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1.
ACS Appl Mater Interfaces ; 16(38): 50125-50138, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39284011

ABSTRACT

Zinc-based alloys, specifically Zn-Mg, have garnered considerable attention as promising materials for biodegradable implants due to their favorable mechanical strength, appropriate corrosion rate, and biocompatibility. Nevertheless, the alloy's lack of mechanical stability and integrity, resulting from ductility loss induced by age hardening at room temperature, hampers its practical bioapplication. In this study, ceramic nanoparticles have been successfully incorporated into the Zn-Mg alloy system, leading to a significant improvement in long-term stability as well as mechanical strength and ductility. In addition, this study represents the first investigation of Zn-based nanocomposites both in vitro and in vivo to comprehend the influence of nanoparticles on the degradation behavior and biocompatibility of the Zn system. The findings indicate that the incorporation of WC nanoparticles effectively refines and stabilizes the degradation behavior of Zn-Mg without negatively impacting the cytocompatibility of the alloy. The subcutaneous implantation and femoral implantation further prove the benefits of nanoparticle incorporation and found no negative effects. Collectively, Zn-Mg-WC nanocomposites yield great potential for implant usage.


Subject(s)
Absorbable Implants , Alloys , Magnesium , Zinc , Zinc/chemistry , Alloys/chemistry , Alloys/pharmacology , Animals , Magnesium/chemistry , Materials Testing , Mice , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Nanoparticles/chemistry , Nanocomposites/chemistry , Nanocomposites/toxicity , Corrosion
2.
Biosensors (Basel) ; 14(9)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39329789

ABSTRACT

Humidity sensors deeply influence human manufacturing production and daily life, while researchers generally focus on developing humidity sensors with higher stability, higher linearity, rapid response time, etc. Yet, few people discuss measuring humidity in the microenvironment by miniaturizing sensor size into a microscale, in which the existing humidity sensors are difficult to reach. Accordingly, this study proposes a methodology for measuring relative humidity in the microscale by utilizing the distinctive morphologies of Equisetum spores across a range of relative humidities between 50% and 90%. Equisetum spores are responsive to changes in ambient relative humidity and remain in their original activities even after iron sputtering, which aims to endow the sensor with magnetic properties. The test performed in this study demonstrated a response time of 3.3 s and a recovery time of 3.6 s. In the first application, we employed such microscale sensors to work in the channel of the microfluidic chip or the cell migration microchip, as an example of working in the microenvironment. COMSOL Multiphysics 6.2 software was also used to simulate the change in relative humidity in such microchannels. Secondly, such microscale sensors are combined with smartphone-based microscopy to measure the humidity of the skin. These microscale sensors pave the new way to sensing humidity in microenvironments.


Subject(s)
Equisetum , Humidity , Iron , Biosensing Techniques , Humans , Spores , Spores, Fungal
3.
Anal Chem ; 96(39): 15808-15815, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39300344

ABSTRACT

Commercial pH paper is a quick and simple tool for measuring a solution's acidity/basicity, but it only provides qualitative or semi-quantitative results, and the synthetic indicator dyes within can be toxic or carcinogenic. Although pH meters enable more accurate and quantitative analysis, they are less convenient to operate and are tedious to calibrate. This presents a need for an alternative pH testing method for applications where it is not easy or possible to use a pH meter, yet quantitative results are desired. We report herein the fabrication of a pH test strip made from superhydrophobic paper and agarose-anthocyanin film discs. In the proposed method, test strips are dipped into samples and then imaged with a portable scanner (or a smartphone). The color of the film is extracted with ImageJ software (or a mobile app), using the RGB color system. By generating a calibration curve relating the film color to the sample pH using standard buffer solutions, we are able to quantify the pH of beverages and other liquids with an accuracy and precision comparable to that of a pH meter. The test strips offer the same convenience as conventional pH paper, with the added capabilities of quantitation and multiplexed testing, which presents a practical tool for point-of-need pH analysis.

