Combination of scavenger receptor-A with anti-cyclic citrullinated peptide antibody for the diagnosis of rheumatoid arthritis.

OBJECTIVES: The routine biomarkers for rheumatoid arthritis (RA), including anticyclic citrullinated peptide antibody (anti-CCP), rheumatoid factor (RF), immunoglobulin M (IgM), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) have limited sensitivity and specificity. Scavenger receptor-A (SR-A) is a novel RA biomarker identified by our group recently, especially for seronegative RA. Here, we performed a large-scale multicentre study to further assess the diagnostic value of SR-A in combination with other biomarkers for RA. METHODS: The performance of SR-A in combination with other biomarkers for RA diagnosis was first revealed by a pilot study, and was further elucidated by a large-scale multicentre study. A total of 1129 individuals from 3 cohorts were recruited in the study, including RA patients, healthy controls, and patients with other common rheumatic diseases. Diagnostic properties were evaluated by the covariate-adjusted receiver-operating characteristic (AROC) curve, sensitivity, specificity and clinical association, respectively. RESULTS: Large-scale multicentre analysis showed that SR-A and anti-CCP dual combination was the optimal method for RA diagnosis, increasing the sensitivity of anti-CCP by 13% (87% vs 74%) while maintaining a specificity of 90%. In early RA patients, SR-A and anti-CCP dual combination also showed promising diagnostic value, increasing the sensitivity of anti-CCP by 7% (79% vs 72%) while maintaining a specificity of 94%. Moreover, SR-A and anti-CCP dual combination was correlated with ESR, IgM, and autoantibodies of RA patients, further revealing its clinical significance. CONCLUSION: SR-A and anti-CCP dual combination could potentially improve early diagnosis of RA, thus improving the prognosis and reducing mortality.

Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study.

BACKGROUND: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

Overexpression of Fgf18 in cranial neural crest cells recapitulates Pierre Robin sequence in mice.

The pivotal role of FGF18 in the regulation of craniofacial and skeletal development has been well established. Previous studies have demonstrated that mice with deficiency in Fgf18 exhibit severe craniofacial dysplasia. Recent clinical reports have revealed that the duplication of chromosome 5q32-35.3, which encompasses the Fgf18 gene, can lead to cranial bone dysplasia and congenital craniosynostosis, implicating the consequence of possible overdosed FGF18 signaling. This study aimed to test the effects of augmented FGF18 signaling by specifically overexpressing the Fgf18 gene in cranial neural crest cells using the Wnt1-Cre;pMes-Fgf18 mouse model. The results showed that overexpression of Fgf18 leads to craniofacial abnormalities in mice similar to the Pierre Robin sequence in humans, including abnormal tongue morphology, micrognathia, and cleft palate. Further examination revealed that elevated levels of Fgf18 activated the Akt and Erk signaling pathways, leading to an increase in the proliferation level of tongue tendon cells and alterations in the contraction pattern of the genioglossus muscle. Additionally, we observed that excessive FGF18 signaling contributed to the reduction in the length of Meckel's cartilage and disrupted the development of condylar cartilage, ultimately resulting in mandibular defects. These anomalies involve changes in several downstream signals, including Runx2, p21, Akt, Erk, p38, Wnt, and Ihh. This study highlights the crucial role of maintaining the balance of endogenous FGF18 signaling for proper craniofacial development and offers insights into potential formation mechanisms of the Pierre Robin sequence.

6-O-angeloylplenolin inhibits osteoclastogenesis in vitro via suppressing c-Src/NF-κB/NFATc1 pathways and ameliorates bone resorption in collagen-induced arthritis mouse model.

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.

Associations Between Depression Symptom Burden and Delirium Risk: A Prospective Cohort Study.

