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1.
Front Public Health ; 12: 1390011, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952723

RESUMO

Objectives: The objective of this study is to develop a consensus among experts on a comprehensive and scientifically sound physical activity-related injuries (PARI) public health education program specifically tailored for undergraduates. Methods: This study designed three rounds of expert consultation by using a Delphi method. A panel of 30 experts from the fields of public health education, sports medicine, anesthesia pain, emergency medicine, and emergency nursing participated in the study. Results: This study successfully established a consensus among experts on the goals, content, teaching methods, and time allocation for the PARI Public Health Education Program for undergraduates. The program encompasses 10 objectives divided into 2 main categories: professional knowledge and skill goals. In terms of content, it includes 5 primary indicators, 22 secondary indicators, and 56 detailed tertiary indicators. Six teaching methods were identified as suitable. Additionally, a typical 60-min educational session was segmented into eight parts, with a proposed time arrangement for each, ensuring comprehensive coverage of all topics. Conclusion: The consensus achieved in this study on the PARI Public Health Education Program for undergraduates lays a crucial foundation for the advancement of health literacy and proactive health management within this demographic. We presented a comprehensive framework for PARI public health education, integrating diverse learning methods and content areas. This systematic approach not only enriched the resources available for undergraduate health education, especially of PARI but also had the potential to significantly impact the implementation and effectiveness of health promotion strategies.


Assuntos
Técnica Delphi , Humanos , China , Saúde Pública/educação , Exercício Físico , Educação em Saúde/métodos , Currículo , Masculino , Feminino , População do Leste Asiático
2.
Sci Total Environ ; 946: 174360, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960190

RESUMO

Increasing attention is being paid to the toxic physiological effects of nanoplastics (NPs) on aquatic organisms. However, few studies have systematically evaluated the regulatory mechanisms of NPs on immune response in crustaceans. In this study, a 28-day chronic exposure experiment was conducted in which shrimps were exposed to various 80-nm polystyrene NPs concentrations (0, 0.1, 1, 5 and 10 mg/L). Transcriptomic analysis was used to investigate the regulatory mechanisms of NPs in immune response of Litopenaeus vannamei. With increasing NPs concentration, the total hemocyte count (THC) content decreased, while phagocytosis rate (PR) and respiratory burst (RB) showed trends of first rising and then falling. High concentration (10 mg/L) of NPs caused the destruction of hepatopancreas tissue structure, the shedding of microvilli, the increase number of hepatocyte apoptosis and autophagy structure. With increasing NPs concentration, the lysozyme (Lys), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities first increased and then decrease, while contents of lipid peroxidation and malondialdehyde increased; the expression levels of Toll, MyD88, GPx, SOD, proPO, Lys, and ALF generally increased at first and then decreased. Transcriptional sequencing analysis showed that the pathway of differentially expressed genes in KEGG enrichment mainly included lysosome (ko04142), apoptosis (ko04210) pathways, indicating that the NPs mainly affected the immune regulatory mechanism. Further analysis by Gene Set Enrichment Analysis (GSEA) showed that the up-regulation pathways of NPs activation mainly included immune response-related pathways such as mitochondrial autophagy, DNA repair, autophagosomes signaling pathway. Our results indicated that NPs exposure induced oxidative stress, apoptosis and autophagy in shrimps. This study provides a basis for further understanding of the mechanisms of antioxidant immune regulation by NPs in shrimp and may serve as a reference for healthy ecological culture of shrimp.

