions. METHODS: Semi-structured interviews were conducted with practitioners from medical institution in March and April 2021. Interviews were audio-recorded, transcribed and analyzed using thematic analysis via the framework approach. RESULTS: Twenty practitioners, representing diverse roles (4 administrators, 7 clinicians, 3 microbiologists, 3 pharmacists, 3 nosocomial infection management personnel) from seven institutions, participated in the study. Substantial efforts have been undertaken to regulate the rational use of antibiotics and enhance the management of hospital infections. Participants demonstrated awareness and concern regarding antimicrobial resistance, with widespread support expressed for the NAP. Among all professions, there were varying opinions on whether they felt restricted in their daily work. The tertiary hospitals have established multidisciplinary cooperation mechanisms. Six main themes were identified as both barriers and facilitators to the implementation of the NAP in the medical institutions: individual factors, leadership, multidisciplinary collaboration, patient factors, training and culture. The capacity for administrative attention is constrained or limited, poor enforcement of guidelines, insufficient specialist staff and the liability pressure on clinicians were perceived barriers. To containing AMR in medical institutions, management of hospital infections, the public's knowledge of antibiotics' usage, routine education and multidisciplinary support would be facilitators. CONCLUSIONS: Practitioners from medical institutions were highly supportive for the NAP. Consideration of practitioners' perceived barriers and facilitators might enhance implementation of the NAP to contain antimicrobial resistance.


Assuntos
Antibacterianos , Infecção Hospitalar , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Pesquisa Qualitativa , Pessoal Administrativo , Infecção Hospitalar/prevenção & controle
5.
BMC Microbiol ; 23(1): 385, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38053056

RESUMO

BACKGROUND: Corynebacterium pyruviciproducens is a recently described species of Corynebacterium. There are few reports on the microbiological characteristics of the new species, and there is a lack of reports on the genomic analysis of the species. RESULTS: This study involved a clinical isolate from the pus of a hospital patient with sebaceous gland abscesses. The clinically isolated strain was identified as C. pyruviciproducens strain WYJY-01. In this study, referring to Koch's postulates, we observed the pathological changes of animal models infected by intraperitoneal injection and subcutaneous injection of pure culture of the strain WYJY-01. Furthermore, the strain WYJY-01 was isolated and cultured again from animal models' subcutaneous abscess drainage fluid. Subsequently, the genomics of the strain WYJY-01 was analyzed. By comparing various gene databases, this study predicted the core secondary metabolite gene cluster of the strain WYJY-01, virulence factor genes carried by prophage, pathogenicity islands, and resistance islands. In addition, the genomes of C. pyruviciproducens strain WYJY-01, ATCC BAA-1742 T, and UMB0763 were analyzed by comparative genomics, and the differential genes of strain WYJY-01 were compared, and their functions were analyzed. CONCLUSION: The findings showed that the strain WYJY-01 had pathogenicity, supplementing the phenotype characteristics of C. pyruviciproducens. Meanwhile, this research revealed the possible molecular mechanism of the pathogenicity of the strain WYJY-01 at the gene level through whole genome sequence analysis, providing a molecular basis for further research.


Assuntos
Corynebacterium , Genômica , Animais , Humanos , Corynebacterium/genética , Virulência/genética , Fenótipo , Genoma Bacteriano , Filogenia
6.
Infect Immun ; 89(12): e0031521, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34543119

RESUMO

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tuberculosis. Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette-Guérin (BCG) and H37Rv infection. By detecting BCG/H37Rv intracellular survival in sod2-silenced and sod2-overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG/H37Rv. miR-495 then was determined to be downregulated by BCG/H37Rv. BCG/H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG/H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.