Background and Objectives: Delirium and depression are prevalent in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer's disease, functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older hospitalized individuals. Research Design and Methods: A total of 319 141 UK Biobank participants between 2006 and 2010 (mean age 58 years [range 37-74, SD = 8], 54% women) reported frequency (0-3) of 4 depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks prior to initial assessment visit and aggregated into a depressive symptom burden score (0-12). New-onset delirium was obtained from hospitalization records during 12 years of median follow-up. 40 451 (mean age 57 ±â€…8; range 40-74 years) had repeat assessment on average 8 years after their first visit. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium. Results: A total of 5 753 (15 per 1 000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1-2, hazards ratio, HR = 1.16, [95% confidence interval (CI): 1.08-1.25], p < .001), modest (scores 3-5, 1.30 [CI: 1.19-1.43], p < .001), and severe (scores ≥ 5, 1.38 [CI: 1.24-1.55], p < .001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across settings (eg, surgical, medical, or critical care) and specialty (eg, neuropsychiatric, cardiorespiratory, or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03-1.88], p = .03) independent of baseline depression burden. The association was strongest in those over 65 years at baseline (p for interaction <.001). Discussion and Implications: Depression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may aid delirium prevention.

Enhanced recovery after surgery program focusing on chest tube management improves surgical recovery after video-assisted thoracoscopic surgery.

OBJECTIVE: Chest drainage is a standard procedure in thoracoscopic surgery for lung cancer. However, chest tube placement may deteriorate the ventilation capacity and increase difficulty of postoperative management of patients. The study investigated on the effects of enhanced recovery after surgery (ERAS) program focusing on chest tube management on surgical recovery of lung cancer patients. METHODS: The study population consisted of 60 patients undergoing video-assisted thoracoscopic surgery (VATS) after implementation of ERAS program and another group of 60 patients undergoing VATS before implementation of ERAS program. RESULTS: The mean time of first food intake was 12.9 h required for the ERAS group, which was significantly shorter than 18.4 h required for the control group (p < 0.0001). The mean time of out-of-bed activity was 14.2 h taken for the ERAS group, which was notably shorter than 22.8 h taken for the control group (p < 0.0001). The duration of chest tube placement was 68.6 h in the ERAS group, which was remarkably shorter than 92.8 h in the control group (p < 0.0001). The rate overall postoperative complications were notably lower in the ERAS group than in the control group (p = 0.018). The visual analogue score (VAS) scores on the second postoperative day exhibited significant differences between the ERAS group and the control group (p = 0.017). The patients in the ERAS group had a shorter hospitalization stay than those in the control group (p < 0.0001). CONCLUSION: The study suggests the ERAS program focusing on chest tube management could improve surgical recovery, remove patient chest tube earlier, and relieve patient pain after VATS.

Spatially resolved current density distribution in GaN-based flip-chip green mini-LEDs by microscopic hyperspectral imaging and modified two-level modeling.

A modified two-level model is proposed to study the spatially resolved current density distribution of GaN-based green miniaturized light-emitting diodes (mini-LEDs), combining with microscopic hyperspectral imaging. We found that the spatially resolved current density distribution reveals both the radiative and non-radiative recombination mappings, which can also be provided separately by this model. In addition, higher current density is not necessarily correlated with higher photon emission, especially for the regions around the electrode edges, where the high current density suggests current crowding and defect-related non-radiative recombination. The current density distribution of mini-LEDs is further verified by the laser-beam-induced current (LBIC) and the spatially resolved mappings of peak wavelength and FWHM. The modified two-level model also offers radiative/non-radiative mappings and is proved to be beneficial to determine the micro-zone current density distribution and to reveal the intrinsic radiative/non-radiative recombination mechanism of mini-LEDs.

