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Abstract Introduction Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia. Methods Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia–Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory. Results Data from 271 dermatologists were included for analysis. About one-third (31.7%) reported that they referred to the Hanifin and Rajka criteria during diagnosis. The majority of dermatologists used clinical impression when assessing AD severity and treatment response. Reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. More than half of dermatologists preferred adding systemic anti-inflammatory medication for patients who did not respond to maximized topical treatment, while 43.6% would switch to another systemic medication for those failing to respond to maximized systemic treatment. Topical corticosteroids were frequently selected by dermatologists. For systemic therapies, oral corticosteroids were most frequently used, followed by cyclosporin and dupilumab. Narrow-band ultraviolet B was the most common phototherapy reported (84.9%). There was considerable variation in estimated average and maximum durations of therapies used to treat AD. Conclusion This study has provided insights on the real-world management of moderate-to-severe AD in the Asia–Pacific region. The diverse approaches in diagnosis and treatment highlight the multifactorial nature of AD, reliance on clinical judgement, and importance of personalized care. To improve outcomes in patients with AD, it will be crucial to develop biomarkers for diagnosis, reduce subjectivity in assessment, as well as promote access to newer and effective therapies.

Abstract Introduction The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs. Methods Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory. Results Median age of enrolled patients (N = 1103) was 41.0 years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2%) and oral steroids (58.7%) were frequently prescribed to manage AD. Common atopic comorbidities were allergic urticaria (64.2%), allergic rhinitis (61.8%), and allergic conjunctivitis (51.5%). Median DLQI score was 13.0 (IQR 11.0), while median EQ-5D-5L (based on China value set) score was 0.8 (IQR 0.4); 87.2% and 77.2% of patients reported pain/discomfort and anxiety/depression on the EQ-5D-5L domains, respectively. Median total annual costs associated with AD were USD 10,128.52 (IQR 12,963.26) per patient, with indirect costs being the largest component. Findings from WPAI indicated that presenteeism is a major contributor to productivity loss. Conclusion This multinational survey study showed that AD is associated with substantial QoL impairment and economic burden among Asian adult patients with moderate-to-severe AD. To alleviate burden of AD, clinicians should be more proactive in managing other concomitant conditions including psychological issues, and advocate for increased reimbursement for AD treatments.

Abstract Introduction It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient–clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia. Methods Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia–Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. Patients and dermatologists completed separate surveys designed to elicit their expectations regarding AD management, and their perceived level of patient–clinician communication. Patients were also asked about their treatment satisfaction and whether they prefer additional treatment beyond what was prescribed. Demographic information and responses were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory, and all participants provided informed consent. Results A total of 1103 patients and 271 dermatologists completed the surveys. Both patients and dermatologists were largely aligned in their top treatment goals in AD management. However, greater proportions of patients prioritized the prevention of exacerbation (78.0% versus 47.2%), minimization of treatment adverse effects (46.4% versus 9.1%), and improvement in mental health (16.0% versus 4.9%), compared with dermatologists. Although patient–clinician communication was observed to be generally good, 10.9% of patients reported dissatisfaction with communication in AD management. The majority of patients were either “very satisfied” or “satisfied” with their latest acute AD treatment, but 65.5% of patients still desired additional treatment. Conclusions This multinational study has provided insights on the perspectives of Asian patients and dermatologists in treatment goals, AD management, and communication. In general, both patients and dermatologists were aligned in treatment goals and there was satisfactory patient–clinician communication in most aspects. However, potential areas of improvement have been identified to further enhance patient-centered care.

Abstract Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg− 1), curcumin (Cur, 40 mg·kg− 1) and metformin (Met, 50 mg·kg− 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml− 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. Conclusion NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020–2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6–7 days/week, and 3.48 (1.29, 9.37) in drinking 1–19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5–≤1.0, >1.0–≤1.5, and >1.5 Liter/week (Ptrend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (Ptrend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men’s association between drinking whisky and CRC risk was J-shaped.