Assuntos
Macrófagos/microbiologia , Macrófagos/fisiologia , MicroRNAs/genética , Mycobacterium tuberculosis/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Tuberculose/etiologia , Tuberculose/metabolismo , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mycobacterium bovis , Superóxido Dismutase/metabolismo , Tuberculose/patologia
7.
J Am Chem Soc ; 143(48): 20343-20355, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34813695

RESUMO

Emergent layered Cu-bearing van der Waals (vdW) compounds have great potentials for use in electrocatalysis, lithium batteries, and electronic and optoelectronic devices. However, many of their alluring properties such as potential superconductivity remain unknown. In this work, using CuP2Se as a model compound, we explored its electrical transport and structural evolution at pressures up to ∼60 GPa using both experimental determinations and ab initio calculations. We found that CuP2Se undergoes a semiconductor-to-metal transition at ∼20 GPa at room temperature and a metal-to-superconductor transition at 3.3-5.7 K in the pressure range from 27.0 to 61.4 GPa. At ∼10 and 20 GPa, there are two isostructural changes in the compound, corresponding to, respectively, the emergence of the interlayer coupling and start of interlayer atomic bonding. At a pressure between 35 and 40 GPa, the vdW layers start to slide and then merge, forming a new phase with high coordination numbers. We also found that the Bardeen-Cooper-Schrieffer (BCS) theory describes quite well the pressure dependence of the critical temperature despite occurrence of a possible medium-to-strong electron-phonon coupling, revealing the determinant roles of the enhanced bulk modulus and electron density of states at high pressure. Moreover, nanosizing of CuP2Se at high pressure further increased the critical temperature even at sizes approaching the Anderson limit. These findings would have important implications for developing novel applications of layered vdW compounds through simple pressure tuning of the interlayer coupling.

8.
Biochem Biophys Res Commun ; 546: 83-89, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33578293

RESUMO

Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in the progression of papillary thyroid cancer (PTC). In this study, we found consistently elevated expression levels of the lncRNA FAM230B in PTC tissues, both in newly generated RNA-seq data and in datasets from the GEO and TCGA databases. We demonstrated that the expression of FAM230B can be used for the diagnosis of PTC and is also strongly associated with lymph node metastasis. The potential biological functions of FAM230B and molecular mechanisms by which it regulates PTC progression were investigated. Functionally, FAM230B promoted the migration and invasion of PTC cells in vitro and in vivo. Mechanistically, FAM230B sponged miR-378a-3p and showed competitive binding to the 3'-UTR of WNT5A. FAM230B overexpression resulted in elevated WNT5A expression and thereby regulated the epithelial-mesenchymal transition in PTC cells. Finally, we verified that both miR-378a-3p overexpression and WNT5A silencing effectively offset the impacts of FAM230B on PTC cell migration and invasion. In conclusion, our study demonstrated the oncogenic function of the lncRNA FAM230B in PTC cells, providing a novel target for PTC diagnosis and therapy.


Assuntos
MicroRNAs/genética , Metástase Neoplásica/genética , RNA Longo não Codificante/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Proteína Wnt-5a/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Regulação para Cima , Proteína Wnt-5a/biossíntese , Proteína Wnt-5a/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
9.
Inorg Chem ; 60(11): 7857-7864, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34015921

RESUMO

Transition metal dichalcogenides (TMDs) have attracted wide attention due to their quasi-two-dimensional layered structure and exotic properties. Plenty of efforts have been done to modulate the interlayer stacking manner for novel states. However, as an equally important element in shaping the unique properties of TMDs, the effect of intralayer interaction is rarely revealed. Here, we report a particular case of pressure-tuned re-arrangement of intralayer atoms in distorted 1T-NbTe2, which was demonstrated to be a new type of structural phase transition in TMDs. The structural transition occurs in the pressure range of 16-20 GPa, resulting in a transformation of Nb atomic arrangement from the trimeric to dimeric structure, accompanied by a dramatic collapse of unit cell volume and lattice parameters. Simultaneously, a charge density wave (CDW) was also found to collapse during the phase transition. The strong increase in the critical fluctuations of CDW induces a significant decline in the electronic correlation and a change of charge carrier type from hole to electron in NbTe2. Our finding reveals a new mechanism of structure evolution and expands the field of pressure-induced phase transition.

