Endosome associated trafficking regulator 1 promotes tumor growth and invasion of glioblastoma multiforme via inhibiting TNF signaling pathway.

PURPOSE: Endosome associated trafficking regulator 1 (ENTR1) is a novel endosomal protein, which can affect multiple cellular biological behavior by remodeling plasma membrane structures. However, little is known regarding its function and underlying mechanisms in glioblastoma multiforme. METHODS: Expression profile and clinical signature were obtained from The Public Database of human tumor. Immunohistochemical staining and western blotting assays were used to measure ENTR1 expression level. Human primary GBM tumor cells and human GBM cell lines A172, U87 and U251 were used to clarify the precise role of ENTR1. CCK-8 assays, wound healing and transwell invasion assays were designed to investigate cell viability, invasion and migration of GBM cells, respectively. Underlying molecular mechanisms of ENTR1 were determined via RNA-seq analysis. Tumor formation assay was used to validate the influence of ENTR1 in vivo. RESULTS: Compared with normal brain tissues, ENTR1 was highly expressed in gliomas and correlated with malignant grades of gliomas and poor overall survival time. The proliferation and invasion of GBM cells could be weaken and the sensitivity to temozolomide (TMZ) chemotherapy increased after knocking down ENTR1. Overexpression of ENTR1 could reverse this effect. RNA-seq analysis showed that tumor necrosis factor (TNF) signaling pathway might be a putative regulatory target of ENTR1. Tumor formation assay validated that ENTR1 was a significant factor in tumor growth. CONCLUSION: Our results indicated that ENTR1 played an important role in cell proliferation, invasion and chemotherapeutic sensitivity of GBM, suggesting that ENTR1 might be a novel prognostic marker and significant therapeutic target for GBM.

Integrating Olefin Carboamination and Hofmann-Löffler-Freytag Reaction by Radical Deconstruction of Hydrazonyl N-N Bond.

As a type of elementary organic compounds containing N-N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2-retention and N2-removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N2-moiety of hydrazone by a radical facilitated N-N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann-Löffler-Freytag reaction by the reaction of N-homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino-N migration and H-atom transfer. Consequently, a series of structurally significant ϵ-N-sulphonamide-α,α-difluoro-γ-amino acid esters are efficiently produced via continuous C-C bond and dual C-N bonds forging.

Association between relative muscle strength and hypertension in middle-aged and older Chinese adults.

BACKGROUND: The association between muscle defects and hypertension is well-established. However, the absence of pertinent and uncomplicated clinical indicators presents a challenge. Relative muscle strength (RMS) may offer a viable indicator. This study aimed to explore the association between RMS and hypertension. METHODS: A total of 12,720 individuals aged ≥ 45 years from the 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. Grip strength was recorded and appendicular skeletal muscle mass (ASM) was estimated using a validated mathematical formula. The RMS was calculated as the ratio of grip strength to ASM. Hypertension was determined based on previous diagnosis, history of hypertension medication use, and current blood pressure. Logistic regression models were employed to investigate the relationship between RMS and hypertension. RESULTS: The prevalence of hypertension was 41.7% (5,307/12,720 patients). RMS was negatively correlated with hypertension with an OR (95% CI) of 0.68 (0.59-0.79) for males, 0.81 (0.73-0.90) for females, and 0.78 (0.72-0.85) for the entire population after adjusting for related covariates including age, education, marital history, smoking history, drinking history, diabetes, hyperlipidemia, and obesity. The trend test showed a linear association among males, females, or the entire population. Stratified analysis showed a consistent negative correlation between RMS and hypertension. CONCLUSIONS: Higher RMS is an independent protective factor against hypertension and efforts to promote RMS may be beneficial for the prevention and management of hypertension.

Hip effusion/synovitis influences results after multiple drilling core decompression for bone marrow edema syndrome of hip.