Abstract Background Improving chewing function of older adults increases the health-related quality of life. Few studies indicated the correlation between tongue, lip strength on masticatory performance in older people. The study aimed to investigate the association between lip, tongue strength on chewing pattern in aging population. Methods The older adults had independent daily intake without assistance were enrolled. They had intact dentition and no periodontitis. To estimate the number of chewing strokes and chewing time by consuming a cornstarch cookie were used to represent chewing pattern. Lip and tongue pressure were evaluated with an Iowa Oral Performance Instrument. Linear regression analysis was used to analyze the lip and tongue pressure associated with the chewing time and strokes. Spearman’s correlation analysis was utilized to evaluate the associations among chewing time and chewing strokes or lip and tongue pressure. Results 35 women and 35 men with an average age of 73.2 years were investigated. Tongue pressure was significantly related to the chewing time and the number of chewing strokes (p = 0.01 and 0.03). There was a close association between chewing time and the number of chewing strokes (p

To overcome the limitations of the oral limitations of capsaicin, this study prepared a thiolated chitosan-zein nanoparticle delivery system loaded with capsaicin. The preparation process was optimized based on particle size and loading capacity, and the efficiency of encapsulation was verified by fluorescence spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The stability and release properties of the capsaicin-loaded nanoparticles were also evaluated during in vitro digestion. The results showed that at a thiolated chitosan to zein to capsaicin of 10:10:1, the particle size of the nanoparticles, which were observed to be regular spherical in shape, was (76.05 ± 1.06) nm, and the loading capacity was (36.85 ± 1.22) μg/mg. The nanoparticles were formed through hydrogen bonds and hydrophobic interactions. In addition, the nanoparticles had good pH stability and ionic strength stability, which could effectively delay the release of capsaicin during simulated digestion in vitro, and the release ratio after 4 h digestion was only (40.08 ± 4.28)%. The nanoparticles can be used for oral delivery of capsaicin.

BackgroundBacillary dysentery (BD) has brought a significant public health concern in China. Temperature is one of the main factors affecting BD incidence. Due to the largely different temperature ranges between regions, the classic multi-region time series studies could only explore the relative temperature-BD association and showed that BD incidence is positively associated with relative temperature (i.e., temperature percentile), which does not conform to the laboratory knowledge that both high and low temperature interfere with the survival of bacteria. The association on relative temperature scale also limits the intuition of epidemiological meanings.MethodsA novel two-stage strategy was proposed to investigate the association between monthly temperature and BD incidence on the original temperature scale in 31 provinces, China. In the first stage, truncated polynomial splines, as the substitute of the common natural splines or B-splines in generalized additive models, were used to characterize the temperature-BD association on the original temperature scale in each province. In the second stage, a multivariate meta-analysis compatible with missing values was used to pool the associations. The classic strategy based on relative temperature was used as a reference.ResultsThe average temperature-BD association presented a U-inverted shape, but not a monotonically increasing shape obtained using the classic strategy. This inverted U-shaped association conforms more to the laboratory knowledge and the original-scale association also provided an intuitive perspective and an easily explanatory result. Another advantage is that the novel strategy can extrapolate the province-specific association outside the observed temperature ranges by utilizing information from other provinces, which is meaningful considering the frequent incidences of extreme temperatures.ConclusionsThe association between temperature and BD incidence presented a U-inverted shape. The proposed strategy can efficiently characterize the association between exposure and outcome on original scale in a multi-region study with largely different exposure ranges.

Background: This prospective study aimed to compare regional soft tissue changes between patients with class III overbite and open bite deformities treated with bimaxillary surgery involving clockwise and counter-clockwise mandibular setback, respectively. Material and methods: Class III deformity adults receiving Le Fort I and bilateral sagittal split osteotomies were grouped according to the incisal occlusion: overbite (n = 30) and open bite (n = 30). Combined cone-beam CT scans and 3D facial photographs preoperative and at least 1-year postoperative were taken to assess the soft tissue changes. Results: Postoperative changes for the overbite and open bite groups included anterior repositioning of nose (−0.8 ± 1.2 mm and −1.1 ± 1.1 mm, respectively) and cheek (−1.9 ± 1.3 mm and −1.7 ± 2.6 mm, respectively), posterior repositioning of chin (5.2 ± 4.0 mm and 4.9 ± 3.2 mm, respectively), and medial (−1.7 ± 2.0 mm and −1.9 ± 2.1 mm, respectively) and posterior (2.7 ± 1.4 mm and 2.8 ± 2.3 mm, respectively) repositioning of bilateral angles. Posterior (1.2 ± 2.0 mm and 5.1 ± 3.3 mm) and inferior (−1.4 ± 2.2 mm and −2.4 ± 2.7 mm) repositioning of upper lip and lower lip occurred in overbite group. Inferior (−2.3 ± 2.4 mm) and superior (3.7 ± 3.4 mm) repositioning of chin occurred in the overbite and open bite groups, respectively. Conclusions: Treatment of class III overbite and open bite deformities with bimaxillary rotational surgery resulted in comparable regional soft tissue changes, except for upper lip, lower lip and chin.