4.
Nature ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322662

ABSTRACT

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras1,2 (LYTACs) and cytokine receptor-targeting chimeras3 (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor. Here we describe computational design approaches for endocytosis-triggering binding proteins (EndoTags) that overcome these challenges. We present EndoTags for insulin-like growth factor 2 receptor (IGF2R) and asialoglycoprotein receptor (ASGPR), sortilin and transferrin receptors, and show that fusing these tags to soluble or transmembrane target protein binders leads to lysosomal trafficking and target degradation. As these receptors have different tissue distributions, the different EndoTags could enable targeting of degradation to different tissues. EndoTag fusion to a PD-L1 antibody considerably increases efficacy in a mouse tumour model compared to antibody alone. The modularity and genetic encodability of EndoTags enables AND gate control for higher-specificity targeted degradation, and the localized secretion of degraders from engineered cells. By promoting endocytosis, EndoTag fusion increases signalling through an engineered ligand-receptor system by nearly 100-fold. EndoTags have considerable therapeutic potential as targeted degradation inducers, signalling activators for endocytosis-dependent pathways, and cellular uptake inducers for targeted antibody-drug and antibody-RNA conjugates.

5.
Int Immunopharmacol ; 142(Pt A): 112989, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39217879

ABSTRACT

OBJECTIVE: To investigate the protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell (BMEC) injury, and elucidate the possible underlying mechanism. METHODS: BMECs were treated with different concentrations of hydrocortisone at different time points, and the viability as well as migration of BMECs were evaluated; furthermore, the release of LDH, levels of VEGF, PAI-1, t-PA, and the content of NO by BMECs have been evaluated by commercially available kits; moreover, the expressions of eNOS, p-PI3K, p-Akt and p-mTOR in BMECs were examined by WB methods. Next, hydrocortisone treated BMECs were co-treated with Gumibao recipe, and the viability, migration and autophagy of BMECs were evaluated. RESULTS: 0.2 mg/ml and 0.3 mg/ml hydrocortisone significantly decreased viability and migration ability of BMECs, and also impeded the endothelial function of BMECs by decreasing the levels of VEGF, t-PA, the content of NO, and increasing the level of PAI-1. Gumibao medicated serum markedly increased the viability and migration of BMECs, and also increased the levels of VEGF, t-PA, the content of NO, meanwhile decreased the level of PAI-1 in 0.3 mg/ml hydrocortisone treated BMECs; moreover, glucocorticoids inhibited the autophagy of BMECs, and Gumibao recipe significantly increased the autophagy of BMECs; meanwhile, autophagy inhibitor 3-MA partially blocked the protective effects of Gumibao recipe. Finally, gumibao recipe partially abrogated the inhibitory effects of hydrocortisone on the activation of PI3K/Akt/mTOR singling, and these effects were further counteracted by PI3K and mTOR inhibitor NVP-BEZ235. CONCLUSIONS: We reported for the first time the protective effects of Gumibao recipe on glucocorticoid-included BMECs injury, and the possible underlying mechanism may be regulating the autophagy of BMECs via PI3K/AKT/mTOR signaling pathway.

6.
J Plant Physiol ; 303: 154360, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39348744

ABSTRACT

Most studies currently focus on traditional illuminant regulating plant growth, while less attention has been given to the LED internal luminescence. This study examined how polarized and vortex light affect the growth and photosynthetic traits of pepper plants, with LED light used as the control. The findings indicated that circular polarized light significantly increased the aboveground biomass of pepper. Additionally, both polarized and vortex light treatment significantly influenced the root development of pepper. In comparison to the control group, the chlorophyll content was highest under circular polarized light, while the Pn, Sc, Tr, and Ci values were highest under linear polarized light, and the enzyme activity of Rubisco was increased. Circular polarized light notably increased the activities of POD, CAT, and SOD, the activity of SOD reached its peak under the left vortex light. Moreover, the content of MDA was observed to be the lowest under linear and right vortex light treatments. The expressions of key genes for chlorophyll synthesis (CaHEMA1 and CaCAO) and antioxidant enzyme synthesis (CaPOD, CaSOD, and CaMDHAR) were significantly altered under varying polarized light conditions, The latter genes, which play crucial roles in antioxidant enzyme activity, also showed significant variations in response to different polarized light treatments. In conclusion, polarized light significantly impacts the growth of pepper and is anticipated to be utilized for plant growth, setting the stage for future research in this area.