BACKGROUND: At present, it is not known whether hip effusion/synovitis affects the therapeutic effect of multiple drilling core decompression (MDCD) in patients with bone marrow edema syndrome of hip (BMESH). The aims were to assess hip effusion/synovitis and its relationship with results of MDCD in patients with BMESH. METHODS: The data of undergoing arthroscopic-assisted MDCD for treatment of BMESH with hip effusion/synovitis by one surgeon were retrospectively reviewed from the associated medical records at the Affiliated Hospital of Zunyi Medical University (2016-2019). Seven patients (9 hips) participated in this study. Patients were followed up at 1, 2, 3, 6, 12 and 24 months. Data included demographics and clinical outcomes. The pre- and postoperative pain and functional outcomes were measured with the visual analogue scale (VAS), Harris Hip Score (HHS), Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), International Hip Outcome Tool-12 (iHOT-12) and range of motion (ROM). RESULTS: Seven patients (9 hips) were followed up. Disappearance of hip pain immediately obtained at rest after surgery. All of 7 patients returned to their former activity level at postoperative 3 months, bone marrow edema had disappeared on Magnetic Resonance Imaging (MRI). The VAS, HHS, HOS-ADL, iHOT-12, and ROM at postoperative 1 month had a significant difference (P < 0.05) compared with preoperative. It was also statistically significant (P < 0.05) when compared with other time points. At the final follow-up, all patients had no limited ROM, which was symmetrical with the contralateral of hip joint. Hip effusion/synovitis were observed in 9 hips. Labral tears, cartilage fissure, and loose bodies were observed in 1 hip, respectively. Kirschner wire tracks bleeding occurred in 1 hip. No other complications occurred. CONCLUSIONS: Hip effusion/synovitis could affect the clinical outcomes after MDCD in patients with BMESH. Arthroscopic procedure of hip effusion/synovitis can shorten postoperative pain relief time, disappearance time of bone marrow edema on MRI. It can simultaneously diagnose and treat other concomitant intraarticular pathologies, and be a safe operation with fewer complications.

Dendrobine Alleviates Cellular Senescence and Osteoarthritis via the ROS/NF-κB Axis.

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1ß-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1ß-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA.

Quantifying Photoinduced Polaronic Distortions in Inorganic Lead Halide Perovskite Nanocrystals.

The development of next-generation perovskite-based optoelectronic devices relies critically on the understanding of the interaction between charge carriers and the polar lattice in out-of-equilibrium conditions. While it has become increasingly evident for CsPbBr3 perovskites that the Pb-Br framework flexibility plays a key role in their light-activated functionality, the corresponding local structural rearrangement has not yet been unambiguously identified. In this work, we demonstrate that the photoinduced lattice changes in the system are due to a specific polaronic distortion, associated with the activation of a longitudinal optical phonon mode at 18 meV by electron-phonon coupling, and we quantify the associated structural changes with atomic-level precision. Key to this achievement is the combination of time-resolved and temperature-dependent studies at Br K and Pb L3 X-ray absorption edges with refined ab initio simulations, which fully account for the screened core-hole final state effects on the X-ray absorption spectra. From the temporal kinetics, we show that carrier recombination reversibly unlocks the structural deformation at both Br and Pb sites. The comparison with the temperature-dependent XAS results rules out thermal effects as the primary source of distortion of the Pb-Br bonding motif during photoexcitation. Our work provides a comprehensive description of the CsPbBr3 perovskites' photophysics, offering novel insights on the light-induced response of the system and its exceptional optoelectronic properties.

Potential effects of allyl isothiocyanate on inhibiting cellular proliferation and inducing apoptotic pathway in human cisplatin-resistant oral cancer cells.