Due to the lack of statistical methods, few studies have investigated the spatial autocorrelated distribution in the association between short-term exposure to PM2.5 and mortality and used a statistical manner to explore the association-clustered regions, which play important roles in identifying high-sensitivity/susceptibility regions. The Sichuan Basin (SCB) is one of the most PM2.5-polluted areas, and the extreme economic imbalance may cause considerable spatial heterogeneity and clustering in PM2.5-mortality association. In this work, we used a recently proposed strategy by us to investigate the spatially autocorrelated and clustered association between daily PM2.5 and cardiorespiratory mortality from 2015 to 2019 in 130 counties of the SCB. First, generalized additive models were independently constructed to obtain the county-level association estimations. Then, an estimation-error-based spatial scan statistic was used to detect the association-clustered regions. Third, multivariate conditional meta autoregression was used to obtain the spatially autocorrelated association distribution, based on which the attributable deaths were mapped and their inequality was evaluated using the Gini coefficient and Lorenz curve. Results showed that two significantly association-clustered regions were detected. One is mainly located in the megacity Chengdu where PM2.5 presented a significantly stronger association with no threshold effect at low-level PM2.5 but a threshold at high-level PM2.5. In the other cluster, a threshold effect at low-level PM2.5 but no threshold at high-level PM2.5 were found. The mortality risk at low/middle-level PM2.5 decreased from Chengdu as the center to the surrounding areas. A total of 29,129 (2.0 %) deaths were attributable to the excess PM2.5 exposure. The attributable deaths also decreased from Chengdu as the center to the surrounding areas with Gini coefficients of 0.43 and 0.3 for absolute and relative attributable deaths, respectively. This novel strategy provided a new epidemiological perspective regarding the association and implicated that Chengdu is significantly deserving of more attention regarding PM2.5-related health loss.

Background: Intracranial teratomas or other cystic lesions with atypical imaging manifestations can still be frequently seen clinically. The specific reasons for unusual imaging manifestations need to be further explored. Observation(s): A case of adult teratoma in the posterior fossa with unusual imaging manifestations was reported. The chemical composition of its cystic fluid was quantitatively detected, and in vitro imaging simulation experiments were performed on some fluid substances with similar cystic fluid properties to explore the reasons for special imaging manifestations. The content of inorganic substances and protein in the cystic fluid were both low, with no melanin detected. In vitro experiments revealed that MR T1 signals could increase with protein content rising and changes in MR T2 signals presented no obvious correlation with it. CT values increased gradually with protein concentration rising. The substances with similar viscosity had similar CT values, whereas substance viscosity showed no significant correlation with changes in MR signals. Conclusion: The abnormality of imaging manifestations cannot be confirmed as the result of “high protein content”, nor can it be simply attributed to bleeding. Further research is required for the impact of the combination of paramagnetic particles and biofluid on imaging.

ObjectivesTo assess antibody responses to an inactivated SARS-CoV-2 vaccine in individuals aged 50 and older.MethodsWe conducted a post-market cross-sectional seroepidemiology study. We recruited 4,632 vaccinated individuals aged 50 and older, measured their total serum SARS-CoV-2-specific antibody (TA), and collected correlates. The primary outcome was the geometric mean titer (GMT) of TA, and the secondary outcome was the decline of TA with age. Univariate, bivariate, and multivariate analyses were used to examine the associations of the TA GMT with age, and trend analyses were used to test whether their associations were significant.ResultsAll participants had a detectable TA, which was generally at a low level across all age groups. The TA GMT (95% CI) in AU/mL was 3.05 (2.93, 3.18); the corresponding arithmetic mean (95% CI) was 17.77 (16.13, 19.42) in all participants and 4.33 (3.88, 4.84), 3.86 (3.49, 4.28), 3.24 (2.92, 3.59), 2.77 (2.60, 2.96), and 2.65 (2.48, 2.83) in the age groups of 50-54, 55-59, 60-64, 65-74, and 75 years or older, respectively. The TA GMT decreased with age with a Ptrend < 0.001. The TA GMT was significantly lower in those with hypertension or diabetes compared to those with neither.ConclusionThe inactivated SARS-CoV-2 vaccine is effective in individuals aged 50 and older. This is the first study that has found an inverse dose-response relationship between ages and the low-level TAs. Older people, especially those with chronic diseases, should get the SARS-CoV-2 vaccine, and their vaccination frequency, dose, and method may need to be different from those of younger people.

