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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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 , Tecidos Suporte , Dióxido de Silício , Poliésteres/farmacologia , Regeneração Óssea , Proliferação de Células , Diferenciação Celular
10.
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
11.
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
12.
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
13.
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.

14.
Materials (Basel) ; 15(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35591523

RESUMO

We demonstrate a cross-linked, 3D conductive network structure, porous silicon@carbon nanofiber (P-Si@CNF) anode by magnesium thermal reduction (MR) and the electrospinning methods. The P-Si thermally reduced from silica (SiO2) preserved the monodisperse spheric morphology which can effectively achieve good dispersion in the carbon matrix. The mesoporous structure of P-Si and internal nanopores can effectively relieve the volume expansion to ensure the structure integrity, and its high specific surface area enhances the multi-position electrical contact with the carbon material to improve the conductivity. Additionally, the electrospun CNFs exhibited 3D conductive frameworks that provide pathways for rapid electron/ion diffusion. Through the structural design, key basic scientific problems such as electron/ion transport and the process of lithiation/delithiation can be solved to enhance the cyclic stability. As expected, the P-Si@CNFs showed a high capacity of 907.3 mAh g-1 after 100 cycles at a current density of 100 mA g-1 and excellent cycling performance, with 625.6 mAh g-1 maintained even after 300 cycles. This work develops an alternative approach to solve the key problem of Si nanoparticles' uneven dispersion in a carbon matrix.

15.
Emerg Microbes Infect ; 11(1): 1186-1190, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35380101

RESUMO

In the fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), monoclonal antibodies (mAbs) serve as key strategies for the rapid prevention and treatment of COVID-19. However, analysis to fully characterize functional SARS-CoV-2 mAbs is still needed. In this study, by interrogating 1,695 published or patented mAbs of human origin and validated SARS-CoV-2-binding potency, we found a highly preferential usage of IGHV3-53/3-66 germline genes that was then revealed as a distinct selectivity of SARS-CoV-2-induced humoral immunity across other coronaviruses. Moreover, among the rare somatic hypermutations, we identified a novel mutation signature of F27 to I, L, or V with high frequency, which was located in the CDR1 region of the heavy chain among IGHV3-53/3-66-encoded antibodies. This convergent mutation contributed to improving SARS-CoV-2 binding affinity and may advance our knowledge of the humoral immunity to SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Imunidade Humoral , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
16.
Virol Sin ; 37(3): 370-379, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35247647

RESUMO

Advancements in high-throughput sequencing (HTS) of antibody repertoires (Ig-Seq) have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale. However, currently, only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions, possibly limited by inadequate sequencing depth and throughput. To better understand how HIV-1 infection would impact humoral immune system, in this study, we systematically analyzed the differences between the IgM (HIV-IgM) and IgG (HIV-IgG) heavy chain repertoires of HIV-1 infected patients, as well as between antibody repertoires of HIV-1 patients and healthy donors (HH). Notably, the public unique clones accounted for only a negligible proportion between the HIV-IgM and HIV-IgG repertoires libraries, and the diversity of unique clones in HIV-IgG remarkably reduced. In aspect of somatic mutation rates of CDR1 and CDR2, the HIV-IgG repertoire was higher than HIV-IgM. Besides, the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire, presumably caused by the great number of novel VDJ rearrangement patterns, especially a massive use of IGHJ6. Moreover, some of the B cell clonotypes had numerous clones, and somatic variants were detected within the clonotype lineage in HIV-IgG, indicating HIV-1 neutralizing activities. The in-depth characterization of HIV-IgG and HIV-IgM repertoires enriches our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies.


Assuntos
Infecções por HIV , HIV-1 , HIV-1/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoglobulina G , Imunoglobulina M
17.
HERD ; 15(3): 126-142, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35164589

RESUMO

OBJECTIVE: This study investigated Chinese nurses' preferences for (a) proximity of break areas, (b) functionality of break areas, (c) amenities, and (d) nature-related environmental features. BACKGROUND: While nurses in China need support to adequately perform their jobs, little is known about how restorative spaces impact their mental and physical health. METHODS: Data were collected through interviews (N = 12), survey questionnaires (N = 88), and visual assessments (N = 88) from nurses who worked in inpatient settings in China. RESULTS: Nurses preferred the break room to be close to nursing stations; to have visual privacy from patients; and to provide space and facilities for drinking, taking naps, dining, and chatting with colleagues. Balconies and windows were shown to have a significant restorative effect. Well-designed break areas were perceived to have positive impacts on nurse perceived levels of well-being and increase nurses' satisfaction levels with their work environment. CONCLUSION: The study outcomes emphasize the importance of restorative spaces for inpatient nurses and recommend including natural elements in the break rooms.