7.
J Neurol Sci ; 464: 123168, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39121524

ABSTRACT

Adult polyglucosan body disease (APBD) is a rare autosomal recessive glycogen storage disorder that leads to slowly progressive multi-organ dysfunction in adulthood. A novel disease-specific patient-reported outcome measure was created and administered to assess symptom burden and health-related quality of life (HR-QOL) in APBD. Thirty-six participants between 30 and 79 years of age (83% ≥60 years, 56% male) completed the anonymous questionnaire independently or with a caregiver proxy (75% self-report). Unemployment predicted an 18.3 (95% CI: 2.8, 33.8; p = 0.028) higher composite disease severity score and a 28.8 (95% CI: 8.2, 49.4; p = 0.010) higher composite HR-QOL score. Use of one or more assistive devices also predicted a 29.3 (95% CI: 8.3, 50.4; p = 0.011) higher composite disease severity score and a 41.8 (95% CI: 10.9, 72.8; p = 0.013) higher composite HR-QOL score. Proxy survey completion predicted a 19.4 (95% CI: 4.1, 34.7; p = 0.020) higher composite disease severity score compared to self-report. Older age at survey completion predicted a 27.4 higher composite HR-QOL score (95% CI: 2.5, 52.4; p = 0.039) for participants in their sixties compared to those between 30 and 59 years old. The development of the Adult Polyglucosan Body Disease questionnaire on Symptom burden and health-related Quality of life (APBD-SQ) marks an important stride forward in capturing the patient experience as a tool for disease monitoring and future research.


Subject(s)
Glycogen Storage Disease , Patient Reported Outcome Measures , Quality of Life , Humans , Male , Quality of Life/psychology , Female , Middle Aged , Adult , Glycogen Storage Disease/psychology , Aged , Severity of Illness Index , Surveys and Questionnaires , Self Report , Nervous System Diseases
8.
Cell ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39208797

ABSTRACT

In mammalian cells, two phosphatidylserine (PS) synthases drive PS synthesis. Gain-of-function mutations in the Ptdss1 gene lead to heightened PS production, causing Lenz-Majewski syndrome (LMS). Recently, pharmacological inhibition of PSS1 has been shown to suppress tumorigenesis. Here, we report the cryo-EM structures of wild-type human PSS1 (PSS1WT), the LMS-causing Pro269Ser mutant (PSS1P269S), and PSS1WT in complex with its inhibitor DS55980254. PSS1 contains 10 transmembrane helices (TMs), with TMs 4-8 forming a catalytic core in the luminal leaflet. These structures revealed a working mechanism of PSS1 akin to the postulated mechanisms of the membrane-bound O-acyltransferase family. Additionally, we showed that both PS and DS55980254 can allosterically inhibit PSS1 and that inhibition by DS55980254 activates the SREBP pathways, thus enhancing the expression of LDL receptors and increasing cellular LDL uptake. This work uncovers a mechanism of mammalian PS synthesis and suggests that selective PSS1 inhibitors have the potential to lower blood cholesterol levels.

9.
Biomimetics (Basel) ; 9(7)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39056864

ABSTRACT

Ti6Al4V superalloy is recognized as a good candidate for bone implants owing to its biocompatibility, corrosion resistance, and high strength-to-weight ratio. While dense metal implants are associated with stress shielding issues due to the difference in densities, stiffness, and modulus of elasticity compared to bone tissues, the surface of the implant/scaffold should mimic the properties of the bone of interest to assure a good integration with a strong interface. In this study, we investigated the additive manufacturing of porous Ti6Al4V scaffolds and coating modification for enhanced osteoconduction using osteoblast cells. The results showed the successful fabrication of porous Ti6Al4V scaffolds with adequate strength. Additionally, the surface treatment with NaOH and Dopamine Hydrochloride (DOPA) promoted the formation of Dopamine Hydrochloride (DOPA) coating with an optimized coating process, providing an environment that supports higher cell viability and growth compared to the uncoated Ti6Al4V scaffolds, as demonstrated by the higher proliferation ratios observed from day 1 to day 29. These findings bring valuable insights into the surface modification of 3D-printed scaffolds for improved osteoconduction through the coating process in solutions.