Abstract Background Obstetrical infection is one of the causes of maternal death and a difficult problem for many clinicians. Changes in the demographic and obstetric background of pregnant women following the Universal Two-Child Policy may have an impact on some fertility phenomena. And with the increase in the number of deliveries, the limited medical resources become more scarce. How will China's health system quickly adapt to the growing needs and expectations for maternal health and ensure the provision of qualified and accessible medical services? In addition, what social support measures should be provided to reduce preventable obstetric complications? Given the relatively low per capita share of medical resources in China, how should China deal with the impact of the Universal Two-Child Policy? Therefore, more studies based on the change of fertility policy are needed. We try to analyze the epidemiological characteristics and risk factors of obstetric infection before and after the Universal Two-Child Policy, with a view to providing reference for the prevention and control of obstetric infection in regions after the change of fertility policy, and also hope to make corresponding contributions to the solution of the above problems through relevant studies. Methods The subjects of the survey were 268,311 pregnant women from Hebei Province Maternal Near Miss Surveillance System (HBMNMSS) of Hebei Women and Children's Health Center from January 1, 2013 to December 31, 2017. We analyzed the region, time and population distribution characteristics of obstetric infection, compared the epidemiological factors of obstetric infection before and after the Universal Two-Child Policy, and analyzed the relevant risk factors of obstetric infection. Results The incidence of obstetric infection increased nearly twice after the Universal Two-Child Policy. The incidence of obstetric infection was highest in Chengde (1.9%), a city with a northward geographical distribution, Baoding (1.6%), Cangzhou (1.5%) followed; The higher the hospital grade, the higher the incidence; The incidence of obstetric infections in hospitals at all levels has increased; The age of onset before the Universal Two-Child Policy was (27.82 ± 5.047) years old, and the age after the Universal Two-Child Policy was (28.97 ± 4.880) years old; The incidence of obstetric infections is higher in winter. The rate of abortion-related infection (increased from 0.61 to 1.65%) and the rate of pregnant women with high school education (increased from 0.35 to 0.74%) increased significantly. The results of multivariate Logistic regression analysis after the Universal Two-Child Policy showed that anemia (OR = 1.249, 95%CI: 1.071–1.458), chronic hypertension (OR = 1.934, 95%CI: 1.375–2.722), mild preeclampsia (OR = 2.103, 95%CI: 1.323–3.344) and severe preeclampsia (OR = 2.228, 95%CI: 1.703–2.916) were independent risk factors for obstetric infection. Gestational age ≥ 37 weeks was a protective factor. Conclusion After the Universal Two-Child Policy, the prevention and control of obstetric infections should be strengthened, especially for abortion-related infections and elderly maternal with obstetric complications and complication in high-grade hospitals in winter. Educational background is also one of the factors that should be considered in the prevention of obstetric sensation. Prolonging gestational age is helpful to reduce the incidence of obstetric infection.

Abstract Background Occlusal force represents masticatory function. Using quantifiable occlusal indicators provides a more objective occlusal force evaluation. In the recent dental practice, digital methods such as the Dental Prescale II (DP2, GC Corp., Tokyo, Japan) and T-scan (T-Scan III v8; Tekscan Inc.) are commonly used in clinics to evaluate treatment outcomes. The T-scan provides the relative bite force (%) compared to the maximal bite force on individual teeth or the unilateral arch. The DP2 can quantify occlusal force, measured in newtons (N), on the half arch or the overall bite, but it is difficult to identify the bite force on an individual tooth. It is difficult to select a device that fulfils all the requirements to record occlusal force. This study aimed to investigate the association between the bite measured by the DPS2 and T-scan to determine whether the measured bite force is comparable through calculation. Methods A total of 80 healthy adults, including 41 women and 39 men with a mean age of 38.2, were requested to bite pressure sensitive film sheets ten minutes apart. Linear regression analysis was used to estimate the measured bite force by the DP2 and T-scan. Results There was a significant positive correlation between the occlusal force measured by the DP2 and T-scan (P

Abstract Cancer stem cells (CSCs) are a subpopulation of cancer cells with stem cell properties that sustain cancers, which may be responsible for cancer metastasis or recurrence. Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in the plasma membrane that mediate various intracellular signaling. The occurrence and progression of cancer are closely related to lipid rafts. Emerging evidence indicates that lipid raft levels are significantly enriched in CSCs compared to cancer cells and that most CSC markers such as CD24, CD44, and CD133 are located in lipid rafts. Furthermore, lipid rafts play an essential role in CSCs, specifically in CSC self-renewal, epithelial-mesenchymal transition, drug resistance, and CSC niche. Therefore, lipid rafts are critical regulatory platforms for CSCs and promising therapeutic targets for cancer therapy.

