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1.
Bioact Mater ; 9: 29-43, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820553

RESUMO

Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system (siSTING@HPgel) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.

2.
Bioact Mater ; 8: 309-324, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541403

RESUMO

Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements.

3.
Front Med (Lausanne) ; 8: 775518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869494

RESUMO

Background: Lifestyle contributors to frailty among the elderly were previously reported in the developed Western countries, while evidence from the less developed East Asian regions was still lacking. Due to the well-acknowledged sex-based disparity of frailty and sex-difference of socioeconomic status and lifestyle, it is worth investigating the sex-specific association between the social and behavioral contributors and the risk of frailty among the East Asian longevous population. Methods: The present study was an observational study based on the four waves of interviews of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. The participants aged ≥65 years and without frailty at baseline were included. Fried criteria (exhaustion, shrink, weakness, low mobility, and inactivity) were adopted to identify the incidence of frailty (≥3 domains) and pre-frailty (1-2 domains) during the follow-up. The sex-specific association between lifestyle (smoke status, drinking status, food intake, sleep, exercise, and physical activity) and the risk of incident pre-frailty and frailty was analyzed using the multinomial logistic regression models. Results: Altogether, 3,327 participants aged 81.2 ± 10.3 (range 65-116) years were included. In total, 964 (29.0%) and 1,249 (37.5%) participants were recognized as having incident pre-frailty and frailty, respectively. Older women were disproportionately uneducated, frequently did housework and labor work, but seldom did exercise. Men had diverse dietary and recreational activities but were frequently exposed to tobacco and alcohol. The protective effects of higher income, exercise, doing housework, and daily intake of fresh fruits/vegetables were found in both the sexes (P < 0.05). Sleep disorders (odds ratio [OR] = 2.16, 95% CI: 1.28-3.62) and labor work (OR = 2.18, 95% CI: 1.42-3.33) were associated with the increased risk of frailty among women. For men, diverse dietary (four types of food added: OR = 0.21, 95% CI: 0.09-0.50) showed a protective effect on the risk of frailty, but daily intake of pickled vegetables showed the opposite effect (OR = 1.86, 95% CI: 1.12-3.07). Conclusion: Socioeconomic status, lifestyle, and the association with the risk of frailty showed substantial difference between the sexes among the longevous population in China. To establish the individualized strategy of behavioral improvement for the frailty prevention should consider the sex disparity.

4.
J Transl Med ; 19(1): 512, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930335

RESUMO

BACKGROUND: Association between blood pressure (BP) and kidney function among the middle and old aged general population without hypertension remains unclear. METHODS: Participants aged ≥ 45 years, with complete data in 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study(CHARLS), and without pre-existing hypertension were included. Systolic BP (SBP) was categorized as low (< 120 mmHg), medium (120-129 mmHg), and high (120-139 mmHg). Diastolic BP (DBP) was categorized as low (< 60 mmHg), medium (60-74 mmHg), and high (75-89 mmHg). Pulse pressure (PP) was categorized as normal (< 60 mmHg) and high (≥ 60 mmHg). The outcome was defined as rapid decline of estimated glomerular filtration rate(eGFR, decline ≥ 4 ml/min/1.73 m2/year). BP combination was designed according to the category of SBP and PP. The association between BP components, types of BP combination, and the risk of rapid decline of eGFR was analyzed using multivariate logistic regression models, respectively. Age-stratified analyses were conducted. RESULTS: Of 4,534 participants included, 695(15.3%) individuals were recognized as having rapid decline of eGFR. High PP[odds ratio(OR) = 1.34, 95%confidence interval(CI) 1.02-1.75], low SBP (OR = 1.28, 95%CI 1.03-1.59), and high SBP (OR = 1.32, 95% CI 1.02-1.71) were significantly associated with the risk of eGFR decline. Low SBP were associated with 65% increment of the risk of eGFR decline among participants aged < 55 years. The combination of high SBP and high PP (OR = 1.79, 95% CI 1.27-2.54) and the combination of low SBP and high PP (OR = 3.07, 95% CI 1.24-7.58) were associated with the increased risk of eGFR decline among the middle and old aged general population. CONCLUSION: Single and combination of high PP and high SBP could be the risk indicators of eGFR decline among the middle and old aged general population.