10.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072443

RESUMO

As an important zoonotic pathogen, Streptococcus suis (S. suis) infection has been reported to be a causative agent for variety of diseases in humans and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which is commonly seen in cases of severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of death. This calls for development of new strategies to avert the damage caused by STSLS. In this study, we found for the first time that Baicalein, combined with ampicillin, effectively improved severe S. suis infection. Further experiments demonstrated that baicalein significantly inhibited the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. Cell-based assays revealed that Baicalein did not exert toxic effects and conferred protection in S. suis-infected cells. Interestingly, compared with ampicillin alone, Baicalein combined with ampicillin resulted in a higher survival rate in mice severely infected with S. suis. At the same time, we found that baicalein can be combined with meropenem against MRSA. In conclusion, these results indicate that baicalein has a good application prospect.


Assuntos
Antibacterianos/farmacologia , Flavanonas/farmacologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/efeitos dos fármacos , Animais , Antibacterianos/química , Citocinas/biossíntese , Modelos Animais de Doenças , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Flavanonas/química , Hemólise/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/metabolismo , Infecções Estreptocócicas/patologia , Relação Estrutura-Atividade
11.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198513

RESUMO

BACKGROUND: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. METHODS: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time-kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. RESULTS: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. CONCLUSIONS: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.


Assuntos
Antibacterianos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/fisiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Terapia de Imunossupressão , Espaço Intracelular/microbiologia , Lipoglicopeptídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1
12.
Arch Biochem Biophys ; 692: 108522, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781051

RESUMO

About one quarter of people worldwide are infected with tuberculosis, and multi-drug resistant tuberculosis (MDR-TB) remains a health threat. It is known that two-Component Signal Transduction Systems (TCSs) of Mycobacterium tuberculosis are closely related to tuberculosis resistance, but the mechanism by which orphan response protein Rv3143 regulates strain sensitivity to drug is still unclear. This study found that Rv3143 overexpression resulted in approximately two-fold increase in Mycobacterium smegmatis antibiotic sensitivity. Transcriptome sequencing indicated that 198 potential genes were regulated by Rv3143, affecting the sensitivity of the strain to rifampicin (RIF). MSMEG_4740 promoter binding with Rv3143, was screened out by surface plasmon resonance (SPR). Rv1524, the homologous gene of MSMEG_4740, belonging to the glycosyltransferase (Gtf) family, was related to cell wall modification. By measuring ethidium bromide (EB) accumulation, we found when Rv3143 or MSMEG_4740, or Rv1524 was overexpressed, the cell wall permeability of Mycobacterium smegmatis was increased. In addition, a combination of Rv3143 and RIF was observed. Our findings provide a new strategy for treating drug-resistant tuberculosis by increasing the expression of Rv3143 to enhance the strain sensitivity to antibiotics.


Assuntos
Proteínas de Bactérias/metabolismo , Parede Celular/metabolismo , Farmacorresistência Bacteriana , Mycobacterium smegmatis/metabolismo , Proteínas de Bactérias/genética , Parede Celular/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Mycobacterium smegmatis/genética , Permeabilidade/efeitos dos fármacos , Rifampina/farmacologia , Transcriptoma/efeitos dos fármacos
13.
Molecules ; 25(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861925