10.
Mikrochim Acta ; 191(8): 454, 2024 07 08.
Article in English | MEDLINE | ID: mdl-38976069

ABSTRACT

An intelligent colorimetric sensing platform integrated with in situ immunomagnetic separation function was developed for ultrasensitive detection of Escherichia coli O157: H7 (E. coli O157: H7) in food. Captured antibody modified magnetic nanoparticles (cMNPs) and detection antibody/horseradish peroxidase (HRP) co-functionalized AuNPs (dHAuNPs) were firstly synthesized for targeted enrichment and colorimetric assay of E. coli O157: H7, in which remarkable signal amplification was realized by loading large amounts of HRP on the surface of AuNPs. Coupling with the optical collimation attachments and embedded magnetic separation module, a highly integrated optical device was constructed, by which in situ magnetic separation and high-quality imaging of 96-well microplates containing E. coli O157: H7 was achieved with a smartphone. The concentration of E. coli O157: H7 could be achieved in one-step by performing digital image colorimetric analysis of the obtained image with a custom-designed app. This biosensor possesses high sensitivity (1.63 CFU/mL), short detecting time (3 h), and good anti-interference performance even in real-sample testing. Overall, the developed method is expected to be a novel field detection platform for foodborne pathogens in water and food as well as for the diagnosis of infections due to its portability, ease of operation, and high feasibility.


Subject(s)
Biosensing Techniques , Colorimetry , Escherichia coli O157 , Food Microbiology , Gold , Horseradish Peroxidase , Immunomagnetic Separation , Metal Nanoparticles , Escherichia coli O157/isolation & purification , Colorimetry/methods , Gold/chemistry , Horseradish Peroxidase/chemistry , Immunomagnetic Separation/methods , Biosensing Techniques/methods , Metal Nanoparticles/chemistry , Food Contamination/analysis , Limit of Detection , Smartphone , Antibodies, Immobilized/immunology , Antibodies, Immobilized/chemistry , Magnetite Nanoparticles/chemistry
11.
Qual Manag Health Care ; 33(3): 192-199, 2024.
Article in English | MEDLINE | ID: mdl-38941584

ABSTRACT

BACKGROUND AND OBJECTIVES: Hospitals and clinicians increasingly are reimbursed based on quality of care through financial incentives tied to value-based purchasing. Patient-centered care, measured through patient experience surveys, is a key component of many quality incentive programs. We hypothesize that operational aspects such as wait times are an important element of emergency department (ED) patient experience. The objectives of this paper are to determine (1) the association between ED wait times and patient experience and (2) whether patient comments show awareness of wait times. METHODS: This is a cross-sectional observational study from January 1, 2019, to December 31, 2020, across 16 EDs within a regional health care system. Patient and operations data were obtained as secondary data through internal sources and merged with primary patient experience data from our data analytics team. Dependent variables are (1) the association between ED wait times in minutes and patient experience ratings and (2) the association between wait times in minutes and patient comments including the term wait (yes/no). Patients rated their "likelihood to recommend (LTR) an ED" on a 0 to 10 scale (categories: "Promoter" = 9-10, "Neutral" = 7-8, or "Detractor" = 0-6). Our aggregate experience rating, or Net Promoter Score (NPS), is calculated by the following formula for each distinct wait time (rounded to the nearest minute): NPS = 100* (# promoters - # detractors)/(# promoters + # neutrals + # detractors). Independent variables for patient age and gender and triage acuity, were included as potential confounders. We performed a mixed-effect multivariate ordinal logistic regression for the rating category as a function of 30 minutes waited. We also performed a logistic regression for the percentage of patients commenting on the wait as a function of 30 minutes waited. Standard errors are adjusted for clustering between the 16 ED sites. RESULTS: A total of 50 833 unique participants completed an experience survey, representing a response rate of 8.1%. Of these respondents, 28.1% included comments, with 10.9% using the term "wait." The odds ratio for association of a 30-minute wait with LTR category is 0.83 [0.81, 0.84]. As wait times increase, the odds of commenting on the wait increase by 1.49 [1.46, 1.53]. We show policy-relevant bubble plot visualizations of these two relationships. CONCLUSIONS: Patients were less likely to give a positive patient experience rating as wait times increased, and this was reflected in their comments. Improving on the factors contributing to ED wait times is essential to meeting health care systems' quality initiatives.