3.
Front Public Health ; 12: 1387789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975360

RESUMO

Objectives: The purpose of this study was to assess the level of knowledge, attitudes, and practices (KAP) of university students in China regarding the need for PARI and public health education. Methods: A cross-sectional online and offline survey was conducted in China website through Wenjuanxing and in different cities such as Changsha Hunan Province, Shanghai, Chongqing and in different public scenarios, such as hospitals, universities, and commercial venues between September 1 and September 7, 2023, using a 28-question questionnaire designed and reviewed by multidisciplinary experts. Results: A total of 4,096 respondents were recruited for this study, with 3,957 valid questionnaires. The mean knowledge score was 1.84 ± 0.52, the mean attitude score was 2.12 ± 0.51, and the mean practice score was 3.18 ± 0.55. Regression analyses found that: region, grade, school, and weekly anaerobic exercise time were influences on the knowledge score; region, grade, school, and weekly anaerobic exercise time were influences on the attitude score; region, grade, school attended, weekly anaerobic exercise time and weekly anaerobic exercise time as influences on the practice score. Subgroup analyses revealed that undergraduates from southern regions and 985 schools had higher knowledge attitude scores and lower practice scores. As the grade level increased, the knowledge and attitude scores showed a V-shaped trend and the behavior scores showed an inverted V-shaped trend. Correlation analysis found a positive correlation between knowledge and attitude scores, and a negative correlation between both and behavior, respectively. The public health education needs survey found that undergraduate students generally preferred guided instruction methods and content centered on the RICE principles, they preferred learning through books and pamphlets, and they were happy to see relevant content promoted in the campus environment. Conclusion: This study shows that Chinese undergraduate students have less knowledge, neutral attitudes, and good behaviors regarding PARI prevention. Special attention should be paid to meeting the needs of undergraduate students for public health education to equip them with relevant knowledge so that they can better behave in PARI prevention.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Estudantes , Humanos , Estudos Transversais , China , Masculino , Feminino , Inquéritos e Questionários , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Universidades , Adulto Jovem , Educação em Saúde , Adulto , Saúde Pública , Adolescente , População do Leste Asiático
4.
Future Microbiol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700283

RESUMO

Aim: A bibliometric analysis and evaluation of research on non-Helicobacter pylori Helicobacter species (NHPHs) is essential to determining future research directions. Materials & methods: A comprehensive search was carried out using predetermined search terms within the Web of Science Core Collection (WoSCC) to gather publications spanning from 1993 to 2023. VOSviewer and Citespace were employed for data analysis and visualization. Results: 308 publications on NHPHs were included. Among these, gastric NHPHs received more publications and attention compared with enterohepatic NHPHs. Key findings included the identification of most productive countries, institutions, journals, authors, keywords, research trends and notable perspectives in the field. Conclusion: The article guides further research and clinical applications on NHPHs.

5.
Updates Surg ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748386

RESUMO

This study attempted to compare short-term outcomes of laparoscopic surgery (LS), robot-assisted laparoscopic surgery (RS), and open surgery (OS) for lateral lymph-node dissection (LLND) in treatment of rectal cancer through network meta-analysis. Embase, Web of Science, PubMed, and The Cochrane Library databases were searched to collect cohort studies on outcomes of LS, RS, and OS for LLND for rectal cancer. Newcastle-Ottawa Scale (NOS) was utilized to evaluate the quality of cohort studies. Primary outcomes should at least include one of the following clinical outcome measures: operative time, blood loss, total lymph-node harvest, positive resection margin rate, postoperative complications, and postoperative hospital stay. A network meta-analysis was conducted using STATA software. Fourteen cohort studies including 8612 patients were eligible for inclusion. The network meta-analysis results showed that, in terms of intraoperative outcomes, the RS group had the longest operative time, while the OS group had the shortest; the LS and RS groups had significantly less blood loss than the OS group. In terms of histological outcomes, there were no significant differences in the total number of lymph nodes harvested and the positive margin rate among the LS, RS, and OS groups (P > 0.05). Regarding postoperative outcomes, the OS group had the highest probability of postoperative complications and the longest hospital stay, followed by the LS group, with the RS group being the lowest. RS was the best method in blood loss, postoperative complication rate, and postoperative hospital stay, followed by LS. OS had the shortest operative time and the highest blood loss.