RESUMO

Background: Tuberculosis remains a global disease that poses a serious threat to human health, but there is lack of new and available anti-tuberculosis agents to prevent the emergence of drug-resistant strains. To address this problem natural products are still potential sources for the development of novel drugs. Methods: A whole-cell screening approach was utilized to obtain a natural compound enniatin A1 from a natural products library. The target compound's antibacterial activity against Mycobacterium tuberculosis (M. tuberculosis) was evaluated by using the resazurin reduction micro-plate assay (REMA) method. The cytotoxicity of the compound against Vero cells was measured to calculate the selectivity index. The intracellular inhibition activity of enniatin A1 was determined. We performed its time-kill kinetic assay against M. tuberculosis. We first tested its synergistic effect in combination with the first and second-line anti-tuberculosis drugs. Finally, we measured the membrane potential and intracellular ATP levels of M. tuberculosis after exposure to enniatin A1. Results: We identified enniatinA1 as a potential antibacterial agent against M. tuberculosis, against which it showed strong selectivity. Enniatin A1 exhibited a time-concentration-dependent bactericidal effect against M. tuberculosis, and it displayed synergy with rifamycin, amikacin, and ethambutol. After exposure to enniatinA1, the membrane potential and intracellular ATP levels of M. tuberculosis was significantly decreased. Conclusions: Enniatin A1 exhibits the positive potential anti-tuberculosis agent characteristics.


Assuntos
Trifosfato de Adenosina/metabolismo , Antituberculosos/farmacologia , Depsipeptídeos/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mycobacterium tuberculosis/metabolismo , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/agonistas , Chlorocebus aethiops , Depsipeptídeos/agonistas , Avaliação de Medicamentos , Sinergismo Farmacológico , Humanos , Células THP-1 , Células Vero
14.
Chem Pharm Bull (Tokyo) ; 66(11): 1065-1071, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30197406

RESUMO

Molecules bearing pyrazole nucleus present diverse biological properties such as antitumor and anti-inflammatory activities that can be associated with DNA interactions. This study aimed to the synthesis of new pyrazol derivatives and evaluated their ability to interact with the DNA and antitumor and topoisomerase inhibition activities. All derivatives were successfully synthesized, and their structures were elucidated by 1H-NMR and high resolution (HR)-MS (electrospray ionization positive mode (ESI+)). Antiproliferative inhibition assays, UV titration assays, fluorescence titration assays, circular dichroism (CD) assays, KI quenching studies, topoisomerase inhibitory activity assays and molecular docking were evaluated for these compounds. Especially, compounds 5e and 5q showed higher antitumor activity with IC50 values <13 µM for the tested cell lines. However, compounds 5e and 5q did not inhibit the topoisomerase activity evaluated by relaxation assay. These results show that the pyrazole nucleus contributes to the incorporation of molecules into the DNA. Moreover, it was highlighted that positive charges are relevant for the design of promising antitumor and DNA binding compounds.


Assuntos
Antineoplásicos/farmacologia , DNA Tumoral Circulante/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Pirazóis/farmacologia , Inibidores da Topoisomerase/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Espectrofotometria Ultravioleta , Relação Estrutura-Atividade , Inibidores da Topoisomerase/síntese química , Inibidores da Topoisomerase/química
15.
Addict Biol ; 21(3): 657-66, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25708696

RESUMO

Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.


Assuntos
Cognição , Tomada de Decisões , Substância Cinzenta/patologia , Dependência de Heroína/genética , Fatores de Transcrição Kruppel-Like/genética , Adulto , Alelos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Feminino , Predisposição Genética para Doença , Substância Cinzenta/diagnóstico por imagem , Haplótipos , Dependência de Heroína/psicologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Polimorfismo de Nucleotídeo Único , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
16.
Front Public Health ; 12: 1339504, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444434