Assuntos
Recursos Humanos de Enfermagem no Hospital , Postos de Enfermagem , China , Humanos , Satisfação no Emprego , Privacidade , Inquéritos e Questionários , Local de Trabalho
18.
Europace ; 24(6): 1025-1035, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34792112

RESUMO

AIMS: The study investigates the role and mechanisms of clinically translatable exercise heart rate (HR) envelope effects, without dyssynchrony, on myocardial ischaemia tolerance compared to standard preconditioning methods. Since the magnitude and duration of exercise HR acceleration are tightly correlated with beneficial cardiac outcomes, it is hypothesized that a paced exercise-similar HR envelope, delivered in a maximally physiologic way that avoids the toxic effects of chamber dyssynchrony, may be more than simply a readout, but rather also a significant trigger of myocardial conditioning and stress resistance. METHODS AND RESULTS: For 8 days over 2 weeks, sedated mice were atrial-paced once daily via an oesophageal electrode to deliver an exercise-similar HR pattern with preserved atrioventricular and interventricular synchrony. Effects on cardiac calcium handling, protein expression/modification, and tolerance to ischaemia-reperfusion (IR) injury were assessed and compared to those in sham-paced mice and to the effects of exercise and ischaemic preconditioning (IPC). The paced cohort displayed improved myocardial IR injury tolerance vs. sham controls with an effect size similar to that afforded by treadmill exercise or IPC. Hearts from paced mice displayed changes in Ca2+ handling, coupled with changes in phosphorylation of calcium/calmodulin protein kinase II, phospholamban and ryanodine receptor channel, and transcriptional remodelling associated with a cardioprotective paradigm. CONCLUSIONS: The HR pattern of exercise, delivered by atrial pacing that preserves intracardiac synchrony, induces cardiac conditioning and enhances ischaemic stress resistance. This identifies the HR pattern as a signal for conditioning and suggests the potential to repurpose atrial pacing for cardioprotection.


Assuntos
Precondicionamento Isquêmico Miocárdico , Animais , Cálcio , Átrios do Coração , Frequência Cardíaca , Humanos , Isquemia , Camundongos
19.
Photoacoustics ; 24: 100309, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34956833

RESUMO

Optical-resolution photoacoustic microscopy (OR-PAM) can provide functional, anatomical, and molecular images at micrometer level resolution with an imaging depth of less than 1 mm in tissue. However, the imaging speed of traditional OR-PAM is often low due to the point-by-point mechanical scanning and cannot capture time-sensitive dynamic information. In this work, we demonstrate a recent effort in improving the imaging speed of OR-PAM, using a newly developed water-immersible two-axis scanner. Driven by water-compatible electromagnetic actuation force, the new scanning mirror employs a novel torsion-bending mechanism to achieve fast 2D scanning. The torsion scanning along the fast-axis works in the resonant model, and the bending scanning along the slow-axis operate at the quasi-static mode. The scanning speed and scanning range along the two axes can be independently adjusted. Steered by the two-axis torsion-bending scanning mirror immersed in water, the focused excitation light and the generated acoustic wave can be confocally aligned over the entire imaging area. Thus, a high imaging speed can be achieved without sacrificing the detection sensitivity. Equipped with the torsion-bending scanner, the high-speed OR-PAM system has achieved a cross-sectional frame rate of 400 Hz, and a volumetric imaging speed of 1 Hz over a field of view of 1.5 × 2.5 mm2. We have also demonstrated high-speed OR-PAM of the hemodynamic changes in response to pharmaceutical and physiological challenges in small animal models in vivo. We expect the torsion-bending scanner based OR-PAM will find matched biomedical studies of tissue dynamics.

20.
Int J Gen Med ; 14: 7639-7646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764677

RESUMO

BACKGROUND: It has been reported that serum periostin levels are significantly higher in postmenopausal patients with osteoporotic fractures. Nonetheless, the levels of serum periostin in postmenopausal women with different bone mass remain unclear. PURPOSE: The objective of the study was to identify the levels of serum periostin in Chinese postmenopausal women with different bone mass, and the correlations between the periostin levels and the classical bone turnover markers (BTMs), and bone mineral densities (BMDs) at different sites. PATIENTS AND METHODS: This study enrolled 331 Chinese postmenopausal women in Shanghai; their clinical features were collected; their levels of serum periostin and traditional BTMs were measured by ELISA or the fully automated immunoassay analyzer; their BMDs at different sites were measured by dual-energy X-ray absorptiometry (DXA). RESULTS: According to the T-value of bone mineral density (BMD), these postmenopausal women were divided into normal group (n=84), osteopenia group (n=126) and osteoporosis group (n=121). There was no significant difference in the serum periostin levels among the above three groups of subjects. In addition, Spearman correlation analysis also revealed that no correlation was observed between the value of serum periostin and those of traditional BTMs, and BMDs at different sites, respectively. The values of traditional BTMs were negatively correlated with those of BMDs at all measured sites. Furthermore, the receiver-operating characteristic (ROC) curves analysis indicated that among the periostin and traditional BTMs mentioned above, the best predictors for postmenopausal osteoporosis in Shanghai Chinese postmenopausal women were osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) [the areas under the ROC curve (AUC)=0.746 and 0.761, respectively]. CONCLUSION: Serum periostin may not be used as a marker of systemic bone metabolism in Shanghai Chinese postmenopausal women without prior fracture. In addition, serum P1NP and OC levels may be the predictors of osteoporosis occurrence in Chinese postmenopausal women.

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