6.
Front Neurol ; 15: 1360434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784898

RESUMO

Objective: To compare the effects of various sports exercise programs on the core symptoms of patients with autism spectrum disorder (ASD). Methods: We searched the China National Knowledge Infrastructure, VIP databases, Wanfang databases, Cochrane Library, PubMed, EMBASE, and Web of Science databases from their inception to February 2023 for randomized controlled trial that investigated the effect of sports exercise on the core symptoms of ASD. The overall risk of bias in the included literature was summarized using the revised Cochrane Randomized Trial Risk of Bias Tool (ROB2), and network meta-analysis was used to compare the intervention effects. Results: A total of 30 studies involving 1,375 participants were included. The results showed that sports exercise programs, including 8-12 weeks of ball sports (SMD = -5.35, 95%CI: -7.57, -3.23), horse riding (SMD = -3.71, 95%CI: -6.18, -1.13), 8-12 weeks of comprehensive sports exercise (SMD = -2.17, 95%CI: -3.99, -0.44), and more than 12 weeks of comprehensive sports exercise (SMD = -3.75, 95%CI: -6.33, -1.24), significantly improved social interaction disorders. Furthermore, 8-12 weeks of ball sports (SMD = -4.36, 95%CI: 2.04, 6.73) and more than 12 weeks of comprehensive sports exercise (SMD = 3.65, 95%CI: 1.40, 6.08) significantly improved repetitive behaviors and restricted interests. Conclusion: Sports exercise can improve the core symptoms of ASD patients, and different symptoms show a selective response to different exercise elements. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023455806.

7.
Ann Rheum Dis ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38684324

RESUMO

OBJECTIVES: In the complex panorama of autoimmune diseases, the characterisation of pivotal contributing autoantibodies that are involved in disease progression remains challenging. This study aimed to employ a global antibody profiling strategy to identify novel antibodies and investigate their association with systemic sclerosis (SSc). METHODS: We implemented this strategy by conducting immunoprecipitation (IP) following on-bead digestion with the sera of patients with SSc or healthy donors, using antigen pools derived from cell lysates. The enriched antigen-antibody complex was proceeded with mass spectrometry (MS)-based quantitative proteomics and over-represented by bioinformatics analysis. The candidate antibodies were then orthogonally validated in two independent groups of patients with SSc. Mice were immunised with the target antigen, which was subsequently evaluated by histological examination and RNA sequencing. RESULTS: The IP-MS analysis, followed by validation in patients with SSc, revealed a significant elevation in anti-PRMT5 antibodies among patients with SSc. These antibodies exhibited robust diagnostic accuracy in distinguishing SSc from healthy controls and other autoimmune conditions, including systemic lupus erythematosus and Sjögren's syndrome, with an area under the curve ranging from 0.900 to 0.988. The elevation of anti-PRMT5 antibodies was verified in a subsequent independent group with SSc using an additional method, microarray. Notably, 31.11% of patients with SSc exhibited seropositivity for anti-PRMT5 antibodies. Furthermore, the titres of anti-PRMT5 antibodies demonstrated a correlation with the progression or regression trajectory in SSc. PRMT5 immunisation displayed significant inflammation and fibrosis in both the skin and lungs of mice. This was concomitant with the upregulation of multiple proinflammatory and profibrotic pathways, thereby underscoring a potentially pivotal role of anti-PRMT5 antibodies in SSc. CONCLUSIONS: This study has identified anti-PRMT5 antibodies as a novel biomarker for SSc.

8.
Sci Adv ; 10(12): eadk1278, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38507481

RESUMO

Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.


Assuntos
Placenta , Placentação , Gravidez , Feminino , Camundongos , Animais , Placenta/diagnóstico por imagem , Microscopia/métodos , Imagem Óptica , Microscopia Intravital
9.
Anal Bioanal Chem ; 416(8): 1971-1982, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38358534

RESUMO

Hand, foot, and mouth disease (HFMD) caused by various enteroviruses is a major public health concern globally. Human enterovirus 71(EVA71), coxsackievirus A16 (CVA16), coxsackievirus A6 (CVA6), and coxsackievirus A10 (CVA10) are four major enteroviruses responsible for HFMD. Rapid, accurate, and specific point-of-care (POC) detection of the four enteroviruses is crucial for the prevention and control of HFMD. Here, we developed two multiplex high-fidelity DNA polymerase loop-mediated isothermal amplification (mHiFi-LAMP) assays for simultaneous detection of EVA71, CVA16, CVA6, and CVA10. The assays have good specificity and exhibit high sensitivity, with limits of detection (LOD) of 11.2, 49.6, 11.4, and 20.5 copies per 25 µL reaction for EVA71, CVA16, CVA6, and CVA10, respectively. The mHiFi-LAMP assays showed an excellent clinical performance (sensitivity 100.0%, specificity 83.3%, n = 47) when compared with four singleplex RT-qPCR assays (sensitivity 93.1%, specificity 100%). In particular, the HiFi-LAMP assays exhibited better performance (sensitivity 100.0%, specificity 100%) for CVA16 and CVA6 than the RT-qPCR assays (sensitivity 75.0-92.3%, specificity 100%). Furthermore, the mHiFi-LAMP assays detected all clinical samples positive for the four enteroviruses within 30 min, obviously shorter than about 1-1.5 h by the RT-qPCR assays. The new mHiFi-LAMP assays can be used as a robust point-of-care testing (POCT) tool to facilitate surveillance of HFMD at rural and remote communities and resource-limited settings.