RESUMO

Purpose: The Diagnosis-Related Group (DRG) or Diagnosis-Intervention Packet (DIP) payment system, now introduced in China, intends to streamline healthcare billing practices. However, its implications for clinical pharmacists, pivotal stakeholders in the healthcare system, remain inadequately explored. This study sought to assess the perceptions, challenges, and roles of clinical pharmacists in China following the introduction of the DRG or DIP payment system. Methods: Qualitative interviews were conducted among a sample of clinical pharmacists. Ten semi-structured interviews were conducted, either online or face to face. Thematic analysis was employed to identify key insights and concerns related to their professional landscape under the DRG or DIP system. Results: Clinical pharmacists exhibited variable awareness levels about the DRG or DIP system. Their roles have undergone shifts, creating a balance between traditional responsibilities and new obligations dictated by the DRG or DIP system. Professional development, particularly concerning health economics and DRG-based or DIP-based patient care, was highlighted as a key need. There were calls for policy support at both healthcare and national levels and a revised, holistic performance assessment system. The demand for more resources, be it in training platforms or personnel, was a recurrent theme. Conclusion: The DRG or DIP system's introduction in China poses both opportunities and challenges for clinical pharmacists. Addressing awareness gaps, offering robust policy support, ensuring adequate resource allocation, and recognizing the evolving role of pharmacists are crucial for harmoniously integrating the DRG or DIP system into the Chinese healthcare paradigm.


Assuntos
Assistência Farmacêutica , Farmacêuticos , Humanos , Hospitais , China , Grupos Diagnósticos Relacionados , Pesquisa Qualitativa
17.
Medicine (Baltimore) ; 102(50): e36557, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115287

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) increases with the survival of late preterm infants, but its relationship with neurodevelopmental outcomes in preterm infants remains controversial. To investigate the relationship between ROP and its severity and adverse neurodevelopmental outcomes in preterm infants. METHODS: We conducted a meta-analysis. All relevant literature before November 2022 were retrieved from PubMed, Embase, Cochrane Library Web of Science, CNKI, CBM, Wan fang Data, and VIP Database. According to the inclusion criteria and exclusion criteria, eligible literature were included to conduct clinical trial quality assessment, and the Newcastle-Ottawa scale was used to evaluate the quality of evidence. Meta-analysis was performed using RevMan5.3. Data extraction, quality assessment, and meta-analysis were performed independently by 2 people. Mean difference or standardized mean difference of motor, language and cognitive scores (Bayley III or Bayley II) were used as effect sizes for continuous data analysis, all of which were represented by 95% CI. For heterogeneity (I2 ≥ 50% or P < .10), a random effects model was used, otherwise a fixed effects model was used. RESULTS: A total of 6 literature were included. The results of the ROP group for motor (comprehensive motor, proportional motor, and fine motor), language and cognitive scores were -5.57 (95%CI, -1.43 to 0.04), -0.95 (95%CI, 1.4-0.50), -1.34 (95% CI, 1.77-0.92), -1.75 (95% CI, 2.26-1.24) and -5.56 (95% CI, 9.56-1.57). Additionally, the results of severe ROP group for motor (comprehensive motor, proportional motor, fine motor), language and cognitive scores were -8.32 (95%CI, -8.91 to 7.74), -1.10 (95%CI, -1.83 to -0.36), -1.08 (95%CI, -1.75 to -0.41), -7.03 (95%CI, -7.71 to 6.35), and -7.96 (95%CI, -8.5 to -7.42). CONCLUSIONS: The Bayley Scale scores of the ROP group were lower than those of the not ROP group, and the scores of the severe ROP were significantly lower than those of the not severe ROP group. These findings suggest that ROP can indeed delay motor, language and cognitive, especially in severe cases.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro
18.
Heliyon ; 9(3): e14638, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36967977

RESUMO

As the first of the six elements of tourism, food is an important part of tourism activities. As an important driving force for the economic development of tourist destinations, food tourism plays an increasingly important role in tourism and has gradually become an important hub connecting tourists, local residents, and tourist destinations. This study takes Yunnan wild mushrooms as a case, obtained data through a questionnaire survey and applied a projection pursuit model (PPM) to explore the driving factors affecting food tourism consumption. Research shows that the quality and abundance of gourmet resources are the most important factors affecting tourist consumption of gourmet foods, and the needs and experiences of tourists also promote their consumption, to a certain extent. This provides a guide for Yunnan Province to expand the source market. Second, we compared PPM with structural equation modeling (SEM) and demonstrated that the former requires less data than the latter and is immune to nonlinearities, interaction effects, and the researchers' excessive prior knowledge. This makes PPM more robust, anti-interference, accurate, and objective than SEM when dealing with problems. Finally, we put forward reasonable suggestions from four aspects of government, enterprises, local residents, and tourists, which provide an effective way for Yunnan Province to develop food tourism. In addition, PPM's advantages in data selection, data processing, and result stability fill the gaps in data processing in the tourism field.