BACKGROUND/PURPOSE: Cisplatin-resistant oral cancer is clinically difficult to manage and the dose-dependent toxicities of cisplatin has been widely concerned. Allyl isothiocyanate (AITC), known as mustard oil, is a plant-derived compound abundant in cruciferous vegetables. It is reported to have anti-cancer potential as a natural dietary chemopreventive compound against a variety of cancers, but the effect of AITC on cisplatin-resistant cancer cells is still little-known. METHODS: Human CAL27-cisplatin-resistant oral cancer cells (CAR cells) were examined to investigate the antitumor properties of AITC. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, IncuCyte™ S3 cell proliferation assay, 4',6-diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as well as Western blot analysis were deployed. RESULTS: AITC decreased CAR cell viability, induced cell death of CAR cells and inhibited the confluences of cultured CAR cells. When CAR cells were treated with AITC, activation of caspase-3 and caspase-9 by AITC was observed and could be reversed by Z-VAD-fmk (pan-caspase inhibitor). Furthermore, the protein expressions of phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) were suppressed in AITC-treated CAR cells, whereas protein expressions of Bax, cytochrome c, Apaf-1, cleaved caspase-3, and cleaved caspase-9 were upregulated in AITC-treated CAR cells. CONCLUSION: AITC can inhibit Akt/mTOR proliferation signaling and promote mitochondria-dependent apoptotic pathway through AITC-enhanced activities of caspase-3 and caspase-9 in CAR cells.

Calpain suppresses cell growth and invasion of glioblastoma multiforme by producing the cleavage of filamin A.

BACKGROUND: Filamin A is the most widely expressed isoform of filamin in mammalian tissues. It can be hydrolyzed by Calpain, producing a 90-kDa carboxyl-terminal fragment (ABP90). Calpeptin is a chemical inhibitor of Calpain, which can inhibit this effect. It has been shown that ABP90 acts as a transcription factor which is involved in mediating cell signaling. However, the significance of ABP90 and its clinical signature with underlying mechanisms have not been well studied in glioblastoma multiforme (GBM). METHODS: ABP90 protein was measured in 36 glioma patients by Western blot. Human GBM cell lines U87 and A172 were used to clarify the precise role of ABP90. CCK-8 assay was used to analyze the cell viability. Transwell invasion assay and wound healing assay were used to analyze the migration and invasion. Expression of matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot. RESULTS: ABP90 protein expression was lower in GBM tissues. The patients with low ABP90 protein expression had a shorter OS time (p = 0.046). After being treated with Calpain, the expression of ABP90 was upregulated, which led to a decline of cell viability, enhanced the efficacy of temozolomide and restrained the cell invasion. Calpeptin could inhibit the effect. The mechanism might be involved in the balance of MMP2/TIMP2. CONCLUSIONS: Our present data suggest that ABP90 expression is a significant prognostic factor and may play an important role in cell viability, chemotherapeutic sensitivity and invasion of GBM.

Micro-focused MHz pink beam for time-resolved X-ray emission spectroscopy.

The full radiation from the first harmonic of a synchrotron undulator (between 5 and 12 keV) at the Advanced Photon Source is microfocused using a stack of beryllium compound refractive lenses onto a fast-moving liquid jet and overlapped with a high-repetition-rate optical laser. This micro-focused geometry is used to perform efficient nonresonant X-ray emission spectroscopy on transient species using a dispersive spectrometer geometry. The overall usable flux achieved on target is above 1015 photons s-1 at 8 keV, enabling photoexcited systems in the liquid phase to be tracked with time resolutions from tens of picoseconds to microseconds, and using the full emission spectrum, including the weak valence-to-core signal that is sensitive to chemically relevant electronic properties.

SMAD6 is frequently mutated in nonsyndromic radioulnar synostosis.