5.
Clin Kidney J ; 14(11): 2428-2436, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34754439

RESUMO

Background: The diagnostic status of chronic kidney disease (CKD) and its underlying reasons provide evidence that can improve CKD management. However, the situation in developing countries remains under-investigated. Methods: Adults with electronic health records (EHRs; 2008-19) in Yinzhou, China were included. The gold standard for CKD was defined as having persistently reduced estimated glomerular filtration rate (eGFR), albuminuria/proteinuria, haematuria or a history of CKD. CKD stages (G1-G5) were defined by eGFR. Clinical diagnosis of CKD in the real world setting was evaluated using International Classification of Diseases (ICD)-10 codes related to primary cause or stages of CKD. The specialty of doctors who administered the serum creatinine (SCr) tests and who made the primary-cause/CKD-staging diagnoses was analysed. The accuracy of CKD-staging codes was assessed. Results: Altogether, 85 519 CKD patients were identified from 976 409 individuals with EHRs. Of them, 10 287 (12.0%) having persistent urinary abnormalities or labelled with CKD-related ICD codes did not receive SCr tests within 12 months before or after the urine tests. Among 75 147 patients who received SCr tests, 46 150 (61.4%) missed any CKD-related codes, 6857 (35.7%) were merely labelled with primary-cause codes, and only 2140 (2.9%) were labelled with CKD-staging codes. The majority of CKD patients (51.6-91.1%) received SCr tests from non-nephrologists, whereas CKD-staging diagnoses were mainly from nephrologists (52.3-64.8%). Only 3 of 42 general hospitals had nephrologists. The CKD-staging codes had high specificity (>99.0%) but low sensitivity (G3-G4: <10.0%). Conclusions: Under-perception of CKD among doctors, rather than unsatisfactory health-seeking behaviour or low detection rates, was the main cause of under-diagnosis of CKD in China. Intensification of CKD education among doctors with different specialties might bring about immediate effective improvement in the diagnosis and awareness of CKD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34816323

RESUMO

Natural killer (NK) cells are cytotoxic lymphocytes that play a major role in the innate immune system. NK cells exhibit potent cytotoxic activity against cancer cells and virally infected cells without antigen priming. These unique cytotoxic properties make NK cells a promising therapeutic against cancer. Limitations of NK cell therapy include deficiencies in high clinical efficacy often due to a need for a high NK cell to target cell ratio to achieve effective killing. In order to address the suboptimal efficacy of current adoptive NK cell therapy, a high throughput screen (HTS) was designed and performed to identify drug-like compounds that increase NK cytotoxic activity against tumor cells without affecting the normal cells. This screen was performed in a 384-well plate format utilizing an expanded primary NK cell product and ovarian cancer cells as a target cell (TC) line. Of the 8000 diverse small molecules screened, 16 hits were identified (0.2% hit rate) based on both a robust Z (RZ) score < -3 and a greater than 10% increase in NK cell killing. A validation screen had a confirmation rate of 70%. Select compounds were further validated and characterized by additional cytotoxicity assays including activity against multiple blood cancer and solid tumor cell lines, with no effect on primary human T cells. This work demonstrates that high-throughput screening can be reliably used to identify compounds that increase NK tumoricidal activity in vitro that can be further investigated and translated for potential clinical application. Précis: Our work led to the identification of promising compound that potently increases NK cell-mediated killing of a variety of different cancer cells, but no impact on the killing of normal cells. This compound demonstrates the utility of this assay.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34794806

RESUMO

Strategies integrating synergistic high-efficiency bacterial killing and antibacterial process monitoring capability are desirable. Herein, a tri-functional surface-enhanced Raman spectroscopy (SERS) nanoplatform, namely 4-mercaptobenzoic acid-encoded gold nanorods@silver coated with a layer of bovine serum albumin (AuNRs@Ag@4-MBA@BSA), with excellent biocompatibility, stability, tunable plasmonic property and activatable photothermal effect is introduced for Ag+/photothermal therapy (PTT) synergistic antibacterial activity and antibacterial process monitoring. An exogenous etchant is used to controllably model the physiological process of metallic silver biodegradation. Ag shell etching causes the surface plasmon resonance band of SERS nanotags to red-shift to near-infrared region, activates the photothermal conversion capability, and triggers PTT, which in turn accelerates Ag shell etching. The antibacterial rates for Staphylococcus aureus and Escherichia coli after 10 min treatment can achieve 99.5% and 99.9%, respectively. Furthermore, the near-field effect and ultrasensitive property render the SERS intensity decrease ratio is dependent on Ag shell etching as well as temperature rising and thus relevant to antibacterial activity. We have demonstrated a strong correlation between SERS signal and antibacterial effect, and have verified the possibility of antibacterial process monitoring in vitro using SERS-based methodology. We envision that our integrated strategy being used for in vivo high-efficiency bacterial killing and antibacterial process monitoring.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34739169

RESUMO

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.