Attributable mortality of ARDS among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Both sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis. METHODS: The data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis. RESULTS: 2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS's overall 30-day attributable mortality was 11.9% (95% CI 7.5-16.3%, p < 0.001). Subgroup analysis showed that the 30-day attributable mortality of mild, moderate, and severe ARDS was 10.5% (95% CI 4.0-16.8%, p < 0.001), 11.6% (95% CI 4.7-18.4%, p < 0.001) and 18.1% (95% CI 4.5-30.9%, p = 0.006), respectively. ARDS was an independent risk factor for 30-day mortality, with adjusted hazard ratios of 1.30 (95% CI 1.03-1.64, p = 0.027), 1.49 (95% CI 1.20-1.85, p < 0.001), and 1.95 (95% CI 1.51-2.52, p < 0.001) for mild, moderate, and severe ARDS, respectively. CONCLUSIONS: The overall 30-day attributable mortality of ARDS among critically ill patients with sepsis was 11.9%. Compared with mild and moderate ARDS, severe ARDS contributed more to death. ARDS was significantly associated with an increase in the 30-day mortality.

Whole Genome Duplication Events Likely Contributed to the Aquatic Adaptive Evolution of Parkerioideae.

As the only aquatic lineage of Pteridaceae, Parkerioideae is distinct from many xeric-adapted species of the family and consists of the freshwater Ceratopteris species and the only mangrove ferns from the genus Acrostichum. Previous studies have shown that whole genome duplication (WGD) has occurred in Parkerioideae at least once and may have played a role in their adaptive evolution; however, more in-depth research regarding this is still required. In this study, comparative and evolutionary transcriptomics analyses were carried out to identify WGDs and explore their roles in the environmental adaptation of Parkerioideae. Three putative WGD events were identified within Parkerioideae, two of which were specific to Ceratopteris and Acrostichum, respectively. The functional enrichment analysis indicated that the lineage-specific WGD events have played a role in the adaptation of Parkerioideae to the low oxygen concentrations of aquatic habitats, as well as different aquatic environments of Ceratopteris and Acrostichum, such as the adaptation of Ceratopteris to reduced light levels and the adaptation of Acrostichum to high salinity. Positive selection analysis further provided evidence that the putative WGD events may have facilitated the adaptation of Parkerioideae to changes in habitat. Moreover, the gene family analysis indicated that the plasma membrane H+-ATPase (AHA), vacuolar H+-ATPase (VHA), and suppressor of K+ transport growth defect 1 (SKD1) may have been involved in the high salinity adaptation of Acrostichum. Our study provides new insights into the evolution and adaptations of Parkerioideae in different aquatic environments.

The Effect of Time Monitoring on the Development of Time-Based Prospective Memory among Children Aged 7-11 Years Old.

Time-based prospective memory (TBPM) refers to the ability of an individual to successfully execute an expected plan in the future at a certain time point or after a definite period of time. This study investigated the potential developmental mechanism of school-age children's TBPM ability from the perspective of time monitoring. Experiment 1 used a between-subjects design of three ages (7, 9, 11) × two TBPM types (time point, time period) to investigate the trends and characteristics of two types of TBPM in children aged 7-11 years old. Experiment 2 used a between-subjects design of three ages (7, 9, 11) × two monitoring conditions (free monitoring, fixed monitoring) to investigate differences in two types of TBPM and monitoring behavior among school-age children under different monitoring conditions. These results showed that the age effect of TBPM was affected by the type of prospective memory (PM) and that time-point PM performance was significantly better than time-period PM performance among school-age children. These findings indicate that clear and definite external cues are helpful for school-age children in performing TBPM tasks. Moreover, there were significant differences found in the TBPM performance of school-age children under different time monitoring conditions. The performance of older children was significantly better than that of younger children. This indicates that older children can better allocate their attentional resources and use time monitoring strategies to improve their performance in PM tasks. Accordingly, this study showed that the TBPM ability of 7- to 11-year-old children is in continuous development and that the time monitoring behavior in the TBPM task is affected by task type and monitoring conditions.

The structure-activity relationship of copper hydride nanoclusters in hydrogenation and reduction reactions.

