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1.
Nano Lett ; 24(22): 6496-6505, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38787288

RESUMEN

Asymmetric surface functionalization of complex nanoparticles to control their directional self-assembly remains a considerable challenge. Here, we demonstrated a conformal DNA design strategy for flexible remodeling of the surface of complex nanoparticles, taking Au nanobipyramids (AuNBPs) as a model. We sheathed one or both tips of AuNBPs into conformal DNA origami with an exceptionally accurate orientation control. Such asymmetrically and symmetrically distributed surface patches possess regioselective, sequence, and site-specific DNA binding capabilities. As a result, we realized a series of prototypical multicomponent "colloidal molecules" made of AuNBPs and Au nanospheres (AuNSs) with defined directionality and number of "bonding valence" as well as 1D and 3D hierarchical assemblies, e.g., inverse core-satellites of AuNBPs and AuNSs, side-by-side and tip-to-tip linear assemblies of AuNBPs, and 3D helical superstructures of AuNBPs with tunable twists. These findings inspire new opportunities for nanoparticle surface engineering and the high-order self-assembly of nanoarchitectures with higher complexity and broadened functionalities.


Asunto(s)
ADN , Oro , Nanopartículas del Metal , Propiedades de Superficie , Oro/química , ADN/química , Nanopartículas del Metal/química , Conformación de Ácido Nucleico
2.
Nano Lett ; 23(24): 11734-11741, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38079633

RESUMEN

Study of the conformational and mechanical behaviors of biomolecular assemblies is vital to the rational design and realization of artificial molecular architectures with biologically relevant functionality. Here, we revealed DNA-modulated and mechanoresponsive excitonic couplings between organic chromophores and verified strong correlations between the excitonic chiroptical responses and the conformational and mechanical states of DNA self-assemblies irrespective of fluorescence background interference. Besides, the excitonic chiroptical effect allowed sensitive monitoring of DNA self-assembled nanostructures due to small molecule bindings or DNA strand displacement reactions. Moreover, we developed a new chiroptical reporter, a DNA-templated dimer of an achiral cyanine5 and an intrinsically chiral BODIPY, that exhibited unique multiple-split spectral line shape of exciton-coupled circular dichroism, largely separated response wavelengths, and enhanced anisotropy dissymmetry factor (g-factor). These results shed light on a promising chiroptical spectroscopic tool for studying biomolecular recognition and binding, conformation dynamics, and soft mechanics in general.


Asunto(s)
Nanoestructuras , Nanoestructuras/química , ADN/química , Conformación Molecular , Dicroismo Circular
3.
Nano Lett ; 22(12): 4784-4791, 2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35649094

RESUMEN

A significant challenge exists in obtaining chiral nanostructures that are amenable to both solution-phase self-assembly and solid-phase preservation, which enable the observation of unveiled optical responses impacted by the dynamic or static conformation and the incident excitations. Here, to meet this demand, we employed DNA origami technology to create quasi-planar chiral satellite-core nanoparticle superstructures with an intermediate geometry between the monolayer and the double layer. We disentangled the complex chiral mechanisms, which include planar chirality, 3D chirality, and induced chirality transfer, through combined theoretical studies and thorough experimental measurements of both solution- and solid-phase samples. Two distinct states of optical responses were demonstrated by the dynamic and static conformations, involving a split or nonsplit circular dichroism (CD) line shape. More importantly, our study on chiral nanoparticle superstructures on a substrate featuring both a dominant 2D geometry and a defined 3D represents a great leap toward the realization of colloidal chiral metasurfaces.


Asunto(s)
Oro , Nanopartículas del Metal , Dicroismo Circular , ADN/química , Oro/química , Nanopartículas del Metal/química , Conformación Molecular
4.
Angew Chem Int Ed Engl ; 61(44): e202210730, 2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36083592

RESUMEN

Hierarchical, chiral hybrid superstructures of chromophores and nanoparticles are expected to give rise to intriguing unveiled chiroptical responses originating from the complex chiral interactions among the components. Herein, DNA origami cavity that could self-assemble into one-dimensional (1D) DNA tubes was employed as a scaffold to accurately organize metal nanoparticles and chromophores. The chiral interactions were studied at the level of individual hybrid particles and their 1D hybrid superstructures. Complex chirality mechanisms involving global structural chirality, plasmon-induced circular dichroism (PICD) and exciton-coupled circular dichroism (ECCD) were disentangled. The multiplexed CD spectrum superposition revealed the chirality evolution at different length scales. These results can offer a model for boosting the theoretical understanding of classical-quantum hybrid systems, and would inspire the future design of optically-active substances across length scales.