PURPOSE: Radioulnar synostosis (RUS) can be syndromic or nonsyndromic. The genetic basis for several RUS syndromes have been reported. However, the genetic cause of nonsyndromic RUS (nsRUS) remains unknown. METHODS: We performed Giemsa (GTG) banding, Sanger sequencing, and exome sequencing on patients (n = 140) and families (n = 11) who suffered from RUS. RESULTS: GTG banding identified 10% RUS sporadic cases affected by sex chromosome aneuploidy. Sanger sequencing on candidate genes revealed noggin (NOG) rarely mutated in nsRUS. Exome sequencing identified 16 loss-of-function (LOF) and 6 missense variants (minor allele frequency [MAF] < 0.0001) in 22/117 nsRUS sporadic patients. Genetic association analysis found a significant association between SMAD6-LOF variants and nsRUS risk (odds ratio [OR] = 430, 95% confidence interval [CI]: 238-780, P < 0.000001). SMAD6 mutated in nsRUS was further confirmed by direct Sanger sequencing of SMAD6-coding regions on other unrelated cohorts of nsRUS cases or families. In summary, we detected 27 SMAD6 rare variants in nsRUS, most of which were LOF variants, 4 were de novo, and 3 were transmitted in families with autosomal dominant inheritance. CONCLUSION: As an intracellular bone morphogenetic protein (BMP) antagonist gene, SMAD6 is frequently mutated in nsRUS. NOG, which encodes an extracellular BMP antagonist, is rarely mutated in nsRUS. This work is the first genetic study on nsRUS.

Correction: SMAD6 is frequently mutated in nonsyndromic radioulnar synostosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Elucidation of the photoaquation reaction mechanism in ferrous hexacyanide using synchrotron x-rays with sub-pulse-duration sensitivity.

Ligand substitution reactions are common in solvated transition metal complexes, and harnessing them through initiation with light promises interesting practical applications, driving interest in new means of probing their mechanisms. Using a combination of time-resolved x-ray absorption spectroscopy and hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations and x-ray absorption near-edge spectroscopy calculations, we elucidate the mechanism of photoaquation in the model system iron(ii) hexacyanide, where UV excitation results in the exchange of a CN- ligand with a water molecule from the solvent. We take advantage of the high flux and stability of synchrotron x-rays to capture high precision x-ray absorption spectra that allow us to overcome the usual limitation of the relatively long x-ray pulses and extract the spectrum of the short-lived intermediate pentacoordinated species. Additionally, we determine its lifetime to be 19 (±5) ps. The QM/MM simulations support our experimental findings and explain the ∼20 ps time scale for aquation as involving interconversion between the square pyramidal (SP) and trigonal bipyramidal pentacoordinated geometries, with aquation being only active in the SP configuration.

XRCC2 mutation causes meiotic arrest, azoospermia and infertility.

BACKGROUND: Meiotic homologous recombination (HR) plays an essential role in gametogenesis. In most eukaryotes, meiotic HR is mediated by two recombinase systems: ubiquitous RAD51 and meiosis-specific DMC1. In the RAD51-mediated HR system, RAD51 and five RAD51 paralogues are essential for normal RAD51 function, but the role of RAD51 in human meiosis is unclear. The knockout of Rad51 or any Rad51 paralogue in mice exhibits embryonic lethality. We investigated a family with meiotic arrest, azoospermia and infertility but without other abnormalities. METHODS: Homozygosity mapping and whole-exome sequencing were performed in a consanguineous family. An animal model carrying a related mutation was created by using a CRISPR/Cas9 system. RESULTS: We identified a 1 bp homozygous substitution (c.41T>C/p.Leu14Pro) on a RAD51 paralogue, namely, XRCC2, in the consanguineous family. We did not detect any XRCC2 recessive mutation in a cohort of 127 males with non-obstructive-azoospermia. Knockin mice with Xrcc2-c.T41C/p.Leu14Pro mutation were generated successfully by the CRISPR/Cas9 method. The homozygotes survived and exhibited meiotic arrest, azoospermia, premature ovarian failure and infertility. CONCLUSION: A XRCC2 recessive mutation causing meiotic arrest and infertility in humans was duplicated with knockin mice. Our results revealed a new Mendelian hereditary entity and provided an experimental model of RAD51-HR gene defect in mammalian meiosis.

Improving the prediction of the trabecular bone microarchitectural parameters using dental cone-beam computed tomography.