Copper hydrides are highly active catalysts in hydrogenation reactions and reduction processes. Three Stryker-type copper hydride nanoclusters (NCs), [(TPP)CuH]6, [(TCP)CuH]6 and [(TOP)CuH]6 (TPP = triphenylphosphine, TCP = tricyclohexylphosphine and TOP = tri-n-octylphosphine), were synthesized in this study. Due to variations in the electron-donating properties of the phosphine ligands, the UV-visible absorption spectra of the three NCs exhibited notable distinctions. The influence of the phosphine ligands on the effectiveness of the NCs as hydride sources in hydrogenation processes, as well as on the applicability as homogeneous catalysts for reduction reactions, was systematically studied. Due to the highest electron-donating properties of the TOP ligand, [(TOP)CuH]6 was found to exhibit superior performance in both hydrogenation reactions and catalytic reduction reactions. Moreover, these hydrophobic NCs worked well as heterogeneous catalysts in the reduction of 4-nitrophenol.

Association between the levels of urinary cell cycle biomarkers and non-recovery of renal function among critically ill geriatric patients with acute kidney injury.

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2-3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p < 0.001), with the optimal threshold set at 0.81 (ng/mL)2/1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score.

Biomass chitosan/sodium alginate colorimetric imprinting hydrogels with integrated capture and visualization detection for cadmium(II).

Due to Cd(II) with highly toxic, persistent and bioaccumulative, the discharge of it into the environment brings serious pollution. Developing strategies that are efficient, low-cost, pollution-free and specific to removing Cd(II) from wastewater is therefore of great urgency and prime importance. A novel chitosan/sodium alginate ionic imprinting(IICA) hydrogels with specific adsorption capacity for Cd(II) was prepared through freeze-thaw and ion imprinting, and finally the colorimetric sensor (IICAS) was prepared via introducing Rhodamine B(RhB) and Victoria blue(VBB) by immersion to achieve visual detection of Cd(II). The IICA hydrogels with imprinted hole structure had higher adsorption capacity and better specific selectivity for Cd(II). As well as internal diffusion, coordination, ion exchange, and hydrogen bonding influenced the adsorption rate. Moreover, the IICAS exhibited good selective detection ability and linearity for Cd(II) with the fitted correlation coefficient (R2) = 0.98, limit of detection (LOD) = 35 nmol/L. Combined with the smartphone platform, portable and quantitative detection of Cd(II) can be achieved, Within the 0-100 mg/L range, R2 remained 0.94, and LOD was 75 nmol/L. This strategy of preparing a novel whole biomass IICAS integrating capture and visual detection provides a new insight into the construction of a promising candidate sensor for the removal and detection of Cd(II).

Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-α in rheumatoid arthritis.

OBJECTIVES: B10 and B10pro cells suppress immune responses via secreting interleukin (IL)-10. However, their regulators and underlying mechanisms, especially in human autoimmune diseases, are elusive. This study aimed to address these questions in rheumatoid arthritis (RA), one of the most common highly disabling autoimmune diseases. METHODS: The frequencies and functions of B10 and B10pro cells in healthy individuals and patients with RA were first analysed. The effects of proinflammatory cytokines, particularly tumour necrosis factor (TNF)-α on the quantity, stability and pathogenic phenotype of these cells, were then assessed in patients with RA before and after anti-TNF therapy. The underlying mechanisms were further investigated by scRNA-seq database reanalysis, transcriptome sequencing, TNF-α-/- and B cell-specific SHIP-1-/- mouse disease model studies. RESULTS: TNF-α was a key determinant for B10 cells. TNF-α elicited the proinflammatory feature of B10 and B10pro cells by downregulating IL-10, and upregulating interferon-γ and IL-17A. In patients with RA, B10 and B10pro cells were impaired with exacerbated proinflammatory phenotype, while anti-TNF therapy potently restored their frequencies and immunosuppressive functions, consistent with the increased B10 cells in TNF-α-/- mice. Mechanistically, TNF-α diminished B10 and B10pro cells by inhibiting their glycolysis and proliferation. TNF-α also regulated the phosphatidylinositol phosphate signalling of B10 and B10pro cells and dampened the expression of SHIP-1, a dominant phosphatidylinositol phosphatase regulator of these cells. CONCLUSIONS: TNF-α provoked the proinflammatory phenotype of B10 and B10pro cells by disturbing SHIP-1 in RA, contributing to the disease development. Reinstating the immunosuppressive property of B10 and B10pro cells might represent novel therapeutic approaches for RA.

Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: preservation of GPX4 via the cycling-selenium storage.

Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by the SELENOP gene) is a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP is thought to be associated with ferroptosis sensitivity through the induction of glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, to elucidate the role of SeP in GBM, we analyzed its expression in GBM patients and found that SeP expression levels were significantly higher when compared to healthy subjects. Knock down of SeP in cultured GBM cells resulted in a decrease in GPX1 and GPX4 protein levels. Under the same conditions, cell death caused by RSL3, a ferroptosis inducer, was enhanced, however this enhancement was canceled by supplementation of selenite. These results indicate that SeP expression contributes to preserving GPX and selenium levels in an autocrine/paracrine manner, i.e., SeP regulates a dynamic cycling-selenium storage system in GBM. We also confirmed the role of SeP expression in ferroptosis sensitivity using patient-derived primary GBM cells. These findings indicate that expression of SeP in GBM can be a significant therapeutic target to overcome anticancer drug resistance.

Methotrexate-loaded hyaluronan-modified liposomes integrated into dissolving microneedles for the treatment of psoriasis.

Methotrexate (MTX) is a first-line drug in treating psoriasis because of its strong anti-proliferation and anti-inflammatory effects. However, systemic administration of MTX will lead to many side effects, such as gastrointestinal irritation, liver and kidney toxicity, etc. Herein, we developed liposome-loaded microneedles (MNs) system to improve transdermal efficiency, which was used to overcome the problems of low transdermal efficiency and poor therapeutic effect of traditional transdermal drug delivery methods. Hyaluronic acid (HA) was modified on the surface of MTX-loaded liposomes. The interaction of HA and CD44 could increase the adhesion of HA-MTX-Lipo to HaCaT cells, thereby promoting the apoptosis or death of HaCaT cells. Results indicated HA-MTX-Lipo MNs could inhibit the development of psoriasis and reduce the degree of skin erythema, scaling, and thickening. The mRNA levels of proinflammatory cytokines such as IL-17A, IL-23, and TNF-α were decreased. The epidermal thickness and proliferative cell-associated antigen Ki67 expression were also reduced. Specifically, the expression of mRNA levels of proinflammatory cytokines was down-regulated. The MNs transdermal delivery of HA-modified-MTX liposomes provided a promising method for treating psoriasis.

Automated vehicles for older adults with cognitive impairment: a survey study.

As the population is ageing, the number of older adults with cognitive impairment (CI) is increasing. Automated vehicles (AVs) can improve independence and enhance the mobility of these individuals. This study aimed to: (1) understand the perception of older adults (with and without CI) and stakeholders providing services and supports regarding care and transportation about AVs, and (2) suggest potential solutions to improve the perception of AVs for older adults with mild or moderate CI. A survey was conducted with 435 older adults with and without CI and 188 stakeholders (e.g. caregivers). The results were analysed using partial least square - structural equation modelling and multiple correspondence analysis. The findings suggested relationships between older adults' level of cognitive impairment, mobility, knowledge of AVs, and perception of AVs. The results provided recommendations to improve older adults' perception of AVs including education and adaptive driving simulation-based training.Practitioner summary: This study investigated the perception of older adults and other stakeholders regarding AVs. The findings suggested relationships between older adults' level of cognitive impairment, mobility, knowledge of AVs, and perception of AVs. The results provided guidelines to improve older adults' perception of AVs.