Asunto(s)
ADN , Nanopartículas del Metal , ADN/química , Nanopartículas del Metal/química , Dicroismo Circular
5.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 1093-1104, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37606757

RESUMEN

Atherosclerosis (AS) is an underlying cause of the majority of coronary artery disease (CAD), in which proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) exert vital roles. It has been reported that circular RNAs (circRNAs) are associated with the VSMCs function. Here, we undertook to explore the biological function and mechanism of hsa_circ_0031891 in a platelet-derived growth factor-BB (PDGF-BB)-induced AS cell model. Hsa_circ_0031891 and microRNA-579-3p (miR-579-3p) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation and migration were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assay. Protein levels of alpha-smooth muscle actin (α-SMA), smooth muscle protein 22-α (SM22-α), Osteopontin, and High mobility group box-1 (HMGB1) were determined using western blot assay. After predicting via a variety of bioinformatics software, the binding between miR-579-3p and hsa_circ_0031891 or HMGB1 was validated using dual-luciferase reporter and RNA pull-down assays. Increased hsa_circ_0031891 and HMGB1 and reduced miR-579-3p were found in CAD patients and PDGF-BB-induced human aortic vascular smooth muscle cells (HA-VSMCs). Moreover, hsa_circ_0031891 deficiency relieved PDGF-BB-mediated HA-VSMC proliferation, migration, and dedifferentiation. Mechanically, hsa_circ_0031891 modulated HMGB1 expression via sponging miR-579-3p. Hsa_circ_0031891 boosted PDGF-BB-induced proliferation, migration, and dedifferentiation partly by regulating the miR-579-3p/HMGB1 axis, hinting at a feasible therapeutic strategy for AS.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Proteína HMGB1 , MicroARNs , Humanos , Becaplermina , Músculo Liso Vascular , Proteína HMGB1/genética , Proliferación Celular , Enfermedad de la Arteria Coronaria/genética , MicroARNs/genética , Movimiento Celular
6.
Nat Commun ; 15(1): 4846, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844481

RESUMEN

The collective light-matter interaction of chiral supramolecular aggregates or molecular ensembles with confined light fields remains a mystery beyond the current theoretical description. Here, we programmably and accurately build models of chiral plasmonic complexes, aiming to uncover the entangled effects of excitonic correlations, intra- and intermolecular charge transfer, and localized surface plasmon resonances. The intricate interplay of multiple chirality origins has proven to be strongly dependent on the site-specificity of chiral molecules on plasmonic nanoparticle surfaces spanning the nanometer to sub-nanometer scale. This dependence is manifested as a distinct circular dichroism response that varies in spectral asymmetry/splitting, signal intensity, and internal ratio of intensity. The inhomogeneity of the surface-localized plasmonic field is revealed to affect excitonic and charge-transfer mixed intermolecular couplings, which are inherent to chirality generation and amplification. Our findings contribute to the development of hybrid classical-quantum theoretical frameworks and the harnessing of spin-charge transport for emergent applications.

7.
Artículo en Inglés | MEDLINE | ID: mdl-37467090

RESUMEN

Information diffusion prediction captures diffusion dynamics of online messages in social networks. Thus, it is the basis of many essential tasks such as popularity prediction and viral marketing. However, there are two thorny problems caused by the loss of spatial-temporal properties of cascade data: "position-hopping" and "branch-independency." The former means no exact propagation relationship between any two consecutive infected users. The latter indicates that not all previously infected users contribute to the prediction of the next infected user. This article proposes the GRU-like Attention Unit and Structural Spreading (GRASS) model for microscopic cascade prediction to overcome the above two problems. First, we introduce the attention mechanism into the gated recurrent unit (GRU) component to expand the restricted receptive field of the recurrent neural network (RNN)-type module, thus addressing the "position-hopping" problem. Second, the structural spreading (SS) mechanism leverages structural features to filter out related users and controls the generation of cascade hidden states, thereby solving the "branch-independency" problem. Experiments on multiple real-world datasets show that our model significantly outperforms state-of-the-art baseline models on both hits@κ and map@κ metrics. Furthermore, the visualization of latent representations by t-distributed stochastic neighbor embedding (t-SNE) indicates that our model makes different cascades more discriminative during the encoding process.