9.
ACS Nano ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34704438

RESUMO

Implant-related infections are serious complications after bone surgery and can compromise the intended functions of artificial implants, leading to surgical failure and even amputation in severe cases. Various strategies have been proposed to endow bone implants with the desirable antibacterial properties, but unfortunately, most of them inevitably suffer from some side effects detrimental to normal tissues. In this study, a multifunctional bone implant is designed to work in conjunction with sequential photothermal mediation, which can deliver antibacterial therapy (<50 °C) in the early stage and foster bone regeneration (40-42 °C) subsequently. Black phosphorus nanosheets (BPs) are coordinated with zinc sulfonate ligand (ZnL2), and the ZnL2-BPs are integrated into the surface of a hydroxylapatite (HA) scaffold to produce ZnL2-BPs@HAP. In this design, BPs produce the photothermal effects and ZnL2 increases the thermal sensitivity of peri-implant bacteria by inducing envelope stress. The biosafety of the antibacterial photothermal treatment is improved due to the mild temperature, and furthermore, gradual release of Zn2+ and PO43- from the scaffold facilitates osteogenesis in the subsequent stage of bone healing. This strategy not only broadens the biomedical applications of photothermal treatment but also provides insights into the design of multifunctional biomaterials in other fields.

10.
Innovation (N Y) ; 2(3): 100148, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34557785

RESUMO

The immune responses are involved in every stage after implantation but the reported immune-regulated materials only work at the beginning without fully considering the different phases of bone healing. Here, poly(aryl-ether-ether-ketone) (PEEK) is coated with a programmed surface, which rapidly releases interleukin-10 (IL-10) in the first week and slowly delivers dexamethasone (DEX) up to 4 weeks. Owing to the synergistic effects of IL-10 and DEX, an aptly weak inflammation is triggered within the first week, followed by significant M2 polarization of macrophages and upregulation of the autophagy-related factors. The suitable immunomodulatory activities pave the way for osteogenesis and the steady release of DEX facilitates bone regeneration thereafter. The sequential immune-mediated process is also validated by an 8-week implementation on a rat model. This is the first attempt to construct implants by taking advantage of both immune-mediated modulation and sequential regulation spanning all bone regeneration phases, which provides insights into the fabrication of advanced biomaterials for tissue engineering and immunological therapeutics.

11.
Nat Commun ; 12(1): 4874, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385442

RESUMO

Biobased poly(γ-methyl-α-methylene-γ-butyrolactone) (PMMBL), an acrylic polymer bearing a cyclic lactone ring, has attracted increasing interest because it not only is biorenewable but also exhibits superior properties to petroleum-based linear analog poly(methyl methacrylate) (PMMA). However, such property enhancement has been limited to resistance to heat and solvent, and mechanically both types of polymers are equally brittle. Here we report the expeditious synthesis of well-defined PMMBL-based ABA tri-block copolymers (tri-BCPs)-enabled by dual-initiating and living frustrated Lewis pairs (FLPs)-which are thermoplastic elastomers showing much superior mechanical properties, especially at high working temperatures (80-130 °C), to those of PMMA-based tri-BCPs. The FLPs consist of a bulky organoaluminum Lewis acid and a series of newly designed bis(imino)phosphine superbases bridged by an alkyl linker, which promote living polymerization of MMBL. Uniquely, such bisphosphine superbases initiate the chain growth from both P-sites concurrently, enabling the accelerated synthesis of tri-BCPs in a one-pot, two-step procedure. The results from mechanistic studies, including the single crystal structure of the dually initiated active species, detailed polymerizations, and kinetic studies confirm the livingness of the polymerization and support the proposed polymerization mechanism featuring the dual initiation and subsequent chain growth from both P-sites of the superbase di-initiator.