Striatal medium spiny neurons (MSNs) and striatal dopamine (DA) innervation are profoundly important for brain function such as motor control and cognition. A widely accepted theory posits that striatal DA loss causes (or leads to) MSN dendritic atrophy. However, examination of the literature indicates that the data from Parkinson's disease (PD) patients and animal PD models were contradictory among studies and hard to interpret. Here we have re-examined the potential effects of DA activity on MSN morphology or lack thereof. We found that in 15-day, 4- and 12-month old Pitx3 null mutant mice that have severe DA denervation in the dorsal striatum while having substantial residual DA innervation in the ventral striatum, MSN dendrites and spine numbers were similar in dorsal and ventral striatum, and also similar to those in normal mice. In 15-day, 4- and 12-month old tyrosine hydroxylase knockout mice that cannot synthesize L-dopa and thus have no endogenous DA in the entire brain, MSN dendrites and spine numbers were also indistinguishable from age-matched wild-type (WT) mice. Furthermore, in adult WT mice, unilateral 6-OHDA lesion at 12 months of age caused an almost complete striatal DA denervation in the lesioned side, but MSN dendrites and spine numbers were similar in the lesioned and control sides. Taken together, our data indicate that in mice, the development and maintenance of MSN dendrites and spines are DA-independent such that DA depletion does not trigger MSN dendritic atrophy; our data also suggest that the reported MSN dendritic atrophy in PD may be a component of neurodegeneration in PD rather than a consequence of DA denervation.

Reducing lipid uptake of macrophages and stimulating cholesterol efflux are two necessary steps for atherosclerotic plaque regression. In this study, a compound of curcumin nicotinate (CN) was synthesized from nicotinic acid which can raise raising high-density lipoprotein (HDL) and curcumin which can lower lipid. However, the shortcomings of CN, such as poor water solubility and low bioavailability, limit its clinical application. In this article, a CN loaded biomimetic nanosystem was constructed by using Prussian blue nanoparticles (PB NPs) to improve its solubility, thereby changing its administration route. In addition, hyaluronic acid (HA) modification on the biomimetic PB NPs was adopted to prolong circulation time and improve the accumulation of drugs in the plaque region. Mechanism studies have shown that the constructed nanosystem could exert anti-AS effects through the pathway of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) /Low-density lipoprotein receptor (LDL-R), ATP Binding Cassette Transporter A1(ABCA1) /Caveolin-1 /Liver X Receptor (LXR). These findings indicated that the designed nano-platform is expected to be used for prevention and targeted therapy of atherosclerosis.

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Intelligent sorting of coal and gangue is of great significance to the intelligent construction of coal mines as well as green development. In this study, we propose a coal and gangue segmentation method with an improved classical segmentation network Mask R‐CNN, denoted as Multichannel Forward‐Linked Confusion Convolution Module (MFCCM)‐Mask R‐CNN. First, we design a MFCCM to construct the feature extraction network by stacking, second, we design a multiscale high‐resolution feature pyramid network structure to realize multipath fusion of feature information to enhance the position and contour information of the target, and finally, we propose a multiscale Mask head to enhance the diversity of information, and capture the more representative and unique features. Training and testing models using self‐built RGB coal and gangue data sets, the accuracy of the improved algorithm reaches 97.38%, which is an improvement of 1.66% compared to the original model. Compared with other segmentation models Unet, Deeplab V3+, Yoloact, Yolov7, and the model after replacing the backbone network, the MFCCM‐Mask R‐CNN has higher precision and recall, and can more accurately realize the efficient segmentation of coal and gangue. [ABSTRACT FROM AUTHOR]

A direct hydrocarbon detection is performed by using multi-attributes based quantum neural networks with gas fields. The proposed multi-attributes based quantum neural networks for hydrocarbon detection use data clustering and local wave decomposition based seismic attenuation characteristics, relative wave impedance features of prestack seismic data as the selected multiple attributes for one tight sandstone gas reservoir and further employ principal component analysis combined with quantum neural networks for giving the distinguishing results of the weak responses of the gas reservoir, which is hard to detect by using the conventional technologies. For the seismic data from a tight sandstone gas reservoir in the Sichuan basin, China, we found that multi-attributes based quantum neural networks can effectively capture the weak seismic responses features associated with gas saturation in the gas reservoir. This study is hoped to be useful as an aid for hydrocarbon detections for the gas reservoir with the characteristics of the weak seismic responses by the complement of the multi-attributes based quantum neural networks.