8.
Am J Transl Res ; 13(4): 3044-3053, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34017472

RESUMEN

OBJECTIVE: To investigate the changes in the cardiac function and quality of life of patients with pacemaker-induced cardiomyopathy (PICM) after they upgrade to left bundle branch pacing (LBBP). METHODS: Ten patients with PICM who upgraded to LBBP were recruited as the study cohort. The LBBP upgrade operations were all performed by the same cardiac intervention expert. The cardiac function index changes, including the left ventricular end-diastolic diameters, the cardiothoracic ratios, the left ventricular ejection fractions, the N-terminal brain natriuretic peptide levels, the 6 min walking test distances, and the quality of life changes, including the SF-36 scores, the European Five-Dimensional Health Scale (EQ-5D-3L) scores, and the Minnesota Heart failure Quality of Life Scale (MLHFQ) scores before and after the LBBP operations were analyzed. The incidences of adverse events during the postoperative follow-up were analyzed. RESULTS: The ten patients were successfully upgraded to LBBP. Compared with before the operation, the left ventricular end-diastolic diameter levels and the cardiothoracic ratios decreased significantly, but the left ventricular ejection fractions and the 6 min walking test distances increased (P<0.05 or P<0.01). The SF-36 and EQ-5D-3L scores increased gradually, but the MLHFQ scores decreased gradually before the operations and at one month and 12 months after the operations. The physical functioning (PF), role-physical (RP), general health (GH), vitality (VT), and the social role (SR) scores of the SF-36 scale, the TTO index and the visual analog scale (VAS) of the EQ-5D-3L scale scores, and the MLHFQ scores at 12 months after the operations were significantly different from the scores before the operations (all P<0.05). In terms of safety, there were no adverse events such as pacemaker electrode dislocation or interventricular septal perforation during the postoperative follow-up. CONCLUSION: Upgrading to LBBP can effectively improve cardiac function and the quality of life in patients with PICM, and the operation is safe.

9.
Trials ; 22(1): 476, 2021 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-34294144

RESUMEN

BACKGROUND: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive effects on human health. Due to the absence of antiviral medicine for COVID-19 thus far, there is a desperate need to develop effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, with the aim of achieving clinical efficacy and decreasing the use of antibiotics and glucocorticoids. The aim of this study was to evaluate the efficacy and safety of Baidu Jieduan granules in treating COVID-19. METHODS/DESIGN: This multicentre, open-label, randomized controlled trial will be conducted in 300 patients with COVID-19. The patients will be randomly (1:1) divided into a treatment group and a control group. All patients will receive standard therapy at the same time. Patients in the experimental group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes will be assessed at baseline and at 3, 5, 7 and 14 days after treatment initiation. The primary outcome will be the rate of symptom (fever, fatigue and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial. DISCUSSION: The study will provide high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granules in the treatment of moderate COVID-19, and enrich the theory and practice of TCM in treating COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029869 . Registered on 15 February 2020.


Asunto(s)
COVID-19 , Medicina Tradicional China , Antivirales/uso terapéutico , China , Humanos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , Resultado del Tratamiento
10.
Trials ; 21(1): 568, 2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32580752

RESUMEN

BACKGROUND: Currently, coronavirus disease 2019 (COVID-19) is continuously and rapidly circulating, causing heavy damage on public health. No effective antiviral treatment has been proved thus far. Traditional Chinese medicine (TCM) has been widely applied in the treatment of a variety of infection diseases in China, hoping to produce clinical effects and reduce the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Shenhuang granule in treatment of severe COVID-19. METHODS/DESIGN: This multicenter, open-label randomized controlled trial is conducted in 160 participants with severe COVID-19. The participants will be randomly (1:1) divided into treatment group or control group. All participants are given standard therapy at the same time. The experiment will receive Shenhuang granule treatment twice a day for 14 days. The clinical indicators of patients will be assessed at baseline and at 3, 5, 7, and 14 days after treatment initiation. The primary outcome is 14-day clinical outcome. Adverse events will be monitored throughout the trial. DISCUSSION: This will be the first randomized controlled trial, which evaluate the effect of Shenhuang granule in patients with severe COVID-19 in China. The results of this trial may not only provide evidence-based recommendations to clinicians to treat severe COVID-19, but also enrich the theory and practice of TCM in treating infectious diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000029777. Registered on 13 February 2020.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Neumonía Viral/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pandemias , Proyectos de Investigación , SARS-CoV-2 , Adulto Joven , Tratamiento Farmacológico de COVID-19
11.
Front Chem ; 7: 379, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31192195