Assuntos
4-Butirolactona/análogos & derivados , Elastômeros/química , Ácidos de Lewis/química , Fosfinas/química , Polímeros/química , 4-Butirolactona/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Cristalografia por Raios X , Elastômeros/síntese química , Cinética , Modelos Químicos , Estrutura Molecular , Polimerização , Polímeros/síntese química , Temperatura
12.
Front Med (Lausanne) ; 8: 719806, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409056

RESUMO

Background: Frailty is an epidemic age-related syndrome addressing heavy burden to the healthcare system. Subject to the rarity, age-, and gender-specific prevalence of frailty and its prognosis among the longevous population remains under-investigated. Methods: Based on the Chinese Longitudinal Healthy Longevity Study (CLHLS, 2008-2018), individuals aged ≥ 65 years having complete data of frailty were recruited. Modified Fried criteria (exhaustion, shrink, weakness, low mobility, and inactivity) were adopted to define pre-frailty (1-2 domains) and frailty (≥3 domains), respectively. The association between pre-frailty/frailty and adverse outcomes (frequent hospitalization, limited physical performance, cognitive decline, multimorbidity, and dependence) was analyzed using logistic regression models. The association between pre-frailty/frailty and mortality was analyzed using Cox proportional hazards models. Age- and gender-stratified analyses were performed. Results: Totally, 13,859 participants aged 85.8 ± 11.1 years, including 2,056 centenarians, were recruited. The overall prevalence of pre-frailty and frailty were 54.1 and 26.3%, respectively. Only 5.0% of centenarians were non-frailty whereas 59.9% of the young-old (65-79 years) showed pre-frailty. Both pre-frailty and frailty were associated with the increased risk of multiple adverse outcomes, such as incident limited physical performance, cognitive decline and dependence, respectively (P < 0.05). Frail males were more vulnerable to the risk of mortality (hazard ratio [HR] = 2.3, 95% confidence interval [CI], 2.1-2.6) compared with frail females (HR = 1.9, 95%CI, 1.7-2.1). The strongest association between frailty and mortality was observed among the young-old (HR = 3.6, 95%CI, 2.8-4.5). Exhaustion was the most common domain among patients with pre-frailty (74.8%) or frailty (83.2%), followed by shrink (32.3%) in pre-frailty and low mobility (83.0%) in frailty. Inactivity among females aged 65-79 years showed the strongest association with the risk of mortality (HR = 3.50, 95%CI, 2.52-4.87). Conclusion: A huge gap exists between longer life and healthy aging in China. According to the age- and gender-specific prevalence and prognosis of frailty, the strategy of frailty prevention and intervention should be further individualized.

13.
Front Med ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241787

RESUMO

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.

14.
Br J Pharmacol ; 178(21): 4352-4367, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34233019

RESUMO

BACKGROUND AND PURPOSE: Metabolic adaptation driven by oestrogen-related receptor-α (ERRα/NR3B1) is required to meet the increased energy demand during osteoclast differentiation. Here, we hypothesize that natural product, andrographolide, acts as an ERRα inverse agonist to inhibit osteoclastogenesis. EXPERIMENTAL APPROACH: Virtual docking and site-directed mutagenesis analysis were employed to study the binding mode of andrographolide to ERRα. Co-immunoprecipitation, luciferase reporter assay, real-time polymerase chain reaction (PCR) and immunoblot analyses were performed to identify andrographolide as an ERRα inverse agonist. The pharmacological effects of andrographolide in vivo were assessed in mice models of osteopenia induced by either a high-fat diet in male or ovariectomy in female mice. KEY RESULTS: ERRα-dependent expression of glutaminase, a rate-limiting enzyme of mitochondrial glutamine anaplerosis, is required for ex vivo bone marrow osteoclast differentiation. Andrographolide inhibited glutaminase expression induced by ERRα and co-activator peroxisome proliferator-activated receptor γ co-activator-1ß (PGC-1ß), leading to reduction in osteoclastogenesis. Andrographolide acted as an inverse agonist of ERRα by disrupting its interaction with co-activator PGC-1ß. Phenylalanine 232, valine 395 and phenylalanine 399 of ERRα ligand-binding domain were confirmed to be essential for this effect. In contrast, glutaminase overexpression restored the impairment triggered by andrographolide. Accordingly, andrographolide suppressed osteoclastic bone resorption and attenuated bone loss in vivo. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that andrographolide acts as an ERRα inverse agonist for perturbation of ERRα/PGC-1ß/glutaminase axis-driven metabolic adaption during osteoclast differentiation, implying that andrographolide may be a promising natural compound for preventing physiological and pathological bone loss.