19.
Heliyon ; 9(6): e16826, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313168

RESUMO

In the post-pandemic era, nighttime tourism is vital in promoting the diversified development of tourism, enhancing the vitality of cities, and improving reemployment rates. Using Kunming City, China, as an example, this study used multi-theory and multi-source data to construct an evaluation model of the spatial distribution and suitability of nighttime tourism. The projection pursuit model and spatial analysis method were used to reveal spatial distribution and explore the suitability characteristics and spatial differences of nighttime tourism development. Our results revealed the following: (1) nighttime tourism resources showed a 'large aggregation, small dispersion' spatial distribution pattern, which is characterized by a distribution along the railway line; (2) at present, the spatial distribution of nighttime tourism in Kunming displays a pattern of 'taking a high-density large gathering area as the center and extending around; ' and (3) the most suitable nighttime tourism area accounts for 11.83% of the total land area of Kunming; highly suitable area accounts for 17.53%. The general suitable and unsuitable areas accounted for 43.29% and 27.35%, respectively. The results of this study assist in providing a scientific basis for the strategic planning and development of the nighttime tourism industry in Kunming.

20.
PeerJ ; 11: e15152, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37009157

RESUMO

Background: Nitrate is the primary type of nitrogen available to plants, which is absorbed and transported by nitrate transporter 2 (NRT2) at low nitrate conditions. Methods: Genome-wide identification of NRT2 genes in G. hirsutum was performed. Gene expression patterns were revealed using RNA-seq and qRT-PCR. Gene functions were characterized using overexpression in A. thaliana and silencing in G. hirsutum. Protein interactions were verified by yeast two-hybrid and luciferase complementation imaging (LCI) assays. Results: We identified 14, 14, seven, and seven NRT2 proteins in G. hirsutum, G. barbadense, G. raimondii, and G. arboreum. Most NRT2 proteins were predicted in the plasma membrane. The NRT2 genes were classified into four distinct groups through evolutionary relationships, with members of the same group similar in conserved motifs and gene structure. The promoter regions of NRT2 genes included many elements related to growth regulation, phytohormones, and abiotic stresses. Tissue expression pattern results revealed that most GhNRT2 genes were specifically expressed in roots. Under low nitrate conditions, GhNRT2 genes exhibited different expression levels, with GhNRT2.1e being the most up-regulated. Arabidopsis plants overexpressing GhNRT2.1e exhibited increased biomass, nitrogen and nitrate accumulation, nitrogen uptake and utilization efficiency, nitrogen-metabolizing enzyme activity, and amino acid content under low nitrate conditions. In addition, GhNRT2.1e-silenced plants exhibited suppressed nitrate uptake and accumulation, hampered plant growth, affected nitrogen metabolism processes, and reduced tolerance to low nitrate. The results showed that GhNRT2.1e could promote nitrate uptake and transport under low nitrate conditions, thus effectively increasing nitrogen use efficiency (NUE). We found that GhNRT2.1e interacts with GhNAR2.1 by yeast two-hybrid and LCI assays. Discussion: Our research lays the foundation to increase NUE and cultivate new cotton varieties with efficient nitrogen use.


Assuntos
Arabidopsis , Gossypium , Gossypium/genética , Proteínas de Plantas/genética , Nitratos/metabolismo , Nitrogênio/metabolismo , Saccharomyces cerevisiae/metabolismo , Arabidopsis/genética , Transportadores de Nitrato
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