RESUMEN

LiFeBO3/C cathode material with hollow sphere architecture is successfully synthesized by a spray-drying method. SEM and TEM results demonstrate that the micro-sized LiFeBO3/C hollow spheres consist of LiFeBO3@C particles and the average size of LiFeBO3@C particles is around 50-100 nm. The thickness of the amorphous carbon layer which is coated on the surface of LiFeBO3 nanoparticles is about 2.5 nm. LiFeBO3@C particles are connected by carbon layers and formed conductive network in the LiFeBO3/C hollow spheres, leading to improved electrical conductivity. Meanwhile, the hollow structure boosts the Li+ diffusion and the carbon layers of LiFeBO3@C particles protect LiFeBO3 from moisture corrosion. Consequently, synthesized LiFeBO3/C sample exhibits good electrochemical properties and storage performance.

12.
Front Chem ; 6: 617, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30619825

RESUMEN

Na3V2(PO4)3/C nanofibers are prepared by a pre-reduction assisted electrospinning method. In order to maintain the perfect fibrous architecture of the Na3V2(PO4)3/C samples after calcining, a series of heat treatment parameters are studied in detail. It is found that the heat treatment process shows important influence on the morphology and electrochemical performance of Na3V2(PO4)3/C composite nanofibers. Under the calcining conditions of 800°C for 10 h with a heating rate of 2.5°C min-1, the well-crystallized uniform Na3V2(PO4)3/C nanofibers with excellent electrochemical performances are successfully obtained. The initial discharge specific capacities of the nanofibers at 0.05, 1, and 10C are 114.0, 106.0, and 77.9 mAh g-1, respectively. The capacity retention still remains 97.0% after 100 cycles at 0.05C. This smooth, uniform, and continuous Na3V2(PO4)3/C composite nanofibers prepared by simple electrospinning method, is expected to be a superior cathode material for sodium-ion batteries.

13.
Hellenic J Cardiol ; 59(1): 8-13, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28212872

RESUMEN

OBJECTIVE: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. METHODS: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP). At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. RESULTS: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05). CONCLUSION: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure.


Asunto(s)
Aterosclerosis/genética , Enfermedad de la Arteria Coronaria/genética , ADN/genética , Polimorfismo Genético , Receptores del Factor Autocrino de Motilidad/genética , Adulto , Aterosclerosis/metabolismo , Western Blotting , Enfermedad de la Arteria Coronaria/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptores del Factor Autocrino de Motilidad/metabolismo , Estudios Retrospectivos
14.
J Autism Dev Disord ; 44(7): 1577-96, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24362849

RESUMEN

A meta-analysis was performed to examine differences in IQ profiles between individuals with Asperger's disorder (AspD) and high-functioning autism (HFA). Fifty-two studies were included for this study. The results showed that (a) individuals with AspD had significantly higher full-scale IQ, verbal IQ (VIQ), and performance IQ (PIQ) than did individuals with HFA; (b) individuals with AspD had significantly higher VIQ than PIQ; and (c) VIQ was similar to PIQ in individuals with HFA. These findings seem to suggest that AspD and HFA are two different subtypes of Autism. The implications of the present findings to DSM-5 Autism Spectrum Disorder are discussed.