Assuntos
Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Técnicas de Amplificação de Ácido Nucleico , Humanos , Doença de Mão, Pé e Boca/diagnóstico , Enterovirus/genética , Enterovirus Humano A/genética , Técnicas de Diagnóstico Molecular , China/epidemiologia , Filogenia
10.
Biochemistry ; 63(3): 251-263, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38243804

RESUMO

The 13 Hsp70 proteins in humans act on unique sets of substrates with diversity often being attributed to J-domain-containing protein (Hsp40 or JDP) cofactors. We were therefore surprised to find drastically different binding affinities for Hsp70-peptide substrates, leading us to probe substrate specificity among the 8 canonical Hsp70s from humans. We used peptide arrays to characterize Hsp70 binding and then mined these data using machine learning to develop an algorithm for isoform-specific prediction of Hsp70 binding sequences. The results of this algorithm revealed recognition patterns not predicted based on local sequence alignments. We then showed that none of the human isoforms can complement heat-shocked DnaK knockout Escherichia coli cells. However, chimeric Hsp70s consisting of the human nucleotide-binding domain and the substrate-binding domain of DnaK complement during heat shock, providing further evidence in vivo of the divergent function of the Hsp70 substrate-binding domains. We also demonstrated that the differences in heat shock complementation among the chimeras are not due to loss of DnaJ binding. Although we do not exclude JDPs as additional specificity factors, our data demonstrate substrate specificity among the Hsp70s, which has important implications for inhibitor development in cancer and neurodegeneration.


Assuntos
Proteínas de Escherichia coli , Proteínas de Choque Térmico , Humanos , Proteínas de Choque Térmico/metabolismo , Proteínas de Escherichia coli/química , Sítios de Ligação , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Peptídeos/metabolismo , Ligação Proteica
11.
Acta Pharmacol Sin ; 45(3): 609-618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38030799

RESUMO

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.


Assuntos
Antineoplásicos , Imunoconjugados , Anticorpos de Domínio Único , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Moléculas de Adesão Celular , Citotoxinas , Ensaios Antitumorais Modelo de Xenoenxerto , Antígeno Carcinoembrionário , Proteínas Ligadas por GPI
12.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1310-1318, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-37005815

RESUMO

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.


Assuntos
Insuficiência Ovariana Primária , Feminino , Humanos , Camundongos , Animais , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente , Proteômica , Transdução de Sinais , Glicosídeos/efeitos adversos
13.
Anesthesiology ; 139(2): 173-185, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37079748

RESUMO

BACKGROUND: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia. METHODS: The authors investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow-up histologic assessment. RESULTS: The authors report three main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 min, P < 0.0001, n = 6) that outlasted the concurrent increase in arterial blood pressure, while larger vessels demonstrated an initial increase in flow (108 ± 6% of baseline at 6 min, P = 0.02, n = 6). Second, oxyhemoglobin decreased significantly within cerebral vessels with a more pronounced effect in smaller vessels (microvessels to 69 ± 8% of baseline at 6 min, P < 0.0001, n = 6). Third, oxyhemoglobin desaturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (from 31 ± 11 mmHg at baseline to 56 ± 12 mmHg, 80% increase, P = 0.01, n = 12). In the aged brains, microvascular constriction was less prominent yet slower to recover compared to young brains, but tissue oxygenation was increased, confirming relative hyperoxia. CONCLUSIONS: Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.