Subject(s)
Emergency Service, Hospital , Patient Satisfaction , Waiting Lists , Humans , Emergency Service, Hospital/statistics & numerical data , Cross-Sectional Studies , Male , Patient Satisfaction/statistics & numerical data , Female , Middle Aged , Adult , Time Factors , Aged , Adolescent , Young Adult
12.
Anal Chim Acta ; 1312: 342742, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38834261

ABSTRACT

Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between µPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators.


Subject(s)
Colorimetry , Hyperuricemia , Paper , Polymers , Uric Acid , Humans , Hyperuricemia/diagnosis , Hyperuricemia/urine , Polymers/chemistry , Uric Acid/urine , Colorimetry/instrumentation , Lab-On-A-Chip Devices , Smartphone , Creatinine/urine , Microfluidic Analytical Techniques/instrumentation , Limit of Detection , Biomarkers/urine , Hydrogen-Ion Concentration
13.
Chemphyschem ; : e202400414, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896533

ABSTRACT

We systematically investigated the stable configurations and catalytic activity in the Oxygen Reduction Reaction (ORR) of graphene co-doped with boron and nitrogen (B-N) using first-principles methods. Compared to single B/N doping, co-doping with BN is energetically favored. We found that intermediate species of ORR process adsorb on boron atoms, which act as catalytic sites. The presence of neighboring nitrogen atoms around boron plays a crucial role in modulating the catalytic activity of boron. For the same adsorption configuration, the adsorption energy of the adsorbate increases with the number of neighboring nitrogen atoms around boron and generally correlates positively with the number of electrons gained by the adsorbate. Regarding the catalytic activity of ORR, excessively strong adsorption of adsorbates impedes their hydrogenation. The best substrates for ORR catalytic activity are B-N-graphene and N-B2-graphene, with the rate-determining step being the hydrogenation of *OO and overpotentials of 0.49 V and 0.54 V, respectively.

14.
Heart Rhythm ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880203

ABSTRACT

BACKGROUND: The causes of symptoms in patients with paroxysmal atrial fibrillation (AF) remains unclear. OBJECTIVE: The purpose of this study was to correlate the magnitudes of skin sympathetic nerve activity (SKNA) with symptoms in patients with AF. METHODS: We prospectively enrolled patients with symptomatic paroxysmal AF for ambulatory electrocardiography and SKNA recording. Heart rhythms at the time of symptoms were categorized as AF or normal sinus rhythm (NSR). Maximal and average skin sympathetic nerve activity (aSKNA) and heart rate (HR) were compared between symptomatic and asymptomatic AF and NSR episodes using mixed effects models to account for within-patient correlations. RESULTS: Among the 31 enrolled patients, 16 (52%) had at least 1 episode of AF, and 24 (77%) endorsed symptoms during the monitoring period. Compared with asymptomatic AF episodes, symptomatic AF episodes had higher maximal aSKNA (1.260 [interquartile range (IQR) 1.114-1.723] µV vs 1.108 [IQR 0.974-1.312] µV; P <0.001) and higher maximal HR (152 ± 24 bpm vs 132 ± 19 bpm; P <.001). Symptomatic NSR episodes were associated with higher maximal aSKNA (1.612 [IQR 1.287-2.027] µV vs 1.332 [IQR 1.033-1.668] µV; P = .001) and higher maximal HR (152 ± 24 bpm vs 105 ± 16 bpm; P <.001) than asymptomatic NSR episodes. Of the symptomatic episodes, 66 (73%) occurred during NSR and 24 (27%) during AF. All P values were obtained from mixed effects models. CONCLUSION: Symptomatic episodes in patients with paroxysmal AF were more frequently associated with NSR than AF. Symptomatic AF and NSR episodes were associated with higher aSKNA than asymptomatic episodes. In patients with paroxysmal AF, symptoms correlate better with SKNA than heart rhythm.