15.
Vet Res Commun ; 45(2-3): 75-86, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34251560

RESUMO

The recent prevalence of coronavirus (CoV) poses a serious threat to animal and human health. Currently, porcine enteric coronaviruses (PECs), including the transmissible gastroenteritis virus (TGEV), the novel emerging swine acute diarrhoea syndrome coronavirus (SADS-CoV), porcine delta coronavirus (PDCoV), and re-emerging porcine epidemic diarrhoea virus (PEDV), which infect pigs of different ages, have caused more frequent occurrences of diarrhoea, vomiting, and dehydration with high morbidity and mortality in piglets. PECs have the potential for cross-species transmission and are causing huge economic losses in the pig industry in China and the world, which therefore needs to be urgently addressed. Accordingly, this article summarises the pathogenicity, prevalence, and diagnostic methods of PECs and provides an important reference for their improved diagnosis, prevention, and control.


Assuntos
Infecções por Coronavirus/veterinária , Doenças dos Suínos/virologia , Alphacoronavirus/genética , Alphacoronavirus/patogenicidade , Animais , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Deltacoronavirus/genética , Deltacoronavirus/patogenicidade , Humanos , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/patogenicidade , Prevalência , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Vírus da Gastroenterite Transmissível/genética , Vírus da Gastroenterite Transmissível/patogenicidade
17.
Acta Biomater ; 126: 524-536, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684537

RESUMO

Orthopedic and dental implants made of ß-type Ti alloys have low elastic modulus which can better relieve the stress shielding effects after surgical implantation. Nevertheless, clinical application of ß-type Ti alloys is hampered by the insufficient mechanical strength and gradual release of pro-inflammatory metallic ions under physiological conditions. In this study, the ß-type Ti-45Nb alloy is subjected to high-pressure torsion (HPT) processing to refine the grain size. After HPT processing, the tensile strength increases from 370 MPa to 658 MPa due to grain boundary strengthening and at the same time, the favorable elastic modulus is maintained at a low level of 61-72 GPa because the single ß-phase is preserved during grain refinement. More grain boundaries decrease the work function and facilitate the formation of thicker and less defective passive films leading to better corrosion resistance. In addition, more rapid repair of the passive layer mitigates release of metallic ions from the alloy and consequently, the inflammatory response is suppressed. The results reveal a strategy to simultaneously improve the mechanical and biological properties of metallic implant materials for orthopedics and dentistry. STATEMENT OF SIGNIFICANCE: The low modulus Ti-45Nb alloy is promising in addressing the complication of stress shielding induced by biomedical Ti-based materials with too-high elastic modulus. However, its insufficient strength hampers its clinical application, and traditional strengthening via heat treatments will compromise the low elastic modulus. In the current study, we enhanced the ultimate tensile strength of Ti-45Nb from 370 MPa to 658 MPa through grain-refinement strengthening, while the elastic modulus was maintained at a low value (61-72 GPa). Moreover, substrate grain-refinement has been proved to improve the corrosion resistance of Ti-45Nb with reduced inflammatory response both in vitro and in vivo. A relationship between the substrate microstructure and the surface passive layer has been established to explain the beneficial effects of substrate grain-refinement.


Assuntos
Ligas , Titânio , Anti-Inflamatórios , Materiais Biocompatíveis , Corrosão , Módulo de Elasticidade , Teste de Materiais
18.
Am J Kidney Dis ; 77(6): 889-897.e1, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33421457