Assuntos
Microscopia , Oxiemoglobinas , Camundongos , Animais , Microcirculação , Oxiemoglobinas/farmacologia , Epinefrina/farmacologia , Oxigênio , Circulação Cerebrovascular
14.
Semin Cancer Biol ; 91: 50-69, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36870459

RESUMO

Cancer immunotherapy is a method of controlling and eliminating tumors by reactivating the body's cancer-immunity cycle and restoring its antitumor immune response. The increased availability of data, combined with advancements in high-performance computing and innovative artificial intelligence (AI) technology, has resulted in a rise in the use of AI in oncology research. State-of-the-art AI models for functional classification and prediction in immunotherapy research are increasingly used to support laboratory-based experiments. This review offers a glimpse of the current AI applications in immunotherapy, including neoantigen recognition, antibody design, and prediction of immunotherapy response. Advancing in this direction will result in more robust predictive models for developing better targets, drugs, and treatments, and these advancements will eventually make their way into the clinical setting, pushing AI forward in the field of precision oncology.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Neoplasias/terapia , Medicina de Precisão/métodos , Oncologia , Imunoterapia
15.
J Med Chem ; 66(1): 677-694, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36516003

RESUMO

A recent study illustrated that a fluorescence polarization assay can be used to identify substrate-competitive Hsp70 inhibitors that can be isoform-selective. Herein, we use that assay in a moderate-throughput screen and report the discovery of a druglike amino-acid-based inhibitor with reasonable specificity for the endoplasmic reticular Hsp70, Grp78. Using traditional medicinal chemistry approaches, the potency and selectivity were further optimized through structure-activity relationship (SAR) studies in parallel assays for six of the human Hsp70 isoforms. The top compounds were all tested against a panel of cancer cell lines and disappointingly showed little effect. The top-performing compound, 8, was retested using a series of endoplasmic reticulum (ER) stress-inducing agents and found to synergize with these agents. Finally, 8 was tested in a spheroid tumor model and found to be more potent than in two-dimensional models. The optimized Grp78 inhibitors are the first reported isoform-selective small-molecule-competitive inhibitors of an Hsp70-substrate interaction.


Assuntos
Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico , Humanos , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/farmacologia , Chaperonas Moleculares/química , Proteínas de Choque Térmico HSP70 , Estresse do Retículo Endoplasmático , Isoformas de Proteínas
16.
Molecules ; 27(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36557965

RESUMO

The strategy of incorporating bioactive inorganic nanomaterials without side effects as osteoinductive supplements is promising for bone regeneration. In this work, a novel biomass nanofibrous scaffold synthesized by electrospinning silica (SiO2) nanoparticles into polycaprolactone/chitosan (PCL/CS) nanofibers was reported for bone tissue engineering. The nanosilica-anchored PCL/CS nanofibrous bioscaffold (PCL/CS/SiO2) exhibited an interlinked continuous fibers framework with SiO2 nanoparticles embedded in the fibers. Compact bone-derived cells (CBDCs), the stem cells derived from the bone cortex of the mouse, were seeded to the nanofibrous bioscaffolds. Scanning electron microscopy and cell counting were used to observe the cell adhesion. The Counting Kit-8 (CCK-8) assay was used. Alkaline phosphatase (ALP), Alizarin red staining, real-time Polymerase Chain Reaction and Western blot tests were performed to confirm the osteogenesis of the CBDCs on the bioscaffolds. The research results demonstrated that the mechanical property of the PCL together with the antibacterial and hydrophilic properties of the CS are conducive to promoting cell adhesion, growth, migration, proliferation and differentiation. SiO2 nanoparticles, serving as bone induction factors, effectively promote the osteoblast differentiation and bone regeneration. This novel SiO2-anchored nanofibrous bioscaffold with superior bone induction activity provides a better way for bone tissue regeneration.