In recent years, small intestine as a key target in the treatment of Inflammatory bowel disease caused by NSAIDs has become a hot topic. Sanguinarine (SA) is one of the main alkaloids in the Macleaya cordata extracts with strong pharmacological activity of anti-tumor, anti-inflammation and anti-oxidant. SA is reported to inhibit acetic acid-induced colitis, but it is unknown whether SA can relieve NSAIDs-induced small intestinal inflammation. Herein, we report that SA effectively reversed the inflammatory lesions induced by indomethacin (Indo) in rat small intestine and IEC-6 cells in culture. Our results showed that SA significantly relieved the symptoms and reversed the inflammatory lesions of Indo as shown in alleviation of inflammation and improvement of colon macroscopic damage index (CMDI) and tissue damage index (TDI) scores. SA decreased the levels of TNF-α, IL-6, IL-1β, MDA and LDH in small intestinal tissues and IEC-6 cells, but increased SOD activity and ZO-1 expression. Mechanistically, SA dose-dependently promoted the expression of Nrf2 and HO-1 by decreasing Keap-1 level, but inhibited p65 phosphorylation and nuclear translocation in Indo-treated rat small intestine and IEC-6 cells. Furthermore, in SA treated cells, the colocalization between p-p65 and CBP in the nucleus was decreased, while the colocalization between Nrf2 and CBP was increased, leading to the movement of gene expression in the nucleus to the direction of anti-inflammation and anti-oxidation. Nrf2 silencing blocked the effects of SA. Together our results suggest that SA can significantly prevent intestinal inflammatory lesions induced by Indo in rats and IEC-6 cells through regulation of the Nrf2 pathway and NF-κBp65 pathway.

Abstract Background Epizootic haemorrhagic disease virus (EHDV) and the Palyam serogroup viruses (PALV) have led to significant economic losses associated with livestock production globally. A rapid, sensitive and specific method for the detection of EHDV and PALV is critical for virus detection, monitoring, and successful control and elimination of related diseases. Results In the present study, a recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD) assay for the co-detection of genome segment 1 (Seg-1) of EHDV and PALV was developed and evaluated. The analytical sensitivities of the established RPA-LFD assay in the detection of EHDV and PALV were 7.1 copies/µL and 6.8 copies/µL, respectively. No cross-reaction with other members of the genus Orbivirus, including African horse sickness virus, bluetongue virus, Guangxi orbivirus, Tibet orbivirus and Yunnan orbivirus was observed. The established RPA-LFD assay accurately detected 39 EHDV strains belonging to 5 serotypes and 29 PALV strains belonging to 3 serotypes. The trace back results of quantitative real-time polymerase chain reaction (qRT-PCR) and the established RPA-LFD assay on sentinel cattle were consistent. The coincidence rates of qRT-PCR and the established RPA-LFD assay in 56 blood samples from which EHDV or PALV had been isolated and 96 blood samples collected from cattle farms were more than 94.8 %. The results demonstrated that the established RPR-LFD assay is specific, sensitive and reliable, and could be applied in early clinical diagnosis of EHDV and PALV. Conclusions This study highlights the development and application of the RPA-LFD assay in the co-detection of EHDV and PALV for the first time. The assay could be used as a potential optional rapid, reliable, sensitive and low-cost method for field diagnosis of EHDV and PALV.

Exercises can be categorized into either unilateral or bilateral movements. Despite the topic popularity, the answer to the question as to which (unilateral or bilateral) is superior for a certain athletic performance enhancement remains unclear. To compare the effect of unilateral and bilateral resistance training interventions on measures of athletic performance. Keywords related with unilateral, bilateral and performance were used to search in the Web of Science, PubMed databases, and Google Scholar and ResearchGate™ websites. 6365 articles were initially identified, 14 met the inclusion criteria and were included in the final analysis, with overall article quality being deemed moderate. The quantitative analysis comprised 392 subjects (aged: 16 to 26 years). Sub-group analysis showed that unilateral exercise resistance training resulted in a large effect in improving unilateral jump performance compared to bilateral training (ES = 0.89 [0.52, 1.26]). In contrast, bilateral exercise resistance training showed a small effect in improving bilateral strength compared to unilateral (ES = -0.43 [-0.71, -0.14]). Non-significant differences were found in improving unilateral strength (ES = 0.26 [-0.03, 0.55]), bilateral jump performance (ES = -0.04 [-0.31, 0.23]), change of direction (COD) (ES = 0.31 [-0.01, 0.63]) and speed (ES = -0.12 [-0.46, 0.21]) performance. Unilateral resistance training exercises should be chosen for improving unilateral jumping performance, and bilateral resistance training exercises should be chosen for improving bilateral strength performance.