BACKGROUND: In this study, we explored how various preprocessing approaches can be employed to enhance the capability of dental CBCT to accurately estimate trabecular bone microarchitectural parameters. METHODS: In total, 30 bovine vertebrae cancellous bone specimens were used for in study. Voxel resolution 18-µm micro-computed tomography (micro-CT) and 100-µm dental CBCT were used to scan each specimen. Micro-CT images were used to calculate trabecular bone microarchitectural parameters; the results were set as the gold standard. Subsequently, before the dental CBCT images were converted into binary images to calculate trabecular bone microarchitectural parameters, three preprocessing approaches were used to process the dental CBCT images. For Group 1, no preprocessing approach was applied. For Group 2, images were sharpened and despeckable noises were removed. For Group 3, the function of local thresholding was added to Group 2 to form Group 3. For Group 4, the air pixels was removed from Group 3 to form Group 4. Subsequently, all images were imported into a software package to estimate trabecular bone microarchitectural parameters (bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN), and trabecular separation (TbSp)). Finally, a paired t-test and a Pearson correlation test were performed to compare the capability of micro-CT with the capability of dental CBCT for estimating trabecular bone microarchitectural parameters. RESULTS: Regardless of whether dental CBCT images underwent image preprocessing (Groups 1 to 4), the four trabecular bone microarchitectural parameters measured using dental CBCT images were significantly different from those measured using micro-CT images. However, after three image preprocessing approaches were applied to the dental CBCT images (Group 4), the BV/TV obtained using dental CBCT was highly positively correlated with that obtained using micro-CT (r = 0.87, p < 0.001); the correlation coefficient was greater than that of Group 1 (r = -0.15, p = 0.412), Group 2 (r = 0.16, p = 0.386), and Group 3 (r = 0.47, p = 0.006). After dental CBCT images underwent image preprocessing, the efficacy of using dental CBCT for estimating TbN and TbSp was enhanced. CONCLUSIONS: Image preprocessing approaches can be used to enhance the efficacy of using dental CBCT for predicting trabecular bone microarchitectural parameters.

A new species of Liquidambar (Altingiaceae) from the late Eocene of South China.

A new fossil leaf species, Liquidambar bella (Altingiaceae), is described from the lower part of the Eocene Huangniuling Formation, Maoming Basin, South China. Suprabasal venation in the fossil lobed Liquidambar leaves is reported for the first time. The new species provides additional palaeobotanical evidence on the morphological variability of this genus supporting the idea of combining the genera Liquidambar, Semiliquidambar and Altingia into the single genus Liquidambar as proposed based on molecular markers.

Effects of mineral trioxide aggregate and bioceramics on macrophage differentiation and polarization in vitro.

BACKGROUND/PURPOSE: Mineral trioxide aggregate (Pro-Root MTA, PR-MTA) and bioceramics (iRoot® SP Injectable Root Canal Sealer, iR-BC) are used for making apical plugs used in apexification, repairing root perforations during root canal therapy, and treating internal root resorption. The purpose of the present in vitro study was to compare the biological effects of PR-MTA- and iR-BC-based dental sealers in the mouse macrophage cell line RAW 264.7. METHODS: Cytotoxicity and cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell hemocytometer, respectively. Protein expression of biomarkers of cell proliferation, autophagy, and osteoclast differentiation was determined by western blotting. Pro-inflammatory gene expression was examined using quantitative reverse transcription-PCR. RESULTS: PR-MTA induced cytotoxicity in RAW 264.7 cells in a dose-dependent manner, and iR-BC was more cytotoxic than PR-MTA. Low-dose and short-term treatments of both PR-MTA and iR-BC induced RAW 264.7 cell proliferation. PR-MTA induced autophagy, whereas iR-BC did not. Neither PR-MTA nor iR-BC induced osteoclastogenesis. Pro-inflammatory genes were activated by both materials. However, the expression of inducible nitric oxide synthase (iNOS) mRNA was upregulated by iR-BC treatment, but not by PR-MTA treatment. CONCLUSION: Overall, dental PR-MTA and iR-BC induced pro-inflammatory genes but did not induce osteoclastogenesis in macrophages. PR-MTA and iR-BC induced M2 and M1 polarization, respectively, of RAW 264.7 cells.