Oxidant-Dependent Sensitizing, Protective, and Mitigative Effects in X-Ray-Irradiated Pulmonary Endothelial Cells.

The primary response of proliferating bovine pulmonary artery endothelial cells (BPAECs) after X-ray irradiation [≤10 gray (Gy)] is shown to be transient cell-cycle arrest. Accompanying oxidant-linked functional changes within the mitochondria are readily measured, but increased autophagy is not. Radiation-induced apoptosis is negligible in this line-important because cells undergoing apoptosis release oxygen-derived species that can overwhelm/mask the radiation-associated species and their effects that we wish to investigate. Cells irradiated and cultured at 3% oxygen exhibited delayed cell-cycle arrest (6-8 hours after 10 Gy irradiation) compared with those maintained at 20% oxygen (2-4 hours after 10 Gy irradiation). At 3% oxygen, either only during or only after irradiation, results intermediate between 20% and 3% oxygen throughout were obtained. No variability in cell-cycle distribution was observed for unirradiated cells cultured under different prevailing oxygen levels. Mitochondrially localized manganese superoxide dismutase delayed the X-ray-induced cell-cycle changes when over-expressed in BPAEC, indicating superoxide to be one of the key oxygen-derived cytotoxic species involved in the radiobiological response. Also, the peroxynitrite biomarker 3-nitrotyrosine was elevated, whereas hydrogen peroxide levels were not. Lastly, the utility of the BPAEC for screening potential countermeasures to ionizing radiation is demonstrated with some quinoline derivatives. Three of the five compounds appeared mitigative, and all were protective. It is suggested that the oxidation-reduction chemistry of these compounds probably offers a reasonable explanation for their observed ameliorative properties. Furthermore, the results suggest a promising new direction in the search for lead compounds as countermeasures to the effects of ionizing radiation. SIGNIFICANCE STATEMENT: The primary radiological response of proliferating bovine pulmonary artery endothelial cells is cell-cycle arrest, starting soon after X-ray irradiation (1-10 Gy) at 20% O2 but delayed by 4 hours at systemic (3%) O2. Oxygen/superoxide is found to be radio-sensitizing in at least two distinct time windows, during and after the irradiation, with both responses antagonized by various hydroxyquinoline derivatives. Similar responses in many other cell lines are likely to be masked by elevated oxidants associated with apoptosis.

Vague-Segment Technique: Automatic Computation of Tumor Stroma Ratio for Breast Cancer on Whole Slides.

The calculation of Tumor Stroma Ratio (TSR) is a challenging medical issue that could improve predictions of neoadjuvant chemotherapy benefits and patient prognoses. Although several studies on breast cancer and deep learning methods have achieved promising results, the drawbacks that pixel-level semantic segmentation processes could not extract core tumor regions containing both tumor pixels and stroma pixels make it difficult to accurately calculate TSR. In this paper, we propose a Vague-Segment Technique (VST) consisting of a designed SwinV2UNet module and a modified Suzuki algorithm. Specifically, the SwinV2UNet identifies tumor pixels and generate pixel-level classification results, based on which the modified Suzuki algorithm extracts the contour of core tumor regions in terms of cosine angle. Through this way, VST obtains vaguely segmentation results of core tumor regions containing both tumor pixels and stroma pixels, where the TSR could be calculated by the formula of Intersection over Union (IOU). For the training and evaluation, we utilize the well-known The Cancer Genome Atlas (TCGA) database to create an annotated dataset, while 150 images with TSR annotations from real cases are also collected. The experimental results illustrate that the proposed VST could generate better tumor identification results compared with state-of-the-art methods, where the extracted core tumor regions lead to more consistencies of calculated TSR with senior experts compared to junior pathologists. The experimental results demonstrate the superiority of our proposed pipeline, which has promise for future clinical application.