ObjectiveCOVID-19 has caused great loss of human life and livelihoods. The dissemination of health information in online social networks increased during the pandemic's quarantine. Older people are the most vulnerable group in sudden public health emergencies, and they have the disadvantage of infection rates and online search for health information. This study explores the relationship between the health risk perception and health information search behavior of older people in social networks, to help them make better use of the positive role of social networks in public health emergencies.MethodBased on the Risk Information Search and Processing model, and in the specific context of COVID-19, this study redefines health risk perception as a second-order construct of four first-order factors (perceived probability, perceived severity, perceived controllability, and perceived familiarity), and constructs a research model of the health risk perception and health information search behavior of older people. An online survey of people over 55 years old was conducted through convenience sampling in China from February 2020 to March 2020.ResultsA total of 646 older adults completed the survey. The structural equation model showed that health risk perception is a second-order factor (H1), that health risk perception has significant positive effects on health information search behavior (H2: β = 0.470, T = 11.577, P < 0.001), and that health risk perception has significant positive effects on affective response (H3: β = 0.536, T = 17.356, P < 0.001). In addition, affective response has a significant positive mediating effect on information sufficiency (H4: β = 0.435, T = 12.231, P < 0.001), and information sufficiency has a significant positive mediating effect on health information search behavior (H5: β = 0.136, T = 3.081, P = 0.002).ConclusionThe study results indicate that the health risk perception of older people during the COVID-19 outbreak not only directly affected their health information search behavior, but also had an indirect impact on their health information search behavior by affecting affective response and information sufficiency.

ObjectiveTo explore the role of surgical treatment modality on prognosis of metastatic esophageal adenocarcinoma (mEAC), as well as to construct a machine learning model to predict suitable candidates.MethodAll mEAC patients pathologically diagnosed between January 2010 and December 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A 1:4 propensity score-matched analysis and a multivariate Cox analysis were performed to verify the prognostic value of surgical treatment modality. To identify suitable candidates, a machine learning model, classification and regression tree (CART), was constructed, and its predictive performance was evaluated by the area under receiver operating characteristic curve (AUC).ResultsOf 4520 mEAC patients, 2901 (64.2%) were aged over 60 years and 4012 (88.8%) were males. There were 411 (9.1%) patients receiving surgical treatment modality. In the propensity score-matched analysis, surgical treatment modality was significantly associated with a decreased risk of death (HR: 0.47, 95% CI: 0.40-0.55); surgical patients had almost twice as much median survival time (MST) as those without resection (MST with 95% CI: 23 [17-27] months vs. 11 [11-12] months, P

The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have shown that ezetimibe alone could inhibit the development and progression of cancer through a variety of mechanisms, including anti-angiogenesis, stem cell suppression, anti-inflammation, immune enhancement and anti-proliferation. In the past decade, there has been heated discussion on whether ezetimibe combined with statins will increase the risk of cancer. At present, more and more evidence shows that ezetimibe does not increase the risk of cancers, which supports the role of ezetimibe in anti-cancer. In this review, we discussed the latest progress in the anti-cancer properties of ezetimibe and elucidated its underlying molecular mechanisms. Finally, we highlighted the potential of ezetimibe as a therapeutic agent in future cancer treatment and prevention.

The synthesis of efficient and sustainable heterogeneous Pd-based catalysts has been an active field of research due to their crucial role in carbon–carbon coupling reactions. In this study, we developed a facile and eco-friendly in situ assembly technique to produce a PdFe bimetallic hyper-crosslinked polymer (HCP@Pd/Fe) to use as a highly active and durable catalyst in the Ullmann reaction. The HCP@Pd/Fe catalyst exhibits a hierarchical pore structure, high specific surface area, and uniform distribution of active sites, which promote catalytic activity and stability. Under mild conditions, the HCP@Pd/Fe catalyst is capable of efficiently catalyzing the Ullmann reaction of aryl chlorides in aqueous media. The exceptional catalytic performance of HCP@Pd/Fe is attributed to its robust absorption capability, high dispersion, and strong interaction between Fe and Pd, as confirmed by various material characterizations and control experiments. Furthermore, the coated structure of a hyper-crosslinked polymer enables easy recycling and reuse of the catalyst for at least 10 cycles without any significant loss of activity.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCβ), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated β-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded β-catenin expression. As β-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with β-catenin function through the activation of a PDE5/cGMP functional axis.