The survey of tinea capitis and scalp dermatophyte carriage in nursing home residents.

Tinea capitis is a contagious dermatophyte infection of scalp and associated hairs. On the other hand, asymptomatic carriage is a status of positive dermatophyte scalp culture, but without signs or symptoms of tinea capitis, and no evidence of hair shaft invasion confirmed by direct microscopy. Tinea capitis and asymptomatic carriage mostly occur in children, but adult females are becoming another population in recent decades. In this study, we focused on the prevalence and related fungi of tinea capitis and asymptomatic carriage in elderly by the shampoo brush method, as well as the source of transmission, in 10 nursing home residents. Two hundred and thirteen residents were screened, and 186 isolates were identified, of which only three were dermatophytes (1.4%). The scalp dermatophyte isolates were identified as Trichophyton rubrum by morphological characters and sequences comparisons in all three cases. After revisiting, these cases were proved to be asymptomatic carriers by negative microscopic and culture examination; however, two cases were found to have concurrent tinea pedis and onychomycosis, which were identified as T. rubrum and Trichophyton interdigitale. The source of the T. rubrum scalp carriage may come from tinea elsewhere on the body of the same subject or from other people in the same institute. Finding and treating the source of carriage, as well as treating scalp carriage patients according to the colony counts, may help prevent disease spreading.

Prevalence of primate and interdental spaces for primary dentition in 3- to 6-year-old children in Taiwan.

BACKGROUND/PURPOSE: Spaced primary dentition plays a critical role in the eruption of permanent teeth and the establishment of ideal occlusion. A lack of these spaces in deciduous dentition may result in disproportionate jaw and tooth sizes. Additionally, spaced primary dentition is significantly affected by ethnic factors. However, few of these studies have been conducted in Asia. The purpose of this study was to investigate the prevalence of spaced primary dentition in Taiwan. METHODS: One hundred and forty-seven 3- to 6-year-old Taiwanese children (58 girls and 89 boys) were recruited for a cross-sectional study. Primate and interdental spaces were recorded by intraoral photos. The prevalence of spaced dentition was evaluated. The interpersonal agreement of spaced dentition between the upper and lower arches was also assessed. RESULTS: Most of the subjects had spaced primary dentition. The prevalence of primate space was 83.7% in the upper arch and 61.2% in the lower arch, whereas the prevalence of interdental space was 44.2% in the upper arch and 53.1% in the lower arch. The prevalence rates of interdental space and upper primate space were significantly higher in boys than in girls. Interdental spaces of the lower arch increased with age. CONCLUSION: Ethnic factors can affect the ratio of spaced dentition. Most of the 3- to 6-year-old Taiwanese children have spaced dentition. The boys have higher incidence of spaced dentition than the girls. Furthermore, primate space is more frequently found in the upper arch than in the lower arch, whereas interdental space is reversed.

Avoiding Obsolescence in Mobile Health: Experiences in Designing a Mobile Support System for Complicated Documentation at Long-term Care Facilities.

This study examined staff perceptions of planned obsolescence during a transition from old to new handheld devices for long-term mobile healthcare. Questionnaires based on the technology acceptance model were used to evaluate perceived ease of use and usefulness. This study recruited 120 staff from 26 long-term care facilities who used the old device and 86 staff from nine of the 26 original facilities who used the new device. Although the new devices with advanced features scored significantly higher in acceptance ratings, users still expressed high acceptance of, satisfaction with, and willingness to use the old device, which featured an effective and carefully designed user interface. Usability design plays an essential role in preventing the obsolescence of mobile handheld technology.