Asunto(s)
Síndrome de Asperger/psicología , Trastorno Autístico/psicología , Inteligencia , Adolescente , Niño , Femenino , Humanos , Pruebas de Inteligencia , Masculino
15.
Chemosphere ; 111: 631-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24997975

RESUMEN

A catalyst system composed of peroxophosphomolybdates as catalytic center and agarose as matrix material had been designed. The [C16H33N(CH3)3]3[PO4{MoO(O2)2}4]/agarose (C16PMo(O2)2/agarose) hybrid was found to be active for oxidation desulfurization (ODS) of dibenzothiophene (DBT) or real fuel into corresponding sulfone by H2O2 as an oxidant, while the sulfur content could be reduced to 5ppm. The higher activity comes from its components including [PO4{MoO(O2)2}4] catalytic sites, the hydrophobic quaternary ammonium cation affinity to low polarity substrates, and agarose matrix affinity to H2O2 and sulfone. During the oxidative reaction, the mass transfer resistance between H2O2 and organic sulfurs could be decreased and the reaction rate could increase by the assistance of agarose and hydrophobic tails of [C16H33N(CH3)3]3[PO4{MoO(O2)2}4]. Meanwhile, the oxidative products could be adsorbed by agarose matrix to give clean fuel avoiding the post-treatment. In addition, the hybrid was easily regenerated to be reused.


Asunto(s)
Molibdeno/química , Ácidos Fosfóricos/química , Sefarosa/química , Azufre/aislamiento & purificación , Tiofenos/química , Adsorción , Catálisis , Restauración y Remediación Ambiental , Peróxido de Hidrógeno/química , Oxidación-Reducción , Azufre/química , Tiofenos/aislamiento & purificación
16.
Chemosphere ; 90(2): 318-22, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22877935

RESUMEN

The nanocatalysts were fabricated by reacting amphiphilic quaternary ammoniums with polyoxoperoxometalates (POPMs) K(n)[PW(12-)(x)Ti(x)O(40-)(x)(O(2))(x)](x=1, 2 and 3; n=5, 7 and 9). Fourier transform infrared spectroscopy (IR), transmission electron microscopy (TEM), and UV-vis-NIR spectrophotometer were used to characterize the resulting samples. This kind of nanocatalysts could provide a kind of nanoreactors to promote the degradation of NH(4)SCN into simple inorganic compounds such as SO(4)(2-), HCO(3)(-) and NO(3)(-) using oxygen as an oxidant under room conditions. The leaching test showed that the POPMs micellar catalyst had excellent stability and could be used as a heterogeneous one at least five times.


Asunto(s)
Contaminantes Ambientales/química , Micelas , Tiocianatos/química , Compuestos de Tungsteno/química , Catálisis , Contaminantes Ambientales/análisis , Microscopía Electrónica de Transmisión , Oxidación-Reducción , Compuestos de Amonio Cuaternario/química , Espectroscopía Infrarroja por Transformada de Fourier , Tiocianatos/análisis
17.
J Autism Dev Disord ; 43(8): 1832-42, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23224594

RESUMEN

This study aimed to identify the factors associated with participation in employment for high school leavers with autism. A secondary data analysis of the National Longitudinal Transition Study 2 (NLTS2) data was performed. Potential factors were assessed using a weighted multivariate logistic regression. This study found that annual household income, parental education, gender, social skills, whether the child had intellectual disability, whether the child graduated from high school, whether the child received career counseling during high school, and whether the child's school contacted postsecondary vocational training programs or potential employers were the significant factors associated with participation in employment. These findings may have implications for professionals who provide transition services and post-secondary programs for individuals with autism.


Asunto(s)
Trastorno Autístico/rehabilitación , Empleo , Instituciones Académicas , Adolescente , Trastorno Autístico/economía , Escolaridad , Empleo/estadística & datos numéricos , Composición Familiar , Femenino , Encuestas Epidemiológicas , Humanos , Renta/estadística & datos numéricos , Modelos Logísticos , Estudios Longitudinales , Masculino , Padres/educación , Valor Predictivo de las Pruebas , Instituciones Académicas/estadística & datos numéricos , Orientación Vocacional
18.
Zhonghua Yi Shi Za Zhi ; 35(4): 245-9, 2005 Oct.
Artículo en Zh | MEDLINE | ID: mdl-16469258

RESUMEN

The study of public health history, bound to follow the development of public health facilities, is an important branch among all the studies of western social history of medicine. The development of public health history has experienced a course from optimism to objectivity as public health facilities. The study of public health history embraces three major aspects, hygiene, social welfare and philanthropy, those all have a distinct sociality and reality.

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