Abstract Background The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury. Methods Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites. Results The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism. Conclusions These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

To assess activity and participation for adults in Taiwan's Disability Eligibility Determination System (DEDS), we developed a measure, the Functioning Disability Evaluation Scale—Adult version (FUNDES-Adult), based on the 36-item interviewer-administered version of the WHO Disability Assessment Schedule 2.0. The purpose of this study was to examine the factor structures of performance and capability dimensions of the FUNDES-Adult. This study followed a methodology research design to investigate the construct validity of the two dimensions of the FUNDES-Adult. Two samples were randomly stratified from the databank of adults with disabilities to examine structural validity by the exploratory factor analysis (EFA) (n = 8,730, mean age of 52.9 ± 16.81) and the confirmatory factor analysis (CFA) (n = 500, mean age of 54.3 ± 16.81). The results demonstrated that the EFA yielded 5-factor structures for both performance dimension (73.5% variance explained) and capability dimension (75.9% variance explained). The CFA indicated that the second-order factor structures of both dimensions were more parsimonious with adequate fit indices (GFI, NFI, CFI, and TLI ≥ 0.95, RMSEA < 0.09). The results of this study provide evidence that the FUNDES-Adult has acceptable structural validity for use in Taiwan's DEDS. Utility of the FUNDES-Adult in rehabilitation, employment, welfare, and long-term care services needs further study.

In this article, we study the existence of at least three distinct weak solutions for nonlocal elliptic problems involving p(x)-biharmonic operator. The results are obtained by means of variational methods. We also provide an example in order to illustrate our main abstract results. We extend and improve some recent results.

Background/purpose: Maxillary protraction with or without expansion appears to be an effective orthopedic treatment in skeletal class III growing patients, but the long-term effect on maxilla changes is less clear. The aim of this meta-analysis was to evaluate long-term three dimensional skeletal effects on maxilla through face mask (FM) with or without rapid maxillary expansion (RME) in skeletal CIII growing patients. Materials and methods: We searched database including PubMed, Science Direct, Embase and Web of Science through Feb 2020. Inclusion criteria were randomized controlled trials or cohort studies recruiting growing patients who received maxillary protraction and/or expansion and comparing the treatment groups with untreated controls. The follow-up periods were more than 3 years. Risk of bias was assessed using the Cochrane tools (RoB2.0 and ROBINS-I). GRADE was used to qualify the evidence. Results: This meta-analysis included 6 studies comprising 327 participants in total. No statistically significant changes were observed on the degree of Sella-Nasion-A point (SNA) in the treated groups when compared with the untreated controls. However, significant increase on maxillary rotation degree (mean difference: 8.20, 95% CI = 6.87–9.53, p

Phenotypic switching is the main cause of the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). We previously showed that Daxx exerted negative regulatory effect on AngII-induced VSMC proliferation and migration. However, the function of Daxx in VSMC phenotype switching remained unknown. Nicotinate-curcumin (NC) is an esterification derivative of niacin and curcumin that can prevent the formation of atherosclerosis. We found that NC significantly decreased AngII-induced VSMC phenotype switching. Furthermore, NC significantly inhibited AngII-induced cell proliferation and migration. Moreover, NC upregulated Daxx expression and regulated the PTEN/Akt signaling pathway. We concluded that NC inhibited AngII-induced VSMC phenotype switching by regulating the PTEN/Akt pathway, and through a mechanism that might be associated with the upregulation of Daxx expression.

Lithium-selenium (Li Se) batteries are promising energy storage devices. However, the long-term durability and high-rate performance of the Se cathode have been limited by significant volume expansion and the troublesome shuttle effect of polyselenides during repeated charging/discharging processes. To revolutionize these issues, we applied a top-down strategy through the in-situ trapping of amorphous Se within bubblelike carbon (BLC) frameworks, which can radically minimize the presence of surface-absorbed Se while enhancing Se loading capacity. This ingenious technique successfully encapsulates all Se species within carbon nanoshells, creating a distinct halffilled core-shell structure known as Se@void@BLC. This in-situ trapping approach ensures the efficient management of Se volume changes during repeated discharge and charge cycles. Moreover, an extraordinary Se loading capacity of up to 65.6 wt % is reached. Using the Se@void@BLC as cathode for LiSe battery, we achieve a high initial Columbic efficiency of 84.2 %, a high reversible capacity of 585 mAhg-1, and an ultralow capacity decay of only 0.0037% per cycle during 4000 cycles at 10 Ag-1. [ABSTRACT FROM AUTHOR]