Assuntos
Quitosana , Nanofibras , Camundongos , Animais , Engenharia Tecidual/métodos , Osteogênese , Quitosana/farmacologia , Alicerces Teciduais , Dióxido de Silício , Poliésteres/farmacologia , Regeneração Óssea , Proliferação de Células , Diferenciação Celular
17.
Science ; 378(6626): 1315-1320, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36548427

RESUMO

Transparency in animals is a complex form of camouflage involving mechanisms that reduce light scattering and absorption throughout the organism. In vertebrates, attaining transparency is difficult because their circulatory system is full of red blood cells (RBCs) that strongly attenuate light. Here, we document how glassfrogs overcome this challenge by concealing these cells from view. Using photoacoustic imaging to track RBCs in vivo, we show that resting glassfrogs increase transparency two- to threefold by removing ~89% of their RBCs from circulation and packing them within their liver. Vertebrate transparency thus requires both see-through tissues and active mechanisms that "clear" respiratory pigments from these tissues. Furthermore, glassfrogs' ability to regulate the location, density, and packing of RBCs without clotting offers insight in metabolic, hemodynamic, and blood-clot research.


Assuntos
Anuros , Mimetismo Biológico , Coagulação Sanguínea , Eritrócitos , Fígado , Animais , Eritrócitos/citologia , Eritrócitos/fisiologia , Hemodinâmica , Fígado/fisiologia , Anuros/anatomia & histologia , Anuros/sangue , Anuros/fisiologia , Mimetismo Biológico/fisiologia , Fenômenos Ópticos , Contagem de Eritrócitos
18.
J Opt Soc Am A Opt Image Sci Vis ; 39(6): B28-B38, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215525

RESUMO

This study examines the human gloss perception of printing papers at various illuminances and distances from a light source to the object's surface. Gloss is evaluated based on not only the intensity of reflected light but also the sharpness of specular highlights. The apparent spread of the reflected light source image, which is also used for gloss evaluations, depends on the distance between the light source and the object's surface. Unlike physical variation of specular image properties, the perception of gloss may exhibit constancy similar to color perception. Our results reveal that illuminance has a strong effect on gloss perception. We found cases where low-gloss samples looked glossier than high-gloss ones-the gloss reversal phenomenon. These results suggest that there is a case in which gloss constancy may not work in every condition.


Assuntos
Percepção de Forma , Sensibilidades de Contraste , Humanos , Propriedades de Superfície
19.
J Exp Bot ; 73(18): 6334-6351, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-35675763

RESUMO

The evolution of C4 photosynthesis involved multiple anatomical and physiological modifications, yet our knowledge of the genetic regulation involved remains elusive. In this study, systematic analyses were conducted comparing the C3-C4 intermediate Moricandia suffruticosa and its C3 relative Brassica napus (rapeseed). We found that the leaves of M. suffruticosa had significantly higher vein density than those of B. napus, and the vein density was further increased in M. suffruticosa under drought and heat stress. Moreover, the bundle sheath distance, as the mean distance from the outer wall of one bundle sheath to the outer wall of an adjacent one, decreased and the number of centripetal chloroplasts in bundle sheath cells was found to be altered in M. suffruticosa leaves under drought and heat treatments. These results suggest that abiotic stress can induce a change in an intermediate C3-C4 anatomy towards a C4-like anatomy in land plants. By integrating drought and heat factors, co-expression network and comparative transcriptome analyses between M. suffruticosa and B. napus revealed that inducible auxin signaling regulated vascular development, and autophagy-related vesicle trafficking processes were associated with this stress-induced anatomical change. Overexpressing three candidate genes, MsERF02, MsSCL01, and MsDOF01, increased leaf vein density and/or enhanced photosynthetic assimilation and drought adaptability in the transgenic lines. The findings of this study may improve our understanding of the genetic regulation and evolution of C4 anatomy.


Assuntos
Brassicaceae , Secas , Fotossíntese/fisiologia , Folhas de Planta/genética , Resposta ao Choque Térmico , Ácidos Indolacéticos
20.
Light Sci Appl ; 11(1): 138, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35577780

RESUMO

High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and tracking fast pathophysiological activities at the microvessel level, which will enable advances in current queries in neurovascular and brain metabolism research, including stroke, dementia, and acute brain injury. Further, real-time imaging of oxygen saturation of hemoglobin (sO2) can capture fast-paced oxygen delivery dynamics, which is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations, including stimulated Raman scattering (SRS) based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm3 with a high spatial resolution of ~10 µm. Using the UFF-PAM system, we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain's fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, with the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.

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