15.
Heart Rhythm ; 21(9): 1669-1676, 2024 09.
Article in English | MEDLINE | ID: mdl-38762134

ABSTRACT

BACKGROUND: Autonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). OBJECTIVE: The purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. METHODS: Simultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. RESULTS: In study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P = .0185) and type 2 (P = .0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. CONCLUSION: A single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias.


Subject(s)
Atrial Fibrillation , Atrial Premature Complexes , Electrocardiography , Sympathetic Nervous System , Humans , Female , Male , Atrial Fibrillation/physiopathology , Atrial Fibrillation/diagnosis , Middle Aged , Atrial Premature Complexes/physiopathology , Atrial Premature Complexes/diagnosis , Sympathetic Nervous System/physiopathology , Aged , Recurrence , Heart Rate/physiology , Skin/innervation , Follow-Up Studies
16.
3D Print Addit Manuf ; 11(2): e529-e536, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38689923

ABSTRACT

With high strength and good fatigue resistance, Al-Cu alloys such as AA2024 are widely used in the aerospace and automotive industries. However, the system's susceptibility to hot cracking and other solidification defects hinders its development in metal additive manufacturing (AM). A nano-treated AA2024 deposition, with the addition of TiC nanoparticles, is successfully additively manufactured without cracks. Microstructural analysis suggests nanoparticles not only mitigate the hot cracking sensitivity but also significantly refine and homogenize grains, resulting in an average size of 23.2 ± 0.4 µm. Microhardness profiles show consistent mechanical performance along the build direction, regardless of cyclic thermal exposure. Finally, excellent tensile strength and elongation up to 428 MPa and 7.4% were achieved after heat treatment. The combined results show a great promise of nano-treating in high-strength aluminum AM.

17.
ACS Appl Mater Interfaces ; 16(20): 26943-26953, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38718354

ABSTRACT

The continuous, noninvasive monitoring of human blood pressure (BP) through the accurate detection of pulse waves has extremely stringent requirements on the sensitivity and stability of flexible strain sensors. In this study, a new ultrasensitive flexible strain sensor based on the interlayer synergistic effect was fabricated through drop-casting and drying silver nanowires and graphene films on polydimethylsiloxane substrates and was further successfully applied for continuous monitoring of BP. This strain sensor exhibited ultrahigh sensitivity with a maximum gauge factor of 34357.2 (∼700% sensitivity enhancement over other major sensors), satisfactory response time (∼85 ms), wide strange range (12%), and excellent stability. An interlayer fracture mechanism was proposed to elucidate the working principle of the strain sensor. The real-time BP values can be obtained by analyzing the relationship between the BP and the pulse transit time. To verify our strain sensor for real-time BP monitoring, our strain sensor was compared with a conventional electrocardiogram-photoplethysmograph method and a commercial cuff-based device and showed similar measurement results to BP values from both methods, with only minor differences of 0.693, 0.073, and 0.566 mmHg in the systolic BP, diastolic BP, and mean arterial pressure, respectively. Furthermore, the reliability of the strain sensors was validated by testing 20 human subjects for more than 50 min. This ultrasensitive strain sensor provides a new pathway for continuous and noninvasive BP monitoring.


Subject(s)
Nanowires , Silver , Humans , Nanowires/chemistry , Silver/chemistry , Blood Pressure/physiology , Graphite/chemistry , Blood Pressure Determination/instrumentation , Blood Pressure Determination/methods , Male , Dimethylpolysiloxanes/chemistry , Nanostructures/chemistry , Adult
18.
Nat Commun ; 15(1): 4386, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782953

ABSTRACT

Sialin, a member of the solute carrier 17 (SLC17) transporter family, is unique in its ability to transport not only sialic acid using a pH-driven mechanism, but also transport mono and diacidic neurotransmitters, such as glutamate and N-acetylaspartylglutamate (NAAG), into synaptic vesicles via a membrane potential-driven mechanism. While most transporters utilize one of these mechanisms, the structural basis of how Sialin transports substrates using both remains unclear. Here, we present the cryogenic electron-microscopy structures of human Sialin: apo cytosol-open, apo lumen-open, NAAG-bound, and inhibitor-bound. Our structures show that a positively charged cytosol-open vestibule accommodates either NAAG or the Sialin inhibitor Fmoc-Leu-OH, while its luminal cavity potentially binds sialic acid. Moreover, functional analyses along with molecular dynamics simulations identify key residues in binding sialic acid and NAAG. Thus, our findings uncover the essential conformational states in NAAG and sialic acid transport, demonstrating a working model of SLC17 transporters.