RESUMO

RATIONALE & OBJECTIVE: The national prevalence of dialysis in China has not been well studied. We aimed to estimate the prevalence of kidney disease treated with dialysis and predict the trend using claims data in order to provide evidence for developing prevention strategies. STUDY DESIGN: Cross-sectional study of insurance claims. SETTING & PARTICIPANTS: Medical claims data from January 1, 2013, to December 31, 2017, were extracted from a large claims database by using a 2-stage sampling design to obtain a national sample covered by the urban basic medical insurance, the most predominant insurance program in China. EXPOSURE: Patients receiving maintenance dialysis, including hemodialysis (HD) and peritoneal dialysis (PD), were identified according to medical billing data and International Classification of Diseases, Tenth Revision (ICD-10) codes. OUTCOMES: The age- and sex-standardized population prevalence of kidney disease treated with dialysis was estimated by year and treatment modality. ANALYTICAL APPROACH: Crude and age- and sex-standardized prevalence of kidney disease treated with dialysis were calculated stratified by year and treatment modality. The gray Verhulst model was used to predict dialysis prevalence from 2018 to 2025. RESULTS: The age-and sex-standardized prevalence of dialysis patients increased from 255.11 per million population (pmp) in 2013 to 419.39 pmp in 2017. The age- and sex-standardized prevalence of HD and PD in 2017 were 384.41 pmp and 34.98 pmp, respectively, and the total number of dialysis patients in China was estimated to be 581,273. The prevalence of dialysis was predicted to rise above 2017 levels, with a predicted prevalence of 534.60 pmp in 2020 and 629.67 pmp in 2025, corresponding to 744,817 and 874,373 patients, respectively. LIMITATIONS: Claims data have potential errors in classification of patients, and population selection bias may have limited inferences to the entire Chinese population. CONCLUSIONS: The prevalence of kidney disease treated with dialysis has risen between 2013 and 2017 in China and is predicted to increase further through 2025. These findings highlight the importance of prevention and control strategies to reduce the escalating burden of kidney failure.


Assuntos
Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Adolescente , Adulto , Idoso , Criança , China , Estudos Transversais , Feminino , Humanos , Formulário de Reclamação de Seguro , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
19.
Nephrol Dial Transplant ; 35(12): 2095-2102, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275762

RESUMO

BACKGROUND: Acute kidney injury (AKI) is an important complication of coronavirus disease 2019 (COVID-19), which could be caused by both systematic responses from multi-organ dysfunction and direct virus infection. While advanced evidence is needed regarding its clinical features and mechanisms. We aimed to describe two phenotypes of AKI as well as their risk factors and the association with mortality. METHODS: Consecutive hospitalized patients with COVID-19 in tertiary hospitals in Wuhan, China from 1 January 2020 to 23 March 2020 were included. Patients with AKI were classified as AKI-early and AKI-late according to the sequence of organ dysfunction (kidney as the first dysfunctional organ or not). Demographic and clinical features were compared between two AKI groups. Their risk factors and the associations with in-hospital mortality were analyzed. RESULTS: A total of 4020 cases with laboratory-confirmed COVID-19 were included and 285 (7.09%) of them were identified as AKI. Compared with patients with AKI-early, patients with AKI-late had significantly higher levels of systemic inflammatory markers. Both AKIs were associated with an increased risk of in-hospital mortality, with similar fully adjusted hazard ratios of 2.46 [95% confidence interval (CI) 1.35-4.49] for AKI-early and 3.09 (95% CI 2.17-4.40) for AKI-late. Only hypertension was independently associated with the risk of AKI-early. While age, history of chronic kidney disease and the levels of inflammatory biomarkers were associated with the risk of AKI-late. CONCLUSIONS: AKI among patients with COVID-19 has two clinical phenotypes, which could be due to different mechanisms. Considering the increased risk for mortality for both phenotypes, monitoring for AKI should be emphasized during COVID-19.


Assuntos
Injúria Renal Aguda/etiologia , COVID-19/complicações , Injúria Renal Aguda/epidemiologia , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , China/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2 , Fatores de Tempo , Adulto Jovem
20.
Entropy (Basel) ; 22(7)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-33286551

RESUMO

The quantum phase transition of a one-dimensional transverse field Ising model in an imaginary longitudinal field is studied. A new order parameter M is introduced to describe the critical behaviors in the Yang-Lee edge singularity (YLES). The M does not diverge at the YLES point, a behavior different from other usual parameters. We term this unusual critical behavior around YLES as the pseudo-YLES. To investigate the static and driven dynamics of M, the (1+1) dimensional ferromagnetic-paramagnetic phase transition ((1+1) D FPPT) critical region, (0+1) D YLES critical region and the (1+1) D YLES critical region of the model are selected. Our numerical study shows that the (1+1) D FPPT scaling theory, the (0+1) D YLES scaling theory and (1+1) D YLES scaling theory are applicable to describe the critical behaviors of M, demonstrating that M could be a good indicator to detect the phase transition around YLES. Since M has finite value around YLES, it is expected that M could be quantitatively measured in experiments.

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