Subject(s)
Cryoelectron Microscopy , Molecular Dynamics Simulation , Humans , N-Acetylneuraminic Acid/metabolism , N-Acetylneuraminic Acid/chemistry , Lysosomes/metabolism , HEK293 Cells , Protein Conformation , Organic Anion Transporters/metabolism , Organic Anion Transporters/chemistry , Organic Anion Transporters/antagonists & inhibitors , Dipeptides/chemistry , Dipeptides/metabolism , Dipeptides/pharmacology , Symporters
19.
Ann Emerg Med ; 84(2): 111-117, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38691067

ABSTRACT

OBJECTIVE: We assessed the concordance of patient-reported race and ethnicity for emergency department (ED) patients compared with what was recorded in the electronic health record. METHODS: We conducted a single-center, prospective, observational study of 744 ED patients (English- and/or Spanish-speaking), asking them to describe their race and ethnicity. We compared the distributions of ethnicity and race between patient-reported and electronic health record data using McNemar's test. We calculated percent agreement and Cohen's kappa, with 95% confidence intervals (CI), for the concordance of patient-reported race and ethnicity with electronic health record data. RESULTS: Of 744 ED patients, 731 participants who completed the survey reported their ethnicity, resulting in 98.2% of electronic health records obtained ethnicities matched self-reported data (kappa = 0.95; 95% CI: 0.92 to 0.98). For those who self-reported as Hispanic, only 92.3% agreement was observed between the self-reported and electronic health record values. For all patients who had race recorded, 85.4% agreement was observed (kappa = 0.75; 95% CI 0.71 to 0.79). High rates of agreement were observed for Black or African American patients (98.7%) and White patients (96.6%), with low rates for those who identified as "More than one race" (22.9%) or "Other" race (1.8%). In the subset of Hispanic patients, low rates of agreement (25.0%) were observed for race (kappa = 0.10; 95% CI 0.01 to 0.19). CONCLUSIONS: Documentation discordance regarding race and ethnicity exists between electronic health records and self-reported data for our ED patients, particularly for ethnically Hispanic and Latino/a patients. Future efforts should focus on ensuring that demographic information in the electronic health record is accurately collected.


Subject(s)
Electronic Health Records , Emergency Service, Hospital , Ethnicity , Racial Groups , Self Report , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Electronic Health Records/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Hispanic or Latino , Prospective Studies , Black or African American , White
20.
Stat Methods Med Res ; 33(6): 966-980, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38592341

ABSTRACT

The Fellegi-Sunter model is a latent class model widely used in probabilistic linkage to identify records that belong to the same entity. Record linkage practitioners typically employ all available matching fields in the model with the premise that more fields convey greater information about the true match status and hence result in improved match performance. In the context of model-based clustering, it is well known that such a premise is incorrect and the inclusion of noisy variables could compromise the clustering. Variable selection procedures have therefore been developed to remove noisy variables. Although these procedures have the potential to improve record matching, they cannot be applied directly due to the ubiquity of the missing data in record linkage applications. In this paper, we modify the stepwise variable selection procedure proposed by Fop, Smart, and Murphy and extend it to account for missing data common in record linkage. Through simulation studies, our proposed method is shown to select the correct set of matching fields across various settings, leading to better-performing algorithms. The improved match performance is also seen in a real-world application. We therefore recommend the use of our proposed selection procedure to identify informative matching fields for probabilistic record linkage algorithms.


Subject(s)
Algorithms , Latent Class Analysis , Medical Record Linkage , Humans , Medical Record Linkage/methods , Models, Statistical , Cluster Analysis , Computer Simulation
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